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.

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.

Connecting the Dots of Care: A pilot study linking Aboriginal and/or Torres Strait Islander peoples with diabetes care in hospital, using hospital pharmacists.

Background: Diabetes is common among Aboriginal and/or Torres Strait Islander peoples, yet often undetected in hospital. Objective: To identify how urban hospital pharmacists can detect if Aboriginal and/or Torres Strait Islander patients have diabetes or a higher chance of getting diabetes. Methods: A multi-methods study used data from patients, and researcher field notes. Aboriginal and/or Torres Strait Islander peoples admitted to hospital over 12-weeks (July-October 2021) were prospectively identified from admissions lists. A hospital pharmacist-researcher visited eligible patients. Consenting participants had their blood glucose and HbA1c checked. Participants with HbA1c > 6.5% (no known diabetes) or 7% (known diabetes) were referred for endocrinology review during their stay. Test results and resultant diabetes plan were shared with their general practitioner. Two days after discharge, participants were called to gauge views on their hospital-based diabetes care. Barcode technology recorded pharmacist time. Voice-recorded field notes were thematically analysed. Ethics approval was obtained. Results: Seventy-two patients were eligible for inclusion, 67/72 (93%) consented to take part. Sixty-one (91%) patients returned a HbA1c < 6.5, of which, 4/61 (6.5%) returned a HbA1c, 6-6.4. They were contacted to yarn about diabetes prevention. Six of the 67 (9%) qualified for endocrine review, 5 had known diabetes, one newly diagnosed. None were known to endocrinology. All participants telephoned were satisfied with their hospital-based diabetes care. Pharmacist time for initial introductory yarn, consenting process, organisation of HbA1c and results discussion was 20 min or 40 min if referred for endocrine review. Field notes guided understanding of service implementation. Conclusion: This novel pharmacist-led diabetes screening service for Aboriginal and/or Torres Strait Islander peoples appeared to provide a unique opportunity for screening and referral links in a holistic way. Future research is required to test this model by upscaling to include more pharmacists and other chronic disease screening and referral pathways.

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.

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.

Clinical Stress and Clinical Performance in Prelicensure Nursing Students: A Systematic Review.

BACKGROUND: Stress within clinical learning environments often has been associated with nursing education. However, in the past decade, the perceived stress levels of prelicensure nursing students have not only been sustained, they have actually increased. Increased and sustained stress levels negatively affect nursing students' perceptions of their competence, confidence, and ultimately, their clinical performance. METHOD: A systematic review of the relationship between nursing students' perceived clinical stress and perceived clinical performance was conducted following PRISMA guidelines. RESULTS: The review highlighted what is currently known about the relationship between perceived clinical stress in prelicensure nursing students and perceived clinical performance, providing implications for future research in clinical education. Three main themes were identified: nursing student gender, academic year, and clinical skill preparation. CONCLUSION: Future research with rigorous methodological designs is necessary to examine the relationship between perceived clinical stress in prelicensure nursing students and perceived clinical performance. [J Nurs Educ. 2023;62(1):36-41.].

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).

Carbonate weathering, phosphate fertilizer, and hydrologic controls on dissolved uranium in rivers in the US Corn Belt: Disentangling seasonal geogenic- and fertilizer-derived sources.

Soil and bedrock weathering and phosphate (P) fertilizers may both contribute to the uranium (U) load of rivers in agricultural regions, but controls over their relative influence are not well known. This study investigates the U sources to rivers in Ohio, United States, part of the Eastern Corn Belt in the Mississippi River watershed. We present a regional picture of seasonal U sources to rivers based on four analyses: 1) a spatial analysis of legacy soil and water data, 2) new measurements of U and carbonate weathering products from rivers at 50 locations across the state collected seasonally over two years, 3) a weekly time series with additional 234U/238U (n = 5) and 87Sr/86Sr (n = 5) measurements from an agricultural river, and 4) a mass-balance approach to U addition to the landscape based on reported P fertilizer use. Uranium concentrations in surface waters collected statewide ranged 0.1-21 nM (n = 132), with significantly higher concentrations in the glaciated agricultural portion of the state (mean = 7.3 nM; n = 105) than the non-glaciated portion (mean = 2.0 nM; n = 24). Concentrations in the glaciated region were highest during the spring and summer and decreased during baseflow. In the time-series, concentrations were ~7 nM during baseflow and ~14 nM during intermediate seasonal discharge conditions, indicating a second more surficial endmember source of U in addition to bedrock weathering that is well correlated with other carbonate weathering products. Systematic increases in 87Sr/86Sr and decreases in 234U/238U with increasing discharge confirm a changing source of carbonate and U weathering and a third surficial endmember during high discharge events. Our mass balance approach and geochemical analysis suggest that elevated U concentrations are the result of carbonate weathering deep in the soil column during elevated seasonal flow. Further work on U dynamics in agricultural rivers is required to understand mechanism controlling seasonal changes in U concentrations and 234U/238U in downstream rivers and U flux.

Clinical yarning with Aboriginal and/or Torres Strait Islander peoples-a systematic scoping review of its use and impacts.

OBJECTIVES: To explore how clinical yarning has been utilised as a health intervention for Aboriginal and/or Torres Strait Islander peoples and if there are any reported impacts yarning might have on health outcomes. STUDY DESIGN: Systematic scoping review of published literature. DATA SOURCES: A one-word search term "yarning" was applied in Scopus, EMBASE, CINAHL, MEDLINE, International Pharmaceutical Abstracts, Australian Public Affairs Information Service-Health, and the Aboriginal and/or Torres Strait Islander Health Bibliography databases. Databases were searched from inception to May 20, 2020. STUDY SELECTION: Studies were included where clinical yarning had been used as a health intervention. Inclusion and exclusion criteria were developed and applied according to PRISMA systematic and scoping review reporting methods. DATA SYNTHESIS: A total of 375 manuscripts were found from the initial data search. After removal of duplicates and removal of manuscripts based on abstract review, a total of 61 studies underwent full-text review. Of these, only five met the inclusion criteria of utilising yarning as a clinical intervention. Four of these studies described consumer self-reported health outcomes, with only one study looking at improvements in objective physiological health outcomes. CONCLUSIONS: Whilst clinical yarning may be a culturally appropriate intervention in healthcare, there are limited studies that have measured the impact of this intervention. Further research may be needed to ascertain the true benefits of this intervention.

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 ciprofloxacin in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study).

INTRODUCTION: This study aimed to describe the pharmacokinetics (PK) of ciprofloxacin in critically ill patients receiving ECMO and recommend a dosing regimen that provides adequate drug exposure. METHODS: Serial blood samples were taken from ECMO patients receiving ciprofloxacin. Total ciprofloxacin concentrations were measured by chromatographic assay and analysed using a population PK approach with Pmetrics®. Dosing simulations were performed to ascertain the probability of target attainment (PTA) represented by the area under the curve to minimum inhibitory concentration ratio (AUC0-24/MIC) ≥ 125. RESULTS: Eight patients were enrolled, of which three received concurrent continuous venovenous haemodiafiltration (CVVHDF). Ciprofloxacin was best described in a two-compartment model with total body weight and creatinine clearance (CrCL) included as significant predictors of PK. Patients not requiring renal replacement therapy generated a mean clearance of 11.08 L/h while patients receiving CVVHDF had a mean clearance of 1.51 L/h. Central and peripheral volume of distribution was 77.31 L and 90.71 L, respectively. ECMO variables were not found to be significant predictors of ciprofloxacin PK. Dosing simulations reported that a 400 mg 8 -hly regimen achieved > 72% PTA in all simulated patients with CrCL of 30 mL/min, 50 mL/min and 100 mL/min and total body weights of 60 kg and 100 kg at a MIC of 0.5 mg/L. CONCLUSION: Our study reports that established dosing recommendations for critically ill patients not on ECMO provides sufficient drug exposure for maximal ciprofloxacin activity for ECMO patients. In line with non-ECMO critically ill adult PK studies, higher doses and therapeutic drug monitoring may be required for critically ill adult patients on ECMO.

Population Pharmacokinetics and Dosing Simulations of Ceftriaxone in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (An ASAP ECMO Study).

BACKGROUND: Despite the surge in use of extracorporeal membrane oxygenation (ECMO) in the adult intensive care unit, little guidance is available on the appropriate dosing of antimicrobials in this setting. Ceftriaxone is an antimicrobial with a high affinity to plasma protein, a property identified in the literature as susceptible to sequestration into extracorporeal circuits and hypothesised to require dosage adjustments in this setting. OBJECTIVE: The aim of this study was to describe the pharmacokinetics of ceftriaxone and identify the best dosing regimen for critically ill adult patients receiving ECMO. METHODS: Serial blood samples were taken from patients receiving both ECMO and ceftriaxone. Total and unbound drug concentrations were measured in plasma by chromatographic assay and analysed using a population pharmacokinetic approach with Pmetrics®. Dosing simulations were performed to identify the optimal dosing strategy: 60 and 100% of time with free (unbound) drug concentration exceeding the minimum inhibitory concentration (fT>MIC). RESULTS: In total, 14 patients were enrolled, of which three were receiving renal replacement therapy (RRT). Total and unbound ceftriaxone was best described in a two-compartment model with total body weight, serum albumin concentrations, creatinine clearance (CrCL), and the presence of RRT included as significant predictors of pharmacokinetics. Patients not on RRT generated a mean renal clearance of 0.90 L/h, non-renal clearance of 0.33 L/h, and central volume of distribution of 7.94 L. Patients on RRT exhibited a mean total clearance of 1.18 L/h. ECMO variables were not significant predictors of ceftriaxone pharmacokinetics. Steady-state dosing simulations found that dosages of 1 g every 12 h and 2 g every 24 h achieved >90% probabilities of target attainment in patients with CrCL of 0 mL/min with RRT and 30 and 100 mL/min and various serum albumin concentrations (17 and 26 g/L). CONCLUSIONS: Dosing recommendations for critically ill adult patients not on ECMO appear to be sufficient for patients on ECMO. Patients exhibiting augmented renal clearance (> 130 mL/min) or treatment of less susceptible pathogens may require higher doses, which requires further investigation.

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.).

Population pharmacokinetics of cefepime in critically ill patients receiving extracorporeal membrane oxygenation (an ASAP ECMO study).

OBJECTIVES: This study aimed to describe the population pharmacokinetics (PK) of cefepime during extracorporeal membrane oxygenation (ECMO) and through dosing simulations, identify a maximally effective and safe dosing strategy. METHODS: Serial cefepime plasma concentrations were measured in patients on ECMO, and data were analysed using a population PK approach with Pmetrics®. Dosing simulations were used to identify the optimal dosing strategy that achieved target trough concentrations (Cmin) of 8-20 mg/L. Six patients were enrolled, of which one was receiving renal replacement therapy. Cefepime was best described in a two-compartment model, with total body weight and creatinine clearance (CrCL) as significant predictors of PK parameters. The mean clearance and central volume of distribution were 2.42 L/h and 15.09 L, respectively. RESULTS: Based on simulations, patients with CrCL of 120 mL/min receiving 1 g 8-hourly dosing achieved a 40-44% probability of efficacy (Cmin > 8 mg/L) and 1-6% toxicity (Cmin > 20 mg/L). Patients with CrCL 30 mL/min and 65 mL/min receiving 1 g 12-hourly dosing achieved an 84-92% and 46-53% probability of efficacy and 8-44% and 1-8% probability of toxicity, respectively. Simulations demonstrated a lower probability of efficacy and higher probability of toxicity with decreasing patient weight. CONCLUSION: This study reported reduced cefepime clearance in patients receiving ECMO, resulting in an increased risk of cefepime toxicity. To avoid drug accumulation, modified dosing regimens should be used in critically ill patients on ECMO. Clinicians should adopt therapeutic drug monitoring when treating less susceptible organisms and in patients with reduced renal clearance on ECMO.

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.

Doctoral nursing students' lived experience of virtual mentoring in the United States.

AIM/OBJECTIVE: To explore the lived experiences of research-focused doctoral students and graduates who participated in a virtual mentoring program. BACKGROUND: Faculty mentoring of doctoral nursing students is at a critical juncture, as a lack of mentors and experienced researchers exists to assist the next generation of nurse educators. Additionally, few nursing schools offer the mentoring support necessary to further the research trajectories of doctorally prepared nurse educators. DESIGN: Descriptive phenomenological approach METHODS: Semi-structured interviews RESULTS: Data analysis revealed four themes: formalizing the mentoring, building the relationship, adapting to the doctoral role, and mentoring others. CONCLUSIONS: As online doctoral nursing educational programs abound, virtual mentoring programs are essential to support doctoral nursing education and doctoral students. However, to date, limited research exists regarding formalized virtual mentoring programs in doctoral nursing education.

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.