Considerations for open-label randomized clinical trials: Design, conduct, and analysis.

Randomization and blinding are regarded as the most important tools to help reduce bias in clinical trial designs. Randomization is used to help guarantee that treatment arms differ systematically only by treatment assignment at baseline, and blinding is used to ensure that differences in endpoint evaluation and clinical decision-making during the trial arise only from the treatment received and not, for example, the expectation or desires of the people involved. However, given that there are times when it is not feasible or ethical to conduct fully blinded trials, we discuss what can be done to improve a trial, including conducting the trial as if it were a fully blinded trial and maintaining confidentiality of ongoing study results. In this article, we review how best to design, conduct, and analyze open-label trials to ensure the highest level of study integrity and the reliability of the study conclusions.

Food and Drug Administration Public Workshop Summary-Development Considerations of Antifungal Drugs to Address Unmet Medical Need.

Pressing challenges in the treatment of invasive fungal infections (IFIs) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics, clinical trial endpoints, prolonged trial duration, difficulties in patient recruitment, including subpopulations (eg, pediatrics), and heterogeneity of the IFIs. On 4 August 2020, the US Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This article summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development.

An Online Module to Promote Self-Care and Resiliency in Nursing Students.

ABSTRACT: Because the demands of nursing education can impact the physical and mental health of nursing students, the American Association of Colleges of Nursing's revised Essentials require inclusion of self-care and resilience education in nursing curricula. This article describes the development, implementation, and evaluation of a self-care module in a new online undergraduate course. Using the REST mnemonic (relationships, exercise, soul, and transformative thinking), students developed personalized self-care plans for the semester. End-of-course evaluations revealed an increase in self-care activities. The most used activities were exercise, humor, intentional rest, and healthy eating.

FDA Public Workshop Summary-Coccidioidomycosis (Valley Fever): Considerations for Development of Antifungal Drugs.

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development.

US Food and Drug Administration (FDA): Benefit-Risk Considerations for Cefiderocol (Fetroja®).

In November 2019, the Food and Drug Administration (FDA) approved cefiderocol for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by susceptible gram-negative bacteria in adults with limited to no alternative treatment options based on a randomized, double-blind, noninferiority cUTI trial (APEKS-cUTI). In a randomized, open-label trial (CREDIBLE-CR) in patients with cUTI, nosocomial pneumonia, bloodstream infections, or sepsis due to carbapenem-resistant gram-negative bacteria, an increase in all-cause mortality was observed in patients treated with cefiderocol as compared to best available therapy. The cause of the increased mortality was not established, but some deaths were attributed to treatment failure. Preliminary data from a randomized, double-blind trial (APEKS-NP) in patients with nosocomial pneumonia due to carbapenem-susceptible gram-negative bacteria showed a similar rate of mortality as compared to meropenem. We describe the uncertainties and challenges in the interpretation of the CREDIBLE-CR trial and some benefit-risk considerations for the use of cefiderocol in clinical practice. Clinical Trials Registration: NCT02321800.

Using health coaching to improve patients' BP management.

Nurses have unique opportunities to influence patient outcomes and reduce healthcare expenditures. Health coaching is one patient-centered strategy nurses can use to improve the limited health literacy often associated with hypertension. This article describes the use of health coaching to help patients understand their medications and give them the knowledge, skills, and confidence to self-manage their hypertension.

A global database of nitrogen and phosphorus excretion rates of aquatic animals.

Animals can be important in modulating ecosystem-level nutrient cycling, although their importance varies greatly among species and ecosystems. Nutrient cycling rates of individual animals represent valuable data for testing the predictions of important frameworks such as the Metabolic Theory of Ecology (MTE) and ecological stoichiometry (ES). They also represent an important set of functional traits that may reflect both environmental and phylogenetic influences. Over the past two decades, studies of animal-mediated nutrient cycling have increased dramatically, especially in aquatic ecosystems. Here we present a global compilation of aquatic animal nutrient excretion rates. The dataset includes 10,534 observations from freshwater and marine animals of N and/or P excretion rates. These observations represent 491 species, including most aquatic phyla. Coverage varies greatly among phyla and other taxonomic levels. The dataset includes information on animal body size, ambient temperature, taxonomic affiliations, and animal body N:P. This data set was used to test predictions of MTE and ES, as described in Vanni and McIntyre (2016; Ecology DOI: 10.1002/ecy.1582).

Using Machine Learning to Determine a Suitable Patient Population for Anakinra for the Treatment of COVID-19 Under the Emergency Use Authorization.

A randomized, double-blind, placebo-controlled study (SAVEMORE trial) provided data to support an Emergency Use Authorization (EUA) of anakinra in hospitalized adults with positive results of direct severe acute respiratory syndrome-coronavirus 2 viral testing with pneumonia requiring supplemental oxygen (low- or high-flow oxygen) who are at risk of progressing to severe respiratory failure and likely to have an elevated plasma soluble urokinase plasminogen activator receptor (suPAR). Currently, the suPAR assay is not commercially available in the United States. An alternative method was needed to identify patients that best reflect the population in the clinical trial selected based on suPAR level ≥ 6 ng/mL at baseline. A machine learning approach based on data from the SAVEMORE trial was used to develop a scoring rule to identify patients who are likely to have a suPAR level ≥ 6 ng/mL at baseline. External validation of the scoring rule was conducted with data from a different trial (SAVE). This clinical scoring rule with high positive predictive value, high specificity, reasonable sensitivity, and biological relevance is expected to identify patients who are likely to have an elevated suPAR level ≥ 6 ng/mL at baseline. As such, it is included in the EUA to identify patients that fall within the authorized population for whom the known and potential benefits outweigh the known and potential risks of anakinra.

The use of multiple daily injections versus insulin pump therapy for HgbA1c reduction in patients with insulin-dependent type 2 diabetes.

BACKGROUND: More than 35 million Americans live with type 2 diabetes (T2D), resulting in the need for newer strategies and technologies to manage the disease. Insulin pump therapy (IPT) has historically been reserved for type 1 diabetes, although emerging data demonstrates improved glucose outcomes for patients with T2D using IPT. PURPOSE: To measure the change in HgbA1c in patients with T2D after changing therapy from multiple daily injections (MDI) to continuous subcutaneous insulin infusion through IPT. METHODOLOGY: A retrospective comparison study was conducted by reviewing the electronic medical record of patients with T2D, older than 18 years, who had been on multiple daily insulin injections for at least 1 year, followed by IPT for at least 1 year. RESULTS: One hundred seventy-one patients met the inclusion criteria. There was a statistically significant reduction in mean HgbA1c from 9.6% to 7.6%. CONCLUSION: Insulin pump therapy may result in lower HgbA1c levels for T2D not at goal on MDI. IMPLICATIONS: Patients on multiple daily insulin injections who are not at goal should be considered for IPT.

Use of the Rasch Model for Fit Statistics and Rating Scale Diagnosis for the Student Perception Appraisal-Revised.

Background and Purpose: Nursing student retention is essential to meet workforce demands. Jeffrey's Nursing Student Retention Student Perception Appraisal-Revised (SPA-R1) has been used extensively to understand factors that impact retention. Psychometric testing of the SPA-R1 contributes to greater confidence in the instrument's reliability and validity. Methods: Item response theory and specifically, the single parameter polytomous Rasch model was used as a framework for fit statistic testing and rating scale diagnostics of the SPA-R1. This was a secondary analysis of a convenience sample of undergraduate prelicensure nursing students. The setting for the previous study was virtual, and the study period was 2022. Results: The model item characteristic curves for the 27 items of the SPA-R1 have similar shapes and are clustered in proximity. Overall, there are three clusters of items evident in the Rasch standardized residual contrast. The Rasch scale diagnostics indicated that the scale appropriately monotonically increases. However, there is a greater than 5 logit distance between does not apply and severely restricts, between severely restricts and moderately restricts, and between does not restrict or support and moderately supports. These large threshold distances indicate that additional steps in the scale may be warranted. The items cover the mid-range of the amount of retention perceptions; however, there are no items that represent the highest magnitude of the perceived amount of influence on retention. Conclusions: This study contributes further evidence to support the validity and reliability of the SPA-R1. We recommend adding steps to the scale, removing the does not apply response option, and considering scoring by three domains or clusters.

Creating a Primary Care Track in Prelicensure Nursing Education.

BACKGROUND: RNs practicing in primary care (PC) increase access to health care and contribute to better patient outcomes and cost savings, yet undergraduate nursing education traditionally focuses on disease-oriented care. This article describes a curricular track for infusing PC prelicensure programs. METHOD: PC content is threaded across four semesters with targeted assignments and clinical experiences. Providing clinical immersion experiences with practicing RNs as preceptors in community and PC settings is a key component of this initiative. RESULTS: Student feedback has been favorable. Students stated they gained insight to the role of RNs in PC through class assignments and clinical rotations. Graduating seniors were offered employment in PC settings where they completed their practicum clinical rotations. CONCLUSION: The PC track contributes to building a nursing workforce to meet health care demands and promote health equity. Nurse educators interested in infusing PC content throughout the curriculum can adapt this model for all student populations. [J Nurs Educ. 2023;62(3):171-174.].

Improvisation Theater Exercises: A Novel Approach to Teach Communication Skills.

BACKGROUND: Nurse practitioner students need effective communication skills to provide patient-centered care and work in diverse health care teams. Improvisation exercises, adapted from theater training, have been used to improve communication skills with health professions education and can be used in nurse practitioner education. METHOD: Fifty-eight family nurse practitioner students participated in a 2-hour workshop where they learned four improvisation exercises to improve listening skills, observational skills, and the ability to respond in the moment. Students learned the application of these skills for health care conversations. RESULTS: The workshop was well received by the students, and evaluations reflected that students anticipated using the skills in professional practice and personal communications. CONCLUSION: Improvisation exercises can be used in nursing education to teach communication skills. [J Nurs Educ. 2021;60(2):116-119.].

New NP job search experience: Opportunities and obstacles.

ABSTRACT: This descriptive study investigated new NPs' job search experience including the job search process, employment negotiation, and compensation. The majority of new graduates found a job through networking within 3 months in a specialty practice or family medicine. Lack of experience and few available positions were employment obstacles.

DNP student mentorship: Empowering students and nurse practitioner organizations.

NP organizations can complement academic programs by providing DNP students with experiential learning and mentorship. This article focuses on a regional NP organization that provided mentoring to DNP students who joined their leadership board. Students gained leadership, advocacy, policy, and advanced practice experience, and the organization experienced growth and innovation.

Preparing students to be ready for practice: An innovative approach to teaching advanced physical assessment skills online.

Distance graduate nursing education has been expanding. Although many didactic courses are taught through an online platform, there are often challenges to providing skill-based courses, such as advanced physical assessment, through an online format. To prepare and assess advanced practice nursing students on their clinical knowledge and physical assessment skills, an online course was developed using multisource feedback and videography. Students used videography to record themselves as they conducted physical assessments on a volunteer patient. Students then critiqued their own video, critiqued two of their colleagues' videos, and the final critiques of the videos were conducted by faculty. All students were expected to perform and pass a complete physical examination on a standardize patient as their final examination. The final scores of the students learning through the online course were equivalent to the scores achieved by the students in the traditional face-to-face physical assessment course.

GABAA receptor availability is not altered in adults with autism spectrum disorder or in mouse models.

Preliminary studies have suggested that γ-aminobutyric acid type A (GABAA) receptors, and potentially the GABAA α5 subtype, are deficient in autism spectrum disorder (ASD). However, prior studies have been confounded by the effects of medications, and these studies did not compare findings across different species. We measured both total GABAA and GABAA α5 receptor availability in two positron emission tomography imaging studies. We used the tracer [11C]flumazenil in 15 adults with ASD and in 15 control individuals without ASD and the tracer [11C]Ro15-4513 in 12 adults with ASD and in 16 control individuals without ASD. All participants were free of medications. We also performed autoradiography, using the same tracers, in three mouse models of ASD: the Cntnap2 knockout mouse, the Shank3 knockout mouse, and mice carrying a 16p11.2 deletion. We found no differences in GABAA receptor or GABAA α5 subunit availability in any brain region of adults with ASD compared to those without ASD. There were no differences in GABAA receptor or GABAA α5 subunit availability in any of the three mouse models. However, adults with ASD did display altered performance on a GABA-sensitive perceptual task. Our data suggest that GABAA receptor availability may be normal in adults with ASD, although GABA signaling may be functionally impaired.

Validation of bioimpedance spectroscopy to assess acute changes in hydration status.

PURPOSE: To validate bioimpedance spectroscopy (BIS) as a field method for measuring small, acute changes in extracellular water (ECW) during a fluid fast/rehydration manipulation. METHODS: Seventeen young adults (15 female, 2 male) participated in a 4-d fluid fast/rehydration protocol designed to induce acute changes in ECW. ECW change (DeltaECW), measured by bioimpedance spectroscopy (BIS-DeltaECW), was compared with DeltaECW, measured by bromide dilution (Br-DeltaECW), and change in body weight (DeltaBW). RESULTS: Regardless of hydration status, BIS-DeltaECW and Br-DeltaECW were similar; during dehydration, the mean difference between these two methods was 0.16 kg (P=0.61), and during rehydration, the mean difference was 0.58 kg (P=0.06). Assuming that DeltaECW=DeltaBW, DeltaECW as estimated from DeltaBW differed significantly from Br-DeltaECW, but not from BIS-DeltaECW. In addition, BIS-DeltaECW correlated significantly with DeltaBW (r=0.57 and 0.65 during dehydration and rehydration, respectively). However, the magnitude of DeltaECW impacted the accuracy of BIS-DeltaECW because BIS measures tended to overestimate DeltaECW at values between 0.0 and 1.0 kg and to underestimate changes at values above 1.0 kg. CONCLUSION: These findings suggest that BIS provides an accurate estimate of DeltaECW compared with bromide dilution during short-term changes in hydration.