Cell-Type Specificity of Mosaic Chromosome 1q Gain Resolved by snRNA-seq in a Case of Epilepsy With Hyaline Protoplasmic Astrocytopathy.

Objectives: Mosaic gain of chromosome 1q (chr1q) has been associated with malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathologic finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown. Methods: We present the case of a child with pharmacoresistant epilepsy who underwent epileptic focus resections at age 3 and 5 years and was found to have mosaic chr1q gain and HPA. We performed single-nuclei RNA sequencing (snRNA-seq) of brain tissue from the second resection. Results: snRNA-seq showed increased expression of chr1q genes specifically in subsets of neurons and astrocytes. Differentially expressed genes associated with inferred chr1q gain included AKT3 and genes associated with cell adhesion or migration. A subpopulation of astrocytes demonstrated marked enrichment for synapse-associated transcripts, possibly linked to the astrocytic inclusions observed in HPA. Discussion: snRNA-seq may be used to infer the cell-type specificity of mosaic chromosomal copy number changes and identify associated gene expression alterations, which in the case of chr1q gain may involve aberrations in cell migration. Future studies using spatial profiling could yield further insights on the molecular signatures of HPA.

Molecularly thin, two-dimensional all-organic perovskites.

Recently, the emergence of all-organic perovskites with three-dimensional (3D) structures has expanded the potential applications of perovskite materials. However, the synthesis and utilization of all-organic perovskites in 2D form remain largely unexplored because the design principle has not been developed. We present the successful synthesis of a metal-free 2D layered perovskite, denoted as the Choi-Loh van der Waals phase (CL-v phase), with the chemical formula A2B2X4, where A represents a larger-sized cation compared to B and X denotes an anion. The CL-v phase exhibits a van der Waals gap enabled by interlayer hydrogen bonding and can be exfoliated or grown as molecularly thin 2D organic crystals. The dielectric constants of the CL-v phase range from 4.8 to 5.5 and we demonstrate their potential as gate dielectrics for thin-film transistors.

Blood Pressure Lowering in Patients With Central Hypertension: A randomized Clinical Trial.

BACKGROUND: Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension. METHODS: This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs. RESULTS: At 24-months, there was a greater reduction in left ventricular mass index (-3.2 [95% CI, -5.0 to -1.3] g/m2; P=0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, -6.16 [-9.60 to -2.72] mm Hg and clinic central systolic BP, -4.96 [-8.06 to -1.86] mm Hg; P≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, ß, 0.17 [0.02-0.31] g/m2) or centrally (24-hour systolic BP, ß, 0.16 [0.01-0.32] g/m2). CONCLUSIONS: Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12613000053729.

Correlation of Extent of Left Ventricular Endocardial Unipolar Low Voltage Zones with Ventricular Tachycardia in Non-ischemic Cardiomyopathy.

BACKGROUND: Endocardial electrogram (EGM) characteristics in non-ischemic cardiomyopathy (NICM) have not been explored adequately for prognostication. OBJECTIVES: We aim to study correlation of bipolar and unipolar EGM characteristics with left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT) in NICM. METHODS: Electroanatomical mapping of LV was performed. Correlation of EGM characteristics with LVEF was performed. Differences between groups with and without VT and predictors of VT were studied. RESULTS: In 43 patients, unipolar EGM variables had better correlation with baseline LVEF than bipolar EGM variables: unipolar voltage (r=+0.36), peak negative unipolar voltage (r=-0.42), peak positive unipolar voltage (r=+0.38), and percentage area of unipolar LVZ (r=-0.41). Global mean unipolar voltage (HR- 0.4; 95% C.I 0.2-0.8), extent of unipolar LVZ (HR- 1.6; 95% CI 1.1-2.3) and % area of unipolar LVZ (HR- 1.6; 95% CI 1.1-2.3) were significant predictors of VT. For classification of patients with VT, extent of unipolar LVZ had AUC of 0.82 (95% CI 0.69-0.95; p<0.001), and % area of unipolar LVZ had AUC of 0.83 (95% CI 0.71-0.96; p=0.01). Cut-off of >3 segments for extent of unipolar LVZ had the best diagnostic accuracies (sensitivity- 90%; specificity- 67%) and cut-off of 33% for percentage area of unipolar LVZ had the best diagnostic accuracy (sensitivity- 95%; specificity- 60%) for VT. CONCLUSION: In NICM, extent and percentage area of unipolar low voltage zones are significant predictors of VT. Cut-offs of >3 segments of unipolar LVZ and >33% area of unipolar LVZ, have good diagnostic accuracies for association with VT.

Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial.

INTRODUCTION: The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS). METHODS: The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers. RESULTS: In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = - 3.9, p < 0.001, adalimumab mean = - 2.6, p < 0.05) compared to placebo (mean = - 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = - 3.7, p < 0.001) versus placebo (mean = - 1.7), improvement with adalimumab did not reach significance (mean = - 2.6, p = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab. CONCLUSION: This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation. TRIAL REGISTRATION NUMBER: NCT02696785.

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol.

INTRODUCTION: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management. METHODS AND ANALYSIS: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used. ETHICS AND DISSEMINATION: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings. TRIAL REGISTRATION NUMBER: NCT05972785.

The ASPREE Healthy Ageing Biobank: Methodology and participant characteristics.

ASPirin in Reducing Events in the Elderly (ASPREE), a placebo-controlled prevention trial of low dose aspirin, provided the opportunity to establish a biospecimen biobank from initially healthy persons aged 70+ years for future research. The ASPREE Healthy Ageing Biobank (ASPREE Biobank) collected, processed and stored blood and urine samples at -80degC or under nitrogen vapour at two timepoints, three years apart, from a willing subset of Australian ASPREE participants. Written informed consent included separate opt-in questions for biomarker and genetic testing. Fractionated blood and urine were aliquoted into multiple low-volume, barcoded cryotubes for frozen storage within 4 hours of collection. Specially designed and outfitted mobile laboratories provided opportunities for participation by people in regional and rural areas. Detailed, high quality demographic, physiological and clinical data were collected annually through the ASPREE trial. 12,219 participants contributed blood/urine at the first timepoint, 10,617 of these older adults provided 3-year follow-up samples, and an additional 1,712 provided saliva for DNA. The mean participant age was 74 years, 54% were female and 46% lived outside major cities. Despite geographical and logistical challenges, nearly 100% of blood/urine specimens were processed and frozen within 4 hours of collection into >1.4 million aliquots. After a median of 4.7 years, major clinical events among ASPREE Biobank participants included 332 with dementia, 613 with cardiovascular disease events, 1259 with cancer, 357 with major bleeds and 615 had died. The ASPREE Biobank houses and curates a large number of biospecimens collected prior to the clinical manifestations of major disease, and 3-year follow-up samples, all linked to high quality, extensive phenotypic information. This provides the opportunity to identify or validate diagnostic, prognostic and predictive biomarkers, and potentially study biological effectors, of ageing-related diseases or maintenance of older-age good health.

Efficacy of left bundle branch area pacing versus biventricular pacing in patients treated with cardiac resynchronization therapy: Select site - cohort study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is typically attempted with biventricular (BiV) pacing. One-third of patients are nonresponders. Left bundle branch area pacing (LBBAP) has been evaluated as an alternative means. OBJECTIVE: The purpose of this study was to assess the feasibility and clinical response of permanent LBBAP as an alternative to BiV pacing. METHODS: Of 479 consecutive patients referred with heart failure, 50 with BiV-CRT and 51 with LBBAP-CRT were included in this analysis after study exclusions. Quality-of-Life (QoL) assessments, echocardiographic measurements, and New York Heart Association (NYHA) class were obtained at baseline and at 6-monthly intervals. RESULTS: There were no differences in baseline characteristics between groups (all P > .05). Clinical outcomes such as left ventricular ejection fraction, left ventricular end-systolic volume, QoL, and NYHA class were significantly improved for both pacing groups compared to baseline. The LBBAP-CRT group showed greater improvement in left ventricular ejection fraction at 6 months (P = .001) and 12 months (P = .021), accompanied by greater reduction in left ventricular end-systolic volume (P = .007). QRS duration < 120 ms (baseline 160.82 ± 21.35 ms vs 161.08 ± 24.48 ms) was achieved in 30% in the BiV-CRT group vs 71% in the LBBAP-CRT group (P ≤ .001). Improvement in NYHA class (P = .031) and QoL index was greater (P = .014). Reduced heart failure admissions (P = .003) and health care utilization (P < .05) and improved lead performance (P < .001) were observed in the LBBAP-CRT group. CONCLUSION: LBBAP-CRT is feasible and effective CRT. It results into a meaningful improvement in QoL and reduction in health care utilization. This can be offered as an alternative to BiV-CRT or potentially as first-line therapy.

Erosions on T1-weighted MRI vs Radiography of Sacroiliac Joints in Recent-onset Axial SpA: 2-year Data (EMBARK Trial and DESIR Cohort).

OBJECTIVE: To (1) compare the capacity to detect sacroiliac joint (SIJ) erosions and baseline-to-Week-104 change in erosions between magnetic resonance imaging (MRI) and radiographs in recent-onset axial spondyloarthritis (axSpA); (2) compare treatment discriminatory capacities of MRI and radiographic scores for erosion detection in patients receiving etanercept in the EMBARK trial vs controls in the DESIR cohort. METHODS: Anonymized SIJ MRI and radiographs were assessed at patient and joint surface levels. Three readers evaluated MRI; 3 different readers evaluated radiographs. Final scores for comparison of radiographs and MRI for detection of erosions were assigned based on agreement of ≥2 of 3 readers' assessments. RESULTS: At baseline, discordance in erosion detection between imaging methods was more frequent for MRI erosions in the absence of radiographic erosions (48/224 [21.4%] patients) than for radiographic erosions in the absence of MRI erosions (14/224 [6.3%] patients; P<0.001). After 104 weeks, decrease in erosions was observed on MRI but not radiographs in 49 (22.2%) patients and on radiographs but not MRI in 6 (2.7%) (P<0.001). In the treatment-discriminant capacity analysis, the largest standardized differences between etanercept and control cohorts at Week 104 were changes in Spondyloarthritis Research Consortium of Canada MRI erosion discrete score, erosion average score, and meeting the modified New York criteria on radiographs, with unadjusted/adjusted Hedge's G effect sizes of 0.40/0.50, 0.40/0.56, and 0.40/0.43, respectively. CONCLUSION: In recent-onset axSpA, SIJ erosions and erosion change were observed more frequently on MRI than radiography. The significance of interval improvement of MRI erosions warrants further research.

Young adults with a 22q11.2 microdeletion and the cost of aging with complexity in a population-based context.

PURPOSE: Information about the impact on the adult health care system is limited for complex rare pediatric diseases, despite their increasing collective prevalence that has paralleled advances in clinical care of children. Within a population-based health care context, we examined costs and multimorbidity in adults with an exemplar of contemporary genetic diagnostics. METHODS: We estimated direct health care costs over an 18-year period for adults with molecularly confirmed 22q11.2 microdeletion (cases) and matched controls (total 60,459 person-years of data) by linking the case cohort to health administrative data for the Ontario population (∼15 million people). We used linear regression to compare the relative ratio (RR) of costs and to identify baseline predictors of higher costs. RESULTS: Total adult (age ≥ 18) health care costs were significantly higher for cases compared with population-based (RR 8.5, 95% CI 6.5-11.1) controls, and involved all health care sectors. At study end, when median age was <30 years, case costs were comparable to population-based individuals aged 72 years, likelihood of being within the top 1st percentile of health care costs for the entire (any age) population was significantly greater for cases than controls (odds ratio [OR], for adults 17.90, 95% CI 7.43-43.14), and just 8 (2.19%) cases had a multimorbidity score of zero (vs 1483 (40.63%) controls). The 22q11.2 microdeletion was a significant predictor of higher overall health care costs after adjustment for baseline variables (RR 6.9, 95% CI 4.6-10.5). CONCLUSION: The findings support the possible extension of integrative models of complex care used in pediatrics to adult medicine and the potential value of genetic diagnostics in adult clinical medicine.

The OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (WIPE) in spondyloarthritis - reference image atlas for the knee region.

OBJECTIVE: To develop a reference image atlas for the Outcome Measures in Rheumatology whole-body MRI scoring system for inflammation in peripheral joints and entheses (OMERACT MRI-WIPE) of the knee region. METHODS: Image examples of each pathology, location and grade, were collected and discussed at web-based, interactive meetings within the OMERACT MRI in Arthritis Working Group. Subsequently, reference images were selected by consensus. RESULTS: Reference images for each grade, pathology and location are depicted, along with definitions, reader rules and recommended MRI-sequences. CONCLUSION: The atlas guides scoring whole-body MRIs for inflammation in joints and entheses of the knee region according to MRI-WIPE methodology in clinical trials and cohorts.

Hip and pelvis region MRI reference image atlas for scoring inflammation in peripheral joints and entheses according to the OMERACT-MRI WIPE scoring system in patients with spondyloarthritis.

OBJECTIVE: To develop a reference image atlas for scoring the hip/pelvis region according to the OMERACT whole-body MRI scoring system for inflammation in peripheral joints and entheses (MRI-WIPE). METHODS: We collected image examples of each pathology, location and grade, discussed them at web-based, interactive meetings and, finally, selected reference images by consensus. RESULTS: Reference images for each grade and location of osteitis, synovitis and soft tissue inflammation are provided, as are definitions, reader rules and recommended MRI-sequences. CONCLUSION: A reference image atlas was created to guide scoring whole-body MRIs for arthritis and enthesitis in the hip/pelvis region in spondyloarthritis/psoriatic arthritis clinical trials and cohorts.

OMERACT validation of a deep learning algorithm for automated absolute quantification of knee joint effusion versus manual semi-quantitative assessment.

OBJECTIVE: To begin evaluating deep learning (DL)-automated quantification of knee joint effusion-synovitis via the OMERACT filter. METHODS: A DL algorithm previously trained on Osteoarthritis Initiative (OAI) knee MRI automatically quantified effusion volume in MRI of 53 OAI subjects, which were also scored semi-quantitatively via KIMRISS and MOAKS by 2-6 readers. RESULTS: DL-measured knee effusion correlated significantly with experts' assessments (Kendall's tau 0.34-0.43) CONCLUSION: The close correlation of automated DL knee joint effusion quantification to KIMRISS manual semi-quantitative scoring demonstrated its criterion validity. Further assessments of discrimination and truth vs. clinical outcomes are still needed to fully satisfy OMERACT filter requirements.

Thresholds for unacceptable work state in radiographic axial Spondyloarthritis of four presenteeism and two clinical outcome measurement instruments.

OBJECTIVES: To a) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; b) determine whether those thresholds accurately predict future adverse work outcomes (AWO) (sick leave or short/long-term disability); c) evaluate the performance of traditional health-outcomes for r-axSpA; d) explore whether thresholds are stable across contextual factors. METHODS: Data from the multinational AS-PROSE study was used. Thresholds to determine whether patients consider themselves in an 'unacceptable work state' were calculated at baseline for four instruments assessing presenteeism and two health-outcomes specific for r-axSpA. Different approaches derived from the receiver operating characteristic methodology were used. Validity of the optimal thresholds was tested across contextual factors and for predicting future AWO over 12 months. RESULTS: Of 366 working patients, 15% reported an unacceptable work state; 6% experienced at least one AWO in 12 months. Optimal thresholds were: WPAI-presenteeism ≥40 (AUC 0.85), QQ-method <97 (0.76), WALS ≥0.75 (AUC 0.87), WLQ-25 ≥ 29 (AUC 0.85). BASDAI and BASFI performed similarly to the presenteeism instruments: ≥4.7 (AUC 0.82) and ≥3.5 (AUC 0.79), respectively. Thresholds for WALS and WLQ-25 were stable across contextual factors, while for all other instruments they overestimated unacceptable work state in lower educated persons. Proposed thresholds could also predict future AWO, although with lower performance, especially for QQ-method, BASDAI and BASFI. CONCLUSIONS: Thresholds of measurement instruments for presenteeism and health status to identify unacceptable work state have been established. These thresholds can help in daily clinical practice to provide work related support to r-axSpA patients at risk for AWO.

Characteristics of the phenotype of mixed cardiomyopathy in patients with implantable cardioverter-defibrillators.

BACKGROUND OR PURPOSE: The prognosis of m ixed cardiomyopathy (CMP) in patients with implanted cardioverter-defibrillators (ICDs) has not been investigated. We aim to study the demographic, clinical, device therapies and survival characteristics of mixed CMP in a cohort of patients implanted with a defibrillator. METHODS: The term mixed CMP was used to categorise patients with impaired left ventricular ejection fraction attributed to documented non-ischemic triggers with concomitant moderate coronary artery disease. This is a single center observational cohort of 526 patients with a mean follow-up of 8.7 ± 3.5 years. RESULTS: There were 42.5% patients with ischemic cardiomyopathy (ICM), 26.9% with non-ischemic cardiomyopathy (NICM) and 30.6% with mixed CMP. Mixed CMP, compared to NICM, was associated with higher mean age (69.1 ± 9.6 years), atrial fibrillation (55.3%) and greater incidence of comorbidities. The proportion of patients with mixed CMP receiving device shocks was 23.6%, compared to 18.4% in NICM and 27% in ICM. The VT cycle length recorded in mixed CMP (281.6 ± 43.1 ms) was comparable with ICM (282.5 ± 44 ms; p = 0.9) and lesser than NICM (297.7 ± 48.7 ms; p = 0.1). All-cause mortality in mixed CMP (21.1%) was similar to ICM (20.1%; p = 0.8) and higher than NICM (15.6%; p = 0.2). The Kaplan-Meier curves revealed hazards of 1.57 (95% CI: 0.91, 2.68) for mixed CMP compared to NICM. CONCLUSION: In a cohort of patients with ICD, the group with mixed CMP represents a phenotype predominantly comprised of the elderly with a higher incidence of comorbidities. Mixed CMP resembles ICM in terms of number of device shocks and VT cycle length. Trends of long-term prognosis of patients with mixed CMP are worse than NICM and similar to ICM.

Systematic calibration reduces sources of variability for the preliminary OMERACT juvenile idiopathic arthritis MRI- sacroiliac joint score (OMERACT JAMRIS-SIJ).

OBJECTIVE: To determine whether systematic calibration enhances scoring proficiency of the OMERACT juvenile idiopathic arthritis MRI-Sacroiliac Joint score (JAMRIS-SIJ) and whether contrast-enhancement enhances its performance. METHODS: MRI SIJ scans of 50 cases with juvenile spondyloarthritis were scored by 7 raters after calibration with 3 different knowledge transfer tools. RESULTS: Calibrated readers achieved greater reliability for scoring certain inflammatory and structural lesions. Sensitivity and reliability for scoring inflammatory lesions was greater on fluid-sensitive compared to contrast-enhanced sequences. CONCLUSION: Systematic calibration should be implemented prior to the use of JAMRIS-SIJ for clinical trials. It is unlikely that contrast-enhanced MRI will improve the performance of this method.

Patterns of multiple chronic conditions in pregnancy: Population-based study using latent class analysis.

BACKGROUND: Adults with multiple chronic conditions (MCC) are a heterogeneous population with elevated risk of future adverse health outcomes. Yet, despite the increasing prevalence of MCC globally, data about MCC in pregnancy are scarce. OBJECTIVES: To estimate the population prevalence of MCC in pregnancy and determine whether certain types of chronic conditions cluster together among pregnant women with MCC. METHODS: We conducted a population-based cohort study in Ontario, Canada, of all 15-55-year-old women with a recognised pregnancy, from 2007 to 2020. MCC was assessed from a list of 22 conditions, identified using validated algorithms. We estimated the prevalence of MCC. Next, we used latent class analysis to identify classes of co-occurring chronic conditions in women with MCC, with model selection based on parsimony, clinical interpretability and statistical fit. RESULTS: Among 2,014,508 pregnancies, 324,735 had MCC (161.2 per 1000, 95% confidence interval [CI] 160.6, 161.8). Latent class analysis resulted in a five-class solution. In four classes, mood and anxiety disorders were prominent and clustered with one additional condition, as follows: Class 1 (22.4% of women with MCC), osteoarthritis; Class 2 (23.7%), obesity; Class 3 (15.8%), substance use disorders; and Class 4 (22.1%), asthma. In Class 5 (16.1%), four physical conditions clustered together: obesity, asthma, chronic hypertension and diabetes mellitus. CONCLUSIONS: MCC is common in pregnancy, with sub-types dominated by co-occurring mental and physical health conditions. These data show the importance of preconception and perinatal interventions, particularly integrated care strategies, to optimise treatment and stabilisation of chronic conditions in women with MCC.

Bimekizumab treatment in patients with active axial spondyloarthritis: 52-week efficacy and safety from the randomised parallel phase 3 BE MOBILE 1 and BE MOBILE 2 studies.

OBJECTIVES: Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated superior efficacy versus placebo in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) at Week 16. Here, the objective is to report the efficacy and safety of BKZ at Week 52. METHODS: BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) comprised a 16-week, double-blind, placebo-controlled period, then a 36-week maintenance period. From Week 16, all patients received subcutaneous BKZ 160 mg every 4 weeks. RESULTS: Improvements versus placebo in Assessment of SpondyloArthritis International Society ≥40% response (primary endpoint), Ankylosing Spondylitis Disease Activity Score, high-sensitivity C-reactive protein levels and MRI inflammation of the sacroiliac joints/spine at Week 16 were sustained to Week 52 in BKZ-randomised patients. At Week 52, responses of patients switching from placebo to BKZ at Week 16 were comparable to BKZ-randomised patients. At Week 52, ≥1 treatment-emergent adverse events (TEAEs) were reported in 183 (75.0%) and 249 (75.5%) patients with nr-axSpA and r-axSpA, respectively. Serious TEAEs occurred in 9 (3.7%) patients with nr-axSpA and 20 (6.1%) patients with r-axSpA. Oral candidiasis was the most frequent fungal infection (nr-axSpA: 18 (7.4%); r-axSpA: 20 (6.1%)). Uveitis occurred in three (1.2%) and seven (2.1%) patients with nr-axSpA and r-axSpA, and inflammatory bowel disease in two (0.8%) and three (0.9%). CONCLUSIONS: At Week 52, dual inhibition of IL-17A and IL-17F with BKZ resulted in sustained efficacy across the axSpA spectrum; the safety profile was consistent with the known safety of BKZ. TRIAL REGISTRATION NUMBER: NCT03928704; NCT03928743.