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1.
Article in English | WPRIM | ID: wpr-968443

ABSTRACT

Objectives@#The coronavirus disease 2019 (COVID-19) pandemic has continued since its first detection in the Republic of Korea on January 20, 2020. This study describes the early countermeasures used to minimize the risk of COVID-19 outbreaks during cohort quarantine and compares the epidemiological characteristics of 2 outbreaks in long-term care facilities (LTCFs) in Gwangju Metropolitan City in summer 2020. @*Methods@#An epidemiological investigation was conducted via direct visits. We investigated epidemiological characteristics, including incidence, morbidity, and mortality rates, for all residents and staff members. Demographic characteristics were analyzed using a statistical program. Additionally, the method of managing infection in LTCFs is described. @*Results@#Residents and caregivers had high incidence rates in LTCF-A and LTCF-B, respectively. LTCF-B had a longer quarantine period than LTCF-A. The attack rate was 20.02% in LTCF-A and 27.9% in LTCF- B. The mortality rate was 2.3% (1/43) in LTCF-B, the only facility in which a COVID-19 death occurred. @*Conclusion@#Extensive management requires contact minimization, which involves testing all contacts to mitigate further transmission in the early stages of LTCF outbreaks. The findings of this study can help inform and prepare public health authorities for COVID-19 outbreaks, particularly for early control in vulnerable facilities.

2.
Article in English | WPRIM | ID: wpr-968435

ABSTRACT

Objectives@#Household contacts of confirmed cases of coronavirus disease 2019 (COVID-19) are exposed to a high risk of viral transmission, and secondary incidence is an important indicator of community transmission. This study analyzed the secondary attack rate and mRNA vaccine effectiveness against transmission (VET) for index cases (patients treated at home) confirmed to be infected with the Delta and Omicron variants. @*Methods@#The subjects of the study were 4,450 index cases and 10,382 household contacts. Logistic regression analysis was performed to compare the secondary attack rate by vaccination status, and adjusted relative risk and 95% confidence intervals were identified. @*Results@#The secondary attack rate of the Delta variant was 27.3%, while the secondary attack rate of the Omicron variant was 29.8%. For the Delta variant, groups with less than 90 days and more than 90 days after 2 doses of mRNA vaccination both showed a VET of 37%. For the Omicron variant, a 64% VET was found among those with less than 90 days after 2 doses of mRNA vaccination. @*Conclusion@#This study provides useful data on the secondary attack rate and VET of mRNA vaccines for household contacts of COVID-19 cases in South Korea.

3.
Article in English | WPRIM | ID: wpr-968432

ABSTRACT

Objectives@#On November 5, 2021, Pfizer Inc. announced Paxlovid (nirmatrelvir+ritonavir) as a treatment method that could reduce the risk of hospitalization or death for patients with confirmed coronavirus disease 2019 (COVID-19). @*Methods@#From February 6, 2022 to April 2, 2022, the incidence of COVID-19 and the effects of treatment with Paxlovid were analyzed in 2,241 patients and workers at 5 long-term care facilities during the outbreak of the Omicron variant of severe acute respiratory syndrome coronavirus 2 in South Korea. @*Results@#The rate of severe illness or death in the group given Paxlovid was 51% lower than that of the non-Paxlovid group (adjusted risk ratio [aRR], 0.49; 95% confidence interval [CI], 0.24−0.98). Compared to unvaccinated patients, patients who had completed 3 doses of the vaccine had a 71% reduced rate of severe illness or death (aRR, 0.29; 95% CI, 0.13−0.64) and a 65% reduced death rate (aRR, 0.35; 95% CI, 0.15−0.79). @*Conclusion@#Patients given Paxlovid showed a lower rate of severe illness or death and a lower fatality rate than those who did not receive Paxlovid. Patients who received 3 doses of the vaccine had a lower rate of severe illness or death and a lower fatality rate than the unvaccinated group.

4.
Article in English | WPRIM | ID: wpr-917655

ABSTRACT

Background@#Recessive dystrophic epidermolysis bullosa (RDEB) manifests in various cutaneous and extracutaneous complications that lead to considerable morbidity and mortality, however, no precise incidence data are available. @*Objective@#To investigate the prevalence of inherited epidermolysis bullosa (EB) stratified by subtypes, demographics, and clinical characteristics in Korean patients with EB, and major clinical events and outcomes in Korean RDEB patients. @*Methods@#A total of 179 patients diagnosed with EB at a single tertiary hospital between January 2005 and January 2020 were retrospectively analyzed. @*Results@#Among the 179 patients, 86 (48.0%) had EB simplex, 45 (25.1%) had dominant dystrophic EB, 38 (21.2%) had RDEB, and 10 (5.6%) had juncttional EB. Symptoms of the disease were present at age 1 year in 38 patients with RDEB (100%), 10 with junctional EB (100%), 41 with dominant dystrophic EB (91.1%), and 63 with EB simplex (73.3%). Among the 38 patients with RDEB, 20 (52.6%) had anemia, 21 (55.3%) had pseudosyndactyly, 9 (23.7%) had cardiac disorder (23.7%) (e.g., dilated cardiomyopathy), 9 (23.7%) had ophthalmic disorders, 11 (28.9%) had methicillin-resistant Staphylococcus aureus skin infection, 7 (18.4%) had esophageal stricture, and 4 (10.5%) developed squamous cell carcinoma at a mean age of 46.7 years. Seventeen subjects (44.7%) underwent hand/foot surgery at a mean age of 6.6 years. Six subjects (15.8%) underwent esophageal dilation at a mean age of 23 years. Five patients (13.2%) died. @*Conclusion@#RDEB affects multiple organ systems and requires a multidisciplinary therapeutic approach. Understanding the incidence and outcomes of milestone clinical events is crucial for optimal management of RDEB patients.

5.
Article in Korean | WPRIM | ID: wpr-938722

ABSTRACT

Sialodochitis fibrinosa is a disease characterized by salivary duct obstruction. A 21-year-old male presented with a painful submandibular gland (SMG) swelling. Serum eosinophilia and Whartons’ duct dilatation with strong enhancement were observed on contrast CT. Core needle biopsy (CNB) for SMG parenchyma revealed lymphocytic infiltration between dilated intralobular ducts. In another case, a 39-year-old male complained of recurrent major salivary glands swelling for ten years with an itching sensation on the overlying skin of the salivary gland. Enhancement of both SMG parenchyma, dilatation of both Wharton’s ducts and elevated serum eosinophilia were observed on contrast CT study. CNB for SMG parenchyma revealed lymphocytic infiltration with many eosinophils around a markedly dilated interlobular duct. The recurrent SMG swelling in both cases were relieved by antihistamine medication, warranting suspicion that these cases might organ-specific eosinophilic disease. We dicuss these two cases with a literature review.

6.
Article in English | WPRIM | ID: wpr-900692

ABSTRACT

Objectives@#Adolescent suicide is a serious national issue in Korea. Recently, life satisfaction has been recognized as a major factor related to this issue. The main purpose of this study was to identify the domains of life satisfaction that affect suicidal behavior in adolescence. @*Methods@#Data were collected from eight middle schools in Incheon, Korea. A total of 1297 students answered questions regarding their demographic characteristics, happiness, self-related life satisfaction domains (appearance, leisure time, physical health, and mental health), depressive symptoms, and suicidal behavior. @*Results@#In the Spearman correlation analysis, female sex, perceived socioeconomic status (SES), happiness, and all four self-related satisfaction scores showed significant correlations with depression and suicidality. Multivariate regression analysis suggested that suicidality was significantly affected by perceived SES, satisfaction with appearance, mental health satisfaction, and depression. Finally, depression was identified as a partial mediator of the association between mental health satisfaction and suicidality, and a complete mediator of the association between female sex and suicidality. @*Conclusion@#Perceived SES, satisfaction with appearance, and mental health satisfaction significantly affected students’ suicidality, with or without the effect of depression. Health authorities, educators, and family members must be aware of this to identify adolescents at suicide risk earlier.

7.
Article in English | WPRIM | ID: wpr-898057

ABSTRACT

Background@#Previously developed prediction models for type 2 diabetes mellitus (T2DM) have limited performance. We developed a deep learning (DL) based model using a cohort representative of the Korean population. @*Methods@#This study was conducted on the basis of the National Health Insurance Service-Health Screening (NHIS-HEALS) cohort of Korea. Overall, 335,302 subjects without T2DM at baseline were included. We developed the model based on 80% of the subjects, and verified the power in the remainder. Predictive models for T2DM were constructed using the recurrent neural network long short-term memory (RNN-LSTM) network and the Cox longitudinal summary model. The performance of both models over a 10-year period was compared using a time dependent area under the curve. @*Results@#During a mean follow-up of 10.4±1.7 years, the mean frequency of periodic health check-ups was 2.9±1.0 per subject. During the observation period, T2DM was newly observed in 8.7% of the subjects. The annual performance of the model created using the RNN-LSTM network was superior to that of the Cox model, and the risk factors for T2DM, derived using the two models were similar; however, certain results differed. @*Conclusion@#The DL-based T2DM prediction model, constructed using a cohort representative of the population, performs better than the conventional model. After pilot tests, this model will be provided to all Korean national health screening recipients in the future.

8.
Article in English | WPRIM | ID: wpr-892988

ABSTRACT

Objectives@#Adolescent suicide is a serious national issue in Korea. Recently, life satisfaction has been recognized as a major factor related to this issue. The main purpose of this study was to identify the domains of life satisfaction that affect suicidal behavior in adolescence. @*Methods@#Data were collected from eight middle schools in Incheon, Korea. A total of 1297 students answered questions regarding their demographic characteristics, happiness, self-related life satisfaction domains (appearance, leisure time, physical health, and mental health), depressive symptoms, and suicidal behavior. @*Results@#In the Spearman correlation analysis, female sex, perceived socioeconomic status (SES), happiness, and all four self-related satisfaction scores showed significant correlations with depression and suicidality. Multivariate regression analysis suggested that suicidality was significantly affected by perceived SES, satisfaction with appearance, mental health satisfaction, and depression. Finally, depression was identified as a partial mediator of the association between mental health satisfaction and suicidality, and a complete mediator of the association between female sex and suicidality. @*Conclusion@#Perceived SES, satisfaction with appearance, and mental health satisfaction significantly affected students’ suicidality, with or without the effect of depression. Health authorities, educators, and family members must be aware of this to identify adolescents at suicide risk earlier.

9.
Article in English | WPRIM | ID: wpr-890353

ABSTRACT

Background@#Previously developed prediction models for type 2 diabetes mellitus (T2DM) have limited performance. We developed a deep learning (DL) based model using a cohort representative of the Korean population. @*Methods@#This study was conducted on the basis of the National Health Insurance Service-Health Screening (NHIS-HEALS) cohort of Korea. Overall, 335,302 subjects without T2DM at baseline were included. We developed the model based on 80% of the subjects, and verified the power in the remainder. Predictive models for T2DM were constructed using the recurrent neural network long short-term memory (RNN-LSTM) network and the Cox longitudinal summary model. The performance of both models over a 10-year period was compared using a time dependent area under the curve. @*Results@#During a mean follow-up of 10.4±1.7 years, the mean frequency of periodic health check-ups was 2.9±1.0 per subject. During the observation period, T2DM was newly observed in 8.7% of the subjects. The annual performance of the model created using the RNN-LSTM network was superior to that of the Cox model, and the risk factors for T2DM, derived using the two models were similar; however, certain results differed. @*Conclusion@#The DL-based T2DM prediction model, constructed using a cohort representative of the population, performs better than the conventional model. After pilot tests, this model will be provided to all Korean national health screening recipients in the future.

10.
Article in English | WPRIM | ID: wpr-915439

ABSTRACT

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel.There may be more transmissions with this VOC in Korea than reported.

11.
Article in English | WPRIM | ID: wpr-896146

ABSTRACT

Plasmodium vivax reemerged in 1993. It has been sustained for more than 25 years and become one of the important indigenous parasitic diseases in northern and western parts of the Republic of Korea near the demilitarized zone. In particular, relapse is a significant concern for the control of malaria, as short- and long-term incubation periods vary among those infected in Korea. In this study, the prevalence of asymptomatic carriers was examined among residents of high endemic areas of vivax malaria during nonseasonal transmission of mosquitoes. Blood samples from 3 endemic regions in northwestern Korea were evaluated by microscopic examination, rapid diagnostic testing, and nested PCR to identify asymptomatic patients carrying malaria parasites in the community. However, no positive malaria case among residents of endemic areas was detected. Additionally, serological analysis was carried out to measure antibodies against 3 antigenic recombinant proteins of P. vivax, merozoite surface protein 1-19, circumsporozoite surface protein-VK210, and liver-stage antigen (PvLSA-N), by the protein array method. Interestingly, seropositivity of sera between previous exposure and samples without exposure to malaria was significantly higher using the PvLSA-N antigen than the other antigens, suggesting that PvLSA-N can be used as a serological marker to analyze the degree of exposure for malaria transmission in endemic areas. This indicates a very low asymptomatic carrier prevalence during the nonmalaria season in the endemic areas of Korea.

12.
Article in English | WPRIM | ID: wpr-896143

ABSTRACT

Clonorchis sinensis is the most common fish-borne intestinal parasite in Korea. The aim of the present investigation was to survey the status of C. sinensis infection and analyze associated risk factors in residents of Haman-gun, Gyeongsangnam-do. A total of 5,114 residents from 10 administrative towns/villages voluntarily agreed to participate in the study, which comprised fecal examination, a questionnaire survey for risk factors, ultrasonography, and enzymelinked immunosorbent assay for cancer biomarker detection in the blood. We detected C. sinensis eggs in 5.3% of the subjects. By region, Gunbuk-myeon had the highest number of residents with C. sinensis eggs. The infection rate and intensity were higher in male than in female residents. Based on the risk factor questionnaire, infection was highly associated with drinking, a history of C. sinensis infection, and the practice of eating of raw freshwater fish. Extension of the bile duct, infection intensity, and cancer biomarker detection significantly correlated with the presence of eggs in the study population. In conclusion, the development of feasible, long-term control policies and strategies for the elimination of C. sinensis in Korea is still required.

13.
Article in English | WPRIM | ID: wpr-786209

ABSTRACT

BACKGROUND AND OBJECTIVES: We aim to explore the additional discriminative accuracy of a deep learning (DL) algorithm using repeated-measures data for identifying people at high risk for cardiovascular disease (CVD), compared to Cox hazard regression.METHODS: Two CVD prediction models were developed from National Health Insurance Service-Health Screening Cohort (NHIS-HEALS): a Cox regression model and a DL model. Performance of each model was assessed in the internal and 2 external validation cohorts in Koreans (National Health Insurance Service-National Sample Cohort; NHIS-NSC) and in Europeans (Rotterdam Study). A total of 412,030 adults in the NHIS-HEALS; 178,875 adults in the NHIS-NSC; and the 4,296 adults in Rotterdam Study were included.RESULTS: Mean ages was 52 years (46% women) and there were 25,777 events (6.3%) in NHIS-HEALS during the follow-up. In internal validation, the DL approach demonstrated a C-statistic of 0.896 (95% confidence interval, 0.886–0.907) in men and 0.921 (0.908–0.934) in women and improved reclassification compared with Cox regression (net reclassification index [NRI], 24.8% in men, 29.0% in women). In external validation with NHIS-NSC, DL demonstrated a C-statistic of 0.868 (0.860–0.876) in men and 0.889 (0.876–0.898) in women, and improved reclassification compared with Cox regression (NRI, 24.9% in men, 26.2% in women). In external validation applied to the Rotterdam Study, DL demonstrated a C-statistic of 0.860 (0.824–0.897) in men and 0.867 (0.830–0.903) in women, and improved reclassification compared with Cox regression (NRI, 36.9% in men, 31.8% in women).CONCLUSIONS: A DL algorithm exhibited greater discriminative accuracy than Cox model approaches.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02931500


Subject(s)
Adult , Female , Humans , Male , Artificial Intelligence , Cardiovascular Diseases , Cohort Studies , Follow-Up Studies , Insurance, Health , Learning , Mass Screening , National Health Programs
14.
Annals of Dermatology ; : 159-163, 2020.
Article in English | WPRIM | ID: wpr-811080

ABSTRACT

Happle-Tinschert syndrome is a rare disease characterized by unilateral, segmentally arranged basaloid follicular hamartoma (BFH) with osseous, dental, and cerebral anomalies. Although BFH has been demonstrated to be associated with mutations in the patched gene, the genetic basis for Happle-Tinschert syndrome is still unknown. We describe a case of Happle-Tinschert syndrome in a 26-year-old female. The patient presented with unilateral skin color change to brownish papules and atrophoderma following the development of Blaschko's lines, plantar pitting, and nail dystrophy on the right side of the body. She also had scoliosis, hemihypotrophy, and dental anomalies. The skin lesions were histologically confirmed as BFHs. Next-generation sequencing of the patient's genomic DNA obtained from a peripheral blood sample identified no pathogenic mutation. This case illustrates the characteristic clinical features of Happle-Tinschert syndrome. Thus far, 14 cases of Happle-Tinschert syndrome have been reported, and we report another case of this syndrome.


Subject(s)
Adult , Female , Humans , DNA , Hamartoma , Rare Diseases , Scoliosis , Skin , Skin Pigmentation
15.
Article | WPRIM | ID: wpr-836324

ABSTRACT

Objectives@#Adolescent suicide, a major cause of adolescent death, is affected by various factors, including attitudes toward suicide.This study investigated the association between parenting style and adolescents’ attitudes toward suicide and the mediating role of attitude toward suicide between parenting style and suicidal ideation. @*Methods@#We surveyed 1,071 adolescents from eight middle schools in Incheon, Korea. The survey included sociodemographic information, attitudes toward suicide, perception of parenting style, depression severity, and suicidality. @*Results@#Students in the authoritarian parenting group had a more permissive attitude toward suicide compared with the democratic and permissive parenting groups. These students considered that suicide is justified in certain situations and that choosing suicide is an individual’s right. They also had a negative attitude toward talking about suicide or intervening in others’ suicide. This association remained statistically significant after adjusting for the impact of confounding factors that could affect attitudes toward suicide, except for suicidal processes and preparedness to prevent suicide. In the mediation analysis, we observed that some factors of the attitudes toward suicide mediated between authoritarian parenting attitudes and suicidal ideation, namely, suicide as a right, preventability, suicide as normal/common, preparedness to prevent suicide, and resignation. @*Conclusion@#This study revealed the significant impact of parenting style on children’s attitudes toward suicide. Educating parents about the appropriate parenting attitudes–sympathetic and rational–can help prevent youth suicide.

16.
Article | WPRIM | ID: wpr-835142

ABSTRACT

Objectives@#The Korea Centers for Disease Control and Prevention has published “A Guideline for Unknown Disease Outbreaks (UDO).” The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future. @*Methods@#The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced. @*Results@#Since September 9th , 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen. @*Conclusion@#Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.

17.
Article | WPRIM | ID: wpr-834008

ABSTRACT

Background@#The prone position is used for a variety of procedures and surgeries, and hypotension is a commonly encountered complication. Case : A 75-year-old obese woman with lumbar spinal stenosis underwent posterior lumbar spinal fusion and posterolateral interbody fusion under general anesthesia. Before the surgery, when she was positioned on a Jackson spinal table in the prone position, sudden severe hypotension and hemodynamic collapse developed. The circulatory collapse was refractory to intravascular volume expansion and administration of inotropes and vasopressors. However, the application of external abdominal support immediately restored hemodynamic stability. The patient successfully underwent the surgery using an external abdominal support, and no post-operative complication was noted, including abdominal compartment syndrome. @*Conclusions@#The Jackson spinal table allowed the abdomen to hang freely, providing abdominal decompression while resulting in a severely sagged abdomen. We suspected that the sagging abdomen had pulled the abdominal contents downwards, kinking the inferior vena cava or causing a venous pool in the abdomen, resulting in the obstruction of venous return to the heart.

18.
Article | WPRIM | ID: wpr-833812

ABSTRACT

Cyclospora cayetanensis is an apicomplexan protozoan and is one of the most common pathogens causing chronic diarrhea worldwide. Eight stool samples with diarrheal symptom out of 18 Korean residents who traveled to Nepal were obtained, and examined for 25 enteropathogens including 16 bacterial species, 5 viral species, and 4 protozoans in stool samples as causative agents of water-borne and food-borne disease. Only C. cayetanensis was detected by nested PCR, and 3 PCR-positive samples were sequenced to confirm species identification. However, the oocysts of C. cayetanensis in fecal samples could not be detected by direct microscopy of the stained sample. As far as we know, this is the first report of a group infection with C. cayetanensis from a traveler visiting Nepal, and the second report of a traveler’s diarrhea by C. cayetanensis imported in Korea.

19.
Article | WPRIM | ID: wpr-833788

ABSTRACT

Majority of the imported malaria cases in Korea is attributed to Plasmodium falciparum and P. vivax infections, whereas P. malariae and P. ovale infections are very rare. Falciparum and ovale malaria are mostly imported from Africa, while most of the vivax malaria cases are imported from Southeast Asia. Here, we report 6 Korean imported ovale malaria cases (4 males and 2 females) who had visited in Africa during 2013-2016. These subjects were diagnosed with P. ovale based on microscopic findings, Plasmodium species-specific nested-PCR, and phylogenetic clade using 18S rRNA gene sequences. We identified 2 P. ovale subtypes, 1 P. ovale curtisi (classic type) and 5 P. ovale wallikeri (variant type). All patients were treated with chloroquine and primaquine, and no relapse or recrudescence was reported for 1 year after treatment. With increase of travelers to the countries where existing Plasmodium species, the risk of Plasmodium infection is also increasing. Molecular monitoring for imported malaria parasites should be rigorously and continuously performed to enable diagnosis and certification of Plasmodium spp.

20.
Article in English | WPRIM | ID: wpr-832992

ABSTRACT

BACKGROUND AND OBJECTIVES@#We aim to explore the additional discriminative accuracy of a deep learning (DL) algorithm using repeated-measures data for identifying people at high risk for cardiovascular disease (CVD), compared to Cox hazard regression.@*METHODS@#Two CVD prediction models were developed from National Health Insurance Service-Health Screening Cohort (NHIS-HEALS): a Cox regression model and a DL model. Performance of each model was assessed in the internal and 2 external validation cohorts in Koreans (National Health Insurance Service-National Sample Cohort; NHIS-NSC) and in Europeans (Rotterdam Study). A total of 412,030 adults in the NHIS-HEALS; 178,875 adults in the NHIS-NSC; and the 4,296 adults in Rotterdam Study were included.@*RESULTS@#Mean ages was 52 years (46% women) and there were 25,777 events (6.3%) in NHIS-HEALS during the follow-up. In internal validation, the DL approach demonstrated a C-statistic of 0.896 (95% confidence interval, 0.886–0.907) in men and 0.921 (0.908–0.934) in women and improved reclassification compared with Cox regression (net reclassification index [NRI], 24.8% in men, 29.0% in women). In external validation with NHIS-NSC, DL demonstrated a C-statistic of 0.868 (0.860–0.876) in men and 0.889 (0.876–0.898) in women, and improved reclassification compared with Cox regression (NRI, 24.9% in men, 26.2% in women). In external validation applied to the Rotterdam Study, DL demonstrated a C-statistic of 0.860 (0.824–0.897) in men and 0.867 (0.830–0.903) in women, and improved reclassification compared with Cox regression (NRI, 36.9% in men, 31.8% in women).@*CONCLUSIONS@#A DL algorithm exhibited greater discriminative accuracy than Cox model approaches.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02931500

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