Flares in IIMs and the timeline following COVID-19 vaccination: a combined analysis of the COVAD-1 and -2 surveys.

OBJECTIVES: Disease flares in the post-coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). METHODS: The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression models. RESULTS: Of 15 165 total respondents, 1278 IIMs (age 63 years, 70.3% female, 80.8% Caucasians) and 3453 AIRDs were included. Flares of IIM were seen in 9.6%, 12.7%, 8.7% and 19.6% patients by definitions (a) to (d), respectively, with a median time to flare of 71.5 (10.7-235) days, similar to AIRDs. Patients with active IIMs pre-vaccination (OR 1.2; 95% CI 1.03, 1.6, P = 0.025) were prone to flares, while those receiving rituximab (OR 0.3; 95% CI 0.1, 0.7, P = 0.010) and AZA (OR 0.3, 95% CI 0.1, 0.8, P = 0.016) were at lower risk. Female gender and comorbidities predisposed to flares requiring changes in IS. Asthma (OR 1.62; 95% CI 1.05, 2.50, P = 0.028) and higher pain visual analogue score (OR 1.19; 95% CI 1.11, 1.27, P < 0.001) were associated with disparity between self-reported and IS-denoted flares. CONCLUSION: A diagnosis of IIMs confers an equal risk of flares in the post-COVID-19 vaccination period to AIRDs, with active disease, female gender and comorbidities conferring a higher risk. Disparity between patient- and physician-reported outcomes represents a future avenue for exploration.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Safety and efficacy of the novel RNA interference therapies for hypertriglyceridemia and mixed hyperlipidemia management: a systematic review and meta-analysis.

BACKGROUND: No meta-analysis has holistically analyzed and summarized the safety and therapeutic efficacy of the newer RNA interference (RNAi) therapies, olezarsen, plozasiran, and zodasiran, in managing conditions associated with hypertriglyceridemia (HTG). METHODS: Randomized controlled trials (RCTs) involving patients with HTG or mixed hyperlipidemia (MHL) receiving either olezarsen, plozasiran, or zodasiran in the intervention arm and a placebo in the control arm were searched through electronic databases. The primary outcome was the safety profile of the drugs studied; secondary outcomes included the percent change from baseline (CFB) in the lipid levels, including triglyceride (TG). RESULTS: Six RCTs with 334 participants were evaluated. Olezarsen, plozasiran, and zodasiran were well-tolerated with no higher risk of serious adverse events or injection-site reactions. After 24 weeks, plozasiran increased alanine aminotransferase and HbA1c more than placebo, although the difference was insignificant at 48 weeks. Plozasiran and zodasiran had little effect on hyperglycemia worsening. Olezarsen increased the likelihood of mild platelet count decreases without clinical harm. At their longest clinical trial follow-up, the highest doses of olezarsen, plozasiran, and zodasiran lowered TG by 55.2%, 50.57%, and 51.2% of baseline levels. All three drugs decreased non-HDL-C and remnant cholesterol. Olezarsen and plozasiran lowered ApoC-III and increased HDL-C, whereas zodasiran reduced HDL-C. Zodasiran decreased LDL-C, whereas olezarsen and plozasiran had no effects on LDL-C. Plozasiran and zodasiran lowered apolipoprotein B, but not olezarsen. CONCLUSION: The newer RNA interference (RNAi) therapies appear safe and have excellent TG-lowering efficacy in patients with HTG and MHL.

Role of Teplizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Managing Newly Diagnosed Type 1 Diabetes: An Updated Systematic Review and Meta-Analysis.

OBJECTIVE: Teplizumab has emerged as a potential disease-modifying drug in type 1 diabetes (T1D). This meta-analysis sought to summarize the therapeutic effect of teplizumab in newly diagnosed patients with T1D. METHODS: Randomized controlled trials involving patients with T1D receiving teplizumab in the intervention arm and placebo (or no active intervention) in the control arm were searched throughout the electronic databases. The primary outcome was the change in area under the curve of C-peptide levels from baseline. RESULTS: Seven reports from 6 studies involving 834 subjects met the inclusion criteria. Compared to teplizumab, greater reductions in area under the curve of C-peptide from the baseline values were observed in the control group after 6 months (mean difference [MD] 0.07 nmol/L [0.01, 0.13], P = .02), after 12 months (MD 0.07 nmol/L [0.04, 0.11], P = .0001), after 18 months (MD 0.10 nmol/L [0.06, 0.14], P < .00001), and after 24 months (MD 0.07 nmol/L [0.01, 0.14], P = .03) of interventions. Moreover, fewer patients treated with teplizumab had a decreased C-peptide response after 6 months (odds ratio [OR] 0.21), after 12 months (OR 0.17), after 18 months (OR 0.30), and after 24 months (OR 0.12) of treatment. The preservation of endogenous insulin production was supported by reduced use of exogenous insulin with maintenance of comparable glycemic control for up to 18 months post-treatment. Teplizumab imparted higher risks of grade 3 or higher adverse events, adverse events leading to study medication discontinuation, nausea, rash, and lymphopenia. CONCLUSION: The results of the meta-analysis support teplizumab as a promising disease-modifying therapy for newly diagnosed T1D.

Role of Resmetirom, a Liver-Directed, Thyroid Hormone Receptor Beta-Selective Agonist, in Managing Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Resmetirom, a liver-directed, thyroid hormone receptor beta-selective agonist, has recently been approved to treat nonalcoholic steatohepatitis (NASH). This meta-analysis aimed to summarize the efficiency and safety of resmetirom in treating NASH. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) of resmetirom vs placebo in patients with NASH. The primary outcomes were the changes from baseline in hepatic fat content, liver histology, including NASH resolution, and noninvasive markers of hepatic fibrosis. RESULTS: Three randomized controlled trials (n = 2231) met the inclusion criteria. Compared to placebo, resmetirom achieved greater reductions from baseline in hepatic fat content assessed by magnetic resonance imaging proton density fat fraction (for resmetirom 80 mg: MD -27.76% [95%CI: -32.84, -22.69]; for resmetirom 100 mg: MD -36.01% [95%CI: -41.54, -30.48]; P < .00001 for both) and FibroScan controlled attenuation parameter (for resmetirom 80 mg: MD -21.45 dBm [95%CI: -29.37, -13.52]; for resmetirom 100 mg: MD -25.51 dBm [95%CI: -33.53, -17.49]; P < .00001 for both). Resmetirom 80 mg outperformed placebo in NASH resolution and ≥2-point nonalcoholic fatty liver disease activity score reduction. Moreover, resmetirom 80 mg and 100 mg were superior to placebo in cytokeratin-18 (M30) reduction. Greater reductions in liver enzymes, lipids, and reverse triiodothyronine were observed in the resmetirom arms with no impact on triiodothyronine. Nausea and diarrhea were more common with resmetirom than with placebo; other adverse events were comparable. CONCLUSION: Resmetirom improves hepatic fat content, liver enzymes, and fibrosis biomarkers in NASH patients. Resmetirom generally does not affect thyroid function and is well-tolerated.

A review of the neurobehavioural, physiological, and reproductive toxicity of microplastics in fishes.

Microplastics (MPs) have emerged as widespread environmental pollutants, causing significant threats to aquatic ecosystems and organisms. This review examines the toxic effects of MPs on fishes, with a focus on neurobehavioural, physiological, and reproductive impacts, as well as the underlying mechanisms of toxicity. Evidence indicates that MPs induce a range of neurobehavioural abnormalities in fishes, affecting social interactions and cognitive functions. Altered neurotransmitter levels are identified as a key mechanism driving behavioural alterations following MP exposure. Physiological abnormalities in fishes exposed to MPs are also reported, including neurotoxicity, immunotoxicity, and oxidative stress. These physiological disruptions can compromise the individual health of aquatic organisms. Furthermore, reproductive abnormalities linked to MP exposure are discussed, with a particular emphasis on disruptions in endocrine signaling pathways. These disruptions can impair reproductive success in fish species, impacting population numbers. Here we explore the critical role of endocrine disruptions in mediating reproductive effects after exposure to MPs, focusing primarily on the hypothalamic-pituitary-gonadal axis. Our review highlights the urgent need for interdisciplinary research efforts aimed at elucidating the full extent of MP toxicity and its implications for aquatic ecosystems. Lastly, we identify knowledge gaps for future research, including investigations into the transgenerational impacts, if any, of MP exposure and quantifying synergetic/antagonistic effects of MPs with other environmental pollutants. This expanded knowledge regarding the potential risks of MPs to aquatic wildlife is expected to aid policymakers in developing mitigation strategies to protect aquatic species.

The impact of sociodemographic, health status and resources, macroeconomic, and environmental factors on infant mortality rates in Qatar, Kingdom of Saudi Arabia, and the United Arab Emirates.

OBJECTIVES: This study aims to study the impact of sociodemographic (SD), health status and resources (HSR), macroeconomic (ME), and Environmental (EV) factors on the infant mortality rate (IMR) in Qatar, Kingdom of Saudi Arabia (KSA), and the United Arab Emirates (UAE) and from 1990 to 2022. DESIGN: A retrospective time-series study employing yearly data was conducted. A generalized least squares model was utilized to construct an exploratory model of IMR determinants for each country. RESULTS: In SD, the risk of IMR may be increased with a higher crude birth rate, adolescent fertility rate, and married women percentage. In HSR, immunization coverage shows a significant effect in preventing neonatal diseases and reducing IMR. In ME, the effect of parents' employment seems contradicted among the three countries. In EV, greenhouse emissions have also had contradictory effects among the three countries, suggesting a complex relationship with IMR. Some were consistent with global findings, whereas others contradicted the prevailing narrative. CONCLUSIONS: This study highlights the need for tailored public health interventions addressing socio-demographic, healthcare, and environmental contexts to effectively reduce IMR and enhance infant health outcomes.

Significance of Contusion at the Vocal Cord and Perivocal Cord Area in Cases of Non-intubated Death.

Every finding during a neck autopsy may be essential for accurately diagnosing and explaining the mechanism of death. In this prospective study in the Department of Forensic Medicine and Toxicology of Jordan University Hospital, 17 out of 95 neck autopsies revealed contusions of the laryngeal mucosa in the vocal or perivocal area. These contusions were found to be associated with various causes of death, including mechanical asphyxia (such as throttling, ligature strangulation, hanging, smothering, choking, plastic bag asphyxia, gagging, and inhalation of blood) and other causes (such as atypical drowning, carbon monoxide poisoning, head injury due to a road traffic accident, burns, electrocution, and brain edema). This study provides insight into the mechanisms of this important lesion and may contribute to a better understanding of the cause of death.

FOXF1 Regulates Alveolar Epithelial Morphogenesis through Transcriptional Activation of Mesenchymal WNT5A.

Mutations in the FOXF1 (forkhead box F1) gene, encoding the mesenchymal FOX (forkhead box) transcription factor, are linked to alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a severe congenital disorder associated with the loss of alveolar capillaries and lung hypoplasia. Although proangiogenic functions of FOXF1 have been extensively studied, the role of FOXF1 in mesenchymal-epithelial signaling during lung development remains uncharacterized. Herein, we used murine lung organoids to demonstrate that the S52F FOXF1 mutation (found in patients with ACDMPV) stimulates canonical WNT/ß-catenin signaling in type 2 alveolar epithelial cells (AEC2s), leading to increased proliferation of AEC2s and decreased differentiation of AEC2s into type 1 alveolar epithelial cells (AEC1s). Alveolar organoids containing Foxf1WT/S52F lung fibroblasts and wild-type epithelial cells grew faster on Matrigel and exhibited AEC2 hyperplasia. AEC2 hyperplasia and loss of AEC1s were found in the lungs of Foxf1WT/S52F embryos, a mouse model of ACDMPV. Activation of canonical WNT/ß-catenin signaling in AEC2s of lung organoids and Foxf1WT/S52F mice was associated with decreased expression of noncanonical WNT5A (Wnt family member 5A) ligand in lung fibroblasts. Mechanistically, FOXF1 directly activates the Wnt5a gene transcription through an evolutionarily conserved +6320/+6326 region located in the first intron of the Wnt5a gene. Site-directed mutagenesis of the +6320/+6326 region prevented the transcriptional activation of the Wnt5a enhancer by FOXF1. Treatment with exogenous WNT5A ligand inhibited the effects of the S52F FOXF1 mutation on canonical WNT/ß-catenin signaling in alveolar organoids, preventing aberrant AEC2 expansion and restoring differentiation of AEC1s. Activation of either FOXF1 or WNT5A may provide an attractive strategy to improve lung function in patients with ACDMPV.

COVID-19 vaccine safety during pregnancy and breastfeeding in women with autoimmune diseases: results from the COVAD study.

OBJECTIVES: We investigated COVID-19 vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares (DF), and AID-related treatment modifications were analyzed upon diagnosis of AID versus healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine. RESULTS: Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, p= 0.01; minor AE 40% vs 25.9%, p= 0.03; major AE 17.5% vs 4.6%, p< 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a DF were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively. CONCLUSION: This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and the fetus by passive immunization appear to outweigh potential risks.

Vaccine hesitancy decreases in rheumatic diseases, long-term concerns remain in myositis: a comparative analysis of the COVAD surveys.

OBJECTIVE: COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys. METHODS: The first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups. RESULTS: We analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs - OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs - OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7-10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8-0.97)]. CONCLUSION: Vaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.

Flares in autoimmune rheumatic diseases in the post-COVID-19 vaccination period-a cross-sequential study based on COVAD surveys.

OBJECTIVE: Flares of autoimmune rheumatic diseases (AIRDs) following COVID-19 vaccination are a particular concern in vaccine-hesitant individuals. Therefore, we investigated the incidence, predictors and patterns of flares following vaccination in individuals living with AIRDs, using global COVID-19 Vaccination in Autoimmune Diseases (COVAD) surveys. METHODS: The COVAD surveys were used to extract data on flare demographics, comorbidities, COVID-19 history, and vaccination details for patients with AIRDs. Flares following vaccination were identified as patient-reported (a), increased immunosuppression (b), clinical exacerbations (c) and worsening of PROMIS scores (d). We studied flare characteristics and used regression models to differentiate flares among various AIRDs. RESULTS: Of 15 165 total responses, the incidence of flares in 3453 patients with AIRDs was 11.3%, 14.8%, 9.5% and 26.7% by definitions a-d, respectively. There was moderate agreement between patient-reported and immunosuppression-defined flares (K = 0.403, P = 0.022). Arthritis (61.6%) and fatigue (58.8%) were the most commonly reported symptoms. Self-reported flares were associated with higher comorbidities (P = 0.013), mental health disorders (MHDs) (P < 0.001) and autoimmune disease multimorbidity (AIDm) (P < 0.001).In regression analysis, the presence of AIDm [odds ratio (OR) = 1.4; 95% CI: 1.1, 1.7; P = 0.003), or a MHD (OR = 1.7; 95% CI: 1.1, 2.6; P = 0.007), or being a Moderna vaccine recipient (OR = 1.5; 95% CI: 1.09, 2.2; P = 0.014) were predictors of flares. Use of MMF (OR = 0.5; 95% CI: 0.3, 0.8; P = 0.009) and glucocorticoids (OR = 0.6; 95% CI: 0.5, 0.8; P = 0.003) were protective.A higher frequency of patients with AIRDs reported overall active disease post-vaccination compared with before vaccination (OR = 1.3; 95% CI: 1.1, 1.5; P < 0.001). CONCLUSION: Flares occur in nearly 1 in 10 individuals with AIRDs after COVID vaccination; people with comorbidities (especially AIDm), MHDs and those receiving the Moderna vaccine are particularly vulnerable. Future avenues include exploring flare profiles and optimizing vaccine strategies for this group.

Stimuli-Responsive Macromolecular Architecture by Butler Cyclopolymerizations: Synthesis and Applications.

This article reviews the synthesis of polyzwitterions (PZs) (poly-carboxybetaines, -phosphonobetaines, and -sulfobetaines) having multiple pH-responsive centers. The synthesis follows the Butler cyclopolymerization protocol involving a multitude of diallylammonium salts and their copolymerization with SO2 and maleic acid. The PZs have been transformed into cationic-, anionic-polyelectrolytes, and polyampholytes under the influence of pH. Particular attention is given to the application of these polymers as antiscalants, mild steel corrosion inhibitors, components in constructing Aqueous Two-Phase Systems (ATPSs), and membrane modifiers. The ATPSs could be used to separate various biomolecules, including proteins. Many amphiphilic polymers incorporating a few mol % hydrophobic monomers have shown enhanced viscosities and could be suitable for applications in oil fields. The progress of applying Butler cyclopolymerization in reversible addition-fragmentation chain transfer (RAFT) chemistry has been discussed. Future works are expected to focus on RAFT cyclopolymerization to construct block copolymers.

Comparison of simplicity, convenience, safety, and cost-effectiveness between use of insulin pen devices and disposable plastic syringes by patients with type 2 diabetes mellitus: a cross-sectional study from Bangladesh.

INTRODUCTION: Insulin pen devices and disposable plastic insulin syringes are two common tools for insulin administration. This study aims to compare the simplicity, convenience, safety, and cost-effectiveness of insulin pens versus syringe devices in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted at 14 diabetes clinics throughout Bangladesh from November 2021 to April 2022 among adults with T2DM injecting insulin by pen devices or disposable insulin syringes at least once a day for at least one year by purposive sampling. The simplicity, convenience, and safety of insulin devices were assessed using a structured questionnaire, and the study subjects were scored based on their answers; higher scores indicated a poorer response. Total scores for simplicity, convenience, and safety were obtained by adding the scores for relevant components. Their average monthly medical expense and cost of insulin therapy were recorded. The median values of the total scores and monthly expenses were compared between pen devices and disposable syringe users. RESULTS: 737 subjects were evaluated; 406 were pen users, and 331 were vial syringe users. The pen users had lower median scores for simplicity [6.0 (5.0-8.0) vs. 7.0 (5.0-9.0), p = 0.002], convenience [4.0 (3.0-6.0) vs. 5.0 (4.0-6.0), p < 0.001], and safety [7.0 (6.0-8.0) vs. 7.0 (6.0-9.0), p = 0.008] than vial syringe users. Pen devices were more expensive than vial syringes in terms of average medical expense per month [BDT 5000 (3500-7000) vs. 3000 (2000-5000), p < 0.001], the total cost of insulin therapy per month [BDT 2000 (1500-3000) vs. 1200 (800-1700), p < 0.001] and cost per unit of insulin used [BDT 2.08 (1.39-2.78) vs. 0.96 (0.64-1.39), p < 0.001]. Non-significant differences in favor of pens were observed in HbA1c levels [8.7 (7.8-10) vs. 8.9 (7.9-10)%, p = 0.607] and proportions of subjects having HbA1c < 7% (6.9 vs. 6.3%, p = 0.991). CONCLUSION: Insulin pens are simpler, more convenient, and safe but more expensive than vial syringes. Glycemic control is comparable between pen and syringe users. Long-term follow-up studies are needed to determine the clinical and economic impacts of such benefits of insulin pens.

Status of lipid control in Bangladeshi subjects with type 2 diabetes mellitus on lipid-lowering drugs: a multicenter, facility-based, cross-sectional study.

BACKGROUND: Achievement of lipid targets is crucial in patients with type 2 diabetes mellitus (T2DM) to mitigate the risk of cardiovascular diseases (CVD). Data on lipid-control status among patients with T2DM in Bangladesh are scarce. This study was conducted to determine the lipid-control status among patients with T2DM who were on lipid-lowering drugs in the country. METHODS: This cross-sectional study was conducted in the diabetes outpatient departments of several tertiary hospitals in Bangladesh from January 2022 to December 2022. Adults of both sexes diagnosed with T2DM for at least one year and were on the lipid-lowering drug(s) for a minimum of 3 months were included in the study by consecutive sampling. Patients' data were collected by face-to-face interviews, and blood samples were collected for fasting lipid profile. The lipid target was set at < 200 mg/dL for total cholesterol (TC), < 150 mg/dL for triglyceride (TG), < 100 mg/dL for low-density lipoprotein cholesterol (LDL-C), > 40 mg/dL for high-density lipoprotein cholesterol (HDL-C), and < 160 mg/dL for non-HDL cholesterol (non-HDL-C). RESULT: Three thousand sixty patients (age 44.7 ± 13.3 years, female 57%) with T2DM were evaluated. Overall, almost 81% of the study subjects achieved the LDL-C target. Besides, TC, TG, HDL-C, and non-HDL-C targets were achieved by 40.8, 21.6, 66.3, and 44.1% of patients, respectively. However, all the lipid parameters were under control in only 8.8% of patients. Almost 77.6% of the patients with ischemic heart disease, 81.5% of patients with stroke, and 65% of patients with CKD had LDL levels < 70 mg/dL. Only 10.03% achieved the HbA1c target of < 7%. 7.4% of patients achieved both HbA1c < 7% and LDL < 100 mg/dL and 5% achieved both HbA1c < 7% and LDL < 70 mg/dL. Advanced age (aOR 0.97, 95% CI 0.96, 0.98, p < 0.001), longstanding T2DM (aOR 0.53, 95% CI 0.39, 0.72, p < 0.001), and non-statin therapy (aOR 0.25, 95% CI 0.16, 0.37, p < 0.001) were negatively associated with lipid control (LDL < 100 mg/dL) while using oral hypoglycemic drugs or insulin (aOR 2.01, 95% CI 1.45, 2.77, p < 0.001) and having cardiovascular comorbidity (aOR 3.92, 95% CI 3.00, 5.12, p < 0.001) were positively associated with lipid control. CONCLUSION: Though most patients with T2DM achieved their target LDL level, the prevalence of both glycemic and overall lipid control was low in our study despite lipid-lowering therapy.

Vitamin D deficiency in pregnancy and the risk of preterm birth: a nested case-control study.

BACKGROUND: Each year, an estimated 15 million babies are born preterm. Micronutrient deficiencies, including vitamin D deficiency (VDD), are common in many low- and middle-income countries (LMICs), and these conditions are often associated with adverse pregnancy outcomes. Bangladesh experiences a high prevalence of VDD. The country also has a high preterm birth (PTB) rate. Using data from a population-based pregnancy cohort, we estimated the burden of VDD during pregnancy and its association with PTB. METHODS: Pregnant women (N = 3,000) were enrolled after ultrasound confirmation of gestational age at 8-19 weeks of gestation. Trained health workers prospectively collected phenotypic and epidemiological data at scheduled home visits. Trained phlebotomists collected maternal blood samples at enrollment and 24 -28 weeks of gestation. Aliquots of serum were stored at -800 C. We conducted a nested case-control study with all PTB (n = 262) and a random sample of term births (n = 668). The outcome, PTB, was defined as live births < 37 weeks of gestation, based on ultrasound. The main exposure was vitamin D concentrations of 24-28 weeks maternal blood samples. The analysis was adjusted for other PTB risk factors. Women were categorized as VDD (lowest quartile of 25(OH)D; < = 30.25 nmol/L) or not deficient (upper-three quartiles of 25(OH)D; > 30.25 nmol/L). We used logistic regression to determine the association of VDD with PTB, adjusting for potential confounders. RESULTS: The median and interquartile range of serum 25(OH)D was 38.0 nmol/L; 30.18 to 48.52 (nmol/L). After adjusting for co-variates, VDD was significantly associated with PTB [adjusted odds ratio (aOR) = 1.53, 95% confidence interval (CI) = 1.10 - 2.12]. The risk of PTB was also higher among women who were shorter (aOR = 1.81, 95% CI: 1.27-2.57), primiparous (aOR = 1.55, 95% CI = 1.12 - 2.12), passive smokers (aOR = 1.60, 95% CI = 1.09 - 2.34), and those who received iron supplementation during pregnancy (aOR = 1.66, 95% CI: 1.17, 2.37). CONCLUSION: VDD is common in Bangladeshi pregnant women and is associated with an increased risk of PTB.

Long-term safety of COVID vaccination in individuals with idiopathic inflammatory myopathies: results from the COVAD study.

Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic inflammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied delayed-onset vaccine adverse events (AEs) in patients with IIMs, other systemic autoimmune and inflammatory disorders (SAIDs), and healthy controls (HCs), using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated self-reporting e-survey was circulated by the COVAD study group (157 collaborators, 106 countries) from Feb-June 2022. We collected data on demographics, comorbidities, IIM/SAID details, COVID-19 history, and vaccination details. Delayed-onset (> 7 day) AEs were analyzed using regression models. A total of 15165 respondents undertook the survey, of whom 8759 responses from vaccinated individuals [median age 46 (35-58) years, 74.4% females, 45.4% Caucasians] were analyzed. Of these, 1390 (15.9%) had IIMs, 50.6% other SAIDs, and 33.5% HCs. Among IIMs, 16.3% and 10.2% patients reported minor and major AEs, respectively, and 0.72% (n = 10) required hospitalization. Notably patients with IIMs experienced fewer minor AEs than other SAIDs, though rashes were expectedly more than HCs [OR 4.0; 95% CI 2.2-7.0, p < 0.001]. IIM patients with active disease, overlap myositis, autoimmune comorbidities, and ChadOx1 nCOV-19 (Oxford/AstraZeneca) recipients reported AEs more often, while those with inclusion body myositis, and BNT162b2 (Pfizer) recipients reported fewer AEs. Vaccination is reassuringly safe in individuals with IIMs, with AEs, hospitalizations comparable to SAIDs, and largely limited to those with autoimmune multimorbidity and active disease. These observations may inform guidelines to identify high-risk patients warranting close monitoring in the post-vaccination period.

Gross total resection of spinal chondrosarcoma is associated with improved locoregional relapse-free survival and overall survival.

BACKGROUND: Spinal chondrosarcomas are rare malignant osseous tumors. The low incidence of spinal chondrosarcomas and the complexity of spine anatomy have led to heterogeneous treatment strategies with varying curative and survival rates. The goal of this study is to investigate prognostic factors for locoregional recurrence-free survival (LRFS) and overall survival (OS) comparing en bloc vs. piecemeal resection for the management of spinal chondrosarcoma. METHODS: We retrospectively identified patients who underwent curative-intent resection of primary and metastatic spinal chondrosarcoma over a 25-year period. Univariate and multivariate survival analyses were conducted with LRFS as primary endpoint and OS as secondary endpoint. LRFS and OS were modeled using the Kaplan-Meier method and assessed using Cox regression analysis. RESULTS: For 72 patients who underwent first resection, the median follow-up time was 5.1 years (95% CI 2.2-7.0). Thirty-three patients (45.8%) had en bloc resection, and 39 (54.2%) had piecemeal resection. Of the 68 patients for whom extent of resection was known, 44 patients had gross total resection (GTR) and 24 patients had subtotal resection. In survival analyses, both LRFS and OS showed statistically significant difference based on the extent of resection (p = 0.001; p = 0.04, respectively). However, only LRFS showed statistically significant difference when assessing the type of resection (p = 0.02). In addition, higher tumor grade and more invasive disease were associated with worse LRFS and OS rates. CONCLUSION: Although in our study en bloc and GTR were associated with improved survival, heterogenous and complex spinal presentations may limit total resection. Therefore, the surgical management should be tailored individually to ensure the best local control and maximum preservation of function.

Opportunities and challenges in delivering maternal and child nutrition services through public primary health care facilities in urban Bangladesh: a qualitative inquiry.

BACKGROUND: Public primary health facilities are an important source of nutrition services for the urban areas in Bangladesh. We aimed to understand the challenges and facilitators of delivering maternal and child nutrition services through public sector from the perspectives of the users and service providers. METHOD: The study was conducted in selected public primary health care facilities and their catchment area in Dhaka city from April-July 2019. We carried out 15 free listing exercises and 43 semi-structured interviews (SSI) with pregnant women and mothers of 0-24 months old children; 6 key informant interviews (KII) with facility managers and healthcare providers; and observed service delivery in 8 health facilities. RESULTS: Findings reveal that public primary health facilities address some economic and cultural barriers to access such as cost and provision of female service providers for maternal and child health services but challenges such as distance, waiting time, and cleanliness remained. In terms of service provision, there were gaps in provision of anthropometric measurement and counseling, and healthcare providers had inadequate training and therefore, knowledge of nutrition. The low priority given to nutrition services during program design hampered the delivery of nutrition services provided through urban public sector health facilities. CONCLUSIONS: There were important gaps in terms of service provision and capacity of healthcare providers, and therefore, the quality of nutrition service provided through public primary health care facilities. To maximize the coverage of quality nutrition services in the urban areas, it is important to think through the design of nutrition service delivery and allocate adequate resources to fill the material and capacity gaps.