Sacroiliitis in inflammatory bowel disease.

PURPOSE OF REVIEW: This review summarizes the recent evidence regarding the epidemiology of inflammatory bowel disease (IBD) associated sacroiliitis, including the prevalence, pathogenesis, role of imaging, and therapeutic challenges. RECENT FINDINGS: Sacroiliitis is an underappreciated musculoskeletal manifestation of IBD, a chronic inflammatory condition of the gut affecting the younger population. Untreated sacroiliitis can lead to joint destruction and chronic pain, further adding to morbidity in IBD patients. Recent publications suggest sacroiliitis can be detected on abdominal imaging obtained in IBD patients to study bowel disease, but only a small fraction of these patients were seen by rheumatologists. Early detection of IBD-associated sacroiliitis could be achieved by utilization of clinical screening tools in IBD clinics, careful examination of existing computed tomography and MRI studies, and timely referral to rheumatologist for further evaluation and treatment. Current treatment approaches for IBD and sacroiliitis include several targeted biologic therapies, but IBD-associated sacroiliitis has limited options, as these therapies may not overlap in both conditions. SUMMARY: With the advances in imaging, sacroiliitis is an increasingly recognized comorbidity in IBD patients. Future studies focusing on this unique patient population will expand our understanding of complex pathophysiology of IBD-associated sacroiliitis and lead to identification of novel targeted therapies for this condition.

Extrarenal symptoms associate with worse quality of life in patients enrolled in the AMP RA/SLE Lupus Nephritis Network.

OBJECTIVE: Lupus nephritis (LN) can occur as an isolated component of disease activity or be accompanied by diverse extrarenal manifestations. Whether isolated renal disease is sufficient to decrease health related quality of life (HRQOL) remains unknown. This study compared Patient-Reported Outcomes Measurement Information System 29-Item (PROMIS-29) scores in LN patients with isolated renal disease to those with extrarenal symptoms to evaluate the burden of LN on HRQOL and inform future LN clinical trials incorporating HRQOL outcomes. METHODS: A total of 181 LN patients consecutively enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership completed PROMIS-29 questionnaires at the time of a clinically indicated renal biopsy. Raw PROMIS-29 scores were converted to standardized T scores. RESULTS: Seventy-five (41%) patients had extrarenal disease (mean age 34, 85% female) and 106 (59%) had isolated renal (mean age 36, 82% female). Rash (45%), arthritis (40%) and alopecia (40%) were the most common extrarenal manifestations. Compared with isolated renal, patients with extrarenal disease reported significantly worse pain interference, ability to participate in social roles, physical function, and fatigue. Patients with extrarenal disease had PROMIS-29 scores that significantly differed from the general population by > 0.5 SD of the reference mean in pain interference, physical function, and fatigue. Arthritis was most strongly associated with worse scores in these three domains. CONCLUSION: Most patients had isolated renal disease and extrarenal manifestations associated with worse HRQOL. These data highlight the importance of comprehensive disease management strategies that address both renal and extrarenal manifestations to improve overall patient outcomes.

Twenty Years of SPARTAN: From Inception to Impact (SPARTAN 2023 Annual Meeting Proceedings).

PURPOSE OF REVIEW: This review takes a look at the past, present, and future of SPARTAN, the Spondyloarthritis Research and Treatment Network, an organization of North American healthcare professionals dedicated to advancing research, education, and patient care in spondyloarthritis. RECENT FINDINGS: In 2022, SPARTAN completed the Classification of Axial SpondyloarthritiS Inception Cohort (CLASSIC) study, a collaboration with the Assessment in SpondyloArthritis International Society (ASAS). CLASSIC aimed to validate the 2009 ASAS classification criteria for axial spondyloarthritis. Other ongoing SPARTAN endeavors include the development of US referral recommendations for axial spondyloarthritis, an update of the 2019 ACR/SAA/SPARTAN treatment recommendations for axial spondyloarthritis and multiple educational initiatives. Twenty years after its inception, SPARTAN continues to grow and broaden its impact, guided by the SPARTAN vision of "a world free of spondyloarthritis through leadership in research and education."

Measurement system for ultraviolet channel modeling and communications.

There has been an increasing interest in ultraviolet (UV) communications as a promising technology for non-line-of-sight (NLOS) networking by exploiting atmospheric scattering at UV wavelengths that enables a unique NLOS UV communication channel. While there has been significant theoretical and simulation-based investigation of the UV channel characteristics, there is limited work in terms of experimental research and validation of the analytical models. In this paper, we present a flexible experimental system for precise UV channel and communications measurements. Specifically, a transceiver system is developed that consists of a gimbal, UV light-emitting-diode array, and photomultiplier tube detector, node synchronization, and LabVIEW-based data acquisition subsystems. Novel techniques to precisely characterize the UV LED array radiation pattern, absolute transmit power, and field of view of the detector are also presented. The utility of the developed system is then demonstrated by performing a variety of experiments including UV channel model validation and steering optimization for UV communication links where the results were in very good agreement with theory and simulation.

Identifying trajectories of radiographic spinal disease in ankylosing spondylitis: a 15-year follow-up study of the PSOAS cohort.

OBJECTIVES: Little is known with certainty about the natural history of spinal disease progression in ankylosing spondylitis (AS). Our objective was to discover if there were distinct patterns of change in vertebral involvement over time and to study associated clinical factors. METHODS: Data were analysed from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) observational cohort. All patients met modified New York Criteria for AS and had ≥2 sets of radiographs scored by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by two independent readers between 2002 and 2017. Group-based trajectory modelling (GBTM) was used to classify patients into distinct groups of longitudinal mSASSS considering sociodemographic and clinical covariables. The optimal trajectory model and number of trajectories was selected using Nagin's Bayesian information criterion (BIC). RESULTS: A total of 561 patients with 1618 radiographs were analysed. The optimum number of trajectory groups identified was four (BIC -4062). These groups were subsequently categorized as: non-progressors (204 patients), late-progressors (147 patients), early-progressors (107 patients) and rapid-progressors (103 patients). Baseline predictors associated with higher spinal disease burden groups included: baseline mSASSS, male gender, longer disease duration, elevated CRP and smoking history. In addition, time-varying anti-TNF use per year was associated with decreased mSASSS progression only in the rapid-progressor group. CONCLUSIONS: GBTM identified four distinct patterns of spinal disease progression in the PSOAS cohort. Male gender, longer disease duration, elevated CRP and smoking were associated with higher spinal disease groups. Independent confirmation in other AS cohorts is needed to confirm these radiographic patterns.

High incidence of proliferative and membranous nephritis in SLE patients with low proteinuria in the Accelerating Medicines Partnership.

OBJECTIVE: Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1. METHODS: A total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year. RESULTS: At biopsy, 54 patients had UPCR <1 and 221 had UPCR ≥1. Independent of UPCR or biopsy number, a majority (92%) of patients had class III, IV, V or mixed histology. Moreover, patients with UPCR <1 and class III, IV, V, or mixed had a median activity index of 4.5 and chronicity index of 3, yet 39% of these patients had an inactive sediment. Neither anti-dsDNA nor low complement distinguished class I or II from III, IV, V or mixed in patients with UPCR <1. Of 29 patients with baseline UPCR <1 and class III, IV, V or mixed, 23 (79%) had a UPCR <0.5 at 1 year. CONCLUSION: In this prospective study, three-quarters of patients with UPCR <1 had histology showing class III, IV, V or mixed with accompanying activity and chronicity despite an inactive sediment or normal serologies. These data support renal biopsy at thresholds lower than a UPCR of 1.

Optimization of ultraviolet communication links based on finite difference stochastic approximation.

The ultraviolet communication (UV) channel has been shown to have unique features that could be exploited for covert ground-to-ground communications in complex non-line-of-sight (NLOS) scenarios. A key challenge is the determination of optimal configuration of pointing directions of the UV nodes in unknown NLOS environments to maximize the link performance. In this paper, we proposed a novel steering optimization approach based on Finite Difference Stochastic Approximation (FDSA) to simultaneously optimize the transmitter (Tx) and receiver (Rx) pointing directions without any knowledge about the locations and relative orientations of the two nodes. We perform parametric analysis using Monte Carlo channel simulations to investigate and select appropriate key algorithmic parameters and analyze the performance of the proposed algorithm. We also carry out experimentation using our custom designed UV Tx and Rx gimbal systems and demonstrate the utility and efficiency of the proposed steering optimization approach and show that the received photon count can be increased significantly.

Chronic inflammatory back pain commencing late in life: a neglected concept.

Chronic inflammatory back pain (CIBP) occurs in up to one-third of those with chronic back pain. Criteria for diagnosis of inflammatory back pain include an onset below 50 years. Using the US National Health and Nutrition Examination Survey data for 2009-2010, we showed that 3% of adults aged 50-69 years have features of CIBP with onset on or after 50 years. There is little information in the literature on CIBP of late onset. Patients with late onset CIBP may be falling through the cracks.

Prevalence of sacroiliitis among patients referred for hip MR arthrography.

OBJECTIVE: To determine the prevalence of sacroiliitis among patients who have been referred for MR arthrography. MATERIALS AND METHODS: A retrospective search identified 130 consecutive MR arthrograms of the hip performed on a 1.5T Siemens Avanto at our institution from August 2013 to August 2014. Four studies were excluded due to the absence of a coronal short tau inversion recovery sequence of the pelvis, leaving 126 studies for analysis. A musculoskeletal radiology fellow and three attending musculoskeletal radiologists reviewed the images for the presence of bone marrow edema affecting the sacroiliac joints. Only cases of bone marrow edema meeting the Assessment of SpondyloArthritis international Society definition were considered positive. The two-tailed Fisher's exact test was used to compare the prevalence of positive MRI findings among age and gender groups. GraphPad InStat (GraphPad Software) was used for statistical calculations. RESULTS: Patients less than 40 years of age demonstrated a statistically higher prevalence of positive MRI findings of sacroiliitis when compared to patients older than 40 (p = 0.0082). No difference in prevalence was found between genders. Overall prevalence of MRI signal alteration suggestive of sacroiliitis as defined by the Assessment of SpondyloArthritis international Society was 4.8%. Among the six patients with positive findings, two were subsequently diagnosed with spondyloarthritis. CONCLUSION: Hip pain may be a presenting symptom of spondyloarthritis and attention should be paid to the sacroiliac joints during screening examinations, particularly in patients less than 40 years of age.

Risk Factors for Spinal Structural Damage in a Chinese Cohort With Ankylosing Spondylitis.

OBJECTIVES: A cross-sectional study was conducted in 270 Chinese patients with ankylosing spondylitis (AS) in order to identify potential risk factors for severity of spinal structural damage. METHODS: Two hundred seventy AS patients fulfilled the Modified New York Criteria. Computed tomography (CT) was used to scan sacroiliac and hip joints, and radiography was used to scan anteroposterior and lateral lumbar spine, as well as lateral cervical spine. Bath Ankylosing Spondylitis Radiology Index and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) were scored in duplicate. RESULTS: One hundred eighty-three patients had low mSASSS (mSASSS, <10), and 87 patients had high mSASSS (mSASSS, ≥10). Univariate analysis revealed that AS age of onset, body mass index (BMI), smoking duration, duration of symptoms, diagnostic delay, hip involvement, and sacroiliitis grade were significantly associated with the risk of having high mSASSS after adjustment (all p's < 0.05). Hip involvement interacted significantly with BMI and smoking duration in a graded manner. Particularly, relative to patients with low BMI-negative hip involvement, those with high BMI-negative hip involvement, low BMI-positive hip involvement, and high BMI-positive hip involvement had a 1.94-fold, 3.29-fold, and 5.07-fold increased risk of high mSASSS (95% confidence interval, 0.84-4.47, 1.37-7.89, and 1.97-13.06, p = 0.118, 0.008, and 0.001, respectively). Finally, a nomogram graph based on 7 significant risk factors was generated with substantial prediction accuracy (concordance index, 0.906). CONCLUSIONS: We have identified 7 potential risk factors for the severity of spinal structural damage in Chinese AS patients. Importantly, positive hip involvement, combined with high BMI or long smoking duration, was associated with a remarkably increased risk of having severe spinal structural damage.

Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting.

OBJECTIVES: Little is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting. METHODS: We screened for serum cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor isotype aAbs in subjects who were at increased risk for rheumatoid arthritis (RA) because they are a first-degree relative of an individual with classified RA (n=1780). We evaluated combinations of aAbs and high titre aAbs, as defined by 2-times (2 x) the standard cut-off and an optimal cut-off, as predictors of our two outcomes, aAb+ persistence and incident IA. RESULTS: 304 subjects (17.1%) tested aAb+; of those, 131 were IA-free and had at least one follow-up visit. Sixty-four per cent of these tested aAb+ again on their next visit. Anti-CCP+ at levels ≥2 x the standard cut-off was associated with 13-fold higher likelihood of aAb +persistence. During a median of 4.4 years (IQR: 2.2-7.2), 20 subjects (15.3%) developed IA. Among subjects that screened anti-CCP+ at ≥ 2 x or ≥an optimal cut-off, 32% and 26% had developed IA within 5 years, respectively. Both anti-CCP cut-offs conferred an approximate fourfold increased risk of future IA (HR 4.09 and HR 3.95, p<0.01). CONCLUSIONS: These findings support that aAb screening in a non-clinical setting can identify RA-related aAb+ individuals, as well as levels and combinations of aAbs that are associated with higher risk for future IA. Monitoring for the development of IA in aAb+ individuals and similar aAb testing approaches in at-risk populations may identify candidates for prevention studies in RA.

Polygenic Risk Scores have high diagnostic capacity in ankylosing spondylitis.

OBJECTIVE: We sought to test the hypothesis that Polygenic Risk Scores (PRSs) have strong capacity to discriminate cases of ankylosing spondylitis (AS) from healthy controls and individuals in the community with chronic back pain. METHODS: PRSs were developed and validated in individuals of European and East Asian ethnicity, using data from genome-wide association studies in 15 585 AS cases and 20 452 controls. The discriminatory values of PRSs in these populations were compared with other widely used diagnostic tests, including C-reactive protein (CRP), HLA-B27 and sacroiliac MRI. RESULTS: In people of European descent, PRS had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.924. This was significantly better than for HLA-B27 testing alone (AUC=0.869), MRI (AUC=0.885) or C-reactive protein (AUC=0.700). PRS developed and validated in individuals of East Asian descent performed similarly (AUC=0.948). Assuming a prior probability of AS of 10% such as in patients with chronic back pain under 45 years of age, compared with HLA-B27 testing alone, PRS provides higher positive values for 35% of patients and negative predictive values for 67.5% of patients. For PRS, in people of European descent, the maximum positive predictive value was 78.2% and negative predictive value was 100%, whereas for HLA-B27, these values were 51.9% and 97.9%, respectively. CONCLUSIONS: PRS have higher discriminatory capacity for AS than CRP, sacroiliac MRI or HLA-B27 status alone. For optimal performance, PRS should be developed for use in the specific ethnic groups to which they are to be applied.

Does hydroxychloroquine improve patient reported outcomes in patients with lupus?

BACKGROUND: Hydroxychloroquine (HCQ) use is associated with less disease activity, flares, damage and improved survival in Systemic Lupus Erythematosus (SLE). However, its effect on patient reported health outcomes (PROs) such as quality of life (QOL) is not known. METHODS: International data from Study on Outcomes of Lupus (SOUL) from 2,161 SLE patients were compared by HCQ use. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC-ACR/SDI. QOL was evaluated using LupusPRO and Lupus Impact Tracker (LIT). Linear regression analyses were performed with LupusPRO summary scores health related HRQOL, non-health related NHRQOL and LIT as dependent and HCQ use as independent variable. Analyses were undertaken to test mediation of effects of HCQ use on QOL through disease activity. RESULTS: Mean age was 40.5 ± 12.8 years, 93% were women. Sixty-three (1363/2161) percent were on HCQ. On univariate analysis, HCQ use was associated with (a) better QOL (LupusPRO-HRQOL: ß 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: ß 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: ß -9.37, 95% CI -12.24, -6.50, P ≤ 0.001). On multivariate and mediational analyses, the effects of HCQ on QOL were indirectly and completely mediated through disease activity. CONCLUSIONS: HCQ use in SLE is associated with better patient reported health outcomes (LupusPRO-HRQOL and NHRQOL and impact on daily life), and the effects are mediated through disease activity. This information can facilitate patients and physician's communication with decision-making regarding the use of HCQ for SLE management.

Genetic fine mapping of systemic lupus erythematosus MHC associations in Europeans and African Americans.

Genetic variation within the major histocompatibility complex (MHC) contributes substantial risk for systemic lupus erythematosus, but high gene density, extreme polymorphism and extensive linkage disequilibrium (LD) have made fine mapping challenging. To address the problem, we compared two association techniques in two ancestrally diverse populations, African Americans (AAs) and Europeans (EURs). We observed a greater number of Human Leucocyte Antigen (HLA) alleles in AA consistent with the elevated level of recombination in this population. In EUR we observed 50 different A-C-B-DRB1-DQA-DQB multilocus haplotype sequences per hundred individuals; in the AA sample, these multilocus haplotypes were twice as common compared to Europeans. We also observed a strong narrow class II signal in AA as opposed to the long-range LD observed in EUR that includes class I alleles. We performed a Bayesian model choice of the classical HLA alleles and a frequentist analysis that combined both single nucleotide polymorphisms (SNPs) and classical HLA alleles. Both analyses converged on a similar subset of risk HLA alleles: in EUR HLA- B*08:01 + B*18:01 + (DRB1*15:01 frequentist only) + DQA*01:02 + DQB*02:01 + DRB3*02 and in AA HLA-C*17:01 + B*08:01 + DRB1*15:03 + (DQA*01:02 frequentist only) + DQA*02:01 + DQA*05:01+ DQA*05:05 + DQB*03:19 + DQB*02:02. We observed two additional independent SNP associations in both populations: EUR rs146903072 and rs501480; AA rs389883 and rs114118665. The DR2 serotype was best explained by DRB1*15:03 + DQA*01:02 in AA and by DRB1*15:01 + DQA*01:02 in EUR. The DR3 serotype was best explained by DQA*05:01 in AA and by DQB*02:01 in EUR. Despite some differences in underlying HLA allele risk models in EUR and AA, SNP signals across the extended MHC showed remarkable similarity and significant concordance in direction of effect for risk-associated variants.

Spondyloarthritis evolution: what is in your history?

PURPOSE OF REVIEW: This review encompasses a detailed history of spondyloarthritis (SpA) evolution as early as the 17th century, continues on to the current concept of SpA, and ends with current gaps in our understandings of SpA. RECENT FINDINGS: Until the early 1960s, ankylosing spondylitis and other SpA family members were considered to be variants of rheumatoid arthritis (RA). The formal medical community separated them from RA at that time, and shortly thereafter they were recognized to be inter-connected based on shared clinical, laboratory, and imaging features. The last two decades have witnessed the formal distinction between axial and peripheral SpA and the connections that exist between nonradiographic and radiographic axial SpA. Recent studies have revealed different microbial compositions among patients with SpA and healthy controls and also between HLA-B27 positive and negative healthy individuals. SUMMARY: Further investigation of the roles of intestinal microbiome and physical force transduction toward SpA pathogenesis, strategies to improve delay in SpA diagnosis, biomarkers to better predict radiographic progression, and modification of current classification criteria to better address the axial and peripheral groups are gaps in our understandings that pose top priorities for SpA research.

Development of ASAS quality standards to improve the quality of health and care services for patients with axial spondyloarthritis.

OBJECTIVES: The Assessment of SpondyloArthritis International Society (ASAS) aimed to develop a set of quality standards (QS) to help improve the quality of healthcare provided to adult patients affected by axial spondyloarthritis (axSpA) worldwide. METHODS: An ASAS task force developed a set of QS using a stepwise approach. First, key areas for quality improvement were identified, discussed, rated and agreed on. Thereafter, areas were prioritised and statements for the most important key areas were phrased on consensus. Appropriate quality measures were defined to allow quantification of the QS at the community level. RESULTS: The ASAS task force, consisting of 20 rheumatologists, two physiotherapists and two patients, selected and proposed 34 potential key areas for quality improvement which were then commented by 140 ASAS members and patients. Within that process three new key areas came up, which led to a re-evaluation of all 37 key areas by 120 ASAS members and patients. Five key areas were identified as most important to determine quality of care: referral including rapid access, rheumatology assessment, treatment, education/self-management and comorbidities. Finally, nine QS were agreed on and endorsed by the whole ASAS membership. CONCLUSIONS: ASAS successfully developed the first set of QS to help improving healthcare for adult patients with axSpA. Even though it may currently not be realistic to achieve the QS in all healthcare systems, they provide high-quality of care framework for patients with axSpA that should be aimed for.

Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis.

OBJECTIVES: Evaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial. METHODS: Patients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse. RESULTS: 188 patients were studied: 95/188 (51%) men, median age 59 years (range 19-89), prior disease duration 5.0 years (range 0.4-34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections. CONCLUSIONS: This large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.

Analysis of the low-probability-of-detection characteristics of ultraviolet communications.

Deep ultraviolet wavelengths have been proposed for low-probability-of-detection (LPD) communications, particularly for non-line-of-sight (NLOS) links, because of the increased atmospheric absorption at these wavelengths. Motivated by this favorable feature, we develop a modeling framework to quantitatively study the LPD characteristics of ultraviolet communications (UVC). We then demonstrate the application of our modeling framework by considering various friendly and adversarial system configurations and quantifying the proposed LPD metric (the range at which an adversary can detect communications that uses the minimum power needed to meet given communications performance requirements), as well as investigating the sensitivity of the analysis to various scenario parameters. The results demonstrate the potential for this modeling and analysis approach to provide key insights into the design and operation of LPD NLOS UVC systems.

A latent class based imputation method under Bayesian quantile regression framework using asymmetric Laplace distribution for longitudinal medication usage data with intermittent missing values.

Evaluating the association between diseases and the longitudinal pattern of pharmacological therapy has become increasingly important. However, in many longitudinal studies, self-reported medication usage data collected at patients' follow-up visits could be missing for various reasons. These pieces of missing or inaccurate/untenable information complicate determining the trajectory of medication use and its complete effects for patients. Although longitudinal models can deal with specific types of missing data, inappropriate handling of this issue can lead to a biased estimation of regression parameters especially when missing data mechanisms are complex and depend upon multiple sources of variation. We propose a latent class-based multiple imputation (MI) approach using a Bayesian quantile regression (BQR) that incorporates cluster of unobserved heterogeneity for medication usage data with intermittent missing values. Findings from our simulation study indicate that the proposed method performs better than traditional MI methods under certain scenarios of data distribution. We also demonstrate applications of the proposed method to data from the Prospective Study of Outcomes in Ankylosing Spondylitis (AS) cohort when assessing an association between longitudinal nonsteroidal anti-inflammatory drugs (NSAIDs) usage and radiographic damage in AS, while the longitudinal NSAID index data are intermittently missing.

Longitudinal associations between depressive symptoms and clinical factors in ankylosing spondylitis patients: analysis from an observational cohort.

OBJECTIVES: Although cross-sectional studies have shown that ankylosing spondylitis-specific factors correlate with depressive symptom severity, the association of these factors over time is unresolved. We examined the demographic and clinical factors associated with longitudinal depressive symptom severity in AS patients. METHODS: We analyzed sociodemographic, clinical, behavioral and medication data from 991 patients from the Prospective Study of Outcomes in Ankylosing spondylitis cohort, and measured depression severity with the Center for Epidemiological Studies Depression (CES-D) Scale administered at approximately 6-month visit intervals. Multivariable longitudinal negative binomial regression models were conducted using generalized estimating equation modeling to assess the demographic, clinical, and medication-related factors associated with depression severity by CES-D scores over time. RESULTS: The median baseline CES-D score (possible range 0-60) was 10.0 (interquartile range = 5, 17). In longitudinal multivariable analyses, higher CES-D scores were associated with longitudinal smoking, greater functional impairment, greater disease activity, self-reported depression, and poor global health scores. Marital status (e.g., being married) was associated with lower CES-D. Adjusted mean CES-D scores in our model decreased over time, with a significant interaction between time and gender observed. CONCLUSION: This study identified longitudinal clinical factors such as greater disease activity, greater functional impairment, and poor global health to be associated with longitudinal depression severity. These factors are potentially modifiable and may help manage depressive symptoms in AS.