Population Studies Research Articles

Gestational Diabetes Mellitus Prevalence and Risk Factors - A Study from a Tertiary Care Centre in North India

Introduction: Type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) pose significant global health challenges. The increasing global prevalence of GDM and its associated complications underscores the need for proactive screening and management. The study aimed to evaluate the prevalence of GDM and its associated risk factors in a tertiary care hospital in North India Methodology: A prospective cross-sectional study conducted at Max Super Speciality Hospital, New Delhi, during 2016-2017, enrolled 900 pregnant women (aged 18-50 years) from the antenatal outpatient department (OPD). Primary objective: To assess impaired oral glucose tolerance prevalence (IADPSG criteria) at 24th-28th weeks. The data covered demographic, socioeconomic, obstetric, and medical details. Descriptive statistics were used to summarize the variables. Chi-square or Fisher's tests were applied to categorical data, while continuous data were analysed using independent t-tests. Multiple regression analysis was conducted to identify risk factors. Results: GDM was diagnosed in 7.4% of participants. Prevalence was highest in the age group >35 years (36.2%, p=0.000), and a significant association was found between increasing body mass index (BMI) and GDM (p=0.04). Adverse obstetric history, including previous abortions and GDM in prior pregnancies, increased the risk of GDM. Complications during pregnancy, such as macrosomia (present in 1 patient with GDM and none in non-GDM), foetal distress (9.09% in GDM), and preeclampsia (4.7% in GDM), were higher in women with GDM. Vaginal delivery prevalence was higher in non-GDM, while GDM had a higher rate of caesarean section delivery (p<0.005). Conclusion: The study discloses a 7.4% GDM prevalence in North Indian tertiary care, accentuating rising diabetes trends. Identified risk factors inform antenatal screening, highlighting the need for early GDM management to mitigate complications and prevent future diabetes. Single-centre limitations emphasise the necessity for broader population studies for accurate prevalence rates.

Association Between Melanoma Metastasis and Metabolic Syndrome: A Cross-Sectional Study in a Chinese Population.

Metabolic syndrome (MetS) remains a significant global public health concern. However, the relationship between MetS, its individual components and melanoma metastasis remains unexplored. We analysed the clinical data of 258 Chinese melanoma patients who had not undergo systemic therapy. Binary logistic regression, adjusted for sex and age, was employed to evaluate the connection between MetS and its components and melanoma metastasis. Of the 258 melanoma patients, 92 met the MetS criteria upon diagnosis. No direct association between MetS and melanoma metastasis was identified. However, specific components of MetS, namely low HDL-cholesterol levels (OR = 2.85, 95% CI:1.50-5.41, p < 0.05) and dysglycaemia (OR = 4.23, 95% CI:1.80-8.96, p < 0.05), were associated with melanoma metastasis. In subgroup analysis, hypertriglyceridemia correlated with melanoma metastasis in non-elderly patients (< 65 years) (OR = 2.69, 95% CI: 1.14-6.33, p < 0.05). Central obesity and hypertension showed no association. A dose-response analysis further indicated that melanoma metastasis risk escalated with increasing fasting blood glucose and blood triglyceride concentrations, and with decreasing blood HDL concentration. Our results suggest that monitoring and managing individual components of the MetS, particularly HDL-cholesterol levels, fasting glucose and triglyceride levels, may have potential prognostic benefits for melanoma in the Chinese population.

Transethnic analysis identifies SORL1 variants and haplotypes protective against Alzheimer's disease.

The SORL1 locus exhibits protective effects against Alzheimer's disease (AD) across ancestries, yet systematic studies in diverse populations are sparse. Logistic regression identified AD-associated SORL1 haplotypes in East Asian (N=5249) and European (N=8588) populations. Association analysis between SORL1 haplotypes and AD-associated traits or plasma biomarkers was conducted. The effects of non-synonymous mutations were assessed in cell-based systems. Protective SORL1 variants/haplotypes were identified in the East Asian and European populations. Haplotype Hap_A showed a strong protective effect against AD in East Asians, linked to less severe AD phenotypes, higher SORL1 transcript levels, and plasma proteomic changes. A missense variant within Hap_A, rs2282647-C allele, was linked to a lower risk of AD and decreased expression of a truncated SORL1 protein isoform. Our transethnic analysis revealed key SORL1 haplotypes that exert protective effects against AD, suggesting mechanisms of the protective role of SORL1 in AD. We examined the AD-protective mechanisms of SORL1 in the general population across diverse ancestral backgrounds by jointly analyzing data from three East Asian cohorts (ie, mainland China, Hong Kong, and Japan) and a European cohort. Comparative analysis unveiled key ethnic-specific SORL1 genetic variants and haplotypes. Among these, the SORL1 minor haplotype, Hap_A, emerged as the primary AD-protective factor in East Asians. Hap_A exerts significant AD-protective effects in both APOE ε4 carriers and non-carriers. SORL1 haplotype Hap_A is associated with cognitive function, brain volume, and the activity of specific neuronal and immune-related pathways closely connected to AD risk. Protective variants within Hap_A are linked to increased SORL1 expression in human tissues. We identified an isoform-specific missense variant in Hap_A that modifies the function and levels of a truncated SORL1 protein isoform that is poorly investigated.

Preventing Severe COVID-19 with Tixagevimab-Cilgavimab in Hematological Patients Treated with Anti-CD20 Monoclonal Antibodies: An International Multicenter Study.

Despite the declining public health emergency status, COVID-19 still poses significant risks, especially for immunocompromised individuals. We aimed to evaluate the effectiveness of tixagevimab-cilgavimab (T-C) prophylaxis in preventing severe COVID-19 in patients with hematologic malignancies (HM) treated with anti-CD20 therapy during the early Omicron variant phase of the pandemic. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Respiratory Viruses (ESGREV) conducted a multicenter retrospective cohort study involving 15 centers from 5 countries. The study included 749 patients with HM treated with anti-CD20 between February 15 and June 30, 2022, comparing 215 who received T-C prophylaxis to 534 who did not. The study revealed a significant reduction in the risk of COVID-19 among patients who received T-C prophylaxis compared to those who did not (11.2% vs 23.4%, p < 0.001), with hazard ratio (HR) of 0.40 (95% CI 0.26-0.63), adjusted for age, sex, vaccination status, baseline HM malignancy and type of anti-CD-20. We also demonstrated a reduction for severe-critical diseases within all study populations, 1.4% vs 5.2%, p = 0.017, HR 0.26 (95% CI 0.08-0.84). T-C prophylaxis effectively prevented COVID-19 and severe-critical COVID-19 in patients with HM treated with anti-CD20 monoclonal antibodies during the early Omicron variant phase of the pandemic. Even though T-C is ineffective against current variants, these findings highlight the importance of additional protective measures and the continued development of monoclonal antibodies to protect immunocompromised individuals to mitigate the impact of COVID-19 and other respiratory viral diseases.

MRI markers of idiopathic normal pressure hydrocephalus in a population study with 791 participants: Exploring reference values and associations.

Epidemiological studies on idiopathic normal pressure hydrocephalus (iNPH) imaging markers and their normal values are scarce. This population-based study aimed to analyze several morphologic and volumetric iNPH-related imaging markers in a large sample, determining their distribution, diagnostic accuracy, suggested cut-offs, and associations with iNPH symptoms. This cross-sectional study included 791 70 year olds, 40 with radiologically probable iNPH (iNPHRadiol) and 751 without iNPH features (reference). MRI measures included Evans index (EI), z-EI, brain per ventricle ratio at anterior (BVRAC) and posterior commissures (BVRPC), sulcal compression, Sylvian fissure enlargement, callosal angle, diameter of temporal horns, 3rd and 4th ventricles, midbrain, and pons. Volumes of ventricles, corpus callosum, and brainstem were computed using automated segmentation. ROC analysis determined imaging markers' cut-offs. Symptoms were evaluated clinically and through self-report. In the reference group, median values (95% CI) for imaging markers were as follows: EI: 0.27 (0.26-0.27), z-EI: 0.28 (0.26-0.31), BVRAC: 1.69 (1.48-1.90), and BVRPC: 2.66 (2.24-3.27). Most imaging markers differed significantly between iNPHRadiol and the reference. Lateral ventricle volumes correlated better with z-EI and BVR than EI (Rs > 0.81 vs 0.68). Optimal cut-off values for z-EI, and BVRAC and BVRPC for distinguishing iNPHRadiol were 0.32, 1.36, and 1.83, respectively. Clinical symptoms correlated moderately with imaging markers (Rs < 0.49 for iNPHRadiol, p < .01). We report population-based reference values and propose cut-offs for iNPH-related imaging markers and volumetric measurements. Z-EI and BVR are likely superior markers for assessing ventricular enlargement in iNPH. Imaging markers of iNPH correlate moderately with iNPH symptoms.

A physically modelled selection function for compact binary mergers in the LIGO-Virgo O3 run and beyond

Abstract Despite the observation of nearly 100 compact binary coalescence (CBC) events up to the end of the Advanced gravitational-wave (GW) detectors' third observing run (O3), there remain fundamental open questions regarding their astrophysical formation mechanisms and environments. Population analysis should yield insights into these questions, but requires careful control of uncertainties and biases. GW observations have a strong selection bias: this is due first to the dependence of the signal amplitude on the source's (intrinsic and extrinsic) parameters, and second to the complicated nature of detector noise and of current detection methods. In this work, we introduce a new physically-motivated model of the sensitivity of GW searches for CBC events, aimed at enhancing the accuracy and efficiency of population reconstructions. In contrast to current methods which rely on re-weighting simulated signals (injections) via importance sampling, we model the probability of detection of binary black hole (BBH) mergers as a smooth, analytic function of source masses, orbit-aligned spins, and distance, fitted to accurately match injection results. The estimate can thus be used for population models whose signal distribution over parameter space differs significantly from the injection distribution. Our method has already been used in population studies such as reconstructing the BBH merger rate dependence on redshift.

Mental health and attitudes toward suicide amongst individuals with gender dysphoria in Iran

IntroductionGender dysphoria (GD) is associated with profound mental health challenges, including heightened suicide risk. This study aimed to explore the mental health status and attitudes toward suicide among individuals with GD in Iran.MethodsA comprehensive assessment was conducted using three validated tools: the General Health Questionnaire (GHQ-28) to gauge emotional distress and psychological well-being, the Beck Depression Inventory (BDI-II) to evaluate the severity of depressive symptoms, and the Predicament Questionnaire (PQ) to measure attitudes toward suicide in the context of social crises.ResultsAmong the 78 participants, 43 (55.1%) were identified as experiencing significant mental health issues, while 21 (26.9%) were found to suffer from severe depression. The average PQ score was 57.92, which aligns with findings from similar populations in previous studies, highlighting a concerning trend in suicide-related attitudes. Further statistical analysis revealed significant correlations between psychological distress (GHQ-28 scores) and attitudes toward suicide (PQ scores), as well as between depressive symptoms (BDI-II scores) and suicide-related attitudes.ConclusionsThese findings indicate a pervasive prevalence of psychological disorders, particularly depression, within this group, and underscore the strong association between depressive states and suicidal ideation. The study underscores the urgent need for targeted mental health interventions and comprehensive healthcare policies tailored to the specific needs of individuals with GD in Iran. Given the substantial mental health burden observed, particularly the risk of suicide, this research highlights the critical importance of integrating mental health care into broader support systems for this population.

The association between type 2 diabetes and dietary antioxidant index: a cross-sectional study in the Iranian population

The association between type 2 diabetes and dietary antioxidant index: a cross-sectional study in the Iranian population

The Relationship Between Adolescent Orthodontic Treatment and Temporomandibular Disorders: A Systematic Review with Meta-Analysis

The relationship between fixed orthodontic treatment and the development of temporomandibular disorders (TMDs) in adolescents has been a topic of considerable debate. This systematic review and meta-analysis aimed to evaluate the impact of fixed orthodontic treatment on the prevalence of TMDs in adolescents. A comprehensive literature search was conducted using PubMed, Web of Science, EMBASE, Google Scholar, and the Cochrane Library, yielding 886 records. After duplicate removal, 665 records were screened, and 8 studies were assessed for eligibility. Following quality assessment using the Joanna Briggs Institute checklist, 4 studies were included in the final analysis. Data were analyzed using a random-effects model in RevMan software. The meta-analysis revealed an overall odds ratio of 0.75 (95% CI: 0.37–1.51, p = 0.42), indicating no statistically significant association between fixed orthodontic treatment and the risk of developing TMDs. Substantial heterogeneity was observed (I2 = 73%), attributed to variations in study designs, populations, and outcome measures. The risk of bias analysis highlighted concerns in several domains, particularly selection bias and measurement of outcomes. While confounding bias and missing data bias were generally well-controlled, deviations in intervention and inconsistent outcome measurements were noted across the studies. These findings suggest that fixed orthodontic treatment does not significantly alter the risk of developing TMDs in adolescents. However, the substantial heterogeneity and potential biases across the included studies emphasize the need for further high-quality, standardized research to confirm these results and provide clearer clinical guidance.

Epidemiology of systemic vasculitis.

Ongoing research contributes to our understanding of the epidemiology of vasculitis and its outcomes across the globe. This review aims to summarize important research studies published on this topic in the last 18 months. The implementation of rapid referral systems and use of large vessel imaging have improved the diagnosis of giant cell arteritis. A population-based study in immunoglobulin G4-related disease provides incidence and prevalence estimates for the United States for the first time. Recently published data supported viral infectious triggers for Kawasaki disease and immunoglobulin A vasculitis. Population studies in antineutrophil cytoplasmic antibody associated vasculitis report an increase in the incidence of eosinophilic granulomatosis with polyangiitis and have provided further insights into the burden of cardiovascular disease in these patients. Data on Behçet's disease continues to show increased all-cause mortality and need for better treatment strategies. Recent literature highlights the heterogeneity of the epidemiology of vasculitis in different parts of the world as well as associated outcomes, comorbidities, and potential triggers. Thought new classification criteria are being employed in some forms of vasculitis, standardization of case identification remains an unmet need in multiple other forms of vasculitis.

Invariance transformations in wave-optics lensing: Implications for gravitational-wave astrophysics and cosmology

Gravitational lensing offers unique opportunities to learn about the astrophysical origin of distant sources, the abundance of intervening objects acting as lenses, and gravity and cosmology in general. However, all this information can only be retrieved as long as one can disentangle each effect from the finite number of observables. In the geometric optics regime, typical of electromagnetic radiation, when the wavelength of the lensed signal is small compared to the size of the lens, there are invariance transformations that change the mass of the lens and the source-lens configuration but leave the observables unchanged. Neglecting this “mass-sheet degeneracy” can lead to biased lens parameters or unrealistic low uncertainties, which could then transfer to an incorrect cosmography study. This might be different for gravitational waves as their long wavelengths can be comparable to the lens size and lensing enters into the wave-optics limit. We explore the existence of invariance transformations in the wave-optics regime of gravitational-wave lensing, extending previous work and examining the implications for astrophysical and cosmological studies. We study these invariance transformations using three different methods of increasing level of complexity: template mismatch, Fisher Matrix, and Bayesian parameter estimation. We find that, for a sufficiently loud signal, the degeneracy is partially broken and the lens and cosmological parameters, e.g. H0, can be retrieved independently and unbiased. In current ground-based detectors, though, considering also population studies, a strong constraint on these parameters seems quite remote and the prevailing degeneracy implies a larger uncertainty in the lens model reconstruction. However, with better sensitivity of the third-generation ground-based detectors, a meaningful constraint on H0 is possible to obtain. Published by the American Physical Society 2024

Management of Acute Ischemic Stroke Following Transcatheter Aortic Valve Implantation: A Systematic Review and Multidisciplinary Treatment Recommendations

Background/Objectives: Acute ischemic stroke is an uncommon but potentially devastating complication of Transcatheter Aortic Valve Implantation (TAVI). Despite improvements in device technology and procedural techniques, stroke rates have remained stable, with cerebral embolic protection devices demonstrating only limited efficacy to date. Therefore, the management of acute ischemic stroke complicating TAVI (AISCT) remains a key priority. We conducted a systematic review of the management of AISCT and provided multidisciplinary consensus recommendations for optimal management. Methods: PubMed, Google Scholar, and Cochrane databases were searched from inception to October 2023. All the original studies focusing on the treatment of AISCT were included. Non-English language studies, review articles, and studies in pediatric populations were excluded. Consensus recommendations were made by a working group comprising experts in stroke medicine and structural interventional cardiology. Results: A total of 18 studies met the inclusion criteria, including 14 case reports/series and 4 observational studies. No clinical trials were identified. The included case reports and series suggest that tissue-type plasminogen activator (tPA) and mechanical thrombectomy (MT) might be effective strategies for managing AISCT. However, significant bleeding complications were reported in two out of the four patients receiving tPA. Four observational studies also suggest an association between tPA and/or MT and improved functional outcomes and survival compared to conservative management. Higher bleeding rates were reported following tPA. Observational data suggest that there is currently little real-world utilization of either reperfusion strategy. Conclusions: There is an absence of high-quality randomized data to guide clinical decision making in this important area. Observational data suggest reperfusion strategies are associated with improved clinical outcomes once important confounders such as stroke severity have been accounted for. While MT can be recommended as the standard of care in appropriately selected patients, significantly increased rates of bleeding with tPA following large-bore arterial access raise important safety concerns. We present simple clinical guidance for AISCT based on the limited available data. Close multidisciplinary work and patient-specific consideration of ischemic and bleeding risk is essential.

A little less concentration, a little more actors, please? Exploring the relationship between populist attitudes and perceptions of concentration of political power practices

ABSTRACT Demand-side studies of populism, adapting a citizen perspective, have grown exponentially during the last decade as a result of a growing political and academic concern over the potential effects of populism on the political system. Nevertheless, how populist attitudes at the citizen level are related to actual proposals for system-change is a surprisingly neglected research topic. One such proposal concerns the future of multiple-mandate-holding (MMH), i.e. the simultaneous exercise of at least two directly elected political functions, a controversial practice in many parts of Europe. By utilizing cross-sectional panel data gathered in Finland in 2022–2023, a country characterized by extensive MMH among Members of Parliament, this study seeks to explore whether and how populist attitudes are related to the idea of representational pluralism in the political system, defined as the level of diversity among directly elected political representatives active within the political system. Using statistical analyses, we confirm our hypothesis that stronger populist attitudes are clearly associated with weaker support for MMH in general and stronger support for limiting the scope of MMH specifically. Our findings contribute to the theory-building of demand-side populism by showing that populist attitudes are also associated with the idea of representational pluralism.

Could APTIMA mRNA Assay Contribute to Predicting Cervical Bacterial Sexually Transmitted Co-Infections? A Colposcopy Population Study

Could APTIMA mRNA Assay Contribute to Predicting Cervical Bacterial Sexually Transmitted Co-Infections? A Colposcopy Population Study

Diversity of Picea omorika (Pančić) Purk. Populations Based on Morpho-anatomical Needle Traits and Bioclimatic Parameters

Picea omorika (Pančić) Purkyne is a well-known endemic conifer species. However, there have been few morpho-anatomical studies to date. Several years ago, preliminary population studies of P. omorika were published, but with the inclusion of additional populations, it became necessary to confirm whether the southernmost population from Mileševka Canyon, also known as var. vukomanii, (Pavlović and Matović 1994), remains distinct from the others. Two-year-old needles from the lower third of the crown were collected in late autumn from seven natural populations of P. omorika from Serbia and from the border with Bosnia and Herzegovina. The variability of ten morpho-anatomical traits and the cross-sectional anatomy of Serbian spruce needles were examined in seven natural populations in Serbia. Needle length was measured with a digital calliper, and the nine other needle traits, needle width, needle thickness, vascular bundle diameter, resin ducts diameter, number of resin ducts, distance between vascular bundle and resin duct, cuticle and epidermal thickness, hypodermal thickness, and hypodermal width, were examined under a light microscope. For most of the traits studied, the Štula population had the highest values, whereas the Bilo population had the lowest. Needles with triangular sections are most common in the southern part of Mt. Tara, while elliptical and rhomboidal sections are characteristic in populations at the edge of the distribution range in Serbia. Multivariate analyses separated populations into two main groups. Both principal component analysis and discriminant analysis indicated population overlap, while cluster analysis identified three main groups. Multivariate analysis of bioclimatic data and a correlation study of morpho-anatomical traits were also performed. Based on bioclimatic parameters, individuals in the populations from Mileševka and Štula showed the most distinct characteristics. Mantel and partial Mantel tests confirmed no correlation between the complete set of morphological traits and bioclimatic parameters, even after adjusting for regional differences.

Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populations

BackgroundNumerous observational studies have shown a potential association between metabolic dysfunction-associated steatotic liver disease (MASLD) and gastroesophageal reflux disease (GERD). However, causality is unclear. This study utilized genome-wide association study (GWAS) genetic data to explore the causal relationship between MASLD and GERD in European and East Asian populations.MethodsThis study utilized a bidirectional, two-sample Mendelian randomization (MR) approach. All disease data were obtained from the GWAS database, and single nucleotide polymorphisms strongly associated with exposure were selected as instrumental variables. The inverse variance weighted (IVW) method is primarily utilized to evaluate the causal relationship between exposure and outcome. Finally, sensitivity analyses were performed to ensure the robustness of the results.ResultsThe IVW estimates indicated that non-alcoholic fatty liver disease (NAFLD) (odds ratio (OR) = 1.054, 95% confidence interval (CI), 0.966–1.150, p = 0.236) and percent liver fat (OR = 0.977, 95% CI, 0.937–1.018, p = 0.258) in European population were not linked to a higher risk of GERD. However, GERD in European population was associated with an increased risk of NAFLD (OR = 1.485, 95% CI, 1.274–1.729, p &amp;lt; 0.001) and percent liver fat (OR = 1.244, 95% CI, 1.171–1.321, p &amp;lt; 0.001). In addition, the IVW analysis in East Asian population showed that alanine aminotransferase (ALT) was associated with an increased risk of GERD (OR = 2.305, 95% CI, 1.241–4.281, p = 0.008), whereas aspartate aminotransferase (AST) had no causal effects on GERD risk (OR = 0.973, 95% CI, 0.541–1.749, p = 0.926). Furthermore, the associations between GERD and ALT (OR = 1.007, 95% CI, 0.998–1.015, p = 0.123) or AST (OR = 1.004, 95% CI, 0.997–1.012, p = 0.246) were not significant. After removing outliers, a significant correlation between GERD and ALT was observed (OR = 1.009, 95% CI, 1.001–1.016, p = 0.020).ConclusionThere was reverse causality between MASLD and GERD in European population, while there was bidirectional causality between a proxie for MASLD (ALT) and GERD in East Asian population. This study can provide novel insights into cross-ethnic genetic research on MASLD and GERD.

Enablers to high vaccination uptake among a disadvantaged minority population: a qualitative study of the Arab population of Israel

BackgroundOver 1.9 million Arabs live in Israel and constitute 21% of the total population. Despite being a disadvantaged minority population with wide gaps in health indicators, Arabs have higher Human Papillomavirus (HPV) and Measles, Mumps, and Rubella (MMR) vaccination rates compared with the general Jewish population.MethodsIn-depth interviews with 21 health care providers, 16 Arab mothers, and 16 teenagers were conducted to collect information about health system enablers to HPV and MMR vaccination. All interviews were conducted in Arabic by an Arab researcher, audio-recorded, transcribed, and analysed using thematic analysis of the transcripts. Themes were mapped according to the WHO Health Systems Building Block Framework.ResultsWe identified several health system enablers. On the service delivery level, accessible and availability of vaccination services, delivery of vaccines through the school system and mother child clinics, and framing vaccinations as the norm were themes. Personable characteristics of the health workforce, the health care providers belonging to the same cultural group, and high levels of trust towards healthcare professionals were reported. Vaccination provided at no cost was also identified. On the leadership/governance level, the Arab community felt equal treatment and distribution of services, which was also an enabler reported. Despite high vaccine uptakes, parents and teenagers had limited knowledge regarding vaccination, particularly HPV.ConclusionsThis study highlights that a combination of good access and delivery to vaccination, delivered by a culturally competent, available, accessible respectful workforce can enable disadvantaged minorities to achieve high vaccine coverage, in particular in a cultural context where the population trusts and follows medical advice. Such evidence can serve as a basis for developing policies, interventions, and guidance to improve vaccine uptake among other underserved minority communities.

Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers.

Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers. This was a Phase I, open-label, parallel group, multiple-dose study. Participants were randomized to five cohorts to receive three doses of obexelimab as 125mg SC every 14days (q14d), 250mg SC q14d, 375mg SC q14d, 250mg IV q14d, and 125mg SC every 7days, then monitored during a 28-day safety follow-up period. PK/PD assessments were performed after the first and third doses. A total of 50 healthy volunteers (25 Japanese and 25 non-Japanese) were enrolled and distributed evenly between dose cohorts. All SC dosing regimens were well-tolerated. Dose-proportional PK was observed following SC doses with a bioavailability of approximately 60%. No clinically meaningful differences in PK parameters were found between healthy Japanese and non-Japanese participants. Antidrug antibodies (ADA) were detected in 6/50 (12%) participants after dosing. ADA had no or minimal impact on PK in all six ADA positive participants. Near-complete CD19 receptor occupancy and an absolute B-cell count nadir of approximately 50% baseline levels were maintained for the duration of the study in both populations. Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD. These results support further clinical development of SC obexelimab to treat B-cell mediated autoimmune diseases. NCT02867098.

Augmenting clinical trials in asthma through digital technology, decentralised designs, and person-centric endpoints: opportunities and challenges.

Digital technologies (eg, smart inhalers, wearables, and sensors) allow for remote, objective, granular, and non-invasive data collection, making them attractive for research evaluating interventions in airways diseases with variable trajectories, such as asthma. Such technologies offer the opportunity to move towards decentralised clinical trials that are done partly or fully outside the classic clinical trial setting and are characterised by remote data collection and monitoring. This approach to evaluating clinical, pharmacological, or behavioural interventions could facilitate recruitment of inclusive and generalisable study populations, enhance personalisation and sustainability, reduce research costs, and accelerate the timeline to novel asthma treatments' market access. This Personal View discusses the application of digital technologies and endpoints within trials; the concept of hybrid and decentralised designs; describes a fully decentralised trial in asthma; and explores the strengths, weaknesses, opportunities, and threats regarding their implementation from the clinician, patient expert, low-resource, and regulator viewpoints.

Pluralising pluralism in the study of populism

Despite the widespread claim that populism and pluralism are incompatible, the latter is rarely defined clearly in the existing literature. This is significant as such purported incompatibility is used to argue that populist politics cannot sit comfortably within liberal democracy. I begin this article by examining the theoretical foundations of research on populism and pluralism, particularly from scholars who adopt the ideational approach. I highlight how this conception of pluralism is limited to protecting minority rights through liberal-democratic institutions, without considering how such institutions are often exclusionary. I then turn to the contributions of Ernesto Laclau and Chantal Mouffe on populism, pluralism, and hegemony. I suggest that while Mouffe sacrifices the counter-hegemonic potential of populism in pursuit of pluralism, Laclau sacrifices pluralism for counter-hegemony through his insistence that the universal can only be articulated through the particular. Moving beyond Laclau’s part-as-whole formulation, I develop an understanding of pluralism rooted in non-belonging, which grounds plurality in shared constitutive lack. This allows for the advancement of an indeterminate concept of ‘the people’ without the imposition of a universalised particular. Thinking of pluralism in these terms provides critical scholars of populism with a conceptualisation which does not depend solely on a liberal vocabulary.