Differences in end-of-life care patterns between types of hospice used for cancer patients: a retrospective cohort study.

BACKGROUND: In response to the rapid aging population and increasing number of cancer patients, discussions on dignified end-of-life (EoL) decisions are active around the world. Therefore, this study aimed to identify the differences in EoL care patterns between types of hospice used for cancer patients. METHODS: In this population-based cohort study, the Korean National Health Insurance Service cohort data containing all registered cancer patients who died between 2017 and 2021 were used. A total of 408,964 individuals were eligible for analysis. The variable of interest, the type of hospice used in the 6 months before death, was classified as follows: (1) Non-hospice users; (2) Hospital-based hospice single users; (3) Home-based hospice single users; (4) Combined hospice users. The outcomes were set as patterns of care, including intense care and supportive care. To identify differences in care patterns between hospice types, a generalized linear model with zero-inflated negative binomial distribution was applied. RESULTS: Hospice enrollment was associated with less intense care and more supportive care near death. Notably, those who used combined hospice care had the lowest probability and frequency of receiving intense care (aOR: 0.18, 95% CI: 0.17-0.19, aRR: 0.47, 95% CI: 0.44-0.49), while home-based hospice single users had the highest probability and frequency of receiving supportive care (Prescription for narcotic analgesics, aOR: 2.95, 95% CI: 2.69-3.23, aRR: 1.45, 95% CI: 1.41-1.49; Mental health care, aOR: 3.40, 95% CI: 3.13-3.69, aRR: 1.35, 95% CI: 1.31-1.39). CONCLUSION: Our findings suggest that although intense care for life-sustaining decreases with hospice enrollment, QoL at the EoL actually improves with appropriate supportive care. This study is meaningful in that it not only offers valuable insight into hospice care for terminally ill patients, but also provides policy implications for the introduction of patient-centered community-based hospice services.

Impact of Cardiac Rehabilitation Health Insurance Coverage on Cardiac Rehabilitation Use in Korea Using an Interrupted Time Series.

BACKGROUND: Since 2017, the cardiac rehabilitation (CR) program in Korea has been included in the coverage provided by the National Health Insurance to alleviate financial burden. Our study aimed to identify changes in the CR program use according to the implementation of CR coverage. METHODS AND RESULTS: We obtained data from the electronic medical records of a tertiary hospital in Seoul, Korea from January 2014 to February 2020. Data from 2988 patients with acute coronary syndrome who underwent percutaneous coronary intervention were included. To examine the CR use trend among patients undergoing percutaneous coronary intervention, the electronic medical records data of the patients were aggregated quarterly, resulting in a maximum of 24 repeated measures for each patient. Segmented regression is often used to estimate the effects of interventions in an interrupted time series. Policy implementation led to a prompt increase in the probability of CR use (odds ratio [OR], 3.99 [95% CI, 2.89-5.51]). After the implementation of CR coverage, no significant change in CR use (OR, 0.97 [95% CI, 0.92-1.01]) was observed. After percutaneous coronary intervention, more patients opted for CR, especially those receiving education compared with exercise (education: OR, 87.44 [95% CI, 36.79-207.83] versus exercise: OR, 1.99 [95% CI, 1.43-2.76]). CONCLUSIONS: The implementation of CR coverage resulted in a rapid increase in the probability of CR use. Use of the educational program was higher than that of the exercise program. Given the persistently low use of CR, it is imperative to stimulate its adoption by increasing its availability.

Open-Label, Multicenter, Randomized, Biomarker-Integrated Umbrella Trial for Second-Line Treatment of Advanced Gastric Cancer: K-Umbrella Gastric Cancer Study.

PURPOSE: This study aimed to screen targeted agents as second-line treatment with a standard-of-care (SOC) controlled umbrella trial design in advanced gastric cancer (AGC). PATIENTS AND METHODS: Patients with HER2-negative AGC from eight Korean cancer centers were screened for druggable targets using immunohistochemistry (IHC) and in situ hybridization, and randomly assigned to the biomarker versus control group at a 4:1 ratio. In the biomarker group, patients were treated with specific targeted agent plus paclitaxel: pan-ERBB inhibitor for epidermal growth factor receptor (EGFR) 2+/3+ patients (afatinib; EGFR cohort), PIK3Cß inhibitor for phosphatase and tensin homolog (PTEN) loss/null patients (GSK2636771; PTEN cohort), and anti-PD-1 inhibitor for PD-L1+, deficient mismatch repair/microsatellite instability-high, or Epstein-Barr virus-related cases (nivolumab; NIVO cohort). NONE cohort in the biomarker group without predefined biomarkers and control group received SOC (paclitaxel with or without ramucirumab). The primary end point was progression-free survival (PFS), and the secondary end points were efficacy and safety. RESULTS: A total of 318 patients were randomly assigned into the control (n = 64) and biomarker (n = 254; EGFR, n = 67; PTEN, n = 37; NIVO, n = 48; NONE, n = 102) groups. Median follow-up was 35 months. Median PFS and overall survival (OS) were 3.7 (95% CI, 3.1 to 4.1) and 8.6 (95% CI, 7.6 to 9.8) months in the biomarker group and 4.0 (95% CI, 3.0 to 4.6) and 8.7 (95% CI, 7.1 to 9.9) months in the control group. Afatinib addition led to marginal survival benefits to patients with EGFR 3+ compared with SOC (PFS, 4.0 v 2.2 months; P = .09), but GSK2636771 did not prolong the survival of patients with PTEN loss. Addition of nivolumab showed a durable survival benefit (median OS, 12.0 v 7.6 months; P = .08). CONCLUSION: Although biomarker group did not show better survival than the control group, IHC-based screening and allocation of patients with AGC to the second-line treatment in an umbrella design were feasible for effective early screening of novel agents.

Second-line chemoimmunotherapy with nivolumab and paclitaxel in immune-related biomarker-enriched advanced gastric cancer: a multicenter phase Ib/II study.

BACKGROUND: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC). METHODS: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m2 or dose level 2, 80 mg/m2) on Days 1, 8, 15 every four weeks. In phase II, patients with Epstein-Barr virus-related, deficient mismatch repair or programmed cell death-ligand-1-positive AGC were enrolled. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and progression-free survival (PFS, phase II). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and exploratory biomarker analysis. RESULTS: Dose level 2 was selected as RP2D. In phase II, 48 patients were enrolled. The median PFS and OS were 3.9 and 11.2 months, respectively. The ORR was 23.3%, and the median response duration was 16.7 months. Grade 3 or higher treatment-related adverse events, mainly neutropenia, occurred in 20 patients (41.7%). Targeted sequencing revealed that patients with RTK/RAS pathway alterations or the HLA-A02 supertype had better survival. Patients with elevated baseline interleukin-1 receptor antagonist levels had worse survival. CONCLUSIONS: Although the study did not meet its primary end point, nivolumab and paclitaxel for AGC demonstrated a durable response with manageable toxicity profiles. Genomic analysis or plasma cytokine analysis may provide information for the selection of patients who would benefit more from immunotherapy combined with chemotherapy.

Impact of frailty on mortality and healthcare costs and utilization among older adults in South Korea.

Frailty has become increasingly relevant in a rapidly aging society, highlighting the need for its accurate identification and exploring associated clinical outcomes. Using a multidimensional framework to estimate frailty in a sample of community dwelling older adults, its effect on mortality, incurred healthcare costs and utilization were investigated. We obtained data from the 2008-2018 Korean Longitudinal Study of Aging (KLoSA). After excluding individuals aged < 65 years and those with missing data, a total of 3578 participants were included in our study. Cox proportional hazard analysis was conducted to investigate the impact of frailty on all-cause mortality by generating hazard ratios (HRs) and population attributable risks (PARs). Healthcare utilization and out-of-pocket costs incurred by frailty were examined using the Generalized Linear Mixed Model (GLMM). Subgroup analyses were conducted according to frailty components. Among 3578 older adults, 1052 individuals died during a 10-year follow up period. Compared to the low risk frailty group, the moderate risk group (HR: 1.52, 95% CI:1.37-1.69) and severe risk group (HR: 3.10, 95% CI: 2.55-3.77) had higher risks for all-cause mortality. 27.4% (95% CI: 19.0-35.3%) of all-cause mortality was attributable to frailty, and the PARs ranged from 0.5 to 22.6% for individual frailty components. Increasing frailty levels incurred higher total healthcare costs and cost per utilization, including inpatient and outpatient costs. Frailty also increased likelihood of inpatient use, longer length of stay and more frequent outpatient visits. Among the frailty components, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) in particular were linked to elevated mortality, higher incurred healthcare costs and utilization. Frailty-tailored interventions are of utmost relevance to policy makers and primary caregivers as frailty threatens the ability to maintain independent living and increases risk of detrimental outcomes such as mortality and increased utilization and out-of-pocket costs of healthcare in older adults.

Combination therapy with moderate-intensity atorvastatin and ezetimibe versus high-intensity atorvastatin monotherapy in patients treated with percutaneous coronary intervention in practice: assessing RACING generalizability.

AIMS: Using rosuvastatin, the RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial showed the beneficial effects of combining moderate-intensity statin with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease. This study investigated whether the beneficial effects of combination lipid-lowering therapy extend to patients treated with atorvastatin, not rosuvastatin, in daily clinical practice. METHODS AND RESULTS: Using stabilized inverse probability of treatment weighting, a total of 31 993 patients who were prescribed atorvastatin after drug-eluting stent (DES) implantation were identified from a nationwide cohort database: 6 215 patients with atorvastatin 20 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 25 778 patients with atorvastatin 40-80 mg monotherapy. The primary endpoint was the 3-year composite of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or non-fatal stroke in accordance with the RACING trial design. Combination lipid-lowering therapy was associated with a lower incidence of the primary endpoint (12.9% vs. 15.1% in high-intensity atorvastatin monotherapy; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.74-0.88, p < 0.001). Compared with high-intensity atorvastatin monotherapy, combination lipid-lowering therapy was also significantly associated with lower rates of statin discontinuation (10.0% vs. 8.4%, HR 0.81, 95% CI 0.73-0.90, p < 0.001) and new-onset diabetes requiring medication (8.8% vs. 7.0%, HR 0.80, 95% CI 0.70-0.92, p = 0.002). CONCLUSIONS: In clinical practice, a combined lipid-lowering approach utilizing ezetimibe and moderate-intensity atorvastatin was correlated with favorable clinical outcomes, drug compliance, and a reduced incidence of new-onset diabetes requiring medications in patients treated with DES implantation. Trial registration: ClinicalTrial.gov (NCT04715594).

Association between physical activity and health-related quality of life in middle-aged and elderly individuals with musculoskeletal disorders: Findings from a national cross-sectional study in Korea.

PURPOSE: This study aimed to identify the association between physical activity and health-related quality of life (HRQoL) in middle-aged and elderly individuals with musculoskeletal disorders. METHODS: This study used data from the 2016-2020 Korea National Health and Nutrition Examination Survey (KNHANES). We included only those over 40 years of age diagnosed with one or more of the following: osteoarthritis, rheumatism, and osteoporosis. In total, 4,731 participants (783 men and 3,948 women) were included as the study population. Multiple logistic regression analysis was performed to examine the association between physical activity and HRQoL. RESULTS: In the case of middle-aged and elderly individuals with musculoskeletal disorders, the likelihood of HRQoL worsening was significantly lower for those who regularly engaged in physical activity compared with that of those who did not engage in physical activity at all (men: OR 0.58, 95% CI 0.37-0.90; women: OR 0.64, 95% CI 0.53-0.79). Stratified analysis by the type and intensity of physical activity revealed that the possibility of poor HRQoL was lowest when leisure-related moderate-intensity physical activities were performed (men: OR 0.44, 95% CI 0.22-0.89; Women: OR 0.50, 95% CI 0.36-0.69). CONCLUSIONS: Our findings suggest that engaging in regular physical activity contributes to preventing exacerbation of HRQoL, even if the individual suffers from musculoskeletal disorders. It is necessary to provide an appropriate type and intensity of physical activity in consideration of the patients' pain and severity.

Association between having a meal together with family and smoking: a cross-sectional nationwide survey.

BACKGROUND: Smoking is a major risk factor that significantly affects public health. Although the South Korean government spends significant money on smoking cessation services, the smoking rate remains stagnant. Families influence health-conscious decisions, and family meals can positively affect smoking suppression and health behaviors. Therefore, this study investigated whether family meals are correlated with adults' smoking behaviors. METHODS: This study used data from the 2019-2021 Korean National Health and Nutrition Examination Survey. Having a meal together with family was defined as "yes" for those who have at least one meal with their family each day and "no" for those who do not. Current smoking status was classified as having smoked at least 5 packs of cigarettes (100 cigarettes) in one's lifetime and having used either conventional cigarettes or e-cigarettes in the last 30 days. Multiple logistic regression analyses were used to examine the association between eating together, smoking, and weight application. RESULTS: When comparing the group that ate with their family compared to the group that did not, the odds ratio for current smoking status was 1.27 (95% confidence interval [CI]: 1.05-1.54) for male participants and 1.90 (95% CI: 1.33-2.71) for female participants. This showed a dose-dependent effect according to the frequency of family meals. Those who smoked conventional cigarettes had a strong association (men: OR 1.28, 95% CI 1.00-1.67; women: OR 2.22, 95% CI 1.42-3.46). However, those who only vaped e-cigarettes or used both conventional cigarettes and e-cigarettes had no statistically significant correlations. CONCLUSION: This study provides evidence suggesting that eating meals as a family is related to smoking behavior and can positively affect smoking cessation intentions in adults. Consequently, a smoking cessation program can be developed that uses social support, such as encouraging family meals.

Effects of ranitidine and nizatidine on the risk of gastrointestinal cancer.

Purpose: Gastrointestinal (GI) cancer occurs in digestive organs such as the stomach, colon, liver, esophagus, and pancreas. About 83,034 cases occurred in Korea alone in 2020. Dietary factors, alcohol consumption, Helicobacter pylori (H. pylori), and lifestyle factors increase the incidence of diseases such as gastritis, peptic ulcer, pancreatitis, and gastroesophageal reflux disease (GERD), which can develop into GI cancer. However, in 2019, the US Food and Drug Administration announced that the drugs ranitidine and nizatidine, which are used for digestive disorders, contain carcinogens. In this study, we investigated the effects of ranitidine and nizatidine on the development of GI cancer. Materials and methods: In this study, using National Health Insurance Service-National Sample Cohort (NHIS-NSC) version 2.5 (updated from 2002 to 2019), subjects who developed GI cancer were enrolled in the case group, and those who were at risk of, but did not develop, cancer were enrolled in the control group. Thereafter, risk-set matching was performed (1:3 ratio) by sex and age at the time of diagnosis of cancer in the case group. Through this procedure, 22,931 cases and 68,793 controls were identified. The associations of ranitidine and/or nizatidine with GI cancer were confirmed by adjusted odds ratios (aORs) and 95% confidence intervals (CIs) calculated through conditional logistic regression analysis. Results: The aORs of ranitidine and/or nizatidine users were lower than those of nonusers in all average prescription days groups (< 30 days/year: aOR [95% CI] = 0.79 [0.75-0.82]; 30-59 days/year: aOR [95% CI] = 0.66 [0.59-0.73]; 60-89 days/year: aOR [95% CI] = 0.69 [0.59-0.81]; ≥ 90 days/year: aOR [95% CI] = 0.69 [0.59-0.79]). Sensitivity analyses were conducted with different lag periods for the onset of GI cancer after drug administration, and these analyses yielded consistent results. Additional analyses were also performed by dividing subjects into groups based on cancer types and CCI scores, and these analyses produced the same results. Conclusion: Our study, using nationwide retrospective cohort data, did not find evidence suggesting that ranitidine and nizatidine increase the risk of GI cancer. In fact, we observed that the incidence of GI cancer was lower in individuals who used the drugs compared to nonusers. These findings suggest a potential beneficial effect of these drugs on cancer risk, likely attributed to their ability to improve digestive function.

A marginal structural model to estimate the effect of antidepressant medication treatment on major cardiovascular events among people with post-traumatic stress disorder.

BACKGROUND: Previous evidence on antidepressant medication and cardiovascular disease (CVD) among patients with posttraumatic stress disorder (PTSD) has been inconclusive. We estimated the association between antidepressant medication and CVD by applying a marginal structural model. METHODS: We analyzed medical utilization records of 27 170 people with PTSD without prior major cardiovascular events in the Korean National Health Insurance Database (NHID). PTSD and CVD were defined in accordance with the recorded ICD-10 diagnostic codes. We acquired information on antidepressant use from the NHID and categorized them by medication type. A composite major adverse cardiovascular events (MACE) outcome was defined as coronary artery disease with revascularization, ischaemic stroke, and/or haemorrhagic stroke. We used inverse probability of treatment weighting to estimate the parameters of a marginal structural discrete-time survival analysis regression model, comparing the resulting estimates to those derived from traditional time-fixed and time-varying Cox proportional hazards regression. We calculated cumulative daily defined doses to test for a dose-response relationship. RESULTS: People exposed to antidepressants showed a higher hazard of MACE [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.18-1.53]. The estimated effects were strongest for selective serotonin reuptake inhibitors (HR 1.24, 95% CI 1.08-1.44) and TCAs (HR 1.33, 95% CI 1.13-1.56). Exposure to serotonin-norepinephrine reuptake inhibitors did not appear to increase the risk of MACE. People exposed to higher doses of antidepressants showed higher risk of MACE. CONCLUSIONS: In a national cohort of people with PTSD, exposure to antidepressant medications increased the risk of MACE in a dose-response fashion.

Combination Lipid-Lowering Therapy in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: The RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial examined the effects of combination therapy with moderate-intensity statin and ezetimibe in patients with atherosclerotic cardiovascular disease compared with high-intensity statin monotherapy. OBJECTIVES: This observational study was conducted to evaluate the impact of 2 treatment strategies used in the RACING trial in clinical practice. METHODS: After stabilized inverse probability of treatment weighting, a total of 72,050 patients who were prescribed rosuvastatin after drug-eluting stent implantation were identified from a nationwide cohort database: 10,794 patients with rosuvastatin 10 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 61,256 patients with rosuvastatin 20 mg monotherapy. The primary endpoint was the 3-year composite event of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or nonfatal stroke in accordance with the RACING trial. RESULTS: Combination lipid-lowering therapy was associated with a lower occurrence of the primary endpoint (11.6% vs 15.2% for those with high-intensity statin monotherapy; HR: 0.75; 95% CI: 0.70-0.79; P < 0.001). Compared with high-intensity statin monotherapy, combination lipid-lowering therapy was associated with fewer discontinuations of statin (6.5% vs 7.6%; HR: 0.85; 95% CI: 0.78-0.94: P < 0.001) and a lower occurrence of new-onset diabetes requiring medication (7.7% vs 9.6%; HR: 0.80; 95% CI: 0.72-0.88; P < 0.001). CONCLUSIONS: In clinical practice, combination lipid-lowering therapy with ezetimibe and moderate-intensity statin was associated with favorable clinical outcomes and drug compliance in patients treated with drug-eluting stent implantation. (CONNECT DES Registry; NCT04715594).

The impact of assisted reproductive technology treatment coverage on marriage, pregnancy, and childbirth in women of childbearing age: an interrupted time-series analysis.

BACKGROUND: Korea is encountering major challenges related to its declining birth rate and aging population. Various policies have been introduced to prevent further population decrease and boost the birth rate, but their effectiveness has not been verified. Therefore, this study examined the effects of assisted reproductive technology (ART) insurance coverage on marriage, pregnancy, and childbirth in women of childbearing age. METHODS: All information on marriage, pregnancy, childbirth of women of childbearing age was obtained from Statistics Korea and Korean National Health Insurance Service database. During a total follow-up period of 54 months (July 2015 to December 2019), an average of 12,524,214 women of childbearing age per month, and 29,701 live births per month were included in the analysis. An interrupted time series with segmented regression was performed to analyze the time trend and changes in outcomes. RESULTS: The implementation of ART coverage policies had no significant impact on marriage or pregnancy rates. However, it did affect multiple pregnancy and multiple birth rates, which increased by 1.0% (Exp(ß3) = 1.010, P-value = 0.0001) and 1.4% (Exp(ß3) = 1.014, P-value = < 0.0001), respectively, compared to the pre-intervention period. Although the effect of covering ART treatment on total birth rates were not confirmed, a slightly slower decline was observed after the intervention (Exp(ß1) = 0.993, P-value = < 0.0001, Exp(ß1 + ß3) = 0.996 P-value = 0.012). CONCLUSION: This study identified the effects of ART health insurance coverage policy on the rates of multiple pregnancies and births. After the policy implementation, the downward trend in the total birth rate reduced slightly. Our findings suggest that interventions to support infertile couples should be expanded to solve the problem of low fertility rates. To address the intricate problems related to low birth rates, the Korean government introduced a policy that provides financial support and health insurance coverage for assisted reproductive technology (ART) treatment for infertile couples. As a result of evaluating the effectiveness of the ART coverage policy, it led to higher rates of pregnancies and births. In addition, although the total birth rate has been continuously decreasing over time, the decline may have been slowed down slightly by this policy.

Evaluation of Assisted Reproductive Technology Health Insurance Coverage for Multiple Pregnancies and Births in Korea.

Importance: While various policies to support couples experiencing infertility have been introduced due to the fertility rate rapidly dropping in developed countries, few large-scale nationwide cohort studies have evaluated the outcomes of assisted reproductive technology (ART) health insurance coverage policies. Objective: To evaluate ART health insurance coverage for multiple pregnancies and births in Korea. Design, Setting, and Participants: This population-based cohort study used delivery cohort data from the Korean National Health Insurance Service database between July 1, 2015, and December 31, 2019. A total of 1 474 484 women were included after exclusion of those who gave birth at nonmedical institutions and those with missing data. Exposure: Two 27-month periods were examined before and after the Korean National Health Insurance Service had begun covering ART treatment (preintervention period, July 1, 2015, to September 30, 2017; postintervention period, October 1, 2017, to December 31, 2019). Main Outcomes and Measures: Multiple pregnancies and multiple births were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes. Total births were defined as the total number of babies born to each pregnant woman during the follow-up period. An interrupted time series with segmented regression was conducted to analyze the time trend and its change in outcomes. Data analysis was conducted between December 2, 2022, and February 15, 2023. Results: Of the 1 474 484 women eligible for the analysis (mean [SD] age, 33.2 [4.6] years), approximately 1.60% had multiple pregnancies and 1.10% had multiple births. After covering ART treatment, the likelihood of multiple pregnancies and multiple births was estimated to increase by 0.7% (estimate, 1.007; 95% CI, 1.004-1.011; P < .001) and 1.2% (estimate, 1.012; 95% CI, 1.007-1.016; P < .001) compared with before coverage. The probability of an increase in the number of total births per pregnant woman after the intervention was estimated to be 0.5% (estimate, 1.005; 95% CI, 1.005-1.005; P < .001). The relatively high-income class above the median income showed a decreasing trend in multiple births and total births before the intervention, but after the intervention, a significant increase was observed. Conclusions and Relevance: This population-based cohort study found that the possibility of multiple pregnancies and births in Korea significantly increased after the implementation of an ART health insurance coverage policy. These findings suggest that the development and coverage of policies to support couples experiencing infertility may help address low fertility rates.

Effect of regional medical disparities on complications in patients with hypertension: Cox's proportional hazard models.

Objective: Complications associated with hypertension can be alleviated by providing necessary medical services. However, there may be disparities in their provision depending on regional differences. Thus, this study aimed to examine the effects of regional healthcare disparities on complications in patients with hypertension in South Korea. Methods: Data from the National Health Insurance Service National Sample Cohort (2004-2019) were analyzed. The position value for the relative composite index was used to identify medically vulnerable regions. The diagnosis of hypertension within the region was also considered. The risk of complications associated with hypertension included cardiovascular, cerebrovascular, and kidney diseases. Cox proportional hazards models were used for statistical analysis. Results: A total of 246,490 patients were included in this study. Patients who lived in medically vulnerable regions and were diagnosed outside their residential area had a higher risk of complications than those living in non-vulnerable regions and were diagnosed outside the residential area (hazard ratio: 1.156, 95% confidence interval: 1.119-1.195). Conclusion: Patients living in medically vulnerable regions who were diagnosed outside their residential areas were more likely to have hypertension complications regardless of the type of complication. Necessary policies should be implemented to reduce regional healthcare disparities.

Trastuzumab Combined With Ramucirumab and Paclitaxel in Patients With Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric or Gastroesophageal Junction Cancer.

PURPOSE: Trastuzumab-containing chemotherapy is the recommended first-line regimen for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. We evaluated the safety and efficacy of trastuzumab combined with ramucirumab and paclitaxel as second-line treatment for HER2-positive G/GEJ cancer. PATIENTS AND METHODS: Patients with HER2-positive advanced G/GEJ cancer who progressed after first-line treatment with trastuzumab-containing chemotherapy were enrolled from five centers in the Republic of Korea. Patients were administered a 28-day cycle of trastuzumab (once on days 1, 8, 15, and 22: 2 mg/kg followed by 4 mg/kg loading dose), ramucirumab (once on days 1 and 15: 8 mg/kg), and paclitaxel (once on days 1, 8, and 15: dose level 1, 80 mg/m2; or dose level -1, 70 mg/m2). Phase II was conducted with the recommended phase II dose (RP2D). Primary end points were determination of RP2D during phase Ib and investigator-assessed progression-free survival (PFS) in patients treated with RP2D. RESULTS: Dose-limiting toxicity at dose level 1 was not documented during phase Ib, and a full dose combination was selected as the RP2D. Among 50 patients with a median follow-up duration of 27.5 months (95% CI, 17.4 to 37.6), median PFS and overall survival were 7.1 months (95% CI, 4.8 to 9.4) and 13.6 months (95% CI, 9.4 to 17.7), respectively. Objective response rate was 54% (27 of 50, including one complete response), and disease control rate was 96% (48 of 50). Loss of HER2 expression was observed in 34.8% (8 of 23) patients after first-line treatment, and no definite association between HER2 expression and the outcome was revealed. Safety profiles were consistent with previous reports. CONCLUSION: Trastuzumab combined with ramucirumab and paclitaxel showed appreciable efficacy with manageable safety profiles in patients with previously treated HER2-positive G/GEJ cancer.

Longitudinal trajectories of sedation level and clinical outcomes in patients who are mechanically ventilated based on a group-based trajectory model: a prospective, multicentre, longitudinal and observational study in Korea.

OBJECTIVES: Changes in sedation levels over a long time in patients who are mechanically ventilated are unknown. Therefore, we investigated the long-term sedation levels of these patients by classifying them into different longitudinal patterns. DESIGN: This was a multicentre, prospective, longitudinal, and observational study. SETTING: Twenty intensive care units (ICUs) spanning several medical institutions in Korea. PARTICIPANTS: Patients who received mechanical ventilation and sedatives in ICU within 48 hours of admission between April 2020 and July 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary objective of this study was to identify the pattern of sedation practice. Additionally, we analysed the associations of trajectory groups with clinical outcomes as the secondary outcome. RESULTS: Sedation depth was monitored using Richmond Agitation-Sedation Scale (RASS). A group-based trajectory model was used to classify 631 patients into four trajectories based on sedation depth: persistent suboptimal (13.2%, RASS ≤ -3 throughout the first 30 days), delayed lightening (13.9%, RASS ≥ -2 after the first 15 days), early lightening (38.4%, RASS ≥ -2 after the first 7 days) and persistent optimal (34.6%, RASS ≥ -2 during the first 30 days). 'Persistent suboptimal' trajectory was associated with delayed extubation (HR: 0.23, 95% CI: 0.16 to 0.32, p<0.001), longer ICU stay (HR: 0.36, 95% CI: 0.26 to 0.51, p<0.001) and hospital mortality (HR: 13.62, 95% CI: 5.99 to 30.95, p<0.001) compared with 'persistent optimal'. The 'delayed lightening' and 'early lightening' trajectories showed lower extubation probability (HR: 0.30, 95% CI: 0.23 to 0.41, p<0.001; HR: 0.72, 95% CI: 0.59 to 0.87, p<0.001, respectively) and ICU discharge (HR: 0.44, 95% CI: 0.33 to 0.59, p<0.001 and HR: 0.80, 95% CI: 0.65 to 0.97, p=0.024) compared with 'persistently optimal'. CONCLUSIONS: Among the four trajectories, 'persistent suboptimal' trajectory was associated with higher mortality.

The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea.

BACKGROUND: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. METHODS: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation-Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. RESULTS: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death (P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.55-0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% CI, 0.56-0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79-1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65-2.17; P = 0.582). CONCLUSION: In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Air pollution is associated with faster cognitive decline in Alzheimer's disease.

OBJECTIVE: Although chronic exposure to air pollution is associated with an increased risk of dementia in normal elderlies, the effect of chronic exposure to air pollution on the rates of cognitive decline in Alzheimer's disease (AD) has not been elucidated. METHODS: In this longitudinal study, a total of 269 patients with mild cognitive impairment or early dementia due to AD with the evidence of brain ß-amyloid deposition were followed-up for a mean period of 4 years. Five-year normalized hourly cumulative exposure value of each air pollutant, such as carbon monoxide (CO), nitrogen dioxide (NO2 ), sulfur dioxide (SO2 ), and particulate matter (PM2.5 and PM10 ), was computed based on nationwide air pollution database. The effects of chronic exposure to air pollution on longitudinal cognitive decline rate were evaluated using linear mixed models. RESULTS: Higher chronic exposure to SO2 was associated with a faster decline in memory score, whereas chronic exposure to CO, NO2 , and PM10 were not associated with the rate of cognitive decline. Higher chronic exposure to PM2.5 was associated with a faster decline in visuospatial score in apolipoprotein E ε4 carriers. These effects remained significant even after adjusting for potential confounders. INTERPRETATION: Our findings suggest that chronic exposure to SO2 and PM2.5 is associated with faster clinical progression in AD.

Regional Differences in Medical Costs of Chronic Kidney Disease in the South Korean Population: Marginalized Two-Part Model.

BACKGROUND: There are regional gaps in the access to medical services for patients with chronic kidney disease (CKD), and it is necessary to reduce those gaps, including the gaps involving medical costs. OBJECTIVE: This study aimed to analyze regional differences in the medical costs associated with CKD in the South Korean population. METHODS: This longitudinal cohort study included participants randomly sampled from the National Health Insurance Service-National Sample Cohort of South Korea. To select those who were newly diagnosed with CKD, we excluded those who were diagnosed in 2002-2003 and 2018-2019. A total of 5903 patients with CKD were finally included. We used a marginalized two-part longitudinal model to assess total medical costs. RESULTS: Our cohort included 4775 (59.9%) men and 3191 (40.1%) women. Of these, 971 (12.2%) and 6995 (87.8%) lived in medically vulnerable and nonvulnerable regions, respectively. The postdiagnosis costs showed a significant difference between the regions (estimate: -0.0152, 95% confidence limit: -0.0171 to -0.0133). The difference in medical expenses between the vulnerable and nonvulnerable regions showed an increase each year after the diagnosis. CONCLUSIONS: Patients with CKD living in medically vulnerable regions are likely to have higher postdiagnostic medical expenses compared to those living in regions that are not medically vulnerable. Efforts to improve early diagnosis of CKD are needed. Relevant policies should be drafted to decrease the medical costs of patients with CKD disease living in medically deprived areas.