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1.
Bioethics ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38984871
2.
J Glaucoma ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38995126

ABSTRACT

PRCIS: Glaucoma eyes with recurrent disc hemorrhage were associated with increased systolic blood pressure and diastolic blood pressure, and increased visit-to-visit diastolic blood pressure variability was associated with glaucoma progression. PURPOSE: In this study, we investigated the effects of the clinical characteristics of disc hemorrhage (DH) and hemodynamic factors on glaucoma progression. METHODS: This retrospective cohort study included 81 eyes with open angle glaucoma and non-recurrent or recurrent DH. Recurrent DH was further classified according to the DH location. Visual field (VF) progression was determined using event-based analysis and Guided Progression Analysis software. The coefficient of variation (CV) of systolic and diastolic blood pressure (SBP and DBP, respectively) was used to measure visit-to-visit variability. Kaplan-Meier survival analysis was used to compare the cumulative risk ratio of progression between groups. RESULTS: The recurrent DH group had significantly higher SBP and DBP (P=0.014 and=0.021, respectively) and a higher proportion of VF progression (P=0.019) than the non-recurrent DH group. In particular, females with recurrent DH had the highest cumulative probability of VF progression (P=0.047, log-rank test). Recurrent DH in a different quadrant was associated with the highest cumulative probability of VF progression than non-recurrent DH (P=0.038, log-rank test). In Cox regression analysis, higher visit-to-visit DBP variability, female sex, and recurrent DH in a different quadrant were significantly associated with glaucoma progression. CONCLUSION: In glaucomatous eyes with DH, increased visit-to-visit DBP variability was associated with glaucoma progression. Our results suggest that hemodynamic factors are involved in the recurrence of DH and progression of glaucoma.

3.
Biomedicines ; 12(6)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38927557

ABSTRACT

Current chemical treatments for cerebrovascular disease and neurological disorders have limited efficacy in tissue repair and functional restoration. Induced pluripotent stem cells (iPSCs) present a promising avenue in regenerative medicine for addressing neurological conditions. iPSCs, which are capable of reprogramming adult cells to regain pluripotency, offer the potential for patient-specific, personalized therapies. The modulation of molecular mechanisms through specific growth factor inhibition and signaling pathways can direct iPSCs' differentiation into neural stem cells (NSCs). These include employing bone morphogenetic protein-4 (BMP-4), transforming growth factor-beta (TGFß), and Sma-and Mad-related protein (SMAD) signaling. iPSC-derived NSCs can subsequently differentiate into various neuron types, each performing distinct functions. Cell transplantation underscores the potential of iPSC-derived NSCs to treat neurodegenerative diseases such as Parkinson's disease and points to future research directions for optimizing differentiation protocols and enhancing clinical applications.

4.
Sci Rep ; 14(1): 14703, 2024 06 26.
Article in English | MEDLINE | ID: mdl-38926519

ABSTRACT

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83-0.94; p < 0.001), particularly among individuals aged ≥ 55 years, women, never smokers, and those with history of asthma or coronary heart disease. Higher cumulative dose groups were associated with a lower mortality risk compared to the lowest cumulative dose group. In conclusion, the administration of ICS seemed to be associated with a lower mortality risk in patients with COPD.


Subject(s)
Adrenal Cortex Hormones , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/mortality , Female , Male , Administration, Inhalation , Middle Aged , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Aged , Republic of Korea/epidemiology , Cohort Studies , Proportional Hazards Models
5.
Article in English | MEDLINE | ID: mdl-38864769

ABSTRACT

Sex differences are recognized in pulmonary hypertension, however the progression of disease with regards to vascular lesion formation and circulating cytokines/chemokines is unknown. To determine whether vascular lesion formation, changes in hemodynamics and alterations in circulating chemokines/cytokines differ between male and female. We used a progressive model of PAH, SU/Hx and analyzed cohorts of male and female rats at timepoints suggested to indicate worsening disease. Our analysis included echocardiograpy for hemodynamics, morphometry, immunofluoresecence and chemokine/cytokine analysis of plasma at each time point in both sexes. We found that male rats had significantly increased Fulton index compared to females at each time point as well as increased medial artery thickening at 8-weeks PAH. Further, females exhibit fewer obliterative vascular lesions than males at our latest time point. Our data also show increased IL-4, GM-CSF, IL-10, and MIP-1 that are not observed in females, while females have increased RANTES and CXCL-10 not found in males. Males also have increased infiltrating macrophages in vascular lesions as compared to females. We found that development of progressive PAH in hemodynamics, morphology and chemokine/cytokine circulation differ significantly between males and females. These data suggest a macrophage driven pathology in males, while there may be T-cell protection from vascular damage in female PAH.

6.
Curr Res Physiol ; 7: 100125, 2024.
Article in English | MEDLINE | ID: mdl-38836245

ABSTRACT

Human monoamine transporters (MATs) are critical to regulating monoaminergic neurotransmission by translocating their substrates from the synaptic space back into the presynaptic neurons. As such, their primary substrate binding site S1 has been targeted by a wide range of compounds for treating neuropsychiatric and neurodegenerative disorders including depression, ADHD, neuropathic pain, and anxiety disorders. We present here a comparative study of the structural dynamics and ligand-binding properties of two MATs, dopamine transporter (DAT) and serotonin transporter (SERT), with focus on the allosteric modulation of their transport function by drugs or substrates that consistently bind a secondary site S2, proposed to serve as an allosteric site. Our systematic analysis of the conformational space and dynamics of a dataset of 50 structures resolved for DAT and SERT in the presence of one or more ligands/drugs reveals the specific residues playing a consistent role in coordinating the small molecules bound to subsites S2-I and S2-II within S2, such as R476 and Y481 in dDAT and E494, P561, and F556 in hSERT. Further analysis reveals how DAT and SERT differ in their two principal modes of structural changes, PC1 and PC2. Notably, PC1 underlies the transition between outward- and inward-facing states of the transporters as well as their gating; whereas PC2 supports the rearrangements of TM helices near the S2 site. Finally, the examination of cross-correlations between structural elements lining the respective sites S1 and S2 point to the crucial role of coupled motions between TM6a and TM10. In particular, we note the involvement of hSERT residues F335 and G338, and E493-E494-T497 belonging to these two respective helices, in establishing the allosteric communication between S1 and S2. These results help understand the molecular basis of the action of drugs that bind to the S2 site of DAT or SERT. They also provide a basis for designing allosteric modulators that may provide better control of specific interactions and cellular pathways, rather than indiscriminately inhibiting the transporter by targeting its orthosteric site.

7.
Regul Toxicol Pharmacol ; : 105664, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38897446

ABSTRACT

Plasticizers are necessary for the usability of various products, including food contact materials. Exposure to plasticizers is most commonly made through the oral route. Several plasticizers have been reported to have adverse effects on humans and the environment. Thus, the present study aimed to determine the long-term toxicity and carcinogenicity of a novel plasticizer called bis(2-ethylhexyl) cyclohexane-1,4-dicarboxylate (Eco-DEHCH), which is an ecofriendly and biologically less harmful replacer. Groups of 50 male and 50 female Han Wistar rats were fed Eco-DEHCH at daily doses of 1,600, 5,000, or 16,000 ppm in their diet for at least 104 weeks. The rats were regularly monitored for mortality, clinical signs, body weight, food consumption, food efficiency, and perceivable mass. All animals were subjected to complete necropsy and histopathological examination. The results indicate that the rats well tolerated chronic exposure to Eco-DEHCH at highest daily doses of 16,000 ppm, with was equivalent to 805.1 mg/kg/day in males and 1,060.6 mg/kg/day in females and did not show signs of toxicity or carcinogenicity. In conclusion, Eco-DEHCH could be a safe and promising alternative plasticizer.

8.
Allergy Asthma Immunol Res ; 16(3): 300-307, 2024 May.
Article in English | MEDLINE | ID: mdl-38910287

ABSTRACT

Severe atopic dermatitis (AD) is not a localized cutaneous disease, but a systemic disease that often accompanies comorbidities. In this nationwide population-based study, we aimed to analyze the prevalence of severe AD and chronic systemic diseases in Koreans aged ≤ 20 years between 2011 and 2019 using the data from the Korean Health Insurance Review and Assessment Service. Total AD and severe AD were defined according to the International Classification of Diseases-10 code L20. In children aged 6-20 years, the prevalence of severe AD significantly increased from 0.02% in 2011 to 0.04% in 2019 (P for trend < 0.001), with the ratio of severe AD to total AD increasing from 0.76% in 2011 to 1.10% in 2019 (P for trend < 0.001). The prevalence rates of severe AD significantly increased between 2011 and 2019 in children aged 6-12 years (P for trend < 0.05) and 13-18 years (P for trend < 0.001). Severe AD was more frequently found in males than in females each year (all P < 0.001, from 2011 to 2019). During the period from 2011 to 2019, the prevalence rate of chronic systemic diseases was higher in subjects with severe AD than in those without AD (P < 0.001) or with mild-to-moderate AD (P < 0.001). In conclusion, our results suggest that the prevalence of severe AD is increasing in Korean children and adolescents and is higher in males and older age groups. Moreover, severe AD is associated with chronic systemic diseases. Therefore, more attention should be paid to managing severe AD.

9.
Intest Res ; 22(2): 186-207, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38720467

ABSTRACT

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

10.
Food Funct ; 15(12): 6684-6691, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38819217

ABSTRACT

We previously demonstrated the beneficial effects of U.S.-grown sugar kelp (Saccharina latissima), a brown seaweed, on reducing serum triglycerides (TG) and total cholesterol (TC) and protecting against inflammation and fibrosis in the adipose tissue of diet-induced obesity mice. In this current study, we aimed to explore whether the dietary consumption of sugar kelp can prevent atherosclerosis using low-density lipoprotein receptor knockout (Ldlr KO) mice fed an atherogenic diet. Eight-week-old male Ldlr KO mice were fed either an atherogenic high-fat/high-cholesterol control (HF/HC) diet or a HF/HC diet supplemented with 6% (w/w) sugar kelp (HF/HC-SK) for 16 weeks. Consumption of sugar kelp significantly increased the body weight gain without altering fat mass and lean mass. Also, there were no significant differences in energy expenditure and physical activities between the groups. The two groups did not show significant differences in serum and hepatic TG and TC levels or the hepatic expression of genes involved in cholesterol and lipid metabolism. Although serum alanine aminotransferase (ALT) activity did not differ significantly between the two groups, there were significant increases in the expression of macrophage markers, including adhesion G protein-coupled receptor E1 and cluster of differentiation 68, as well as tumor necrosis factor alpha in the HF/HC-SK group compared to the HF/HC mice. The consumption of sugar kelp did not elicit a significant effect on the development of aortic lesions. Moreover, lipopolysaccharide-stimulated splenocytes isolated from HF/HC-SK-fed mice showed no significant changes in the mRNA levels of pro-inflammatory genes compared with those from the HF/HC mice. In summary, the consumption of dietary sugar kelp did not elicit anti-atherogenic and hepatoprotective effects in Ldlr KO mice.


Subject(s)
Atherosclerosis , Mice, Knockout , Receptors, LDL , Animals , Receptors, LDL/genetics , Receptors, LDL/metabolism , Mice , Male , Atherosclerosis/prevention & control , Atherosclerosis/genetics , Atherosclerosis/metabolism , Triglycerides/blood , Triglycerides/metabolism , Kelp , Mice, Inbred C57BL , Diet, High-Fat/adverse effects , Liver/metabolism , Cholesterol/blood , Cholesterol/metabolism , Humans , Lipid Metabolism , Edible Seaweeds , Laminaria
11.
PLoS One ; 19(5): e0300353, 2024.
Article in English | MEDLINE | ID: mdl-38820369

ABSTRACT

Tidal flats provide critical habitat for migratory waterbird species; however, populations of migratory waterbirds have significantly declined due to tidal flat loss and degradation caused by human activities, particularly in Asia. Gochang getbol is one of tidal flats located on the southwest coast of South Korea and a center of clam production. Using bird monitoring data collected at five zones (zone1 to zone5) established across Gochang getbol and near coastal area, we examined distribution patterns of migratory bird diversity and conservation-related species along the coast of Gochang getbol. The intensity of human activity ‒ mudflat culture (mostly bivalve) and aquaculture was relatively high at zone2 and zone3, occupying > 30% of 2km circular area surrounding most sample points of these zones. Zone1 and particularly zone4 contained more natural/semi-natural habitats (less disturbed mudflats and wetlands) and zone5 had smallest mudflat than others. Shannon diversity, species richness, and abundance of migratory birds differed between zones (Anova test, P ≤ 0.02) except Shannon diversity in winter. In fall, all values were higher at zone4 than zone3 and zone5. In winter, zone1 showed greatest species richness and higher abundance than zone2, zone3, and zone5. In spring, while most differences were found between zone4 and zone5, abundance at zone4 was somewhat higher than zone2. The results from the fourth corner analysis indicated that abundance of species foraging at mudflat level was positively associated with zone1 (winter) but negatively with zone3 (fall). Sandpipers were positively associated with zone4. Abundance distribution maps of conservation-related species, created by inverse distance-weighted interpolation modeling, also showed high abundance of most conservation-related species at zone4 and 1. The findings of our study suggest the importance of natural/semi-natural habitat, and the possible link between human activity and distribution patterns of migratory birds in Gochang getbol. While we need further investigation on direct response of migratory birds to human activity, areas with low human activity with more natural/semi-natural habitat, e.g., zone4 and zone1 may be crucial for the conservation of migratory birds.


Subject(s)
Animal Migration , Biodiversity , Birds , Animals , Animal Migration/physiology , Birds/physiology , Republic of Korea , Seasons , Ecosystem , Conservation of Natural Resources , Spatio-Temporal Analysis , Humans
12.
Microb Cell Fact ; 23(1): 147, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783320

ABSTRACT

Aminopyrrolnitrin (APRN), a natural halogenated phenylpyrrole derivative (HPD), has strong antifungal and antiparasitic activities. Additionally, it showed 2.8-fold increased photostability compared to pyrrolnitrin, a commercially available HPD with antimicrobial activity. For microbial production of APRN, we first engineered anthranilate phosphoribosyltransferase encoded by trpD from Corynebacterium glutamicum, resulting in a TrpDA162D mutation that exhibits feedback-resistant against L-tryptophan and higher substrate affinity compared to wild-type TrpD. Plasmid-borne expression of trpDA162D in C. glutamicum TP851 strain with two copies of trpDA162D in the genome led to the production of 3.1 g/L L-tryptophan in flask culture. Subsequent step for L-tryptophan chlorination into 7-chloro-L-tryptophan was achieved by introducing diverse sources of genes encoding tryptophan 7-halogenase (PrnA or RebH) and flavin reductase (Fre, PrnF, or RebF). The combined expression of prnA from Serratia grimesii or Serratia plymuthica with flavin reductase gene from Escherichia coli, Pseudomonas fluorescens, or Lechevalieria aerocolonigenes yielded higher production of 7-chloro-L-tryptophan in comparison to other sets of two-component systems. In the next step, production of putative monodechloroaminopyrrolnitrin (MDAP) from 7-chloro-L-tryptophan was achieved through the expression of prnB encoding MDAP synthase from S. plymuthica or P. fluorescens. Finally, an artificial APRN biosynthetic pathway was constructed by simultaneously expressing genes coding for tryptophan 7-halogenase, flavin reductase, MDAP synthase, and MDAP halogenase (PrnC) from different microbial sources within the L-tryptophan-producing TP851 strain. As prnC from S. grimesii or S. plymuthica was introduced into the host strain, which carried plasmids expressing prnA from S. plymuthica, fre from E. coli, and prnB from S. plymuthica, APN3639 and APN3638 accumulated 29.5 mg/L and 28.1 mg/L of APRN in the culture broth. This study represents the first report on the fermentative APRN production by metabolically engineered C. glutamicum.


Subject(s)
Corynebacterium glutamicum , Metabolic Engineering , Corynebacterium glutamicum/metabolism , Corynebacterium glutamicum/genetics , Metabolic Engineering/methods , Pyrrolnitrin/biosynthesis , Pyrrolnitrin/metabolism , Fermentation , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Tryptophan/biosynthesis , Tryptophan/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Oxidoreductases
13.
Sci Rep ; 14(1): 11894, 2024 05 24.
Article in English | MEDLINE | ID: mdl-38789484

ABSTRACT

Although immunotherapy has not yet been as successful in ovarian cancer (OC), it remains a potential therapeutic strategy. Preclinical models of OC are necessary to evaluate the efficacy of immuno-oncology (IO) drugs targeting human immune components but have been underutilized. Developing mouse models with a humanized (Hu) immune system can help understand the human immune response to IO drugs which have demonstrated limited effectiveness in OC patients. We established OC xenograft Hu-mouse models by intraperitoneally injecting luciferase-expressing SKOV-3 Luc and OVCAR-3 Luc OC cells into CD34+ Hu-mice. Tumor growth was monitored through bioluminescence imaging (BLI). In the SKOV-3 Luc Hu-mouse model, we assessed the efficacy of PD-1 blockade with pembrolizumab. We observed the presence of human lymphocyte and myeloid cell subsets within the tumors, lymph nodes, blood, and spleens in these models. Notably, these tumors exhibited a high prevalence of tumor-infiltrating macrophages. Furthermore, we identified HDAC class I target genes, and genes associated with epithelial-mesenchymal transition (EMT) and fibroblasts in the tumors of Hu-mice treated with pembrolizumab. Our xenograft Hu-mouse model of OC provides a valuable tool for investigating the efficacy of IO drugs. The insights gained from this model offer useful information to explore potential mechanisms associated with unresponsive anti-PD-1 treatment in OC.


Subject(s)
Antibodies, Monoclonal, Humanized , Gene Expression Profiling , Ovarian Neoplasms , Peritoneal Neoplasms , Xenograft Model Antitumor Assays , Animals , Ovarian Neoplasms/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/drug therapy , Female , Humans , Mice , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Cell Line, Tumor , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/genetics , Epithelial-Mesenchymal Transition/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Disease Models, Animal , Transcriptome
14.
medRxiv ; 2024 May 18.
Article in English | MEDLINE | ID: mdl-38798434

ABSTRACT

Genome-wide association studies (GWAS) have been predominantly conducted in populations of European ancestry, limiting opportunities for biological discovery in diverse populations. We report GWAS findings from 153,950 individuals across 36 quantitative traits in the Korean Cancer Prevention Study-II (KCPS2) Biobank. We discovered 616 novel genetic loci in KCPS2, including an association between thyroid-stimulating hormone and CD36. Meta-analysis with the Korean Genome and Epidemiology Study, Biobank Japan, Taiwan Biobank, and UK Biobank identified 3,524 loci that were not significant in any contributing GWAS. We describe differences in genetic architectures across these East Asian and European samples. We also highlight East Asian specific associations, including a known pleiotropic missense variant in ALDH2, which fine-mapping identified as a likely causal variant for a diverse set of traits. Our findings provide insights into the genetic architecture of complex traits in East Asian populations and highlight how broadening the population diversity of GWAS samples can aid discovery.

15.
J Med Ethics ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802140
17.
Article in English | MEDLINE | ID: mdl-38766682

ABSTRACT

BACKGROUND AND AIM: Reliable bowel preparation assessment is important in colonoscopy. However, current scoring systems are limited by laborious and time-consuming tasks and interobserver variability. We aimed to develop an artificial intelligence (AI) model to assess bowel cleanliness and evaluate its clinical applicability. METHODS: A still image-driven AI model to assess the Boston Bowel Preparation Scale (BBPS) was developed and validated using 2361 colonoscopy images. For evaluating real-world applicability, the model was validated using 113 10-s colonoscopy video clips and 30 full colonoscopy videos to identify "adequate (BBPS 2-3)" or "inadequate (BBPS 0-1)" preparation. The model was tested with an external dataset of 29 colonoscopy videos. The clinical applicability of the model was evaluated using 225 consecutive colonoscopies. Inter-rater variability was analyzed between the AI model and endoscopists. RESULTS: The AI model achieved an accuracy of 94.0% and an area under the receiver operating characteristic curve of 0.939 with the still images. Model testing with an external dataset showed an accuracy of 95.3%, an area under the receiver operating characteristic curve of 0.976, and a sensitivity of 100% for the detection of inadequate preparations. The clinical applicability study showed an overall agreement rate of 85.3% between endoscopists and the AI model, with Fleiss' kappa of 0.686. The agreement rate was lower for the right colon compared with the transverse and left colon, with Fleiss' kappa of 0.563, 0.575, and 0.789, respectively. CONCLUSIONS: The AI model demonstrated accurate bowel preparation assessment and substantial agreement with endoscopists. Further refinement of the AI model is warranted for effective monitoring of qualified colonoscopy in large-scale screening programs.

18.
J Int Med Res ; 52(5): 3000605241247684, 2024 May.
Article in English | MEDLINE | ID: mdl-38818888

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of fezolinetant for moderate to severe vasomotor symptoms (VMS) associated with menopause in East Asian women. METHODS: In this phase 3, randomized, double-blind study, postmenopausal women with moderate to severe VMS (minimum average frequency in the 10 days before randomization, ≥7/day or 50/week) received fezolinetant 30 mg/day or placebo (weeks 1-12), followed by an open-label extension phase with fezolinetant 30 mg/day (weeks 13-24). The co-primary endpoints were the mean changes in the daily frequency and severity of VMS at weeks 4 and 12. RESULTS: Among 301 participants, the difference in the least squares mean change (95% confidence interval) from baseline in the daily frequency of moderate to severe VMS versus placebo was -0.65 (-1.41 to 0.12) at week 4 and -0.55 (-1.35 to 0.26) at week 12. The differences in the least squares mean change from baseline in the VMS severity score versus placebo were -0.06 (-0.14 to 0.03) and -0.13 (-0.27 to 0.01) at weeks 4 and 12, respectively. Serious adverse events occurred in 0.7% of participants receiving fezolinetant in weeks 1 to 12, compared with 1.3% of those receiving placebo. CONCLUSIONS: Fezolinetant was generally safe but did not reduce the frequency or severity of VMS versus placebo in postmenopausal women in this study.ClinicalTrials.Gov Identifier: NCT04234204.


Subject(s)
Hot Flashes , Menopause , Humans , Female , Middle Aged , Hot Flashes/drug therapy , Double-Blind Method , Menopause/drug effects , Menopause/physiology , Treatment Outcome , Asia, Eastern , Vasomotor System/drug effects , Vasomotor System/physiopathology , Severity of Illness Index , Adult
19.
BMJ Open Qual ; 13(2)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38626940

ABSTRACT

OBJECTIVE: System-level safety measures do not exist to ensure that patients with iron deficiency anaemia (IDA) undergo proper diagnostic evaluations. We sought to determine if a set of EHR (electronic health record) tools and an expedited referral workflow increase short-term completion of bidirectional endoscopy in higher risk patients with IDA. MATERIALS AND METHODS: We conducted a pragmatic, cluster-randomised trial randomised by primary care physician (PCP) that included 16 PCPs and 316 patients with IDA. Physicians were randomised to intervention or control groups. Intervention components included a patient registry visible within the EHR, point-of-care alert and expedited diagnostic evaluation workflow for IDA. Outcomes were assessed at 120 days. The primary outcome was completion of bidirectional endoscopy. Secondary outcomes were any endoscopy completed or scheduled, gastroenterology consultation completed, and gastroenterology referral or endoscopy ordered or completed. RESULTS: There were no differences in the primary or secondary outcomes. At 120 days, the primary outcome had occurred for 7 (4%) of the intervention group and 5 (3.5%) of the control group. For the three secondary outcomes, rates were 15 (8.6%), 12 (6.9%) and 39 (22.4%) for the immediate intervention group and 10 (7.0%), 9 (6.3%) and 25 (17.6%) for the control group, respectively, p>0.2. Lack of physician time to use the registry tools was identified as a barrier. DISCUSSION AND CONCLUSION: Providing PCPs with lists of patients with IDA and a pathway for expedited evaluation did not increase rates of completing endoscopic evaluation in the short term. TRIAL REGISTRATION NUMBER: NCT05365308.


Subject(s)
Anemia, Iron-Deficiency , Physicians , Humans , Anemia, Iron-Deficiency/diagnosis , Electronic Health Records , Referral and Consultation
20.
Asia Pac J Public Health ; 36(4): 378-386, 2024 May.
Article in English | MEDLINE | ID: mdl-38600733

ABSTRACT

This study aimed to identify factors influencing compliance with social distancing, a key nonpharmaceutical intervention during the early stages of the coronavirus disease (COVID-19) pandemic. The study population comprised 182 758 Koreans who participated in the 2020 Community Health Survey. Personal characteristics were classified into sociodemographic, health behavioral, and psychosocial factors, and factors associated with social distancing compliance were identified. Health behaviors and psychosocial factors were highly related to compliance with social distancing. Approximately 13% of smokers were less likely to practice physical distancing and 50% of high-risk drinkers were less likely to limit going out or attending gatherings and events. Higher concern about COVID-19 and a more positive perception of the government's response policy were associated with a higher compliance with social distancing. Strategic public health policies considering the characteristics of the public are needed to enhance compliance with nonpharmaceutical interventions during disease outbreaks lacking effective treatments and vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , Physical Distancing , Humans , COVID-19/prevention & control , COVID-19/epidemiology , Republic of Korea/epidemiology , Cross-Sectional Studies , Female , Male , Adult , Middle Aged , COVID-19 Vaccines/administration & dosage , Young Adult , Aged , Health Behavior , Adolescent , Pandemics/prevention & control
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