Adverse Childhood Experiences and Associations with Mental Health, Substance Use, and Violence Perpetration among Young Adults in sub-Saharan Africa.

Background: Adverse childhood experiences (ACEs) can have debilitating effects on child well-being, with consequences persisting into adulthood. Most ACE studies have been conducted in high-income countries and show a graded relationship between multiple ACE exposures and adverse health outcomes. Less is known about the types and burden of ACEs in sub-Saharan Africa (SSA). Objective: To estimate the pooled prevalence of six individual and cumulative ACE exposures (physical, sexual, and emotional violence; orphanhood; witnessing interparental and community violence) and assess their association with mental health outcomes, substance use, and violence perpetration among young adults in SSA. Participants and setting: Aggregate data from the Violence Against Children and Youth Survey (VACS) in Cote d'Ivoire 2018, Kenya 2019, Lesotho 2018, Mozambique 2019, and Namibia 2019 included a sample of 11,498 young adults aged 18-24 years. Methods: Cumulative ACEs were defined by an integer count of the total number of individual ACEs (0 to 6). Weighted prevalence and adjusted odds ratios were estimated. Result: ACEs prevalence ranged from 7.8% (emotional violence) to 55.0% (witnessing community violence). Strong graded relationships between cumulative ACE exposure and all study outcomes for both males and females were observed. Among females, witnessing interparental violence was the only individual ACE risk factor significantly associated with increased odds of substance use; among males, emotional violence was significantly associated with all outcomes. Conclusion: ACEs are associated with adverse mental health, substance use, and violence perpetration in SSA. Gender-specific and culturally sensitive intervention strategies are needed to effectively mitigate ACEs in this population.

Comparative Analysis of Single-Cell RNA Sequencing Methods with and without Sample Multiplexing.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful technique for investigating biological heterogeneity at the single-cell level in human systems and model organisms. Recent advances in scRNA-seq have enabled the pooling of cells from multiple samples into single libraries, thereby increasing sample throughput while reducing technical batch effects, library preparation time, and the overall cost. However, a comparative analysis of scRNA-seq methods with and without sample multiplexing is lacking. In this study, we benchmarked methods from two representative platforms: Parse Biosciences (Parse; with sample multiplexing) and 10x Genomics (10x; without sample multiplexing). By using peripheral blood mononuclear cells (PBMCs) obtained from two healthy individuals, we demonstrate that demultiplexed scRNA-seq data obtained from Parse showed similar cell type frequencies compared to 10x data where samples were not multiplexed. Despite relatively lower cell capture affecting library preparation, Parse can detect rare cell types (e.g., plasmablasts and dendritic cells) which is likely due to its relatively higher sensitivity in gene detection. Moreover, a comparative analysis of transcript quantification between the two platforms revealed platform-specific distributions of gene length and GC content. These results offer guidance for researchers in designing high-throughput scRNA-seq studies.

Evaluation of the European Society of Cardiology Risk Assessment Score in Incident Systemic Sclerosis-Associated Pulmonary Arterial Hypertension.

OBJECTIVE: Patients with pulmonary arterial hypertension (PAH) may be stratified as low, intermediate, or high risk of 1-year mortality. In 2022, the European Society of Cardiology (ESC) updated and simplified its risk stratification tool, based on three variables: World Health Organization functional class, serum N-terminal pro-brain type natriuretic peptide and six-minute walk distance, applied at follow-up visits, intended to guide therapy over time. METHODS: We applied the 2022 ESC risk assessment tool at baseline and follow-up (within 2 years) to a multinational incident cohort of systemic sclerosis-associated PAH (SSc-PAH). Kaplan-Meier curves, Cox hazards regression, and accelerated failure time models were used to evaluate survival by risk score. RESULTS: At baseline (n = 260), the majority of SSc-PAH (72.2%) were graded as intermediate risk of death according to the 2022 tool. At follow-up, according to 2022 tool, half (55.5%) of the cohort were classified as low or intermediate-low risk. The 2022 risk model at follow-up was able to differentiate survival between risk strata. All three individual parameters (World Health Organization functional class, N-terminal pro-brain type natriuretic peptide, six-minute walk distance) were significantly associated with mortality at baseline and/or follow-up. CONCLUSION: The 2022 ESC risk assessment strategy applied at baseline and follow-up predicts survival in SSc-PAH. Treatment decisions for SSc-PAH should include risk assessments, aiming to achieve low-risk status according to the 2022 ESC guidelines.

Investigating the Associations between Drought, Poverty, High-Risk Sexual Behaviours, and HIV Incidence in Sub-Saharan Africa: A Cross-Sectional Study.

Climate change is increasing the likelihood of drought in sub-Saharan Africa, where HIV prevalence is high. Drought could increase HIV transmission through various mediating mechanisms; we investigated these associations. We used data on people aged 15-59 from Population-Based HIV Impact Assessment surveys from 2016 in Eswatini, Lesotho, Tanzania, Uganda, and Zambia. Survey data were geospatially linked to precipitation data for 2014-2016, with local droughts defined as cumulative rainfall between 2014 and 2016 being in < 15th percentile of all 2-year periods over 1981-2016. Using multivariable logistic regression, stratified by sex and rural/urban residence, we examined associations between (a) drought and poverty, (b) wealth quintiles and sexual behaviours (transactional, high-risk, and intergenerational sex), (c) sexual behaviours and recently acquiring HIV, and (d) drought and recent HIV. Among 102,081 people, 31.5% resided in areas affected by drought during 2014-2016. Experiencing drought was positively associated with poverty for women and men in rural, but not urban, areas. For each group, increasing wealth was negatively associated with transactional sex. For rural women, intergenerational sex was positively associated with wealth. Women reporting each sexual behaviour had higher odds of recent HIV, with strong associations seen for high-risk sex, and, for urban women, intergenerational sex, with weaker associations among men. Women in rural areas who had been exposed to drought had higher odds of having recently acquired HIV (2.10 [95%CI: 1.17-3.77]), but not women in urban areas, or men. Droughts could potentially increase HIV transmission through increasing poverty and then sexual risk behaviours, particularly among women in rural areas.

Parenting-related positive childhood experiences, adverse childhood experiences, and mental health-Four sub-Saharan African countries.

BACKGROUND: Adverse Childhood Experiences (ACEs) are associated with poor mental health outcomes and risk-taking behaviors. Positive childhood experiences (PCEs) may mitigate these negative impacts. OBJECTIVE: This study 1) assessed the associations between ACEs and negative health outcomes and risk-taking behaviors among young adults, and 2) evaluated whether - and which - PCEs moderate the association between ACEs and these outcomes in sub-Saharan Africa. METHODS: This multi-country analysis combined cross-sectional representative survey data from young adults, ages 18-24 years, from the 2019 Kenya, 2018 Lesotho, 2019 Mozambique, and 2019 Namibia Violence Against Children and Youth Surveys. The association between experiencing any ACEs and each health outcome was assessed using Wald's chi-square tests. Multivariable logistic regression analyses assessed the association between each PCE and each outcome of interest. RESULTS: Females who experienced any ACEs had higher odds of experiencing moderate to severe mental distress (aOR = 2.7, 95%CI: 1.9, 3.9). Males who experienced any ACEs had higher odds of experiencing suicidal/self-harm behaviors (aOR = 6.7, 95%CI: 2.8, 16.0) and substance use (aOR = 2.5, 95%CI: 1.4, 4.2). In females, strong mother-child relationship was protective against moderate to severe mental distress (aOR = 0.7, 95%CI: 0.6, 0.9), suicidal/self-harm behaviors (aOR = 0.6, 95%CI: 0.4, 0.9), and substance use (aOR = 0.6, 95%CI: 0.4, 0.9). For males, a strong mother-child relationship was protective against suicidal/self-harm behaviors (aOR = 0.5, 95%CI: 0.2, 0.9), and a strong father-child relationship was protective against suicidal/self-harm behaviors (aOR = 0.4, 95%CI: 0.2, 0.7) and substance use (aOR = 0.6, 95%CI: 0.4, 0.8). CONCLUSIONS: Strong parenting programs may likely play an important role in improving the psychosocial health of young adults.

Associations of inter-annual rainfall decreases with subsequent HIV outcomes for persons with HIV on antiretroviral therapy in Southern Africa: a collaborative analysis of cohort studies.

BACKGROUND: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. METHODS: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981-2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm3, viral loads > 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre. RESULTS: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32-46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07-1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01-1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm3 or > 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66-0.98] per 10 percentile rainfall rank decrease). CONCLUSIONS: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required.

How does HIV-related stigma correlate with HIV prevalence in African countries? Distinct perspectives from individuals living with and living without HIV.

BACKGROUND: Population-level research evaluating HIV-related stigma among countries with varied national HIV prevalence is scarce. To better understand HIV-related stigma and mitigate its potential negative effects, it is necessary to evaluate its relationship with HIV prevalence, as well as the mechanisms that influence it. This study aimed to analyze how HIV-related stigma correlates with subnational HIV prevalence in three African countries with varied HIV epidemics. METHODS: This paper used data from the nationally representative Population-based HIV Impact Assessment (PHIA) surveys conducted from 2015-2017 in Malawi, Zambia, and Tanzania. Each country's sub-national geographic divisions were used to categorize them as low (0-5.4%), middle (5.5-11.2%), and high (11.3-17.1%) HIV prevalence regions in the main analysis. Questions from the survey stigma module were used to measure HIV-related stigma. Logistic regression and multilevel models were performed to assess the associations between the level of sub-national HIV prevalence and HIV-related stigma measures among persons living with, and without, HIV. RESULTS: The results show that the odds of people living without HIV expressing stigmatizing behavior towards PLWH was significantly lower in regions of middle (OR = 0.80, 90%CI = (0.68-0.96)) and high (OR = 0.65, 90%CI = (0.53-0.80)) HIV prevalence when compared to low prevalence regions. The odds of reporting discriminatory attitudes were also lower for those in middle (OR = 0.87, 90%CI = (0.78-0.98)) and high (OR = 0.64, 90%CI = (0.56-0.73)) HIV prevalence regions compared to others. Living in middle and high HIV prevalence regions was associated with lower odds of expressing prejudice toward PLWH (OR = 0.84, 90%CI = (0.71-0.99) and OR = 0.60, 90%CI = (0.45-0.80), respectively) among people living without HIV. Notably, PLWH living in high prevalence regions had higher odds of reporting internalized stigma (OR = 1.48, 90%CI = (1.02-2.14)) compared to those living in low prevalence regions. CONCLUSIONS: The results indicate that among people not living with HIV, subnational HIV prevalence was negatively associated with discriminatory attitudes and prejudice towards PLWH, but HIV prevalence was positively associated with self-reported internalized stigma among PLWH. These results provide insight on how resources could be invested to reduce HIV related stigma among both PLWH and those not living with HIV.

Social cognitive theory to improve symptom appraisal and help-seeking among patients with autoimmune rheumatic diseases: A qualitative study.

AIM: Social cognitive theory (SCT) has been successfully employed to improve symptom appraisal and help-seeking among patients with various conditions but is yet to be applied in the context of autoimmune rheumatic diseases (ARDs). This study aimed to explore the applicability of SCT in and possible approaches to improving symptom appraisal and help-seeking of patients with ARDs, one of the key barriers to earlier diagnosis. METHODS: Semi-structured interviews were conducted with 33 ARD patients with a prolonged pre-diagnosis interval (>3 months). We coded the transcripts deductively using SCT as the overarching framework and inductively for approaches identified from the interviews. RESULTS: All six main concepts of SCT (behavioral capacity, expectations, self-efficacy, observational learning, reinforcements, and reciprocal determinism) were observed in the three stages of symptom appraisal and help-seeking (detection, interpretation, and response) of patients with ARDs. While many participants reported that they were able and confident to detect their symptoms, they lacked the behavioral capacity and self-efficacy to interpret symptoms correctly, which resulted in delayed help-seeking and diagnosis. Possible approaches to address this suggested by participants (such as education of the general population) could improve behavioral capacity and self-efficacy in symptom interpretation and enhance expectations, observational learning, reinforcements, and reciprocal determinism in symptom response. CONCLUSION: Lack of behavioral capacity and self-efficacy was observed in symptom interpretation of patients with ARDs, which resulted in delayed help-seeking. Approaches could target the behavioral capacity and self-efficacy for symptom interpretation to facilitate early help-seeking and, in turn, earlier diagnosis among individuals with possible ARDs.

The Pathogenesis of Systemic Sclerosis: The Origin of Fibrosis and Interlink with Vasculopathy and Autoimmunity.

Systemic sclerosis (SSc) is an autoimmune disease associated with increased mortality and poor morbidity, impairing the quality of life in patients. Whilst we know that SSc affects multiple organs via vasculopathy, inflammation, and fibrosis, its exact pathophysiology remains elusive. Microvascular injury and vasculopathy are the initial pathological features of the disease. Clinically, the vasculopathy in SSc is manifested as Raynaud's phenomenon (reversible vasospasm in reaction to the cold or emotional stress) and digital ulcers due to ischemic injury. There are several reports that medications for vasculopathy, such as bosentan and soluble guanylate cyclase (sGC) modulators, improve not only vasculopathy but also dermal fibrosis, suggesting that vasculopathy is important in SSc. Although vasculopathy is an important initial step of the pathogenesis for SSc, it is still unclear how vasculopathy is related to inflammation and fibrosis. In this review, we focused on the clinical evidence for vasculopathy, the major cellular players for the pathogenesis, including pericytes, adipocytes, endothelial cells (ECs), and myofibroblasts, and their signaling pathway to elucidate the relationship among vasculopathy, inflammation, and fibrosis in SSc.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study.

OBJECTIVE: To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). METHODS: A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. CONCLUSION: About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Recommendations for enhanced primary series (third dose) COVID-19 vaccination for people with rheumatic diseases: Chapter of Rheumatologists, College of Physicians, Singapore.

Introduction: This review aims to provide evidence-based recommendations for an enhanced primary series (third dose) coronavirus disease 2019 (COVID-19) vaccination in people with rheumatic diseases (PRDs) in the local and regional context. Methods: Literature reviews were performed regarding the necessity, efficacy, safety and strategies for enhanced primary series COVID-19 vaccination in PRDs. Recommendations were developed based on evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence was synthesised by eight working group members, and the consensus was achieved by a Delphi method with nine members of an expert task force panel. Results: Two graded recommendations and one ungraded position statement were developed. PRDs have impaired immunogenicity from the COVID-19 vaccine and are at an increased risk of postvaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poor clinical outcomes, compared to the general population. We strongly recommend that PRDs on immunomodulatory drugs be offered a third dose of the messenger RNA (mRNA) vaccine as part of an enhanced primary series, after the standard two-dose regimen. We conditionally recommend that the third dose of mRNA vaccine against SARS-CoV-2 be given at least 4 weeks after the second dose or as soon as possible thereafter. There is insufficient data to inform whether the third mRNA vaccine should be homologous or heterologous in PRDs. Conclusion: These recommendations that were developed through evidence synthesis and formal consensus process provide guidance for an enhanced primary series COVID-19 vaccination in PRDs.

Symptom Appraisal and Help-Seeking Among Patients With Autoimmune Rheumatic Diseases: A Qualitative Study.

OBJECTIVE: Long diagnostic delay remains an unsolved problem in many autoimmune rheumatic diseases (ARDs). One of the major contributing factors is poor symptom appraisal and the resulting delays in help-seeking by patients themselves. We therefore aimed to understand the symptom appraisal and help-seeking experience among patients with ARDs in a multiethnic urban Asian population and to explore its influencing factors. METHODS: Semistructured interviews with 33 patients with ARDs were audio recorded and transcribed verbatim. We coded the transcripts deductively using the reported 3 stages of symptom appraisal (detection, interpretation, and response) as the framework, and inductively for newly emerging themes and subthemes. RESULTS: All 3 stages of the symptom appraisal and help-seeking journey (ie, symptom detection [by self and by others], symptom interpretation [causes, consequences, and required actions] and symptom response [no action, self-management, seeking help from nonhealthcare professionals, and seeking help from healthcare professionals]) were observed among patients. Interactions among these 3 stages were also observed: symptom interpretation was found to influence subsequent symptom detection, and the outcome of symptom response was found to influence both subsequent symptom detection and symptom interpretation. Various personal and socioenvironmental factors (eg, knowledge and cultural beliefs about the symptom) that influenced symptom appraisal and help-seeking were identified from the interviews. CONCLUSION: The symptom appraisal and help-seeking journey of patients with ARDs is an iterative process of detection, interpretation, and response, and is influenced by various personal and socioenvironmental factors. Addressing modifiable factors could shorten the symptom appraisal and help-seeking interval and improve patient outcomes.

Contraception and intersection with HIV services in 11 high HIV burden sub-Saharan African countries: Results from the population-based HIV Impact Assessment cross-sectional studies conducted from 2015 to 2018.

OBJECTIVE: The United Nations' Sustainable Development Goal 3.7.1 addresses the importance of family planning. The objective of this paper is to provide information on family planning to policymakers to help increase access to contraceptive methods to women in sub-Saharan Africa. METHODS: We analyzed data from the Population-based HIV Impact Assessment studies conducted in 11 sub-Saharan African countries from 2015 to 2018 to assess the relationship between HIV services and family planning. Analyses were restricted to women aged 15-49 years who reported being sexually active within the past 12 months and had data on contraceptive use. RESULTS: Approximately 46.4% of participants reported using any form of contraception; 93.6% of whom used modern contraceptives. Women with a positive HIV status were more likely to use contraceptives (P < 0.0001) than HIV-negative women. Unmet need was higher among women who were confirmed to be HIV-negative in Namibia, Uganda, and Zambia than confirmed to be positive. Women aged 15-19 years used contraception less than 40% of the time. CONCLUSION: This analysis highlights crucial gaps in progress among HIV-negative and young women (aged 15-19 years). To provide access to modern contraception for all women, programs and governments need to focus on women who desire but do not have access to these family planning resources.

The state of the pediatric HIV epidemic in Lesotho.

OBJECTIVE: Lesotho does not have reliable data on HIV prevalence in children, relying on estimates generated from program data. The 2016 Lesotho Population-based HIV Impact Assessment (LePHIA) aimed to determine HIV prevalence among children 0-14 years to assess the effectiveness of the prevention of mother-to-child transmission (PMTCT) program and guide future policy. METHODS: A nationally representative sample of children under 15 years underwent household-based, two-stage HIV testing from November 2016-May 2017. Children <18 months with a reactive screening test were tested for HIV infection using total nucleic acid (TNA) PCR. Parents (61.1%) or legal guardians (38.9%) provided information on children's clinical history. Children aged 10-14 years also answered a questionnaire on knowledge and behaviors. RESULTS: HIV prevalence was 2.1% [95% confidence interval (CI): 1.5-2.6]. Prevalence in 10-14 year olds (3.2%; 95% CI: 2.1, 4.2) was significantly greater compared to 0-4 year olds (1.0%; 95% CI: 0.5, 1.6). HIV prevalence in girls and boys was 2.6% (95% CI: 1.8-3.3) and 1.5% (95% CI: 1.0-2.1), respectively. Based on reported status and/or the presence of detectable antiretrovirals, 81.1% (95% CI: 71.7-90.4) of HIV-positive children were aware of their status, 98.2% (95% CI: 90.7-100.0) of those aware were on antiretroviral therapy (ART) and 73.9% (95% CI: 62.1-85.8) of those on ART were virally suppressed. CONCLUSIONS: Despite the roll-out of Option B+ in Lesotho in 2013, pediatric HIV prevalence remains high. Further research is required to understand the greater prevalence among girls, barriers to PMTCT, and how to better achieve viral suppression in children with HIV.

Improvements in work productivity among patients with inflammatory arthritis and osteoarthritis in the first six months after diagnosis: an inception cohort study.

OBJECTIVES: Reduced work productivity (WP), measured by work productivity loss (WPL) and work disability (WD), is common in patients with inflammatory arthritis (IA) and osteoarthritis (OA) but is not well characterised. We aimed to assess if there were any improvements in WP (WPL and WD) from diagnosis (T1) to six months later (T2) and to explore associations between WP at T2 and health status at T1 among these patients. METHODS: Patients were surveyed for work characteristics, work ability, WP and health status including physical functioning and vitality at T1 and T2. Associations between WP at T2 and health status at T1 were explored using regression models. RESULTS: Patients with IA (n=109) were younger than those with OA (n=70) (mean age: 50.5 vs. 57.7 years). The median WPL score decreased from 30.0 to 10.0 in patients with IA and from 20.0 to 0.0 in patients with OA, while the proportion reporting WD decreased from 52.3% to 45.3% in patients with IA and increased from 52.2% to 56.5% in patients with OA from T1 to T2. Physical functioning at T1 (coefficient = -0.35) was significantly associated with WPL at T2. Vitality at T1 (coefficient = 0.03) was associated with WD at T2. CONCLUSIONS: Greater improvements in WP were observed among patients with IA than those with OA in the first six months after diagnosis. This provides a basis for healthcare professionals to aim for greater improvements in work and health status for patients with IA.

Advances in biological and targeted therapies for systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a severe, and often life-threatening, autoimmune disease, which causes inflammation and fibrosis of the skin and internal organs. There are currently limited effective therapeutic options for patients with SSc. There are recently completed and ongoing phase 2 and 3 studies looking at biologic therapies for SSc that target the underlying pathogenesis of the disease. AREAS COVERED: The purpose of this review is to describe completed and ongoing trials of different biologic therapies for the treatment of SSc. This review discusses biologic therapy directed at multiple pathways that are believed to contribute to inflammation and fibrosis in SSc including T cell, B cell, direct cytokines, and JAK signaling. Data presented is based on authors' expertise of completed and ongoing trials. EXPERT OPINION: Tocilizumab and rituximab have supporting data to advocate for use in early SSc. Data from tocilizumab showed preservation of forced vital capacity (FVC) and beneficial effects on global composite measure. Recent data from different trials with rituximab in SSc (with and without interstitial lung disease) show beneficial effects on skin and FVC with good tolerability. We highlight the molecular heterogeneity in early SSc phenotype and the need to account for this in future trials.

Gut microbiome profiling in systemic sclerosis: a metagenomic approach.

OBJECTIVES: The early gastrointestinal (GI) manifestation of systemic sclerosis (SSc) suggests a possible GI microbiota engagement in the pathophysiology and/or progression of SSc. Previous studies have revealed dysbiosis among Caucasian SSc patients. This study extends these findings to Asian SSc patients. METHODS: Adult SSc patients, stratified according to 1) on immunosuppressive (On-IS) drugs or 2) no immunosuppressive drugs (No-IS), and age-and-sex-matched healthy controls (HC) were recruited. Metagenomic sequencing of stool DNA was compared between SSc patients and HC, and between SSc (On-IS) and (No-IS) patients. Alpha and beta-diversity, taxonomic and functional profiling were evaluated. RESULTS: Twenty-three female SSc patients (12 On-IS; 11 No-IS; 5 diffuse and 18 limited SSc subtype) and 19 female HC, with median age of 54 years and 56 years, respectively, were recruited. Median SSc disease duration was 3.3 years. Alpha diversity was significantly higher in SSc versus HC (p=0.014) and in SSc (No-IS) versus HC (p=0.006). There was no significant difference in beta diversity between SSc and HC (p=0.307). At the phyla level, there were significantly increased abundance of Firmicutes and Actinobacteria in SSc versus HC, and reduced abundance of Bacteroidetes (all p<0.001). At the species level, there were significantly increased abundance of several Lactobacillus, Bifidobacterium, and Coprococcus species in SSc, and increased abundance of Odoribacter, Bacteroides and Prevotella species in HC. KEGG pathway analysis demonstrated distinct differences between SSc versus HC, and between SSc (No-IS) and SSc (On-IS). CONCLUSIONS: Using metagenomic sequencing, our study further underlines distinct alterations in microbiota profiling among Asian SSc patients.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Evaluation of Nailfold Capillaroscopy Online Training Using the Fast Track Algorithm.

OBJECTIVE: Nailfold capillaroscopy (NFC) is increasingly used in the early identification of systemic sclerosis (SSc)-related disorders. A consensus "Fast Track algorithm" was developed by the European Alliance of Associations for Rheumatology to aid differentiation of scleroderma from nonscleroderma pattern on NFC. Our objective was to evaluate the online training of NFC using the Fast Track algorithm in the assessment of scleroderma vs nonscleroderma NFC pattern. METHODS: Participants attended the NFC online training workshop and were taught the Fast Track algorithm. Following the training, participants independently evaluated 45 NFC images in the same session, and then 2 to 4 weeks later, through the online platform. Participants had to differentiate between scleroderma vs nonscleroderma pattern, and additionally nonscleroderma pattern (normal) vs nonscleroderma pattern (nonspecific). The inter- and intrarater Cohen [Formula: see text] agreement was calculated. RESULTS: Ninety-eight participants took part in the baseline evaluation, and 61 in the reevaluation session. For identification of scleroderma vs nonscleroderma pattern, the mean (95% CI) inter- and intrarater [Formula: see text] were 0.86 (0.83-0.88) and 0.83 (0.79-0.87), respectively. The overall inter- and intrarater [Formula: see text] in the identification of scleroderma, nonscleroderma (normal), and nonscleroderma (nonspecific) patterns were 0.71 (0.69-0.74) and 0.71 (0.67-0.75), respectively. For nonscleroderma (normal) vs nonscleroderma (nonspecific) pattern, the inter- and intrarater [Formula: see text] were 0.59 (0.55-0.63) and 0.59 (0.54-0.65), respectively. CONCLUSION: In this first study evaluating NFC online training using the Fast Track algorithm, we showed very good inter- and intrarater agreement for the identification of scleroderma and nonscleroderma NFC pattern, supporting the feasibility of online NFC standardized training workshops.