An overview and policy implications of national nurse identifier systems: A call for unity and integration.

There is a clear and growing need to be able record and track the contributions of individual registered nurses (RNs) to patient care and patient care outcomes in the US and also understand the state of the nursing workforce. The National Academies of Sciences, Engineering, and Medicine report, The Future of Nursing 2020-2030: Charting a Path to Achieve Health Equity (2021), identified the need to track nurses' collective and individual contributions to patient care outcomes. This capability depends upon the adoption of a unique nurse identifier and its implementation within electronic health records. Additionally, there is a need to understand the nature and characteristics of the overall nursing workforce including supply and demand, turnover, attrition, credentialing, and geographic areas of practice. This need for data to support workforce studies and planning is dependent upon comprehensive databases describing the nursing workforce, with unique nurse identification to support linkage across data sources. There are two existing national nurse identifiers- the National Provider Identifier and the National Council of State Boards of Nursing Identifier. This article provides an overview of these two national nurse identifiers; reviews three databases that are not nurse specific to understand lessons learned in the development of those databases; and discusses the ethical, legal, social, diversity, equity, and inclusion implications of a unique nurse identifier.

Sex-Specific Platelet Activation Through Protease-Activated Receptors Reverses in Myocardial Infarction.

OBJECTIVE: The platelet phenotype in certain patients and clinical contexts may differ from healthy conditions. We evaluated platelet activation through specific receptors in healthy men and women, comparing this to patients presenting with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. Approach and Results: We identified independent predictors of platelet activation through certain receptors and a murine MI model further explored these findings. Platelets from healthy women and female mice are more reactive through PARs (protease-activated receptors) compared with platelets from men and male mice. Multivariate regression analyses revealed male sex and non-ST-segment-elevation myocardial infarction as independent predictors of enhanced PAR1 activation in human platelets. Platelet PAR1 signaling decreased in women and increased in men during MI which was the opposite of what was observed during healthy conditions. Similarly, in mice, thrombin-mediated platelet activation was greater in healthy females compared with males, and lesser in females compared with males at the time of MI. CONCLUSIONS: Sex-specific signaling in platelets seems to be a cross-species phenomenon. The divergent platelet phenotype in males and females at the time of MI suggests a sex-specific antiplatelet drug regimen should be prospectively evaluated.

Characteristics of family nurse practitioners and their preparation for practice in rural vs urban employment settings.

BACKGROUND: Policymakers are increasingly interested in using nurse practitioners to provide health care to rural populations, yet little is known about their characteristics and preparation for independent practice. METHODS: We obtained data from the 2018 National Sample Survey of Registered Nurses and compared characteristics of family nurse practitioners (FNPs) employed in rural areas versus those employed in non-rural areas. Regression analysis was used to determine the relationship between the outcome variable of interest, preparation for practice and other covariates. FINDINGS: FNPs practicing in a rural setting felt less prepared for independent practice than their counterparts in non-rural settings except for those prepared with a doctoral degree. DISCUSSION: The majority of FNPs working in rural areas believed they were not as well prepared for independent practice. Because rural FNPs often practice autonomously and without medical back up, nursing educators need to educate FNPs with the skills and knowledge necessary to practice effectively in rural settings.

Physician and nurse practitioner perceptions of social worker and community health worker roles in primary care practices caring for frail elders: Insights for social work.

Social workers (SW) and community health workers (CHW) have emerged as key workforce personnel in efforts to care for elders in the U.S. However, little is known about the presence and roles of SW and CHW in primary care practices. This paper presents findings from a nationally representative survey of geriatrics and primary care practices. Physician and nurse practitioner clinicians were randomly selected within practices, stratifying by practice staffing and presence/absence of geriatric clinicians; our final sample for this analysis included 341 practices. Key findings include: reported challenges in meeting the social service needs of elders, underutilization of SW, and fuller utilization of social work competencies in practices in which both SW and CHW were present. These findings offer a unique perspective of SW on interprofessional teams and have implications for the future of the profession.

The Cytotoxic Natural Product Vioprolide†A Targets Nucleolar Protein 14, Which Is Essential for Ribosome Biogenesis.

Novel targets are needed for treatment of devastating diseases such as cancer. For decades, natural products have guided innovative therapies by addressing diverse pathways. Inspired by the potent cytotoxic bioactivity of myxobacterial vioprolides A-D, we performed in-depth studies on their mode of action. Based on its prominent potency against human acute lymphoblastic leukemia (ALL) cells, we conducted thermal proteome profiling (TPP) and deciphered the target proteins of the most active derivative vioprolide A (VioA) in Jurkat cells. Nucleolar protein 14 (NOP14), which is essential in ribosome biogenesis, was confirmed as a specific target of VioA by a suite of proteomic and biological follow-up experiments. Given its activity against ALL cells compared to healthy lymphocytes, VioA exhibits unique therapeutic potential for anticancer therapy through a novel mode of action.

Dmpk gene deletion or antisense knockdown does not compromise cardiac or skeletal muscle function in mice.

Myotonic dystrophy type 1 (DM1) is a genetic disorder in which dominant-active DM protein kinase (DMPK) transcripts accumulate in nuclear foci, leading to abnormal regulation of RNA processing. A leading approach to treat DM1 uses DMPK-targeting antisense oligonucleotides (ASOs) to reduce levels of toxic RNA. However, basal levels of DMPK protein are reduced by half in DM1 patients. This raises concern that intolerance for further DMPK loss may limit ASO therapy, especially since mice with Dmpk gene deletion reportedly show cardiac defects and skeletal myopathy. We re-examined cardiac and muscle function in mice with Dmpk gene deletion, and studied post-maturity knockdown using Dmpk-targeting ASOs in mice with heterozygous deletion. Contrary to previous reports, we found no effect of Dmpk gene deletion on cardiac or muscle function, when studied on two genetic backgrounds. In heterozygous knockouts, the administration of ASOs reduced Dmpk expression in cardiac and skeletal muscle by > 90%, yet survival, electrocardiogram intervals, cardiac ejection fraction and muscle strength remained normal. The imposition of cardiac stress by pressure overload, or muscle stress by myotonia, did not unmask a requirement for DMPK. Our results support the feasibility and safety of using ASOs for post-transcriptional silencing of DMPK in muscle and heart.

Biosynthesis and Heterologous Production of Vioprolides: Rational Biosynthetic Engineering and Unprecedented 4-Methylazetidinecarboxylic Acid Formation.

Vioprolides are a promising class of anticancer and antifungal lead compounds produced by the myxobacterium Cystobacter violaceus Cb vi35. Previously nothing had been reported about their biosynthesis, including the origin of the unusual 4-methylazetidinecarboxylic acid (MAZ) moiety. We describe the vioprolide biosynthetic gene cluster and solve the production obstacle by expression in three heterologous hosts. Starting from unstable production in the wild type at the single-digit mg L-1 scale, we developed a stable host that eventually allowed for yields of up to half a gram per liter in fermenters. Gene inactivations coupled with isotope feeding studies identified an S-adenosylmethionine (SAM)-dependent enzyme and a methyltransferase as being responsible for the generation of the MAZ building block by a proposed mechanism unprecedented in bacteria. Furthermore, nonnatural vioprolide derivatives were generated via rational genetic engineering.

The Impact of Using Mid-level Providers in Face-to-Face Primary Care on Health Care Utilization.

BACKGROUND: There has been concern that greater use of nurse practitioners (NP) and physician assistants (PA) in face-to-face primary care may increase utilization and spending. OBJECTIVE: To evaluate a natural experiment within Kaiser Permanente in Georgia in the use of NP/PA in primary care. STUDY DESIGN: From 2006 through early 2008 (the preperiod), each NP or PA was paired with a physician to manage a patient panel. In early 2008, NPs and PAs were removed from all face-to-face primary care. Using the 2006-2010 data, we applied a difference-in-differences analytic approach at the clinic level due to patient triage between a NP/PA and a physician. Clinics were classified into 3 different groups based on the percentage of visits by NP/PA during the preperiod: high (over 20% in-person primary care visits attended by NP/PAs), medium (5%-20%), and low (<5%) NP/PA model clinics. MEASURES: Referrals to specialist physicians; emergency department visits and inpatient admissions; and advanced diagnostic imaging services. RESULTS: Compared with the low NP/PA model, the high NP/PA model and the medium NP/PA model were associated with 4.9% and 5.1% fewer specialist referrals, respectively (P<0.05 for both estimates); the high NP/PA model and the medium NP/PA model also showed fewer hospitalizations and emergency department visits and fewer advanced diagnostic imaging services, but none of these was statistically significant. CONCLUSIONS: We find no evidence to support concerns that under a physician's supervision, NPs and PAs increase utilization and spending.

How fast will the registered nurse workforce grow through 2030? Projections in nine regions of the country.

BACKGROUND: After an unprecedented increase in nursing school enrollment and graduates in the past 10 years, projected shortages of nurses have been erased at a national level. However, nursing markets are local, and an uneven distribution of health care providers of all types is a longstanding feature of health care in the United States. PURPOSE: The purpose of this study was to understand how the outlook for future registered nurse (RN) supply varies regionally across the United States. METHODS: We apply our nursing supply model to the nine U.S. Census Divisions to produce separate supply forecasts for each region. DISCUSSION: We find dramatic differences in expected future growth of the nursing workforce across U.S. regions. These range from zero expected growth in the number of RNs per capita in New England and in the Pacific regions between 2015 and 2030 to 40% growth in the East South Central region (Mississippi, Alabama, Tennessee, Kentucky) and in the West South Central region (Texas, Oklahoma, Arkansas, Louisiana). CONCLUSION: Assuming growth in the demand for RNs per population, some regions of the United States are expected to face shortfalls in their nursing workforce if recent trends do not change.

Solving the Puzzle of One-Carbon Loss in Ripostatin Biosynthesis.

Ripostatin is a promising antibiotic that inhibits RNA polymerase by binding to a novel binding site. In this study, the characterization of the biosynthetic gene cluster of ripostatin, which is a peculiar polyketide synthase (PKS) hybrid cluster encoding cis- and trans-acyltransferase PKS genes, is reported. Moreover, an unprecedented mechanism for phenyl acetic acid formation and loading as a starter unit was discovered. This phenyl-C2 unit is derived from phenylpyruvate (phenyl-C3) and the mechanism described herein explains the mysterious loss of one carbon atom in ripostatin biosynthesis from the phenyl-C3 precursor. Through in vitro reconstitution of the whole loading process, a pyruvate dehydrogenase like protein complex was revealed that performs thiamine pyrophosphate dependent decarboxylation of phenylpyruvate to form a phenylacetyl-S-acyl carrier protein species, which is supplied to the subsequent biosynthetic assembly line for chain extension to finally yield ripostatin.

Recent Changes in the Number of Nurses Graduating from Undergraduate and Graduate Programs.

Since the 1970s, a number of initiatives have attempted to increase the proportion of nursing graduates with a baccalaureate degree, but with little national effect. Now market forces, health reforms, and an Institute of Medicine report (2011) have combined to transform the educational composition of the nursing workforce. Today, there are considerably more graduates of baccalaureate nursing programs than associate degree programs. The educational transformation of the nursing workforce is not limited to baccalaureate education but includes the rapidly increasing numbers of registered nurses who have earned graduate degrees. These changes in nursing education are increasing the readiness of nursing professionals to capitalize on new opportunities, overcome challenges, and take on new roles and responsibilities as the nation's health care delivery and payments systems evolve in coming years.

Scn1b deletion leads to increased tetrodotoxin-sensitive sodium current, altered intracellular calcium homeostasis and arrhythmias in murine hearts.

KEY POINTS: Na(+) current (INa) results from the integrated function of a molecular aggregate (the voltage-gated Na(+) channel complex) that includes the ß subunit family. Mutations or rare variants in Scn1b (encoding the ß1 and ß1B subunits) have been associated with various inherited arrhythmogenic syndromes, including Brugada syndrome and sudden unexpected death in patients with epilepsy. We used Scn1b null mice to understand better the relation between Scn1b expression, and cardiac electrical function. Loss of Scn1b caused, among other effects, increased amplitude of tetrodotoxin-sensitive INa, delayed after-depolarizations, triggered beats, delayed Ca(2+) transients, frequent spontaneous calcium release events and increased susceptibility to polymorphic ventricular arrhythmias. Most alterations in Ca(2+) homeostasis were prevented by 100 nM tetrodotoxin. We propose that life-threatening arrhythmias in patients with mutations in Scn1b, a gene classically defined as ancillary to the Na(+) channel α subunit, can be partly consequent to disrupted intracellular Ca(2+) homeostasis. ABSTRACT: Na(+) current (INa) is determined not only by the properties of the pore-forming voltage-gated Na(+) channel (VGSC) α subunit, but also by the integrated function of a molecular aggregate (the VGSC complex) that includes the VGSC ß subunit family. Mutations or rare variants in Scn1b (encoding the ß1 and ß1B subunits) have been associated with various inherited arrhythmogenic syndromes, including cases of Brugada syndrome and sudden unexpected death in patients with epilepsy. Here, we have used Scn1b null mouse models to understand better the relation between Scn1b expression, and cardiac electrical function. Using a combination of macropatch and scanning ion conductance microscopy we show that loss of Scn1b in juvenile null animals resulted in increased tetrodotoxin-sensitive INa but only in the cell midsection, even before full T-tubule formation; the latter occurred concurrent with increased message abundance for the neuronal Scn3a mRNA, suggesting increased abundance of tetrodotoxin-sensitive NaV 1.3 protein and yet its exclusion from the region of the intercalated disc. Ventricular myocytes from cardiac-specific adult Scn1b null animals showed increased Scn3a message, prolonged action potential repolarization, presence of delayed after-depolarizations and triggered beats, delayed Ca(2+) transients and frequent spontaneous Ca(2+) release events and at the whole heart level, increased susceptibility to polymorphic ventricular arrhythmias. Most alterations in Ca(2+) homeostasis were prevented by 100 nM tetrodotoxin. Our results suggest that life-threatening arrhythmias in patients with mutations in Scn1b, a gene classically defined as ancillary to the Na(+) channel α subunit, can be partly consequent to disrupted intracellular Ca(2+) homeostasis in ventricular myocytes.

Will the RN Workforce Weather the Retirement of the Baby Boomers?

IMPORTANCE: After forecasts made more than a decade ago suggested dire nursing shortages, enrollment in nursing schools doubled. The implications of this unprecedented change for the nursing workforce have not yet been fully explored. OBJECTIVE: To forecast the size and age distribution of the nursing workforce to the year 2030 and to compare to demand recently projected by the Health Resources and Services Agency. DESIGN: A retrospective cohort analysis of employment trends by birth year and age were used to project age and employment of registered nurses (RNs) through 2030. SETTING: Data on employed RNs from the United States Bureau of the Census Current Population Survey (1979-2000, N=72,222) and American Community Survey (2001-2013, N=342,712). PARTICIPANTS: RNs between the ages of 23 and 69 years. MAIN OUTCOME MEASURE: Annual full-time equivalent (FTE) employment of RNs in total and by single year of age. RESULTS: Annual retirements from the nursing workforce will accelerate from 20,000 a decade ago to near 80,000 in the next decade as baby boomer RNs continue to age. We project that this outflow will be more than offset by continued strong entry of new RNs into the workforce. Overall, we project that the registered nursing workforce will increase from roughly 2.7 million FTE RNs in 2013 to 3.3 million in 2030. We also find that the workforce will reach its peak average age in 2015 at 44.4. This increase in workforce size, which was not expected in forecasts made a decade ago, is contingent on new entry into nursing continuing at its current rate. Even then, supply would still fall short of demand as recently projected by the Health Resources and Services Agency in the year 2025 by 128,000 RNs (4%). CONCLUSIONS: The unexpected surge of entry of new RNs into the workforce will lead to continued net growth of the nursing workforce, both in absolute FTE and FTE per capita. While this growth may not be sufficient to meet demand, such projections are uncertain in the face of a rapidly evolving health care delivery system.

Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor.

The natural history of HIV-1 infection is highly variable in different individuals, spanning from a rapidly progressive course to a long-term asymptomatic infection. A major determinant of the pace of disease progression is the in vivo level of HIV-1 replication, which is regulated by a complex network of cytokines and chemokines expressed by immune and inflammatory cells. The chemokine system is critically involved in the control of HIV-1 replication by virtue of the role played by specific chemokine receptors, most notably CCR5 and CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained within the α-granules of platelets, is a broad-spectrum inhibitor of HIV-1 infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits infection by the majority of primary HIV-1 isolates regardless of their coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral phenotype specificity, blockade of HIV-1 infection occurs at the level of virus attachment and entry via a unique mechanism that involves direct interaction of CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4-binding site. The identification of a platelet-derived chemokine as an endogenous antiviral factor may have relevance for the pathogenesis and treatment of HIV-1 infection.

Dynamic reciprocity of sodium and potassium channel expression in a macromolecular complex controls cardiac excitability and arrhythmia.

The cardiac electrical impulse depends on an orchestrated interplay of transmembrane ionic currents in myocardial cells. Two critical ionic current mechanisms are the inwardly rectifying potassium current (I(K1)), which is important for maintenance of the cell resting membrane potential, and the sodium current (I(Na)), which provides a rapid depolarizing current during the upstroke of the action potential. By controlling the resting membrane potential, I(K1) modifies sodium channel availability and therefore, cell excitability, action potential duration, and velocity of impulse propagation. Additionally, I(K1)-I(Na) interactions are key determinants of electrical rotor frequency responsible for abnormal, often lethal, cardiac reentrant activity. Here, we have used a multidisciplinary approach based on molecular and biochemical techniques, acute gene transfer or silencing, and electrophysiology to show that I(K1)-I(Na) interactions involve a reciprocal modulation of expression of their respective channel proteins (Kir2.1 and Na(V)1.5) within a macromolecular complex. Thus, an increase in functional expression of one channel reciprocally modulates the other to enhance cardiac excitability. The modulation is model-independent; it is demonstrable in myocytes isolated from mouse and rat hearts and with transgenic and adenoviral-mediated overexpression/silencing. We also show that the post synaptic density, discs large, and zonula occludens-1 (PDZ) domain protein SAP97 is a component of this macromolecular complex. We show that the interplay between Na(v)1.5 and Kir2.1 has electrophysiological consequences on the myocardium and that SAP97 may affect the integrity of this complex or the nature of Na(v)1.5-Kir2.1 interactions. The reciprocal modulation between Na(v)1.5 and Kir2.1 and the respective ionic currents should be important in the ability of the heart to undergo self-sustaining cardiac rhythm disturbances.

Doctor of nursing practice by 2015: an examination of nursing schools' decisions to offer a doctor of nursing practice degree.

OBJECTIVES: The American Association of Colleges of Nursing recommends that nursing schools transition their advanced practice registered nurse (APRN) programs to doctor of nursing practice (DNP) programs by 2015. However, most schools have not yet made this full transition. The purpose of this study was to understand schools' decisions regarding the full transition to the DNP. METHODS: Key informant interviews and an online survey of nursing school deans and program directors were performed. DISCUSSION: The vast majority of schools value the DNP in preparing APRNs for the future of the health care system. However, other important factors influence many schools to fully transition or not to the postbaccalaureate DNP, including perceived student and employer demand, issues concerning accreditation and certification, and resource constraints. CONCLUSION: Multiple pathways to becoming an APRN are likely to remain until various factors (e.g., student and employer demand, certification and accreditation issues, and resource constraints) yield a more favorable environment for a full transition to the DNP.