Population pharmacokinetics of fluconazole in critically ill patients receiving extracorporeal membrane oxygenation and continuous renal replacement therapy: an ASAP ECMO study.

This multicenter study describes the population pharmacokinetics (PK) of fluconazole in critically ill patients receiving concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and includes an evaluation of different fluconazole dosing regimens for achievement of target exposure associated with maximal efficacy. Serial blood samples were obtained from critically ill patients on ECMO and CRRT receiving fluconazole. Total fluconazole concentrations were measured in plasma using a validated chromatographic assay. A population PK model was developed and Monte Carlo dosing simulations were performed using Pmetrics in R. The probability of target attainment (PTA) of various dosing regimens to achieve fluconazole area under the curve to minimal inhibitory concentration ratio (AUC0-24/MIC) >100 was estimated. Eight critically ill patients receiving concomitant ECMO and CRRT were included. A two-compartment model including total body weight as a covariate on clearance adequately described the data. The mean (±standard deviation, SD) clearance and volume of distribution were 2.87 ± 0.63 L/h and 15.90 ± 13.29 L, respectively. Dosing simulations showed that current guidelines (initial loading dose of 12 mg/kg then 6 mg/kg q24h) achieved >90% of PTA for a MIC up to 1 mg/L. None of the tested dosing regimens achieved 90% of PTA for MIC above 2 mg/L. Current fluconazole dosing regimen guidelines achieved >90% PTA only for Candida species with MIC <1 mg/L and thus should be only used for Candida-documented infections in critically ill patients receiving concomitant ECMO and CRRT. Total body weight should be considered for fluconazole dose.

Antimicrobial Exposures in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation.

Rationale: Data suggest that altered antimicrobial concentrations are likely during extracorporeal membrane oxygenation (ECMO). Objectives: The primary aim of this analysis was to describe the pharmacokinetics (PKs) of antimicrobials in critically ill adult patients receiving ECMO. Our secondary aim was to determine whether current antimicrobial dosing regimens achieve effective and safe exposure. Methods: This study was a prospective, open-labeled, PK study in six ICUs in Australia, New Zealand, South Korea, and Switzerland. Serial blood samples were collected over a single dosing interval during ECMO for 11 antimicrobials. PK parameters were estimated using noncompartmental methods. Adequacy of antimicrobial dosing regimens were evaluated using predefined concentration exposures associated with maximal clinical outcomes and minimal toxicity risks. Measurements and Main Results: We included 993 blood samples from 85 patients. The mean age was 44.7 ± 14.4 years, and 61.2% were male. Thirty-eight patients (44.7%) were receiving renal replacement therapy during the first PK sampling. Large variations (coefficient of variation of ⩾30%) in antimicrobial concentrations were seen leading to more than fivefold variations in all PK parameters across all study antimicrobials. Overall, 70 (56.5%) concentration profiles achieved the predefined target concentration and exposure range. Target attainment rates were not significantly different between modes of ECMO and renal replacement therapy. Poor target attainment was observed across the most frequently used antimicrobials for ECMO recipients, including for oseltamivir (33.3%), piperacillin (44.4%), and vancomycin (27.3%). Conclusions: Antimicrobial PKs were highly variable in critically ill patients receiving ECMO, leading to poor target attainment rates. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000559819).

Nursing Faculty Workforce Development Project.

A proposed nursing faculty workforce development project by a college of nursing within a research-intensive institution will increase the number of nurse faculty from the current population of BSN-prepared nurses from underserved communities in a state to earn a master of science in nursing (MSN) degree with a nursing education specialty. This project will be accomplished through partnerships between a college of nursing and academic institutions with large nursing student populations from underserved communities. In addition, the project will incorporate the employment of MSN students at academic partner institutions within a clinical nurse faculty role. The proposed project will continue after an initial federally funded grant to continue the project and address the nurse faculty shortage from diverse populations and advance health equity and culturally congruent health care in the state. The project will also enhance partnership building with stakeholders, such as statewide academic institutions, to impact underserved communities.

Population Pharmacokinetics of Vancomycin in Critically Ill Adult Patients Receiving Extracorporeal Membrane Oxygenation (an ASAP ECMO Study).

Our study aimed to describe the population pharmacokinetics (PK) of vancomycin in critically ill patients receiving extracorporeal membrane oxygenation (ECMO), including those receiving concomitant renal replacement therapy (RRT). Dosing simulations were used to recommend maximally effective and safe dosing regimens. Serial vancomycin plasma concentrations were measured and analyzed using a population PK approach on Pmetrics. The final model was used to identify dosing regimens that achieved target exposures of area under the curve (AUC0-24) of 400-700 mg · h/liter at steady state. Twenty-two patients were enrolled, of which 11 patients received concomitant RRT. In the non-RRT patients, the median creatinine clearance (CrCL) was 75 ml/min and the mean daily dose of vancomycin was 25.5 mg/kg. Vancomycin was well described in a two-compartment model with CrCL, the presence of RRT, and total body weight found as significant predictors of clearance and central volume of distribution (Vc). The mean vancomycin renal clearance and Vc were 3.20 liters/h and 29.7 liters respectively, while the clearance for patients on RRT was 0.15 liters/h. ECMO variables did not improve the final covariate model. We found that recommended dosing regimens for critically ill adult patients not on ECMO can be safely and effectively used in those on ECMO. Loading doses of at least 25 mg/kg followed by maintenance doses of 12.5-20 mg/kg every 12 h are associated with a 97-98% probability of efficacy and 11-12% probability of toxicity, in patients with normal renal function. Therapeutic drug monitoring along with reductions in dosing are warranted for patients with renal impairment and those with concomitant RRT. (This study is registered with the Australian New Zealand Clinical Trials Registry [ANZCTR] under number ACTRN12612000559819.).

The Lived Experience of DACA Recipients Who Are US Nursing Program Graduates and Their Pathways to Professional Licensure: A Phenomenological Study.

AIM: This phenomenological study explored the experiences of Deferred Action for Childhood Arrivals (DACA) recipients who are nursing program graduates in the United States and their pathways to professional licensure. BACKGROUND: DACA is a federal program facilitating lawful employment and higher education to qualified US immigrants. Understanding the experience of DACA recipients who have become registered nurses will inform nurse educators' advocacy to create a more diverse nursing workforce. METHOD: DACA recipients ( n = 17) who were US nursing program graduates were interviewed to explore the phenomenon of a pathway to professional licensure. RESULTS: The pathway to professional licensure emerged within four themes: pursuing the dream, finding support, figuring it out, and advocating for others. CONCLUSION: To contribute to a diverse nursing workforce, the authors recommend that nurse educators advocate for policies to support DACA recipients who graduate from US nursing programs to achieve professional nursing licensure.

Population Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation: an ASAP ECMO Study.

Our study aimed to describe the population pharmacokinetics (PK) of piperacillin and tazobactam in patients on extracorporeal membrane oxygenation (ECMO), with and without renal replacement therapy (RRT). We also aimed to use dosing simulations to identify the optimal dosing strategy for these patient groups. Serial piperacillin and tazobactam plasma concentrations were measured with data analyzed using a population PK approach that included staged testing of patient and treatment covariates. Dosing simulations were conducted to identify the optimal dosing strategy that achieved piperacillin target exposures of 50% and 100% fraction of time free drug concentration is above MIC (%fT>MIC) and toxic exposures of greater than 360 mg/liter. The tazobactam target of percentage of time free concentrations of >2 mg/liter was also assessed. Twenty-seven patients were enrolled, of which 14 patients were receiving concurrent RRT. Piperacillin and tazobactam were both adequately described by two-compartment models, with body mass index, creatinine clearance, and RRT as significant predictors of PK. There were no substantial differences between observed PK parameters and published parameters from non-ECMO patients. Based on dosing simulations, a 4.5-g every 6 hours regimen administered over 4 hours achieves high probabilities of efficacy at a piperacillin MIC of 16 mg/liter while exposing patients to a <3% probability of toxic concentrations. In patients receiving ECMO and RRT, a frequency reduction to every 12 hours dosing lowers the probability of toxic concentrations, although this remains at 7 to 9%. In ECMO patients, piperacillin and tazobactam should be dosed in line with standard recommendations for the critically ill.

Coupled laboratory and field investigations resolve microbial interactions that underpin persistence in hydraulically fractured shales.

Hydraulic fracturing is one of the industrial processes behind the surging natural gas output in the United States. This technology inadvertently creates an engineered microbial ecosystem thousands of meters below Earth's surface. Here, we used laboratory reactors to perform manipulations of persisting shale microbial communities that are currently not feasible in field scenarios. Metaproteomic and metabolite findings from the laboratory were then corroborated using regression-based modeling performed on metagenomic and metabolite data from more than 40 produced fluids from five hydraulically fractured shale wells. Collectively, our findings show that Halanaerobium, Geotoga, and Methanohalophilus strain abundances predict a significant fraction of nitrogen and carbon metabolites in the field. Our laboratory findings also exposed cryptic predatory, cooperative, and competitive interactions that impact microorganisms across fractured shales. Scaling these results from the laboratory to the field identified mechanisms underpinning biogeochemical reactions, yielding knowledge that can be harnessed to potentially increase energy yields and inform management practices in hydraulically fractured shales.

Uncovering the Process of Reasonable Academic Accommodations for Prelicensure Nursing Students With Learning Disabilities.

AIM: The purpose of the study was to explore the process by which nursing faculty make reasonable academic accommodations in the classroom setting for students with learning disabilities. BACKGROUND: Nursing students with identified learning disabilities require academic accommodations. The process of reasonable academic accommodations for nursing students with learning disabilities has not been examined within nursing education literature and clarification is needed. METHOD: Constructivist grounded theory methods, as described by Charmaz, guided data collection and analysis. RESULTS: Literature supports the categories, themes, and subthemes of the academic accommodations process found in this investigation. However, further research is necessary regarding the academic accommodations process and faculty development to support nursing students with identified learning disabilities. CONCLUSION: Nursing education needs standards of academic accommodations for students with learning disabilities.

Comparative genomics and physiology of the genus Methanohalophilus, a prevalent methanogen in hydraulically fractured shale.

About 60% of natural gas production in the United States comes from hydraulic fracturing of unconventional reservoirs, such as shales or organic-rich micrites. This process inoculates and enriches for halotolerant microorganisms in these reservoirs over time, resulting in a saline ecosystem that includes methane producing archaea. Here, we survey the biogeography of methanogens across unconventional reservoirs, and report that members of genus Methanohalophilus are recovered from every hydraulically fractured unconventional reservoir sampled by metagenomics. We provide the first genomic sequencing of three isolate genomes, as well as two metagenome assembled genomes (MAGs). Utilizing six other previously sequenced isolate genomes and MAGs, we perform comparative analysis of the 11 genomes representing this genus. This genomic investigation revealed distinctions between surface and subsurface derived genomes that are consistent with constraints encountered in each environment. Genotypic differences were also uncovered between isolate genomes recovered from the same well, suggesting niche partitioning among closely related strains. These genomic substrate utilization predictions were then confirmed by physiological investigation. Fine-scale microdiversity was observed in CRISPR-Cas systems of Methanohalophilus, with genomes from geographically distinct unconventional reservoirs sharing spacers targeting the same viral population. These findings have implications for augmentation strategies resulting in enhanced biogenic methane production in hydraulically fractured unconventional reservoirs.

Surface Interactions and Confinement of Methane: A High Pressure Magic Angle Spinning NMR and Computational Chemistry Study.

Characterization and modeling of the molecular-level behavior of simple hydrocarbon gases, such as methane, in the presence of both nonporous and nanoporous mineral matrices allows for predictive understanding of important processes in engineered and natural systems. In this study, changes in local electromagnetic environments of the carbon atoms in methane under conditions of high pressure (up to 130 bar) and moderate temperature (up to 346 K) were observed with 13C magic-angle spinning (MAS) NMR spectroscopy while the methane gas was mixed with two model solid substrates: a fumed nonporous, 12 nm particle size silica and a mesoporous silica with 200 nm particle size and 4 nm average pore diameter. Examination of the interactions between methane and the silica systems over temperatures and pressures that include the supercritical regime was allowed by a novel high pressure MAS sample containment system, which provided high resolution spectra collected under in situ conditions. For pure methane, no significant thermal effects were found for the observed 13C chemical shifts at all pressures studied here (28.2, 32.6, 56.4, 65.1, 112.7, and 130.3 bar). However, the 13C chemical shifts of resonances arising from confined methane changed slightly with changes in temperature in mixtures with mesoporous silica. The chemical shift values of 13C nuclides in methane change measurably as a function of pressure both in the pure state and in mixtures with both silica matrices, with a more pronounced shift when meso-porous silica is present. Molecular-level simulations utilizing GCMC, MD, and DFT confirm qualitatively that the experimentally measured changes are attributed to interactions of methane with the hydroxylated silica surfaces as well as densification of methane within nanopores and on pore surfaces.

Virtual Mentoring Program within an Online Doctoral Nursing Education Program: A Phenomenological Study.

The purpose of this study was to explore the lived experiences of doctoral nursing education students who participated in a virtual mentoring program. A phenomenological design was used to enable the researchers to gain an understanding of the research phenomenon. The three patterns that emerged during the study were Confirmation of Mentoring, Building Communities, and Learning the Role of Doctoral Student. Under the pattern of Confirmation of Mentoring were the themes of Receiving Academic Support and Receiving Personal Support. Under the pattern of Building Communities were the themes of Getting to Know Mentors and Understanding the Importance of Relationships. Under the pattern of Learning of Role of Doctoral Student were the themes of Balancing Time and Learning Technology. Additional research is needed to more fully explore virtual mentoring within doctoral programs.

CNE Certification Drive and Exam Results.

The Certified Nurse Educator (CNE) is the only credential recognizing the advanced practice role of the academic nurse educator. This article provides information regarding a CNE Certification Drive for faculty in one school of nursing. Descriptive findings include pass rates and content-specific averages. An analysis of the relationship between the variables is offered for role (faculty vs. recent graduate), years of teaching, and differences in test scores. Results indicate no significant relationship between role and test results, χ(1) = 1.11, p = .29, and between years of teaching for those who passed (M = 10.38, SD = 9.81) versus those who failed (M = 4.75, SD = 6.36, t(18) = 1.56, p = .14). Additional research is needed to provide further understanding of variables linked with the CNE exam in multiple schools of nursing.

A retrospective audit of insulin infusion management involving a locally developed dynamic insulin infusion guideline in a tertiary ICU.

BACKGROUND: The ideal target blood glucose range for intensive care patients on insulin infusions is controversial. Avoidance of hyperglycaemia and hypoglycaemia are well supported goals. METHODS: An audit of insulin infusion management was conducted following the institution of an insulin infusion guideline in a tertiary adult intensive care unit (ICU). The primary aim was to evaluate this guideline for safety and efficacy. Secondary aims were to compare outcomes such as ICU and hospital mortality, rate of severe hypoglycaemia, length of time within target zones, length of stay in ICU and hospital, ventilator hours and use of renal replacement therapy. Data analysis involved descriptive statistical techniques to allow comparison with other reported outcomes. RESULTS: Thirty-eight (38) patients were included, representing 137 days of insulin infusions and 2537 blood glucose readings. The mean insulin infusion treatment time was 86.4h (sd ± 86.4), median 48 h (IQR 14.4-141.6). The mean insulin dose per day was 97.6 units (sd ± 115.7), with a median of 68.7 (IQR 38.9-108.3). Blood glucose level (BGL) readings were within the desired target (6-9 mmols/L) and/or the buffer zones (4-6 and 9-12 mmols/L), 92.3% of the time. There were no episodes of severe hypoglycaemia (BGL ≤ 2.2 mmols/L). The median length of ICU stay was 5.9 days. Eighty-four (84) % of the cohort received mechanical ventilation and 26% received renal replacement therapy. The mean ventilation and renal replacement duration were days 6.9 and 9.4 days, respectively. The ICU and hospital mortality was 13.2% and 18.4%, respectively. CONCLUSION: The use of this locally developed insulin infusion guideline for hyperglycaemia within this ICU appears safe and effective. When compared to related published randomised controlled trials, the outcomes of this small scale single centre retrospective audit appear congruent. It achieved a severe hypoglycaemic rate of zero, with BGLs within target and buffer zones greater than 90%. It may be worthwhile for intensive care units to consider evaluating their own locally developed insulin infusion guidelines to ensure safety and efficacy.

The combined effects of extracorporeal membrane oxygenation and renal replacement therapy on meropenem pharmacokinetics: a matched cohort study.

INTRODUCTION: The scope of extracorporeal membrane oxygenation (ECMO) is expanding; however, optimal drug prescription during ECMO remains a developing science. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This open-label, descriptive, matched-cohort pharmacokinetics (PK) study aimed to compare the PK of meropenem in ECMO patients to critically ill patients with sepsis not receiving ECMO (controls). METHODS: Eleven adult patients on ECMO (venovenous (VV) ECMO, n = 6; venoarterial (VA) ECMO, n = 5) receiving intravenous (IV) meropenem were included. Meropenem plasma concentrations were determined using validated chromatography. Population PK analysis was performed using non-linear mixed effects modelling. This data was compared with previously published meropenem PK data from 10 critically ill adult patients not on ECMO (preserved renal function (n = 5) or receiving renal replacement therapy (RRT) (n = 5). Using these data, we then performed Monte Carlo simulations (n = 1,000) to describe the effect of creatinine clearance on meropenem plasma concentrations. RESULTS: In total, five (two VV, three VA) out of eleven ECMO patients received RRT. The other six patients (four VV, two VA) had no significant impairment in renal function. A two-compartment model adequately described the data. ECMO patients had numerically higher volume of distribution (0.45 ± 0.17 versus 0.41 ± 0.13 L/kg, P = 0.21) and lower clearance compared to controls (7.9 ± 5.9 versus 11.7 ± 6.5 L/h, P = 0.18). Variability in meropenem clearance was correlated with creatinine clearance or the presence of RRT. The observed median trough concentrations in the controls were 4.2 (0.0 to 5.7) mg/L. In ECMO patients, while trough meropenem concentrations >2 mg/L were achieved in all patients, a more aggressive target of >8 mg/L for less susceptible microorganisms was observed in only eight out of eleven patients, with five of them being on RRT. CONCLUSIONS: ECMO patients exhibit high PK variability. Decreased meropenem CL on ECMO appears to compensate for ECMO and critical illness-related increases in volume of distribution. Routine target concentrations >2 mg/L are maintained with standard dosing (1 g IV 8-hourly). However, an increase in dose may be necessary when targeting higher concentrations or in patients with elevated creatinine clearance.

Accuracy of general practitioner medication histories for patients presenting to the emergency department.

BACKGROUND: Clinical handover and obtaining best possible medication histories (BPMH) at transition points in care are key patient safety pri-orities. This study aimed to determine the accuracy of medication histories documented on general practitioner (GP) referral letters for patients referred to emergency departments. METHODS: This was a multicentre prospective observational study in eight emergency departments. Patients taking ≥1 regular medication, referred to the emergency department with a GP letter and seen by a pharmacist were included. GP medication regimens were compared with BPMH documented by the emergency department pharmacist. RESULTS: Of the GP letters (total 414), 361 (87%) had one or more discrepancies in the patients' regular medications and 62% had one or more regular medication discrepancies of moderate-high significance. Omission of medication was more prevalent in hand-written letters (P DISCUSSION: GP referral letters should not be used in isolation to determine the medication regimen taken before an emergency department presentation. Interventions are indicated to improve awareness and accuracy of medication documentation.

A systematic review and quality appraisal of interprofessional behavioral assessment instruments for nursing education.

Instruments to assess interprofessional behaviors in prelicensure interprofessional education (IPE) lack validity and reliability data. No individual behavioral assessment instrument met all standards of the Quality Appraisal of Interprofessional Learning Scales (QuAILS) checklist (Oates & Davidson, 2015). The IPA and iSOFT instruments provided the most substantial validity and reliability evidence. Future validation research studies of interprofessional education (IPE) behavioral instruments that evaluate interprofessional professionalism (IPP) domains are needed in nursing education.

Effectiveness of classroom response systems within an active learning environment.

In nursing education, the inclusion of pedagogical tools is necessary to transform Millennial classrooms. One such pedagogical tool currently offered is classroom response systems (CRS). The purpose of this study was to evaluate the effectiveness of CRS as a pedagogical tool in improving nursing students' examination performance within an active learning environment. A pretest-posttest design was used to determine whether there was a relationship between the use of CRS (independent variable) and nursing students' examination performance in a first-year Professional Practice course (dependent variable). Paired t tests revealed no greater improvement in posttest scores. Therefore, the use of CRS technology was not effective in increasing nursing students' examination scores in the Professional Practice course. Additional research is needed to provide adequate understanding of the effectiveness of CRS within the nursing education classroom.

A Theory for Prelicensure Nursing Student Satisfaction With Clinical Learning Experiences: An Integrative Review.

The satisfaction of prelicensure nursing students is a prominent and essential component of programmatic outcome data for accreditation agencies and ongoing program improvement. Nursing student satisfaction correlates with student retention, graduation rates, and future employment and can assist nurse educators in determining if supportive clinical experiences exist. However, nursing students report moderate-to-high levels of clinical stress within clinical environments, impacting both satisfaction and future role preparation. Additional research is necessary regarding prelicensure nursing student satisfaction within their clinical environments, yet a theoretical gap exists to guide such future research. The purpose of this integrative review was twofold. First, perform an integrative review to explore factors associated with prelicensure undergraduate nursing student satisfaction in clinical learning experiences. Second, provide a theory to guide future research regarding the topic.