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Active rheumatoid arthritis (RA) is associated with increased cardiovascular risk and impaired function of high-density lipoprotein (HDL). Previous work suggests that HDL may become dysfunctional through oxidative modifications within the RA joint. The current work evaluates an association of synovial power doppler ultrasound signal (PDUS) with HDL function and structure. Two open-label clinical therapeutic studies using PDUS as a disease outcome measure were included in this analysis, including a 12-month trial of subcutaneous abatacept in 24 RA patients and a 6-month trial of IV tocilizumab in 46 RA patients. Laboratory assays included assessments of HDL function and structure, HDL and total cholesterol levels, and a cytokine/chemokine panel. Patients with the highest baseline PDUS scores in both clinical studies, had worse HDL function, including suppression of paraoxonase 1 (PON1) activity as well as lower HDL-C levels. Associations between other disease assessments (DAS28 and CDAI) and HDL function/structure were noted but were generally of lesser magnitude and consistency than PDUS across the HDL profile. Treatment with tocilizumab for 6 months was associated with increases in cholesterol levels and improvements in the HDL function profile, which correlated with greater decreases in PDUS scores. Similar trends were noted following treatment with abatacept for 3 months. Higher baseline PDUS scores identified patients with worse HDL function. This data supports previous work suggesting a direct association of joint inflammation with abnormal HDL function.

Introduction/objectivesPsychological stress worsens rheumatoid arthritis (RA) disease activity, and the COVID-19 pandemic has increased stress/anxiety in rheumatic patients. The purpose of this study was to determine if stress during the COVID-19 pandemic specifically impacts RA disease activity as reported by the patient.MethodThis was a cross-sectional COVID-19 RA survey study. University of California, Los Angeles rheumatology clinic patients were emailed a link to a survey in July and November 2020. The 30-question survey pertained to COVID-19-related stress, RA disease activity, and demographics. For the survey responders, anti-cyclic citrullinated antibody, rheumatoid factor, and age were extracted from the electronic health record. Analyses were performed to examine the association between the 4-item Perceived Stress Scale (PSS-4) and other COVID-19-related stress measures with the Routine Assessment of Patient Index Data 3 (RAPID3).ResultsA total of 1138/5037 subjects completed the emailed survey (22.6% response rate). When examining responses across RAPID3 categories (near remission, low, moderate, and high disease severity), there were significant increases in PSS-4 and other stress variables. Multiple linear regression models showed that PSS-4, financial stress, age, seropositivity, disease duration, and Black race were independently associated with worsened RAPID3 scores, when controlling for other confounding factors.ConclusionsThis study suggests that stress overall negatively impacts RAPID3, and Black RA patients had a higher RAPID3 scores during the COVID-19 pandemic. Despite colossal efforts to combat the pandemic, RA patients currently suffer from stress/anxiety, and methods to mitigate these psychological effects are needed.

Patients from historically underrepresented racial and ethnic groups are enrolled in cancer clinical trials at disproportionately low rates in the United States 1-3. As these patients often have limited English proficiency4-7, we hypothesized that one barrier to their inclusion is the cost to investigators of translating consent documents. To test this hypothesis, we evaluated more than twelve-thousand consent events at a large Cancer Center and assessed whether patients requiring translated consent documents would sign consent documents less frequently in studies lacking industry sponsorship (for which the principal investigator pays translation costs) than for industry sponsored studies (for which this cost is covered by the sponsor). Here, we show that the proportion of consent events for patients with limited English proficiency in studies not sponsored by industry was approximately half of that seen in industry sponsored studies. We also show that among those signing consent documents, the proportion of consent documents translated into the patient’s primary language in studies without industry sponsorship was approximately half of that seen in industry sponsored studies. Our results suggest that the cost of consent document translation in trials not sponsored by industry is a potentially modifiable barrier to the inclusion of patients with limited English proficiency.

Musculoskeletal ultrasound real-time image acquisition and scoring are complex, and many factors affect reliability. Static image reliability does not guarantee real-time scoring. This study aimed to identify factors and solutions to improve real-time scoring reliability for the grey scale and power Doppler evaluation of synovitis. We also report on using a novel musculoskeletal ultrasound synovitis rule-based scoring atlas.In four stages, we evaluated inter- and intra-reader reliability among three ultrasonographers (US1-3). Intra- and inter-reader reliability was calculated using weighted-kappa, intraclass correlation coefficient, and Spearman correlation. Reliability statistics were compared between stages using permutation tests to compute empirical distributions for differences in those statistics. At each stage, factors that diminished reliability were identified and addressed. After intensive reliability exercises, a RA MSUS atlas with in-depth scoring rules was generated to improve interpretive reliability.The three ultrasonographers had good to excellent intra-reader reliability for real-time acquisition scoring over 2432 views (weighted kappa 0.52-0.80, intraclass correlation coefficient 0.59-0.86, and Spearman correlation 0.64-0.86). Inter-reader reliability was good to excellent between US1/US2 and US1/US3 (weighted kappa 0.51-0.66, intraclass correlation coefficient 0.66-0.75, Spearman correlation 0.59-0.73). US1 achieved significant improvement in intra-reader reliability from stage 1 to stage 2 (

Within rheumatoid arthritis (RA) patients treated with intravenous tocilizumab (IV-TCZ), it is unclear if power Doppler ultrasonography (PDUS) can predict future clinical response. This study sought to determine if baseline PDUS or its early changes can predict 12-week and 24-week disease activity outcomes, and quantify the need for dose escalation (4 to 8 mg/kg). Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24 weeks using 34-joint PDUS (US34-PDUS), clinical disease activity index (CDAI), 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR), ACR 20/50/70, health assessment questionnaire-disability index (HAQ-DI), and PDUS 20/50/70, a novel measure. Logistic regression models evaluated the predictive utility of US34-PDUS of DAS28-ESR response after adjusting for covariates. Ninety-four percent of patients required dose escalation to 8 mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24 weeks (p

Musculoskeletal ultrasound quantifies the total synovial inflammatory burden in rheumatoid arthritis (RA) but is time consuming when scanning numerous joints. This study evaluated a novel patient-centered method for constructing a longitudinal ultrasound score in RA patients. Fifty-four RA patients starting intravenous tocilizumab were evaluated with power Doppler ultrasound (PDUS) of 34 joints and DAS28-ESR was assessed at baseline and weeks 4, 12, 16, and 24. The sentinel joint score (SJS) was derived from the reduced subset of joints with PDUS ≥ 1 at baseline. Total PDUS (tPDUS) score and US7 were also calculated. Changes in tPDUS and SJS were correlated. Effect sizes were calculated for tPDUS, SJS, and US7. The proportion of “flipped” joints without baseline PDUS signal that later developed PDUS signal was estimated. At baseline, 1236/1829 joints scanned (67.5%) did not have PDUS signal. The proportion of “flipped” joints at 24 weeks was 5.6% for ≥ 1, 2.9% for ≥ 2, and 1.0% for = 3 PD. tPDUS and SJS scores were highly correlated (r = 0.91 to 0.97). Overall the effect sizes for tPDUS, SJS, and US7 increased over 24 weeks, where SJS was the highest (SJS 1.00 4-week, 1.07 12-week, 1.26 24-week) and tPDUS and US7 were comparable (tPDUS 0.32 4-week, 0.52 12-week, 0.84 24-week; US7 0.23 4-week, 0.52 12-week, 0.74 24-week). In RA patients starting a biologic, scanning only joints with baseline PDUS signal can substantially reduce the number of joints requiring follow-up scanning by 67.5% and improves feasibility. “Flipped” joints are infrequently seen after starting therapy. ClinicalTrials.gov NCT01717859

Objective To examine whether a weight loss intervention programme improves RA disease activity and/or musculoskeletal ultrasound synovitis measures in obese RA patients. Methods We conducted a proof-of-concept, 12-week, single-blind, randomized controlled trial of obese RA patients (BMI ≥ 30) with 28-joint DAS (DAS28) ≥ 3.2 and with evidence of power Doppler synovitis. Forty patients were randomized to the diet intervention (n = 20) or control group (n = 20). Diet intervention consisted of a hypocaloric diet of 1000–1500 kcal/day and high protein meal replacements. Co-primary outcomes included change in DAS28 and power Doppler ultrasound (PDUS)-34. Clinical disease activity, imaging, biomarkers, adipokines and patient-reported outcomes were monitored throughout the trial. Recruitment terminated early. All analyses were based on intent-to-treat for a significance level of 0.05. Results The diet intervention group lost an average 9.5 kg/patient, while the control group lost 0.5 kg (P Conclusion Obese RA patients on the diet intervention achieved weight loss. There were significant between group improvements for RAPID3, adiponectin and leptin levels, and positive trends for DAS28 and HAQ-DI. Longer-term, larger weight loss studies are needed to validate these findings, and will allow for further investigative work to improve the clinical management of obese RA patients. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02881307

Prior research has identified frailty, comorbidity, and age as predictors of outcomes for patients with coronavirus disease 2019 (COVID-19), including mortality. However, it remains unclear how these factors play different roles in COVID-19 prognosis. This study focused on correlations between frailty, comorbidity and age, and their correlations to discharge outcome and length-of-stay in hospitalized patients with COVID-19. Clinical data was collected from 56 patients who were ≥50 years old and admitted from March 2020 to June 2020 primarily for COVID-19. Frailty Risk Score (FRS) and the Charlson Comorbidity Index (CCI) were used for assessment of frailty and comorbidity burden, respectively. Age had significant positive correlation with FRS and CCI (P .001, P .001, respectively). There was also significant positive correlation between FRS and CCI (P .001). For mortality, patients who died during their hospitalization had significantly higher FRS and CCI (P = .01 and P .001, respectively) but were not significantly older than patients who did not. FRS, CCI, and age were all significantly associated when looking at overall adverse discharge outcome (transfer to other facility or death) (P .001, P = .005, and P = .009, respectively). However, none of the 3 variables were significantly correlated with length-of-stay. Multivariate analysis showed FRS (P = .007) but not patient age (P = .967) was significantly associated with death. We find that frailty is associated with adverse outcomes from COVID-19 and supplants age in multivariable analysis. Frailty should be part of risk assessment of older adults with COVID-19.

PURPOSE To evaluate the effects of a short web-based educational program on Japanese nurses' self-reported attitudes toward tobacco cessation and their use of interventions to help smokers to quit. DESIGN Prospective, single-group design with a pre-educational survey, a short web-based educational program, and a follow-up survey at 3 months. METHODS Clinical nurses were asked to view two prerecorded webcasts about helping smokers quit. They completed two online surveys, one at baseline and one at a 3-month follow-up. Generalized linear models were used to determine changes in nurses' self-reported routine practice after the study intervention. FINDINGS A total of 1401 nurses responded to the baseline survey, 678 of whom completed the follow-up survey. Compared with baseline, nurses at follow-up were more likely to advise smokers to quit (odds ratio [OR] = 1.45, 95% confidence interval [CI: 1.15, 1.82]), assess patients' interest in quitting (OR = 1.46, 95% CI [1.01, 1.04]), and assist patients with smoking cessation (OR = 1.34, 95% CI [1.04, 1.72]). However, the proportion of nurses who consistently recommended resources for tobacco cessation did not significantly improve at follow-up. CONCLUSIONS This study provides preliminary evidence that a web-based educational program can increase nurses' implementation of tobacco dependence interventions in cancer care practice. Sustaining these educational efforts could increase nurses' involvement in providing these interventions, encourage nurses to refer patients to cessation resources, and support nurses' attitudes towards their role in smoking cessation. CLINICAL RELEVANCE Our short web-based educational program can increase nurses' use of tobacco-dependence interventions in cancer care practice. This role can be enhanced with additional information about existing cessation resources that nurses could use to refer patients for support post-discharge. Japanese nurses, when properly educated, are willing and significant contributors to promote tobacco use cessation for cancer patients. The contribution can be facilitated through nursing care protocol that integrate tobacco use cessation interventions within evidence-based cancer care approaches.

Within rheumatoid arthritis (RA) patients treated with intravenous tocilizumab (IV-TCZ), it is unclear if power Doppler ultrasonography (PDUS) can predict future clinical response. This study sought to determine if baseline PDUS or its early changes can predict 12-week and 24-week disease activity outcomes, and quantify the need for dose escalation (4 to 8 mg/kg).Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24 weeks using 34-joint PDUS (US34-PDUS), clinical disease activity index (CDAI), 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR), ACR 20/50/70, health assessment questionnaire-disability index (HAQ-DI), and PDUS 20/50/70, a novel measure. Logistic regression models evaluated the predictive utility of US34-PDUS of DAS28-ESR response after adjusting for covariates.Ninety-four percent of patients required dose escalation to 8 mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24 weeks (p 0.001). Baseline PDUS and 12-week PDUS change correlated with CDAI at 24 weeks (p 0.05). Logistic regression demonstrated baseline US34-PDUS was independently associated with DAS28-ESR ≥ 1.2 response, even after adjusting for baseline DAS28-ESR (p = 0.03). CDAI, DAS28-ESR, and their components increased across PDUS 20/50/70 categories; however, HAQ-DI did not.RA patients treated with IV-TCZ for 24 weeks demonstrated significant improvement, and baseline/early changes in PDUS were predictive of later clinical response. The PDUS 20/50/70 measure is a novel metric of response. This study suggests that IV-TCZ 4 mg/kg may not be sufficient to attain low RA disease activity at 12 weeks, in RA patients with moderate to severe disease (DAS28 ≥ 4.4 and US34-PDUS ≥ 10).ClinicalTrials.gov NCT01717859 Key Points • Over 90% of RA patients with baseline DAS28-ESR ≥ 4.4 and PDUS34 ≥ 10 required intravenous tocilizumab dose escalation from 4 to 8 mg/kg at 12 weeks. • Reduction in power Doppler ultrasonography (US34-PDUS) scores correlate with DAS28-ESR and CDAI over 24 weeks in rheumatoid arthritis patients with moderate to severe disease activity. • Baseline US34-PDUS predicts future improvements in clinical disease activity outcomes, independent of baseline DAS28-ESR. • Clinical response measures, DAS28-ESR and CDAI, improved across US34-PDUS 20/50/70 categories, while patient-reported outcomes did not.

6533 Background: Racial/ethnic minority patients (pts) are underrepresented in cancer clinical trials. Challenges specific to LEPPs include the need for translated CDs, which can cause research delays and add cost. While most enrollment barriers are similar between industry sponsored studies (ISS) and NISS, costs of CD translation are typically covered by the sponsor in ISS. NISS often have limited, or no funds allocated for CD translation. Although it is required that LEPPs sign translated CDs, we hypothesized that investigators on NISS would find ways to avoid incurring the cost of CD translation. Methods: All pts who consented to studies at the UCLA Jonsson Comprehensive Cancer Center from 2013-2018 were included. Electronic health record data was reviewed. Adult LEPPs had a primary language other than English and their chart either flagged them as needing an interpreter or the pt used an interpreter in their care 6 months before or after the consent date. For pediatric patients, regardless of the pt’s primary language, LEPPs had a guardian who needed an interpreter within 6 months of the consent date. CD language was documented when available by chart review, but when not, we evaluated all IRB-approved CDs for the corresponding study and assumed that the pt signed appropriately translated CDs if available at the time of consent or within the following month. Chi square tests were used to compare the proportion of LEPPs who consented to NISS vs ISS and the proportion of LEPPs who consented with CDs not in their primary language. All analyses were performed using JMP, Version 16. SAS Institute Inc., Cary, NC, 1989–2021. Results: Although we do not have access to data on to whom consents were offered, of the 12202 consenting events during the study period, the proportion of consenting events for LEPPs was 2.7% in NISS vs 5.4% for ISS (p < 0.01). This difference did not appear to be driven by study type, as results were similar when only consenting events for interventional studies (n = 9886) were considered, with LEPPs representing 2.4% in NISS vs 5.5% in ISS (p < 0.01). Among LEPPs, 67.2% of participants who consented to NISS consented with CDs in a language other than their primary language vs 32.2% in ISS (p < 0.01). LEPPs who consented with language appropriate CDs represented 0.9% of those consenting to NISS vs 3.7% for ISS (p < 0.01). Conclusions: LEPPs consented less frequently to NISS compared to ISS, and when they did consent to NISS, the CDs were usually not translated into the pt’s primary language. We posit that the cost of translating CD discourages investigators from consenting LEPPs to NISS. Approaches that reduce or eliminate translation costs should increase the availability of translated CDs, potentially increasing enrollment of LEPPs to NISS while ensuring that they are fully informed about the purpose, procedures, and risks involved in these trials.

Musculoskeletal ultrasound quantifies the total synovial inflammatory burden in rheumatoid arthritis (RA) but is time consuming when scanning numerous joints. This study evaluated a novel patient-centered method for constructing a longitudinal ultrasound score in RA patients.Fifty-four RA patients starting intravenous tocilizumab were evaluated with power Doppler ultrasound (PDUS) of 34 joints and DAS28-ESR was assessed at baseline and weeks 4, 12, 16, and 24. The sentinel joint score (SJS) was derived from the reduced subset of joints with PDUS ≥ 1 at baseline. Total PDUS (tPDUS) score and US7 were also calculated. Changes in tPDUS and SJS were correlated. Effect sizes were calculated for tPDUS, SJS, and US7. The proportion of "flipped" joints without baseline PDUS signal that later developed PDUS signal was estimated.At baseline, 1236/1829 joints scanned (67.5%) did not have PDUS signal. The proportion of "flipped" joints at 24 weeks was 5.6% for ≥ 1, 2.9% for ≥ 2, and 1.0% for = 3 PD. tPDUS and SJS scores were highly correlated (r = 0.91 to 0.97). Overall the effect sizes for tPDUS, SJS, and US7 increased over 24 weeks, where SJS was the highest (SJS 1.00 4-week, 1.07 12-week, 1.26 24-week) and tPDUS and US7 were comparable (tPDUS 0.32 4-week, 0.52 12-week, 0.84 24-week; US7 0.23 4-week, 0.52 12-week, 0.74 24-week).In RA patients starting a biologic, scanning only joints with baseline PDUS signal can substantially reduce the number of joints requiring follow-up scanning by 67.5% and improves feasibility. "Flipped" joints are infrequently seen after starting therapy.ClinicalTrials.gov NCT01717859 Key messages • Only a small percent of joints develop power Doppler signal after baseline scanning. • Changes in the SJS correlate well with changes in clinical activity measured by DAS28-ESR over time. • The SJS effect size is higher than total PDUS and US7 scores, and may improve examination feasibility.

Background Musculoskeletal ultrasound (MSUS) and the multi-biomarker disease activity (MBDA) score are outcome measures that may aid in the management of rheumatoid arthritis (RA) patients. This study evaluated tofacitinib response by MSUS/MBDA scores and assessed whether baseline MSUS/MBDA scores or their early changes predict later clinical response. Methods Twenty-five RA patients treated with tofacitinib were assessed at baseline, 2, 6 and 12-weeks. Power doppler (PDUS) and gray scale (GSUS) ultrasound scores, MBDA score, clinical disease activity index (CDAI), and disease activity score (DAS28) were obtained. Pearson correlations and multiple linear regression models were used to evaluate associations and identify predictors of response to therapy. Results MSUS, MBDA scores, CDAI, and DAS28 improved significantly over 12 weeks (p p p p p = 0.03). Conclusions RA patients treated with tofacitinib for 12 weeks demonstrated improvement by clinical, imaging, and biomarker end-points. Baseline PDUS and MBDA score were predictive of CDAI and DAS28 responses. This is the first study to evaluate early measurements of MSUS and MBDA score as predictors of clinical response in RA patients treated with tofacitinib. Trial registration ClinicalTrials.gov NCT02321930 (registered 12/22/2014).

Background Joint replacements continue to occur during a rheumatoid arthritis (RA) patient’s lifetime despite significant advances in available treatment options. The purpose of this study was to examine and quantify synovitis in surgically operated joints by ultrasound (US) in RA patients starting a new therapeutic agent. Methods RA subjects were enrolled in either tocilizumab or tofacitinib open-label, investigator-initiated trials and were assessed by ultrasound. In a subset of RA patients with joint replacements and/or operations of joint areas (OJA; e.g. joint arthroscopies, fusions, and synovectomies), joint-level scores of synovitis were compared between replaced joints, OJAs, and native joints. Joint-level synovitis was measured by grayscale (GSUS (0–3)) and power Doppler (PDUS (0–3)) at baseline and follow-up (3–6 months). McNemar’s test or Wilcoxon signed rank test utilized the mixed effects ordinal logistic regression models. Results Twenty RA patients had a total of 25 replaced joints and 24 OJA. All replaced joints had GSUS> 1 and 92% had PDUS> 1 at baseline, while OJA and native joints had lower evidence of GSUS> 1 (37.5, 38% respectively) and PDUS> 1 (45.8, 62% respectively). GSUS and PDUS semiquantitative scores improved significantly with treatment in replaced joints (p = 0.01, p = 0.007), and native joints (p Conclusions In RA, joint replacement does not eliminate or prevent ultrasound measured synovitis, where all replaced joints have some evidence of US synovitis. US can also act as a potential marker of response to therapy in replaced joints. Scoring US synovitis in replaced joints should be considered in ultrasound RA clinical trials. Trial registration ClinicalTrials.gov NCT01717859 (registered 10/31/2012); ClinicalTrials.gov NCT02321930 (registered 12/22/2014).

Author(s): Bialous, Stella A; Nohavova, Iveta; Kralikova, Eva; Wells, Marjorie J; Brook, Jenny; Sarna, Linda | Abstract: IntroductionProperly educated nurses delivering evidence-based tobacco dependence treatment could contribute to improving health and reducing regional disparities in tobacco-related disease and death in Central and Eastern Europe. The aims of this study are to describe development of the Eastern European Nurses' Centre of Excellence for Tobacco Control (COE) and evaluate its online educational program on tobacco dependence treatment using the 5As framework.MethodsThe online education evaluation followed a prospective, single group, pre- and post-assessment of changes in nurses' self-reported tobacco cessation interventions. Leaders from five Eastern European countries (Hungary, Czech Republic, Romania, Slovakia, Slovenia) developed protocols for in-country tobacco control education. Nurses responded to a baseline survey, accessed an online nursing educational program, and completed a follow-up survey at 3 months, in the period December 2015 to June 2016. A total of 695 nurses from five countries answered questions on cessation interventions at baseline and of these 507 (73%) completed a follow-up survey at 3 months.ResultsAt the follow-up at 3 months, the 507 nurses self-reported a significant increase in providing all 5A components, i.e. nurses were significantly (pl0.0001) more likely to always /usually advise a patient to quit, assess interest in quitting (p=0.002), assist with a quit plan, review barriers to quitting and recommend a smoke-free home post-discharge (all pl0.0001). They were also significantly more likely (p=0.01) to agree or strongly agree that nurses have an obligation to advise patients on the risks of smoking. There was a significant increase (pl0.0001) in nurses' estimate of the number of patients they provided a cessation intervention the previous week. Nurses who smoked were 60% more likely to assist and arrange compared to nurses who never smoked.ConclusionsCoordinating multi-country activities through a COE was successful in engaging a network of nurses to use an online educational program and participate in other tobacco control activities.

Aims and objectives The aims were to evaluate an educational program about nurses’ role in tobacco dependence treatment, and its webcast component, on the long-term impact of increasing the frequency of nurses’ self-reported changes in practice related to delivery of smoking cessation interventions. Background Healthcare professionals’ knowledge about evidence-based tobacco dependence treatment using the 5As framework (Ask about tobacco use, Advise users to quit, Assess willingness to quit, Assist in making a quit plan, and Arrange for follow-up, including referral to a quitline) is essential to increase smoking cessation rates in the United States. Design A six-month pre-post design. Methods A convenience sample of nurses (N = 283) from Kentucky and Louisiana was provided access to the webcast and printed toolkit. Responses from those who completed an online survey at baseline, and at three- or six-months post-implementation of the educational program were included in an analysis of changes in the consistent (always/usually) delivery of the 5As plus referral to the quitline. Results After three-months, the intervention had a significant impact on increasing nurses’ reports of consistently providing the 5As to patients who smoked, which was largely sustained at six-months. Nurses who viewed the webcast were three times more likely to refer smokers to a quitline at three-months; and four times more likely at six-months than those who did not. Conclusions An online educational program, plus printed toolkit about tobacco dependence treatment increased nurses’ delivery of smoking cessation interventions over time. This study provided preliminary evidence that including a webcast in a nurse-targeted educational program could significantly increase the proportion of nurses who referred smokers to a quitline beyond the benefit of access to printed materials and web-based resources. Relevance to practice Distance learning is a feasible mechanism to enhance nurses’ involvement in tobacco dependence treatment and promoting evidence-based clinical practice. This article is protected by copyright. All rights reserved.

Background Tobacco use is the leading cause of preventable disease and death in Europe and worldwide. Nurses, if properly educated, can contribute to decreasing the burden of tobacco use in the region by helping smokers quit smoking. Aims To assess: (a) the feasibility of an online program to educate nurses in Czech Republic and Poland on evidence-based smoking cessation interventions for patients and (b) self-reported changes in practices related to consistently (usually or always) providing smoking cessation interventions to smokers, before and 3 months after participation in the program. Methods A prospective single-group pre-post design. Results A total of 280 nurses from Czech Republic and 156 from Poland completed baseline and follow-up surveys. At 3 months, nurses were significantly more likely to provide smoking cessation interventions to patients who smoke and refer patients for cessation services (p < .01). Nurses significantly improved their views about the importance of nursing involvement in tobacco control. Implications for Practice Education about tobacco control can make a difference in clinical practice, but ongoing support is needed to maintain these changes. Health system changes can also facilitate the expectation that delivering evidence-based smoking cessation interventions should be routine nursing care. Linking Evidence to Action Educating nurses on cessation interventions and tobacco control is pivotal to decrease tobacco-related disparities, disease, and death. Online methods provide an accessible way to reach a large number of nurses.

Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aβ), tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aβ, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP)., Highlights • We researched the correlations of hippocampal radial distance with Alzheimer's pathology. • Hippocampal radial distance was associated with mean neuronal count and diagnosis. • Our findings support for the use of hippocampal surface mapping in AD research.

To evaluate use of a British English version of the validated French FLARE-RA questionnaire among American English speaking patients. In addition, to create a culturally adapted American English (AmE) FLARE-RA questionnaire and to examine its attributes of patient-reported RA flare status.Using standardized cultural adaptation guidelines, we cognitively debriefed 25 American English speaking rheumatoid arthritis (RA) outpatients and created AmE-FLARE-RA with their input. One hundred three additional RA patients were recruited. Patients completed the Routine Assessment of Patient Index Data 3 (RAPID3), patient global visual analogue scale (VAS), AmE-FLARE-RA, and self-reports of flare. Physician global VAS, physician-assessed flare, swollen and tender joint count (TJC), and clinical disease activity index (CDAI) were documented. AmE-FLARE-RA and disease activity measures were compared between patient-reported and physician-reported flare categories.Patients were female (89%), with mean (SD) age 51.1 (± 15.3) years and mean disease duration (SD) 11.9 (± 10.1) years, with 26% in remission/low disease activity. Total AmE-FLARE-RA scores, RAPID3, CDAI, and patient global VAS were significantly higher for both patient-reported flares and physician-reported flares compared with non-flaring patients by self- or physician report (p 0.05). Total AmE-FLARE-RA scores correlated significantly with RAPID3 (corr = 0.50, p 0.0001) and with CDAI (corr = 0.45, p 0.0001). Across "no flares," "one flare," and "several flare" groups, there was a non-significant increase in AmE-FLARE-RA scores (p = 0.07).The British English FLARE-RA was successfully adapted for AmE-speaking RA patients. AmE-FLARE-RA significantly correlated with RAPID3 and CDAI and distinguished between patient-reported and physician-reported flares, making it useful to detect flares in American RA patients.Key Points• The American English FLARE-RA (AmE-FLARE-RA) questionnaire is the result of cognitive debriefing with American RA patients using the British English version of the validated French FLARE-RA and incorporates patient-recommended language modifications..• Patients self-reporting flares had significantly higher AmE-FLARE-RA scores, compared with those without flares at the time of visit. AmE-FLARE-RA scores correlate with RAPID3 and CDAI.• There was a non-statistically significant trend using the AmE-FLARE-RA scores when examining patients with no flare, one flare, or several flares.• AmE-FLARE-RA total scores are uniformly elevated (~ 6.0 on a 0-10 scale), regardless of discordance between patient and MD assessment of flare at time of visit (~ 30%).

Author(s): Wiley, Dorothy J; Hsu, Hilary K; Ganser, Martha A; Brook, Jenny; Elashoff, David A; Moran, Matthew G; Young, Stephen A; Joste, Nancy E; Mitsuyasu, Ronald; Darragh, Teresa M; Morris, David H; Martinez-Maza, Otoniel M; Detels, Roger; Rao, Jian Yu; Bolan, Robert K; Shigeno, Eric T; Rodriguez, Ernesto | Abstract: BackgroundAn anal histological high-grade squamous intraepithelial lesion (hHSIL) is an anal cancer precursor. Experts recommend Dacron swab anal cytology as a primary screen for anal hHSILs, especially among human immunodeficiency virus-infected and -uninfected men who have sex with men (MSM). Studies have shown that Dacron cytology inaccurately predicts anal hHSILs and results in unnecessary diagnostic procedures. Nylon-flocked (NF) swabs have been shown to trap pathogens and cells well. Thus, this study compared test characteristics of anal cytology using NF and Dacron swab collection protocols to predict anal hHSILs.MethodsA single-visit, randomized clinical trial compared NF and Dacron swab anal cytology specimens to predict high-resolution anoscopy and biopsy-diagnosed anal hHSILs. Data for 326 gay men, bisexual men, other MSM, and male-to-female transgender women contributed descriptive and tabular statistics with which unadjusted and fully adjusted logistic regression models were constructed. The models estimated the odds of hHSILs, test accuracy (area under the curve [AUC]) and sensitivity, and specificity as well as the positive and negative predictive values of abnormal NF and Dacron cytology for predicting hHSILs.ResultsIn the fully adjusted model, the sensitivities for NF and Dacron cytology were nearly equal (48% vs 47%), but the specificity was higher with NF cytology (76% vs 69%). Comparisons of the areas under receiver operating characteristic curves showed that NF cytology alone predicted hHSILs better than the covariate model (AUC, 0.69 vs 0.63; Pn=n.02), but NF and Dacron cytology comparisons showed no statistically significant differences (AUC, 0.69 vs 0.67; Pn=n.3).ConclusionsNF cytology and Dacron cytology provide modest sensitivity, but NF cytology has higher specificity and accuracy, and this is important for lowering the costs of population-based screening.

Author(s): MacKenzie-Graham, Allan; Brook, Jenny; Kurth, Florian; Itoh, Yuichiro; Meyer, Cassandra; Montag, Michael J; Wang, He-Jing; Elashoff, Robert; Voskuhl, Rhonda R | Abstract: IntroductionProgressive gray matter (GM) atrophy is a hallmark of multiple sclerosis (MS). Cognitive impairment has been observed in 40%-70% of MS patients and has been linked to GM atrophy. In a phase 2 trial of estriol treatment in women with relapsing-remitting MS (RRMS), higher estriol levels correlated with greater improvement on the paced auditory serial addition test (PASAT) and imaging revealed sparing of localized GM in estriol-treated compared to placebo-treated patients. To better understand the significance of this GM sparing, the current study explored the relationships between the GM sparing and traditional MRI measures and clinical outcomes.MethodsSixty-two estriol- and forty-nine placebo-treated RRMS patients underwent clinical evaluations and brain MRI. Voxel-based morphometry (VBM) was used to evaluate voxelwise GM sparing from high-resolution T1-weighted scans.ResultsA region of treatment-induced sparing (TIS) was defined as the areas where GM was spared in estriol- as compared to placebo-treated groups, localized primarily within the frontal and parietal cortices. We observed that TIS volume was directly correlated with improvement on the PASAT. Next, a longitudinal cognitive disability-specific atlas (DSA) was defined by correlating voxelwise GM volumes with PASAT scores, that is, areas where less GM correlated with less improvement in PASAT scores. Finally, overlap between the TIS and the longitudinal cognitive DSA revealed a specific region of cortical GM that was preserved in estriol-treated subjects that was associated with better performance on the PASAT.ConclusionsDiscovery of this region of overlap was biology driven, not based on an a priori structure of interest. It included the medial frontal cortex, an area previously implicated in problem solving and attention. These findings indicate that localized GM sparing during estriol treatment was associated with improvement in cognitive testing, suggesting a clinically relevant, disability-specific biomarker for clinical trials of candidate neuroprotective treatments in MS.

Aims To describe the self-reported frequency of Chinese nurses’ interventions to help smokers quit, using the 5 As (i.e. Ask, Advise, Assess, Assist, Arrange), attitudes towards tobacco control and differences in consistency interventions by demographic and professional characteristics prior to an educational intervention to increase nurses’ support for quit efforts. Background Tobacco use is the leading cause of preventable death in China; quitting smoking reduces health risks and premature death. The China Tobacco Cessation Treatment Guideline supports the 5 As model for intervention, but nurses’ frequency of delivering smoking cessation interventions is unknown. Design Descriptive survey using a convenience sample. Methods Nurses from eight hospitals in Beijing and Hefei, China completed a web-based survey in 2012. Differences in consistency of the 5 As by nurse characteristics were determined using multivariate logistic regression. Overall importance of nurses in tobacco control was evaluated on a 1-5 scale (5 = most important). Results Nurses (N = 2440; 1404 Beijing, 1036 Hefei) participated. 64% consistently asked about smoking status, 85% advised patients to quit, 52% assessed readiness to quit and assisted with smoking cessation and 17% arranged for follow-up. Interventions varied by nurses’ education and clinical setting. Nurses positively viewed involvement in tobacco control (4·3/5) and thought nurses should be smoke-free role models (4·8/5·0). Conclusions This study demonstrates that the majority of nurses asked about smoking status, but few assisted patients with quitting. Further efforts are needed to help nurses actively promote smoking cessation interventions.

Background Research has revealed that manifest Alzheimer’s disease (AD) dementia is preceded by preclinical and prodromal phases during which pathology is accumulating but function remains intact. This understanding and concern that disease-modifying interventions initiated at the dementia stage may come too late in the neurodegenerative process to be successful has led to a paradigm shift in AD clinical trials. AD trials now enroll patients with mild cognitive impairment (MCI) and persons with no cognitive symptoms. Trial designs are similar to those enrolling dementia participants. We set out to test the hypothesis that attitudes towards trial design features differ among different potential AD trial populations. Methods We sent a survey composed of 37 items assessing specific trial elements to 246 cognitively normal, MCI, and AD dementia participants at the University of California Los Angeles (UCLA) Alzheimer’s Disease Research Center (ADRC), from whom we received 91 responses (37 cognitively normal, 32 MCI, and 22 dementia). To quantify willingness to enroll, we created three composite scenarios by summing responses and fitting proportional odds models with a binary outcome variable for whether patients were highly willing to participate in low-, moderate-, or high-risk and burden trials. Results MCI participants less frequently correctly self-identified their diagnoses than those with dementia or normal cognition. Compared to dementia patients, the odds of participating in a low-risk, low-burden trial were 12% lower for MCI patients (odds ratio (OR) = 0.88, 95% confidence interval (CI) 0.23–3.29) and 70% lower (OR = 0.30, 95% CI 0.08–1.09) for cognitively normal participants. With increasing risk and burden, willingness to enroll decreased and the gap in relative willingness between diagnostic groups increased. In the medium-risk, medium-burden scenario, the estimated OR was 0.64 (95% CI 0.17–2.40) for MCI and 0.21 for the cognitively normal (95% CI 0.06–0.77). In the high-risk, high-burden scenario, the estimated OR indicated reduced willingness for MCI (OR = 0.27, 95% CI 0.06–1.15) and cognitively normal respondents (OR = 0.12, 95% CI 0.03–0.54). Conclusions These results suggest that AD trials enrolling predementia populations, especially those requiring frequent visits and implementing biomarker testing procedures, may encounter challenges to enrollment. Electronic supplementary material The online version of this article (doi:10.1186/s13195-017-0311-5) contains supplementary material, which is available to authorized users.

Background Despite advances in rheumatoid arthritis (RA) therapeutic agents, difficulty in managing RA flares persists, and remission or the persistent absence of inflammation remains challenging to achieve. The French FLARE (F-FLARE) was developed to facilitate and standardize detection and measurement of RA flares between clinic visits.1,2 We have previously reported the cognitive debrief for the published British English version, which determined that revision of wording and presentation of items was required. Here we report validation of the American English version of FLARE (Am-E FLARE-RA).3 Objectives To assess whether the Am-E FLARE questionnaire performs comparably to the French version of FLARE in detecting RA flare in an American English-speaking clinic population. Methods We enrolled patients attending UCLA rheumatology clinics. After informed consent, patients completed a questionnaire to collect demographics, Am-E FLARE, RAPID3, patient global visual analog scale (VAS), and self-reported flare at time of visit or between visits (yes/no). Questionnaires were provided to patients without specific instruction. From the electronic medical records, we extracted MD global VAS, MD-reported flare, seropositivity, disease duration, swollen/tender joint counts (SJC/TJC), and calculated the clinical disease activity index (CDAI). Analyses included Wilcoxon rank sum tests and Spearman correlations to assess criterion and concurrent construct validity. Results Eighty-five RA patients diagnosed by the1987 American College of Rheumatology (ACR) criteria enrolled in our study. For the study population as a whole, mean age was about 50 years and most were female. Mean disease duration was about 10 years and about 65% were seropositive. (see Table). Am-E FLARE scores were significantly higher in patients9 self-reporting flare compared to patients who reported no flare (p=0.005), and also for patients with MD-reported flare compared to those without flare (p=0.008) (see Table). Interestingly, there were no significant differences in SJC (p=0.82) and physician global (p=0.19) between patients who self-reported flare versus those who reported no flare. In addition, the Am-E FLARE scores correlated moderately with both CDAI (corr=0.46) and RAPID3 (corr=0.57). Conclusions The Am-E FLARE is feasible for use in clinic, and shows good criterion validity, with scores significantly higher in patients who self-report flare. In addition, Am-E FLARE shows good discriminant validity, distinguishing patients who are flaring according to MD or patient self-report from those who are not. Finally, Am-E FLARE demonstrates construct validity comparable to that of the original French version of FLARE. References Jean-Marie Berthelot, Michel De Bandt, Jacques Morel, et al. A tool to identify recent or present rheumatoid arthritis flare from both patient and physician perspectives: The “FLARE” instrument. Ann Rheum Dis 2012;71:1110–1116. Fautrel B, Morel J, Berthelot JM, et al. Validation of FLARE-RA, a self-administered tool to detect recent or current rheumatoid arthritis flare. Arthritis Rheumatol. 2016 Sep. 16. EULAR14-SCIE-4820. Disclosure of Interest None declared

Purpose To evaluate a brief educational program about smoking cessation on the frequency of nurses’ interventions with smokers, and impact of nurses’ smoking status on outcomes. Design Prospective, single group design with prestudy and 3 months post-study data. Methods Nurses in the Czech Republic attended hospital-based 1-hr educational programs about helping smokers quit. They completed surveys about the frequency (i.e., always, usually, sometimes, rarely, never) of their smoking cessation interventions with patients using the five A's framework (i.e., ask, advise, assess, assist, arrange), and their attitudes prior to and 3 months after the course. Demographic data included smoking status. Findings Among the 98 nurses with prestudy and post-study data, all were female, mean age was 43 years, 33% were current smokers, and 64% worked in a medical or surgical or oncology settings. At 3 months, compared to baseline, significantly (p < .05) more nurses assessed patients’ interest in quitting, assisted with quit attempts, and recommended the use of the quitline for cessation. At 3 months after the program, nurses who smoked were less likely to ask about smoking status (odds ratio [OR] = 4.24, 95% confidence interval [CI; 1.71, 10.53]), advise smokers to quit (OR = 3.03, 95% CI [1.24,7.45]), and refer patients to a quitline (OR = 2.92, 95% CI [0.99, 8.63]) compared to nonsmokers, despite no differences in delivery of interventions at baseline. Conclusions Three months after attendance at an educational program focused on the nurses’ role in supporting smoking cessation efforts, more nurses engaged in interventions to help smokers quit. However, the program was less effective for nurses who smoked. Clinical Relevance This program demonstrated promise in building capacity among Czech nurses to assist with smoking cessation, but nurses’ smoking poses a challenge.

Background: Behavioral symptoms are common in both mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: We analyzed the Neuropsychiatric Inventory Questionnaire data of 3,456 MCI and 2,641 mild AD National Alzheimer's Coordinating Center database participants. Using factor analysis and logistic regression we estimated the effects of age, sex, race, education, Mini-Mental State Examination, functional impairment, marital status and family history on the presence of behavioral symptoms. We also compared the observed prevalence of behavioral symptoms between amnestic and nonamnestic MCI. Results: Four factors were identified: affective behaviors (depression, apathy and anxiety); distress/tension behaviors (irritability and agitation); impulse control behaviors (disinhibition, elation and aberrant motor behavior), and psychotic behaviors (delusions and hallucinations). Male gender was significantly associated with all factors. Younger age was associated with a higher prevalence of distress/tension, impulse control and psychotic behaviors. Being married was protective against psychotic behaviors. Lower education was associated with the presence of distress/tension behaviors. Caucasians showed a higher prevalence of affective behaviors. Functional impairment was strongly associated with all behavioral abnormalities. Amnestic MCI patients had more elation and agitation relative to nonamnestic MCI patients. Conclusions: Younger age, male gender and greater functional impairment were associated with higher overall presence of behavioral abnormalities in MCI and mild AD. Marital status, lower education and race had an effect on selected behaviors.

Objective Clinical trials in incipient and clinical Alzheimer disease (AD) often include informant-reported outcomes. Whereas informant reports in AD dementia may be modulated by the nature of participant–informant relationships, whether informant type affects reporting at earlier disease stages is less certain. We sought to determine the effects of participant–informant relationships on informant assessments of quality of life (QOL), functional abilities, and behavioral symptoms in individuals with normal cognition (NC), mild cognitive impairment (MCI), and mild-to-moderate AD dementia. Design Cross-sectional. Setting Easton Center for Alzheimer Disease Research at the University of California, Los Angeles. Participants A total of 399 individuals who met criteria for NC (N = 100), MCI [amnestic (N = 125) and nonamnestic (N = 61)], and AD (N = 113). Participants were subdivided into groups based on informant–participant relationships (spouse versus other). Measurements We examined informant effects on the Quality of Life-Alzheimer's Disease (QOL-AD) scale, the Functional Activities Questionnaire (FAQ), and the Neuropsychiatric Inventory (NPI). Results After adjustments for demographic and cognitive factors, spouse informants reported higher participant QOL in the amnestic MCI and AD groups than did other informants. No informant effects were seen on QOL-AD ratings in the nonamnestic MCI or NC groups or on the FAQ or NPI in the MCI and AD groups. Conclusions Participant–informant relationships may modulate informant responses on subjective measures such as the QOL-AD in both incipient and clinical AD. Clinical trials that use informant measures may need to address these effects.

Background: Numbering about 90,000, nurses represent the largest group of health care providers in the Czech Republic. Therefore, nurses can make a significant impact in the treatment of tobacco dependence, particularly in applying brief interventions to smokers. Methods: During 2014, 279 nurses from the Czech Republic participated in an e-learning education programme consisting of two Webcasts with additional web-based resources about smoking cessation in relation to health and treatment options in daily clinical practice, particularly regarding brief intervention methods. Before viewing the e-learning programme, and three months after viewing it, the nurses completed a questionnaire documenting their interventions with smokers and their knowledge, attitudes and opinions regarding nurses' roles in smoking cessation. Results: The responses in all of the following categories significantly improved: usually/always asking patients about smoking from 58% to 69% (OR 1.62, CI=1.14-2.29, p=0.007); recommendations to stop smoking from 56% to 66% (OR 1.46, CI=1.03-2.06, p=0.03); assessing willingness to quit from 49% to 63% (OR 1.72, CI=1.23-2.42, p=0.002); assisting with cessation from 21% to 33% (OR 1.85, CI=1.26-2.71, p=0.002); and recommending a smoke-free home from 39% to 58% (OR 2.16, CI=1.54-3.04, p

Aims To evaluate a web-based educational smoking cessation programme on changes in the frequency of hospital-based nurses’ self-reported interventions to help smokers quit using the 5 As (i.e. Ask, Advise, Assess, Assist, Arrange), to reduce exposure to second-hand smoke and to change attitudes about nurses’ involvement in tobacco control. Background Few nurses in China support smokers’ quit attempts using evidence-based smoking cessation interventions based on the 5 As. Limited knowledge is a barrier to intervention. Web-based tobacco cessation programs have the potential to reach a large population of nurses. Design A prospective single-group design with pre-, 3- and 6-month follow-up after the educational programme evaluated the feasibility of conducting web-based educational programs in two cities in China in 2012–2013. Methods Frequency of interventions was assessed using a valid and reliable web-based survey with a convenience sample of nurses from eight hospitals in Beijing and Hefei, China. Generalized linear models, adjusting for age, clinical setting, education and site were used to determine changes in the consistent (usually/always) use of the 5 As from baseline to 3 and to 6 months. Results Nurses (N = 1386) had baseline and/or 3- and 6-month data. At 6 months, nurses were significantly more likely to Assess, Assist and Arrange for smoking cessation and recommend smoke-free home environments. There was significant improvement in attitudes about tobacco control. Conclusions Nurses receiving web-based smoking cessation education significantly increased self-reports of frequency of providing interventions to patients who smoke, including recommending smoke-free home environments to support quit attempts.

Background Tobacco is the leading cause of cancer in the Czech Republic. More than one-third of the population older than 15 years smokes, including many nurses. Most smokers want to quit, but the extent of nurses' involvement in tobacco cessation is unknown. Objective The purposes of this study are to describe the frequency of nurses' interventions in helping smokers quit, examine their attitudes and skills, and explore the relationship of nurses' smoking status to level of intervention. Methods A convenience sample of nurses in the Czech Republic completed a survey about their frequency of interventions according to the 5As for tobacco dependence treatment (i.e., ask, advise, assess, assist, arrange), their attitudes and perceived skills, and their smoking status (never, former, current). Results A total of 157 nurses completed the survey; 26% "always" or "usually" assisted patients with smoking cessation. Few (22%) reported that nurses could play an important role in helping patients quit, and 65% rated their ability to help smokers quit as "fair/poor." Nurse who smoked (30%) were less likely to consistently assess smoking status or arrange for follow-up support. Conclusion Few nurses in the Czech Republic consistently provide smoking cessation support to patients, have the skills to do so, or view this role as an important part of their role. Implications for practice To reduce tobacco-related cancers in the Czech Republic, capacity-building efforts are needed to enhance nurses' skills and confidence in providing smoking cessation interventions. Support is also need to help nurses who smoke quit.

The pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).Temporal lobes of nine Alzheimer's disease (AD) and seven cognitively normal subjects were scanned post-mortem at 7 Tesla. Hippocampal volumes were obtained with HarP. Six-micrometer-thick hippocampal slices were stained for amyloid beta (Aβ), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, Aβ, and tau burden for each hippocampal subfield were obtained.We found significant correlations between hippocampal volume and Braak and Braak staging (ρ = -0.75, P = .001), tau (ρ = -0.53, P = .034), Aβ burden (ρ = -0.61, P = .012), and neuronal count (ρ = 0.77, P.001). Exploratory subfield-wise significant associations were found for Aβ in Cornu Ammonis (CA)1 (ρ = -0.58, P = .019) and subiculum (ρ = -0.75, P = .001), tau in CA2 (ρ = -0.59, P = .016), and CA3 (ρ = -0.5, P = .047), and neuronal count in CA1 (ρ = 0.55, P = .028), CA3 (ρ = 0.65, P = .006), and CA4 (ρ = 0.76, P = .001).The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD and pathologic validation of HarP.

Persons at risk for autosomal dominant neurodegenerative diseases provide the opportunity to efficiently test preventive interventions. Only a minority of such persons, however, choose to undergo revealing genetic testing, presenting a challenge to enrollment. Thirty-four preclinical Latinos (n=26) and non-Latinos at risk for familial Alzheimer's disease (FAD) unaware of their genetic status were administered a questionnaire exploring their interest in undergoing revealing genetic testing at baseline and in the context of eligibility for four prevention trials of increasing invasiveness. Forty-four percent of subjects expressed a baseline interest in undergoing revealing testing which increased to 85% in order to be eligible for a study of an oral drug “felt to be very safe.” If there were a 50% chance of receiving placebo, this number dropped to 62% (p=0.02). Among those not interested in a study involving a 50% chance of receiving placebo, a range of 5% to 40% chance of receiving placebo was given as acceptable. For more invasive studies, living in the United States (as opposed to Mexico) positively influenced the likelihood of participating. Our data suggest that clinical trial designs in which persons must confront their genetic status prior to enrollment are feasible. Study designs to minimize the likelihood of being placed on placebo or provide the eventual administration of the drug through open-label extensions should be considered.

Background MSK-US is widely used for assessing disease severity and response to therapy in RA clinical trials. Although reliability exercises have been published, there is sparse literature on standardizing numerous factors that may affect reliability. Objectives The aim of this study was to optimize MSK-US acquisition and scoring reliability prior to embarking on a multicenter MSK-US based RA study. Methods This two-site MSK-US study evaluated the following joints: bilateral radio-carpal, intercarpal, radioulnar, MCP 1-5, PIP 1-5, knees and MTP 2-5. The reliability among our two main ultrasonographers with >5 years MSK-US experience was assessed in 3 phases (pre-face-to-face [pre-F2F], F2F, and post-F2F). A 1st draft MSK-US RA atlas was utilized as an initial reference for intensive teleconferences, which resulted in a 2nd draft atlas (images refined and scoring rules further delineated). Pre-F2F: The 2 ultrasonographers scored still images of 2 patients independently. Inter-reader reliability was calculated and most discrepant scores discussed. F2F: Each ultrasonographer scanned the same 6 patients independently, and then re-scanned 2 patients. The inter- and intra-reader reliability were calculated, and again discussion of most discrepant scores. Factors affecting discordance were identified and addressed: agreeing on cutoffs for synovitis scores, focal point positioning, positioning of deformed joints, room temperature, layer of gel used, prior familiarity with the machine, and color adjustment for PD to accommodate for color blindness (present is 7% of males and 0.5% in females). The 3rd and final atlas was developed as a reference for the post-F2F; clearly delineated the discrepancies among scores. Post-F2F: Each ultrasonographer rescored 2 patients9 scans acquired during F2F study. The intra- and inter-reader reliability was calculated using percent agreement, weighted-kappa, intraclass correlation coefficient (ICC), and spearman correlation. Results The F2F and post-F2F intra-reader reliability ranged between 79%_94% for exact agreement and 0.64-0.89 spearman correlation. The pre-F2F, F2F, and post-F2F inter-reader reliability ranged from 64-82% for exact agreement, 0.59-0.83 Spearman correlation (Tables 1&2). Inter-reader reliability improved from pre-F2F (64% agreement and 0.77 spearman correlation) to post-F2F (82%agreement and 0.83 spearman correlation). Conclusions Our study highlights the importance of standardizing acquisition of MSK-US in RA clinical trials and provides practical tools to improve reliability. we recommend standardization of acquisition to be pursued, prior to commencement of multicenter MSK-US based RA trials. Disclosure of Interest None declared