Identifying predictive factors for mood recurrence in early-onset major mood disorders: A 4-year, multicenter, prospective cohort study.

We investigate the predictive factors of the mood recurrence in patients with early-onset major mood disorders from a prospective observational cohort study from July 2015 to December 2019. A total of 495 patients were classified into three groups according to recurrence during the cohort observation period: recurrence group with (hypo)manic or mixed features (MMR), recurrence group with only depressive features (ODR), and no recurrence group (NR). As a result, the baseline diagnosis of bipolar disorder type 1 (BDI) and bipolar disorder type 2 (BDII), along with a familial history of BD, are strong predictors of the MMR. The discrepancies in wake-up times between weekdays and weekends, along with disrupted circadian rhythms, are identified as a notable predictor of ODR. Our findings confirm that we need to be aware of different predictors for each form of mood recurrences in patients with early-onset mood disorders. In clinical practice, we expect that information obtained from the initial assessment of patients with mood disorders, such as mood disorder type, family history of BD, regularity of wake-up time, and disruption of circadian rhythms, can help predict the risk of recurrence for each patient, allowing for early detection and timely intervention.

Development and multicenter validation of deep convolutional neural network-based detection of colorectal cancer on abdominal CT.

OBJECTIVES: This study aims to develop computer-aided detection (CAD) for colorectal cancer (CRC) using abdominal CT based on a deep convolutional neural network. METHODS: This retrospective study included consecutive patients with colorectal adenocarcinoma who underwent abdominal CT before CRC resection surgery (training set = 379, test set = 103). We customized the 3D U-Net of nnU-Net (CUNET) for CRC detection, which was trained with fivefold cross-validation using annotated CT images. CUNET was validated using datasets covering various clinical situations and institutions: an internal test set (n = 103), internal patients with CRC first determined by CT (n = 54) and asymptomatic CRC (n = 51), and an external validation set from two institutions (n = 60). During each validation, data from the healthy population were added (internal = 60; external = 130). CUNET was compared with other deep CNNs: residual U-Net and EfficientDet. The CAD performances were evaluated using per-CRC sensitivity (true positive/all CRCs), free-response receiver operating characteristic (FROC), and jackknife alternative FROC (JAFROC) curves. RESULTS: CUNET showed a higher maximum per-CRC sensitivity than residual U-Net and EfficientDet (internal test set 91.3% vs. 61.2%, and 64.1%). The per-CRC sensitivity of CUNET at false-positive rates of 3.0 was as follows: internal CRC determined by CT, 89.3%; internal asymptomatic CRC, 87.3%; and external validation, 89.6%. CUNET detected 69.2% (9/13) of CRCs missed by radiologists and 89.7% (252/281) of CRCs from all validation sets. CONCLUSIONS: CUNET can detect CRC on abdominal CT in patients with various clinical situations and from external institutions. KEY POINTS: • Customized 3D U-Net of nnU-Net (CUNET) can be applied to the opportunistic detection of colorectal cancer (CRC) in abdominal CT, helping radiologists detect unexpected CRC. • CUNET showed the best performance at false-positive rates ≥ 3.0, and 30.1% of false-positives were in the colorectum. CUNET detected 69.2% (9/13) of CRCs missed by radiologists and 87.3% (48/55) of asymptomatic CRCs. • CUNET detected CRCs in multiple validation sets composed of varying clinical situations and from different institutions, and CUNET detected 89.7% (252/281) of CRCs from all validation sets.

A nationwide real-world study for evaluation of effectiveness and safety of T-DM1 in patients with HER2-positive metastatic breast cancer in Korea (KCSG BR19-15).

Purpose: This study aimed to investigate clinical practices and factors related to the outcomes of T-DM1 use in patients with HER2-positive metastatic breast cancer (mBC). Methods: We included patients with HER2-positive mBC who received T-DM1 as a palliative therapy between August 2017 and December 2018. The safety and outcomes of T-DM1, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) for mortality or progression to HER2-positive mBC. Results: In total, 824 patients were enrolled during the study period. The mean age of patients was 58 years, and 516 (62.6%) patients relapsed after curative treatment. Excluding a history of endocrine therapy, 341 (41.4%) patients previously received none or first-line chemotherapy, 179 (21.7%) received second-line therapy, and 303 (36.9%) received third-or later-line chemotherapy before T-DM1 therapy. During a median follow-up of 16.8 months, the ORR was 35%, the median PFS was 6.6 months, and the median OS was not reached. The clinical factors associated with the hazard of progression were age (<65 years), poor performance status (⩾2), advanced line of palliative chemotherapy (⩾2), prior pertuzumab use, and treatment duration of palliative trastuzumab (<10 months). Common grade 3-4 adverse events were thrombocytopenia (n = 107, 13.2%), neutropenia (n = 23, 2.8%), anemia (n = 21, 2.6%), and elevated liver enzyme (n = 20, 2.5%). Hypokalemia (⩽3.0 mmol/L) and any-grade bleeding events occurred in 25 (3.1%) and 94 (22.6%) patients, respectively. Conclusion: This is the first nationwide real-world study of T-DM1 use in patients with HER2-positive mBC in Korea. The effectiveness and toxicity profiles of T-DM1 in real-world practice were comparable to those in randomized trials. Moreover, patient factors and previous anti-HER2 therapy could predict the outcomes of T-DM1 therapy.

Prevalence of Loneliness and Its Association With Suicidality in the General Population: Results From a Nationwide Survey in Korea.

BACKGROUND: Although it is known that a substantial proportion of the population experience loneliness, the consequence of loneliness remains unclear by countries and ages. Accordingly, this study aimed to assess the association between loneliness and suicidality in the general population of Korea. METHOD: A total of 5,511 Koreans aged 18-79 completed a tablet-assisted personal interview using the Korean version of the Composite International Diagnostic Interview and responded to questions about loneliness and lifetime suicidal ideation, plans, and attempts. A logistic regression analysis was used to examine the association between loneliness and suicidality. RESULTS: Approximately one-third of the Korean general population reported loneliness. Being older, never married, widowed, separated, or divorced, unemployed, and having a part-time job were all significantly related to loneliness. After adjusting for sociodemographic factors, individuals with loneliness were significantly associated with increased suicidal ideation (adjusted odd ratio [aOR], 4.05; 95% confidence interval [CI], 3.36-4.88), suicidal plans (aOR, 4.91; 95% CI, 3.34-7.21), and suicidal attempts (aOR, 4.82; 95% CI, 3.03-7.66). Even after adjusting for sociodemographic factors and mental disorders, suicidality remained statistically significant. Moreover, frequent, moderate-to-severe, and long-term loneliness were all associated with increased ORs for suicidality, regardless of sociodemographic factors and mental disorders. CONCLUSION: Loneliness was associated with suicidal ideation, plans, and attempts. This study lays the foundation for public health policymakers to establish early intervention and mental health care support for lonely people.

Pivotal Clinical Study to Evaluate the Efficacy and Safety of Assistive Artificial Intelligence-Based Software for Cervical Cancer Diagnosis.

Colposcopy is the gold standard diagnostic tool for identifying cervical lesions. However, the accuracy of colposcopies depends on the proficiency of the colposcopist. Machine learning algorithms using an artificial intelligence (AI) system can quickly process large amounts of data and have been successfully applied in several clinical situations. This study evaluated the feasibility of an AI system as an assistive tool for diagnosing high-grade cervical intraepithelial neoplasia lesions compared to the human interpretation of cervical images. This two-centered, crossover, double-blind, randomized controlled trial included 886 randomly selected images. Four colposcopists (two proficient and two inexperienced) independently evaluated cervical images, once with and the other time without the aid of the Cerviray AI® system (AIDOT, Seoul, Republic of Korea). The AI aid demonstrated improved areas under the curve on the localization receiver-operating characteristic curve compared with the colposcopy impressions of colposcopists (difference 0.12, 95% confidence interval, 0.10-0.14, p < 0.001). Sensitivity and specificity also improved when using the AI system (89.18% vs. 71.33%; p < 0.001, 96.68% vs. 92.16%; p < 0.001, respectively). Additionally, the classification accuracy rate improved with the aid of AI (86.40% vs. 75.45%; p < 0.001). Overall, the AI system could be used as an assistive diagnostic tool for both proficient and inexperienced colposcopists in cervical cancer screenings to estimate the impression and location of pathologic lesions. Further utilization of this system could help inexperienced colposcopists confirm where to perform a biopsy to diagnose high-grade lesions.

Long-term survival benefits of intrathecal autologous bone marrow-derived mesenchymal stem cells (Neuronata-R®: lenzumestrocel) treatment in ALS: Propensity-score-matched control, surveillance study.

Objective: Neuronata-R® (lenzumestrocel) is an autologous bone marrow-derived mesenchymal stem cell (BM-MSC) product, which was conditionally approved by the Korean Ministry of Food and Drug Safety (KMFDS, Republic of Korea) in 2013 for the treatment of amyotrophic lateral sclerosis (ALS). In the present study, we aimed to investigate the long-term survival benefits of treatment with intrathecal lenzumestrocel. Methods: A total of 157 participants who received lenzumestrocel and whose symptom duration was less than 2 years were included in the analysis (BM-MSC group). The survival data of placebo participants from the Pooled-Resource Open-Access ALS Clinical Trials (PROACT) database were used as the external control, and propensity score matching (PSM) was used to reduce confounding biases in baseline characteristics. Adverse events were recorded during the entire follow-up period after the first treatment. Results: Survival probability was significantly higher in the BM-MSC group compared to the external control group from the PROACT database (log-rank, p < 0.001). Multivariate Cox proportional hazard analysis showed a significantly lower hazard ratio for death in the BM-MSC group and indicated that multiple injections were more effective. Additionally, there were no serious adverse drug reactions found during the safety assessment, lasting a year after the first administration. Conclusion: The results of the present study showed that lenzumestrocel treatment had a long-term survival benefit in real-world ALS patients.

Short-term and long-term predictors of balance function in stroke patients: a 6-month follow-up study.

We aimed to determine early predictors of balance function (Berg Balance Scale, BBS) at 3 and 6 months after stroke using clinical, neurophysiological, and neuroimaging variables. Seventy-nine patients with hemiparesis after a stroke were included. Demographics, stroke characteristics, and clinical variables [Mini-Mental State Examination, BBS, strength in the hemiparetic hip, knee, and ankle muscles, and Fugl-Meyer Assessment Lower Extremity (FMA-LE)] were evaluated 2 weeks post-stroke, on average. Somatosensory-evoked potentials (SEP) from both tibial nerves and diffusion tensor imaging data were collected respectively within 3 weeks and 4 weeks post-onset to calculate the SEP amplitude ratio and the laterality index of fractional anisotropy of the corticospinal tract. In multiple linear regression analysis, younger age, higher FMA-LE score, and stronger hemiparetic hip extensors were independent predictors of higher BBS at 3 months post-stroke (adjusted R2 = 0.563, P < 0.001). At 6 months post-stroke, significant predictors of higher BBS were younger age, higher FMA-LE, stronger hemiparetic hip extensors, and larger SEP amplitude ratio (adjusted R2 = 0.552, P < 0.001), although the incremental contribution of the latter was rather small ( R2 = 0.019). We conclude that age and the initial motor impairment of the affected lower limb can inform the state of balance function at 3 and 6 months after stroke.

Prevalence of Mental Disorders and Associated Factors in Korean Adults: National Mental Health Survey of Korea 2021.

OBJECTIVE: Mental health is a global concern and needs to be studied more closely. We aimed to estimate the prevalence of mental disorders and their associated factors among the general population in Korea. METHODS: The National Mental Health Survey of Korea 2021 was conducted between June 19 and August 31, 2021 and included 13,530 households; 5,511 participants completed the interview (response rate: 40.7%). The lifetime and 12-month diagnosis rates of mental disorders were made using the Korean version of the Composite International Diagnostic Interview 2.1. Factors associated with alcohol use disorder (AUD), nicotine use disorder, depressive disorder, and anxiety disorder were analyzed, and mental health service utilization rates were estimated. RESULTS: The lifetime prevalence of mental disorders was 27.8%. The 12-month prevalence rates of alcohol use, nicotine use, depressive, and anxiety disorders were 2.6%, 2.7%, 1.7%, and 3.1%, respectively. The risk factors associated with 12-month diagnosis rates were as follows: AUD: sex and age; nicotine use disorder: sex; depressive disorder: marital status and job status; anxiety disorder: sex, marital status, and job status. The 12-month treatment and service utilization rates for 12-month AUD, nicotine use disorder, depressive disorder, and anxiety disorder were 2.6%, 1.1%, 28.2%, and 9.1%, respectively. CONCLUSION: Approximately 25% of adults in the general population were diagnosed with mental disorders during their lifetime. The treatment rates were substantially low. Future studies on this topic and efforts to increase the mental health treatment rate at a national level are needed.

Efficacy and Safety of Escitalopram, Desvenlafaxine, and Vortioxetine in the Acute Treatment of Anxious Depression: A Randomized Rater-blinded 6-week Clinical Trial.

Objective: Anxious depression is associated with greater chronicity, higher severity of symptoms, more severe functional impairment, and poor response to drug treatment. However, evidence for first-choice antidepressants in patients with anxious depression is limited. This study aimed to compare the efficacy and safety of escitalopram, desvenlafaxine, and vortioxetine in the acute treatment of anxious depression. Methods: Patients (n = 124) with major depressive disorder and high levels of anxiety were randomly assigned to an escitalopram treatment group (n = 42), desvenlafaxine treatment group (n = 40), or vortioxetine treatment group (n = 42) in a 6-week randomized rater-blinded head-to-head comparative trial. Changes in overall depressive and anxiety symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA), respectively. Results: Patients demonstrated similar baseline-to-endpoint improvement in scores and similar response and remission rates for HAMD and HAMA. Analysis of the individual HAMD items revealed that desvenlafaxine significantly reduced anxiety somatic scores (p = 0.013) and hypochondriasis scores (p = 0.014) compared to escitalopram. With respect to the individual HAMA items, desvenlafaxine treatment showed significantly lower scores for respiratory symptoms (p = 0.013) than escitalopram treatment and cardiovascular symptoms (p = 0.005) than vortioxetine treatment. The treatments were well tolerated, with no significant differences. Conclusion: Our results indicated no significant differences in the efficacy and tolerability of escitalopram, desvenlafaxine, and vortioxetine in this subtype of patients with anxious depression during the acute phase of treatment.

Age, Sex, and Body Mass Index Should Be Considered When Assessing Spleen Length in Patients with Compensated Advanced Chronic Liver Disease.

Background/Aims: We investigated the factors related to spleen length and the diagnostic accuracy of a model using spleen length corrected by related factors, for the prediction of varices needing treatment (VNT). Methods: Various prediction models for VNT including spleen length were analyzed in the cohort of compensated advanced chronic liver disease (cACLD), defined as liver stiffness (LS) ≥10 kPa in a recent study. The associated factors for spleen length were identified in healthy subjects to improve the prediction of VNT. Results: Among 1,218 cACLD patients, VNT was noted in 249 patients (20.4%). On multivariate analysis, longer spleen length, lower platelet count, and higher LS value were independent predictors for VNT (all p<0.001). In multivariate analysis of 1,041 healthy subjects, age (ß=-0.027), sex (ß=0.762), and body mass index (ß=0.097) were found to be significant factors for spleen length (all p<0.001). Using the ß values, the estimated spleen length was calculated. To improve the prediction of VNT, the ratio of measured and estimated spleen length was calculated. Based on binary regression analysis results, the LS value-spleen ratio to platelet score (LSRPS) was calculated as follows: 0.027×LS value (kPa)+2.690×measured/estimated spleen ratio-0.011×platelet count (cells×109/L)-4.215. The area under the receiver operating characteristic of the LSRPS for VNT was 0.820, which was significantly higher than 0.797 of LS value-spleen diameter to platelet ratio score (LSPS) (p=0.006). Conclusions: Spleen length is influenced by age, sex, and body mass index in the Asian population. The LSRPS using the measured/estimated spleen ratio had higher diagnostic accuracy than LSPS in predicting VNT in patients with cACLD.

Item non-response imputation in the Korea National Health and Nutrition Examination Survey.

OBJECTIVES: The Korea National Health and Nutrition Examination Survey (KNHANES) is a public health survey that assesses individuals' health and nutritional status and monitors the prevalence of major chronic diseases. In general, sampling weights are adjusted for unit non-responses and imputation is conducted for item non-responses. In this study, we proposed strategies for imputing item non-responses in the KNHANES in order to improve the usefulness of data, minimize bias, and increase statistical power. METHODS: After applying logical imputation, we adopted 2 separate imputation methods for each variable type: unweighted sequential hot-deck imputation for categorical variables and sequential regression imputation for continuous variables. For variance estimation, multiple imputations were applied to the continuous variables. To evaluate the performance of the proposed strategies, we compared the marginal distributions of imputed variables and the results of multivariable regression analysis for the complete-case data and the expanded data with imputed values, respectively. RESULTS: When comparing the marginal distributions, most non-responses were imputed. The multivariable regression coefficients presented similar estimates; however, the standard errors decreased, resulting in statistically significant p-values. The proposed imputation strategies may cope with the loss of precision due to missing data, thus enhancing statistical power in analyses of the KNHANES by providing expanded data with imputed values. CONCLUSIONS: The proposed imputation strategy may enhance the utility of data by increasing the number of complete cases and reducing the bias in the analysis, thus laying a foundation to cope with the occurrence of item non-responses in further surveys.

Data collection framework for electronic medical record-based real-world data to evaluate the effectiveness and safety of cancer drugs: a nationwide real-world study of the Korean Cancer Study Group.

Background: Electronic medical records (EMRs) have the highest value among real-world data (RWD). The aim of the present study was to propose a data collection framework of EMR-based RWD to evaluate the effectiveness and safety of cancer drugs by conducting a nationwide real-world study based on the Korean Cancer Study Group. Methods: We considered all patients who received ramucirumab plus paclitaxel (RAM/PTX) for gastric cancer and trastuzumab emtansine (T-DM1) for breast cancer at relevant institutions in South Korea. Standard operating procedures for systematic data collection were prospectively developed. Investigator reliability was evaluated using the concordance rate between the recommended input value for representative fictional cases and the input value of each investigator. Reliability of collected data was evaluated twice during the study period at three institutions randomly selected using the concordance rate between the previously collected data and data collected by an independent investigator. The reliability results of the investigators and collected data were used for revision of the electronic data capture system and site training. Results: Between the starting date of medical insurance coverage and December 2018, a total of 1063 patients at 56 institutions in the RAM/PTX cohort and 824 patients at 60 institutions in the T-DM1 cohort were included. Mean investigator reliability in the RAM/PTX and T-DM1 cohorts was 73.5% and 71.9%, respectively. Mean reliability of collected data in the RAM/PTX and T-DM1 cohort was 90.0% for both cohorts in the first analysis and 89.0% and 84.0% in the second analysis, respectively. Mean missing values of the RAM/PTX and T-DM1 cohorts at the time of simulation of fictional cases and final data analysis decreased from 20.7% to 0.46% and from 18.5% to 0.76%, respectively. Conclusion: This real-world study provides a framework that ensures relevance and reliability of EMR-based RWD for evaluating the effectiveness and safety of cancer drugs.

The relationship between morningness-eveningness and mood symptoms and quality of life in euthymic state of mood disorders: Results from a prospective observational cohort study.

BACKGROUND: The clinical importance of morningness-eveningness, especially in mood disorders, is prevailing. The differential relation of chronotype with diagnoses of early-onset mood disorders, mood symptoms, anxiety, and quality of life was evaluated. METHODS: Early-onset mood disorder patients [n = 419; 146 major depressive disorder (MDD); 123 bipolar I disorder (BDI); 150 bipolar II disorder (BDII)] from the Mood Disorder Cohort Research Consortium were assessed for chronotype using the composite scale for morningness (CSM) and its association with clinical variables obtained during the clinician-verified euthymic state. RESULTS: The mean total CSM of BDI was significantly higher than MDD and BDII (p < 0.001). In all types of mood disorders, higher total CSM was associated with lower Quick inventory of depressive symptomatology (p < 0.005) and higher WHO quality of life (p < 0.005). Such negative correlations between the total CSM and Montgomery-Asberg depression rating were significant in MDD and BDI (p < 0.05) and marginally significant in BDII (p = 0.077). CSM was a significant contributor to quality of life in BDI (p < 0.001) and BDII (p = 0.011), but it was not for MDD. LIMITATIONS: The defined 'euthymic state' that may not fully reflect the remission of episode; limited generalizability due to clinical characteristic of early-onset mood disorder; the disparity between diurnal preference measured by the CSM and chronotype; possible effects of the last mood episode polarity and medication; and, lack of control group. CONCLUSION: Less eveningness was associated with less severe depressive symptoms and better quality of life. This suggests that morningness may reduce residual depressive symptoms and recover function of patients.

Endoscopic variceal obturation and retrograde transvenous obliteration for acute gastric cardiofundal variceal bleeding in liver cirrhosis.

BACKGROUND/AIMS: We retrospectively compared the effect of endoscopic variceal obturation (EVO) and retrograde transvenous obliteration (RTO) in acute cardiofundal variceal bleeding. METHODS: Patients with acute cardiofundal variceal bleeding treated with EVO or RTO at two hospitals were included. RESULTS: Ninety patients treated with EVO and 86 treated with RTO were analyzed. The mean model for end-stage liver disease score was significantly higher in EVO group than in RTO group (13.5 vs. 11.7, P = 0.016). The bleeding control rates were high (97.8% vs. 96.5%), and the treatment-related complication rates were low in both EVO and RTO groups (2.2% vs. 3.5%). During the median follow-up of 18.0 months, gastric variceal (GV) and esophageal variceal rebleeding occurred in 34 (19.3%) and 7 (4.0%) patients, respectively. The all-variceal rebleeding rates were comparable between EVO and RTO groups (32.4% vs. 20.8% at 2-year, P = 0.150), while the GV rebleeding rate was significantly higher in EVO group than in RTO group (32.4% vs. 12.8% at 2-year, P = 0.003). On propensity score-matched analysis (71 patients in EVO vs. 71 patients in RTO group), both all-variceal and GV rebleeding rates were significantly higher in EVO group than in RTO group (all P < 0.05). In Cox regression analysis, EVO (vs. RTO) was the only significant predictor of higher GV rebleeding risk (hazard ratio 3.132, P = 0.005). The mortality rates were similar between two groups (P = 0.597). CONCLUSIONS: Both EVO and RTO effectively controlled acute cardiofundal variceal bleeding. RTO was superior to EVO in preventing all-variceal and GV rebleeding after treatment, with similar survival outcomes.

Acute Efficacy and Safety of Escitalopram Versus Desvenlafaxine and Vortioxetine in the Treatment of Depression With Cognitive Complaint: A Rater-Blinded Randomized Comparative Study.

OBJECTIVE: This study aimed to compare the efficacy and safety of escitalopram, vortioxetine, and desvenlafaxine for acute treatment of major depressive disorder (MDD) with cognitive complaint (CC). METHODS: A total of 129 patients with MDD who also complained of CC were randomized evenly to either escitalopram, vortioxetine, or desvenlafaxine group and underwent a multi-center, six-week, rater-blinded, and head-to-head comparative trial. Differences in depressive symptoms following treatment were measured using the Hamilton Depression Rating Scale (HAMD) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Subjective cognitive function and the presence of adverse events were assessed. RESULTS: The three antidepressant treatment groups did not show significant differences in the improvement of depressive symptoms as measured by HAMD and MADRS. Desvenlafaxine treatment was associated with a superior treatment response rate in depressive symptoms compared to vortioxetine or escitalopram treatment. However, no significant differences were found in the remission rate of depressive symptoms. The three antidepressant treatment groups did not show significant differences in the improvement of CC. Adverse profiles of each treatment group were tolerable, with no significant differences. CONCLUSION: In acute antidepressant treatment for MDD with CC, escitalopram, vortioxetine, and desvenlafaxine presented similar efficacy in relief of depressive symptoms; however, desvenlafaxine was associated with a superior treatment. Further studies are needed to confirm these results by investigating the therapeutic efficacy and safety profile of long-term antidepressant treatment of MDD with CC (Clinical Trial Registry, http://cris.nih.go.kr/cris/en/: KCT0002173).

Korean Guidelines for Pharmacoeconomic Evaluations: Updates in the Third Version.

The first version of the pharmacoeconomic (PE) guidelines was published in South Korea in 2006. Despite its first revision in 2011, there were still ambiguities in its interpretation. Moreover, methodologies for estimating effectiveness and costs have also evolved since then. Under these circumstances, the Health Insurance Review and Assessment Service published the third version in January 2021. This article reviews the revision process and major changes made in the new edition of the PE guidelines. The revision was processed through reviews of the previous 50 PE submissions, international guidelines, academic literature, and surveys and advisory meetings to obtain stakeholders' opinions. The analysis perspective has changed from a limited societal perspective to a healthcare system perspective. In addition to the drug with the highest market share, drugs used in clinical trials can be selected as comparators under certain conditions. The discount rate decreased from 5% to 4.5%. Furthermore, the revised guidelines provide more detailed and specific instructions for items including non-inferiority margin, extrapolation, utility elicitation, and uncertainty. Treatment switch and co-dependent technology guidelines are newly included; the budget impact analysis guideline is deleted. Through this revision, transparency and consistency of decision-making is expected to improve.

Ramucirumab plus paclitaxel as a second-line treatment in HER2-positive gastric cancer: subgroup analysis of a nationwide, real-world study in Korea (KCSG-ST19-16).

BACKGROUND: A subgroup analysis of data from a nationwide study (KCSG-ST19-16) was performed to evaluate the efficacy and safety of second-line ramucirumab plus paclitaxel treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma. METHODS: The KCSG-ST19-16 study enrolled a total of 1063 patients from 56 hospitals in South Korea with advanced gastric or GEJ adenocarcinoma, who had received second-line treatment with ramucirumab plus paclitaxel. HER2 status was known for 994 (93.5%) of these patients, who were thus included in the subgroup analysis. RESULTS: In total, 163 of 994 patients (16.4%), had HER2-positive gastric or GEJ adenocarcinoma. The objective response rate to ramucirumab plus paclitaxel treatment was significantly higher in patients with HER2-positive disease compared to those with HER2-negative disease (23.0% [95% confidence interval (CI), 15.9-30.1] vs. 15.1% [95% CI, 12.3-17.9], p = 0.025). The median progression-free survival was longer in patients with HER2-positive versus HER2-negative disease, but the difference was not statistically significant (4.3 months [95% CI, 3.7-5.3] vs 3.7 months [95% CI, 3.4-4.0], p = 0.054). There was no statistically significant difference in median overall survival (OS) between the groups (9.8 months [95% CI, 8.9-12.3] vs 10.1 months [95% CI, 9.2-10.9], p = 0.564). CONCLUSIONS: In patients with HER2-positive gastric or GEJ adenocarcinoma, the objective response rate to second-line treatment with ramucirumab plus paclitaxel was significantly higher compared to patients with HER2-negative disease. However, an increased response to treatment was not associated with an improvement in OS.

Accuracy of MRI for predicting anterior peritoneal reflection involvement in locally advanced rectal cancer: a comparison with operative findings.

PURPOSE: To assess the diagnostic accuracy of preoperative rectal MRI for anterior peritoneal reflection (APR) involvement in rectal cancer through comparison with the surgeon's operative findings. METHODS: This retrospective study was approved by the institutional review board; informed consent was waived. We enrolled 55 consecutive patients with suspected locally advanced mid-to-upper rectal cancer. All patients underwent rectal MRI using a 3T system. APR involvement in rectal cancer was assessed radiologically using a 5-point scale by two independent board-certified abdominal radiologists. The surgeon's evaluation during surgery was regarded as the gold standard for APR involvement. The accuracy of rectal MRI in predicting APR involvement was obtained. RESULTS: Rectal MRI showed good APR identification (rater 1, 92.7%; rater 2, 94.7%). On preoperative rectal MRI, rater 1 diagnosed 19 (34.5%) patients as having APR involvement and rater 2 diagnosed 28 (50.9%) as having APR involvement. There was moderate agreement (κ = 0.602, p < 0.001) between the two raters with regard to the evaluation of APR involvement. During surgery, the surgeon confirmed APR involvement in 13 (23.6%) patients. The sensitivity, specificity, PPV, and NPV of preoperative MRI for APR involvement were 69.2%, 76.2%, 47.4%, and 88.9%, respectively. The diagnostic accuracy of MRI for predicting APR involvement was 74.6%. CONCLUSION: Preoperative rectal MRI provides accurate anatomical information regarding APR involvement with high conspicuity. However, MRI has relatively low sensitivity (< 70%) and a low PPV (< 50%) with regard to the assessment of APR involvement in rectal tumors. Both rater 1 and rater 2 evaluated these images as positive involvement of APR. The patient underwent laparoscopic low anterior resection after preoperative evaluation. However, during surgery, the surgeon evaluated APR involvement as negative, and the final pathologic staging was confirmed as T3.

Clinical effectiveness and safety of amlodipine/losartan-based single-pill combination therapy in patients with hypertension: Findings from real-world, multicenter observational databases.

Various single-pill combinations (SPCs) have been introduced to improve drug compliance and clinical efficacy. However, there is a lack of real-world evidence regarding the effectiveness of these SPCs for hypertension. This study evaluated the real-world clinical efficacy and safety of amlodipine/losartan-based SPC therapies in patients with hypertension in a real-world setting. A total of 15 538 patients treated with amlodipine/losartan-based SPCs [amlodipine + losartan (AL), amlodipine + losartan + rosuvastatin (ALR), and amlodipine + losartan + chlorthalidone (ALC)] were selected from the database of three tertiary hospitals in Korea. The efficacy endpoints were target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) achievement rates. Safety was evaluated based on laboratory parameters. Drug adherence was defined as the proportion of medication days covered (PDC). The target BP attainment rate was above 90% and was similar among the three groups. Although many patients in the AL and ALC groups took statins, the target LDL-C attainment rate was significantly higher in the ALR group than in the AL and ALC groups. Safety endpoints were not significantly different among the groups, except serum uric acid level and incidence rate of new-onset hyperuricemia, which were significantly lower in the AL and ALR groups than in the ALC group. The PDC was > 90% in all groups. In the real-world hypertensive patients, amlodipine/losartan-based SPC therapy demonstrated good target BP achievement rates. Especially, rosuvastatin-combination SPC showed better target LDL-C goal achievement rate compared to the other SPCs. All three amlodipine/losartan-based SPC had excellent drug adherence.