Pain is a frequent symptom in people with inflammatory arthritis (IA), which has substantial impact on their quality of life. Analyses of electronic health record data indicate that UK pain care in people with IA often involves prescribing long-term opioids and gabapentinoids, despite absent trial evidence for efficacy. Patient survey data suggest that non-pharmacological pain care with supportive trial evidence is underused. A UK-specific guideline on pain management for people with IA is required to address this. This comprehensive life-course guideline is the first British Society for Rheumatology Guideline to specifically address pain in people with IA. It provides evidence-based recommendations on how pain can be best managed in people with IA. It was developed using the methods outlined in the British Society for Rheumatology's 'Creating Clinical Guidelines' protocol by a multidisciplinary Guideline Working Group, comprising healthcare professionals with expertise in paediatric and adult rheumatology and people with lived experience. By undertaking and considering the evidence from several systematic literature and umbrella reviews, 23 recommendations were developed. These address how pain should be assessed in people with IA alongside the role of the following treatments in IA pain management: DMARDs, glucocorticoids, analgesics, neuromodulators, exercise and physical activity, psychological interventions, ergonomic and orthotic interventions (excluding orthoses for foot pain), education, weight management and diet, addressing sleep problems, fatigue management, digital technologies and medical devices, complementary therapies, and support from others. An audit tool is provided to support the Guideline's implementation, and key recommendations made for future research.
To compare the effects of two physiotherapist-guided, personalized, stepwise-adapted exercise interventions-a home-based program (HomeEX) and an immersive virtual reality (IVR) exergaming program (JiaFitXR)-on physical fitness, functional capacity and physical activity in adolescents with Juvenile Idiopathic Arthritis (JIA). This randomized controlled trial included 50 adolescents aged 13-18 years with JIA, randomly assigned (1:1) to HomeEX or JiaFitXR. Both programs targeted balance, strength, endurance and agility, delivered twice weekly for 8 weeks under physiotherapist supervision. Functional capacity (6-Min Walk Test, Sit-to-Stand, Step-Up/Step-Down tests) and physical fitness (FitnessGram components, muscle strength, EMG activation, grip force) were assessed pre- and post-intervention by blinded physiotherapists. Analyses were performed using paired and independent t-tests and repeated-measures ANOVA, following the intention-to-treat principle. Both physiotherapist-guided interventions significantly improved physical fitness, functional capacity and daily activity (P < 0.05). Greater gains in 1-Min Sit-to-Stand, Step-Up and Step-Down tests, as well as in lower-extremity endurance and neuromuscular activation, were observed in the JiaFitXR group (P < 0.05). The HomeEX group showed superior improvements in flexibility and upper-extremity strength (P < 0.05). Step counts increased similarly in both the groups, while perceived exertion remained stable throughout the program. Both physiotherapist-guided exercise approaches effectively enhanced physical and functional outcomes in adolescents with JIA. The IVR-based intervention provided additional benefits in lower-extremity endurance and engagement, supporting its potential as an innovative and motivating adjunct to paediatric rheumatology rehabilitation. ClinicalTrials.gov; NCT06176846.
To evaluate the real-world use of advanced cardiovascular imaging in less common and rare rheumatic immune-mediated inflammatory diseases (IMIDs) and identify variation in practice to inform future studies and clinical guidelines. A retrospective, multicentre quality improvement project was conducted across four major hospitals in the UK. Adults with SLE, SSc, idiopathic inflammatory myopathy, vasculitis or SS who underwent cardiovascular magnetic resonance (CMR), CT coronary angiography (CTCA) or PET between January 2023 and December 2024 were included. Demographics, IMID characteristics, cardiovascular risk factors, imaging indications, findings and management were extracted using a standardized proforma and analysed. A total of 294 imaging studies were performed in 261 patients (72.4% female, 65.9% aged 40-74 years) comprising 137 (46.6%) CMR, 40 (13.6%) CTCA and 117 (39.8%) PET scans. Indications varied by modality and centre. Cardiovascular abnormalities were reported in 175/294 (59.5%), most commonly in vasculitis (53.7%). Notably, 54/63 (85.7%) of abnormal PET and 61/89 (68.5%) of abnormal CMR scans were in asymptomatic patients. Imaging findings prompted cardiology referral/ongoing follow-up in 59.5% and changes to IMID treatment in 31.3%, but only 23.1% were discussed in a formal multidisciplinary team (MDT). Advanced cardiovascular imaging frequently identifies cardiovascular involvement in rheumatic IMIDs, including in asymptomatic patients. Treatment adjustments occurred in a third of patients, although largely undertaken outside established MDT processes. These findings emphasize the need for better understanding of imaging-based findings and for cardio-rheumatology MDTs to support integrated decision-making to improve patient outcomes.
To characterize clinical features and outcomes of paediatric macrophage activation syndrome (MAS) and examine associations with immune-regulatory genetic variation. This retrospective study included 120 children with MAS. Clinical, laboratory and outcome data were analysed. A subgroup underwent genetic testing for Hemophagocytic Lymphohistiocytosis (HLH)-related variants. Multivariable logistic regression identified factors associated with outcomes. Aetiologies included multisystem inflammatory syndrome in children (MIS-C) (36.7%), systemic juvenile idiopathic arthritis (sJIA) (26.7%), infection-triggered MAS (23.3%), other rheumatologic diseases (10.8%) and lymphoma (2.5%). Intensive care unit (ICU) admission and acute organ failure occurred in 60% and 45%, and mortality was 17.5%. Compared with sJIA, non-sJIA had higher ICU admission (72.7% vs 25.0%, P = 0.02) and mortality (21.6% vs 6.3%, P = 0.04), whereas recurrence was more common in sJIA (28.1% vs 9.1%, P = 0.04). Stratified analyses (MIS-C, other MAS and sJIA) showed higher ICU admission in MIS-C and other MAS, highest mortality in other MAS and highest recurrence in sJIA, with rates of 77.3%, 68.2% and 25.0% (P < 0.001), 6.8%, 36.4% and 6.3% (P < 0.001), and 2.3%, 15.9% and 28.1% (P = 0.01), respectively. Among tested patients, 22.4% carried HLH-related variants. Variant positivity was independently associated with higher ferritin, younger MAS onset, recurrence, acute organ dysfunction and sJIA aetiology. Higher peak ferritin predicted mortality (OR 2.01) and reduced remission off therapy (OR 0.70), whereas sJIA aetiology was associated with lower mortality (OR 0.21). Paediatric MAS is aetiologically heterogeneous, with inflammatory burden and organ dysfunction driving poor outcomes. Immune-regulatory variants are linked to severe or relapsing disease, supporting phenotype-guided stratification.
Progressive interstitial lung disease (ILD) is the leading cause of mortality in SSc. Early recognition of progression is crucial to timely treatment, but reliable early markers are lacking. Automated quantitative analysis of chest high-resolution CT (HRCT) may provide an objective tool to detect early progression. This study aims to compare automated and visual assessment in identifying early SSc-ILD progression and evaluate their predictive value for subsequent functional decline. In this retrospective longitudinal study, 33 patients with SSc-ILD underwent HRCT and pulmonary function tests (PFTs) at baseline (T1) and after 1 year (T2; IQR 0.75-2.5 years). PFTs were repeated 12 months after T2 (T3; IQR 9-14.5 months, T3). Two radiologists performed blinded semi-quantitative visual scoring of fibrosis and ground-glass opacity (GGO), while automated analysis was conducted using Thoracic VCAR (GE Healthcare). Associations with PFTs and prediction of functional progression (Erice/INBUILD criteria) and treatment escalation were analysed. Both visual and automated analyses detected fibrosis progression (visual: 1.5 → 1.6, P = 0.0005; software: 0.34% → 0.4%, P = 0.01). Only automated analyses identified increases in GGO (15.5% → 15.8%, P = 0.04) and reduced normal lung tissue (75.6% → 73%, P = 0.009). Software-derived parameters correlated strongly with PFT changes, whereas visual scores showed weaker correlations. Early (T1-T2) automatically-detected GGO increases predicted subsequent functional decline at T3 (P = 0.04), with changes >50 ml (8.2%) yielding 81% sensitivity and 77% specificity. Automated quantitative HRCT analysis, but not visual evaluation, predicts long-term functional progression in SSc-ILD.
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To assess the effectiveness of canakinumab (CAN) in controlling clinical and laboratory inflammation by achieving complete control of cardinal disease manifestations and full normalization of laboratory inflammatory markers. Data were obtained from the international AutoInflammatory Disease Alliance (AIDA) network registry, dedicated to monogenic autoinflammatory diseases. The assessment included both retrospective and prospective real-world data. In total, 158 FMF patients treated with CAN were enrolled. Complete clinical-laboratory response was observed in 45.6% of patients at 3 months, 58.6% at 12 months and 55.2% at the last follow-up, after a mean treatment duration of 45 months. Partial response occurred in 16.5%, 12.5% and 16.8% at the same timepoints, respectively. Complete absence of clinical manifestations was observed in more than 80% of patients at each timepoint. Inflammatory markers normalized significantly by the 3-month assessment. The probability of achieving and maintaining complete response and full laboratory control appeared higher in patients reaching these outcomes by 3 months, although it remained substantial in other patients as well. Complete response was associated with a relapsing-remitting disease course and fewer annual attacks. Nearly all patients maintained stable organ damage scores, and therapy discontinuation due to inefficacy was rare (≤6%). CAN is effective in achieving rapid and sustained clinical and laboratory control in FMF, including stringent endpoints of complete response. Early effectiveness may favour better long-term outcomes, but delayed achievement of complete response and full laboratory control is not uncommon. This study confirms CAN as an effective, and durable therapeutic option in FMF.
The aetiopathogenesis of SLE encompasses genetic, environmental and epigenetic factors. We investigated associations between an SLE methylation risk score (MRS), HLA-DRB1*03:01, a non-HLA polygenic risk score (PRS) and clinical and immunological phenotypes. DNA methylation in whole blood from patients fulfilling ≥4 ACR-82 criteria and controls were investigated using the Illumina HM450K array. The discovery cohort included 311 patients and 400 controls, and the replication cohort comprised 175 patients and 187 controls. Seventeen independent, top differentially methylated CpG sites (Δβ of ≥ 0.1) from case-control comparisons, were used to calculate the MRS. Genotyping was performed using the Immunochip, and the PRS included 57 non-HLA SLE SNVs. Clinical data were collected from patient charts, and serum IFN-α2 was measured using Simoa. Higher MRS was strongly associated with serum IFN-α2 levels (p = 1.04 × 10-14). In both cohorts, higher MRS associated with discoid lupus, immunologic involvement, and anti-SSA/SSB/RNP/Sm autoantibodies (all p < 0.05), and with higher disease activity in the discovery cohort (p = 1.50 × 10-4). MRS was also elevated in patients with multiple autoantibodies (p < 1.0 × 10-15) and in HLA-DRB1*03:01 carriers (p < 1.0 × 10-3). In contrast, higher PRS was associated with nephritis, anti-dsDNA positivity, and lower prevalence of anti-SSB antibodies (all p < 0.05). No correlation was observed between the MRS and the PRS (p = 0.35). The MRS defines an interferon-high, HLA-DRB1*03:01-linked SLE subset with multiple autoantibodies, partly distinct from PRS-associated nephritis risk, highlighting potentially divergent pathogenic pathways. These findings underscore the value of integrating genetic and epigenetic data to better understand underlying disease mechanisms in SLE.
Glucocorticoid (GC) bridging therapy is recommended in patients with rheumatoid arthritis commencing a disease-modifying anti-rheumatic drug (DMARD). It is not clear whether GC therapy is better administered intramuscularly or orally and at what dose level. The aim of the LEADER trial is to identify the most effective and safest way of using steroids in patients with uncontrolled RA who are starting a DMARD. A multicentre, randomised, open-label, four-arm, parallel-group clinical trial with an internal pilot phase, economic evaluation and qualitative study of acceptability. Participants will be randomised to one of four arms: arm A, 30 mg oral prednisolone tapering over 6 weeks; arm B, 15 mg oral prednisolone tapering over 4 weeks; arm C, Intramuscularly 120 mg methylprednisolone; and arm D, Intramuscularly 80 mg methylprednisolone. Participants will be assessed at baseline (pre-GC intervention), 4, 12 and 24 weeks. The primary outcome measure is the mean DAS(CRP)-28 over 12 weeks. The primary comparison will be according to route of administration (oral vs intramuscular GC treatment) with secondary comparisons within route of administration to provide evidence of dose effectiveness. Toxicity will be measured using the Glucocorticoid Toxicity Index, a clinical outcome assessment and early morning cortisol level. LEADER will be conducted in ~30 sites delivering NHS care, recruiting a sample size of 448. Economic evaluation will compare cost-effectiveness within a trial and over a lifetime horizon from the English National Health Service perspective. The LEADER trial received MHRA and Leicester Central Research Ethics Committee ethics approval (REC reference: 24/EM/0277, IRAS 1010280), opened to recruitment on Protocol Version 4.0 and is currently recruiting on Protocol Version 5.0. Participants will provide written informed consent in accordance with the Declaration of Helsinki and applicable regulatory requirements. Trial results will be disseminated via presentations at national and international meetings, published in open-access journals and to patients. ISRCTN32090559.
To assess whether fluctuations in immunoglobulin G anti-double stranded DNA (IgG anti-dsDNA) antibodies and C3 levels predict flares and sustained activity in patients with prolonged serologically active clinically quiescent (SACQ) systemic lupus erythematosus (SLE), and to explore additional risk factors for flare. SLE patient data from the University College London Hospital Lupus cohort were collected (2020-2025). Prolonged SACQ was defined as ≥6 months of elevated IgG anti-dsDNA and/or low C3 without clinical activity (BILAG-2004 index D/E in all domains). Associations between biomarker changes and outcomes, adjusted for main confounders, were tested longitudinally with generalized estimating equations (GEE). Sixty patients (531 visits) were included. Over a mean 3.3-year follow-up, 38 patients (63.3%) experienced ≥1 flare. Baseline characteristics were comparable between patients with and without flares, except for longer follow-up duration (P = 0.005) and a higher prevalence of anti-Ro positivity (P = 0.018) among those who developed flares. In GEE-models, higher IgG anti-dsDNA and lower C3 levels independently predicted flares and sustained activity at the subsequent visit, including moderate-to-severe cases. Most SACQ patients developed clinical flares. Changes in IgG anti-dsDNA and C3 levels emerged as strong predictors of flare in prolonged SACQ patients in a visit-by-visit analysis, supporting close clinical monitoring and highlighting the value of serological trends despite the presence of prolonged clinical quiescence and sustained biomarker abnormalities.
Data regarding progression from oligoarticular to polyarticular psoriatic arthritis (PsA) are sparse. Using FOREMOST, we identify progression predictors and evaluate apremilast's treatment effect in early PsA. FOREMOST (NCT03747939) randomized N = 308 patients with early (mean duration, 9.9 months) PsA and limited joint involvement (>1 to ≤4 swollen and >1 to ≤4 tender joints; not confirmed by imaging) to apremilast or placebo for 24 weeks, followed by open-label apremilast through week 48. Multivariable logistic regression modelled predictors of progression from oligoarticular (≤4 active [swollen and/or tender] joints) to polyarticular (>4 active joints) PsA at week 16 and the effect of apremilast. Disease progression, disease activity, clinical signs/symptoms and tolerability were summarized through week 48 for N = 291 patients receiving ≥1 apremilast dose (from randomization or switched from placebo). Most (268/308 [87.0%]) patients had oligoarticular PsA at baseline; 25.1% (59/235) progressed to polyarticular PsA by week 16 (data as observed). Apremilast reduced odds of progression vs placebo by 58% (odds ratio [OR; 95% CI]: 0.42 [0.22, 0.77]). In placebo-treated patients, being female, being csDMARD-naïve, and having dactylitis significantly increased odds of progression (OR: 3.35 [1.20, 9.34], 3.42 [1.18, 9.93], and 9.26 [1.32, 65.09], respectively). Apremilast treatment for up to 48 weeks maintained low rates of disease progression and improvements in disease activity/clinical signs and symptoms, with no new safety signals. Initiating apremilast treatment during the early, oligoarticular phase of PsA reduced disease activity and delayed progression to polyarticular disease, with benefits maintained with up to 48 weeks of treatment. ClinicalTrials.gov; NCT03747939.
We examined whether annual gout flare frequency, as a marker of cumulative inflammatory burden, predicts long-term major adverse cardiovascular events (MACEs). Using the TriNetX Global Collaborative Network, we identified adults with a first EHR-recorded treated gout flare in 2017. Using a 12-month landmark exposure window, patients were classified as low (≤3), moderate (4-6) or high (≥7) flares/year. Modified MACE (myocardial infarction, stroke, heart failure) was followed from the landmark. Groups were compared using 1:1 propensity score matching. A sensitivity analysis applied a stricter flare definition (gout diagnosis with colchicine, corticosteroid or intra-articular injection within 0-3 days; NSAIDs excluded). Among 44 705 patients, matching produced balanced cohorts (high vs low, 13 179 pairs; moderate vs low, 9700 pairs). A graded dose-response was observed: at 7 years, MACE risk was higher in the high (RR 1.45; 95% CI 1.37-1.53) and moderate (RR 1.24; 1.15-1.33) groups vs low. Heart failure risk was elevated in both the groups (HR 1.27 [high]; 1.17 [moderate]); stroke and myocardial infarction were elevated only in the high group (7-year HR 1.28 each), with stroke significant from 3 years. Findings were consistent under the stricter sensitivity definition (7-year MACE HR 1.19 [high] and 1.12 [moderate]). Annual gout flare frequency is a graded marker of sustained cardiovascular risk. Heart failure risk rises with both moderate and high burden, whereas atherothrombotic events emerge predominantly with high-flare frequency, suggesting they require greater cumulative inflammatory exposure.
Chemokine CXCL10 plays an important role in PsA, an inflammatory arthritis associated with psoriasis. CXCL10 is post-translationally regulated by dipeptidyl peptidase-4 (DPPIV). The objectives of this study were to measure levels of DPPIV, CXCL10 and DPPIV enzyme activity (EA) in patients with PsA, psoriasis without arthritis (PsC), OA and healthy controls (HC), and in PsA patients before and after MTX treatment initiation. Serum samples were acquired from 80 PsA, 80 PsC, 40 HC and 40 patients before and after 24 weeks of MTX treatment. SF and matched serum were collected from 14 PsA and 14 sex-matched OA patients. Levels of DPPIV and CXCL10 were quantified using ELISA, DPPIV EA was measured using a luminescent protease assay. Patients with PsA had higher DPPIV levels than PsC, whereas HC had the highest level compared with both. Significant increase in DPPIV levels was observed in PsA patients after MTX treatment, whereas CXCL10 levels decreased significantly. DPPIV levels were negatively correlated with CXCL10 levels after MTX treatment (r = -0.27, P = 0.02). DPPIV levels were significantly higher in SF of PsA compared with OA patients. Higher DPPIV levels were detected in SF compared with serum samples of PsA patients. CXCL10 concentration in SF displayed similar patterns to DPPIV. Our exploratory findings suggest that DPPIV SF levels may be an important indicator of joint inflammation in PsA patients. In PsA patients, DPPIV may be associated with MTX response. CXCL10 may be regulated post translationally by DPPIV.
NLRC4-associated autoinflammatory diseases (NLRC4-AID) cover a clinical spectrum from relatively mild familial cold autoinflammatory syndrome 4 (FCAS4) to life-threatening macrophage activation syndrome (MAS). Free IL-18 has been shown to pathogenically promote MAS, but the pathological relevance of free IL-18 in NLRC4-AID without MAS has not been explored. We investigated free IL-18 and related cytokines in five germline p.S445P and one somatic p.V341L NLRC4-AID patients without MAS. Clinical, genetic and laboratory data, as well as serum samples were obtained from NLRC4-AID patients without MAS. Human IL-6, soluble CD25, CXCL9, CXCL10, IL-12p70, IFN-γ, total IL-18, IL-1β, TNF-α and IL-1Ra were assessed using a bead-based assay. Free IL-18 was assessed using a proprietary ELISA. Total and free IL-18 were elevated both in the FCAS4 patients and the NLRC4-AID patient harbouring a heterozygous somatic NLRC4 variant restricted to the haematopoietic compartment. Despite the association between free IL-18 and MAS, we found no relevant correlation between total and free IL-18 and laboratory markers of inflammation or MAS. Accordingly, MAS-associated cytokines IFN-γ, CXCL9 and CXCL10 were not elevated in NLRC4-AID patients without MAS. Germline and somatic NLRC4-AID without MAS are associated with elevated levels of both total and free IL-18. Our findings in the somatic NLRC4-AID patient suggest that free IL-18 originating from the haematopoietic system alone is not sufficient to drive MAS. Our findings indicate that IL-18 is necessary but not sufficient to drive MAS and suggest a pathological role of IL-18 beyond MAS in NLRC4-AID.
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People with inflammatory arthritis (IA) frequently experience work instability, absenteeism, and reduced productivity, culminating in early job loss. This study evaluated the effectiveness and cost-effectiveness of WORKWELL job retention vocational rehabilitation (JRVR) delivered by occupational therapists, compared to a control group receiving written self-help advice. A pragmatic, multi-centre randomised controlled trial was conducted across 18 UK NHS Trusts. Employed adults (n = 249) with IA experiencing moderate to severe work instability, were randomised (1:1) to intervention or control groups. WORKWELL included structured work assessment, individually tailored action plans, and interventions over 2-4 months. Follow-up was at 6, 12, and 36 months. The primary outcome was the Work Limitations Questionnaire-25 (WLQ-25). Analyses used linear mixed-effects regression adjusted for baseline characteristics and occupational skill level. An NHS perspective was used for the within-trial cost-effectiveness analysis. Much of the trial was affected by the COVID-19 pandemic. At 12 months, there was no significant difference in WLQ-25 between groups (adjusted mean difference: -1.8; 95% CI -7.4 to 3.8; p = 0.53), or in most secondary outcomes at 12- or 36-months. However, absenteeism showed a relative reduction of 46% at 12 months (p = 0.08), and employment retention at 36 months was higher in the intervention (93%) vs. control group (85%). The intervention was not cost-effective from an NHS perspective. WORKWELL did not lead to improved work productivity compared to self-help advice. Future research should explore more flexible delivery methods, including digital tools, to support sustainable employment for people with IA. A plain-language abstract is available in the supplementary material. ClinicalTrials.gov; NCT03942783. ISRCTN Registry; ISRCTN61762297.
Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Recent reductions in global health funding have threatened TB control, making comprehensive assessment of TB, HIV-related TB, and drug-resistant TB burdens before these disruptions essential for shaping effective responses. The WHO End TB Strategy sets targets of a 95% reduction in TB deaths and a 90% reduction in TB incidence between 2015 and 2035. Using results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, this study aims to assess the burden of TB and multidrug-resistant TB (MDR-TB) across 204 countries and territories, and to evaluate progress towards the WHO End TB incidence and mortality targets. We quantified TB mortality using the Cause of Death Ensemble modelling platform with global vital registration, surveillance, verbal autopsy, and minimally invasive tissue sampling data. For TB morbidity estimation, we simultaneously modelled incidence, prevalence, and mortality by age and sex using DisMod-MR 2.1. A population attributable fraction (PAF) approach was applied to stratify morbidity and mortality estimates by HIV and drug-resistance status. We also calculated disability-adjusted life-years (DALYs) as the sum of years of life lost and years lived with disability. For the risk factor analysis, a comparative risk assessment framework was used and PAFs were derived for alcohol use, smoking, and high fasting plasma glucose to determine the proportion of TB burden associated with these risk factors. In 2023, there were an estimated 9·11 million (95% uncertainty interval 8·04-10·3) incident cases of all-form TB, 1·22 million (0·98-1·49) deaths, and 54·6 million (43·8-65·5) DALYs globally. HIV-related TB comprised 781 000 (690 000-879 000) incident cases and 210 000 (142 000-279 000) deaths, contributing 11·0 million (7·56-14·3) DALYs. MDR-TB accounted for 466 000 (198 000-1 080 000) incident cases, 102 000 (31 700-238 000) deaths, and 3·96 million (1·31-9·01) DALYs. From 2015 to 2023, global all-form TB incidence rates declined by 19·2% (17·8-20·5) and deaths declined by 22·6% (4·7-35·7); declines were larger for drug-susceptible TB than for MDR-TB. Sub-Saharan Africa and south Asia had the highest mortality burdens in 2023; reductions in all-form TB incidence and mortality were uneven between 2000 and 2023, with limited progress in both measures in Latin America and the Caribbean. Removing smoking, alcohol use, and high fasting plasma glucose would reduce global TB deaths to 768 000 (592 000-970 000) and DALYs to 34·9 million (27·8-43·8) in 2023; MDR-TB deaths would decrease to 77 200 (23 400-183 000) and DALYs to 3·12 million (1·03-7·29). Global progress towards WHO End TB targets is disparate and fragile. Although many regions achieved meaningful gains, others have stagnated in recent years. The complexity of TB prevention is amplified by divergent MDR-TB trends, the persistent burden of HIV, and growing exposure to modifiable risk factors. Recent volatility in global health financing threatens to further destabilise this vulnerable epidemiological landscape; concerted action is urgently needed to temper disruptions and preserve progress. Gates Foundation.
Stickler syndrome is a skeletal dysplasia that is widely under-recognised yet the most common cause of inherited retinal detachment in children. The most prevalent subtype is Stickler syndrome type 1 (STL1), with an autosomal dominant variant in COL2A1 typically resulting in ophthalmic, orofacial, auditory and musculoskeletal manifestations. However, manifestations across these domains are not as prominent in children, making identification of individuals suitable for further assessment difficult. Thus, we sought to test an easy-to-use screening tool capable of differentiating children with STL1 from the general paediatric population. Children aged 4-10 years with and without COL2A1-confirmed STL1 were recruited from a single specialist centre and online via the national patient support group Stickler Syndrome UK (Registered Charity number 1060421). A screening tool was administered, and planned analysis of the median final score and individual components of the questionnaire was completed. 26 general paediatric and 28 STL1 participants were recruited. STL1 participants scored higher on screening tool final score with a median score (IQR) of 7 (3.5) versus 0 (1), which was statistically significant on a Mann-Whitney U test (p < 0.001). The sensitivity and specificity were 93% and 96% respectively, and STL1 participants were more likely to have myopia, palate abnormalities, family history of cleft palate, and hypermobility on secondary analysis of the individual screening tool components (Hochberg-corrected all p < 0.005). We demonstrate a clinically powerful screening tool capable of identifying children with underlying STL1, and thus this questionnaire can now be applied to at-risk children to inform the need for further specialist assessment.
Arthritis is a common manifestation of systemic lupus erythematosus (SLE). We examined the prevalence and associations of arthritis subtypes in SLE, focusing on associations with type I interferon (IFN) scores. In this observational cohort study at the University of Toronto Lupus Clinic (July 1970-August 2024), arthritis was defined clinically as non-deforming arthritis (NDA), Jaccoud's arthropathy (JA) and arthritis with clinically irreducible deformities (CIDA). Univariable and multivariable (MV) logistic regression was used to assess associations with arthritis subtypes with NDA as reference in the prevalent cohort and subgroup with available IFN scores (reported as high/low). Among 2264 patients, 1248 (55.1%) had arthritis: 908 (72.8%) had NDA, 239 (19.2%) JA, and 101 (8.1%) CIDA. In the multivariable logistic regression analysis, JA was associated with longer disease duration (odds ratio [OR] 1.05 [95% CI: 1.03, 1.08]) and female sex (2.06 [1.11, 3.83]) whereas CIDA was associated with neurological involvement (1.79 [1.13, 2.84]), anti-Ro antibodies (1.71 [1.01, 2.90]), higher adjusted mean joint count (1.09 [1.03, 1.77]) and lower adjusted mean SLEDAI-2K over follow-up (0.89 [0.81, 0.98]) compared with NDA. In patients with available IFN scores (n = 475), CIDA was associated with a low IFN signature in unadjusted analysis, whereas both JA and NDA had a high IFN signature. Distinct clinical and serological patterns differentiate JA and CIDA, suggesting unique underlying mechanisms of deforming arthritis in SLE. Both NDA and JA exhibited a high IFN signature, while CIDA showed a higher joint burden, lower disease activity and lower IFN signature relative to NDA.