Effects and safety of transcranial direct current stimulation on multiple health outcomes: an umbrella review of randomized clinical trials.

Transcranial direct current stimulation (tDCS), which delivers a direct current to the brain, emerged as a non-invasive potential therapeutic in treating a range of neurological and neuropsychiatric disorders. However, a comprehensive quantitative evidence synthesis on the effects of tDCS on a broad range of mental illnesses is lacking. Here, we systematically assess the certainty of the effects and safety of tDCS on several health outcomes using an umbrella review of randomized controlled trials (RCTs). The methodological quality of each included original meta-analysis was assessed by the A Measurement Tool for Assessing Systematic Reviews 2 (AMSTAR2), and the certainty of the evidence for each effect was evaluated with Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). We followed an a priori protocol (PROSPERO CRD42023458700). We identified 15 meta-analyses of RCTs (AMSTAR 2; high 3, moderate 3, and low 9) that included 282 original articles, covering 22 unique health endpoints across 22 countries and six continents. From meta-analyses of RCTs supported by very low to high certainty of evidence, it was found that tDCS improved symptoms related to post-stroke, including post-stroke depression scale score (equivalent standardized mean difference [eSMD], 1.61 [95% confidence level, 0.72-2.50]; GRADE=moderate), activities of daily living independence (7.04 [3.41-10.67]; GRADE=high), motor recovery of upper and lower extremity (upper extremity: 0.15 [0.06-0.24], GRADE=high; lower extremity: 0.10 [0.03-0.16], GRADE=high), swallowing performance (GRADE=low), and spasticity (GRADE=moderate). In addition, tDCS had treatment effects on symptoms of several neurological and neuropsychiatric disorders, including obsessive-compulsive disorder (0.81 [0.44-1.18]; GRADE=high), pain in fibromyalgia (GRADE=low), disease of consciousness (GRADE=low), insight score (GRADE=moderate) and working memory (0.34 [0.01-0.67]; GRADE=high) in schizophrenia, migraine-related pain (-1.52 [-2.91 to -0.13]; GRADE=high), attention-deficit/hyperactivity disorder (reduction in overall symptom severity: 0.24 [0.04-0.45], GRADE=low; reduction in inattention: 0.56 [0.02-1.11], GRADE=low; reduction in impulsivity: 0.28 [0.04-0.51], GRADE=low), depression (GRADE=low), cerebellar ataxia (GRADE=low), and pain (GRADE=very low). Importantly, tDCS induced an increased number of reported cases of treatment-emergent mania or hypomania (0.88 [0.62-1.13]; GRADE=moderate). We found varied levels of evidence for the effects of tDCS with multiple neurological and neuropsychiatric conditions, from very low to high certainty of evidence. tDCS was effective for people with stroke, obsessive-compulsive disorder, fibromyalgia, disease of consciousness, schizophrenia, migraine, attention-deficit/hyperactivity disorder, depression, cerebellar ataxia, and pain. Therefore, these findings suggest the benefit of tDCS for several neurological and neuropsychiatric disorders; however, further studies are needed to understand the underlying mechanism and optimize its therapeutic potential.

Association between high levels of nitrogen dioxide and increased cumulative incidence of lung cancer in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Lung cancer is a fatal complication of idiopathic pulmonary fibrosis (IPF) with a poor prognosis. However, the association between individual exposure to air pollutants and lung cancer development in patients with IPF is unknown. This study aimed to assess the effect of individual exposure to nitrogen dioxide (NO2) on lung cancer development in patients with IPF. METHODS: We enrolled 1085 patients from an IPF cohort in the Republic of Korea (mean age 65.6 years, males 80.6%). We estimated individual-level long-term exposures to NO2 at the patients' residential addresses using a national-scale exposure prediction model based on data from air quality regulatory monitoring stations. To evaluate the association between NO2 levels and lung cancer development in IPF, we used an individual- and area-level covariates adjusted model as our primary model. RESULTS: The estimated average annual NO2 concentration was 23.1 ppb. During a median follow-up of 4.3 years, 86 patients (7.9%) developed lung cancer. NO2 concentration was associated with lung cancer development in an unadjusted model (HR 1.219; p=0.042), while a marginal association was found in the primary model (HR 1.280; p=0.084). When NO2 concentration was stratified by the median value (21.0 ppb), exposure to high NO2 levels (≥21.0 ppb) was associated with a 2.0-fold increase in the risk of lung cancer development (HR 2.023; p=0.047) in the primary model. CONCLUSION: Individual exposure to high NO2 levels may increase the risk of lung cancer development in patients with IPF.

National Trends in Allergic Rhinitis and Chronic Rhinosinusitis and COVID-19 Pandemic-Related Factors in South Korea, from 1998 to 2021.

INTRODUCTION: Existing studies provide insights into the prevalence and environmental factors associated with allergic rhinitis (AR) and chronic rhinosinusitis (CRS) globally. However, limitations still persist in these studies, particularly regarding cohort sizes and the duration of follow-up periods, indicating a need for more comprehensive and long-term research in these fields. Our study aimed to investigate the prevalence, long-term trends, and underlying factors of these conditions in the general population of adult participants (≥19 years) in Korea. METHOD: We analyzed data from adult participants (≥19 years) from the Korea National Health and Nutrition Examination Survey (KNHANES) study to determine the prevalence of AR and CRS from 1998 to 2021. To analyze prevalence trends before and during the COVID-19 pandemic, we employed a weighted linear regression model and obtained ß-coefficients with 95% confidence intervals (CI). RESULTS: Between 1998 and 2021, over a span of 24 years, the comprehensive KNHANES study included 146,264 adult participants (mean age: 47.80 years, standard deviation: 16.49 years; 66,177, 49.3% men). The prevalence of AR and CRS increased from 1998 to 2021, with AR prevalence rising from 5.84% (95% CI, 5.57-6.10) in 1998-2005 to 8.99% (8.09-9.91) in 2021 and CRS from 1.84% (1.70-1.97) in 1998-2005 to 3.70% (3.18-4.23) in 2021. However, the increasing trend has slowed down during the COVID-19 pandemic era. CONCLUSIONS: The significance of continuous monitoring and focused interventions for AR and CRS is underscored by this study. The observed deceleration in the rising prevalence of AR and CRS during the pandemic indicates the possibility of beneficial impacts from lifestyle modifications triggered by the pandemic. These findings call for additional research to explore potential protective effects in greater depth.

National Trends and Prevalence of Atopic Dermatitis and Pandemic-Related Factors among Korean Adults, 2007-2021.

INTRODUCTION: Previous studies have variably reported inconclusive trends in the prevalence of atopic dermatitis (AD) among adults, and there are limited data on the impact of the COVID-19 pandemic. We aimed to investigate the national trends and age-stratified prevalence of AD among adults from 2007 to 2021 in South Korea, focusing mainly on the impact of the COVID-19 pandemic-related factors. METHODS: A nationwide cross-sectional study was conducted using the Korea National Health and Nutrition Examination Survey data from 2007 to 2021. Overall and age-stratified prevalence for AD were assessed using weighted beta coefficients or odds ratios. RESULTS: A total of 83,566 adults over 20 years (male, 49.40%) were included. During the observation period, the prevalence of AD was stable in the overall population from 2.61% (95% CI, 2.29-2.93) in 2007-2009 to 2.15% (1.68-2.63) in 2020 and 2.38% (1.81-2.95) in 2021. However, the weighted prevalence of AD in adults aged 40-59 years old decreased during the pre-pandemic era, and the prevalence of AD in adults aged above 60 years significantly decreased during the pandemic, with a significant decline observed after the initial outbreak. From age-stratification analysis, the adults aged 40-59 years showed a significant increase after the pandemic outbreak which was evident in specific variables: individuals with rural residence, lower education, and lower household income quartiles. Adults aged above 60 years showed a significant decrease in the slope after the outbreak, evident in specific variables: individuals of female, rural residence, lower education, and lower household income quartiles. CONCLUSION: We observed a stable overall prevalence of AD throughout the 15-year observation period. However, the age-stratified analysis suggested significantly different trends according to age-stratified groups and the impact of the COVID-19 pandemic on the prevalence of AD.

Effects of ambient air pollution on brain cortical thickness and subcortical volume: A longitudinal neuroimaging study.

INTRODUCTION: Long-term exposure to air pollutants is associated with an increased risk of Alzheimer's disease and mild cognitive impairment. Therefore, we investigated the association between long-term air pollution exposure and changes in neuroimaging markers. METHODS: In this longitudinal study, we studied a prospective cohort of 361 adults residing in four cities in the Republic of Korea. Long-term concentrations of particulate matter with aerodynamic diameters of ≤10 µm (PM10) and ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2) at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images at baseline (August 2014 to March 2017) and at the 3-year follow-up (until September 2020). Linear mixed-effects models were used, adjusting for covariates. RESULTS: A 10-µg/m3 increase in PM10 was associated with reduced whole-brain mean (ß= -0.45, standard error (SE)= 0.10, P< 0.001), frontal (ß= -0.53, SE= 0.11; P< 0.001) and temporal thicknesses (ß= -0.37, SE= 0.12; P= 0.002). A 10-ppb increase in NO2 was associated with a decline in the whole brain mean cortical thickness (ß= -0.23, SE= 0.05; P< 0.001), frontal (ß= -0.25, SE= 0.05; P< 0.001), parietal (ß= -0.12, SE= 0.05; P= 0.025), and temporal thicknesses (ß= -0.19, SE= 0.06; P= 0.001). Subcortical structures associated with air pollutants include the thalamus volume. CONCLUSIONS: Long-term exposure to PM10 and NO2 may lead to cortical thinning in adults.

Clinical and laboratory findings in scrub typhus associated Guillain-Barré syndrome in South Korea.

BACKGROUND AND AIMS: Scrub typhus is an endemic disease in the fall season that occurs in a limited number of places known as the Tsutsugamushi Triangle. Peripheral neuropathy is a common complication of scrub typhus. Herein, we encountered several patients with ascending paralysis after scrub typhus infection, who were diagnosed with Guillain-Barré syndrome (GBS). We aimed to investigate the clinical and laboratory characteristics of patients who developed GBS after scrub typhus. METHODS: Patients were retrospectively recruited from six nationwide tertiary centers in South Korea from January 2017 to December 2021. Patients who had been clinically diagnosed with GBS and confirmed to have scrub typhus via laboratory examination and/or the presence of an eschar before the onset of acute limb paralysis were included. The GBS-associated clinical and electrophysiological characteristics, outcomes, and scrub typhus-associated features were collected. RESULTS: Of the seven enrolled patients, six were female and one was male. The median time from scrub typhus infection to the onset of limb weakness was 6 (range: 2-14) days. All patients had eschar on their bodies. Four patients (57.1%) were admitted to the intensive care unit and received artificial ventilation for respiratory distress. At 6 months, the median GBS disability score was 2 (range, 1-4) points. INTERPRETATION: Patients with scrub typhus-associated GBS have a severe clinical presentation and require intensive treatment with additional immunotherapies. Therefore, GBS should be included in the differential diagnosis when peripheral neuropathies develop during scrub typhus treatment. Notably, scrub typhus is associated to GBS.

Global association of secondhand smoke exposure locations and smoking behaviour among adolescents in 99 countries.

AIM: This study classified 99 countries into four income groups and then analysed the impact of secondhand smoke (SHS) exposure at home, in public places and at school, on current cigarette smoking prevalence. METHODS: We utilised data from the WHO Global Youth Tobacco Survey and a meta-analysis was conducted to evaluate the prevalence and weighted odds ratios (wORs) of adolescent smoking behaviour and SHS exposure locations. RESULTS: Both smoking behaviours increased with higher national income levels. Smoking behaviours in high and upper-middle-income countries (HICs and UMICs) exhibited an association with SHS exposure in public places (HIC: wOR, 3.50 [95% CI, 2.85-4.31]; UMIC: wOR, 2.90 [2.60-3.23]) compared to home. Low- and lower-middle-income countries (LICs and LMICs) showed an association with SHS exposure in the home (LIC: wOR, 5.33 [3.59-7.93]; LMIC: wOR, 2.71 [2.33-3.17]) than public places. The association between current cigarette smoking and SHS exposure at home increased with lower income levels, while anticipated future use of any form of tobacco with SHS exposure in public places rose in lower income countries. CONCLUSIONS: Targeted interventions based on income levels are essential, emphasising home strategies in lower income countries and public place efforts in higher income countries.

Effects of Hormone Replacement Therapy on Bone Mineral Density in Korean Adults With Turner Syndrome.

BACKGROUND: Turner syndrome (TS) is a common chromosomal abnormality, which is caused by loss of all or part of one X chromosome. Hormone replacement therapy in TS is important in terms of puberty, growth and prevention of osteoporosis however, such a study has never been conducted in Korea. Therefore, the purpose of our study was to determine relationship between the starting age, duration of estrogen replacement therapy (ERT) in TS and develop a hormone replacement protocol suitable for the situation in Korea. METHODS: This is retrospective study analyzed the medical records in TS patients treated at the Severance hospital, Yonsei University College of Medicine, Seoul, Korea from 1997 to 2019. Total of 188 subjects who had received a bone density test at least once were included in the study. Korean National Health and Nutrition Examination Survey (KNHANES) was used for achieving bone mineral density (BMD) of normal control group. Student's t-test, Mann-Whitney U test, ANOVA and correlation analysis were performed using SPSS 18.0. RESULTS: Each BMD measurement was significantly lower in women with TS than in healthy Korean women. Early start and longer duration of ERT is associated with higher lumbar spine BMD but not femur neck BMD. Femur neck BMD, but not lumbar spine BMD was significantly higher in women with mosaicism than 45XO group. CONCLUSION: Early onset and appropriate duration of hormone replacement therapy is important for increasing bone mineral density in patients with Turner syndrome. Also, ERT affects differently to TS patients according to mosaicism.

Cervical enamel projections from a periodontal perspective: A scoping review.

Cervical enamel projections (CEPs) represent a unique developmental and anatomical anomaly wherein the enamel structure extends apically beyond the cemento-enamel junction of the tooth. In this scoping review, the existing literature on CEPs was evaluated to delineate their characteristics, prevalence, predilection for specific teeth and surfaces, clinical significance, and management approaches. Searches were conducted on MEDLINE (PubMed), Cochrane Library, and Embase databases using the keywords "enamel projection(s)" or "ectopic enamel." In total, 24 studies meeting inclusion criteria were included in the review. The prevalence of CEPs varied widely (8.3%-85.1%), predominantly manifesting as grade I or grade III. Mandibular first and second molars exhibited a higher incidence of CEPs, with a notable predilection for buccal surfaces. The consensus in most studies was that CEPs are associated with localized periodontal diseases. Recommendations inclined toward the removal of ectopic enamel during periodontal surgery to enhance periodontal attachment formation. However, decision-making should involve careful consideration of the benefits and drawbacks based on individual circumstances.

Successful interventional occlusion of muscular ventricular septal defect in a dog.

Ventricular septal defect (VSD) is a rare congenital heart disease in dogs. Hemodynamically important interventricular defects must be closed to improve the prognosis. This case report describes successful interventional transcatheter closure of a muscular VSD in a young Maltese and poodle mixed-breed dog with a large muscular interventricular defect (~5 mm in diameter) with a high rate of left-to-right shunt flow. The VSD was closed with a customized Amplatzer-type VSD occluder via a percutaneous transvenous (jugular) approach. We concluded that interventional occlusion of a muscular VSD with an Amplatzer-type occluder is a viable treatment option for dogs. A regular follow-up study for this dog is ongoing and has not detected complications. Key clinical message: Interventional occlusion of a muscular VSD with an Amplatzer-type occluder is a viable treatment option for dogs.

Occlusion interventionnelle réussie d'une communication interventriculaire musculaire chez un chien. La communication interventriculaire (VSD) est une maladie cardiaque congénitale rare chez le chien. Les anomalies interventriculaires hémodynamiquement importantes doivent être fermées pour améliorer le pronostic. Ce rapport de cas décrit la fermeture interventionnelle réussie par cathéter d'un VSD musculaire chez un jeune chien de race mixte (maltais et caniche) présentant un défaut interventriculaire musculaire important (~5 mm de diamètre) avec un débit de shunt élevé de gauche à droite. Le VSD a été fermé avec un obturateur VSD personnalisé de type Amplatzer via une approche trans-veineuse percutanée (jugulaire). Nous avons conclu que l'occlusion interventionnelle d'un VSD musculaire avec un obturateur de type Amplatzer est une option de traitement viable pour les chiens. Une étude de suivi régulière de ce chien est en cours et aucune complication n'a été détectée.Message clinique clé :L'occlusion interventionnelle d'un VSD musculaire avec un obturateur de type Amplatzer est une option de traitement viable pour les chiens.(Traduit par Dr Serge Messier).

Novel rAAV vector mediated intrathecal HGF delivery has an impact on neuroimmune modulation in the ALS motor cortex with TDP-43 pathology.

Recombinant adeno-associated virus (rAAV)-based gene therapies offer an immense opportunity for rare diseases, such as amyotrophic lateral sclerosis (ALS), which is defined by the loss of the upper and the lower motor neurons. Here, we describe generation, characterization, and utilization of a novel vector system, which enables expression of the active form of hepatocyte growth factor (HGF) under EF-1α promoter with bovine growth hormone (bGH) poly(A) sequence and is effective with intrathecal injections. HGF's role in promoting motor neuron survival had been vastly reported. Therefore, we investigated whether intrathecal delivery of HGF would have an impact on one of the most common pathologies of ALS: the TDP-43 pathology. Increased astrogliosis, microgliosis and progressive upper motor neuron loss are important consequences of ALS in the motor cortex with TDP-43 pathology. We find that cortex can be modulated via intrathecal injection, and that expression of HGF reduces astrogliosis, microgliosis in the motor cortex, and help restore ongoing UMN degeneration. Our findings not only introduce a novel viral vector for the treatment of ALS, but also demonstrate modulation of motor cortex by intrathecal viral delivery, and that HGF treatment is effective in reducing astrogliosis and microgliosis in the motor cortex of ALS with TDP-43 pathology.

Export of Diverse and Bioactive Small Proteins through a Type I Secretion System.

Small proteins perform a diverse array of functions, from microbial competition, to endocrine signaling, to building biomaterials. Microbial systems that can produce recombinant small proteins enable discovery of new effectors, exploration of sequence activity relationships, and have the potential for in vivo delivery. However, we lack simple systems for controlling small-protein secretion from Gram-negative bacteria. Microcins are small-protein antibiotics secreted by Gram-negative bacteria that inhibit the growth of neighboring microbes. They are exported from the cytosol to the environment in a one-step process through a specific class of type I secretion systems (T1SSs). However, relatively little is known about substrate requirements for small proteins exported through microcin T1SSs. Here, we investigate the prototypic microcin V T1SS from Escherichia coli and show that it can export a remarkably wide range of natural and synthetic small proteins. We demonstrate that secretion is largely independent of the cargo protein's chemical properties and appears to be constrained only by protein length. We show that a varied range of bioactive sequences, including an antibacterial protein, a microbial signaling factor, a protease inhibitor, and a human hormone, can all be secreted and elicit their intended biological effect. Secretion through this system is not limited to E. coli, and we demonstrate its function in additional Gram-negative species that can inhabit the gastrointestinal tract. Our findings uncover the highly promiscuous nature of small-protein export through the microcin V T1SS, which has implications for native-cargo capacity and the use of this system in Gram-negative bacteria for small-protein research and delivery. IMPORTANCE Type I secretion systems for microcin export in Gram-negative bacteria transport small antibacterial proteins from the cytoplasm to the extracellular environment in a single step. In nature, each secretion system is generally paired with a specific small protein. We know little about the export capacity of these transporters and how cargo sequence influences secretion. Here, we investigate the microcin V type I system. Remarkably, our studies show that this system can export small proteins of diverse sequence composition and is only limited by protein length. Furthermore, we demonstrate that a wide range of bioactive small proteins can be secreted and that this system can be used in Gram-negative species that colonize the gastrointestinal tract. These findings expand our understanding of secretion through type I systems and their potential uses in a variety of small-protein applications.

Comparison of clinical manifestations in mpox patients living with HIV versus without HIV: A systematic review and meta-analysis.

Currently, many cases of mpox patients living with the human immunodeficiency virus (HIV) have been reported. Immunocompromised mpox patients, including those living with HIV are noted for an increased risk for severe symptoms; however, existing studies did not focus on the statistical comparison of mpox outcomes associated with HIV. Thus, we conducted a systematic review and meta-analysis to evaluate and compare the clinical manifestations of mpox in people living with HIV (PLWH) and people without HIV. In this systematic review and meta-analysis, PubMed/MEDLINE, Embase, and Google Scholar were searched up to March 7, 2023. A random effects model was used to calculate the pooled prevalence along with the 95% confidence intervals (CI), and the odds ratio and its corresponding 95% CIs were calculated to elucidate the significance of each clinical feature for mpox patients with and without HIV. In this study, we included 99 published papers with 2413 patients with mpox (median age, 35.5 years; PLWH n = 1151) from 27 countries across six continents. The odds ratio of the mpox outcomes with PLWH in comparison to patients without HIV was found to be significant for skin rash (1.24, 95% CI: 1.01-1.53), proctitis (2.03, 95% CI: 1.36-3.04), cough (0.57, 95% CI: 0.33-0.98), and diarrhea (3.85, 95% CI: 1.24-11.98). The odds ratio of mpox patients with HIV for historical infections of syphilis was 2.14 (95% CI: 1.38-3.32), compared with those without HIV. This is the first international and comprehensive study that performed a systematic review and meta-analysis to statistically measure mpox manifestations according to HIV status. As clinical features related to mucosal contact were characteristically pronounced in PLWH, our systematic review provides insight that the primary invasion site of infection strongly relates to the outcomes of mpox.

ITC-6102RO, a novel B7-H3 antibody-drug conjugate, exhibits potent therapeutic effects against B7-H3 expressing solid tumors.

BACKGROUND: The B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors. METHODS: In this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo. RESULTS: ITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues. CONCLUSIONS: Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.

Early rituximab treatment reduces long-term disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD. METHODS: This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis. RESULTS: In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment. CONCLUSIONS: Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.

Barriers against and strategies for malaria control during the COVID-19 pandemic in low- and middle-income countries: a systematic review.

BACKGROUND: The COVID-19 pandemic has disrupted malaria control activities globally. Notably, high levels of excess malaria morbidity and mortality in low- and middle-income countries (LMICs) were reported. Although it is crucial to systematically understand the main causes of the disruption to malaria control and synthesize strategies to prepare for future pandemics, such studies are scarce. Therefore, this study aims to better identify barriers against and strategies for malaria control. METHODS: Following the PRISMA guidelines and through searches of electronic databases and Google Scholar, a systematic literature review was conducted to identify studies pertaining to malaria control published between January 2020 and December 2021. Only studies that discussed reported barriers and/or strategies related to malaria were included for the review. The Mixed Methods Quality Appraisal Tool (MMAT) and the Authority, Accuracy, Coverage, Objectivity, Date and Significance (AACODS) checklist were used for quality appraisal. Key information such as literature type, study design, setting and population, interventions, outcomes, barriers, and strategies were extracted. With an existing framework of four dimensions (accessibility, affordability, availability, and acceptability) further subdivided by the supply and demand sides, this study synthesized information on barriers and strategies related to malaria control and further categorized the strategies based on the time frame. RESULTS: From the 30 selected studies, 27 barriers and 39 strategies were identified. The lockdown measures, which mainly threatened geographic accessibility and availability of malaria control services, were identified to be the main barrier hindering effective mobilization of community health workers and resources. Among the identified strategies, clear risk communication strategies would alleviate psychosocial barriers, which challenged acceptability. Some strategies that cross-cut points across all four dimensions would, require systems-level integration to enhance availability and affordability of malaria control. The strategies were distinguished between short-term, for instant response, and mid to long-term for future readiness. CONCLUSIONS: The pandemic resulted in complex barriers to malaria control, particularly imposing a double burden on LMICs. Identifying strategies to overcome said barriers provides useful insights in the decision-making processes for the current and future pandemic. Cross-cutting strategies that integrate all dimensions need to be considered. Health system strengthening and resilience strategy appropriate for country-specific context is fundamental.

The association between cognition and gait disturbance in central nervous system demyelinating disorder with mild disability.

INTRODUCTION: Gait disturbance in central nervous system (CNS) demyelinating disorders, including multiple sclerosis (MS) and neuromyelitis optica (NMO) is one of the most troublesome problems that has a direct impact on the quality of life. However, the associations between gait disturbance and other clinical variables of these two diseases have not been fully elucidated. OBJECTIVE: This study aimed to evaluate gait disturbance using a computerized gait analysis system and its association with various clinical variables in patients with MS and NMO. METHODS: A total of 33 patients (14 with MS and 19 with NMO) with minor disabilities, who were able to walk independently and had passed their acute phase, were enrolled in the study. Gait analysis were performed using a computer-based instrumented walkway system. (Walk-way MG-1000, Anima, Japan) Clinical variables, such as disease duration, medication, body mass index (BMI), hand grip power, and muscle mass were recorded. The Montreal Cognitive Assessment (MOCA), Beck Depression Inventory score-II (BDI), and fatigue scale were measured using the Functional Assessment of Chronic Illness Therapy-fatigue scale (FACIT-fatigue) scale. A trained neurologist scored the Expanded Disability Status Scale (EDSS). RESULTS: Gait speed was the single parameter that showed a significant positive correlation with MOCA (p < 0.001). The stance phase time was the single parameter that showed a significant negative correlation with EDSS (p < 0.001). Hand grip strength showed a significant positive correlation with skeletal muscle mass as assessed by bioimpedance analysis (p < 0.05). The FACIT-fatigue scale score showed a significant negative correlation with the BDI (p < 0.001). CONCLUSION: In our patients with MS/NMO with mild disability, cognitive impairment was significantly correlated with gait speed, and the degree of disability was significantly correlated with stance phase time. Our findings may imply that early detection of a decrease in gait speed and an increase in stance phase time can predict the progression of cognitive impairment in patients with MS/NMO with mild disability.

Exposure assessment for air pollution epidemiology: A scoping review of emerging monitoring platforms and designs.

BACKGROUND: Both exposure monitoring and exposure prediction have played key roles in assessing individual-level long-term exposure to air pollutants and their associations with human health. While there have been notable advances in exposure prediction methods, improvements in monitoring designs are also necessary, particularly given new monitoring paradigms leveraging low-cost sensors and mobile platforms. OBJECTIVES: We aim to provide a conceptual summary of novel monitoring designs for air pollution cohort studies that leverage new paradigms and technologies, to investigate their characteristics in real-world examples, and to offer practical guidance to future studies. METHODS: We propose a conceptual summary that focuses on two overarching types of monitoring designs, mobile and non-mobile, as well as their subtypes. We define mobile designs as monitoring from a moving platform, and non-mobile designs as stationary monitoring from permanent or temporary locations. We only consider non-mobile studies with cost-effective sampling devices. Then we discuss similarities and differences across previous studies with respect to spatial and temporal representation, data comparability between design classes, and the data leveraged for model development. Finally, we provide specific suggestions for future monitoring designs. RESULTS: Most mobile and non-mobile monitoring studies selected monitoring sites based on land use instead of residential locations, and deployed monitors over limited time periods. Some studies applied multiple design and/or sub-design classes to the same area, time period, or instrumentation, to allow comparison. Even fewer studies leveraged monitoring data from different designs to improve exposure assessment by capitalizing on different strengths. In order to maximize the benefit of new monitoring technologies, future studies should adopt monitoring designs that prioritize residence-based site selection with comprehensive temporal coverage and leverage data from different designs for model development in the presence of good data compatibility. DISCUSSION: Our conceptual overview provides practical guidance on novel exposure assessment monitoring for epidemiological applications.

Role of geographic characteristics in the spatial cluster detection of cancer: Evidence in South Korea, 1999-2013.

BACKGROUND: Identification of high-risk areas of cancer, referred to as spatial clusters, can inform targeted policies for cancer control. Although cancer cluster detection could be affected by various geographic characteristics including sociodemographic and environmental factors which impacts could also vary over time, studies accounting for such influence remain limited. This study aims to assess the role of geographic characteristics in the spatial cluster detection for lung and stomach cancer over an extended period. METHODS: We obtained sex-specific age-standardized incidence and mortality rates of lung and stomach cancer as well as geographic characteristics across 233 districts in South Korea for three five-year periods between 1999 and 2013. We classified geographic characteristics of each district into four categories: demography, socioeconomic status, behaviors, and physical environments. Specifically, we quantified physical environments using measures of greenness, concentrations of particulate matter and nitrogen dioxide, and air pollution emissions. Finally, we conducted cluster detection analyses using weighted normal spatial scan statistics with the residuals from multiple regression analyses performed with the four progressive sets of geographic attributes. RESULTS: We found that the size of clusters reduced as we progressively adjusted for geographic covariates. Among the four categories, physical environments had the greatest impact on the reduction or disappearance of clusters particularly for lung cancer consistently over time. Whereas older population affected a decrease of lung cancer clusters in the early period, the contribution of education was large in the recent period. The impact was less clear in stomach cancer than lung cancer. CONCLUSION: Our findings highlight the importance of geographic characteristics in explaining the existing cancer clusters and identifying new clusters, which jointly provides practical guidance to cancer control.

Nitrogen dioxide increases the risk of disease progression in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Air pollution affects clinical course and prognosis of idiopathic pulmonary fibrosis (IPF). However, the effect of individual exposure to air pollutants on disease progression is unclear. We aimed to identify the effect of individual exposure to nitrogen dioxide (NO2 ) and particulate matter (aerodynamic diameter ≤ 10 µm [PM10 ]) on disease progression in patients with IPF. METHODS: The serial lung function data of 946 IPF patients (mean age: 65.4 years, male: 80.9%) were analysed. Individual-level long-term exposures to NO2 and PM10 at the residential addresses of patients were estimated using a national-scale exposure prediction model, constructed based on air quality regulatory monitoring data. Progression was defined as a relative decline (≥10%) in forced vital capacity. Individual- and area-level covariates were adjusted in the primary analysis model. RESULTS: Overall, 547 patients (57.8%) experienced progression during a median follow-up of 1.0 year (interquartile range: 0.4-2.6 years). In the primary model, a 10-ppb increase in NO2 concentration was associated with a 10.5% increase in the risk of progression (hazard ratio [HR] = 1.105; 95% CI = 1.000-1.219) in patients with IPF. There was also an increasing trend of progression in patients with IPF according to the second to fourth quartiles of NO2 (Q2 [HR = 1.299; 95% CI = 0.972-1.735], Q3 [1.409; 1.001-1.984], Q4 [1.598; 1.106-2.310]) compared to the first quartile. We found no association between PM10 and progression in IPF patients. CONCLUSION: Our data suggest that increased individual exposure to NO2 can increase the risk of progression in patients with IPF.