Publications by authors named "Jung-Hun Kang"

151 Publications

Relationship between heavy metal exposure and type 2 diabetes: a large-scale retrospective cohort study using occupational health examinations.

BMJ Open 2021 Mar 4;11(3):e039541. Epub 2021 Mar 4.

Internal Medicine, Dong-A University Medical Center, Busan, The Republic of Korea

Objectives: To investigate the associations between heavy metal exposure and serum ferritin levels, physical measurements and type 2 diabetes mellitus (DM).

Design: A retrospective cohort study.

Setting: Changwon, the location of this study, is a Korean representative industrial city. Data were obtained from medical check-ups between 2002 and 2018.

Participants: A total of 34 814 male subjects were included. Of them, 1035 subjects with lead exposure, 200 subjects with cadmium exposure and the 33 579 remaining were assigned to cohort A, cohort B and the control cohort, respectively. Data including personal history of alcohol and smoking, age, height, weight, the follow-up duration, haemoglobin A1c (HbA1c), fasting blood sugar (FBS), ferritin levels, and lead and cadmium levels within 1 year after exposure were collected.

Primary Outcome Measure: In subjects without diabetes, changes in FBS and HbA1c were analysed through repeated tests at intervals of 1 year or longer after the occupational exposure to heavy metals.

Results: In Cohort A, DM was diagnosed in 33 subjects. There was a significant difference in lead concentrations between the subjects diagnosed with DM and those without DM during the follow-up period (3.94±2.92 mg/dL vs 2.81±2.03 mg/dL, p=0.002). Simple exposure to heavy metals (lead and cadmium) was not associated with DM in Cox regression models (lead exposure (HR) 1.01, 95% CI: 0.58 to 1.77, p 0.971; cadmium exposure HR 1.48, 95% CI: 0.61 to 3.55, p=0.385). Annual changes in FBS according to lead concentration at the beginning of exposure showed a positive correlation (r=0.072, p=0.032).

Conclusion: Our findings demonstrated that simple occupational exposure to heavy metals lead and cadmium was not associated with the incidence of DM. However, lead concentrations at the beginning of the exposure might be an indicator of DM and glucose elevations.
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http://dx.doi.org/10.1136/bmjopen-2020-039541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934714PMC
March 2021

Korean Version of the Patient Dignity Inventory: Translation and Validation in Patients With Advanced Cancer.

J Pain Symptom Manage 2021 Jan 20. Epub 2021 Jan 20.

Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Context: The goal of palliative care is to maximize the quality of life and thus maintain the dignity of patients facing problems associated with a life-threatening illness. The Patient Dignity Inventory (PDI) is an instrument used to measure various sources of distress that can impact patients' sense of dignity at the end of life.

Objectives: We aimed to obtain a Korean translation of the PDI (PDI-K) and evaluate its psychometric properties in patients with advanced cancer.

Methods: Translation and cultural adaptation of the PDI were performed to obtain the Korean version. In a sample of 131 inpatients and outpatients with advanced cancer, psychometric properties, including factor structure, internal consistency, and concurrent validity, were examined. Concurrent validity was evaluated using the Edmonton Symptom Assessment System, the Hospital Anxiety and Depression Scale, and the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being.

Results: Cronbach's α for the PDI-K was 0.96. Four factors were identified by exploratory factor analysis, accounting for 68.7% of the overall variance: Dependency and Physical Symptoms, Psychological Distress, Existential Distress, and SocialSupport. Concurrent validity was confirmed by significant correlations between PDI-K and Edmonton Symptom Assessment System (r = 0.40 to 0.59, P < 0.001), Hospital Anxiety and Depression Scale (r = 0.78 to 0.81, P < 0.001), and Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (r = -0.32 to -0.57, P < 0.001).

Conclusion: Our findings indicate that the PDI-K is a valid and reliable instrument to measure dignity-related distress in patients with advanced cancer. This tool provides a four-factor Korean language alternative to the PDI.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.01.003DOI Listing
January 2021

One health approach to genetic relatedness in SCCmec between methicillin-resistant Staphylococcus isolates from companion dogs with pyoderma and their owners.

Vet Microbiol 2021 Feb 13;253:108957. Epub 2020 Dec 13.

Laboratory of Veterinary Dermatology and The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address:

Staphylococcal cassette chromosome mec (SCCmec) confers methicillin resistance and shows ability for horizontal transfer. However, little is known about the potential transfer of SCCmec between different species of staphylococci in a clinical setting. In this study, we investigated the genetic relationship of SCCmec between staphylococci isolated from dogs affected with pyoderma and their owners. Clinical isolates were collected from pyoderma lesions of dogs and from the nasal cavity and finger of owners. Clonal lineages were characterized using multi-locus sequence typing. Genetic relatedness of SCCmec in the isolates from dogs and owners was first evaluated with dru and SCCmec typing, and whole-genome sequencing (WGS) was used to confirm the similarity of DNA sequences and the structural composition of SCCmec. A total of 100 Staphylococcus strains were isolated from 31 dog-owner pairs. One pair with isolates carrying the same SCCmec type V and dru type 11a was detected: 18D20-1 (S. pseudintermedius, dog), 18D20-2 (S. schleiferi, dog), and 18H20-F2 (S. epidermidis, dog owner). WGS revealed that these three isolates showed remarkable genetic similarity in SCCmec with respect to DNA sequences, dru type, structure composition of ccrC and the mec complex, and DR-1 in orfX, which is considered to be the insertion site of SCCmec. Entire identical nucleotide sequences of the whole SCCmec region in different Staphylococcus strains were absent between dogs and owners. However, the remarkable genetic similarity of SCCmec from staphylococci isolated from a dog and owner pair emphasizes that antimicrobial resistance surveillance adopted One Health concept should be continuously performed.
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http://dx.doi.org/10.1016/j.vetmic.2020.108957DOI Listing
February 2021

The Attitudes of Physicians and the General Public toward Prognostic Disclosure of Different Serious Illnesses: a Korean Nationwide Study.

J Korean Med Sci 2020 Dec 7;35(47):e401. Epub 2020 Dec 7.

Department of Family Medicine, Seoul National University Hospital, Seoul, Korea.

Background: Although international guidelines recommend palliative care approaches for many serious illnesses, the palliative needs of patients with serious illnesses other than cancer are often unmet, mainly due to insufficient prognosis-related discussion. We investigated physicians' and the general public's respective attitudes toward prognostic disclosure for several serious illnesses.

Methods: We conducted a cross-sectional survey of 928 physicians, sourced from 12 hospitals and the Korean Medical Association, and 1,005 members of the general public, sourced from all 17 administrative divisions in Korea.

Results: For most illnesses, most physicians (adjusted proportions - end-organ failure, 99.0%; incurable genetic or neurologic disease, 98.5%; acquired immune deficiency syndrome [AIDS], 98.4%; stroke or Parkinson's disease, 96.0%; and dementia, 89.6%) and members of the general public (end-organ failure, 92.0%; incurable genetic or neurologic disease, 92.5%; AIDS, 91.5%; stroke or Parkinson's disease, 92.1%; and dementia, 86.9%) wanted to be informed if they had a terminal prognosis. For physicians and the general public, the primary factor to consider when disclosing terminal status was "the patient's right to know his/her condition" (31.0%). Yet, the general public was less likely to prefer prognostic disclosure than physicians. Particularly, when their family members were patients, more than 10% of the general public did not want patients to be informed of their terminal prognosis. For the general public, the main reason for not disclosing prognosis was "psychological burden such as anxiety and depression" (35.8%), while for the physicians it was "disclosure would have no beneficial effect" (42.4%).

Conclusion: Most Physicians and the general public agreed that disclosure of a terminal prognosis respects patient autonomy for several serious illnesses. The low response rate of physicians might limit the generalizability of the results.
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http://dx.doi.org/10.3346/jkms.2020.35.e401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721562PMC
December 2020

Dexamethasone-Induced Hiccups: An Important But Inconspicuous Symptom in Cancer.

J Palliat Med 2020 11;23(11):1421

Department of Internal Medicine, College of Medicine, Gyeongsand National University, Jinju, Republic of Korea.

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http://dx.doi.org/10.1089/jpm.2020.0260DOI Listing
November 2020

rhEGF Treatment Improves EGFR Inhibitor-Induced Skin Barrier and Immune Defects.

Cancers (Basel) 2020 Oct 25;12(11). Epub 2020 Oct 25.

Department of Pathology, Dong-A University College of Medicine, Busan 49201, Korea.

The mechanisms of epidermal growth factor (EGF) affecting EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF's positive effects. Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). As a result, rhEGF increased EGFR and pEGFR expression. Furthermore, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. In addition, rhEGF bound to EGFR after than cetuximab, but cetuximab bound to EGFR more strongly than rhEGF. Moreover, expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRI-treated tissue. However, in rhEGF and EGFRI co-treated tissue, those expressions were increased. Expression of IL-1α, IL-8, and TNF-α was increased by EGFRIs and down-regulated by rhEGF. Furthermore, hBD-2 and hBD-3 protein expressions were inhibited by cetuximab or gefitinib treatment, and those decrements were increased by rhEGF treatment. In patients' tissue evaluation, compared with controls, patients' Ki-67 and EGFR expression were decreased ( = 0.015, = 0.001). Patients' IL-17 and TNF-α expression intensity was higher than that of the control group ( = 0.038, = 0.037). After treatment with EGF ointment, average values of Ki-67, EGFR, and Melan-A were changed to normal values. Oppositely, patients' proportions of IL-17 and TNF-α were decreased to low stain level. In conclusion, treatment of rhEGF improved EGFRI-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.
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http://dx.doi.org/10.3390/cancers12113120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692663PMC
October 2020

Choosing Wisely: The Korean Perspective and Launch of the 'Right Decision in Cancer Care' Initiative.

Cancer Res Treat 2020 Jul 2;52(3):655-660. Epub 2020 Jun 2.

Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Korea.

Government healthcare expenditure is rising in Korea, and the costs incurred by patients in Korea exceed those incurred by patients in other Organization for Economic Co-operation and Development countries. Despite the increasing health expenditure, patient demand for services is increasing as well, so it is now becoming recognized that cancer care needs to be balanced. The most important measure in cancer care optimization is to provide high-quality care while keeping costs sustainable. The Korean Cancer Association considers the current situation of cancer therapy in Korea the foremost issue, which has led to the implementation of the nationwide 'Right Decisions in Cancer Care' initiative. This initiative is based on the concepts of medical professionalism in that it should be led by physicians working in the field of oncology, that education should be offered to patients and clinicians, and that it should influence healthcare policy. In this article, we introduce the nationwide 'Right Decision in Cancer Care' initiative and highlight the five initial items on its agenda. The agenda is open to expansion and update as the medical environment evolves and additional clinical evidence becomes available.
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http://dx.doi.org/10.4143/crt.2020.221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373865PMC
July 2020

Regorafenib in patients with advanced Child-Pugh B hepatocellular carcinoma: A multicentre retrospective study.

Liver Int 2020 10 9;40(10):2544-2552. Epub 2020 Jul 9.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Introduction: Regorafenib is an approved agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib, but little is known about its clinical outcomes in Child-Pugh B patients. We aimed to investigate the safety and effectiveness of regorafenib in Child-Pugh B HCC patients.

Methods: This multicentre retrospective study included 59 patients with Child-Pugh B HCC who received regorafenib. Comparative analyses were performed with an independent cohort of Child-Pugh class A patients from the same registry (n = 440).

Results: The median age was 58 years (range, 19-83). All patients had progression on prior sorafenib. Regorafenib was given as 2nd line, and 3rd-4th line systemic therapy in 37 (62.7%) and 22 (37.3%) patients respectively. Compared to Child-Pugh A cohort, grade 3-4 AEs were more common in the Child-Pugh B cohort (27.1% vs 14.1%, P = .017). The median progression-free survival (PFS) and overall survival (OS) were 1.8 and 4.6 months, respectively, and these were significantly poorer than the Child-Pugh A cohort (P = .008 and P < .001 respectively). Child-Pugh B patients with albumin-bilirubin (ALBI) grade 3 had a significantly higher frequency of increased bilirubin (P = .01 for any grade and P = .01 for grade 3-4) and showed significantly poorer OS (P = .021), compared to those with ALBI grade 1 or 2.

Conclusion: Regorafenib's poor clinical outcomes and increased frequency of severe adverse events lead us to discourage its use in the Child-Pugh B population. In particular, regorafenib should not be used in Child-Pugh B patients with ALBI grade 3.
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http://dx.doi.org/10.1111/liv.14573DOI Listing
October 2020

Impact of family caregivers' awareness of the prognosis on their quality of life/depression and those of patients with advanced cancer: a prospective cohort study.

Support Care Cancer 2021 Jan 6;29(1):397-407. Epub 2020 May 6.

Department of Family Medicine, Seoul National University Hospital, Seoul, South Korea.

Purpose: A caregiver's prognostic awareness can affect clinical decisions for the patient. The purpose of this study was to examine the impact of family caregivers' prognostic awareness on the quality of life (QOL) and emotional state of both patients with advanced cancer and their caregivers.

Methods: This prospective cohort study was conducted from December of 2016 to January of 2018. A total of 159 patients with advanced cancer and an equal number of caregivers participated. The investigation tools used include the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C15-Palliative, the McGill Quality of Life Questionnaire, and the Patient Health Questionnaire-9, and evaluation was performed at baseline, 3 months, and 6 months. Covariance analysis with a general linear modeling was used to compare changes in quality of life scores according to the caregivers' awareness of the prognosis.

Results: Mean patient overall QOL score increased in the group of caregivers who were aware of prognosis and decreased in the caregivers who were not aware of the prognosis (p = 0.018). The changes over time in the patients' QOL scores associated with symptoms improved with caregiver awareness (pain, p = 0.017; dyspnea, p = 0.048; appetite loss, p = 0.045). The percentage of depressed patients was smaller after 3 months in the group with caregivers aware of the prognosis (baseline to 3 months p = 0.028). Caregivers who did not understand their patients' prognosis exhibited better existential well-being (p = 0.036), and the incidence of depression was lower in this group at 3 months (p = 0.024).

Conclusion: Caregivers' prognostic awareness may improve the quality of life and mood in patients with advanced cancer; however, this awareness may harm the quality of life and mood of the caregivers. These results may aid in developing in-depth interventions regarding prognosis for both patients and their caregivers.
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http://dx.doi.org/10.1007/s00520-020-05489-8DOI Listing
January 2021

Interference with daily functioning by breakthrough pain in patients with cancer.

Support Care Cancer 2020 Nov 14;28(11):5177-5183. Epub 2020 Feb 14.

Department of Internal Medicine, Yeungnam University, Daegu, Republic of Korea.

Purpose: To investigate the association between quality of life (QOL) and breakthrough cancer pain (BTCP) intensity in patients who met the commonly accepted definition of BTCP.

Methods: This study was a subset analysis of a South Korean multicenter, non-interventional, cross-sectional, nationwide survey. Participants were recruited from March 2016 to December 2017. BTCP was defined as a controlled background pain of less than a numeric rating scale (NRS) of 3 and any flare-up pain intensity. Pain intensity data were collected using the Brief Pain Inventory (BPI), which includes an interference assessment of the affective and physical domains. Patients were categorized by BTCP intensity into mild (NRS 1-3), moderate (4-6), and severe (7-10) groups.

Results: Of the 969 screened patients with cancer, 679 had ≤ NRS 3 background pain, of whom 438 completed the BPI. Of these 438 patients, 40, 204, and 194 were in the mild, moderate, and severe BTCP groups, respectively. The median NRS of BTCP was 6.0 (interquartile range = 5.0-8.0). Patients with moderate-severe BTCP had significantly higher interference with daily functioning (IDF) scores than did mild BTCP patients (3.3 vs. 5.7; p < 0.01). Both domains of IDF were significantly hampered proportionally by increased BTCP intensity (p < 0.001). The median total IDF scores of the no, moderate, and severe BTCP groups were 3.3, 5.0, and 6.9, respectively. Furthermore, IDF depended on BTCP intensity, duration, and frequency (p < 0.01) but not on pain type and cause.

Conclusion: An increase in BTCP intensity is likely to result in IDF, regardless of the cause or type of BTCP.
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http://dx.doi.org/10.1007/s00520-020-05329-9DOI Listing
November 2020

The Impacts of Prognostic Awareness on Mood and Quality of Life Among Patients With Advanced Cancer.

Am J Hosp Palliat Care 2020 Nov 13;37(11):904-912. Epub 2020 Feb 13.

Department of Family Medicine, Seoul National University Hospital, Seoul, Korea.

Background: Accurate awareness of the prognosis is an important factor in the treatment decision of patients with advanced cancer; however, prognostic disclosure is still subject to debate because it can reduce patient's satisfaction and increase depression.

Aim: The purpose of this study is to assess whether patients' prognostic awareness is associated with decreased quality of life (QoL) or increased depressive mood in patients with advanced cancer.

Design And Participants: In this cohort study, 386 patients with advanced cancer were recruited across 3 periods from December 2016 to August 2018. The outcome of this study was a change in QoL and depression according to the patients' prognostic awareness at baseline, 3 months, and 6 months.

Results: This study found significant differences in changes of QoL based on patients' prognostic awareness. From baseline to 3 months, emotional functioning ( = .039), pain ( = .042), existential well-being ( = .025), and social support ( = .038) subscale scores improved significantly more in those with lack of prognostic awareness. Over 6 months, the group without prognostic awareness improved significantly in terms of physical functioning ( = .037), emotional functioning ( = .002), nausea/vomiting ( = .048), and constipation ( = .039) subscale scores and existential well-being scores ( = .025). No significant difference between the groups was found in terms of depression.

Conclusion: Accurate prognostic awareness may pose harm and may provide no additional benefits in terms of QoL and mood among patients with advanced cancer for a short period of time.
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http://dx.doi.org/10.1177/1049909120905789DOI Listing
November 2020

Debatable Issues in Palliative Sedation; Authors' Reply to the Response by Robert Twycross.

J Pain Symptom Manage 2020 05 31;59(5):e2-e3. Epub 2020 Jan 31.

Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jpainsymman.2020.01.010DOI Listing
May 2020

Capecitabine plus Oxaliplatin as a Second-Line Therapy for Advanced Biliary Tract Cancers: A Multicenter, Open-Label, Phase II Trial.

J Cancer 2019 15;10(25):6185-6190. Epub 2019 Oct 15.

Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Centre, Seoul, South Korea.

Although biliary tract cancer (BTC) has a very aggressive nature, some patients maintain a relatively good performance status after failure with first-line treatment of gemcitabine plus cisplatin (GC). Thus, tolerable, feasible, and useful second-line treatments are needed for these patients. We investigated the efficacy of capecitabine plus oxaliplatin (XELOX) as a second-line therapy for patients with advanced BTC who failed first-line GC treatment. In this prospective, phase II trial, we investigated XELOX (capecitabine 1,000 mg/m twice daily on days 1-14 and oxaliplatin 130 mg/m on day 1) as a second-line treatment, given every 3 weeks, totaling 8 cycles in patients with metastatic BTC who failed first-line GC treatment. The primary outcome was progression-free survival (PFS). From December 2015 to November 2016, 50 patients with metastatic intrahepatic or extrahepatic cholangiocarcinoma or gall bladder (GB) cancer were enrolled. The regimen was well tolerated. Toxicities mainly consisted of grade 1 or 2 events, and thrombocytopenia and neuropathy had the highest incidence. In intent-to-treat analysis, one complete response (CR) and six partial responses (PRs) were recorded with XELOX treatment. The overall response rate and the disease control rate from the intent-to-treat analysis were 14% and 52%, respectively. With a median follow-up of 15.6 months, PFS after XELOX was a median of 15.4 weeks (95% CI, 8.5-22.3). This PFS value supported the statistical hypothesis of this study. The median overall survival was 32.7 weeks (95% CI, 21.4-43.9). This phase II trial showed that XELOX treatment was efficacious and had a tolerable toxicity profile in patients with advanced BTC who failed first-line treatment of gemcitabine and cisplatin.
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http://dx.doi.org/10.7150/jca.37610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856733PMC
October 2019

Association of illness understanding with advance care planning and end-of-life care preferences for advanced cancer patients and their family members.

Support Care Cancer 2020 Jun 26;28(6):2959-2967. Epub 2019 Nov 26.

Department of Medical Informatics, Seoul National University College of Medicine, Seoul, South Korea.

Purpose: Little has been determined regarding the association between patients' and families' illness understanding and preferences for medical care. We aimed to evaluate the association of illness understanding with advance care planning (ACP) and preferences for end-of-life care, such as aggressive care, early palliative care (EPC), and hospice care, among advanced cancer patients and their family caregivers.

Methods: Patients were recruited for a prospective cohort study at outpatient and inpatient facilities in nine university hospitals in Korea (n = 150), and their primary family caregivers were also asked to participate (n = 101). Data on ACP and end-of-life care preferences were collected only at baseline in the cohort study with optional questions and were used to analyze these study results.

Results: Patients with illness understanding were more likely to have documented physician orders for life-sustaining treatment (POLSTs) (adjusted odds ratio [aOR] of 4.94) and to have discussed ACP with their families (aOR 2.15) than those who did not. Being expected to live for several months, they were unlikely to prefer active treatment. Caregivers understanding patients' illness were more likely to write advance directives (ADs) and to discuss ACP; furthermore, they had already discussed ACP with family members. They did not prefer active treatment or life-sustaining treatments when their family members were expected to die within a few weeks. There was no significant association between illness understanding and preferences for EPC.

Conclusion: Accurately recognizing an incurable disease is associated with preferences for more ACP and less aggressive care but not with preferences for EPC or hospice care among both advanced cancer patients and their family caregivers.
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http://dx.doi.org/10.1007/s00520-019-05174-5DOI Listing
June 2020

In vitro antibacterial activity of the manuka essential oil from Leptospermum scoparium combined with Tris-EDTA against Gram-negative bacterial isolates from dogs with otitis externa.

Vet Dermatol 2020 Apr 15;31(2):81-85. Epub 2019 Nov 15.

Laboratory of Veterinary Dermatology, The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, South Korea.

Background: The increasing prevalence of antimicrobial resistance among bacteria in dogs with otitis externa has led to a need for novel therapeutic agents.

Hypothesis/objective: To examine the antibacterial effects of manuka oil combined with ethylenediaminetetraacetic acid-tromethamine (Tris-EDTA) against Gram-negative bacteria isolates from dogs with otitis externa.

Methods And Materials: A total of 53 clinical isolates including Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae ssp. pneumoniae and Proteus mirabilis. Antimicrobial susceptibility was determined using disk diffusion; the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of manuka essential oil, with or without Tris-EDTA, were investigated.

Results: A total of 44 isolates were resistant to at least one antibiotic and 19 strains were multidrug-resistant, with resistance to at least one agent in three or more antimicrobial classes. The MICs and MBCs of manuka oil alone were ≥1% (v/v) and ≥2% (v/v), respectively. There was no antimicrobial effect of Tris-EDTA (1.125:0.3 mg/mL) without manuka oil. However, the combination of manuka oil with Tris-EDTA significantly decreased the MICs (ranging from 0.06% to 0.5%, v/v; P < 0.001) and MBCs (ranging from 0.06% to 1%, v/v; P < 0.001). There also was no significant difference between multidrug-resistant and nonresistant bacterial isolates in terms of the antimicrobial activity of manuka oil with Tris-EDTA.

Conclusions And Clinical Importance: The study findings suggest that manuka oil, especially when combined with Tris-EDTA, may be a promising alternative therapeutic option for Gram-negative otic pathogens. Clinical studies are needed to assess potential for in vivo ototoxic effects and efficacy.
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http://dx.doi.org/10.1111/vde.12807DOI Listing
April 2020

First detection of multiresistance pRE25-like elements from Enterococcus spp. in Staphylococcus pseudintermedius isolated from canine pyoderma.

J Glob Antimicrob Resist 2020 03 4;20:304-308. Epub 2019 Sep 4.

Laboratory of Veterinary Dermatology and The Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul 08826, South Korea. Electronic address:

Objectives: Enterococcus pRE25 is a conjugative and mobilising multiresistance plasmid from Enterococcus faecalis RE25. pRE25-like enterococcal plasmid pWZ909 mediates the delivery of vancomycin resistance to methicillin-resistant Staphylococcus aureus via a Tn1546-like transposon. However, whether pRE25-like elements contribute to multidrug resistance in Staphylococcus spp. has not yet been investigated. Here we describe the first detection of multiresistance pRE25-like elements in the chromosomal DNA of multidrug-resistant Staphylococcus pseudintermedius (MDRSP).

Methods: A total of 46 MDRSP clinical strains were isolated from canine pyoderma in Korea. Their genetic characteristics were analysed by multilocus sequence typing (MLST) and PCR targeting pRE25-like elements. Whole-genome sequencing (WGS) was performed on four isolates.

Results: WGS detected that the chromosomal 22-kb pRE25-like elements contained five antimicrobial resistance genes [cat, erm(B), aphA-3, aadK and sat4], IS1252, IS256, and a toxin-antitoxin system within copies of IS1216. BLASTn alignment analysis revealed that 84% of the chromosomal 22-kb pRE25-like elements sequence is homologous (99.8% identity) to the enterococcal pRE25 plasmid sequence. PCR assay showed that 52.2% of MDRSP isolates were positive for pRE25-like elements and were presumed to contain pRE25-like elements (pRE25 group). The sequence types (STs) of the pRE25 group were diverse, with 18 STs identified, among which 12 STs were first reported in Korea.

Conclusion: Enterococcal pRE25-like elements are suspected to be widespread in MDRSP isolated from companion dogs in Korea. Considering that companion dogs live in a closely shared environment with humans, continuous surveillance of pRE25-like elements is needed for other staphylococci commonly isolated from humans.
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http://dx.doi.org/10.1016/j.jgar.2019.08.022DOI Listing
March 2020

A Randomized Controlled Trial of Epidermal Growth Factor Ointment for Treating Epidermal Growth Factor Receptor Inhibitor-Induced Skin Toxicities.

Oncologist 2020 01 6;25(1):e186-e193. Epub 2019 Sep 6.

Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea.

Background: The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs).

Materials And Methods: This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily.

Results: Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm.

Conclusion: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.
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http://dx.doi.org/10.1634/theoncologist.2019-0221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964120PMC
January 2020

Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial.

Cancer Discov 2019 10 17;9(10):1388-1405. Epub 2019 Jul 17.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups ( aberration, mutation, mutation/amplification, amplification, MET overexpression, all negative, deficient, or amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), adavosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high copy number by ctDNA and response to savolitinib. SIGNIFICANCE: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility..
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http://dx.doi.org/10.1158/2159-8290.CD-19-0442DOI Listing
October 2019

Correction to: Priorities of a "good death" according to cancer patients, their family caregivers, physicians, and the general population: a nationwide survey.

Support Care Cancer 2019 Oct;27(10):3921-3926

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

While recently extending that research, however, we discovered that 236 members of the general population were mistakenly duplicated by the investigating agency (Word Research) and 1241 were reported rather than 1005. Here, we present corrections and discuss the relevant data.
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http://dx.doi.org/10.1007/s00520-019-04985-wDOI Listing
October 2019

Romiplostim-related myelofibrosis in refractory primary immune thrombocytopenia: A Case report.

Medicine (Baltimore) 2019 Jun;98(25):e15882

Division of Hemato-oncology, Department of Internal Medicine, Gyeongsang National University of Medicine and Gyeongsang National University Hospital, Republic of Korea.

Rationale: Primary immune thrombocytopenia (ITP) is an immune-mediated disease that is defined as increased platelet destruction and impaired platelet production. Treatment is recommended for highly selected patients, the standard regimen includes glucocorticoid, intravenous immunoglobulin (IVIG). The recombinant thrombopoietin (TPO) receptor agonists, romiplostim, stimulate platelet production and have approved for glucocorticoid or IVIG, splenectomy-refractory chronic ITP patients.

Patient Concerns: A patient has been diagnosed with ITP, reftractory to steroid, IVIG, splenectomy, danazol, and cyclosporine. The patient received romiplostim to normalize his platelet count, however, over the course of the following year, his platelet counts progressively decreased despite increasing the romiplostim dosing.

Diagnoses: A peripheral blood smear showed a severe leukoerythroblastic reaction and bone marrow biopsy demonstrated myelofibrosis due to romiplostim.

Outcomes: Since this diagnosis, romiplostim was discontinued for a while, after 3 months, romiplostim was re-administered to improve thrombocytopenia. His platelet count recovered to 70,000/mm after the administration of romiplostim at 2 μg/kg, and he did not experience complications for 6 months.

Lessons: This report represents the first evidence of romiplostim-induced myelofibrosis, which was associated with increased levels of bone marrow reticulin and Masson trichrome staining.
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http://dx.doi.org/10.1097/MD.0000000000015882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636978PMC
June 2019

Behaviors and Attitudes toward the Use of Complementary and Alternative Medicine among Korean Cancer Patients.

Cancer Res Treat 2019 Jul 7;51(3):851-860. Epub 2019 Jun 7.

Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.

Purpose: A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea.

Materials And Methods: Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution.

Results: In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians.

Conclusion: Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.
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http://dx.doi.org/10.4143/crt.2019.137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639220PMC
July 2019

Canine pyoderma gangrenosum with recurring skin lesions of unknown origin and splenic involvement.

Vet Dermatol 2019 Aug 14;30(4):359-e105. Epub 2019 May 14.

Department of Veterinary Clinical Sciences, Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, 08826, Korea.

Background: Reports of canine pyoderma gangrenosum (PG) are uncommon in the veterinary literature. Rarer still are cases describing dogs with both skin lesions and internal organ involvement.

Objective: To describe a case of canine PG with skin and internal organ involvement.

Animals: A client-owned dog.

Methods And Materials: Complete blood count, serum chemistry, C-reactive protein and SNAP cPL tests, and abdominal ultrasonography and fine-needle aspiration of the spleen were performed.

Results: The dog was treated with oral prednisolone and ciclosporin. After three months of therapy, ultrasonography revealed normalization of the spleen and resolution of skin lesions.

Conclusion And Clinical Importance: Dogs with skin lesions compatible with PG should be screened carefully for internal organ involvement. Ciclosporin may be a useful treatment for the immediate and long-term management of canine PG.
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http://dx.doi.org/10.1111/vde.12756DOI Listing
August 2019

Clinical Patterns of Continuous and Intermittent Palliative Sedation in Patients With Terminal Cancer: A Descriptive, Observational Study.

J Pain Symptom Manage 2019 07 23;58(1):65-71. Epub 2019 Apr 23.

Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Republic of Korea; Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju, Republic of Korea. Electronic address:

Context: Limited information is available regarding the detailed clinical patterns of palliative sedation (PS), that is, the symptom control rate, salvage medication, and the effectiveness of intermittent PS (IPS) versus continuous PS (CPS).

Objectives: The primary aim was to investigate clinical outcomes of PS in a real clinical setting.

Methods: Clinical information was prospectively collected for patients who were treated according to a prescribed protocol and assessment tools in a hospice unit affiliated with a tertiary cancer center between September 2015 and March 2017. Data were analyzed retrospectively. Midazolam was used as the first medication for PS, and propofol and phenobarbital were subsequently used as salvage medications. Indications of PS, the depth of sedation, the quality of sleep, and the level of consciousness were assessed.

Results: A total of 306 patients were enrolled, 89 of whom (29.1%) received PS. No difference in survival time was found between patients with and without PS (median survival, 34.0 vs 25.0 days, P = 0.109). Delirium was the most common indication of PS. The symptoms of 73 (82.0%) of 89 patients with PS were relieved with midazolam. Twelve (75.0%) of 16 midazolam-failure patients responded to propofol, five of whom (31%) exhibited respiratory depression. Of the 89 patients receiving PS, 61 (68.5%) received IPS and 28 patients (31.5%) received CPS. The median survival times from PS initiation to death were six days in the IPS group and one day in the CPS group (P < 0.001). Interestingly, consciousness levels were significantly improved after IPS in the delirium group compared with those in the other group (41.7% vs 16.7%, P = 0.002).

Conclusion: The refractory symptoms of end-of-life patients with cancer can ultimately be relieved with various medications for PS. IPS may improve the consciousness level of patients with delirium.
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http://dx.doi.org/10.1016/j.jpainsymman.2019.04.019DOI Listing
July 2019

Correction to: The impact of caregiver's role preference on decisional conflicts and psychiatric distresses in decision making to help caregiver's disclosure of terminal disease status.

Qual Life Res 2019 Jun;28(6):1693

Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.

In the original publication of the article, the incorrect grant number HC13C1391 was published in the acknowledgement section. The correct grant number is HC15C1391.
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http://dx.doi.org/10.1007/s11136-019-02124-wDOI Listing
June 2019

Sedation for terminally ill cancer patients: A multicenter retrospective cohort study in South Korea.

Medicine (Baltimore) 2019 Feb;98(5):e14278

Department of Internal Medicine, Gyeongsang National University Hospital, Jinju.

Sedation therapy is a potential solution to providing relief from refractory symptoms at end of life. The aim of this study was to investigate actual sedation practice and physician characteristics associated with the use of sedation for terminally ill cancer patients in South Korea.A retrospective review was conducted on consecutive patients who had died from cancer at seven tertiary medical centers between January 2010 and October 2015. The use of sedation was defined as the administration of sedative agents to relieve intolerable symptoms within the last 2 weeks preceding death. Patients and physician characteristics and information on the use of sedation were collected.A total of 8309 patients were included in the study. Sedatives were administered in 1334 patients (16.1%) for the following indications: delirium in 39.3%, intractable pain in 23.1%, and dyspnea in 21.9%. Median duration of sedation from initiation to death was 3 days. The use of sedation depended on physician specialty and experience. Family physicians used sedation most often (57.6%), followed by medical oncologists (13.9%), other internists (10.7%), and surgical oncologists (9.4%). The use of sedation was highest for physicians with >5 to 10 years practice experience (22.1%) and lowest for those in practice for 5 years or less (10.2%). The proportion of patients receiving sedation also varied markedly across participating institutions (range, 7.0%-49.7%).This large cohort study provides insight into sedation practice for terminally ill cancer patients in South Korea. Our study shows that the use of sedation depends on physician background and institution. A nation-wide guidelines and continued education on end-of-life sedation are required in South Korea.
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http://dx.doi.org/10.1097/MD.0000000000014278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380862PMC
February 2019

Attitudes of the General Public, Cancer Patients, Family Caregivers, and Physicians Toward Advance Care Planning: A Nationwide Survey Before the Enforcement of the Life-Sustaining Treatment Decision-Making Act.

J Pain Symptom Manage 2019 04 27;57(4):774-782. Epub 2018 Dec 27.

Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Family Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Health Policy and Management, Seoul National University, Seoul, Seoul, Republic of Korea. Electronic address:

Context: To respect a patient's wish for end-of-life care, "the Act on Decisions on Life-Sustaining Treatment for Patients at the End-of-Life" was enacted in South Korea in 2016. Current understanding of people who would be involved in advance care planning (ACP) is crucial to disseminate it systematically.

Objectives: The objective of this study was to investigate awareness and attitudes toward ACP in South Korea.

Methods: A multicenter, nationwide cross-sectional study was conducted, a survey regarding ACP among four groups that would have different positions and experiences: 1001 cancer patients, 1006 family caregivers, 928 physicians, and 1241 members of the general public.

Results: A total of 15% of the general population, 33% of the patients and caregivers, and 61% of the physicians had knowledge of advance directives. More than 64% of the general population, above 72% of the patients and caregivers, and 97% of the physicians were willing to do so when the disease status was aggravated or terminal. The possibility for changing the plan, uncertainty as to whether directives would actually be followed, and psychological discomfort were common reasons for not wanting to engage in ACP. Routine recommendations for a specific medical condition, heightened accessibility, and health insurance support were common factors that could help facilitate ACP.

Conclusion: Our findings suggest that strategies for promoting ACP should reflect different perspectives among the general public, patients, family caregivers, and physicians. Public advocacy, resources for approaching and integrating ACP into routine health care, as well as systematic support provisions are needed.
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http://dx.doi.org/10.1016/j.jpainsymman.2018.12.332DOI Listing
April 2019

Safety and efficacy of trastuzumab administered as a 30-min infusion in patients with HER2-positive advanced gastric cancer.

Cancer Chemother Pharmacol 2019 03 8;83(3):501-508. Epub 2018 Dec 8.

CELLTRION Healthcare Co. Ltd, Incheon, Republic of Korea.

Purpose: To investigate the safety and efficacy of 30-min maintenance infusions of trastuzumab in advanced gastric cancer positive for human epidermal growth factor receptor 2 (HER2).

Methods: This was a retrospective study conducted across five Korean hospitals in patients with HER2-positive gastric or gastroesophageal junction adenocarcinoma treated with first-line, 3-weekly trastuzumab plus chemotherapy. The first dose of trastuzumab (8 mg/kg) was administered as a 90-min infusion, with all subsequent maintenance infusions (6 mg/kg) given over 30 min. The primary aim was to investigate infusion-related reactions and cardiac events with 30-min infusions of trastuzumab. Objective response rate, progression-free survival, and overall survival were secondary endpoints.

Results: The study included 128 patients (efficacy population), of whom 123 received both induction and maintenance infusions and formed the safety population. The median age was 63 years; 80% were presenting for the first time with metastatic disease, and 94% were treated with trastuzumab plus capecitabine/cisplatin. Infusion-related reactions were observed in 32 of 123 patients (26%). There were no cardiac events. The most frequent adverse events were anorexia and nausea, followed by vomiting, fatigue, mucositis, sensory neuropathy, and hand-foot syndrome. Most events were grade 1-2 and were manageable. No patient discontinued study treatment due to adverse events. The objective response rate was 63%, and included 6 complete responses.

Conclusions: Trastuzumab 30-min maintenance infusions were well tolerated with a good safety profile, and resulted in sustained efficacy in patients with HER2-positive advanced gastric cancer.
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http://dx.doi.org/10.1007/s00280-018-3753-yDOI Listing
March 2019

Discordance between Physician and the General Public Perceptions of Prognostic Disclosure to Children with Serious Illness: a Korean Nationwide Study.

J Korean Med Sci 2018 Dec 26;33(49):e327. Epub 2018 Nov 26.

Department of Biomedical Informatics, Seoul National University College of Medicine, Seoul, Korea.

Background: It is difficult to decide whether to inform the child of the incurable illness. We investigated attitudes of the general population and physicians toward prognosis disclosure to children and associated factors in Korea.

Methods: Physicians working in one of 13 university hospitals or the National Cancer Center and members of the general public responded to the questionnaire. The questionnaire consisted of the age appropriate for informing children about the prognosis and the reason why children should not be informed. This survey was conducted as part of research to identify perceptions of physicians and general public on the end-of-life care in Korea.

Results: A total of 928 physicians and 1,241 members of the general public in Korea completed the questionnaire. Whereas 92.7% of physicians said that children should be informed of their incurable illness, only 50.7% of the general population agreed. Physicians were also more likely to think that younger children should know about their poor prognosis compared with the general population. Physicians who opposed incurable illness disclosure suggested that children might not understand the situation, whereas the general public was primarily concerned that disclosure would exacerbate the disease. Physicians who were women or religious were more likely to want to inform children of their poor prognosis. In the general population, gender, education, comorbidity, and caregiver experience were related to attitude toward poor prognosis disclosure to children.

Conclusion: Our findings indicate that physicians and the general public in Korea differ in their perceptions about informing children of poor prognosis.
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http://dx.doi.org/10.3346/jkms.2018.33.e327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262186PMC
December 2018