Real-world effectiveness, satisfaction, and optimization of ubrogepant for the acute treatment of migraine in combination with onabotulinumtoxinA: results from the COURAGE Study.

BACKGROUND: Individuals using onabotulinumtoxinA as a preventive migraine treatment often use acute treatments for breakthrough attacks. Data on real-world effectiveness of the small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist ubrogepant in combination with onabotulinumtoxinA are limited. METHODS: COURAGE, a prospective, multiple attack, observational study, evaluated the real-world effectiveness of ubrogepant (50 or 100 mg) for acute treatment of migraine in people receiving onabotulinumtoxinA, an anti-CGRP monoclonal antibody (mAb), or both. This analysis focused only on onabotulinumtoxinA users. The Migraine Buddy app was used to identify eligible participants and track response to treated attacks. For each ubrogepant-treated attack, meaningful pain relief (MPR) and return to normal function (RNF) at 2 and 4 h post-dose over 30 days was assessed. MPR was defined as a level of relief that is meaningful to the participant, usually occurring before the pain is all gone. After 30 days, satisfaction was reported on a 7-point scale and overall acute treatment optimization was evaluated using the migraine Treatment Optimization Questionnaire-4 (mTOQ-4). RESULTS: This analysis included 122 participants who received ubrogepant and onabotulinumtoxinA and reported on 599 ubrogepant-treated attacks. Following the first ubrogepant-treated attack, MPR was achieved in 53.3% of participants 2 h post-dose and in 76.2% of participants 4 h post-dose. RNF was achieved in 25.4% of participants 2 h post-dose and in 45.9% of participants 4 h post-dose. MPR and RNF results were similar across up to 10 ubrogepant-treated attacks. After 30 days, satisfaction with ubrogepant in combination with onabotulinumtoxinA was reported by 69.8% of participants and acute treatment optimization (defined as mTOQ-4 score ≥ 4) was achieved in 77.6%. CONCLUSIONS: In this prospective real-world effectiveness study, ubrogepant treatment in onabotulinumtoxinA users with self-identified migraine was associated with high rates of MPR and RNF at 2 and 4 h as well as satisfaction and acute treatment optimization. Although the lack of a contemporaneous control group limits causal inference, these findings demonstrate the feasibility of using a novel, app-based design to evaluate the real-world effectiveness and satisfaction of treatments.

Cyclooxygenase-2 contributes to diabetic nephropathy through glomerular EP4 receptor.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of mortality in diabetic patients. Cyclooxygenase (COX) and COX-derived prostanoids are documented to participate in the pathogenesis of diabetic nephropathy. Herein, we found an increased COX2 expression level in diabetic kidneys of STZ-induced DBA mice. The COX2 inhibitor significantly attenuated albuminuria and histological lesions, accompanied by up-regulation of the renal angiopoietin-1/tie-2 system. This finding is consistent with the presence of an angiogenic signature in endothelial cells during the development of DN. Prostaglandin E2 (PGE2) is the most abundant prostanoid in the kidney, and its receptor EP4 is expressed in the glomerulus, as determined by in situ hybridization. To test the hypothesis that diabetes-associated COX2 overexpression induces renal PGE2 production and endothelial dysfunction by activating glomerular EP4 receptors, the effect of an EP4 antagonist on Akita/DBA mice was investigated. Our results showed that blockade of EP4 receptor significantly reduced albuminuria in diabetic mice. Owing to the established adverse effect of COX2 inhibitors, our study provided new insight into meaningful renal benefits for diabetic nephropathy by targeting the EP4 receptor.

Coronavirus Disease Contact Tracing Outcomes and Cost, Salt Lake County, Utah, USA, March-May 2020.

Outcomes and costs of coronavirus disease (COVID-19) contact tracing are limited. During March-May 2020, we constructed transmission chains from 184 index cases and 1,499 contacts in Salt Lake County, Utah, USA, to assess outcomes and estimate staff time and salaries. We estimated 1,102 staff hours and $29,234 spent investigating index cases and contacts. Among contacts, 374 (25%) had COVID-19; secondary case detection rate was ≈31% among first-generation contacts, ≈16% among second- and third-generation contacts, and ≈12% among fourth-, fifth-, and sixth-generation contacts. At initial interview, 51% (187/370) of contacts were COVID-19-positive; 35% (98/277) became positive during 14-day quarantine. Median time from symptom onset to investigation was 7 days for index cases and 4 days for first-generation contacts. Contact tracing reduced the number of cases between contact generations and time between symptom onset and investigation but required substantial resources. Our findings can help jurisdictions allocate resources for contact tracing.

Nonselective Cyclooxygenase Inhibition Retards Cyst Progression in a Murine Model of Autosomal Dominant Polycystic Kidney Disease.

Aim: Autosomal dominant polycystic kidney disease is one of the most common genetic renal diseases. Cyclooxygenase plays an important role in epithelial cell proliferation and may contribute to the mechanisms underlying cyst formation. The aim of the present study was to evaluate the role of cyclooxygenase inhibition in the cyst progression in polycystic kidney disease. Method: Pkd2WS25/- mice, a murine model which harbors a compound cis-heterozygous mutation of the Pkd2 gene were used. Cyclooxygenase expression was assessed in both human and murine kidney specimens. Pkd2WS25/- mice were treated with Sulindac (a nonselective cyclooxygenase inhibitor) or vehicle for 8 months starting at three weeks age, and then renal cyst burden was assessed by kidney weight and volume. Results: Cyclooxygenase-2 expression was up-regulated compared to control kidneys as shown by RNase protection in human polycystic kidneys and immunoblot in mouse Pkd2WS25/- kidneys. Cyclooxygenase-2 expression was up-regulated in the renal interstitium as well as focal areas of the cystic epithelium (p<0.05). Basal Cyclooxygenase-1 levels were unchanged in both immunohistochemistry and real-time PCR. Administration of Sulindac to Pkd2WS25/- mice and to control mice for 8 months resulted in reduced kidney weights and volume in cystic mice. Renal function and electrolytes were not significantly different between groups. Conclusion: Thus treatment of a murine model of polycystic kidney disease with Sulindac results in decreased kidney cyst burden. These findings provide additional implications for the use of Cyclooxygenase inhibition as treatment to slow the progression of cyst burden in patients with polycystic kidney disease.

Family Involvement in Adult Chronic Disease Care: Reviewing the Systematic Reviews.

Health care providers, policy makers, and investigators are dependent upon the quality and accuracy of published research findings to inform and guide future practice and research in their field. Systematic reviews, the synthesis of outcomes across studies are increasingly more common in the family literature; however, published review reports often lack information on strategies reviewers used to insure dependability of findings, and minimize methodological bias in the review. In this article, we summarize findings from systematic reviews of interventions and outcomes from family involvement in adult chronic disease care published between 2007 and 2016. In addition, we explore procedures reviewers used to insure the quality and methodologic rigor of the review. Our discussion provides guidance and direction for future studies of family involvement in chronic disease care.

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile.

PURPOSE: Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been tested specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. METHODS: Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy-Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). RESULTS: Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p < 0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p < 0.05). CONCLUSIONS: Exercise and dietary counseling led to loss of body fat and improved quality of life in survivors of triple-negative breast cancer. BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity with intervention. Exercise and healthy eating may be equally effective in this high-risk population as in other breast cancer survivors and should be encouraged as a part of a cancer survivorship program.

Effects of nurse-managed protocols in the outpatient management of adults with chronic conditions: a systematic review and meta-analysis.

BACKGROUND: Changes in federal health policy are providing more access to medical care for persons with chronic disease. Providing quality care may require a team approach, which the American College of Physicians calls the "medical home." One new model may involve nurse-managed protocols. PURPOSE: To determine whether nurse-managed protocols are effective for outpatient management of adults with diabetes, hypertension, and hyperlipidemia. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and CINAHL from January 1980 through January 2014. STUDY SELECTION: Two reviewers used eligibility criteria to assess all titles, abstracts, and full texts and resolved disagreements by discussion or by consulting a third reviewer. DATA EXTRACTION: One reviewer did data abstractions and quality assessments, which were confirmed by a second reviewer. DATA SYNTHESIS: From 2954 studies, 18 were included. All studies used a registered nurse or equivalent who titrated medications by following a protocol. In a meta-analysis, hemoglobin A1c level decreased by 0.4% (95% CI, 0.1% to 0.7%) (n = 8); systolic and diastolic blood pressure decreased by 3.68 mm Hg (CI, 1.05 to 6.31 mm Hg) and 1.56 mm Hg (CI, 0.36 to 2.76 mm Hg), respectively (n = 12); total cholesterol level decreased by 0.24 mmol/L (9.37 mg/dL) (CI, 0.54-mmol/L decrease to 0.05-mmol/L increase [20.77-mg/dL decrease to 2.02-mg/dL increase]) (n = 9); and low-density-lipoprotein cholesterol level decreased by 0.31 mmol/L (12.07 mg/dL) (CI, 0.73-mmol/L decrease to 0.11-mmol/L increase [28.27-mg/dL decrease to 4.13-mg/dL increase]) (n = 6). LIMITATION: Studies had limited descriptions of the interventions and protocols used. CONCLUSION: A team approach that uses nurse-managed protocols may have positive effects on the outpatient management of adults with chronic conditions, such as diabetes, hypertension, and hyperlipidemia. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

Finding the New Normal: Accepting Changes After Combat-Related Mild Traumatic Brain Injury.

INTRODUCTION: More than 300,000 soldiers have returned from Southwest Asia (i.e., Iraq and Afghanistan) with combat-related mild traumatic brain injuries (mTBIs). Despite less visible physical injuries, these soldiers demonstrate various physical and cognitive symptoms that impact their ability to reintegrate post-mTBI. This study explores family reintegration experiences, as described by married dyads, following a combat-related mTBI. METHODS: Nine soldiers with mTBI and their spouses participated, and a total of 27 interviews, both joint and individual, were conducted. Strauss and Corbin's grounded theory methodology and semistructured interviews were used to collect participants' perceptions and analyze the data. FINDINGS: The overarching theme of the reintegration experience is described as finding the "new normal." A new normal was defined by participants as the couple's new, post-mTBI expectation of the family unit or family routine. Some participants indicated that they had accepted the post-mTBI changes and were working toward this new normal, whereas others indicated these changes were unacceptable and continued their efforts to return to pre-injury functioning. CONCLUSIONS: Individuals with mTBI and their families may benefit from interventions that directly address mismatched expectations and promote the acceptance of a new normal.

Increased dietary sodium induces COX2 expression by activating NFκB in renal medullary interstitial cells.

High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective IκB kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E2 (PGE2). These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium.

Adapters, strugglers, and case managers: a typology of spouse caregivers.

Although family home care problems are frequently described in the health care literature, the ways in which families and other informal caregivers manage those problems are not often addressed. We conducted a descriptive analysis of interviews in which spouses caring for a partner with Alzheimer's or Parkinson's disease were asked to describe difficult home care problems and how they managed those problems. Analysis of these interviews indicated three recurring management styles. Adapters told stories about applying pre-existing skills to manage home care problems. Strugglers told stories of reoccurring home care problems for which they had few or no management strategies. Case managers' interview stories focused on the challenges of finding and coordinating home care services. These findings suggest that caregiving burden might be influenced more by the caregiver's management style than the demands of the care situation. Suggestions for tailoring support programs for the three types of caregivers are proposed.

"Don't know" and accuracy of breast cancer risk perceptions among Appalachian women attending a mobile mammography program: implications for educational interventions and patient empowerment.

Risk perceptions are motivating factors for engaging in preventive health behaviors. Yet, almost one third of women attending a mobile mammography program targeted to rural and medically underserved Appalachian women respond "don't know" to their perceived 5-year risk of breast cancer. This study used cross-sectional data from women aged >40 years participating in Bonnie's Bus Mammography Screening and Preventive Care Survey from 2009 to 2011 to identify factors associated with "don't know" responses and accuracy of perceived risk according to constructs of the health belief model and sociodemographic characteristics. Women who responded "don't know" were more likely to be less educated, of lower income, insured by Medicaid, and less knowledgeable about breast cancer. Conversely, women who accurately perceived their risk were more likely to be of higher education, more knowledgeable about breast cancer, and have a family history of breast cancer. However, women with a high objective 5-year risk of breast cancer and older age at childbirth or were nulliparous were less likely to accurately perceive their risk. These findings suggest that women who indicate "don't know" responses and hold inaccurate risk perceptions are a population vulnerable to health disparities and may benefit from educational interventions focused on improving breast cancer knowledge and perceptions to empower them to take an active role in their preventive health and make informed decisions based on their individual level of risk.

Compassion fatigue in adult daughter caregivers of a parent with dementia.

Adult daughters face distinct challenges caring for parents with dementia and may experience compassion fatigue: the combination of helplessness, hopelessness, an inability to be empathic, and a sense of isolation resulting from prolonged exposure to perceived suffering. Prior research on compassion fatigue has focused on professional healthcare providers and has overlooked filial caregivers. This study attempts to identify and explore risk factors for compassion fatigue in adult daughter caregivers and to substantiate further study of compassion fatigue in family caregivers. We used content analysis of baseline interviews with 12 adult daughter caregivers of a parent with dementia who participated in a randomized trial of homecare training. Four themes were identified in adult daughter caregiver interviews: (a) uncertainty; (b) doubt; (c) attachment; and (d) strain. Findings indicated adult daughter caregivers are at risk for compassion fatigue, supporting the need for a larger study exploring compassion fatigue in this population.

Fatigue and recovery in 12-hour dayshift hospital nurses.

AIM: The study investigated the status of acute fatigue, chronic fatigue and inter-shift recovery among 12-hour shift nurses and how they differed by organisational and individual factors. BACKGROUND: While the 12-hour shift has been a widely accepted staffing solution in hospitals, the fatigue-recovery process in nurses working 12-hour shifts remains unclear. METHODS: A cross-sectional survey was completed by 130 full-time nurses working 12-hour dayshifts in three hospitals to assess the perceived levels of acute fatigue, chronic fatigue and inter-shift recovery, as well as their associations with selected organisational and individual factors. RESULTS: Nurses experienced a moderate to high level of acute fatigue and moderate levels of chronic fatigue and inter-shift recovery. Fatigue and recovery levels differed by the interaction between hospital and unit after controlling for individual factors. Lack of regular exercise and older age were associated with higher acute fatigue. CONCLUSIONS: An unhealthy fatigue-recovery process was found for nurses working a 12-hour shift during the day. IMPLICATIONS FOR NURSING MANAGEMENT: There appears to be a need to establish fatigue intervention programmes for 12-hour shift nurses in hospitals. Hospital administration, unit managers and staff nurses need to collaborate to achieve a healthy fatigue-recovery balance when implementing 12-hour shifts.

The obesity-inflammation-eicosanoid axis in breast cancer.

Inflammation of the adipose tissues occurs in association with obesity. This inflammatory process leads to the induction of cyclooxygenase-2 (COX-2) expression and a consequent elevation in prostaglandin (PG) production, which, together with proinflammatory cytokines, induce aromatase expression and estrogen synthesis. Infiltrating macrophages support the growth of breast epithelial cells and vascular endothelial cells by producing a milieu of cytokines and growth factors. This scenario creates a microenvironment favorable to breast cancer growth and invasion. The eicosanoids promote further development and growth of breast cancers indirectly by the induction of aromatase, particularly in estrogen positive breast cancers, or by direct stimulatory effect of PGE2 and lipoxygenase (LOX) products on the more aggressive, estrogen-independent tumors. Beyond this, the local production of estrogens and proinflammatory cytokines which occurs in association with breast adipose tissue inflammation, and consequent activation of the estrogen receptor and nuclear factor-κB, provides a mechanism by which breast cancers develop resistance to selective estrogen receptor modulation and aromatase inhibitor therapy. The obesity-inflammation-eicosanoid axis in breast cancer does offer a therapeutic target for the prevention of relapse in breast cancer by improving the efficacy of antiaromatase therapy using COX/LOX inhibitors; however, careful consideration of menopausal status and obesity in patients is warranted.

Quantitative profiling of PrP(Sc) peptides by high-performance liquid chromatography mass spectrometry to investigate the diversity of prions.

Prions are proteins that can exist in two (or more) folding states, a normal or cellular form and a series of infectious or prion forms, which are prone to aggregate. The prion form can induce conversion of the cellular form and so transmit phenotypic effects of this structural rearrangement within and between cells and organisms. The conversion of PrP(C), the mammalian prion glycoprotein, to its prion form, PrP(Sc), in the brain is a precursor to progressive neurological degeneration, and the various folded forms of PrP(Sc) (defined by the size and glycosylation of protease-resistant core peptides of the PrP aggregates, PrP(res)) are characteristic of a particular neurodegenerative phenotype or prion disease. Here, quantitative multiplex mass spectrometry was used for N-terminal amino acid profiling (N-TAAP) of PrP(res) from sheep affected by scrapie, the prion disease of small ruminants, to rapidly assess the diversity of prions within particular flocks. In 29 cases, PrP(res) concentrations varied from below the limit of detection (350 fmol/g) to 15 pmol/g wet brain. Although most had a single N-TAAP profile, two novel variants were identified: one common to the ARH/ARQ animals in this study and one in an animal of the wild-type sheep PrP genotype (ARQ/ARQ).

Finding meaning in caring for a spouse with dementia.

Dementia caregiving can be burdensome with many challenges, especially for spousal caregivers who are elderly and may have limited resources and chronic conditions of their own. However, it can also be an opportunity for growth and transcendence. Thematic qualitative analysis was conducted with 11 caregiver interviews to investigate how spousal caregivers of individuals with dementia found personal meaning in their caregiving experience. Caregivers commonly had altruistic values, and the discipline to live those values. They found meaning by believing in a choice of attitude and perceiving satisfaction in living according to their values in life. They had faith in a higher power, a strong sense of love for their spouses and they derived strength from past challenges. Positive attitudes among caregivers of individuals with dementia may be enhanced by sharing these stories and strategies. Study results also provide an expansion beyond commonly held views of caregiving for nurses.

Factors influencing adherence to mammography screening guidelines in Appalachian women participating in a mobile mammography program.

The objectives of this study were to evaluate the characteristics (demographic, access to care, health-related behavioral, self and family medical history, psychosocial) of women age 40 years and above who participated in a mobile mammography screening program conducted throughout West Virginia (WV) to determine the factors influencing their self-reported adherence to mammography screening guidelines. Data were analyzed using the Andersen Behavioral Model of Healthcare Utilization framework to determine the factors associated with adherence to mammography screening guidelines in these women. Of the 686 women included in the analysis, 46.2% reported having had a mammogram in the past 2 years. Bivariate analyses showed predisposing factors such as older age and unemployed status, visit to a obstetrician/gynecologist (OB/GYN) in the past year (an enabling factor) and need-related factors such as having a family history of breast cancer (BC), having had breast problems in the past, having had breast biopsy in the past, having had a Pap test in past 2 years, and having had all the screenings for cholesterol, blood glucose, bone mineral density and high blood pressure in past 2 years to be significant predictors of self-reported adherence to mammography guidelines. In the final model, being above 50 years (OR=2.132), being morbidly obese (OR=2.358), having BC-related events and low knowledge about mammography were significant predictors of self-reported adherence. Breast cancer related events seem to be associated with mammography screening adherence in this rural Appalachian population. Increasing adherence to mammography screening may require targeted, community-based educational interventions that precede and complement visits by the mobile mammography unit.

Managing migraine on the frontline: Identifying disease, understanding burden, and incorporating CGRP pathway-targeting therapies in primary care.

Migraine is a common neurologic disorder with clinical phenotypes encompassing a variety of symptoms which all contribute to the burden felt by patients. In addition to negative impacts on a patient's quality of life, migraine has both direct medical costs and indirect costs related to missed work and decreased productivity that affect individuals as well as society at large. Unfortunately, migraine diagnoses are often missed, and many patients do not receive appropriate treatment. Primary care providers are in a key position to provide timely diagnosis and effectively manage migraine for many patients. This review aims to be a guide for improving migraine management in the primary care setting by providing strategies to overcome common challenges in migraine diagnosis; summarizing current knowledge on the mechanism of action, efficacy, and safety of calcitonin gene-related peptide (CGRP) pathway-targeting therapies; and reviewing approaches to incorporate traditional and emerging treatment options into a patient-centric migraine management strategy.

Advances in mediation analysis can facilitate nursing research.

BACKGROUND: Two recent advances in the statistical methods for testing hypotheses about mediation effects are important for nursing science. First, bootstrap sampling distributions provide more accurate tests of hypotheses about mediated effects. Second, methods for testing statistical hypotheses about subgroup differences in mediation models (moderated mediation) are now well developed. OBJECTIVE: The aims of this study were to demonstrate the use and relatively simple computation of bootstrap sampling distributions in tests of mediation effects and to demonstrate a recently refined method for testing hypotheses about moderated mediation. METHOD: Using hypothetical data, a step-by-step demonstration was provided of the construction of a bootstrap sampling distribution for a correlation coefficient. Then, tests of mediation and moderated mediation were demonstrated using data from a clinical trial of an intervention for caregivers of patients with Parkinson's disease or Alzheimer's disease. In a model hypothesizing that mutuality between caregiver and care recipient mediates the effect of objective on subjective levels of caregiver burden, the bootstrap sampling distribution was calculated of the mediation effect and, from that, two types of 95% confidence intervals for it. Then the hypothesis was tested that the mediating effect of mutuality was stronger for caregivers of patients with Parkinson's disease than for caregivers of patients with Alzheimer's disease. CONCLUSIONS: Statistical hypothesis testing should never dictate all conclusions. However, the statistical advances in mediation analysis described here will facilitate nursing research as both nurse scientists and methodologists understand their assumptions and logic.