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Background@#Although bronchoscopic cryotherapy (BC) is a pragmatic modality for recanalization of central airway obstruction (CAO), the risk of complications, such as bleeding, remains a concern. This study aimed to present the clinical outcomes of BC and evaluate the factors associated with its complications. @*Methods@#In this retrospective study, we reviewed the medical records of patients who underwent BC for CAO at the Asan Medical Center, South Korea. Most sessions were conducted via flexible bronchoscopy under moderate sedation. A multivariate logistic regression analysis was used to identify the factors associated with the success rate and complications. @*Results@#BC was performed in 262 sessions in 208 patients between January 2009 and December 2020. The most common cause of cryotherapy was recanalization of the endobronchial tumor related CAO (233/262, 88.9%). More than partial re-establishment of airway patency was achieved in 211 of 233 (90.6%) sessions. The success rate did not differ significantly in the multivariate logistic regression analysis. The most common complication was intrabronchial bleeding (78/233, 35.5%); however, severe bleeding occurred only in one case (0.4%). Univariate and multivariate logistic regression analyses revealed that diabetes mellitus (odds ratio [OR] = 2.820, P = 0.011), respiratory failure before BC (OR = 3.546, P = 0.028), and presence of distal airway atelectasis (OR = 0.417, P = 0.021) were independently associated with moderate to severe intrabronchial bleeding, while the histologic type of tumor was not related to bleeding. BC for CAO caused by blood clot or foreign body was successful in most cases, and there were no complications. @*Conclusion@#BC is an efficient and relatively safe intervention for patients with CAO. Our findings suggest that diabetes, respiratory failure before BC, and the absence of distal airway atelectasis may be risk factors of moderate to severe intrabronchial bleeding.
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Microbial community profiling using 16S rRNA amplicon sequencing allows for taxonomic characterization of diverse microorganisms. While amplicon sequence variant (ASV) methods are increasingly favored for their fine-grained resolution of sequence variants, they often discard substantial portions of sequencing reads during quality control, particularly in datasets with large number samples. We present a streamlined pipeline that integrates FastP for read trimming, HmmUFOtu for operational taxonomic units (OTU) clustering, Vsearch for chimera checking, and Kraken2 for taxonomic assignment. To assess the pipeline’s performance, we reprocessed two published stool datasets of normal Korean populations: one with 890 and the other with 1,462 independent samples. In the first dataset, HmmUFOtu retained 93.2% of over 104 million read pairs after quality trimming, discarding chimeric or unclassifiable reads, while DADA2, a commonly used ASV method, retained only 44.6% of the reads. Nonetheless, both methods yielded qualitatively similar β-diversity plots. For the second dataset, HmmUFOtu retained 89.2% of read pairs, while DADA2 retained a mere 18.4% of the reads. HmmUFOtu, being a closed-reference clustering method, facilitates merging separately processed datasets, with shared OTUs between the two datasets exhibiting a correlation coefficient of 0.92 in total abundance (log scale). While the first two dimensions of the β-diversity plot exhibited a cohesive mixture of the two datasets, the third dimension revealed the presence of a batch effect. Our comparative evaluation of ASV and OTU methods within this streamlined pipeline provides valuable insights into their performance when processing large-scale microbial 16S rRNA amplicon sequencing data. The strengths of HmmUFOtu and its potential for dataset merging are highlighted.
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Aged people are challenged by serious complications from chronic diseases, such as mood disorder, diabetes, heart disease, and infectious diseases, which are also the most common causes of death in older people. Therefore, elderly care facilities are more important than ever. The most common causes of death in elderly care facilities were reported to be diabetes, cardiovascular disease, and pneumonia. Recently, the coronavirus disease 2019 (COVID-19) pandemic have a great impact on blind spots of safety where aged people were isolated from society. Elderly care facilities were one of the blind spots in the midst of the pandemic, where major casualties were reported from COVID-19 complications because most people had one or two mortality risk factors, such as diabetes or cardiovascular disease. Therefore, medical governance of public health center and hospital, and elderly care facility is becoming important issue of priority. Thus, remote health monitoring service by the Internet of Medical Things (IoMT) sensors is more important than ever. Recently, technological breakthroughs have enabled healthcare professionals to have easy access to patients in medical blind spots through the use of IoT sensors. These sensors can detect medically urgent situations in a timely fashion and make medical decisions for aged people in elderly care facilities. Real-time electrocardiograms and blood sugar monitoring sensors are approved by the medical insurance service. Real-time monitoring services in medical blind spots, such as elderly care facilities, has been suggested. Heart rhythm monitoring could play a role in detecting early cardiovascular disease events and monitoring blood glucose levels in the management of chronic diseases, such as diabetes, in aged people in elderly care facilities. This review presents the potential usefulness of remote monitoring with IoMT sensors in medical blind spots and clinical suggestions for applications.
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An esophageal duplication cyst (EDC) is a congenital anomaly of the foregut. EDCs are often asymptomatic, so they are found incidentally on chest radiographs. In symptomatic patients, EDCs present with cough, dyspnea, vomiting, dysphagia, and chest pain. Potential complications of EDCs include perforation, obstruction, bleeding, and infection. The rarity of this condition may hinder timely diagnosis, which may lead to life-threatening complications. This article describes a case of esophagitis and mediastinitis developed in a 12-month-old infant with an EDC. We emphasize that although rare, EDCs should be considered in the differential diagnosis of non-specific respiratory signs such as cough, dyspnea, and stridor.
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A 7-year-old spayed female Shih Tzu dog was presented for evaluation of recurrent hypoglycemia. Serum insulin levels during hypoglycemia were 35.3 μIU/mL. Ultrasonography and computed tomography showed a mesenteric nodule between the kidney and the portal vein, but no pancreatic mass was observed. During surgery, the nodule had neither anatomical adhesions nor vascular connections to the pancreas. Pancreatic inspection and palpation revealed no abnormalities. Hypoglycemia improved after resection of the nodule.Histopathological examination confirmed the nodule to be an islet cell carcinoma. Although extremely rare, ectopic insulinoma should be considered as a possible cause of insulininduced hypoglycemia in dogs.
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Hemorrhage after pancreaticobiliary surgery is an infrequent but fatal complication. It is primarily caused by rupture of the pseudoaneurysm, and treatment options include endovascular coil embolization or endovascular stent-graft placement. Herein, we report a case of migration of an arterial stent-graft that was placed in the common hepatic artery to treat pseudoaneurysm after pylorus-preserving pancreaticoduodenectomy. The stent-graft migrated to the jejunum and was eventually excreted from the body.
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Purpose@#To identify changes in medical expenditures and health care utilization before and after visual impairment onset, then analyze differences according to visual impairment severity. @*Methods@#Patients aged ≥ 18 years who were registered as visually disabled from 2005 to 2013 were selected using the database from the registry of the disabled and the National Health Insurance Service. The observation period of 3 years before and after the registration was divided into 6-month units (12 points of interest). At each point of interest, medical cost, number of outpatient visits, and length of hospital stay (LOS) were analyzed. The control group was obtained through 1:10 stratification randomization to match sex and age; individuals in the control group were then selected via 1:1 propensity score matching for the premium quantile and residential area. @*Results@#In total, 131,434 patients with visual disability and the same number of non-visually impaired controls were included. Compared with non-disabled individuals, the mean medical cost and number of outpatient visits were higher for patients with visual disability (1.9- and 1.4-fold, respectively, p < 0.001); the LOS was also 3.5 days longer (p < 0.001). The mean medical cost and number of outpatient visits were greater in severely visually disabled patients than in mildly disabled patients (1.6- and 0.5-fold, respectively, p < 0.001); the LOS was also 12 days longer in severely disabled patients (p < 0.001). From 18 months before disability registration, medical costs and LOS increased according to the presence and severity of visual disability; the number of outpatient visits increased uniformly, regardless of disability and severity. @*Conclusions@#More severe cases of visual impairment are associated with greater health care utilization and expenditures. Policy intervention is necessary to ensure that patients receive appropriate treatment and steady health care by reducing the burden of medical expenditures.
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Few studies have been conducted among Asian children and adolescents with type 1 diabetes mellitus (T1DM) using do-it-yourself artificial pancreas system (DIY-APS). We evaluated real-world data of pediatric T1DM patients using DIY-APS. Data were obtained for 10 patients using a DIY-APS with algorithms. We collected sensor glucose and insulin delivery data from each participant for a period of 4 weeks. Average glycosylated hemoglobin was 6.2%±0.3%. The mean percentage of time that glucose level remained in the target range of 70 to 180 mg/dL was 82.4%±7.8%. Other parameters including time above range, time below range and mean glucose were also within the recommended level, similar to previous commercial and DIY-APS studies. However, despite meeting the target range, unadjusted gaps were still observed between the median basal setting and temporary basal insulin, which should be handled by healthcare providers.
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The association between lung injury and exposure to humidifier disinfectant (HD) containing a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) has been controversial in South Korea. This study conducts a literature review in order to evaluate the likelihood of CMIT/MIT reaching the lower part of the respiratory tract and causing lung injury. A literature review focused on the inhalation risk of HD containing a mixture of CMIT and MIT. The major contents included the physicochemical properties of CMIT and MIT contained in HDs and methodological reviews on substance analysis, toxicity tests and clinical cases. HD products marketed in South Korea have been reported to contain approximately 1–2% CMIT and 0.2–0.6% MIT along with magnesium nitrate (20–25%), magnesium chloride (0.2–1.0%), and water (70–75%). The types of CMIT and MIT dispersed into the air and deposited in the respiratory tract are assumed to be either gaseous substances or nanoparticles mixed with magnesium salts. The result of the literature review including clinical cases of lung injury among CMIT/MIT HD product users, demonstrated that these chemicals likely reach the lower respiratory tract and accordingly cause lung injury.A number of humidifier disinfectant-associated lung injury cases with clinical evidence should be prioritized in risk assessment of HD containing CMIT and MIT, even though there might be insufficient evidence in all related areas, including inhalation exposure assessment studies, animal testing, and epidemiological studies.
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Acute pancreatitis (AP) rarely occurs in association with food allergy (FA), and the mechanism is not clearly explored. We herein report a rare case of egg protein-induced AP. A 5-year-old girl was brought to the hospital because of tongue pruritus and an increased level of egg white-specific immunoglobulin E. During an oral food challenge, she developed hives, abdominal pain and vomiting after ingestion of a cumulative of 610 mg of boiled egg white (70 mg of protein). After management with intramuscular injection of epinephrine and orally administered prednisolone and levocetirizine, her skin symptoms improved. The next day, blood tests showed elevated levels of amylase and lipase, and computed tomography revealed a swollen pancreas with a low-attenuated necrotic portion. She was diagnosed with AP and treated with food restriction, intravenous methylprednisolone and gabexate mesilate. The serum levels of amylase and lipase were reduced to normal levels on day 5 and her symptoms completely resolved on day 10. A suspicion of food-induced AP is required for correct diagnosis and proper management in children with FA when they manifest severe abdominal pain.
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Background and Objectives@#Menkes disease (MNK) is a rare X-linked recessive disease, caused by mutations in the copper transporting ATP7A gene that is required for copper homeostasis. MNK patients experience various clinical symptoms including neurological defects that are closely related to the prognosis of MNK patients. Neural stem cells (NSCs) in the hippocampal dentate gyrus (DG) produce new neurons throughout life, and defects in DG neurogenesis are often correlated with cognitive and behavioral problems. However, neurodevelopmental defects in the DG during postnatal period in MNK have not been understood yet. @*Methods@#and Results: Mottled-brindled (Mo Br/y ) mice (MNK mice) and littermate controls were used in this study. In vivo microCT imaging and immunohistochemistry results demonstrate that blood vasculatures in hippocampus are abnormally decreased in MNK mice. Furthermore, postnatal establishment of NSC population and their neurogenesis are severely compromised in the DG of MNK mice. In addition, in vitro analyses using hippocampal neurosphere culture followed by immunocytochemistry and immunoblotting suggest that neurogenesis from MNK NSCs is also significantly compromised, corresponding to defective neurogenic gene expression in MNK derived neurons. @*Conclusions@#Our study is the first reports demonstrating that improper expansion of the postnatal NSC population followed by significant reduction of neurogenesis may contribute to neurodevelopmental symptoms in MNK. In conclusion, our results provide new insight into early neurodevelopmental defects in MNK and emphasize the needs for early diagnosis and new therapeutic strategies in the postnatal central nerve system damage of MNK patients.
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Background@#Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM. @*Methods@#A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD. @*Results@#Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters. @*Conclusion@#The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinicalpractice.
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BACKGROUND/OBJECTIVES@#The study was performed to investigate health-related lifestyle, dietary habits, and depression according to exercise frequency to understand complex factors that affect effective health management. Thus, exercise frequency, health-related lifestyle, dietary habits, and depression were evaluated in college students in Seoul and Gyeonggi-do areas. @*SUBJECTS/METHODS@#A survey was conducted on college students, aged 19–29, in Seoul and Gyeonggi-do areas from May 13 to May 31, 2020. A total of 594 questionnaires were collected and 566 (269 from males, 297 from females) were statistically analyzed, except 28 with incomplete responses. Collected data were analyzed using SPSS WIN 21.0 program. @*RESULTS@#The sex distribution of the 3 groups according to exercise frequency was significantly different; the ratio of males in over 3 times/week group was significantly higher than those in 1–2 times/week group and no-exercise group (P < 0.001). The height (P < 0.001), weight (P < 0.001), and body mass index (P < 0.05) were significantly higher in over 3 times/week group compared to no-exercise group. The ratio of subjects who answered ‘good’ or ‘very good’ for subjective health condition was significantly high in the order of ‘over 3 times/week’ group (59.1%), ‘1–2 times/week’ group (34.5%), and ‘no-exercise’ group (25.0%) (P < 0.001). The ratio for meal regularity was high as 56.6% in ‘over 3 times/week’ group and the ratio for irregular meals was significantly higher in ‘no-exercise’ group (67.2%) and ‘1–2 times/week’ group (54.9%) (P < 0.001). Among questions on dietary habits, ‘Eat meat, fish, egg or beans’ (P < 0.01) and ‘Eat fruit’ (P < 0.01) were significantly higher in ‘over 3 times/ week’ group compared to ‘no-exercise’ group. ‘Drink more than 2 liters of water’ (P < 0.001) was 0.70 in ‘over 3 times/week’ group, which was significantly higher than 0.54 in ‘1–2 times/ week’ group and 0.38 in ‘no-exercise’ group. Moderate depression and severe depression that need treatments were significantly lower in ‘over 3 times/week’ group (18.7%) compared to ‘1–2 times/week’ group (26.0%) and ‘no-exercise’ group (29.7%) (P < 0.05). @*CONCLUSIONS@#It is considered that combined intervention for exercise habits, proper dietary habits, and depression management is needed for effective health management.
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BACKGROUND/OBJECTIVES@#The study was performed to investigate the degree of perceived stress by sex in middle-aged people, and to provide basic data for appropriate nutrition education and interventional measures for middle-aged subjects through comparative analysis of association between stress and dietary habits, emotional eating behavior, and insomnia. @*SUBJECTS/METHODS@#A survey was conducted in 670 middle-aged subjects (320 men and 350 women) aged 40–64 years, resided in Seoul and Gyeonggi area. Collected data were analyzed using SPSS WIN 25.0 program. @*RESULTS@#Perceived stress in middle-aged subjects was not different by sex. Stress was higher in men with low dietary habits level compared to other groups (P < 0.001), and was higher in women with low and moderate dietary habits level compared to women with high dietary habits level (P < 0.05). Stress in men was higher in the group with emotional eaters (P < 0.05), and the same result was shown in women (P < 0.001). Stress was higher in both men and women with poor sleep quality (P < 0.001). Stress score was positively correlated with emotional dietary behavior and insomnia (P < 0.001) and negatively correlated with dietary habits (P < 0.001). @*CONCLUSIONS@#It is considered that proper nutrition education and interventional measures according to sex are needed for stress control and proper dietary behavior and lifestyle in middle-aged people population, along with projects and policies at the national level.
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Purpose@#To analyze the incidence and treatment costs associated with vision-threatening diabetic retinopathy (VTDR) in type 2 diabetes and to predict future VTDR populations and treatment expenditures. @*Methods@#Using the data from the National Health Insurance Service from 2006 to 2017, we analyzed VTDR treatment costs by year, sex, and age. Based on the results and changes in future population distributions, we estimated the future number and cost of treatments for VTDR. @*Results@#The number of treatments increased by 2.5-fold from 37,634 in 2006 to 96,214 in 2017, and treatment costs increased 3.4-fold from $13,528,587 in 2006 to $45,643,561 in 2017. When analyzed by year, age, and sex, all showed an increasing trend. Future number of treatments was estimated to increase from approximately 96,000 in 2017 to 220,000 by 2030 and treatment costs were projected to increase by 129% from about $45,643,561 in 2017 to about $1,043,055,262 by 2030. @*Conclusions@#As the incidence of VTDR rises due to an aging population and the frequency of intravitreal injections increases due to insurance reimbursement, future treatment expenditures for VTDR are expected to increase as well. Therefore, appropriate policies must be put in place now to secure medical and financial resources to manage VTDR and reduce medical expenditures in the future.
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Background@#Despite the lack of official COVID-19 statistics, various workplaces and occupations have been at the center of COVID-19 outbreaks. We aimed to compare legal measures and governance established for managing COVID-19 infection risks at workplaces in nine Asia and Pacific countries and to recommend key administrative measures. @*Methods@#We collected information on legal measures and governance from both general citizens and workers regarding infection risks such as COVID-19 from industrial hygiene professionals in nine countries (Indonesia, India, Japan, Malaysia, New Zealand, Republic of the Philippines, Republic of Korea, Taiwan, and Thailand) using a structured questionnaire. @*Results@#A governmental body overseeing public health and welfare was in charge of containing the spread and occurrence of infectious diseases under an infectious disease control and prevention act or another special act, although the name of the pertinent organizations and legislation vary among countries. Unlike in the case of other traditional hazards, there have been no specific articles or clauses describing the means of mitigating virus risk in the workplace that are legally required of employers, making it difficult to define the responsibilities of the employer. Each country maintains own legal systems regarding access to the duration, administration, and financing of paid sick leave. Many workers may not have access to paid sick leave even if it is legally guaranteed. @*Conclusion@#Specific legal measures to manage infectious disease risks, such as providing proper personal protective equipment, education, engineering control measures, and paid sick leave are recommended to be stipulated in Industrial safety and health-related acts.
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Background@#The need for regulatory science development to evaluate advanced regulatory products is gradually increasing without hindering the technological development. Creating a research environment and fostering experts through the establishment of regulatory agency-led policies are essential for the development of regulatory science. Method: This is a comparative study of the United States, Japan, Singapore, and Korea. The literature and websites of each regulatory agency were reviewed, and the focus was on advantages and comparing advantages based on definition, development trends, and expert training projects. @*Results@#The United States is striving to develop regulatory science in response to changes in the new pharmaceutical industry through the regulatory science report, and to foster expert both inside and outside the Food and Drug Administration (FDA). Japan is promoting regulatory science centered on regulatory science centers, and is focusing on researching work-related regulatory science within the Pharmaceuticals and Medical Devices Agency (PMDA) and improving employees’ ability to make regulatory decisions. Singapore was aiming to improve Southeast Asia’s regulatory capabilities under the leadership of Centre of Regulatory Excellence (CoRE) within Duke-NUS University. In 2021, Korea is in its early stages, starting to run a university's degree program related to regulatory science this year. @*Conclusion@#Regulatory science should be developed with the aim of improving the regulatory ability of the Ministry of Food and Drug Safety with Korea’s independent concept of regulatory science.
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Background@#Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts. @*Methods@#Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice. @*Results@#EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea’s regulatory science expert training project in 2021 and the EU’s IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea’s project is focused on the Ministry of Food and Drug Safety and universities. @*Conclusion@#Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.
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Purpose@#To analyze changes in the incidences of chronic and traumatic diseases before and after registration as visually disabled. @*Methods@#The incidence and risk of chronic and traumatic diseases were compared between patients registered as visually disabled from 2005 to 2013 and a control group, selected through 1:1 propensity score matching for age, sex, premium quantile, and residential area distribution. Data from the National Health Insurance Service were used and the observation period was set from 2 years before to 5 years after the time of registration as visually disabled. The incidences (%) of chronic and traumatic diseases at the point of interest were determined as the mean values according to year of registration, and the risk was measured by conditional logistic regression analysis. @*Results@#131,434 visually disabled patients and the same number of non-visually impaired controls were included. The incidences of chronic disease and fall-related injury were higher in the visually disabled group before registration, but gradually decreased and became similar to the control group after registration. In addition, the risk of developing chronic diseases was higher in the visually disabled group until 2 years after registration, while the risk of fall-related injury remained consistently higher in the visually disabled group during the observation period. The incidence and risk of hip fracture in the visually disabled group increased gradually from approximately 1 year before registration and remained consistently higher than in the control group. @*Conclusions@#People with visual disability have higher incidences of chronic diseases than do non-visually impaired people and are at greater risk of traumatic injuries, such as hip fractures or falls. There is a need to establish community infrastructure and expand welfare services for the prevention and early treatment of comorbidities, both for patients with registered visual disabilities and for patients who have not yet registered.
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The study examined the perceived health status, dietary habits, and health-related lifestyle habits of middle-aged men and women in Seoul and Gyeonggi-do areas. The survey was conducted on 670 individuals (320 men and, 350 women), aged 40∼64 years, in Seoul and Gyeonggi-do areas. The online and written data were analyzed using the SPSS WIN 25.0 program. Although there was a significant difference in the perceived health status (P＜0.01), there were no significant differences in the subjective stress and the current disease status according to sex. For dietary habits, the scores for fruit intake (P＜0.05), meat and fish intake (P＜0.05), milk and dairy products intake (P＜0.01), and seaweed intake (P＜0.05) were higher in women than men. The scores for three-meal eating (P＜0.05) and water intake (P＜0.01) were higher in men than women. For the health-related habits, alcohol-drinking frequency, daily alcohol consumption, smoking experience, and daily smoking were higher in men than women (P＜0.001). In contrast, caffeinated beverage intake, exercise frequency, and daily smart-phone, computer, and TV using time were similar in both sexes. The meal-eating time was faster in men than women (P＜0.01). For dietary behavior changes, only appetite showed a significant gender difference (P＜0.05). This study provides essential information on the perceived health status, dietary habits, and health-related lifestyle habits in middle-aged men and women. Nevertheless, further research and a practical nutrition program will be needed to solve undesirable dietary habits and improve the health and lifestyle of middle-aged adults according to sex.