Future advancement of health care through standardized nursing terminologies: reflections from a Friends of the National Library of Medicine workshop honoring Virginia K. Saba.

OBJECTIVE: To honor the legacy of nursing informatics pioneer and visionary, Dr. Virginia Saba, the Friends of the National Library of Medicine convened a group of international experts to reflect on Dr. Saba's contributions to nursing standardized nursing terminologies. PROCESS: Experts led a day-and-a-half virtual update on nursing's sustained and rigorous efforts to develop and use valid, reliable, and computable standardized nursing terminologies over the past 5 decades. Over the course of the workshop, policymakers, industry leaders, and scholars discussed the successful use of standardized nursing terminologies, the potential for expanded use of these vetted tools to advance healthcare, and future needs and opportunities. In this article, we elaborate on this vision and key recommendations for continued and expanded adoption and use of standardized nursing terminologies across settings and systems with the goal of generating new knowledge that improves health. CONCLUSION: Much of the promise that the original creators of standardized nursing terminologies envisioned has been achieved. Secondary analysis of clinical data using these terminologies has repeatedly demonstrated the value of nursing and nursing's data. With increased and widespread adoption, these achievements can be replicated across settings and systems.

A double-blind, randomized, placebo-controlled trial of suvorexant for the treatment of vasomotor symptom-associated insomnia disorder in midlife women.

STUDY OBJECTIVES: The neuropeptide orexin promotes wakefulness, modulates thermoregulation, increases after menopause, and is normalized in women receiving estrogen therapy, suggesting a role for orexin antagonism as a treatment for the vasomotor symptom (VMS)-associated insomnia disorder. We tested the efficacy of the dual orexin receptor antagonist suvorexant for chronic insomnia related to nighttime VMS. METHODS: In a double-blind, placebo-controlled trial, 56 women with chronic insomnia associated with nighttime VMS, Insomnia Severity Index (ISI) scores ≥15, and >30 min of diary-rated wake after sleep-onset (WASO) were randomized to receive oral suvorexant 10-20 mg (n = 27) or placebo (n = 29) nightly for 4 weeks. Analysis of within-person change in ISI was adjusted for baseline ISI and race. RESULTS: Mean baseline ISI scores were 18.1 (95% CI, 16.8 to 19.4) and 18.3 (95% CI, 17.2 to 19.5) in the suvorexant and placebo groups, respectively (p = .81). The average 4-week ISI within-person decrease from baseline was greater on suvorexant (-8.1 [95% CI, -10.2 to -6.0]) compared to placebo (-5.6 [95% CI, -7.4 to -3.9], p = .04). Compared to placebo, nighttime diary-rated VMS frequency was significantly reduced with suvorexant (p < .01). While diary-rated WASO and total sleep time trended toward improvement on suvorexant, findings were not significant after adjustment for multiple comparisons. Daytime VMS and other sleep-related outcomes did not differ between groups. Suvorexant was well tolerated. CONCLUSION: These results suggest that suvorexant is likely a well-tolerated and efficacious treatment for VMS-associated insomnia disorder and reduces nighttime VMS. Antagonism of orexin receptors could provide a novel therapeutic option for midlife women with VMS-associated chronic insomnia. CLINICAL TRIAL INFORMATION: Efficacy of Suvorexant in the Treatment of Hot Flash-associated Insomnia, https://clinicaltrials.gov/ct2/show/NCT03034018, ClinicalTrials.gov Identifier: NCT03034018.

Applying the Nursing Ecosystem Concept to Developing Strategic Innovation and Entrepreneurial Leadership for Valued Patient Care.

Research confirms entrepreneurial leadership encourages entrepreneurial behaviour and an entrepreneurial culture supports the development of 'entrepreneurial mindset'. Nurses implementing and optimizing information technology need to work with numerous stakeholders that collectively make up their ecosystem. Indeed, nurses with an entrepreneurial mindset increase their ability to sense opportunities and mobilize the resources and knowledge required to seek' informatics' opportunities to deliver patient centred care across the whole ecosystem.

Hypothalamic-pituitary-adrenal axis, subjective, and thermal stress responses in midlife women with vasomotor symptoms.

OBJECTIVE: Dysregulated responses to experimental stress paradigms may indicate exposure to chronic stress. Vasomotor symptoms (VMS) are linked with diminished quality of life and psychological stress, but induced stress responsivity has received limited investigation. We examined whether women with and without VMS differ in their evoked hypothalamic-pituitary-adrenal axis, subjective, hemodynamic, and thermal stress responses. METHODS: A total of 37 midlife women (27 VMS+; 10 VMS-) completed 2 experimental stress paradigms: (1) Montreal Imaging Stress Task (MIST; computerized social-evaluative stressor) and (2) Quantitative Sensory Testing (QST; thermal stress task). Responses on a five-domain (range 0-50) Visual Analog Scale, salivary cortisol (hypothalamic-pituitary-adrenal axis), and hemodynamic indices (blood pressure, heart rate) were measured before and after each task to compare within-person change between groups. Thermal sensitivity was assessed on the QST. RESULTS: On the MIST, the VMS+ group showed a smaller cortisol release (0.01 vs 0.07 µg/dL; P = 0.046; corresponding to 54% vs 83% increases), and subjective stress response (21.2- vs 31.1-point Visual Analog Scale increase, P = 0.05; corresponding to 2427% vs 2863% increases) but no hemodynamic difference, compared to the VMS- group. The QST did not provoke stress responses via cortisol release or subjective report, but the VMS+ group tended to perceive heat at a higher temperature (38.5°C vs 36.4°C, P = 0.08). CONCLUSIONS: Women with VMS exhibited both diminished cortisol and subjective stress responses to the MIST, and reduced thermal sensitivity on QST compared to women without VMS. Dysregulated stress responsivity provides preliminary evidence suggesting that VMS may represent a chronic stress condition.

Early pubertal timing predicts onset and recurrence of depressive episodes in boys and girls.

BACKGROUND: Recurrent depressive episodes during adolescence result in significant impairment and increased risk for subsequent adverse outcomes throughout the life span. Evidence suggests that early pubertal timing predicts the onset of depressive episodes (particularly for girls); however, it is not known if pubertal timing prospectively predicts recurrent depressive episodes in youth. METHODS: At baseline, 603 youth (56% female, at baseline: Mage  = 12.09, SD = 2.35) reported on their pubertal development. Youth and their parents completed a semistructured diagnostic interview to assess depressive episodes at baseline and then evaluated for onset repeatedly every 6 months for a period of 36 months. RESULTS: Controlling for past history of depression, Cox proportional hazards models examined whether earlier pubertal timing predicted (a) days to first depressive episode from baseline and (b) days to a second (recurrent) depressive episode from the end of the first episode. Early pubertal timing predicted the onset of the first depressive episode after baseline (b = .19, Wald = 5.36, p = .02, HR = 1.21), as well as a recurrent episode during course of study follow-up episode (b = .32, Wald = 6.16, p = .01, HR = 1.38). CONCLUSIONS: Findings reinforce the importance of considering the impact of early pubertal timing on depression risk. Investigation on how pubertal timing interacts with other risk factors to predict depression recurrence is needed.

Pubertal Maturation and Trajectories of Depression During Early Adolescence.

Beginning at puberty, prevalence of depression in females rises dramatically. The physical changes of puberty coincide with a period of social flux, during which relationships become less stable and more prone to conflict. While this social upheaval is normatively distressing for girls, it may be especially so for girls with cognitive styles that leave them more susceptible to depression. The present study investigated depressive symptoms at two time points during early pubertal maturation. N = 110 girls (M age = 11.57, SD = 0.98) reported on depressive symptomology, pubertal maturation, ruminative coping style, frequency of peer conflict, and rejection sensitivity. Multivariate analyses suggest more advanced pubertal development and greater rejection sensitivity at Time 1 predicted higher levels of depressive symptoms at Time 2, after accounting for baseline levels of depressive symptoms and all other social and cognitive correlates of depression. This effect was also found in early maturing girls. Menarche status was not significant. Since menarche occurs toward the end of puberty, results suggest that risk for worsening depression is not associated with completing puberty, or with menstruation itself. Rather, increases in depressive symptoms seem to be associated with physical changes that emerge early in the pubertal transition, especially for early maturing girls, paired with anticipatory concerns about social rejection.

Cardiovascular reactivity and psychological hyperarousal in hot flash-associated insomnia disorder.

OBJECTIVES: Given the neurocognitive hyperarousal observed in patients with insomnia disorder and associations of nocturnal hot flashes with cardiovascular disease risk, we examined whether women with hot flash-associated insomnia disorder demonstrate exaggerated cardiovascular responsivity to acute stressors, and also a profile of psychological hyperarousal. METHODS: Peri and postmenopausal women with and without hot flash-associated insomnia disorder underwent assessments of cardiovascular autonomic responsivity to acute stress paradigms and psychological hyperarousal. Hemodynamic responses (heart rate, blood pressure) to nociceptive, social-evaluative, and cognitive stress paradigms were measured in the morning. Psychological hyperarousal was evaluated using questionnaires assessing daytime and presleep hyperarousal, anxiety, and sleep-related cognitions. RESULTS: Women (25 with and 15 without hot flash-associated insomnia) aged 53.4 ±â€Š4.8 years reported a range of insomnia symptoms. Resting-state hemodynamics were similar between groups. Heart rate and blood pressure responses to stress paradigms did not differ by group nor did they correlate with insomnia severity. Women with insomnia disorder had higher generalized anxiety disorder scores (mean 2.7 ±â€Š3.0 vs 1.0 ±â€Š1.4; P = 0.05) and sleep-related cognitions than those without insomnia (P ≤ 0.05). Insomnia symptom severity was moderately correlated with presleep and daytime hyperarousal, anxiety, and sleep-related cognition (all r ≥ 0.43). CONCLUSIONS: Though hot flash-associated insomnia is characterized by psychological hyperarousal before sleep and during the daytime, it does not relate to cardiovascular responsiveness to acute stressors. Our findings do not support the hypothesis that altered cardiovascular control is a potential mechanism by which hot flash-associated insomnia confers higher cardiovascular disease risk.

Together into the future...Pharmacogenomics and documentation.

New partnerships target optimal care quality and outcomes.

Understanding New Types of Evidence Ready for Translation into Nursing Informatics.

Nurses are the primary deliverers of patient care and observers of patient side effects to medications. The primary objective of this tutorial is to bring the participants up to date in genomic applications for nursing from birth until death. A secondary objective is to define at least 17 pharmacogenomics evidence guidelines ready for implementation into the Electronic Health Record. The target audience are nurses in practice, implementers of EHRs, nursing in leadership and policy-making positions, those focused on defining new areas for nursing research, and educators who are in need of defining criteria for integrating genomics into nursing education.

Individualizing cancer care with interoperable information systems.

There are three levels of interoperable informatics that are co-occurring in the United States to link data to provide more comprehensive care to patients. One is the National Health Information Network (NHIN) that is establishing use case scenarios and standards for interoperability for patients with multiple conditions. The second is the National Cancer Institute's project that supports the enterprise work called the Cancer Bioinformatics Grid (caBIG) in linking clinical care with bioinformatics, tissue repositories, and imaging for patients with cancer. The third is in the area of translating the discoveries of biology to bedside care through the National Institutes of Health (NIH) translational research efforts to get these new biomedical and genomic discoveries in practice in multiple healthcare delivery environments. These developments are becoming global networks in the diagnosis and cure of cancer as the primary outcome. This paper describes the national efforts and the global connection to Europe through the caBIG program. The European program that is beginning to link to cancer research internationally is the National Cancer Research Institute (NCRI) in the United Kingdom. They are developing the NCRI Oncology Information Exchange (ONIX) to provide the cancer research community with the ability to share information.

Estrogen effects on skeletal muscle insulin-like growth factor 1 and myostatin in ovariectomized rats.

Previous work showed that estrogen replacement attenuates muscle growth in immature rats. The present study examined muscle insulin-like growth factor-1 (IGF-1) and myostatin expression to determine whether these growth regulators might be involved in mediating estrogen's effects on muscle growth. IGF-1 and myostatin message and protein expression in selected skeletal muscles from 7-week-old sham-ovariectomized (SHAM) and ovariectomized rats that received continuous estrogen (OVX/E2) or solvent vehicle (OVX/CO) from an implant for 1 week or 5 weeks was measured. In the 1-week study, ovariectomy increased IGF-1 mRNA expression in fast extensor digitorum longus and gastrocnemius muscles; the increase was reversed by estrogen replacement. A similar trend was observed in the slow soleus muscle, although the change was not statistically significant. In contrast to mRNA, muscle IGF-1 protein expression was not different between SHAM and OVX/ CO animals in the 1-week study. One week of estrogen replacement significantly decreased IGF-1 protein level in all muscles examined. Myostatin mRNA expression was not different among the 1-week treatment groups. One week of estrogen replacement significantly increased myostatin protein in the slow soleus muscle but not the fast extensor digitorum longus and gastrocnemius muscles. There was no treatment effect on IGF-1 and myostatin expression in the 5-week study; this finding suggested a transient estrogen effect or upregulation of a compensatory mechanism to counteract the estrogen effect observed at the earlier time point. This investigation is the first to explore ovariectomy and estrogen effects on skeletal muscle IGF-1 and myostatin expression. Results suggest that reduced levels of muscle IGF-1 protein may mediate estrogen's effect on growth in immature, ovariectomized rats. Increased levels of muscle myostatin protein may also have a role in mediating estrogen's effects on growth in slow but not fast skeletal muscle.

Basal, but not overload-induced, myonuclear addition is attenuated by NG-nitro-L-arginine methyl ester (L-NAME) administration.

The purpose of this study was to examine the effect of blocking nitric oxide synthase (NOS) activity via NG-nitro-L-arginine methyl ester (L-NAME) on myonuclear addition in skeletal muscle under basal and overloaded conditions. Female Sprague-Dawley rats (approx. 220 g) were placed into 1 of the following 4 groups (n = 7-9/group): 7-day skeletal muscle overload (O), sham operation (S), skeletal muscle overload with L-NAME treatment (OLN), and sham operation with L-NAME treatment (SLN). Plantaris muscles were overloaded via bilateral surgical ablation of the gastrocnemius muscles and L-NAME (0.75 mg/mL) was administered in the animals' daily drinking water starting 2 days prior to surgery and continued until sacrifice. Myonuclear addition was assessed as subsarcolemmal incorporation of nuclei labeled with 5-bromo-2'-deoxyuridine (approx. 25 mg.(kg body mass)-1.day-1) delivered via osmotic pump during the overload period. As expected, muscle wet mass, total protein content, fiber cross-sectional area, and myonuclear addition were significantly higher (p

Episodic hypoxia exacerbates respiratory muscle dysfunction in DMD(mdx) mice.

Many patients with Duchenne muscular dystrophy (DMD) are eventually diagnosed with sleep-disordered breathing (SDB). SDB is associated with reduced ventilation, decreased arterial oxygen tension, and increased respiratory muscle recruitment during sleep, factors that could be especially detrimental to respiratory muscles in DMD. To assess whether SDB impacts dystrophin-deficient respiratory muscle function and fibrosis, diaphragm strength, and collagen content were evaluated in dystrophic mice (Dmd(mdx)) exposed to experimental SDB. Diurnal exposure to episodic hypoxia resulted in a 30% reduction in diaphragm strength without affecting collagen content. Episodic hypoxia secondary to SDB can exacerbate respiratory muscle dysfunction in DMD.

Guideposts to the future--an agenda for nursing informatics.

As new directions and priorities emerge in health care, nursing informatics leaders must prepare to guide the profession appropriately. To use an analogy, where a road bends or changes directions, guideposts indicate how drivers can stay on course. The AMIA Nursing Informatics Working Group (NIWG) produced this white paper as the product of a meeting convened: 1) to describe anticipated nationwide changes in demographics, health care quality, and health care informatics; 2) to assess the potential impact of genomic medicine and of new threats to society; 3) to align AMIA NIWG resources with emerging priorities; and 4) to identify guideposts in the form of an agenda to keep the NIWG on course in light of new opportunities. The anticipated societal changes provide opportunities for nursing informatics. Resources described below within the Department of Health and Human Services (HHS) and the National Committee for Health and Vital Statistics (NCVHS) can help to align AMIA NIWG with emerging priorities. The guideposts consist of priority areas for action in informatics, nursing education, and research. Nursing informatics professionals will collaborate as full participants in local, national, and international efforts related to the guideposts in order to make significant contributions that empower patients and providers for safer health care.

Satellite cells express distinct patterns of myogenic proteins in immature skeletal muscle.

Satellite cells are the myogenic cells lying between the myofiber sarcolemma and basal lamina. The objective of this study was to determine the expression patterns of MyoD, myogenin, and Pax7 within the satellite cell population in the growing rat soleus and extensor digitorum longus (EDL) muscles. Secondly, the expression of the myogenic markers was also studied within the interstitial cell compartment and myonuclei. It was discovered that the soleus contained a higher number of Pax7, MyoD, or myogenin-positive nuclei compared with the EDL. Similarly, myogenin was expressed at a lower level in the myonuclei of the soleus compared with the EDL, and myogenin was expressed at a higher level in the interstitial compartment of the soleus compared with the EDL. When interstitial nuclei, myonuclei, and double-labeled nuclei were used in the estimate of the satellite cell population, it was discovered that approximately of 13% of the myofibers in a transverse section of the soleus muscle and 4.1% of EDL myofibers exhibit a labeled satellite cell nucleus. Overall, results from this study suggest that expression patterns of these markers vary predictably among muscles with different growth dynamics and phenotypic characteristics.

Effect of oestrogen on myofibre size and myosin expression in growing rats.

This study examined the effect of oestrogen deprivation and replacement on plantaris muscle size and myosin heavy chain (MHC) isoform composition in rats during a period of physiological growth. Seven-week-old female Sprague-Dawley rats were assigned to one of the three treatment groups: (1) control animals (Sham); (2) ovariectomized animals without oestrogen replacement (OVX/CO); and (3) ovariectomized animals with 17beta-oestradiol replacement (OVX/E2). OVX/CO and OVX/E2 animals were pair-fed with Sham animals to rule out the potentially confounding effects of differences in food intake and weight gain. Rats were killed 4 weeks after surgery and the plantaris muscle was removed for analysis. Ovariectomy had no effect on muscle fibre size, but reduced the relative amount of type IIx MHC. This was reversed with oestrogen replacement, suggesting that the reduction in type IIx MHC expression was an oestrogen-mediated effect. Oestrogen replacement reduced type IIb MHC expression and fast muscle fibre size. Changes in fast fibre size and type IIb MHC expression were not seen with ovariectomy, indicating that these changes were not simply due to the presence of oestrogen in the ovariectomized, oestrogen-replaced animals. These results suggest that another ovarian hormone may counteract the effect of oestrogen on fast fibre size and type IIb MHC expression in intact animals.

Gender and sodium-ascorbate transporter isoforms determine ascorbate concentrations in mice.

We evaluated the hypothesis that sodium-dependent vitamin C (ascorbate) transporters SVCT1 and SVCT2 (encoded by genes Slc23a1 and Slc23a2) regulate ascorbate concentrations in tissues of adult mice. Slc23a2+/- and Slc23a2+/+ mice were fed an ascorbate-free diet for 10-12 wk, and then segregated according to gender and genome, and were placed in groups of 3-4 in metabolic cages for 24-h urine collection. RT-PCR analysis showed that liver and kidney expressed mainly SVCT1, and brain, skeletal muscle, and spleen expressed predominantly SVCT2. Slc23a2+/- mice had low SVCT2 but normal SVCT1 messenger RNA (mRNA) levels, which did not differ between genders. Ascorbate concentrations were lower in Slc23a2+/- than Slc23a2+/+ mice in tissues where SVCT2 was the main isoform. Compared with males, females had lower ascorbate excretion and ascorbate:creatinine ratio in urine and had higher ascorbate concentrations in plasma and SVCT1-predominant tissues. SVCT2 contributed to a gender effect in spleen because males had higher spleen ascorbate concentration than females in wild-type but not in Slc23a2+/- mice. Hepatic gulonolactone oxidase mRNA and activity levels did not differ with genotype or gender, indicating no differences in ascorbate synthesis. We concluded that SVCT2 is a major determinant of ascorbate accumulation in tissues lacking SVCT1. The SVCT isoforms appear to function independently of one another because SVCT1 expression and ascorbate concentrations in SVCT1-predominant organs were not affected by SVCT2 deficiency. Additionally, lower ascorbate excretion in females may elevate the vitamin's concentrations in plasma and tissues expressing SVCT1 that, unlike SVCT2, is not saturated by plasma ascorbate concentrations.