Integrating Biomarkers From Virtual Reality and Magnetic Resonance Imaging for the Early Detection of Mild Cognitive Impairment Using a Multimodal Learning Approach: Validation Study.

BACKGROUND: Early detection of mild cognitive impairment (MCI), a transitional stage between normal aging and Alzheimer disease, is crucial for preventing the progression of dementia. Virtual reality (VR) biomarkers have proven to be effective in capturing behaviors associated with subtle deficits in instrumental activities of daily living, such as challenges in using a food-ordering kiosk, for early detection of MCI. On the other hand, magnetic resonance imaging (MRI) biomarkers have demonstrated their efficacy in quantifying observable structural brain changes that can aid in early MCI detection. Nevertheless, the relationship between VR-derived and MRI biomarkers remains an open question. In this context, we explored the integration of VR-derived and MRI biomarkers to enhance early MCI detection through a multimodal learning approach. OBJECTIVE: We aimed to evaluate and compare the efficacy of VR-derived and MRI biomarkers in the classification of MCI while also examining the strengths and weaknesses of each approach. Furthermore, we focused on improving early MCI detection by leveraging multimodal learning to integrate VR-derived and MRI biomarkers. METHODS: The study encompassed a total of 54 participants, comprising 22 (41%) healthy controls and 32 (59%) patients with MCI. Participants completed a virtual kiosk test to collect 4 VR-derived biomarkers (hand movement speed, scanpath length, time to completion, and the number of errors), and T1-weighted MRI scans were performed to collect 22 MRI biomarkers from both hemispheres. Analyses of covariance were used to compare these biomarkers between healthy controls and patients with MCI, with age considered as a covariate. Subsequently, the biomarkers that exhibited significant differences between the 2 groups were used to train and validate a multimodal learning model aimed at early screening for patients with MCI among healthy controls. RESULTS: The support vector machine (SVM) using only VR-derived biomarkers achieved a sensitivity of 87.5% and specificity of 90%, whereas the MRI biomarkers showed a sensitivity of 90.9% and specificity of 71.4%. Moreover, a correlation analysis revealed a significant association between MRI-observed brain atrophy and impaired performance in instrumental activities of daily living in the VR environment. Notably, the integration of both VR-derived and MRI biomarkers into a multimodal SVM model yielded superior results compared to unimodal SVM models, achieving higher accuracy (94.4%), sensitivity (100%), specificity (90.9%), precision (87.5%), and F1-score (93.3%). CONCLUSIONS: The results indicate that VR-derived biomarkers, characterized by their high specificity, can be valuable as a robust, early screening tool for MCI in a broader older adult population. On the other hand, MRI biomarkers, known for their high sensitivity, excel at confirming the presence of MCI. Moreover, the multimodal learning approach introduced in our study provides valuable insights into the improvement of early MCI detection by integrating a diverse set of biomarkers.

Gemcitabine-cisplatin versus MVAC chemotherapy for urothelial carcinoma: a nationwide cohort study.

This study assessed the trends in methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine-cisplatin (GC) regimens in Korean patients with metastatic urothelial carcinoma (UC) and compared the side effects and overall survival (OS) rates of the two regimens using nationwide population-based data. The data of patients diagnosed with UC between 2004 and 2016 were collected using the National Health Insurance Service database. The overall treatment trends were assessed according to the chemotherapy regimens. The MVAC and GC groups were matched by propensity scores. Cox proportional hazard analysis and Kaplan-Meier analysis were performed to assess survival. Of 3108 patients with UC, 2,880 patients were treated with GC and 228 (7.3%) were treated with MVAC. The transfusion rate and volume were similar in both the groups, but the granulocyte colony-stimulating factor (G-CSF) usage rate and number were higher in the MVAC group than in the GC group. Both groups had similar OS. Multivariate analysis revealed that the chemotherapy regimen was not a significant factor for OS. Subgroup analysis revealed that a period of ≥ 3 months from diagnosis to systemic therapy enhanced the prognostic effects of the GC regimen. The GC regimen was widely used as the first-line chemotherapy in more than 90% of our study population with metastatic UC. The MVAC regimen showed similar OS to the GC regimen but needed greater use of G-CSF. The GC regimen could be a suitable treatment option for metastatic UC after ≥ 3 months from diagnosis.

Incidence of Retinal Artery Occlusion and Related Mortality in Korea, 2005 to 2018.

Importance: It remains unclear whether comorbidities in patients with retinal artery occlusion (RAO), a rare retinal vascular disorder, differ by subtype and whether mortality is higher. Objective: To examine the nationwide incidence of clinically diagnosed, nonarteritic RAO, causes of death, and mortality rate in patients with RAO compared with that in the general population in Korea. Design, Setting, and Participants: This retrospective, population-based cohort study examined National Health Insurance Service claims data from 2002 to 2018. The population of South Korea was 49 705 663, according to the 2015 census. Data were analyzed from February 9, 2021, to July 30, 2022. Main Outcomes and Measures: The nationwide incidence of any RAO, including central RAO (CRAO; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code, H34.1) and noncentral RAO (other RAO; ICD-10 code, H34.2) was estimated using National Health Insurance Service claims data from 2002 to 2018, with 2002 to 2004 as the washout period. Furthermore, the causes of death were evaluated and the standardized mortality ratio was estimated. The primary outcomes were the incidence of RAO per 100 000 person-years and the standardized mortality ratio (SMR). Results: A total of 51 326 patients with RAO were identified (28 857 [56.2%] men; mean [SD] age at index date: 63.6 [14.1] years). The nationwide incidence of any RAO was 7.38 (95% CI, 7.32-7.44) per 100 000 person-years. The incidence rate of noncentral RAO was 5.12 (95% CI, 5.07-5.18), more than twice that of CRAO (2.25 [95% CI, 2.22-2.29]). Mortality was higher in patients with any RAO than in the general population (SMR, 7.33 [95% CI, 7.15-7.50]). The SMR for CRAO (9.95 [95% CI, 9.61-10.29]) and for noncentral RAO (5.97 [95% CI, 5.78-6.16]) showed a tendency toward a gradual decrease with increasing age. The top 3 causes of death in patients with RAO were diseases of the circulatory system (28.8%), neoplasms (25.1%), and diseases of the respiratory system (10.2%). Conclusions and Relevance: This cohort study found that the incidence rate of noncentral RAO was higher than that of CRAO, whereas SMR was higher for CRAO than noncentral RAO. Patients with RAO show higher mortality than the general population, with circulatory system disease as the leading cause of death. These findings suggest that it is necessary to investigate the risk of cardiovascular or cerebrovascular disease in patients newly diagnosed with RAO.

Neoadjuvant versus adjuvant chemotherapy in upper tract urothelial carcinoma: A nationwide cohort study.

PURPOSE: This study aimed to evaluate the trend of adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC) in patients who underwent radical nephroureterectomy with bladder cuff excision (NUx) for upper tract urothelial carcinoma (UTUC) to compare the perioperative outcomes and overall survival (OS) between AC and NAC using nationwide population-based data. MATERIALS AND METHODS: We collected data on patients diagnosed with UTUC and treated with NUx between 2004 and 2016 using the National Health Insurance Service database, and evaluated the overall treatment trends. The AC and NAC groups were propensity score-matched. Cox proportional hazard and Kaplan-Meier analyses were used to assess survival. RESULTS: Of the 8,705 enrolled patients, 6,627 underwent NUx only, 94 underwent NAC, and 1,984 underwent AC. The rate of NUx without perioperative chemotherapy increased from 70.8 to 78.2% (R2 = 0.632; p < 0.001). The rates of dialysis (p = 0.398), TUR-BT (p = 1.000), and radiotherapy (p = 0.497) after NUx were similar. In the Kaplan-Meier curve, the NAC and AC groups showed no significant difference (p = 0.480). In multivariate analysis, treatment with AC or NAC was not associated with OS (hazard ratio 0.83, 95% confidence interval 0.49-1.40, p = 0.477). CONCLUSION: The use of NUx without perioperative chemotherapy has tended to increase in South Korea. Dialysis, TUR-BT, and radiotherapy rates after NUx were similar between the NAC and AC groups. There was no significant difference in OS between the NAC and AC groups. Proper perioperative chemotherapy according to patient and tumor conditions should be determined by obtaining more evidence of UTUC.

Early psychiatric referral after attempted suicide helps prevent suicide reattempts: A longitudinal national cohort study in South Korea.

Introduction: Although people who attempted suicide tend to repeat suicide attempts, there is a lack of evidence on the association between psychiatric service factors and suicide reattempt among them. Methods: We used a nationwide, population-based medical record database of South Korea to investigate the use of psychiatric services before and after the index suicide attempt and the association between psychiatric service factors after the index suicide attempt with the risk of suicide reattempt. Results: Among 5,874 people who had attempted suicide, the all-cause mortality within 3 months after the suicide attempt was 11.6%. Among all subjects who attempted suicide, 30.6% of them had used psychiatric services within 6 months before the suicide attempt; 43.7% of them had used psychiatric services within 3 months after the suicide attempt. Among individuals who had visited clinics following attempted suicide, the cumulative incidence of suicide reattempt over a mean follow-up period of 5.1 years was 3.4%. About half of suicide reattempts occurred within 1 year after the index suicide attempt. Referral to psychiatric services within 7 days was associated with a decreased risk of suicide reattempt (adjusted hazard ratio, 0.51; 95% confidence intervals, 0.29-0.89). Conclusion: An early psychiatric referral within 1 week after a suicide attempt was associated with a decreased risk of suicide reattempt.

Neoadjuvant versus adjuvant chemotherapy in bladder cancer: a nationwide cohort study.

PURPOSE: Radical cystectomy is the standard of care for muscle-invasive bladder cancer. However, the 5-year survival rate is only about 50%. Therefore, additional treatments are needed. We compared the perioperative outcomes, overall survival, and treatment trends in patients with bladder cancer who underwent radical cystectomy and either neoadjuvant or adjuvant chemotherapy using nationwide population-based data. MATERIALS AND METHODS: We collected the data of patients diagnosed with bladder cancer treated with radical cystectomy between 2004 and 2016 using the National Health Insurance Service database. We evaluated overall treatment trends. The neoadjuvant chemotherapy and adjuvant chemotherapy groups were matched by propensity score. Cox proportional hazard analysis and Kaplan-Meier analysis were used to assess survival. RESULTS: Of 6134 patients, 1379 underwent adjuvant chemotherapy and 389 underwent neoadjuvant chemotherapy. The utilization rate of neoadjuvant chemotherapy increased from 6.4 to 12.2% from 2004 to 2016 (p = 0.018). The administration rate and number of granulocyte colony-stimulating factor cycles were lower in the neoadjuvant chemotherapy group than in the adjuvant chemotherapy group (p < 0.001 and p = 0.027, respectively). After propensity score matching, the neoadjuvant chemotherapy group had significantly better overall survival than the adjuvant chemotherapy group (p = 0.004). In multivariate analysis, neoadjuvant chemotherapy was associated with better overall survival (hazard ratio 0.77, 95% confidence interval 0.65-0.92, p = 0.003). CONCLUSIONS: Neoadjuvant chemotherapy was associated with lower granulocyte colony-stimulating factor administration and better overall survival than adjuvant chemotherapy. Neoadjuvant chemotherapy should be considered for patients with bladder cancer who undergo radical cystectomy.

Psychological autopsy study comparing suicide decedents with and without a history of suicide attempts in a nationwide sample of South Korea.

The majority of suicide decedents die on their initial attempt. To bring attention to suicide decedents without a suicide attempt history, the current study explored their demographic, clinical, and suicide-related characteristics. The data were derived from the Korea National Investigation of Suicide Victims Study, which assessed all suicide cases from 2013 to 2017 recorded in police investigation reports. We compared suicide decedents with and without a history of nonfatal attempts using the Korea Psychological Autopsy Checklist for Police Records (K-PAC). Out of 5228 cases included in our study, 3147 (60.2%) died on their first suicide attempt. Demographically, those who were male, older than 65, employed, and married/widowed were more likely to die on their initial attempt. Clinically, those who died on their initial attempt were more likely to have never been diagnosed with psychiatric disorders, whereas those who died on a repeated attempt were more likely to have been diagnosed with mood disorders. In terms of suicide-related factors, experiencing relationship problems and complaining about physical discomfort were associated with dying on an initial attempt. Depressed affect, self-harming behaviors, and talking about suicide or death were associated with repeated attempts.

Comparing warning signs of suicide between suicide decedents with depression and those non-diagnosed psychiatric disorders.

OBJECTIVE: Early recognition of a high-risk group impending suicide is important. We aimed to compare warning signs depending on the nature of the psychiatric disorder and whether it was a documented diagnosis. METHODS: Data of suicide decedents were collected from police records from 2013 to 2017. We evaluate psychiatric symptoms and warning signs in three aspects (language, behavior, and affect) using the Korea-Psychological Autopsy Checklist for Police Records (K-PAC-PR). RESULTS: A total of 13,265 suicide decedents were recruited for this study. Of them, 66.9% of females and 46.7% of males diagnosed psychiatric disorders, with depressive disorder being the most common one. Warning signs were observed in 93.0% of suicide decedents. They were observed more in those who were diagnosed with psychiatric disorders, especially in those with a depressive disorder. "Talking about dying or suicide" was the most common warning sign in all groups, and "apathetic behavior" was the most related warning sign for depressive disorder. Especially for "talking about dying or suicide," the proportion of observed "within a week" was high, making it valuable as a warning sign. CONCLUSION: Warning signs were commonly found in suicide decedents regardless of gender. They were more common among the decedents diagnosed with psychiatric disorders, especially among those with a depressive disorder.

Predictive Factors Associated With Methods of Suicide: The Korean National Investigations of Suicide Victims (The KNIGHTS Study).

Background: Because the suicide mortality depends on the lethality of suicide methods, the identification and prediction of suicide methods are important for suicide prevention. Methods: Examination data of suicide decedents were collected based on police reports. Suicide decedents were divided into groups according to the suicide methods (hanging, gas poisoning, pesticide poisoning, jumping, drug poisoning, and drowning) they used. Predictive factors for each suicide method in comparison to other suicide methods were identified. Results: Among 23,647 subjects, hanging was the most common method of suicide. Regarding gas poisoning, the history of previous suicide attempt was a risk factor and being age of 65 or older was a protective factor. Being age of 65 or older showed a highly strong association with suicide by pesticide poisoning. Being age of 18 or younger and the presence of schizophrenia were associated with jumping. A history of psychiatric outpatient treatment was a risk factor for drug poisoning. Regarding suicide by drowning, schizophrenia was a risk factor, while being age of 65 or older was a protective factor. Limitations: Only eight out of a total of 17 regions in South Korea were examined and included in the data of this study. Also, the methods of suicide were defined as one method that directly caused the death, which could undermine other less fatal methods used. Conclusions: There were differences in predictive factors according to the method of suicide. Predicting the method of suicide in people at high risk for suicide stands to be an important strategy for suicide prevention in clinical settings.

Increased risk of depression before and after unilateral or bilateral oophorectomy: A self-controlled case series study using a nationwide cohort in South Korea.

BACKGROUND: There is insufficient evidence of the association between oophorectomy and depression. METHODS: A nationwide medical records database of South Korea was used to investigate incidence rate ratios (IRRs) of major depressive disorder before and after oophorectomy (n = 36,284) using a self-controlled case series design. Outcomes before and after hysterectomy (n = 25,415) were identified to compare with those around oophorectomy. RESULTS: In all oophorectomy and hysterectomy groups, the risk of depression was increased before and after surgery, peaking immediately before or after the operation, with no significant difference in the pattern of the results according to type of surgery. In the bilateral oophorectomy group, the IRR was increased between 2-3 months before the surgery, peaking immediately before surgery at 1.39 (95% CI: 1.30-1.49, p < .0001), and remained heightened for one-year postexposure. Subgroup analyses performed according to ovarian cancer, age group, and hormone replacement therapy produced results similar to those of the main outcome. LIMITATIONS: Because we used claims data, the detailed clinical information related to oophorectomy is lacking. There is possibility that time-varying confounder besides age and season might have affected the results CONCLUSIONS: The risk of depression increased before and after oophorectomy. The increase in risk of depression started before oophorectomy and peaked immediately before or after the operation, but no significant differences between unilateral and bilateral surgery and cancer and noncancer or among age groups were noted.

Risk of Suicide Attempt after Thyroidectomy: A Nationwide Population Study in South Korea.

OBJECTIVE: To investigate the association between thyroidectomy and suicide attempt. METHODS: A nationwide population-based electronic medical records database of South Korea between January 1, 2009 and June 30, 2016 was used to investigate incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts before and after thyroidectomy using a self-controlled case series design. RESULTS: In 2,986 patients who attempted suicide or probable suicide, the IRRs of suicidal behaviors during risk periods one year before and after thyroidectomy were investigated. Generally, after thyroidectomy, there was no increase in IRR compared to the non-risk period. When data were analyzed according to thyroidectomy type, after partial thyroidectomy, IRR increased up to 1.43 (95% CI: 1.03-1.98, p=0.032) in the days 91-181 period. In the subgroup with major depressive disorder (MDD), the IRR increased up to 1.74 (95% CI: 1.21-2.51, p=0.003) before thyroidectomy, and increased up to 1.67 (95% CI: 1.16-2.41, p=0.006) after thyroidectomy. CONCLUSION: Although the general risk of suicide attempt was not increased after thyroidectomy, patients with MDD showed increased risk of suicide attempt before and after thyroidectomy. These results suggest that suicidality should be evaluated when depressive symptoms are present in patients who have undergone thyroidectomy.

Predictive factors of diagnostic conversion from major depressive disorder to bipolar disorder in young adults ages 19-34: A nationwide population study in South Korea.

BACKGROUND: Predicting patients who convert to bipolar disorder is important for deciding appropriate treatment for young adults with major depressive disorder (MDD). We focused on the predictive factors of bipolar conversion in a large population of young adults. METHODS: A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment service of South was used to investigate adjusted hazard ratio (HR) of each potential predictor of the bipolar converter group compared to the non-converter group using Cox regression analysis including age of onset, medication use, clinical features, comorbid disorders, admission, self-harm, and negative life events in childhood. RESULTS: Among 291,721 subjects who were initially diagnosed with MDD in young adults, 12,376 subjects experienced diagnostic conversion to bipolar disorder. The cumulative incidence was 6.46% during the average 3.26 years of follow-up. Among the predictive factors during diagnosis of MDD, antipsychotic use (HR 3.12, 95%CI, 2.99-3.26, p < 0.0001) and mood stabilizers (HR 2.45, 95%CI, 2.35-2.55, p < 0.0001) showed the strongest association with diagnostic conversion to bipolar disorder. In addition, female sex, younger age of onset, mood stabilizer use, recurrent depression, psychotic symptoms, and admission to a psychiatric ward during diagnosis of MDD were also associated with diagnostic conversion to bipolar disorder. CONCLUSION: In young adults with MDD, antipsychotic and mood stabilizer use during diagnosis of MDD were the strongest predictive factors with diagnostic conversion to bipolar disorder during follow-up. If young adults with MDD need antipsychotics or mood stabilizer, patients should be carefully evaluated for possibility of bipolar disorder.

Risks of suicide attempts after prescription of zolpidem in people with depression: a nationwide population study in South Korea.

OBJECTIVES: To investigate the association between zolpidem prescription and suicide attempts in people with depression. METHODS: A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment Service of South was used to investigate the incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts in people with depression before and after zolpidem prescription using self-controlled case series design. RESULTS: In a total of 445 people who attempted suicide and 23 141 people who attempted probable suicide attempt, the IRRs of suicidal behavior during the risk periods before and after zolpidem prescription increased compared with those at the baseline. The IRRs gradually increased and peaked immediately before the prescription of zolpidem. The IRR was 70.06 (95% CI: 25.58-191.90) on day 2 before zolpidem prescription and 63.35 (95% CI: 22.99-174.59) on day 1 after zolpidem prescription in the suicide attempt group. The IRR was 24.07 (95% CI: 20.50-28.26) on the day before zolpidem prescription and 14.96 (95% CI: 12.21-18.34) on the day after zolpidem prescription in the probable suicide attempt group. The ratios declined eventually after zolpidem was prescribed. CONCLUSIONS: Although zolpidem prescription was associated with an increased risk of suicide attempts in people with depression, the risk increased and peaked immediately before zolpidem prescription. The risk declined gradually thereafter. This result indicates that the risk of suicide attempts increases at the time of zolpidem prescription. However, zolpidem prescription does not contribute to additional increase in the risk of suicide attempts.

Increased Morbidity of Major Depressive Disorder After Thyroidectomy: A Nationwide Population-Based Study in South Korea.

Background: The number of thyroidectomies in South Korea has been increasing rapidly due to extensive checkups for thyroid cancer. However, few studies have examined the association between thyroidectomy and major depressive disorder (MDD). We investigated the association between thyroidectomy and the risk of MDD. Methods: A population-based electronic medical records database from South Korea was used to identify 187,176 individuals who underwent partial or total thyroidectomy between 2009 and 2016. A self-controlled case series design and Cox regression analyses were used to identify risk factors for MDD. Results: Among the 187,176 individuals who underwent thyroidectomy, 16,744 (8.9%) were diagnosed with MDD during the observation period. Of those, 3837 (22.9%) underwent partial thyroidectomy and 12,907 (77.1%) underwent total thyroidectomy. An elevated MDD risk was found during the one-year period before thyroidectomy, with incidence rate ratios (IRRs) of 1.29 ([95% confidence interval [CI] 1.18-1.41], p < 0.0001) for subjects with partial thyroidectomy and 1.27 ([95% CI 1.21-1.33], p < 0.0001) for subjects with total thyroidectomy. After total thyroidectomy, the IRR increased for 31-60 days (IRR 1.81; [95% CI 1.59-2.06], p < 0.0001) and remained elevated for up to 540 days, whereas after partial thyroidectomy, the IRR increased for 31-60 days (IRR 1.68; [95% CI 1.32-2.13], p < 0.0001) but returned to baseline levels after 270 days. Total thyroidectomy was associated with a prolonged risk of MDD compared with partial thyroidectomy in patients with cancer, which was different from the results in patients without cancer. Conclusion: The incidence of MDD increased in the period immediately after thyroidectomy and remained high for one to two years. This study highlights the importance of relatively long-term regular psychiatric assessments in patients who undergo partial or total thyroidectomy.

Effects of Visual Game Experience on Auditory Processing Speed.

Games are one of the fastest growing and most exciting forms of entertainment. Whether casual mobile game playing has a cognitive, physiological, or behavioral effect on players whose game use is not pathological is unknown. Here we explored whether preattentive auditory processing is linked to the behavioral inhibition system (BIS) in frequent and infrequent game players. A total of 74 subjects who were enrolled in our study were divided into two groups, 40 subjects were frequent gamers and 34 subjects were age-, gender-, IQ-, and education-matched infrequent gamers. All participants underwent a passive auditory oddball paradigm and completed the behavioral inhibition/behavioral activation system scales. The mismatch negativity (MMN) latency was shorter for the frequent gamers relative to the infrequent gamers, whereas no difference in MMN amplitude was found between groups. MMN amplitude was negatively associated with the degree of behavioral inhibition in the frequent and infrequent gaming group. We also found that those who frequently play games show an enhanced processing speed, which could be an effect of game practice. Greater behavioral inhibition induces increased vigilance, and this may have enhanced the MMN amplitude in the infrequent gamers. This differential pattern of correlations suggests that differences in the BIS could lead to different approaches to auditory information processing.