Consent document translation expense hinders inclusive clinical trial enrolment.

Patients from historically under-represented racial and ethnic groups are enrolled in cancer clinical trials at disproportionately low rates in the USA1-3. 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 12,000 consent events at a large cancer centre 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 the translation costs) than for industry-sponsored studies (for which the translation costs are 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. The results suggest that the cost of consent document translation in trials not sponsored by industry could be a potentially modifiable barrier to the inclusion of patients with limited English proficiency.

Improved outcomes in rheumatoid arthritis with obesity after a weight loss intervention: randomized trial.

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 < 0.001). Routine Assessment of Patient Index Data 3 (RAPID3) improved, serum leptin decreased and serum adiponectin increased significantly within the diet group and between the groups (all P < 0.03). DAS28 decreased, 5.2 to 4.2, within the diet group (P < 0.001; -0.51 [95% CI -1.01, 0.00], P = 0.056, between groups). HAQ-Disability Index (HAQ-DI) improved significantly within the diet group (P < 0.04; P = 0.065 between group). Ultrasound measures and the multi-biomarker disease activity score did not differ between groups (PDUS-34 -2.0 [95% CI -7.00, 3.1], P = 0.46 between groups). 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.

Power doppler ultrasound signal predicts abnormal HDL function in patients with rheumatoid arthritis.

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.

Impact of a web-based educational program on Japanese nurses tobacco cessation practice and attitudes in oncology settings.

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.

Impact of Perceived Stress During the SARS-CoV-2 Pandemic on Rheumatoid Arthritis Patients' Disease Activity: An Online Survey.

INTRODUCTION/OBJECTIVES: Psychological 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. METHOD: This 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). RESULTS: A 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. CONCLUSIONS: This 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.

Impact of a webcast on nurses' delivery of tobacco dependence treatment.

AIMS AND OBJECTIVES: To evaluate an educational programme 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 6-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 3 or 6 months postimplementation of the educational programme were included in an analysis of changes in the consistent (always/usually) delivery of the 5As plus referral to the quitline. RESULTS: After 3 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 6 months. Nurses who viewed the webcast were three times more likely to refer smokers to a quitline at 3 months; and four times more likely at 6 months than those who did not. CONCLUSIONS: An online educational programme, 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 programme 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 CLINICAL PRACTICE: Distance learning is a feasible mechanism for enhancing nurses' involvement in tobacco dependence treatment and promoting evidence-based clinical practice.

Participant-Informant Relationships Affect Quality of Life Ratings in Incipient and Clinical Alzheimer Disease.

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.

Impact of Online Education on Nurses' Delivery of Smoking Cessation Interventions With Implications for Evidence-Based Practice.

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.

Evaluation of a web-based educational programme on changes in frequency of nurses' interventions to help smokers quit and reduce second-hand smoke exposure in China.

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.

Helping smokers quit: behaviours and attitudes of Chinese Registered Nurses.

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.

Nurses' Attitudes toward Intervening with Smokers: Their Knowledge, Opinion and E-Learning Impact.

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<0.001). The increase in arranging follow-up from 7% to 10% did not constitute a statistically significant improvement, however, this finding is understandable in relation to the status of nurses in the Czech Republic. However, nurses' confidence in helping smokers to quit smoking, their senses of responsibility and determining the appropriateness of these interventions remains inadequate. CONCLUSION: The nurses' brief intervention skills improved significantly after the completion of the e-learning programme, even though reservations remain among this group. The systematic education of nurses aimed at smoking cessation intervention and analyzing their motivation for treatment may contribute to improved nursing care, and thus lead to a reduction of smoking prevalence in the general population.

Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol.

OBJECTIVE: The pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP). METHODS: 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 (Aß), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, Aß, and tau burden for each hippocampal subfield were obtained. RESULTS: We found significant correlations between hippocampal volume and Braak and Braak staging (ρ = -0.75, P = .001), tau (ρ = -0.53, P = .034), Aß burden (ρ = -0.61, P = .012), and neuronal count (ρ = 0.77, P < .001). Exploratory subfield-wise significant associations were found for Aß 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). CONCLUSIONS: The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD and pathologic validation of HarP.

Risk factors for behavioral abnormalities in mild cognitive impairment and mild Alzheimer's disease.

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.

Impact of a smoking cessation educational program on nurses' interventions.

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.

Predictors of COVID-19 outcomes: Interplay of frailty, comorbidity, and age in COVID-19 prognosis.

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.

Optimizing Reliability of Real-Time Sonographic Examination and Scoring of Joint Synovitis in Rheumatoid Arthritis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (p<0.05, weighted-kappa 0.63 to 0.80, intraclass correlation coefficient 0.71 to 0.86, Spearman 0.67 to 0.86) with use of the atlas.  Conclusion: This rheumatoid arthritis musculoskeletal ultrasound study addressed complex factors affecting musculoskeletal ultrasound acquisition-scoring reliability. Systematic identification and amelioration of many factors and using a novel rule-based scoring atlas significantly improved intra-reader reliability.

Sentinel joint scoring in rheumatoid arthritis: an individualized power Doppler assessment strategy.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. TRIAL REGISTRATION: 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.

Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis patients.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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). TRIAL REGISTRATION: 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.

Building capacity in tobacco control by establishing the Eastern Europe Nurses' Center of Excellence for Tobacco Control.

INTRODUCTION: Properly 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. METHODS: The 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. RESULTS: At the follow-up at 3 months, the 507 nurses self-reported a significant increase in providing all 5A components, i.e. nurses were significantly (p<0.0001) 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 p<0.0001). 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 (p<0.0001) 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. CONCLUSIONS: Coordinating 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.