1.Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework
Ha Ryong KIM ; Jun Woo KIM ; Jong-Hyeon LEE ; Younghee KIM ; Jungyun LIM ; Yong-Wook BAEK ; Sunkyoung SHIN ; Mina HA ; Hae-Kwan CHEONG ; Kyu Hyuck CHUNG ;
Epidemiology and Health 2024;46(1):e2024060-
OBJECTIVES:
Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease.
METHODS:
We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases.
RESULTS:
By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases.
CONCLUSIONS
The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.
2.Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework
Ha Ryong KIM ; Jun Woo KIM ; Jong-Hyeon LEE ; Younghee KIM ; Jungyun LIM ; Yong-Wook BAEK ; Sunkyoung SHIN ; Mina HA ; Hae-Kwan CHEONG ; Kyu Hyuck CHUNG ;
Epidemiology and Health 2024;46(1):e2024060-
OBJECTIVES:
Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease.
METHODS:
We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases.
RESULTS:
By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases.
CONCLUSIONS
The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.
3.Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework
Ha Ryong KIM ; Jun Woo KIM ; Jong-Hyeon LEE ; Younghee KIM ; Jungyun LIM ; Yong-Wook BAEK ; Sunkyoung SHIN ; Mina HA ; Hae-Kwan CHEONG ; Kyu Hyuck CHUNG ;
Epidemiology and Health 2024;46(1):e2024060-
OBJECTIVES:
Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease.
METHODS:
We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases.
RESULTS:
By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases.
CONCLUSIONS
The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.
4.Toxicological evidence integration to confirm the biological plausibility of the association between humidifier disinfectant exposure and respiratory diseases using the AEP-AOP framework
Ha Ryong KIM ; Jun Woo KIM ; Jong-Hyeon LEE ; Younghee KIM ; Jungyun LIM ; Yong-Wook BAEK ; Sunkyoung SHIN ; Mina HA ; Hae-Kwan CHEONG ; Kyu Hyuck CHUNG ;
Epidemiology and Health 2024;46(1):e2024060-
OBJECTIVES:
Exposure to humidifier disinfectants has been linked to respiratory diseases, including interstitial lung disease, asthma, and pneumonia. Consequently, numerous toxicological studies have explored respiratory damage as both a necessary and sufficient condition for these diseases. We systematically reviewed and integrated evidence from toxicological studies by applying the evidence integration method established in previous research to confirm the biological plausibility of the association between exposure and disease.
METHODS:
We conducted a literature search focusing on polyhexamethylene guanidine phosphate (PHMG) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT), the primary ingredients in humidifier disinfectants. We selected relevant studies based on their quality and the population, exposure, comparator, outcome (PECO) statements. These studies were categorized into three lines of evidence: hazard information, animal studies, and mechanistic studies. Based on a systematic review, we integrated the evidence to develop an aggregate exposure pathway–adverse outcome pathway (AEP-AOP) model for respiratory damage. The reliability and relevance of our findings were assessed by comparing them with the hypothesized pathogenic mechanisms of respiratory diseases.
RESULTS:
By integrating toxicological evidence for each component of the AEP-AOP framework for PHMG and CMIT/MIT, we developed an AEP-AOP model that elucidates how disinfectants released from humidifiers expose target sites, triggering molecular initiating events and key events that ultimately lead to respiratory damage. This model exhibits high reliability and relevance to the pathogenesis of respiratory diseases.
CONCLUSIONS
The AEP-AOP model developed in this study provides strong evidence, based on evidence-based toxicology, that exposure to humidifier disinfectants causes respiratory diseases. This model demonstrates the pathways leading to respiratory damage, a hallmark of these conditions.
5.Evidence integration on health damage for humidifier disinfectant exposure and legal presumption of causation
Mina HA ; Taehyun PARK ; Jong-Hyun LEE ; Younghee KIM ; Jungyun LIM ; Yong-Wook BAEK ; Sol YU ; Hyen-Mi CHUNG ; Kyu Hyuck CHUNG ; Hae-Kwan CHEONG ;
Epidemiology and Health 2023;45(1):e2023095-
OBJECTIVES:
Inhalation exposure to humidifier disinfectants has resulted to various types of health damages in Korea. To determine the epidemiological correlation necessary for presuming the legal causation, we aimed to develop a method to synthesize the entire evidence.
METHODS:
Epidemiological and toxicological studies are systematically reviewed. Target health problems are selected by criteria such as frequent complaints of claimants. Relevant epidemiologic studies are reviewed and the risk of bias and confidence level of the total evidence are evaluated. Toxicological literature reviews are conducted on three lines of evidence including hazard information, animal studies, and mechanistic studies, considering the source-to-exposure-to-outcome continuum. The confidence level of the body of evidence is then translated into the toxicological evidence levels for the causality between humidifier disinfectant exposure and health effects. Finally, the levels of epidemiological and toxicological evidence are synthesized.
RESULTS:
Under the Special Act revised in 2020, if the history of exposure and the disease occurred/worsened after exposure were approved, and the epidemiological correlation between the exposure and disease was verified, the legal causation is presumed unless the company proves the evidence against it. The epidemiological correlation can be verified through epidemiological investigations, health monitoring, cohort investigations and/or toxicological studies. It is not simply as statistical association as understood in judicial precedents, but a general causation established by the evidence as a whole, i.e., through weight-of-the-evidence approach.
CONCLUSIONS
The weight-of-the-evidence approach differs from the conclusive single study approach and this systematic evidence integration can be used in presumption of causation.
6.Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09)
Jieun LEE ; Keun Seok LEE ; Sung Hoon SIM ; Heejung CHAE ; Joohyuk SOHN ; Gun Min KIM ; Kyung-Hee LEE ; Su Hwan KANG ; Kyung Hae JUNG ; Jae-ho JEONG ; Jae Ho BYUN ; Su-Jin KOH ; Kyoung Eun LEE ; Seungtaek LIM ; Hee Jun KIM ; Hye Sung WON ; Hyung Soon PARK ; Guk Jin LEE ; Soojung HONG ; Sun Kyung BAEK ; Soon Il LEE ; Moon Young CHOI ; In Sook WOO
Cancer Research and Treatment 2023;55(1):123-135
Purpose:
The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.
Materials and Methods:
We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.
Results:
The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).
Conclusion
Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.
7.A Study of Retinal and Choroidal Vessel Changes in Chronic Alcoholics
Inkee KIM, ; Sung Won LEE ; Hae Lim LEE ; Ho RA ; Jiwon BAEK
Journal of the Korean Ophthalmological Society 2023;64(6):507-513
Purpose:
To compare the retinal and choroidal vessels of chronic alcoholics with non-alcoholics.
Methods:
This study included alcohol-associated liver disease (ALD) patients admitted between December 2020 and October 2021, along with age-matched controls. Retinal and choroidal vessel densities, measured using image binarization at the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris, and choroidal layers, were compared between ALD patients and controls. Correlations between clinical parameters and vessel densities in ALD patients were also analyzed.
Results:
Vessel densities at SCP, DCP, choriocapillaris, and choroidal layers were not significantly different between controls and ALD patients (p = 0.496, 0.988, 0.909, and 0.317, respectively). Platelet time and international normalized ratio (INR) were positively correlated with SCP density in ALD patients (r = 0.393 and 0.393; p = 0.015 and 0.015, respectively).
Conclusions
ALD does not significantly affect vessel densities in the retina and choroid. The positive correlations of platelet time and INR with SCP may be related to vessel dilatation, but they require further investigation.
8.Investigation of Dental Hygienists’ Practice about Rules on Dental Disputes Prevention
Hae-in YOON ; Im-hee JUNG ; Chae-lin LEE ; Eun-su LEE ; Yoo-jin BAEK ; Ju-hee SUK ; Ye-jun PARK ; Tae-yang KIM ; Jun-yeong KWON ; Hee-jung LIM
Journal of Dental Hygiene Science 2022;22(4):206-214
Background:
This study analyzed the practice of dental medical dispute prevention rules of dental hygienists to present an improvement plan for improving perceived importance and practice and provide data for the development of effective medical dispute prevention programs.
Methods:
A self-administered questionnaire survey was conducted targeting dental hygienists who were providing assistance at dental hospitals and dental clinics in Seoul and Gyeonggi-do regions from March 22 to April 28, 2022. The questionnaire collected from 273 dental hygienists consisted of eight questions on general characteristics, 30 questions on medical dispute experience, and 14 questions on medical dispute prevention.
Results:
Complaints showed a high experience rate in ‘Consultation & reservation’, medical disputes in ‘Patient handling (unkind) related’, and ‘Prosthesis installation and cement removal’. In both the importance and practice of medical dispute prevention rules, Preservation of medical records and other medical-related data’ was high, and ‘Management of patients on standby for a long time’was low in terms of practice. ‘Lack of time’ and ‘Lack of manpower’ were cited as reasons for not resolving dental treatment disputes. The importance of dental dispute prevention rules was found to be significant according to age and position, and it was also found to affect the level of practice.
Conclusion
Seventy-six-point six percent of the respondents said that education on the prevention of medical disputes was necessary, although they lacked recognition of prevention rules compared to their perceptions and experiences. This study suggested specifying prevention rules in dental hygiene subjects and expanding education, improvement of dental treatment system, revise the law on the range of work to improve the recognition and practice of prevention rules.
9.Multimodal Assessment of Neural Substrates in Computerized Cognitive Training: A Preliminary Study.
Hae Ri NA ; Jae Sung LIM ; Woo Jung KIM ; Jae Won JANG ; Min Jae BAEK ; Jeongeun KIM ; Young Ho PARK ; So Young PARK ; SangYun KIM
Journal of Clinical Neurology 2018;14(4):454-463
BACKGROUND AND PURPOSE: Several studies have validated the clinical efficacy of computerized cognitive training applications. However, few studies have investigated the neural substrates of these training applications using simultaneous multimodal neuroimaging modalities. We aimed to determine the effectiveness of computerized cognitive training and corresponding neural substrates through a multimodal approach. METHODS: Ten patients with mild cognitive impairment (MCI), six patients with subjective memory impairment (SMI), and 10 normal controls received custom-developed computerized cognitive training in the memory clinic of a university hospital. All of the participants completed 24 sessions of computerized cognitive training, each lasting 40 minutes and performed twice weekly. They were assessed using neuropsychological tests (both computerized and conventional), electroencephalography, fluorodeoxyglucose positron-emission tomography (FDG-PET), volumetric magnetic resonance imaging (MRI), and diffusion-tensor imaging (DTI) at pre- and posttraining. RESULTS: The patients with MCI exhibited significant improvements in the trail-making test–black & white-B, and memory domain of the computerized cognitive assessment. Subjects with normal cognition exhibited significant improvements in scores in the language and attention-/psychomotor-speed domains. There were no significant changes in subjects with SMI. In the pre- and posttraining evaluations of the MCI group, FDG-PET showed focal activation in the left anterior insula and anterior cingulate after training. Volumetric MRI showed a focal increase in the cortical thickness in the rostral anterior cingulate. DTI revealed increased fractional anisotropy in several regions, including the anterior cingulate. CONCLUSIONS: The anterior cingulate and anterior insula, which are parts of the salience network, may be substrates for the improvements in cognitive function induced by computerized cognitive training.
Anisotropy
;
Cognition
;
Electroencephalography
;
Gyrus Cinguli
;
Humans
;
Magnetic Resonance Imaging
;
Memory
;
Mild Cognitive Impairment
;
Neuroimaging
;
Neuropsychological Tests
;
Positron-Emission Tomography
;
Treatment Outcome
10.Prevalence and Factors Associated with the Use of Eye Care Services in South Korea: Korea National Health and Nutrition Examination Survey 2010–2012.
Yong Seok PARK ; Hwan HEO ; Byeong Jin YE ; Young Woo SUH ; Seung Hyun KIM ; Shin Hae PARK ; Key Hwan LIM ; Sung Jin LEE ; Song Hee PARK ; Seung Hee BAEK
Korean Journal of Ophthalmology 2017;31(1):58-70
PURPOSE: To estimate the factors and prevalence of eye care service utilization in the South Korean population. METHODS: This cross-sectional, population-based study included data from 22,550 Koreans aged ≥5 years who participated in the Korea National Health and Nutrition Examination Survey from 2010 to 2012. For people aged 5 to 11 years (young children), information was based on self-reports of contact with eye care service in the past year; for people aged ≥12 years (older population), the information was based on the self-reported lifetime contact with eye care service. Univariate and multivariate logistic regression analyses of the complex sample survey data were performed. RESULTS: The prevalence of eye care service use in young children during the past year was 61.1% (95% confidence interval, 58.1%–64.1%), while that in the older population during their lifetime was 73.5%. Subjects aged 7 to 11 years were more likely to have had an eye examination in the past year than subjects aged 5 to 6 years (odds ratio, 3.83; 95% confidence interval, 2.37–6.19). Multivariate logistic regression analysis indicated that higher monthly household income, being a National Health Insurance holder, and having private health insurance were related to more frequent use of eye care services in young children. For the older population and women, those living in an urban area and those with a best-corrected visual acuity less than 20 / 40 in the worse-seeing eye were more likely to have had an eye examination during their lifetime. Low education level was associated with low lifetime use of eye care services in the older population. CONCLUSIONS: There are sociodemographic disparities with use of eye care services in South Korea. This population-based study provides information that is useful for determining different intervention programs based on sociodemographic disparities to promote eye care service utilization in South Korea.
Child
;
Education
;
Family Characteristics
;
Female
;
Healthcare Disparities
;
Humans
;
Insurance, Health
;
Korea*
;
Logistic Models
;
National Health Programs
;
Nutrition Surveys*
;
Prevalence*
;
Socioeconomic Factors
;
Visual Acuity

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