A Randomized Internet-Based Pilot Feasibility and Planning Study of Cherry Extract and Diet Modification in Gout.

OBJECTIVE: The aim of this study was to conduct a 9-month pilot Internet randomized controlled trial (RCT) of cherry extract and diet modification in gout to assess the feasibility of an Internet study and obtain effect estimates. METHODS: After providing online informed consent in response to Internet advertisements and social media or clinic flyers, 84 people with physician-confirmed gout were randomized to either cherry extract 3,600 mg/d (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via Internet and phone calls. The primary objective was the feasibility of an Internet study, and secondary objectives were to obtain effect estimates for gout flares, functional ability assessed with the Health Assessment Questionnaire (HAQ), and adverse events (AEs) for future trials. RESULTS: Of the 84 people randomized, overall completion rates were more than 80% for most study procedures up to 6 months and similar for the 2 active comparators. Improvements were seen in gout flares and HAQ scores in cherry extract and diet modification groups at 9 months compared with baseline: gout flares per month, 0.22 versus 0.36 (p = 0.049) and 0.28 versus 0.31 (p = 0.76); proportion with any gout flare, 56% versus 98% (p < 0.0001) and 65% versus 98% (p = 0.0002); and mean ± standard deviation HAQ score, 0.28 ± 0.54 versus 0.55 ± 0.68 (p = 0.001) and 0.23 ± 0.40 versus 0.48 ± 0.61 (p = 0.06), respectively. Any AEs and gastrointestinal symptoms/AEs at 9 months in cherry extract and diet modification groups were 3% versus 0% and 28% versus 27%, respectively. CONCLUSIONS: An Internet gout RCT is feasible for nonpharmacological gout treatments. A hypothesis-testing, large Internet RCT of cherry extract versus placebo is needed.

Patient-Centered Outcomes and Key Study Procedure Finalization in the Pilot Feasibility Gout Randomized Trial: Comparative Feasibility Study in GOUt, CHerry Extract Versus Diet Modification (Mini-GOUCH).

OBJECTIVE: The aim of this study was to report patient-centered outcomes and finalization of key study procedures from a 9-month pilot internet randomized controlled trial of cherry extract versus diet modification. METHODS: We randomized 84 people with physician-confirmed gout in an internet study to cherry extract (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via internet and phone calls. We finalized key study procedures. We assessed acceptability and feasibility of the intervention and satisfaction with study website. RESULTS: Study participant satisfaction with the intervention was high. The intervention was perceived as easy, enjoyable, understandable, and helpful (scores 65-88 for all; higher = better). The amount of time spent for the study was acceptable. Participant satisfaction with website interaction and content was very high; 85% or more were moderately to extremely satisfied. Significantly lower total calories, total carbohydrate, and saturated fat intake were noted at 6 months in the diet modification versus cherry extract group; differences were insignificant at 9 months. Six of the 8 Health Assessment Questionnaire sections/domains improved significantly from baseline to 9 months in cherry extract versus 2 Health Assessment Questionnaire sections/domains in the diet modification group. Key study procedures were finalized for a future trial, including an internet diet assessment tool, gout flare assessment, provider confirmation of gout diagnosis, patient reporting of classification criteria, and centralized laboratory-assisted serum urate testing. CONCLUSIONS: High patient acceptability and feasibility of study/intervention and finalization of key study procedures indicate that hypothesis-testing internet gout trials of cherry extract and/or diet modification can be conducted in the future.

Individualized decision aid for diverse women with lupus nephritis (IDEA-WON): A randomized controlled trial.

BACKGROUND: Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis. METHODS AND FINDINGS: In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence. CONCLUSIONS: An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02319525.

Individualized patient decision-aid for immunosuppressive drugs in women with lupus nephritis: study protocol of a randomized, controlled trial.

BACKGROUND: Systemic Lupus erythematosus (SLE), also commonly referred to as lupus, is a rare, but sometimes, fatal disease, that primarily affects young women. Lupus nephritis, a common manifestation of lupus, is more common and more devastating in patients of minority race/ethnicity. Patients have negative views of immunosuppressive drugs for lupus nephritis due to a concern about side effects and under-appreciation of its benefit. We designed a study to assess the effectiveness of individualized, computerized patient decision-aid for immunosuppressive drugs for lupus nephritis compared to a standard pamphlet for patient decision-making. METHODS: Adult women with lupus nephritis, with a current lupus nephritis flare or at risk of a future lupus nephritis flare will be randomized to individualized, computerized patient decision-aid for immunosuppressive drugs vs. standard pamphlet with information about lupus and its treatment including immunosuppressive drugs and outcomes. Patients will complete outcome assessments immediately after the intervention has been administered. Patients will be followed at 3-months with a brief survey, either in person or on the phone, and at 6-months with medical record review for exploratory outcomes. Co-primary outcomes are decisional conflict and informed choice regarding immunosuppressive drugs (combines values, knowledge and choice). Secondary outcomes include: (1) assessment of patient-physician communication by assessing audio-taped physician-patient communication after intervention administration; (2) concordance between patient's desired and actual role in immunosuppressive drugs decision-making using the control preference scale (CPS); and (3) patient perception of physician interaction using the interpersonal process of care- short form (IPC-SF). DISCUSSION: This is one of the first studies to evaluate the effectiveness of an educational intervention targeting minorities with lupus nephritis. This patient-centered lupus nephritis decision-aid will be available in the public domain in English and Spanish. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02319525 ; registered on November 5, 2014.

Antimicrobial effects of interferon-inducible CXC chemokines against Bacillus anthracis spores and bacilli.

Based on previous studies showing that host chemokines exert antimicrobial activities against bacteria, we sought to determine whether the interferon-inducible Glu-Leu-Arg-negative CXC chemokines CXCL9, CXCL10, and CXCL11 exhibit antimicrobial activities against Bacillus anthracis. In vitro analysis demonstrated that all three CXC chemokines exerted direct antimicrobial effects against B. anthracis spores and bacilli including marked reductions in spore and bacillus viability as determined using a fluorometric assay of bacterial viability and CFU determinations. Electron microscopy studies revealed that CXCL10-treated spores failed to undergo germination as judged by an absence of cytological changes in spore structure that occur during the process of germination. Immunogold labeling of CXCL10-treated spores demonstrated that the chemokine was located internal to the exosporium in association primarily with the spore coat and its interface with the cortex. To begin examining the potential biological relevance of chemokine-mediated antimicrobial activity, we used a murine model of inhalational anthrax. Upon spore challenge, the lungs of C57BL/6 mice (resistant to inhalational B. anthracis infection) had significantly higher levels of CXCL9, CXCL10, and CXCL11 than did the lungs of A/J mice (highly susceptible to infection). Increased CXC chemokine levels were associated with significantly reduced levels of spore germination within the lungs as determined by in vivo imaging. Taken together, our data demonstrate a novel antimicrobial role for host chemokines against B. anthracis that provides unique insight into host defense against inhalational anthrax; these data also support the notion for an innovative approach in treating B. anthracis infection as well as infections caused by other spore-forming organisms.

How Community Nurses Manage Ethical Conflicts: A Grounded Theory Study.

Research is limited on how nurses in community settings manage ethical conflicts. To address this gap, we conducted a study to uncover the process of behaviors enacted by community nurses when experiencing ethical conflicts. Guided by Glaserian grounded theory, we developed a theoretical model (Moral Compassing) that enables us to explain the process how 24 community nurses managed challenging ethical situations. We discovered that the main concern with which nurses wrestle is moral uncertainty ("Should I be addressing what I think is a moral problem?"). Moral Compassing comprises processes that resolve this main concern by providing community nurses with the means to attain the moral agency necessary to decide to act or to decide not to act. The processes are undergoing a visceral reaction, self-talk, seeking validation, and mobilizing support for action or inaction. We also discovered that community nurses may experience continuing distress that we labeled moral residue.

Contributions of histamine, prostanoids, and neurokinins to edema elicited by edema toxin from Bacillus anthracis.

Bacillus anthracis edema toxin (ET), composed of protective antigen and an adenylate cyclase edema factor (EF), elicits edema in host tissues, but the target cells and events leading from EF-mediated cyclic-AMP production to edema are unknown. We evaluated the direct effect of ET on several cell types in vitro and tested the possibility that mediators of vascular leakage, such as histamine, contribute to edema in rabbits given intradermal ET. ET increased the transendothelial electrical resistance of endothelial monolayers, a response that is mechanistically inconsistent with the in vivo vascular leakage induced by ET. Screening of several drugs by intradermal treatment prior to toxin injection demonstrated reduced ET-induced vascular leakage with a cyclo-oxygenase inhibitor (indomethacin), agents that interfere with histamine (pyrilamine or cromolyn), or a neurokinin antagonist (spantide). Systemic administration of indomethacin or celecoxib (cyclo-oxygenase inhibitors), pyrilamine, aprepitant (a neurokinin 1 receptor antagonist), or indomethacin with pyrilamine significantly reduced vascular leakage associated with ET. Although the effects of pyrilamine, cromolyn, or aprepitant on ET-induced vascular leakage suggest a possible role for mast cells (MC) and sensory neurons in ET-induced edema, ET did not elicit degranulation of human skin MC or substance P release from NT2N cells in vitro. Our results indicate that ET, acting indirectly or directly on a target yet to be identified, stimulates the production/release of multiple inflammatory mediators, specifically neurokinins, prostanoids, and histamine. These mediators, individually and through complex interactions, increase vascular permeability, and interventions directed at these mediators may benefit hosts infected with B. anthracis.

Adenylate cyclase toxin (ACT) from Bordetella hinzii: characterization and differences from ACT of Bordetella pertussis.

Bordetella hinzii is a commensal respiratory microorganism in poultry but is increasingly being recognized as an opportunistic pathogen in immunocompromised humans. Although associated with a variety of disease states, practically nothing is known about the mechanisms employed by this bacterium. In this study, we show by DNA sequencing and reverse transcription-PCR that both commensal and clinical strains of B. hinzii possess and transcriptionally express cyaA, the gene encoding adenylate cyclase toxin (ACT) in other pathogenic Bordetella species. By Western blotting, we also found that B. hinzii produces full-length ACT protein in quantities that are comparable to those made by B. pertussis. In contrast to B. pertussis ACT, however, ACT from B. hinzii is less extractable from whole bacteria, nonhemolytic, has a 50-fold reduction in adenylate cyclase activity, and is unable to elevate cyclic AMP levels in host macrophages (nontoxic). The decrease in enzymatic activity is attributable, at least in part, to a decreased binding affinity of B. hinzii ACT for calmodulin, the eukaryotic activator of B. pertussis ACT. In addition, we demonstrate that the lack of intoxication by B. hinzii ACT may be due to the absence of expression of cyaC, the gene encoding the accessory protein required for the acylation of B. pertussis ACT. These results demonstrate the expression of ACT by B. hinzii and represent the first characterization of a potential virulence factor of this organism.

MyD88-dependent signaling contributes to protection following Bacillus anthracis spore challenge of mice: implications for Toll-like receptor signaling.

Bacillus anthracis is a spore-forming, gram-positive organism that is the causative agent of the disease anthrax. Recognition of Bacillus anthracis by the host innate immune system likely plays a key protective role following infection. In the present study, we examined the role of TLR2, TLR4, and MyD88 in the response to B. anthracis. Heat-killed Bacillus anthracis stimulated TLR2, but not TLR4, signaling in HEK293 cells and stimulated tumor necrosis factor alpha (TNF-alpha) production in C3H/HeN, C3H/HeJ, and C57BL/6J bone marrow-derived macrophages. The ability of heat-killed B. anthracis to induce a TNF-alpha response was preserved in TLR2-/- but not in MyD88-/- macrophages. In vivo studies revealed that TLR2-/- mice and TLR4-deficient mice were resistant to challenge with aerosolized Sterne strain spores but MyD88-/- mice were as susceptible as A/J mice. We conclude that, although recognition of B. anthracis occurs via TLR2, additional MyD88-dependent pathways contribute to the host innate immune response to anthrax infection.