Quality improvement projects conducted by interprofessional teams of learners: Implementation and impact.

Students in their second year of the Vanderbilt Program of Interprofessional Learning (VPIL) complete team-based quality improvement (QI) projects in their assigned clinic as part of the core curriculum. This report describes the creation and implementation of the student teams' QI curriculum and investigates how clinical preceptors view the project impact. Between 2012-2019, the VPIL teams designed and implemented 69 improvement projects. Improvement projects fell primarily into three categories: improving clinic care delivery (n = 25, 36%), patient education and health coaching (n = 21, 30%), and quality measures such as screening tests/prophylaxis (n = 10, 14%). Clinic preceptors received a survey about the sustainability and effectiveness of the projects. Survey feedback was received from 44/69 (64%) preceptors. Many (70%) projects resulted in perceived improvements, and some projects (34%) had improvements that are still in use. Despite barriers and challenges, interprofessional student teams can successfully learn the basics of QI and work together to design and implement a project. These projects have the potential to make meaningful changes in clinic practices and are helpful to the clinic preceptors.

An Educational Tool for Promoting Transitional Health Care Planning by Nurses From the Hospital to the Community.

Although nurses are an invaluable component of successful health care transition, a large gap exists on methods to educate future health care professionals regarding roles and necessary transition components. The Transitional Nursing History tool introduces prelicensure students to transitional health care planning needs and the essential roles of nurses. The Transitional Nursing History tool provides experiential student learning, promotes understanding of determinants of health influences on transitional planning needs, and encourages active student engagement. Students report increased recognition of the value of transitional health care planning and actively apply the concepts in other clinical settings.

Disease Status and Pubertal Stage Predict Improved Growth in Antitumor Necrosis Factor Therapy for Pediatric Inflammatory Bowel Disease.

BACKGROUND: Growth failure is well-recognized in pediatric inflammatory bowel disease (PIBD; <18 years). We aimed to examine whether antitumor necrosis factor (TNF) therapy improves growth in a PIBD population-based cohort. METHODS: A retrospective review of all Scottish children receiving anti-TNF (infliximab [IFX] and adalimumab [ADA]) from 2000 to 2012 was performed; height was collected at 12 months before anti-TNF (T-12), start (T0), and 12 (T+12) months after anti-TNF. RESULTS: Ninety-three of 201 treated with IFX and 28 of 49 with ADA had satisfactory growth data; 66 had full pubertal data. Univariate analysis demonstrated early pubertal stages (Tanner 1-3 n = 44 vs T4-5 n = 22), disease remission, disease duration ≥2 years, and duration of IFX ≥12 months were associated with improved linear growth for IFX; for ADA only improvement was seen in Tanner 1-3. For IFX, Tanner 1-3 median Δ standard deviation scores for height (Ht SDS) -0.3 (-0.7, 0.2) at T0 changed to 0.04 (-0.5, 0.7) at T+12 (P < 0.001) versus -0.01 (-0.5, 0.9) at T0 in T4-5 changed to -0.01 (-0.4, 0.2) at T+12 (P > 0.05). For IFX disease duration ≥2 year, median Δ Ht SDS was -0.13 (-0.6, 0.3) at T0 then 0.07 (-0.3, 0.6) at T+12 (P < 0.001). Remission improved Δ Ht SDS (median Δ Ht SDS -0.14 [-0.6, 0.3] at T0 to 0.17 [-0.2, 0.7] at T+12 [P < 0.001]). Multiple regression analysis demonstrated corticosteroid usage at T0 predicted improved Δ Ht SDS at T+12 for IFX and ADA. CONCLUSIONS: Anti-TNF therapy is more likely to be associated with growth improvement when used at earlier stages of puberty with remission a key growth-promoting strategy in pediatric Crohn disease.

Intravenous xenogeneic transplantation of human adipose-derived stem cells improves left ventricular function and microvascular integrity in swine myocardial infarction model.

OBJECTIVES: The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery. METHODS: Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n = 7), the single bolus group (SB) (n = 7, 15 × 10(7) ASCs), or the divided dose group (DD) (n = 7, 5 × 10(7) ASCs/day for three consecutive days). Myocardial perfusion defect area and coronary flow reserve (CFR) were compared during the 28-day follow-up. Also, serial changes in the absolute number of circulating CD4(+) T and CD8(+) T cells were measured. RESULTS: The increases in ejection fraction were significantly greater in both the SB and the DD groups compared to the placebo group (5.4 ± 0.9%, 3.7 ± 0.7%, and -0.4 ± 0.6%, respectively), and the decrease in the perfusion defect area was significantly greater in the SB group than the placebo group (-36.3 ± 1.8 and -11.5 ± 2.8). CFR increased to a greater degree in the SB and the DD groups than in the placebo group (0.9 ± 0.2, 0.8 ± 0.1, and 0.2 ± 0.2, respectively). The circulating number of CD8(+) T cells was significantly greater in the SB and DD groups than the placebo group at day 7 (3,687 ± 317/µL, 3,454 ± 787/µL, and 1,928 ± 457/µL, respectively). The numbers of small vessels were significantly greater in the SB and the DD groups than the placebo group in the peri-infarct area. CONCLUSIONS: Both intravenous SB and DD delivery of ASCs are effective modalities for the treatment of MI in swine. Intravenous delivery of ASCs, with its immunomodulatory and angiogenic effects, is an attractive noninvasive approach for myocardial rescue.

Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution.

OBJECTIVES: To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery. BACKGROUND: Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. METHODS: In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery. RESULTS: IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. CONCLUSIONS: Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.

"Employment and arthritis: making it work" a randomized controlled trial evaluating an online program to help people with inflammatory arthritis maintain employment (study protocol).

BACKGROUND: Arthritis and musculoskeletal conditions are the leading cause of long-term work disability (WD), an outcome with a major impact on quality of life and a high cost to society. The importance of decreased at-work productivity has also recently been recognized. Despite the importance of these problems, few interventions have been developed to reduce the impact of arthritis on employment. We have developed a novel intervention called "Making It Work", a program to help people with inflammatory arthritis (IA) deal with employment issues, prevent WD and improve at-work productivity. After favorable results in a proof-of-concept study, we converted the program to a web-based format for broader dissemination and improved accessibility. The objectives of this study are: 1) to evaluate in a randomized controlled trial (RCT) the effectiveness of the program at preventing work cessation and improving at-work productivity; 2) to perform a cost-utility analysis of the intervention. METHODS/DESIGN: 526 participants with IA will be recruited from British Columbia, Alberta, and Ontario in Canada. The intervention consists of a) 5 online group sessions; b) 5 web-based e-learning modules; c) consultations with an occupational therapist for an ergonomic work assessment and a vocational rehabilitation counselor. Questionnaires will be administered online at baseline and every 6 months to collect information about demographics, disease measures, costs, work-related risk factors for WD, quality of life, and work outcomes. Primary outcomes include at-work productivity and time to work cessation of > 6 months for any reason. Secondary outcomes include temporary work cessation, number of days missed from work per year, reduction in hours worked per week, quality adjusted life year for the cost utility analysis, and changes from baseline in employment risk factors. Analysis of Variance will evaluate the intervention's effect on at-work productivity, and multivariable Cox regression models will estimate the risk of work cessation associated with the intervention after controlling for risk factors for WD and other important predictors imbalanced at baseline. DISCUSSION: This program fills an important gap in arthritis health services and addresses an important and costly problem. Knowledge gained from the RCT will be useful to health care professionals, policy planners and arthritis stakeholders. TRIAL REGISTRATION: ClinicalTrials.gov NCT01852851; registered April 13, 2012; first participant randomized on July 6, 2013.

Bridging Didactic Learning and the Complexity of Practice Through Clinical Immersion: Evaluating the Sexual Assault Nurse Examiner Trainee Experience.

ABSTRACT: In this article, we discuss the development and evaluation of the Vanderbilt Nursing Education Program for Sexual Assault Nurse Examiners (VEP-SANE), a 3-day clinical immersion (CI) program, including the lessons learned and the challenges experienced with the completion of two trainee cohorts. To bridge didactic learning and the complexity of practice, the VEP-SANE team designed an innovative, competency-based CI. Fifteen trainees from Cohort 1 and 19 trainees from Cohort 2 met requirements for CI participation. Trainees in Cohort 1 represented the advanced practice registered nurse specialties of emergency, women's health, and pediatrics. For Cohort 2 recruitment, enrollment was expanded to include family and midwifery advanced practice registered nurse specialties. Trainees were required to complete online training modules before CI participation. Online surveys assessed trainee perceptions about levels of knowledge and confidence related to sexual assault nurse examiner competencies (pre/post CI), each CI session, and the overall CI experience. Separate focused discussions were conducted with trainees and faculty after each CI. Both cohorts rated CI sessions as "excellent" or "very good" over 93% of the time. Perceived levels of knowledge and confidence increased from pre-CI to post-CI for both cohorts. Similar CI strengths were identified across trainees and faculty including speakers, high interactivity, safe environment, reality of cases, and surrogate practice. All trainees indicated readiness for preceptorships and interest in a virtual community of practice. Suggestions included more time for laboratory sessions, documenting photos, and interaction with individuals from the lesbian, gay, bisexual and transgender (LGBT) community and presenters. Future efforts focus on CI conversion to a virtual format because of the impact of COVID-19, increased VEP-SANE community of practice interaction, and expanded engagement with practicing sexual assault nurse examiners.

Eliminating false positive C4 sugar tests on New Zealand Manuka honey.

Carbon isotope analyses (delta(13)C) of some New Zealand Manuka honeys show that they often fail the internationally recognised Association of Official Analytical Chemists sugar test (AOAC method 998.12) which detects added C(4) sugar, although these honeys are from unadulterated sources. Failure of these high value products is detrimental to the New Zealand honey industry, not only in lost export revenue, but also in brand and market reputation damage. The standard AOAC test compares the carbon isotope value of the whole honey and corresponding protein isolated from the same honey. Differences between whole honey and protein delta(13)C values should not be greater than +1.0 per thousand, as it indicates the possibility of adulteration with syrups or sugars from C(4) plants such as high fructose corn syrup or cane sugar.We have determined that during the standard AOAC method, pollen and other insoluble components are isolated with the flocculated protein. These non-protein components have isotope values which are considerably different from those of the pure protein, and can shift the apparent delta(13)C value of protein further away from the delta(13)C value of the whole honey, giving a false positive result for added C(4) sugar. To eliminate a false positive C(4) sugar test for Manuka honey, prior removal of pollen and other insoluble material from the honey is necessary to ensure that only the pure protein is isolated. This will enable a true comparison between whole honey and protein delta(13)C isotopes. Furthermore, we strongly suggest this modification to the AOAC method be universally adopted for all honey C(4) sugar tests.

Occupational respiratory health: a survey of Wisconsin workers who wear respirators.

CONTEXT: Little is known about Wisconsin workers who wear respirators and the prevalence of work-related asthma (WRA) in that population. To understand this problem, we questioned workers who wear respirators. OBJECTIVES: The primary objective was to learn more about the health experiences of workers who wear respirators. A secondary objective was to evaluate the utility of the survey in WRA surveillance. DESIGN: A survey was mailed to an opportunistic sample of workers who received medical evaluation for respirator fit testing. PARTICIPANTS: Surveys were sent to 1356 workers medically evaluated to wear a respirator; 192 surveys were completed and returned. RESULTS: The majority of respondents were men who have been medically evaluated for respirator wear an average of 3 times during their career. Every time, most respirator medical evaluations used 3 evaluation tools: questionnaire, physical exam and breathing test. Thirty-two percent of survey respondents had some asthma symptoms while at work in the last 30 days, and half reported discussing these symptoms with a physician. Lifetime prevalence of asthma as determined by this survey was 18%. Lifetime prevalence for WRA amongthis population was 3% (18% among those with asthma). CONCLUSIONS: This survey was an efficient and effective way to learn more about workers' respirator experiences and to determine the prevalence of asthma in this population. Few differences existed between those with asthma and those without. However, some differences were noted between those with asthma and those with WRA. Data also suggest that the respirator medical evaluation process provides an opportunity for health practitioners to discuss asthma and asthma prevention with workers.

The Vanderbilt Program in Interprofessional Learning: Sustaining a Longitudinal, Clinical Experience That Aligns Practice With Education.

PROBLEM: Designing and sustaining a longitudinal, clinic-based interprofessional learning experience is logistically challenging, which has limited the educational opportunities available in health professions schools. The authors discuss the Vanderbilt Program in Interprofessional Learning (VPIL), which addresses some of the challenges facing clinic-based interprofessional experiences. APPROACH: VPIL places first- and second-year students from 4 professional degree programs (medicine, nursing, pharmacy, social work) in Nashville, Tennessee, on teams where they work and learn together in authentic clinical environments over a 2-year period. The program was implemented in 2010 and includes 3 components: a summer immersion experience, seminar-based classroom and simulation sessions, and a weekly clinical experience. Students also complete a capstone quality improvement project. VPIL administrators have set up structures at the institutional, clinic, faculty, and student levels that have contributed to the sustainability of the program. OUTCOMES: Between 2010 and 2019, VPIL admitted 398 students who participated on 91 clinical teams. In addition, 55 clinical preceptors and 12 core faculty trained students for future collaborative practice. The program has received consistently high ratings from students, who have produced 69 quality improvement projects at their clinics. These projects have addressed aspects of the care delivery process and produced durable materials, showing that the program has contributed to important innovations in the health system. NEXT STEPS: VPIL faculty continue to improve the curriculum and administrative structures and work to expand the program to reach a wider variety of health professions students. Going forward, lessons from the program could assist educators in creating opportunities for students to learn interprofessionally and deliver high value health care in increasingly complex delivery systems.

The selective Alzheimer's disease indicator-1 gene (Seladin-1/DHCR24) is a liver X receptor target gene.

The nuclear hormone receptors liver X receptor alpha (LXRalpha) and LXRbeta function as physiological receptors for oxidized cholesterol metabolites (oxysterols) and regulate several aspects of cholesterol and lipid metabolism. Seladin-1 was originally identified as a gene whose expression was down-regulated in regions of the brain associated with Alzheimer's disease. Seladin-1 has been demonstrated to be neuroprotective and was later characterized as 3beta-hydroxysterol-Delta24 reductase (DHCR24), a key enzyme in the cholesterologenic pathway. Seladin-1 has also been shown to regulate lipid raft formation. In a whole genome screen for direct LXRalpha target genes, we identified an LXRalpha occupancy site within the second intron of the Seladin-1/DHCR24 gene. We characterized a novel LXR response element within the second intron of this gene that is able to confer LXR-specific ligand responsiveness to reporter gene in both HepG2 and human embryonic kidney 293 cells. Furthermore, we found that Seladin-1/DHCR24 gene expression is significantly decreased in skin isolated from LXRbeta-null mice. Our data suggest that Seladin-1/DHCR24 is an LXR target gene and that LXR may regulate lipid raft formation.

Regulation of human 3 alpha-hydroxysteroid dehydrogenase (AKR1C4) expression by the liver X receptor alpha.

Type I human hepatic 3alpha-hydroxysteroid dehydrogenase (AKR1C4) plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism. Utilization of a hidden Markov model for predictive modeling of nuclear hormone receptor response elements coupled with chromatin immunoprecipitation/microarray technology revealed a putative binding site in the AKR1C4 promoter for the nuclear hormone receptor known as liver X receptor alpha, (LXRalpha [NR1H3]), which is the physiological receptor for oxidized cholesterol metabolites. The putative LXRalpha response element (LXRE), identified by chromatin immunoprecipitation, was approximately 1.5 kilobase pairs upstream of the transcription start site. LXRalpha was shown to bind specifically to this LXRE and mediate transcriptional activation of the AKR1C4 gene, leading to increased AKR1C4 protein expression. These data suggest that LXRalpha may modulate the bile acid biosynthetic pathway at a unique site downstream of CYP7A1 and may also modulate the metabolism of steroid hormones and certain xenobiotics.

Relationship between circadian oscillations of Rev-erbalpha expression and intracellular levels of its ligand, heme.

The nuclear hormone receptors, REV-ERBalpha [NR1D1] and REV-ERBbeta [NR1D1], were recently demonstrated to be receptors for the porphyrin, heme. Heme regulates the ability of these receptors to repress transcription of their target genes via modulation of the affinity of the receptor's ligand binding domain for the corepressor, NCoR. The REV-ERBs function as critical components of the mammalian clock and their expression oscillates in a circadian manner. Here, we show that in NIH3T3 cells intracellular heme levels also oscillate in a circadian fashion. These data are the first to show the temporal relationship of intracellular heme levels to the expression of its receptor, Rev-erbalpha, and suggest that the rapid oscillations in heme levels may an important component regulating REV-ERB transcriptional activity.

ARF differentially modulates apoptosis induced by E2F1 and Myc.

The ARF tumor suppressor participates in a p53-dependent apoptotic pathway that is stimulated in response to some oncogenic stimuli. The E2F1 transcription factor is a critical downstream target of the Rb tumor suppressor and, when active, can promote proliferation as well as apoptosis. The finding that E2F1 transcriptionally regulates the ARF gene has led to the suggestion that ARF contributes to E2F1-induced apoptosis. Counter to this hypothesis, this study demonstrates not only that ARF is unnecessary for E2F1 to induce apoptosis but also that inactivation of ARF actually enhances the ability of E2F1 to promote apoptosis. Inactivation of ARF also cooperates with E2F1 activity to promote entry into the S phase of the cell cycle. This relationship between ARF and E2F1 is demonstrated in transgenic epidermis in vivo and in mouse embryo fibroblast cultures in vitro. In contrast, the ability of Myc to induce apoptosis is diminished in the absence of ARF. E2F1 induces the accumulation of p53 in the absence of ARF, and this is associated with the phosphorylation of p53 on several residues. These findings demonstrate that ARF is a negative regulator of E2F1 activity and is not required for E2F1-induced apoptosis.

Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: implications for current clinical trials.

BACKGROUND: Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. METHODS AND RESULTS: Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26+/-3% (IM), 47+/-1% (IC), and 43+/-3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11+/-3%) compared with IC (2.6+/-0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2+/-1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. CONCLUSIONS: The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

Inactivation of E2f1 enhances tumorigenesis in a Myc transgenic model.

Previous studies have demonstrated both oncogenic and tumor suppressive properties for the E2F1 transcription factor. In this study, E2f1-null mice were crossed with transgenic mice expressing Myc under the control of an epithelial-specific keratin 5 promoter to determine whether the absence of E2F1 would modulate the oncogenic activity of Myc. Inactivation of E2f1 was found to significantly accelerate tumor development in keratin 5 Myc transgenic mice. Acceleration of tumorigenesis occurred despite the fact that apoptosis levels were increased in transgenic tissue and tumors null for E2f1, whereas Myc-induced proliferation was unaffected by the status of E2f1. These findings provide new insight into the tumor suppressive activity of E2F1 and identify for the first time a specific oncogenic alteration that cooperates with the loss of E2F1 in tumorigenesis.

E2F1 uses the ATM signaling pathway to induce p53 and Chk2 phosphorylation and apoptosis.

The p53 tumor suppressor protein is phosphorylated and activated by several DNA damage-inducible kinases, such as ATM, and is a key effector of the DNA damage response by promoting cell cycle arrest or apoptosis. Deregulation of the Rb-E2F1 pathway also results in the activation of p53 and the promotion of apoptosis, and this contributes to the suppression of tumor development. Here, we describe a novel connection between E2F1 and the ATM DNA damage response pathway. In primary human fibroblasts lacking functional ATM, the ability of E2F1 to induce the phosphorylation of p53 and apoptosis is impaired. In contrast, ATM status has no effect on transcriptional activation of target genes or the stimulation of DNA synthesis by E2F1. Cells containing mutant Nijmegen breakage syndrome protein (NBS1), a component of the Mre11-Rad50 DNA repair complex, also have attenuated p53 phosphorylation and apoptosis in response to E2F1 expression. Moreover, E2F1 induces ATM- and NBS1-dependent phosphorylation of the checkpoint kinase Chk2 at Thr68, a phosphorylation site that stimulates Chk2 activity. Delayed gammaH2AX phosphorylation and absence of ATM autophosphorylation at Ser1981 suggest that E2F1 stimulates ATM through a unique mechanism that is distinct from agents that cause DNA double-strand breaks. These findings identify new roles for several DNA damage response factors by demonstrating that they also participate in the oncogenic stress signaling pathway between E2F1 and p53.

Multiattribute health utility scoring for the computerized adaptive measure CAT-5D-QOL was developed and validated.

OBJECTIVES: The CAT-5D-QOL is a previously reported item response theory (IRT)-based computerized adaptive tool to measure five domains (attributes) of health-related quality of life. The objective of this study was to develop and validate a multiattribute health utility (MAHU) scoring method for this instrument. STUDY DESIGN AND SETTING: The MAHU scoring system was developed in two stages. In phase I, we obtained standard gamble (SG) utilities for 75 hypothetical health states in which only one domain varied (15 states per domain). In phase II, we obtained SG utilities for 256 multiattribute states. We fit a multiplicative regression model to predict SG utilities from the five IRT domain scores. The prediction model was constrained using data from phase I. We validated MAHU scores by comparing them with the Health Utilities Index Mark 3 (HUI3) and directly measured utilities and by assessing between-group discrimination. RESULTS: MAHU scores have a theoretical range from -0.842 to 1. In the validation study, the scores were, on average, higher than HUI3 utilities and lower than directly measured SG utilities. MAHU scores correlated strongly with the HUI3 (Spearman ρ = 0.78) and discriminated well between groups expected to differ in health status. CONCLUSION: Results reported here provide initial evidence supporting the validity of the MAHU scoring system for the CAT-5D-QOL.

Multimodality imaging methods for assessing retinoblastoma orthotopic xenograft growth and development.

Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux ([Formula: see text]) through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed [Formula: see text], as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, [Formula: see text] in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of [Formula: see text] modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future.

Safety of infliximab treatment in patients with rheumatoid arthritis in a real-world clinical setting: description and evaluation of infusion reactions.

OBJECTIVE: To describe acute and delayed infusion reactions in a large cohort of patients with inflammatory arthritis, treated with infliximab (IFX). METHODS: We conducted a retrospective chart review of patients treated with IFX at the Mary Pack Arthritis Centre between 2000 and 2008. The primary outcome was the occurrence of acute infusion reactions during infusions or 1-2 hours after each infusion, and secondary outcome was the occurrence of delayed infusion reactions 1-14 days after an infusion. Descriptive analyses were conducted to summarize study outcomes and identify trends over followup. RESULTS: Since 2000, 376 patients were referred to the Mary Pack IFX clinic and 200 received 4399 IFX infusions over a mean 140 ± 132 weeks of followup. Of these, 135 were patients with RA who received 2977 IFX infusions over mean followup of 138 ± 132 weeks. In total 258 episodes of acute reactions were observed for an overall acute reaction rate of 5.8%. Acute infusion reactions were mostly mild (42.6%) and moderate (43.8%) and commonly affected sites were head and neck (31.5%) and cutaneous (21.1%). A total of 37 delayed infusion reaction episodes were observed (0.9% rate); reactions were also mostly mild (16.2%) and moderate (64.9%). CONCLUSION: These clinical data from 200 patients treated with IFX demonstrate that acute and delayed infusion reactions occur infrequently and are mostly mild to moderate in presentation.