Search

Background: Despite the proven effectiveness of oral antivirals against severe acute respiratory syndrome coronavirus 2 in randomized trials, their clinical reevaluation is vital in the context of widespread immunity and milder prevalent variants. This study aimed to assess the effectiveness of oral antivirals for coronavirus disease 2019 (COVID-19)., Methods: This retrospective cohort study utilized a target trial emulation framework to analyze patients with COVID-19 aged 60+ from January to December 2022. Data were obtained from the Korea Disease Control and Prevention Agency and Health Insurance Review and Assessment Service. The study involved 957,036 patients treated with nirmatrelvir/ritonavir and 243,360 treated with molnupiravir, each compared with the matched control groups. Primary outcome was progression to critical COVID-19 requiring advanced respiratory support. Secondary outcomes included progression to severe COVID-19, need for supplemental oxygen, and death within 30 days of the onset of COVID-19. Number needed to treat (NNT) derived from the absolute risk reduction., Results: Nirmatrelvir/ritonavir was significantly associated with a reduced risk of severe (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.803-0.843), critical (aOR, 0.560; 95% CI, 0.503-0.624), and fatal COVID-19 (aOR, 0.694; 95% CI, 0.647-0.744). Similarly, molnupiravir reduced the risk of severe (aOR, 0.895; 95% CI, 0.856-0.937), critical (aOR, 0.672; 95% CI, 0.559-0.807), and fatal cases (aOR, 0.679; 95% CI, 0.592-0.779). NNTs for nirmatrelvir/ritonavir were 203.71 (severe), 1,230.12 (critical), and 691.50 (death); for molnupiravir, they were 352.70 (severe), 1,398.62 (critical), and 862.98 (death). Higher effectiveness was associated with older adults, unvaccinated individuals, and the late pandemic phase., Conclusion: Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

There had been concerns about the acute complications during or shortly after coronavirus disease 2019 (COVID-19) treatment with nirmatrelvir/ritonavir (NMVr) and molnupiravir (MOL). This study aimed to compare the risks of selected acute safety events in patients treated with or without NMVr or MOL using the COVID-19 oral treatment safety assessment data, constructed through the linkage of nationwide databases: National COVID-19 registry, Real-time Prescription Surveillance, and National Health Insurance data. We identified all adults diagnosed with COVID-19 between January and November 2022, and then constructed two cohorts by matching up to four patients without antiviral treatment records to NMVr or MOL users using propensity score matching. Outcomes of interest were incident-selected cardiac (i.e., atrial fibrillation, other arrhythmia, bradycardia), neurological (i.e., seizure, neuropathy, encephalomyelitis), and miscellaneous (i.e., acute pancreatitis, acute liver injury, dysgeusia) events. A total of 739,935 NMVr users were matched with 2,951,690 comparators and 150,431 MOL users with 759,521 comparators. NMVr users were at lower risk for developing selected cardiac events (hazard ratio 0.74 [95% CI 0.65-0.87] for atrial fibrillation, 0.81 [0.65-0.99] for other arrhythmia, and 0.82 [0.70-0.96] for bradycardia) and dysgeusia (0.58 [0.45-0.74]). For MOL users, the risk was lower for atrial fibrillation (0.72 [0.53-0.96]) and dysgeusia (0.34 [0.18-0.65]). Overall, there were no increased risks of acute complications during and shortly after treatment with oral COVID-19 antivirals. Rather, the findings underscore their effectiveness in attenuating the risk of potential acute sequelae of COVID-19., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Asthma is a widespread pediatric chronic disease, but there is limited understanding of its impact on participation (other than physical activity) and the conceptualization of participation. We conducted a scoping review to explore the evidence on the relationship between pediatric asthma and participation in several domains of occupation outlined in the Occupational Therapy Practice Framework 4th Edition. A structured literature search was implemented in PubMed/MEDLINE, Elsevier EMBASE, CINAHL, SCOPUS, Clarivate Web of Science Core Collection, and APA PsycINFO. Data were extracted by occupational domain and analyzed using a stoplight categorization. Of the 3444 identified articles, 10 met inclusion criteria, five of which were categorized as green (addressing specific occupational activities). No article explicitly defined participation. Asthma's influence on nonphysical activity occupations remains unclear. Future research must clarify both the meaning and measures that best capture participation, and further explore the relationship between asthma and participation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Occupational therapists address physical environments, which can improve outcomes for youth with asthma, a prevalent chronic childhood illness. This study examines pediatric occupational therapists' perceptions of their role supporting youth with asthma, perceived usability of an occupational therapy asthma home assessment, and the impact of asthma on participation. A cross-sectional exploratory survey of 171 participants found that despite lack of tools for asthma trigger reduction assessment and intervention, therapists believe it is within their scope of practice and that they would benefit from an occupational therapy-based asthma tool. Occupational therapists should be members of multidisciplinary asthma teams, and assess and address environmental triggers.

An Electron Cyclotron Emission (ECE) modeling code has been developed to model ECE radiation with an arbitrary electron momentum distribution, a small oblique angle, both ordinary (O-mode) and extraordinary polarizations (X-mode), and multiple cyclotron frequency harmonics. The emission and absorption coefficients are calculated using the Poynting theorem from the cold plasma dispersion and the electron-microwave interaction from the full anti-Hermitian tensor. The modeling shows several ECE radiation signatures that can be used to diagnose the population of suprathermal electrons in a tokamak. First, in an n = 2 X-mode (X2) optically thick plasma and oblique ECE view, the modeling shows that only suprathermal electrons, which reside in a finite region of the velocity and space domains, can effectively generate cyclotron emissions to the ECE receiver. The code also finds that the O1 mode is sensitive to suprathermal electrons of both a high v⊥ and v‖, while the X2 mode is dominantly sensitive to suprathermal electrons of a high v⊥. The modeling shows that an oblique ECE system with both X/O polarization and a broad frequency coverage can be used to effectively yield information of the suprathermal electron population in a tokamak., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: This study was conducted to assess the efficacy of nirmatrelvir/ritonavir treatment in patients with coronavirus disease 2019 (COVID-19), particularly those aged 60 years and older. Using real-world data, the period during which the BN.1 Omicron variant was dominant was compared to the period dominated by the BA.5 variant., Methods: In this retrospective cohort study, data were collected regarding 2,665,281 patients infected with severe acute respiratory syndrome coronavirus 2 between July 24, 2022, and March 31, 2023. Propensity score matching was utilized to match patients who received nirmatrelvir/ ritonavir in a 1:4 ratio between BN.1 and BA.5 variant groups. Multivariable logistic regression analysis was employed to assess the effects of nirmatrelvir/ritonavir within these groups., Results: Compared to the prior period, the efficacy of nirmatrelvir/ritonavir did not significantly differ during the interval of Omicron BN.1 variant dominance in the Republic of Korea. Among patients treated with nirmatrelvir/ritonavir, a significantly lower risk of mortality was observed in the BN.1 group (odds ratio [OR], 0.698; 95% confidence interval [CI], 0.557-0.875) compared to the BA.5 group. However, this treatment did not significantly reduce the risk of severe or critical illness, including death, for those in the BN.1 group (OR, 0.856; 95% CI, 0.728-1.007)., Conclusion: Nirmatrelvir/ritonavir has maintained its effectiveness against COVID-19, even with the emergence of the BN.1 Omicron subvariant. Consequently, we strongly recommend the administration of nirmatrelvir/ritonavir to patients exhibiting COVID-19-related symptoms, irrespective of the dominant Omicron variant or their vaccination status, to mitigate disease severity and decrease the risk of mortality.

Background: COVID-19 remains an ongoing public health crisis. Black Americans remain underrepresented among those vaccinated and overrepresented in both COVID-19 morbidity and mortality. Medical misinformation, specifically related to COVID-19, has exacerbated the impact of the disease in Black American communities. Communication tools and strategies to build relationships and disseminate credible and trustworthy diagnostic and preventative health information are necessary to improve outcomes and equity for historically oppressed populations., Objective: As the initial phase of a larger mixed methods project to develop, pilot, and evaluate a mobile health (mHealth) intervention among a population at high risk for COVID-19 and cardiovascular comorbidities, this study sought to explore COVID-19 information behavior among Black Americans. Specifically, this study examined (1) preferences for COVID-19 education via mHealth, (2) barriers and facilitators to COVID-19 education and diagnostic testing and routine care for associated cardiovascular and respiratory comorbidities in the local community, and (3) key content for inclusion in a COVID-19 mHealth app., Methods: This qualitative study used principles of community-based participatory research and information systems research to conduct 7 focus groups across 3 sites. Focus groups were audio recorded and transcribed for thematic analysis using an abductive approach., Results: The study sample included 54 individuals across sites with a mean age of 50.24 (SD 11.76; range 20-71) years. Participants were primarily female (n=42, 78%) and Black (n=54, 100%) with varied education levels. Over half (n=29, 54%) of the participants were employed full-time, and nearly three-fourths (n=40, 74%) had household incomes

Background: The MOVe-OUT (efficacy and safety of molnupiravir [MK-4482] in non-hospitalized adult participants with COVID-19 [MK-4482-002]) trial reported that the administration of molnupiravir in unvaccinated patients with coronavirus disease 2019 (COVID-19) before the Omicron epidemic showed a preventive effect of 31% against hospitalization and death. However, studies on the preventive effect of molnupiravir against progression to severe disease and death in patients with COVID-19 during the Omicron epidemic are limited. This study aimed to evaluate the preventive effect of molnupiravir against severe/critical illness or death and death in Korean patients with COVID-19 who were vaccinated mostly during the Omicron epidemic., Materials and Methods: This study used large-scale retrospective cohort data to select patients with COVID-19 who were either treated or not treated with molnupiravir, between August 2022 and March 2023, at a ratio of 1 : 4 using the propensity score matching method. In total, 762,768 patients comprised the non- administered group, and 190,692 patients comprised the molnupiravir-administered group. The preventive effect of molnupiravir against severe/critical illness or death and death was analyzed using logistic regression analysis., Results: The preventive effect of molnupiravir against severe/critical illness or death and death, represented by the odds ratio (OR) and 95% confidence interval (CI), in the molnupiravir-administered and non-administered group was (OR: 0.714; CI: 0.667 - 0.764) and (OR: 0.749; CI: 0.682 - 0.823), respectively. As age increased, the preventive effect against severe/critical illness or death and death increased. The preventive effect against severe/critical illness or death at ≥60 years was (OR: 0.669; CI: 0.624 - 0.717), at ≥70 years was (OR: 0.614; CI: 0.570 - 0.661), and at ≥80 years was (OR: 0.563; CI: 0.515 - 0.615). The preventive effect against death at ≥60 years was (OR: 0.729; CI: 0.663 - 0.802), at ≥70 years was (OR: 0.676; CI: 0.612 - 0.747), and at ≥80 years was (OR: 0.622; CI: 0.554 - 0.698)., Conclusion: Although molnupiravir showed a relatively weak preventive effect against severe/critical illness or death (29%) and death (25%) among patients with COVID-19, it exhibited a stronger protective effect in older patients than in younger patients. In particular, the preventive effect against severe/critical illness or death (44%) and death (38%) in those aged ≥80 years was pronounced. This study strongly suggests that molnupiravir administration can alleviate the burden on the medical system, and treat patients with COVID-19 effectively by reducing its progression to severe disease and death., Competing Interests: No conflict of interest, (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Climate change may be the most pressing existential threat to human health and wellbeing in the twenty first century. In this paper, the authors provide context and critique on barriers to climate action in the United States and other high-income countries, including the profit-driven approach to health, consumerism, and the climate change countermovement. The reciprocal connections between occupational engagement and climate damage are examined from a lens of collective and irresponsible occupations and subsequent accountability. The authors propose the United Nations' Sustainable Development Goals as a basis for recommendations occupational therapy practitioners could implement within the priorities of adaptation, mitigation, and resilience.

Background: Glutamate is a major neurotransmitter, although it causes cytotoxicity and inflammation in nonneuronal organs. This study aimed to investigate the metabolic disorders in which glutamate, associated with type 2 diabetes onset, is induced in the liver., Methods: An analysis of Korean community-based Ansan-Ansung cohort study data as well as functional research using in vitro and mouse models were performed., Results: Groups with high plasma glutamate levels (T2, T3) had a significantly increased risk of diabetes incidence after 8 years, compared to the group with relatively low glutamate levels (T1). Analysis of the effect of glutamate on diabetes onset in vitro showed that glutamate induces insulin resistance by increasing glucose-related protein 78 (GRP78) and phosphoenolpyruvate carboxykinase (PEPCK) expression in SK-Hep-1 human liver cells. In addition, three different genes, FRMB4B, PLG, and PARD3, were significantly associated with glutamate and were identified via genome-wide association studies. Among glutamate-related genes, plasminogen (PLG) levels were most significantly increased in several environments in which insulin resistance was induced, and was also upregulated by glutamate. Glutamate-induced increase in PLG in liver cells was caused by metabotropic glutamate receptor 5 activation, and PLG levels were also upregulated after extracellular secretion. Moreover, glutamate increased the expression of plasminogen activator inhibitor-1 (PAI-1). Thus, extracellular secreted PLG cannot be converted to plasmin (fibrinolytic enzyme) by increased PAI-1., Conclusions: Increased glutamate is closely associated with the development of diabetes, and it may cause metabolic disorders by inhibiting the fibrinolytic system, which plays an important role in determining blood clots, a hallmark of diabetes., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Paxlovid is an oral antiviral drug that received emergency use authorization in South Korea for the treatment of patients with mild-to-moderate coronavirus disease 2019 (COVID-19) on January 14, 2022. Since the onset of the severe acute respiratory syndrome coronavirus 2 pandemic, the virus has continued to evolve. The emergence of new variants has raised concerns about possible reductions in the effectiveness of vaccines and drugs. The effectiveness of Paxlovid in patients infected with the omicron variant and subvariants has not yet been determined. This study assessed the effectiveness of Paxlovid at reducing the risk of severe/critical illness or death and death in patients with mild-to-moderate COVID-19 caused by omicron subvariant BA.5., Methods: In this nationwide retrospective cohort study, data on 8,902,726 patients were collected from four sources (the Drug Utilization Review database, COVID-19 Patient Information Management System, confirmed patient information, and basic epidemiological investigation data) between July 1 and November 30, 2022. Multivariable logistic regression analysis was conducted, with adjustment for age, sex, severe acute respiratory syndrome coronavirus 2 immunity (vaccination), and comorbidities., Results: A total of 1,936,925 patients with COVID-19 were included in the analysis, including 420,996 patients treated with Paxlovid, and 1,515,959 patients not treated with Paxlovid. Paxlovid treatment in patients aged ≥ 60 years of age was associated with significantly reduced risk of severe/critical illness or death (46.0%), and death rate (32.5%), and its effectiveness was high, regardless of vaccination status., Conclusion: Paxlovid is effective at reducing the risk of death due to COVID-19 in patients with omicron BA.5 infection, especially in older patients, regardless of vaccination status. This suggests that older patients with COVID-19-related symptoms should be administered Paxlovid, regardless of their vaccination status, to reduce severity and risk of death., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Scrub typhus is an acute febrile, mite-borne disease endemic to the Asia-Pacific region. In South Korea, it is a seasonal disease that occurs frequently in the autumn, and its incidence has increased steadily. In this study, we used a liquid chromatography and flow injection analysis-tandem mass spectrometry-based targeted urine metabolomics approach to evaluate the host response to Orientia tsutsugamushi infection. Balb/c mice were infected with O. tsutsugamushi Boryong, and their urine metabolite profile was examined. Metabolites that differed significantly between the experimental groups were identified using the Kruskal-Wallis test. Sixty-five differential metabolites were identified. The principal metabolite classes were acylcarnitines, glycerophospholipids, biogenic amines, and amino acids. An ingenuity pathway analysis revealed that several toxic (cardiotoxic, hepatotoxic, and nephrotoxic) metabolites are induced by scrub typhus infection. This is the first report of urinary metabolite biomarkers of scrub typhus infection and it enhances our understanding of the metabolic pathways involved.

A tokamak, a torus-shaped nuclear fusion device, needs an electric current in the plasma to produce magnetic field in the poloidal direction for confining fusion plasmas. Plasma current is conventionally generated by electromagnetic induction. However, for a steady-state fusion reactor, minimizing the inductive current is essential to extend the tokamak operating duration. Several non-inductive current drive schemes have been developed for steady-state operations such as radio-frequency waves and neutral beams. However, commercial reactors require minimal use of these external sources to maximize the fusion gain, Q, the ratio of the fusion power to the external power. Apart from these external current drives, a self-generated current, so-called bootstrap current, was predicted theoretically and demonstrated experimentally. Here, we reveal another self-generated current that can exist in a tokamak and this has not yet been discussed by present theories. We report conclusive experimental evidence of this self-generated current observed in the KSTAR tokamak., (© 2022. The Author(s).)

Alcohol consumption is associated with a high increased lipid profile and this association may depend on genetic risk factors. In this study, we aimed to assess the effects of genetic variation associated with alcohol consumption on lipid profiles using data from two Korean population studies. We performed a genotype association study using the HEXA (n = 51,349) and KNHANES (n = 9158) data. Genotype analyses of the two sets of Korean population data showed associations of increased total cholesterol and high-density lipoprotein (HDL)-cholesterol with CETP rs708272. The HEXA and KNHANES populations revealed differences in HDL cholesterol according to the presence of CETP rs708272, independent of ALDH2 rs671 and alcohol consumption. In contrast, total cholesterol levels were associated with alcohol consumption and ALDH2 rs671 in men with CETP rs708272 (CT and TT genotypes). Furthermore, in drinkers with ALDH2 rs671 (GA and AA genotypes), higher total cholesterol was associated with the CETP rs708272 TT minor homozygous genotype based on both HEXA and KNHANES data. Our findings demonstrated that alcohol consumption and genetic variation in either CETP or ALDH2 may be associated with cholesterol levels. We hope these findings will provide a better understanding of the relationship between alcohol consumption and cholesterol according to each individual's genetic background., (© 2022. The Author(s).)

Excessive alcohol intake is an important cause of major public health problem in East Asian countries. Growing evidence suggests that genetic factors are associated with alcohol consumption and the risk for alcohol-associated disease, and these factors contribute to the risk of developing chronic diseases, including diabetes. This study aims to investigate the association of type 2 diabetes with genetic polymorphisms within HECTD4 based on alcohol exposure. We performed a genome-wide association study involving the cohorts of the KoGES-HEXA study (n = 50,028) and Ansan and Ansung study (n = 7,980), both of which are prospective cohort studies in Korea. The top three single-nucleotide polymorphisms (SNPs) of the HECTD4 gene, specifically rs77768175, rs2074356 and rs11066280, were found to be significantly associated with alcohol consumption. We found that individuals carrying the variant allele in these SNPs had lower fasting blood glucose, triglyceride, and GGT levels than those with the wild-type allele. Multiple logistic regression showed that statistically significant associations of HECTD4 gene polymorphisms with an increased risk of type 2 diabetes were found in drinkers. Namely, these SNPs were associated with decreased odds of diabetes in the presence of alcohol consumption. As a result of examining the effect of alcohol on the expression of the HECTD4 gene, ethanol increased the expression of HECTD4 in cells, but the level was decreased by NAC treatment. Similar results were obtained from liver samples of mice treated with alcohol. Moreover, a loss of HECTD4 resulted in reduced levels of CYP2E1 and lipogenic gene expression in ethanol-treated cells, while the level of ALDH2 expression increased, indicating a reduction in ethanol-induced hepatotoxicity., (© 2022. The Author(s).)

Potassium voltage-gated channel subfamily Q member 1 (KCNQ1) is one of the strongest susceptibility genes for type 2 diabetes mellitus (T2DM). Association studies between KCNQ1 genetic variants and T2DM have been reported. The multifactorial disease T2DM is caused by interactions between genetic susceptibility and environmental factors. In this study, we examined the associations between the KCNQ1 haplotype, which consists of the major alleles rs3852528, rs11024175, and rs2237892 (ht: ACC), and environmental factors such as alcohol consumption, which are related to the risk of T2DM, in two independent Korean populations. Data from health examination studies, i.e., HEXA (n = 50,357 subjects) and the Ansung-Ansan community-based Korean cohort study (n = 7603), were analyzed. In both cohorts, fasting blood glucose levels were significantly increased in moderate-to-heavy drinkers and carriers of the homozygous ACC haplotype. A significant association between the KCNQ1 haplotype and alcohol consumption in the risk of diabetes was observed in the HEXA (OR 1.587; 95% CI 1.128-2.234) and Ansung-Ansan (OR 2.165; 95% CI 1.175-3.989) cohorts compared with abstainers not carrying the KCNQ1 haplotype. Associations of the KCNQ1 haplotype with alcohol consumption and β-cell function were observed in the Ansung-Ansan cohort. Moderate-to-heavy drinkers with the ACC haplotype had lower fasting insulin levels and mean 60 min insulinogenic index (IGI 60 ) compared with light drinkers and abstainers not carrying the ACC haplotype. These findings indicate that KCNQ1 variants play a synergistic role with alcohol consumption in the development of T2DM and impaired β-cell function., (© 2021. The Author(s).)