Challenges with computing scalar and ad-hoc implicatures in Mandarin-speaking 4-8-year-old autistic children.

INTRODUCTION: Mixed findings have been reported about the computation of scalar or/and ad-hoc implicatures in primarily school-age autistic verbal children and adolescents: while some studies reported their struggles with both implicatures, others observed their strengths in computing scalar implicatures. This study extends the previous investigation by testing the derivation of scalar (including both number and quantifier) and ad-hoc implicatures of a younger group of Mandarin-speaking autistic 4-8-year-olds; moreover, we assess the biological, linguistic, and cognitive factors affecting children's implicature acquisition. METHODS: The participants included 22 4-8-year-old autistic verbal children (mean age = 67.64 months) and 19 typically developing (TD) children who did not significantly differ in age, receptive vocabulary, and non-verbal IQ. Both groups completed a computer-based Truth Value Judgment task, assessing their knowledge of scalar (involving the number 'three' and the quantifier 'some') and ad-hoc implicatures. We also examined whether their implicature computation was linked to age, receptive vocabulary, non-verbal IQ, and Theory of Mind (ToM). RESULTS: Compared with the TD controls, autistic children derived significantly fewer scalar and ad-hoc implicatures. Specifically, TD children successfully computed number and ad-hoc implicatures, contrasting to the bimodal distribution of their pragmatic vs. logical responses to quantifier implicatures. Though autistic children performed better with number implicatures slightly above the chance level, they had difficulties in computing quantifier and ad-hoc implicatures. Further, autistic children's knowledge of the number and ad-hoc implicatures was linked to their ToM skills. CONCLUSIONS: These findings underscore the overall delayed implicature knowledge of young autistic children, and their low sensitivity to the implicatures is related to the core ToM deficits. Furthermore, our data confirm the coherent pattern of the earlier acquisition of number over quantifier implicatures and illuminate the distinct mechanisms underlying the computation of scalar vs. ad-hoc implicatures.

Expressive Language Profiles in a Clinical Screening Sample of Mandarin-Speaking Preschool Children With Autism Spectrum Disorder.

PURPOSE: This cross-sectional study aimed to depict expressive language profiles and clarify lexical-grammatical interrelationships in Mandarin-speaking preschoolers with autism spectrum disorder (ASD) during the administration of the simplified Chinese Psychoeducational Profile-Third Edition screening. METHOD: We collected naturalistic language samples from 81 (74 boys, seven girls) 2- to 7-year-old (Mage = 55.6 months, SD = 15.17) Mandarin-speaking children with ASD in clinician-child interactions. The child participants were divided into five age subgroups with 12-month intervals according to their chronological age. Computer-assisted part-of-speech tagging, constituency analysis, and dependency analysis addressed the developmental trajectories of early lexical and grammatical growth in each age subgroup. RESULTS: Significant within-ASD differences were observed in content words, function words, and lexical categories. Nouns and verbs were the predominant lexical categories, while noun types overwhelmed verb types in children over 3 years old. The grammatical development of 5- to 6-year-old Mandarin-speaking children with ASD was better than that of 3- to 4-year-old children. The trends of syntactic structures, grammatical relations, and grammatical complexity in each age group were similar. CONCLUSIONS: Mandarin-speaking preschoolers with ASD produce more lexicons with increasing age. They preserve the noun bias as a universal mechanism in early lexical learning. Moreover, their developmental trajectories of grammatical growth were comparable in each age subgroup. In addition, their lexicons and grammar were synchronically developed during early language acquisition.

Isolated Nodal Recurrence After Definitive Stereotactic Ablative Radiation Therapy for Non-Small Cell Lung Cancer.

PURPOSE: Stereotactic ablative radiation therapy (SABR) results in high rates of primary tumor control for early-stage non-small cell lung cancer (NSCLC). For patients with isolated hilar or mediastinal nodal recurrence (INR) after SABR, the optimal salvage treatment strategy is unclear. The purpose of this study was to determine the rate of INR after SABR for early-stage NSCLC and to describe patterns of care and treatment outcomes after salvage therapy. METHODS AND MATERIALS: This retrospective cohort study included 342 patients with stage T1-3N0M0 NSCLC treated with definitive SABR from 2003 to 2018. We evaluated the incidence of INR and baseline factors between patients who did and did not experience INR. Among patients who experienced INR, we described treatment patterns and outcomes including overall survival (OS) and progression free survival (PFS) from the time of nodal failure using the Kaplan-Meier method. RESULTS: With a median follow-up of 3.3 years, the 3-year INR rate was 10.6% (95% CI, 6.6%-13.4%). Among the 34 patients experiencing INR, the 3-year rates of OS and PFS were 39.3% (24.4%-63.3%) and 26.7% (14.1%-0.3%), respectively. The 34 patients with INR were treated with radiation therapy alone (26.7%), concurrent chemoradiation therapy (43.3%), chemotherapy alone (13.3%), or observation (16.7%). Patients treated with concurrent chemoradiation therapy had the best survival outcomes, with a 3-year OS and PFS of 81.5% (61.1%-100.0%) and 63.9% (40.7%-100.0%), respectively. Of the patients treated with salvage radiation therapy or concurrent chemoradiation therapy, 14.3% experienced grade 3 toxic effects, and no patients had grade ≥4 toxic effects. CONCLUSIONS: In this study, INR occurred in approximately 10% of patients treated with SABR for early-stage NSCLC. The highest rates of OS and PFS among patients with INR were observed in those treated with salvage chemoradiation therapy.

Perspectives on nonmedical switching and the COVID-19 pandemic: a narrative review.

OBJECTIVES: Nonmedical switching (NMS) is a change in a patient's treatment regimen for reasons other than lack of efficacy, intolerance, adverse effects, or poor adherence. We describe the impact of NMS on patients, health care workers, and health systems, focusing on NMS to in-class biologic alternatives in US patients with chronic, immune-mediated rheumatic and dermatologic conditions. Additionally, we evaluate the ways in which the COVID-19 pandemic may exacerbate the physical, psychological, and economic impacts of NMS. STUDY DESIGN: Narrative review. METHODS: We performed a search of MEDLINE's PubMed database from October 2015 to October 2020, with a repeat search in October 2021. Search terms included relevant keywords pertaining to NMS, biologics, and disease areas. Results were supplemented by a search of key congress abstracts from 2015 to 2021 and a targeted internet search. RESULTS: NMS increases medication abandonment, errors, and adverse effects, and it can lead to longer patient visits, increased follow-up visits, additional laboratory tests and procedures, and greater overall health care resource utilization (HCRU). The increased HCRU associated with NMS increases patients' financial burden due to additional co-pays and out-of-pocket costs. CONCLUSIONS: The decision to switch treatments should result from shared decision-making between health care providers (HCPs) and patients to achieve the best clinical outcomes and optimal HCRU. The issues related to NMS may be compounded by the financial and psychosocial stress on HCPs and patients created by the COVID-19 pandemic. HCPs should advocate for continuous patient treatment and be familiar with continuity of care legislation, appeals processes, and manufacturer assistance programs.

Health care utilization and costs associated with functional status in patients with psoriatic arthritis.

BACKGROUND: The Health Assessment Questionnaire Disability Index (HAQ-DI) has been validated and widely used in psoriatic arthritis (PsA) clinical trials for the assessment of patient functional status. Significant improvements in the HAQ-DI have been reported in response to therapeutic interventions; however, few US studies have evaluated the economic impact of functional disability in patients with PsA. OBJECTIVE: To evaluate the association of functional status with health care resource utilization (HCRU) and total health care costs in US patients diagnosed with PsA. METHODS: This retrospective study included adult patients with PsA enrolled in FORWARD between July 2009 and June 2019 who completed 1 or more HAQ-DI questionnaires between January 2010 and December 2019. Patient demographics, clinical characteristics, and patient-reported outcomes were collected from the most recent questionnaire. HCRU and total health care costs (2019 US dollars) for all hospitalizations, emergency department (ED) visits, outpatient visits, diagnostic tests, and procedures were assessed for the 6 months prior to survey completion. Negative binomial regression models (HCRU outcomes) and generalized linear models with γ distribution and log-link function (cost outcomes) were used to assess the relationship between HAQ-DI and HCRU and cost outcomes, respectively. RESULTS: A total of 828 patients with PsA who completed HAQ-DI questionnaires were included. The mean (SD) age was 58.5 (13.5) years, 72.3% were female, and 92.3% were White. The mean (SD) disease duration was 17.5 (12.4) years, and the mean (SD) HAQ-DI score at the time of the patients' most recent questionnaire was 0.9 (0.7). More severe functional disability, measured by higher HAQ-DI score, was significantly associated with increased risk (incident rate ratio [95% CI]) of hospitalizations (1.68 [1.11-2.55]), ED visits (2.09 [1.47-2.96]), outpatient visits (1.14 [1.05-1.24]), and diagnostic tests (1.42 [1.16-1.74]). There was also a significant positive association between greater HAQ-DI score and increased total annualized health care costs (incremental amount [95% CI], 1.13 [1.03-1.23]) and medical costs (1.38 [1.13-1.69]), but there was no significant association found with pharmacy costs. Total adjusted average patient medical costs increased with increasing HAQ-DI score. CONCLUSIONS: Among patients with PsA enrolled in FORWARD, more functional disability-as measured by higher HAQ-DI scores-was associated with greater HCRU and increased total health care costs. These results suggest that improving functional status in patients with PsA may reduce economic burden for health care payers and systems. DISCLOSURES: Dr Ogdie has received consulting fees from Amgen, AbbVie, Bristol Myers Squibb, Celgene, CorEvitas (formerly Corrona), Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB and has received grant support from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Rheumatology Research Foundation, National Psoriasis Foundation, Pfizer (University of Pennsylvania), Amgen (FORWARD), and Novartis (FORWARD). Dr Hwang has received consulting fees from Novartis and UCB and has received grant support (5KL2TR003168-03) from the University of Texas Health Science Center at Houston Center of Clinical and Translational Sciences KL2 program. Drs Veeranki and Shafrin were employees of PRECISIONheor at the time of this analysis. Ms Portelli and Mr Sison are employees of PRECISIONheor. Ms Pedro has nothing to disclose. Dr Hass is an employee of H. E. Outcomes, providing consulting services to Novartis. Dr Hur was an employee of Novartis at the time of this analysis. Dr Kim was a postdoctoral fellow at the University of Texas at Austin and Baylor Scott and White Health, providing services to Novartis at the time of this analysis. Dr Yi is an employee of Novartis. Dr Michaud received grant funding from the Rheumatology Research Foundation at the time of this analysis. This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ.

Association of health care utilization and costs with patient-reported outcomes in patients with ankylosing spondylitis.

BACKGROUND: Interventions for ankylosing spondylitis (AS) have improved patient-reported outcomes (PROs) in clinical studies. However, limited data exist associating these improvements with health care resource utilization (HCRU) or cost savings. Few studies have evaluated the economic impact of patient-reported physical status and related disease burden in patients with AS in the United States. OBJECTIVE: To assess the association of PRO measures with HCRU and health care costs in patients with AS from a national US registry. METHODS: This cohort study included adults with a diagnosis of AS enrolled in the FORWARD registry from July 2009 to June 2019 who completed at least 1 questionnaire from January 2010 to December 2019 and completed the Health Assessment Questionnaire Disability Index (HAQ-DI) (0-3) and/or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (0-10). Patient-reported data for demographics, clinical characteristics, and PROs were collected through questionnaires administered biannually and reported from the most recent questionnaire. Patient-reported HCRU and total health care costs (2019 US dollars) for hospitalizations, emergency department (ED) visits, outpatient visits, diagnostic tests, and procedures were captured during the 6 months prior to the most recent survey completion. The relationship between HAQ-DI or BASDAI and HCRU outcomes was assessed using negative binomial regression models, and the relationship between HAQ-DI or BASDAI and the cost outcomes was evaluated using generalized linear models with γ distribution and log-link function. RESULTS: Overall, 334 patients with AS who completed the HAQ-DI (n = 253) or BASDAI (n = 81) were included. The mean (SD) HAQ-DI and BASDAI scores at the time of patients' most recent surveys were 0.9 (0.7) and 3.7 (2.3), respectively. HAQ-DI score was positively associated with number of hospitalizations, ED visits, outpatient visits, and diagnostic tests, whereas BASDAI was not associated with HCRU outcomes. Overall annualized mean (SD) total health care, medical, and pharmacy costs for patients with AS were $44,783 ($40,595); $6,521 ($12,733); and $38,263 ($40,595), respectively. Annualized total health care, medical, and pharmacy costs adjusted for confounders increased by 35%, 76%, and 26%, respectively, for each 1.0-unit increase in HAQ-DI score (coefficient [95% CI]: 1.35 [1.15-1.58], 1.76 [1.22-2.55]; both P < 0.01 and 1.26 [1.04-1.52]; P < 0.05, respectively); BASDAI score was not significantly associated with cost outcomes. CONCLUSIONS: Higher HAQ-DI scores were associated with higher HCRU and total health care costs among patients with AS in FORWARD, but BASDAI scores were not. These findings indicate that greater functional impairment may impose an increased economic burden compared with other patient-reported measures of AS. DISCLOSURES: A. Ogdie has received consulting fees from Amgen, AbbVie, Bristol Myers Squibb, Celgene, CorEvitas (formerly Corrona), Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB and has received grant support from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Rheumatology Research Foundation, National Psoriasis Foundation, Pfizer (University of Pennsylvania), Amgen (FORWARD), and Novartis (FORWARD). M. Hwang has received consulting fees from Novartis and UCB and has received grant support (5KL2TR003168-03) from the University of Texas Health Science Center at Houston Center of Clinical and Translational Sciences KL2 program. P. Veeranki and J. Shafrin were employees of PRECISION-heor at the time of this analysis. A. Portelli and S. Sison are employees of PRECISION-heor. S. Pedro does not have anything to disclose. N. Kim was a postdoctoral fellow at the University of Texas at Austin and Baylor Scott and White Health, providing services to Novartis at the time of this study. E. Yi is an employee of Novartis. K. Michaud received grant funding from the Rheumatology Research Foundation at the time of this analysis. This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ.

Development and test-retest reliability of a screening tool for axial spondyloarthritis.

BACKGROUND: People with axial Spondyloarthritis (axSpA) suffer from lengthy diagnostic delays of ~7 years. The usage of screening tools to identify axSpA patients in primary care can reduce diagnostic delays by facilitating early referral to rheumatologic care. The purpose of this study was to examine the psychometric properties of a potential screening tool for patients with axSpA. METHOD: Content validity was evaluated by soliciting feedback from 7 rheumatologists regarding the relevance and content representativeness of the proposed screening questions. For the test-retest study, participants ≥18 years of age with chronic back pain (≥3 months) without a diagnosis of mechanical or inflammatory back pain (n = 91) were e-recruited through ResearchMatch. Participation included completing identical baseline and follow-up questionnaires ~14 days apart. Weighted quadratic kappa was used to measure test-retest reliability between the two ratings of the ordinal scales. Construct validity was examined using exploratory factor analysis (EFA) and items with factor loadings ≥0.6 were extracted. Scale dimensionality and simplified factorial solutions were measured using Kaiser's criteria (Eigenvalue >1). Cronbach's alpha was used to measure internal consistency. RESULTS: Most participants were women, non-Hispanic white, and had at least some college education, with a mean age of 45 years. On average, the age at onset of back pain was 31 years. Eleven questions yielded test-retest reliabilities ranging from 0.6 to 0.76. Results from EFA extracted two factors relating to: 1) how pain affects daily life functioning and 2) whether pain improves with movement. Internal consistency was high for questions evaluating how pain affects life, with a Cronbach's alpha of 0.81. Following assessment for validity and reliability, the questionnaire was revised to create the 6-item screening tool. CONCLUSIONS: The 6-item SpA-SED screening tool designed to identify potential cases of axSpA was found to have good test-retest reliability and high internal consistency.

Psychological Distress and COVID-19 Related Anxiety among Malaysian Women during the COVID-19 Pandemic.

The combination of COVID-19 outbreaks and nationwide lockdown led to an increased prevalence of psychological distress among the population, especially women, as they have to cope with greater family and work demands. We aimed to identify the factors contributing to psychological distress among Malaysian women during the COVID-19 pandemic. A cross-sectional study was conducted between October 2020 and April 2021, in a teaching hospital in Kuala Lumpur, Malaysia. A self-administered questionnaire was distributed among women, which consisted of (1) Participant's demographics, (2) COVID-19 knowledge and awareness, (3) Depression, Anxiety, Stress Scale-21 (DASS-21), and (4) COVID-19-related anxiety. Chi-square test and univariate analysis were performed to determine the significant factors associated with psychological distress. The mean scores for knowledge, COVID-19 anxiety, and DASS-21 subcomponents were compared using the Mann-Whitney U test. A total of three hundred and thirty-eight women completed the survey. The majority of respondents demonstrated adequate knowledge (95.6%) on COVID-19. The proportion of our women who reported symptoms of depression, anxiety, and stress were 17.2%, 25.1%, and 0.9%, respectively, resulting in a prevalence of psychological distress of 27.8%. Low education level (p = 0.017), unemployment (p = 0.028), loss of income (p = 0.033), and hospital admission for surgical procedures (p = 0.021) were significantly associated with a higher psychological burden. A greater level of COVID-19 anxiety was found among Malays (p = 0.027), pregnant women (p = 0.013), and those who suffered a loss of income (p = 0.038) during this pandemic. The COVID-19 pandemic had a negative effect on women's psychological wellbeing, especially those from the lower socio-economic background. Therefore, adequate information, as well as support, must be provided to the vulnerable groups during the ongoing pandemic, to lessen their psychological burden.

Does Gender Impact a Diagnosis of Ankylosing Spondylitis?

OBJECTIVE: The study objective was to explore differences in ankylosing spondylitis (AS) diagnosis experiences between men and women by examining the coding of health events over the 2 years preceding AS diagnosis. METHODS: Claims data (January 2006-April 2019) from the MarketScan databases were examined. Patients who had received two or more AS diagnoses at least 30 days apart and had at least 2 years of insurance enrollment before their first AS diagnosis were analyzed. Men were matched 1:1 to women by age, diagnosis date, insurance type, and enrollment duration. Health events (diagnosis and provider codes) were examined over 2 years before AS diagnosis and stratified by gender. Data were analyzed using univariate χ2 tests. RESULTS: Among 7744 patients, 274 of 1906 AS-related codes showed statistically significant differences between men and women. Women received more diagnosis codes than men across diagnoses and providers; the largest difference in diagnosis codes among women versus men was in peripheral symptom coding (57.7% vs. 43.9%, respectively). More women than men received diagnosis codes for depression (21.2% vs. 9.8%) and other musculoskeletal symptoms (52.8% vs. 40.0%); only gout was more common in men (6.5%) than in women (2.2%). Among men, backache codes gradually increased 12 months before AS diagnosis, whereas axial and sacroiliitis coding increased sharply immediately before diagnosis. The greatest difference in physician types visited was for rheumatologists: 64.2% of women had visits compared with 45.1% of men. CONCLUSION: Further investigation into the dissimilarities in diagnostic experiences between men and women is needed to determine whether differences are due to disease phenotype or potential cognitive bias influencing diagnostic decision-making.

Development of a screening tool to identify patients with axial spondyloarthritis: a cognitive interview study.

OBJECTIVE: To further refine the wording of screening questions and examine their face validity through cognitive interviews with axial spondyloarthritis (axSpA) and chronic mechanical back pain patients. METHODS: In-depth, semi-structured cognitive interviews were conducted with 30 patients (10 axSpA; 20 chronic mechanical back pain patients) to assess the face validity and comprehensibility of the screening questions. The interview protocol focused on 12 questions/domains including participants' feedback/thoughts on the duration of suffering from back pain, age at onset of back pain, pace of back pain development, improvement of pain with movement or rest, nocturnal back pain improving upon awakening, pain in other parts of the body, responsiveness of pain to nonsteroidal anti-inflammatory drug (NSAID) use, history of autoimmune conditions, and domains such as sleep, sitting, and stiffness. The Flesch-Kincaid grade level and Flesch reading ease scores were then analyzed for the revised versions of screening questions. RESULTS: Participants preferred questions that allowed them to provide more details regarding the frequency of their symptoms. Questions were refined for clarity and eliminated if participants considered them to be irrelevant (e.g., NSAIDs). Two sample screeners were derived from twelve questions each with an overall reading grade of 7.5 and reading ease of 65.7%. CONCLUSIONS: It is feasible to design a screening tool that is accessible to most (e.g., reading level) and clear to individuals with back pain. An evidence-based approach to demonstrate the validity of the screening tool will be critical for it to be implemented widely into clinical practice. Key Points • Our study developed two sample screeners that are clear to individuals with back pain and accessible to most with an overall Flesch-Kincaid reading grade of 7.5 and Flesch reading ease of 65.7%. • Questions that were considered irrelevant to participants were eliminated such as responsiveness of pain to nonsteroidal anti-inflammatory drug (NSAID). • It is feasible to design a screening tool that is accessible to most (e.g., reading level) and clear to individuals with back pain.

The disease burden of axial spondyloarthritis: through a gendered lens.

INTRODUCTION: Axial spondyloarthritis (axSpA) affects patients' health-related quality of life (HRQoL). Prior studies have documented gender differences in axSpA across the disease spectrum. Our study aims to assess gender differences on the effects of axSpA on patients' HRQoL. METHOD: A secondary qualitative thematic analysis was conducted using data from in-depth interviews (n = 24) of patients with a rheumatologist-confirmed axSpA diagnosis. This analysis focused on gender and HRQoL themes including activity, occupation, sleep, healthcare system, mental health, medication usage, and relationships. RESULTS: While men on average waited a year longer than women to tell healthcare providers about symptoms (2.5 years men versus 1.6 years women), the interval between first report of symptoms to diagnosis was ~ 2 years longer for women relative to men (7.5 women versus 9.3 years men). Women and men with axSpA shared more similarities than differences regarding the impact of disease on HRQoL including (1) physical health, (2) limited mobility, (3) occupation, (4) sleep, (5) healthcare system obstacles, (6) mental health, (7) medication usage, and (8) relationships. Some women reported being dismissed by doctors due to their gender, and some described the pain experienced during pregnancy and complications during birth. CONCLUSIONS: axSpA adversely impacts HRQoL regardless of gender, but women seeking care for axSpA may experience greater challenges reaching a diagnosis. It is essential that providers recognize impaired HRQoL among men and women with axSpA. Future studies with larger sample sizes are needed to identify aspects of HRQoL to adequately address people with axSpA. Key Points • While men waited on average a year longer to tell their healthcare provider about their symptoms, the diagnostic delay is 2 years longer for women. • Women and men with axSpA have similar experiences regarding impacts on their health-related quality of life. • Some women describe difficulty during pregnancy and being dismissed by doctors due to their gender.

Dimensionality of the State-Trait Inventory of Cognitive and Somatic Anxiety.

The State-Trait Inventory of Cognitive and Somatic Anxiety (STICSA) is a commonly administered self-report instrument of state-trait cognitive and somatic anxiety. Extant research has consistently supported the intended oblique two-factor scoring structure for the STICSA. However, this model assumes that population-level data have (or approximate) a simple structure and that item-level variance is unidimensional. These assumptions may not be tenable and have unintended consequences for STICSA subscore interpretation. Consequently, we tested these assumptions by fitting confirmatory and exploratory structural equation models to STICSA scores for a diverse sample of college students enrolled at a large Southwestern university in the United States (n = 635). Results indicated that cognitive and somatic factors are not equally robust and that STICSA items appear to measure a nonnegligible mixture of both latent cognitive and somatic anxiety. It is recommended that future research use exploratory structural equation model in tandem with CFA to directly model data complexity.

Reasons for Initiating Canakinumab among Patients with Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still's Disease in the U.S. Real-World Settings.

INTRODUCTION: The aim of this study was to understand the reasons for canakinumab initiation among patients with Still's disease, including systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still's disease (AOSD), in US clinical practice. METHODS: Physicians retrospectively reviewed the medical charts of patients with Still's disease (regardless of age at symptom onset) who were prescribed canakinumab from 2016 to 2018. Patients aged < 16 years at symptom onset were classified as having SJIA and those aged ≥ 16 years at symptom onset (calculated from case-record forms) were classified as having AOSD. Patient treatment history and physician reasons for canakinumab initiation were analyzed. Overall results were presented as SJIA/AOSD. Sensitivity analyses were performed for the robustness of the results. RESULTS: Forty-three physicians in the USA (rheumatologists/dermatologists/immunologists/allergists: 51.2/27.9/11.6/9.3%; subspecialty in adults/pediatrics: 67.4/32.6%) abstracted information for 72 patients with SJIA/AOSD (SJIA/AOSD/age unknown at symptom onset: 75.0/18.1/6.9%; mean age 19.4 years; children 61.1%; females 56.9%). Most patients (90.3%) received treatment directly preceding canakinumab initiation (etanercept 27.7%; anakinra 18.5%; adalimumab 16.9%); the respective treatment was discontinued due to lack of efficacy/effectiveness (43.1%) and availability of a new treatment (27.8%). Most common reasons for canakinumab initiation were physician perceived/experienced efficacy/effectiveness of canakinumab (77.8%; children/adults: 81.8/71.4%), lack-of-response to previous treatment (45.8%; children/adults: 36.4/60.7%), convenient administration/dosing (26.4%; children/adults: 29.5/21.4%) and ability to discontinue/spare steroids (25.0%; children/adults: 20.5/32.1%). The sensitivity analysis provided similar results. CONCLUSIONS: In US clinical practice, physician perceived/experienced efficacy/effectiveness of canakinumab and lack-of-response to previous treatment were the primary reasons for canakinumab initiation among patients with SJIA/AOSD. Physician perceived/experienced efficacy/effectiveness and convenient administration/dosing of canakinumab were the most common reasons for canakinumab initiation among children, whereas lack-of-response to previous treatment and ability to discontinue/spare steroids being the most frequent reasons among adults.

Comparison of Clinical Manifestations in Rheumatoid Arthritis vs. Spondyloarthritis: A Systematic Literature Review.

INTRODUCTION: Misclassification of spondyloarthritis (SpA) as rheumatoid arthritis (RA) may lead to delayed SpA diagnosis and suboptimal therapeutic outcomes. Here, we evaluate the literature on clinical manifestations in patients with SpA and RA, particularly seronegative RA, to understand the potential overlap, distinctions, and most reliable approaches to accurate diagnosis. METHODS: In this systematic literature review, conducted according to PRISMA guidelines, we searched key biomedical databases for English-language publications of original research articles (up to July 23, 2020) and rheumatology conference abstracts (January 1, 2018-July 31, 2020) reporting key SpA clinical presentations in patients with SpA or RA. Publications were assessed for eligibility by two independent reviewers; discrepancies were resolved by a third. Studies were evaluated for publication quality using the Downs and Black checklist. RESULTS: Of 4712 records retrieved, 79 met the inclusion criteria and were included in the analysis. Of these, 54 included study populations with SpA and RA, and 25 with seropositive and/or seronegative RA. Entheseal abnormalities were more frequently reported among patients with SpA than RA and with seronegative vs. seropositive RA. Psoriasis, nail psoriasis, and dactylitis were exclusively seen in SpA vs. RA. In most publications (70 of 79), advanced imaging techniques allowed for more accurate distinction between SpA and RA. Overlapping clinical characteristics occur in SpA and RA, including inflammation and destruction of joints, pain, diminished functional ability, and increased risk for comorbidities. However, of 54 studies comparing SpA and RA populations, only seven concluded that no distinction can be made based on the SpA manifestations and outcomes examined. CONCLUSIONS: Typical SpA-related clinical symptoms and signs were observed in patients with RA, suggesting that misclassification could occur. Availability of advanced imaging modalities may allow for more prompt and comprehensive evaluation of peripheral manifestations in SpA and RA, reducing misclassification and delayed diagnosis.

Spondyloarthritis (SpA) is a group of chronic, inflammatory diseases that includes axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), in addition to other peripheral forms of SpA. AxSpA primarily affects the spine and can cause chronic back pain. PsA occurs in patients with the skin condition psoriasis and patients often experience symptoms including joint pain, stiffness, and swelling. Quick and accurate diagnosis of SpA is necessary to prevent joint damage and physical limitations. Rheumatoid arthritis (RA) is characterized by pain, swelling, and stiffness in multiple joints, and delayed diagnosis and treatment can have lasting effects. However, many patients with SpA and RA who initially seek medical care often experience delayed diagnoses. This study evaluated the literature on symptoms in patients with SpA and RA, particularly patients with RA without antibodies typically associated with the disease, to understand the potential overlap, differences, and most reliable ways to accurately diagnose patients. Data from 79 records were included in the analysis, 54 of which included study populations with SpA and RA. Skin and nail psoriasis, as well as swelling of the fingers and toes, was only seen in patients with SpA. Most studies showed that enhanced imaging allowed for distinguishing between SpA and RA. This study showed that typical signs and symptoms of SpA, including inflammation and joint pain, could also be seen in patients with RA, which suggests that challenges exist for accurately identifying SpA. This highlights the importance of advanced imaging to diagnose and treat patients with SpA in a timely manner.

Patient perspectives on health care provider practices leading to an axial spondyloarthritis diagnosis: an exploratory qualitative research study.

BACKGROUND: The average time to a diagnosis for people with axial spondyloarthritis (axSpA) is 7-10 years. Delayed diagnosis may result in increased structural damage, worse physical function, and worse quality of life relative to patients with a timely axSpA diagnosis. Understanding patient experiences may provide insights for how to reduce diagnostic delays. OBJECTIVE: To provide foundational knowledge about patient experiences with healthcare providers leading to an axSpA diagnosis. METHODS: We conducted an exploratory qualitative research study with six focus groups interviews with participants recruited from three rheumatology clinics within the United States (MA (n = 3); CO (n = 2); PA (n = 1)) that included a total of 26 adults (10 females, 16 males) with rheumatologist confirmed diagnosis of axSpA in 2019. Focus groups were ~ 2 h, audio recorded, transcribed, and subject to dual coding. The codes reviewed were in relation to the patients' diagnostic experiences. RESULTS: Patients described frustrating and lengthy diagnostic journeys. They recognized that the causes of diagnostic delays in axSpA are multifactorial (e.g., no definitive diagnostic test, disease characteristics, lack of primary care provider's awareness about axSpA, trust). Patients described how doctors minimized or dismissed complaints about symptoms or told them that their issues were psychosomatic. Patients believed the healthcare system contributed to diagnostic delays (e.g., lack of time in clinical visits, difficulty accessing rheumatologists, health insurance challenges). Advice to physicians to reduce the diagnostic delay included allowing time for patients to give a complete picture of their illness experience, listening to, and believing patients, earlier referral to rheumatology, provision of HLA-B27 gene testing, and that physicians need to partner with their patients. CONCLUSIONS: Patients desire a definitive test that could be administered earlier in the course of axSpA. Until such a test is available, patients want clinicians who listen to, believe, and partner with them, and who will follow them until a diagnosis is reached. Educating primary care clinicians about guidelines and referral for diagnosis of axSpA could reduce diagnostic delay.

Personal Experiences with Diagnostic Delay Among Axial Spondyloarthritis Patients: A Qualitative Study.

INTRODUCTION: On average, patients with axial spondyloarthritis (axSpA) suffer from symptoms up to 13 or more years before diagnosis, contributing to psychological distress and healthcare burden METHODS: We conducted six semi-structured focus groups with 26 axSpA patients (from 3 rheumatology practices located in the states of Massachusetts, Colorado, and Pensylvania, USA) exploring early disease and diagnostic experiences. Verbatim transcripts were coded using a start list with emerging thematic codes added. A qualitative thematic analysis was performed RESULTS: Many participants described meandering and frustrating diagnostic journeys. Participants reported that intermittent axSpA symptoms and idiopathic pain contributed to physician confusion and delay in patients seeking care. Participants were sometimes perceived as somaticizing, drug-seeking, or "crazy." Diagnostic delay led to frustration and mental suffering. Doctors "giving up" was considered profoundly negative. Stories of symptoms fell into five areas: (1) pain; (2) stiffness; (3) impact on sleep; (4) impact on daily activities; and (5) changes with weather. Self-advocacy and family advocacy were considered essential. Participants suggested wider use of HLA-B27 testing and development of a definitive diagnostic test CONCLUSION: Most participants described significant suffering prior to axSpA diagnosis which could have been avoided with earlier intervention. Further research on the early disease experiences of axSpA patients is needed.

Primary care physician perspectives on screening for axial spondyloarthritis: A qualitative study.

BACKGROUND: Many patients with axial spondylarthritis (axSpA) experience lengthy diagnostic delays upwards of 14 years. (5-14 years). Screening tools for axSpA have been proposed for use in primary care settings, but whether this approach could be implemented into busy primary care settings remains unknown. OBJECTIVE: To solicit feedback from primary care physicians regarding questions from the Inflammatory Back Pain Assessment: the Assessment of Spondyloarthritis International Society (ASAS) Expert Criteria and gain insight about barriers and facilitators for implementing axSpA screening in primary care. METHODS: Guided by Consolidated Criteria for reporting Qualitative Research (COREQ-criteria), we recorded, transcribed, and analyzed in-depth interviews with eight family medicine physicians and ten internists (purposeful sampling) using immersion/crystallization techniques. RESULTS: Few physicians reported awareness of existing classification criteria for axSpA, and many reported a lack of confidence in their ability to distinguish between inflammatory and mechanical back pain. From three domains, 10 subthemes emerged: 1) typical work-up of axSpA patients in primary care, with subthemes including the clues involved in work-up and role of clinical examinations for axSpA; 2) feedback on questions from the Inflammatory Back Pain Assessment: ASAS Expert Criteria, with subthemes to evaluate contents/questions of a potential screening tool for axSpA; and 3) implementation of the screening tool in primary care settings, with subthemes of perceived barriers including awareness, time, other conditions to screen, rare disease, and lack of structured questionnaire for back pain and perceived facilitators including workflow issues and awareness. CONCLUSIONS: Primary care physicians believed that an improved screening instrument and a strong evidence-base to support the need for screening for axSpA are required. The implementation of axSpA screening into a busy primary care practice requires integration into the practice workflow, with use of technology suggested as a possible way to improve efficiency.

Comparison of Men and Women With Axial Spondyloarthritis in the US-based Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: To compare patient characteristics and disease burden between men and women with axial spondyloarthritis (axSpA) in the US-based Corrona Psoriatic Arthritis/Spondyloarthritis (PsA/SpA) Registry. METHODS: Patients aged ≥ 18 years with axSpA enrolled in the Corrona PsA/SpA Registry between March 2013 and November 2018 who were not concurrently diagnosed with PsA were included. Patient demographics, clinical characteristics, disease activity, patient-reported symptoms, work productivity, and treatment history at enrollment were compared between men and women, using t tests or Wilcoxon rank-sum tests for continuous variables and chi-square or Fisher exact tests for categorical variables. RESULTS: Of 498 patients with axSpA and available sex information, 307 (61.6%) were men and 191 (38.4%) were women. Compared with men, women had higher disease activity as measured by Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and physician global assessment, and had higher tender/swollen joint counts and enthesitis scores (all P ≤ 0.01). Women also had worse patient-reported symptoms (pain, fatigue, Health Assessment Questionnaire for the Spondyloarthropathies, and EuroQol visual analogue scale; all P < 0.05), had greater work and activity impairment, and were less likely to work full time than men. Prior conventional synthetic disease-modifying antirheumatic drug and prednisone use was more common in women than in men (both P < 0.05). Additionally, women were more likely to have diagnoses of depression and fibromyalgia (both P < 0.01). CONCLUSION: In this US registry of patients with axSpA, women had higher overall disease burden and more peripheral manifestations than men. Improved awareness of sex differences in the presentation of axSpA may aid physicians in earlier identification and improved disease management.