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Objective: Gout is associated with a higher risk of fracture; however, findings on the associations of hyperuricemia and urate‐lowering therapy (ULT) with the risk of fracture have been inconsistent. We examined whether lowering serum urate (SU) levels with ULT to a target level (i.e., <360 μmoles/liter) reduces the risk of fracture among individuals with gout. Methods: We emulated analyses of a hypothetical target trial using a "cloning, censoring, and weighting" approach to examine the association between lowering SU with ULT to the target levels and the risk of fracture using data from The Health Improvement Network, a UK primary care database. Individuals with gout who were age 40 years or older and for whom ULT was initiated were included in the study. Results: Among 28,554 people with gout, the 5‐year risk of hip fracture was 0.5% for the "achieving the target SU level" arm and 0.8% for the "not achieving the target SU level" arm. The risk difference and hazard ratio for the "achieving the target SU level" arm was –0.3% (95% confidence interval [95% CI] –0.5%, –0.1%) and 0.66 (95% CI 0.46, 0.93), respectively, compared with the "not achieving the target SU level" arm. Similar results were observed when the associations between lowering SU level with ULT to the target levels and the risk of composite fracture, major osteoporotic fracture, vertebral fracture, and nonvertebral fracture were assessed. Conclusion: In this population‐based study, lowering the SU level with ULT to the guideline‐based target level was associated with a lower risk of incident fracture in people with gout. [ABSTRACT FROM AUTHOR]

Objectives Angiotensin II is implicated in GCA pathology. We examined whether the use of angiotensin receptor blockers (ARBs) is associated with GCA risk compared with angiotensin-converting enzyme inhibitors (ACEis) or other antihypertensives. Methods We performed a matched cohort study including adults who were initiators of antihypertensives in UK primary care data between 1995 and 2019. Treatment-naïve individuals without prior GCA or PMR were categorized into three groups—ARB initiators, ACEi initiators, or other antihypertensive initiators (beta-blockers, calcium channel blockers, diuretics or alpha-adrenoceptor blockers)—and followed for up to 5 years. Incident GCA was defined using validated Read codes, with age of onset ≥50 years and two or more glucocorticoid prescriptions. Inverse probability–weighted Cox models were used to model outcome risk, adjusting for lifestyle parameters, comorbidities and comedications. Results Among >1 million new starters of antihypertensives (81 780 ARBs, 422 940 ACEis and 873 066 other antihypertensives), the incidence rate of GCA per 10 000 patient-years was 2.73 (95% CI 2.12, 3.50) in the ARB group, 1.76 (95% CI 1.25, 2.39) in the ACEi group and 1.90 (95% CI 1.37, 2.56) in the other antihypertensives group. The hazard of GCA was higher in ARB initiators [hazard ratio (HR) 1.55; 95% CI 1.16, 2.06] than initiators of ACEis, but similar between initiators of other antihypertensives and ACEis (HR 1.08; 95% CI 0.87, 1.35). Conclusions Initiation of ARBs is associated with a higher risk of GCA compared with ACEis or other antihypertensives. Mechanistic studies of angiotensin receptor biology will provide further clarity for our findings. [ABSTRACT FROM AUTHOR]

To compare the biomechanical stability of slide compression anatomic plates of the femoral neck, cannulated compression screws and dynamic hip screws with derotation screws for stabilizing unstable femoral neck fractures (Pauwels angle = 70°). Pauwels III femoral neck fractures were created on 45 Sawbones femurs and randomly assigned to three implant groups (1:1:1). The biomechanical stability of all Sawbones in each treatment group was evaluated with three tests. First, in the static loading test, the load–displacement curve, vertical stiffness (load/vertical displacement [N/mm]) and 5 mm failure load were recorded. Second, in the incremental cyclic loading test (700, 1000, and 1400 N), the cyclic−displacement curve and the displacement of the fragments were recorded. Third, in the torsion test, the torsional rigidity, maximum torque, and torsional angle corresponding to the maximum torque were recorded. The static compression test showed that slide compression anatomic place‐femoral neck (SCAP‐FN) had the largest vertical stiffness (275 ± 11 N/mm, p < 0.01) and 5 mm failure load (1232 ± 156, p < 0.01). The cyclic loading test showed that SCAP‐FN had the lowest change in displacement after 30000 cycles of loading. The torsional stiffness and the maximum torque followed the order SCAP‐FN > dynamic hip screw systems (DHS) + derotational screw (DS) > CCS, and the torsional angle corresponding to the maximum torque followed the order SCAP‐FN < DHS + DS < CCS. The SCAP‐FN construct provides stiffness and stability compared with other standard fixation techniques (3CS and DHS + DS). The fixation strategy of SCAP‐FN might be sufficient for clinical use, indicating studies in the human body are warranted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of preoperative anemia on postoperative complications after hip fracture surgery. Patients and Methods: We conducted a retrospective study including hip fracture patients at a teaching hospital between 2005 and 2022. We defined preoperative anemia as the last hemoglobin measurement level before surgery < 130 g/L for men and < 120 g/L for women. The primary outcome was a composite of in-hospital major complications, including pneumonia, respiratory failure, gastrointestinal bleeding, urinary tract infection, incision infection, deep venous thrombosis, pulmonary embolism, angina pectoris, arrhythmia, myocardial infarction, heart failure, stroke, and death. Secondary outcomes were cardiovascular events, infection, pneumonia, and death. We used multivariate negative binomial or logistic regression to evaluate the impact of anemia and its severity, categorized as mild (90– 130 g/L for men, 90– 120 g/L for women) or moderate-to-severe (< 90 g/L for both) anemia on outcomes. Results: Of the 3540 included patients, 1960 had preoperative anemia. 188 anemic patients experienced 324 major complications, while 63 non-anemic patients had 94 major complications. The risk of major complications was 165.3 (95% CI, 149.5– 182.4) and 59.5 (95% CI, 48.9– 72.3) per 1000 persons in anemic and non-anemic patients, respectively. Anemic patients were more likely to have major complications than non-anemic patients (adjusted incidence rate ratio (aIRR), 1.87; 95% CI, 1.30– 2.72), which was consistent in mild (aIRR, 1.77; 95% CI, 1.22– 2.59) and moderate-to-severe (aIRR, 2.97; 95% CI, 1.65– 5.38) anemia. Preoperative anemia also increased the risk of cardiovascular events (aIRR, 1.96; 95% CI, 1.29– 3.01), infection (aIRR, 1.68; 95% CI, 1.01– 2.86), pneumonia (adjusted odds ratio (aOR), 1.91; 95% CI, 1.06– 3.57), and death (aOR, 3.17; 95% CI, 1.06– 11.89). Conclusion: Our findings suggest that even mild preoperative anemia is associated with major postoperative complications in hip fracture patients. This finding highlights considering preoperative anemia as a risk factor in surgical decision-making for high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown.Objective: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD.Design: Cohort study.Setting: The Health Improvement Network U.K. primary care database (2000 to 2019).Participants: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD.Measurements: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators.Results: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07).Limitation: Residual confounding cannot be ruled out.Conclusion: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD.Primary Funding Source: Project Program of National Clinical Research Center for Geriatric Disorders. [ABSTRACT FROM AUTHOR]

Objectives: There is still a large unmet need for novel osteoarthritis (OA) treatments that could provide clinically important effects on long-term pain relief (≥12 months). We examined the relation of bariatric surgery along with weight loss to analgesic prescription and all-cause mortality among individuals with OA.Methods: We conducted a cohort study among individuals with OA using The Health Improvement Network. We compared the rate of no analgesic prescription ≥12 consecutive months and the risk of all-cause mortality using inverse probability weighting Cox-proportional hazard models and the difference in number of analgesic prescriptions (non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in the 50th, 75th and 90th percentiles using quantile regression model between bariatric and non-bariatric cohorts.Results: Included were 588,494 individuals (694 had bariatric surgery). Compared with non-bariatric group, the rate of no analgesic prescription ≥12 consecutive months was higher (HR = 1.23, 95% CI: 1.08-1.38) in bariatric surgery group, and the number of analgesic prescriptions was lower in the 75th (44 vs 58) and 90th (74 vs 106) percentiles during a mean follow-up of 4.3 years. All-cause mortality in bariatric surgery group was lower than comparison group (HR = 0.46, 95% CI: 0.41-0.51).Conclusion: This study presents the first evidence that bariatric surgery was associated with decreased long-term analgesic prescription and decreased all-cause mortality among individuals with OA. However, our findings may be overestimated owing to intractable confounding by indication for bariatric surgery; thus, future studies (e.g., clinical trials) are warranted. [ABSTRACT FROM AUTHOR]

Objective: Systemic inflammatory factors have been implicated in symptomatic hand osteoarthritis (OA). Gut microbiome dysbiosis promotes systemic inflammation. The aim of this study was to examine the association between the gut microbiome and the presence of symptomatic hand OA in a population‐based study. Methods: Study participants were subjects of the Xiangya Osteoarthritis Study, a community‐based observational study conducted in the Hunan Province of China. Symptomatic hand OA was defined as the presence of both symptoms and radiographic OA in the same hand. The gut microbiome was analyzed using 16S ribosomal RNA gene sequencing in stool samples. We examined the relation of α‐diversity, β‐diversity, relative abundance of taxa, and potential bacterial functional pathways to symptomatic hand OA. Results: A total of 1,388 participants (mean age 61.3 years, 57.4% women) were included in the study, of whom 72 had symptomatic hand OA (prevalence of symptomatic hand OA 5.2%). Beta‐diversity of the gut microbiome, but not α‐diversity, was significantly associated with the presence of symptomatic hand OA (P = 0.003). Higher relative abundance of the genera Bilophila and Desulfovibrio as well as lower relative abundance of the genus Roseburia was associated with symptomatic hand OA. Most functional pathways (i.e., those annotated in the KEGG Ortholog hierarchy) that were observed to be altered in participants with symptomatic hand OA belonged to the amino acid, carbohydrate, and lipid metabolic pathways. Conclusion: This large, population‐based study provides the first evidence that alterations in the composition of the gut microbiome were observed among study participants who had symptomatic hand OA, and a low relative abundance of Roseburia but high relative abundance of Bilophila and Desulfovibrio at the genus level were associated with prevalent symptomatic hand OA. These findings may help investigators understand the role of the microbiome in the development of symptomatic hand OA and could contribute to potential translational opportunities. [ABSTRACT FROM AUTHOR]

Objective: To describe the secular trends in comorbidities and postoperative complications of geriatric hip fracture patients from the Chinese People's Liberation Army General Hospital Hip Fracture Cohort between 2000 and 2019. Methods: We included 2,805 hip fracture patients aged 65 years or older and received surgical treatment from 25 January 2000 to 19 December 2019. Demographic characteristics, comorbidities, postoperative complications, length of hospital stay, and the time to surgery were extracted and examined in each 5‐year period based on the admission year, namely 2000–2004, 2005–2009, 2010–2014, and 2015–2019. Categorical data were analyzed by chi‐squared or Fisher's exact test, with ordinal data by row mean scores difference test and continuous data by one‐way analysis of variance. Trends in comorbidities and postoperative complications were examined by the Cochran–Armitage trend test. Results: The average age of the included population was 79.1 ± 7.3 years (mean ± standard deviation), and 69.1% were female. From 2000 to 2019, the proportion of females increased from 59.8% to 73.0% (P for trend <0.05). Hypertension (51.8%), type 2 diabetes (23.6%), coronary heart disease (20.9%), stroke (18.7%), and arrhythmia (11.2%) were the most prevalent five comorbidities. The proportion of hypertension was 27.0%, 45.4%, 53.0%, and 57.2% in each 5‐year period with an increasing trend (P for trend <0.05). The proportion of type 2 diabetes was 9.8%, 22.8%, 23.5%, and 26.0% in each 5‐year period (P for trend <0.05). Similar increasing trends were found in myocardial infarction, arrhythmia, and tumor. On the contrary, the proportion of patients with major postoperative complications decreased from 2000 to 2019, with 23.0%, 14.6%, 6.5%, and 5.6% in each 5‐year period (P for trend <0.05). For each specific postoperative complication, i.e. pneumonia, cardiovascular event, respiratory failure, and in‐hospital death, similar decreasing trends were found (all P for trend <0.05). Conclusion: This descriptive analysis sheds light on the fact that the health status of the hip fracture population tends to shift gradually. Improving concepts and practices of clinical interventions may help reduce postoperative complications, whereas challenges in the management of comorbidities increase. [ABSTRACT FROM AUTHOR]

Objective: Identifying pseudogout in large data sets is difficult due to its episodic nature and a lack of billing codes specific to this acute subtype of calcium pyrophosphate (CPP) deposition disease. The objective of this study was to evaluate a novel machine learning approach for classifying pseudogout using electronic health record (EHR) data. Methods: We created an EHR data mart of patients with ≥1 relevant billing code or ≥2 natural language processing (NLP) mentions of pseudogout or chondrocalcinosis, 1991–2017. We selected 900 subjects for gold standard chart review for definite pseudogout (synovitis + synovial fluid CPP crystals), probable pseudogout (synovitis + chondrocalcinosis), or not pseudogout. We applied a topic modeling approach to identify definite/probable pseudogout. A combined algorithm included topic modeling plus manually reviewed CPP crystal results. We compared algorithm performance and cohorts identified by billing codes, the presence of CPP crystals, topic modeling, and a combined algorithm. Results: Among 900 subjects, 123 (13.7%) had pseudogout by chart review (68 definite, 55 probable). Billing codes had a sensitivity of 65% and a positive predictive value (PPV) of 22% for pseudogout. The presence of CPP crystals had a sensitivity of 29% and a PPV of 92%. Without using CPP crystal results, topic modeling had a sensitivity of 29% and a PPV of 79%. The combined algorithm yielded a sensitivity of 42% and a PPV of 81%. The combined algorithm identified 50% more patients than the presence of CPP crystals; the latter captured a portion of definite pseudogout and missed probable pseudogout. Conclusion: For pseudogout, an episodic disease with no specific billing code, combining NLP, machine learning methods, and synovial fluid laboratory results yielded an algorithm that significantly boosted the PPV compared to billing codes. [ABSTRACT FROM AUTHOR]

Background: Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect.Objective: To estimate the risk for fracture among users of denosumab who delayed subsequent doses compared with users who received doses on time.Design: Population-based cohort study.Setting: The Health Improvement Network U.K. primary care database, 2010 to 2019.Patients: Persons aged 45 years or older who initiated denosumab therapy for osteoporosis.Measurements: Observational data were used to emulate an analysis of a hypothetical trial with 3 dosing intervals: subsequent denosumab injection given within 4 weeks after the recommended date ("on time"), delay by 4 to 16 weeks ("short delay"), and delay by more than 16 weeks ("long delay"). The primary outcome was a composite of all fracture types at 6 months after the recommended date. Secondary outcomes were major osteoporotic fracture, vertebral fracture, hip fracture, and nonvertebral fracture.Results: Investigators identified 2594 patients initiating denosumab therapy. The risk for composite fracture over 6 months was 27.3 in 1000 for on-time dosing, 32.2 in 1000 for short delay, and 42.4 in 1000 for long delay. Compared with on-time injections, short delay had a hazard ratio (HR) for composite fracture of 1.03 (95% CI, 0.63 to 1.69) and long delay an HR of 1.44 (CI, 0.96 to 2.17) (P for trend = 0.093). For vertebral fractures, short delay had an HR of 1.48 (CI, 0.58 to 3.79) and long delay an HR of 3.91 (CI, 1.62 to 9.45).Limitation: Dosing schedules were not randomly assigned.Conclusion: Although delayed administration of subsequent denosumab doses by more than 16 weeks is associated with increased risk for vertebral fracture compared with on-time dosing, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with long delay.Primary Funding Source: National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation. [ABSTRACT FROM AUTHOR]

Objective: Methotrexate (MTX) increases the risk of alopecia and stomatitis, but the prevalence of these adverse events among rheumatic patients taking MTX is poorly defined. We conducted a systematic literature review and meta-analysis to estimate the prevalence of alopecia and stomatitis with MTX in rheumatic diseases.Methods: We searched PubMed, The Cochrane Library, and CINAHL databases for double-blind randomized controlled trials (RCTs) with an MTX monotherapy arm. Alopecia, stomatitis, and oral/mouth ulcers data were extracted. The quality of trials was assessed by 2 authors. We included trials published since 1990 that used at least 10 mg of MTX weekly, coadministered with folic or folinic acid. We estimated the prevalence using random-effects models because heterogeneity was anticipated. Two estimates of prevalence were included; the lower bound estimate included all trials (assuming no alopecia and stomatitis if not mentioned), and the upper bound estimate included only those that specifically described prevalence estimates of alopecia or stomatitis.Results: Of 3,954 studies identified, 20 RCTs were included, with a total of 24 MTX monotherapy arms, of which 10 reported the prevalence of alopecia (n = 1,113), and 21 reported stomatitis or mouth/oral ulcers (n = 2,056). The prevalence of alopecia was between 1.0% and 4.9%. The prevalence of stomatitis was between 5.7% and 8.0%.Conclusion: This meta-analysis gives more precise estimates of mucocutaneous adverse events that occur in rheumatic disease patients taking MTX. These estimates will help inform patient decision-making regarding MTX. [ABSTRACT FROM AUTHOR]

Objectives: Target trial emulation is an intuitive design framework that encourages investigators to formulate their comparative effectiveness research (CER) question as a hypothetical randomised controlled trial (RCT). Our aim was to systematically review CER studies in rheumatoid arthritis (RA) to provide examples of design limitations that could be avoided using target trial emulation, and how these limitations might introduce bias.Methods: We searched for head-to-head CER studies of biologic disease modifying anti-rheumatic drugs (DMARDs) in RA. Study designs were reviewed for seven components of the target trial emulation framework: eligibility criteria, treatment strategies, assignment procedures, follow-up period, outcome, causal contrasts of interest (ie, intention-to-treat (ITT) or per-protocol effect) and analysis plan. Hypothetical trials corresponding to the reported methods were assessed to identify design limitations that would have been avoided with an explicit target trial protocol. Analysis of the primary effectiveness outcome was chosen where multiple analyses were performed.Results: We found 31 CER studies, of which 29 (94%) had at least one design limitation belonging to seven components. The most common limitations related to: (1) eligibility criteria: 19/31 (61%) studies used post-baseline information to define baseline eligibility; (2) causal contrasts: 25 (81%) did not define whether ITT or per-protocol effects were estimated and (3) assignment procedures: 13 (42%) studies did not account for confounding by indication or relied solely on statistical confounder selection.Conclusions: Design limitations were found in 94% of observational CER studies in RA. Target trial emulation is a structured approach for designing observational CER studies that helps to avoid potential sources of bias. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare achievement of remission in 2 early rheumatoid arthritis (RA) treat‐to‐target (TTT) cohorts, a tight control cohort with a target of stringent remission in a randomized controlled trial and an observational cohort targeting a looser definition of remission in clinical practice. Methods: We analyzed data from the Aiming for Remission in Rheumatoid Arthritis: a randomised trial examining the benefit of ultrasound in a Clinical Tight Control regimen (ARCTIC) trial and the Norwegian Very Early Arthritis Clinic (NOR‐VEAC) observational study. Both were Norwegian multicenter studies that included disease‐modifying antirheumatic drug (DMARD)–naive RA patients and implemented TTT. The target in the ARCTIC trial was remission defined as a Disease Activity Score (DAS) of <1.6 plus 0 swollen joints on a 44‐joint count, while the target in the NOR‐VEAC study was the less stringent remission target of a DAS28 of <2.6. We assessed achievement of the study‐specific targets and compared the odds of achieving the American College of Rheumatology(ACR)/European League Against Rheumatism (EULAR) Boolean remission during 2 years of follow‐up. Results: We included 189 patients from the ARCTIC trial and 330 patients from the NOR‐VEAC study. The study‐specific target had been achieved in more than half of the patients in each cohort at 6 months, increasing to >60% at 12 and 24 months. The odds of achieving ACR/EULAR Boolean remission during follow‐up were higher in the ARCTIC trial than in the NOR‐VEAC study, with significant differences at 3 months (odds ratio 1.73 [95% confidence interval 1.03–2.89]), 12 months (odds ratio 1.97 [95% confidence interval 1.21–3.20]), and 24 months (odds ratio 1.82 [95% confidence interval 1.05–3.16]). Conclusion: A majority of patients in both cohorts reached the study‐specific treatment targets. More patients in the ARCTIC trial than in the NOR‐VEAC study achieved ACR/EULAR Boolean remission during follow‐up, suggesting that targeting a more stringent definition of remission provides further potential for favorable outcomes of a TTT strategy. [ABSTRACT FROM AUTHOR]

Objective To conduct a systematic literature review and meta-analysis to estimate the incidence of anaemia, leucopoenia, neutropenia and thrombocytopenia associated with MTX plus folic acid among patients with rheumatic diseases. Methods We searched MEDLINE, PubMed and EMBASE through August 2016 for all randomized controlled clinical trials with a MTX monotherapy arm. We excluded randomized controlled clinical trials for cancer and included only double-blind studies that reported on haematologic adverse events. Studies were excluded if patients did not receive folic acid or leucovorin supplementation. Full text articles were assessed by two independent reviewers. Incidence estimates were calculated using random-effects models. Results Of 1601 studies identified, 30 (1.87%) were included, representing 3858 patients; all had RA. Seventeen trials reported on anaemia (n = 2032), 17 reported on leucopoenia (n = 2220), 16 reported on neutropenia (n = 2202) and 12 reported on thrombocytopenia (n = 1507). The incidence for any anaemia was 2.55% (95% CI 0.60–5.47%), any leucopoenia 1.17% (95% CI 0.16–2.80%), any neutropenia 1.77% (95% CI 0.33–4.00%), and any thrombocytopenia 0.19% (95% CI 0.00–0.86%). Four cases of severe anaemia were reported, as defined by authors, along with three cases of severe neutropenia. No cases of severe leucopoenia, severe thrombocytopenia or pancytopenia were reported. Conclusion Cytopenias are an uncommon side effect of low-dose MTX with folic acid supplementation among RA patients. Further research is needed to reach a more precise estimate. [ABSTRACT FROM AUTHOR]

Objective: Observational data facilitate examination of treatment-effect heterogeneity, but the risk of bias is substantial. The present study was undertaken to highlight methodologic considerations through an analysis of whether smoking affects response to tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (SpA).Methods: We used longitudinal data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis. Participants fulfilling the Assessment of SpondyloArthritis international Society criteria for axial SpA who started their first TNFi were eligible for analysis. In comparing the impact of smoking status, weighted generalized estimating equations were used to examine changes in several continuous outcome measures, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Inverse probability weights were used to account for differences in baseline covariates and excluded participants. We separately assessed response in the first 3 months to account for nonrandom dropout.Results: For 840 participants who started on TNFi, 1,641 assessments from 627 individuals were analyzed (69% male, mean age 46 years). A total of 33% were current smokers and 30% ex-smokers. Ex-smokers and current smokers had worse disease than never smokers at baseline. Accounting for these differences, response did not differ according to smoking status. Compared to never smokers, ex-smokers (β = -0.6, 95% confidence interval [95% CI] -1.4, 0.3) and current smokers (β = -0.4, 95% CI -1.1, 0.4) had a similar response according to the BASDAI and ASDAS (ex-smokers β = -0.1, 95% CI -0.5, 0.3; current smokers β = -0.01, 95% CI -0.4, 0.4) at 3 months.Conclusion: TNFi response did not differ according to baseline smoking status in this UK cohort. Conflicting results from previous studies were likely due to methodologic differences. This analysis highlights potential sources of bias that should be addressed in future studies. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to compare comorbidities and biologic DMARD (bDMARD) use between AS and non-radiographic axial SpA (nr-axSpA) patients, using a large cohort of patients from routine clinical practice in the United States. Methods We performed a cross-sectional study using electronic medical records from two academic hospitals in the United States. Data were extracted using automated searches (⩾3 ICD codes combined with text searches) and supplemented with manual chart review. Patients were categorized into AS or nr-axSpA according to classification criteria. Disease features, comorbidities (from a list of 39 chronic conditions) and history of bDMARD prescription were compared using descriptive statistics. Results Among 965 patients identified, 775 (80%) were classified as having axSpA. The cohort was predominantly male (74%) with a mean age of 52.5 years (s. d. 16.8). AS patients were significantly older (54 vs 46 years), more frequently male (77% vs 64%) and had higher serum inflammatory markers than those with nr-axSpA (median CRP 3.4 vs 2.2 mg/dl). Half of all patients had at least one comorbidity. The mean number of comorbidities was 1.5 (s. d. 2.2) and similar between AS and nr-axSpA groups. A history of bDMARD-use was seen in 55% of patients with no difference between groups. The most commonly prescribed bDMARDs were adalimumab (31%) and etanercept (29%). Ever-prescriptions of individual bDMARDs were similar between AS and nr-axSpA. Conclusion Despite age differences, nr-axSpA patients had similar comorbidity burdens as those with AS. Both groups received comparable bDMARD treatment in this United States clinic-based cohort. [ABSTRACT FROM AUTHOR]

Purpose In observational research, equipoise concerns whether groups being compared are similar enough for valid inference. Empirical equipoise was previously proposed as a tool to assess patient similarity based on propensity scores (PS). We extended this work for multigroup observational studies. Methods: We modified the tool to allow for multinomial exposures such that the proposed definition reduces to the original when there are only two groups. We illustrated how the tool can be used as a method to assess study design within three‐group clinical examples. We then conducted three‐group simulations to assess how the tool performed in a setting with residual confounding after PS weighting. Results: In a clinical example based on rheumatoid arthritis, 44.5% of the sample fell within the region of empirical equipoise when considering first‐line biologics, whereas 57.7% did so for second‐line biologics, consistent with the expectation that a second‐line design results in better equipoise. In a simulation where the unmeasured confounder had the same magnitude of association with the treatment as the measured confounders and a 25% greater association with the outcome, the tool crossed the proposed threshold for empirical equipoise at a residual confounding of 20% on the ratio scale. When the unmeasured variable had a twice larger association with treatment, the tool became less sensitive and crossed the threshold at a residual confounding of 30%. Conclusion: Our proposed tool may be useful in guiding cohort identification in multigroup observational studies, particularly with similar effects of unmeasured and measured covariates on treatment and outcome. [ABSTRACT FROM AUTHOR]

Crump et al. (Biometrika. 2009;96(1):187–199), Stürmer et al. (Am J Epidemiol. 2010;172(7):843–854), and Walker et al. (Comp Eff Res. 2013;2013(3):11–20) proposed propensity score (PS) trimming methods as a means to improve efficiency (Crump) or reduce confounding (Stürmer and Walker). We generalized the trimming definitions by considering multinomial PSs, one for each treatment, and proved that these proposed definitions reduce to the original binary definitions when we have only 2 treatment groups. We then examined the performance of the proposed multinomial trimming methods in the setting of 3 treatment groups, in which subjects with extreme PSs more likely had unmeasured confounders. Inverse probability of treatment weights, matching weights, and overlap weights were used to control for measured confounders. All 3 methods reduced bias regardless of the weighting methods in most scenarios. Multinomial Stürmer and Walker trimming were more successful in bias reduction when the 3 treatment groups had very different sizes (10:10:80). Variance reduction, seen in all methods with inverse probability of treatment weights but not with matching weights or overlap weights, was more successful with multinomial Crump and Stürmer trimming. In conclusion, our proposed definitions of multinomial PS trimming methods were beneficial within our simulation settings that focused on the influence of unmeasured confounders. [ABSTRACT FROM AUTHOR]