Secondary Cancer after Androgen Deprivation Therapy in Prostate Cancer: A Nationwide Study.

PURPOSE: Androgen signaling is associated with various secondary cancer, which could be promising for potential treatment using androgen deprivation therapy (ADT). This study investigated whether ADT use was associated with secondary cancers other than prostate cancer in a nationwide population-based cohort. MATERIALS AND METHODS: A total, 278,434 men with newly diagnosed prostate cancer between January 1, 2002 and December 31, 2017 were identified. After applying the exclusion criteria, 170,416 men were enrolled. The study cohort was divided into ADT and non-ADT groups by individual matching followed by propensity score matching (PSM). Study outcomes were incidence of all male cancers. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of events. RESULTS: During a median follow-up of 4.5 years, a total of 11,059 deaths (6,329 in the ADT group and 4,730 in the non-ADT group) after PSM were found. After PSM, the overall all-cause of secondary cancer incidence risk of the ADT group was higher than that of the non-ADT group (HR: 1.312, 95% CI: 1.23-1.36; adjusted HR: 1.344, 95% CI: 1.29-1.40). The ADT group showed higher risk of overall brain and other central nervous system (CNS) cancer-specific incidence than the non-ADT group (adjusted HR: 1.648, 95% CI: 1.21-2.24). The ADT group showed lower risks of overall cancer-specific incidence for stomach, colon/rectum, liver/inflammatory bowel disease (IBD), gall bladder/extrahepatic bile duct, lung, bladder, and kidney cancers than the non-ADT group. When the duration of ADT was more than 2 years of ADT, the ADT group showed higher risk of cancer-specific incidence for brain and other CNS cancers but lower risk of cancer-specific incidence for liver/IBD and lung cancers than the non-ADT group. CONCLUSIONS: This study demonstrates that ADT could affect cancer-specific incidence for various cancers.

Vaccination and the risk of post-acute sequelae after COVID-19 in the Omicron-predominant period.

OBJECTIVES: To assess the association of primary and third doses of vaccination with the risk of post-acute sequelae of COVID-19. METHODS: This retrospective cohort study utilized a combined database of nationwide health care claims data, COVID-19 patient registry, and vaccination records from South Korea. Individuals diagnosed with COVID-19 in the Omicron variant-dominant period of January-March 2022 were tracked for 30-120 days post-infection. The exposure of interest was the receipt of primary and third doses of the SARS-CoV-2 vaccine. The occurrence of 26 specific conditions in eight domains was compared using Cox regression with inverse probability of treatment weighting. RESULTS: This study included 394 773 unvaccinated individuals and 7 604 081 individuals receiving ≥2 doses of vaccine. Compared with unvaccinated individuals, vaccination with at least two doses was associated with a reduced risk (adjusted hazard ratio; 95% CI) of several conditions, including ischaemic heart disease (0.73; 0.57-0.94), heart failure (0.55; 0.48-0.63), cardiac dysrhythmia (0.72; 0.61-0.85), cardiac arrest (0.41; 0.33-0.51), pulmonary embolism (0.66; 0.52-0.84), venous thromboembolism (0.54; 0.44-0.66), acute renal failure (0.56; 0.46-0.67), new dialysis (0.45; 0.34-0.59), chronic obstructive pulmonary disease (0.74; 0.65-0.84), acute pancreatitis (0.64; 0.51-0.80), and diabetes (0.82; 0.71-0.95). The risks of heart failure, cardiac dysrhythmias, cardiac arrest, pulmonary embolism, and new dialysis were lower in those who were vaccinated with three doses compared with those who were vaccinated with two doses. DISCUSSION: Vaccination was associated with a decreased risk of post-acute sequelae of COVID-19, suggesting its potential role in mitigating the indirect impacts of COVID-19.

Outcomes of prostate cancer patients after robot-assisted radical prostatectomy compared with open radical prostatectomy in Korea.

Limited evidence exists regarding the value of robot-assisted radical prostatectomy (RARP) in promoting health outcomes in patients with prostate cancer (PCa) in Korea, prompting a study to determine its clinical impact. The study included 15,501 patients with PCa who underwent RARP (n = 12,268) or radical prostatectomy (RP) (n = 3,233) between 2009 and 2017. The outcomes were compared using a Cox proportional hazards model after propensity score matching. Hazard ratios of all-cause overall mortality after RARP compared to that after RP within 3 and 12 months were (6.72, 2.00-22.63, p = 0.002) and (5.55, 3.31-9.31, p < 0.0001), respectively. The RARP group in four hospitals with the largest PCa surgery volume during the study period had worse percentile deaths than the total RARP patients within 3- (1.6% vs. 0.63%) and 12-month post-op (6.76% vs. 2.92%). The RARP group showed specific surgical complications, like pneumonia and renal failure, more than the RP group. A significantly higher short-term mortality and only modestly lower surgical complications occurred in RARP than RP group. RARP performance status may not be superior to that of RP as previously reported and perceived, possibly due to increased robotic surgery in the elderly. More meticulous measures are needed for robotic surgery in the elderly.

Restarting anticoagulant therapy after intracranial hemorrhage in patients with atrial fibrillation: A nationwide retrospective cohort study.

Background: Resuming anticoagulation after an intracranial hemorrhage (ICH) poses a clinical conundrum. The absence of relevant guidelines has led to wide variations in the decision on resuming anticoagulation therapies after ICH. This study aimed to evaluate the risks of an anticoagulation therapy on severe thrombotic events (STE) and severe hemorrhage events (SHE) in Korea and compare the effects of novel direct oral anticoagulants (NOACs) and warfarin in patients with AF. Methods: This study was performed using the Korean national health insurance claims data obtained between 2002 and 2017 from individuals who had recently survived an ICH with comorbid AF. The endpoints of this study were STE and SHE. Anticoagulants, antiplatelet agents, and non-antithrombotic users were analyzed for survival with propensity score matching. Results: Among the 4,964 participants analyzed, 878 (17.7%) and 2,070 (41.7%) used anticoagulant and antiplatelet agents, respectively. Anticoagulant (hazard ratio [HR] for STE: 0.385, P < 0.0001; HR for SHE: 0.578, P < 0.0001) or antiplatelet users (HR for STE: 0.545, P < 0.0001; HR for SHE: 0.637, P < 0.0001) had a lower risk of STE and SHE than non-antithrombotic users. Anticoagulation 6-8 weeks post-ICH showed a tendency of the lowest risk of all-cause mortality (HR: 0.614, P = 0.0552). However, there was no difference in the risk between the anticoagulant and antiplatelet users. Further, NOACs were associated with a lower risk of STEs than warfarin (HR, 0.263; P < 0.0001). Conclusions: Our results showed that in patients with AF, resuming anticoagulants and antiplatelets after ICH improved the STEs and SHEs. Further, NOAC had additional benefits as compared to warfarin.

Severe Retinopathy of Prematurity Associated With Neurodevelopmental Disorder in Children.

OBJECTIVE: This study aimed to investigate whether severe retinopathy of prematurity (ROP) could be an association factor for neurodevelopmental disorders in premature infants without other risk factors-such as congenital anomalies, birth injuries, and neurological diseases-that may cause developmental delay. METHODS: We used health claims data recorded between 2007 and 2018 in the Korean National Health Insurance Service (KNHIS) database. We recruited a total of 18,256 premature infant born between 2007 and 2008 without congenital anomaly or birth injury (with ROP 6,995, without ROP 11,261) and divided them into four groups as follows: Group A, 209 extremely premature infants [gestational age (GA) < 28] with mild ROP; Group B, 75 extremely premature infants (GA < 28) with severe ROP; Group C, 6,510 other premature infants (28 ≤ GA <37)with mild ROP; and Group D, 201 other premature infants (28 ≤ GA < 37) with severe ROP. Using regression analysis, we analyzed whether there was a correlation between ROP prevalence, severity, and developmental delay in premature infants without other risk factors. RESULTS: The prevalence of developmental delay, according to GA and ROP severity, was higher in patients with severe ROP than in the other patients. The prevalence gradually decreased after birth. Among extremely premature infants with ROP, those with severe ROP had a 3.082-fold higher association with neurodevelopmental complications than those with mild ROP (p < 0.001). Compared with other premature infants with ROP, those with severe ROP had a 3.269-fold higher association with neurodevelopmental complications than those with mild ROP. CONCLUSION: The severity of ROP may be associated with neurodevelopmental disorders in premature infants.

Ophthalmic complications in retinopathy of prematurity in the first decade of life in Korea using the national health insurance database.

The aim of this study is to investigate the epidemiology of ophthalmic complications of retinopathy of prematurity (ROP) after preterm birth using population-based database in South Korea. Using the National Health Insurance database, ophthalmic complications among premature infants born in 2007-2008 during their 10-year follow-up period were identified. Annual cumulative incidence rate and period prevalence of complications at each age were analyzed among those with ROP and those who underwent treatment for ROP (tROP). The hazard ratios (HRs) according to the presence of ROP and treatment for ROP were also analyzed. We identified 18,256 premature infants, 6995 of whom had ROP. The prevalence at 10th year for overall ophthalmic complications was 11.1% and 35.9% among ROP and tROP, respectively. Strabismus, amblyopia, and glaucoma were the three most common complications. The presence of ROP was associated with higher risk of complications (HR 1.53, 95%CI 1.44-1.61) among premature infants, and the presence of treatment for ROP was associated with higher risk of complications (HR 4.31, 95%CI 3.74-4.98) among ROP cases. This study reports the nationwide epidemiologic data on ophthalmic complications of ROP during the first decade of life, which will help advance our understandings and establish national strategies in managing ROP.

Mortality is not associated with paclitaxel-coated devices usage in peripheral arterial disease of lower extremities.

A recent meta-analysis addressed increased risk of death following revascularization with paclitaxel-coated devices in femopopliteal artery. We evaluated differences in all-cause mortality and amputation free survival between peripheral arterial disease (PAD) patients who were treated with paclitaxel-coated devices and non-paclitaxel-coated devices. This was retrospective population-based cohort study from the National Health Insurance Service claims in South Korea from 2015 to 2019. Multivariate Cox regression analyses after propensity score matching were applied to identify all-cause mortality and amputation-free survival. After propensity score matching, there were 6090 patients per group. The median follow-up days was 580 days (interquartile range [IQR] 240-991 days) and 433 days (IQR 175-757 days) for the non-paclitaxel-coated device group and paclitaxel-coated device group, respectively. Multivariate analysis adjusted for age, sex, diabetes, hypertension, warfarin, and new oral anticoagulants showed that the mortality rate associated with paclitaxel-coated devices was not significantly higher than non-paclitaxel-coated devices (hazard ratio [HR] 0.992; 95% CI 0.91-1.08). The rate of amputation events was higher in patients with paclitaxel-coated devices than those with non-paclitaxel-coated devices (HR 1.614; 95% CI 1.46-1.78). In this analysis, the mortality rate in patients with PAD was not associated with the use of paclitaxel-coated devices, despite a higher amputation rate.

Radiotherapy for brain metastasis and long-term survival.

Patients with brain metastases (BM) can benefit from radiotherapy (RT), although the long-term benefits of RT remain unclear. We searched a Korean national health insurance claims database and identified 135,740 patients with newly diagnosed BM during 2002-2017. Propensity score matching (PSM) was used to evaluate survival according to RT modality, which included whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS). The 84,986 eligible patients were followed for a median interval of 6.6 months, and 37,046 patients underwent RT (43.6%). After the PSM, patients who underwent RT had significantly better overall survival after 1 year (42.4% vs. 35.3%, P < 0.001), although there was no significant difference at 2.6 years, and patients who did not undergo RT had better survival after 5 years. Among patients with BM from lung cancer, RT was also associated with a survival difference after 1 year (57.3% vs. 32.8%, P < 0.001) and a median survival increase of 3.7 months. The 1-year overall survival rate was significantly better for SRS than for WBRT (46.4% vs. 38.8%, P < 0.001). Among Korean patients with BM, especially patients with primary lung cancer, RT improved the short-term survival rate, and SRS appears to be more useful than WBRT in this setting.

Nationwide incidence and treatment pattern of retinopathy of prematurity in South Korea using the 2007-2018 national health insurance claims data.

The aim of this study is to investigate the nationwide incidence and treatment pattern of retinopathy of prematurity (ROP) in South Korea. Using the population-based National Health Insurance database (2007-2018), the nationwide incidence of ROP among premature infants with a gestational age (GA) < 37 weeks (GA < 28 weeks, GA28; 28 weeks ≤ GA < 37 weeks; GA28-37) and the percentage of ROP infants who underwent treatment [surgery (vitrectomy, encircling/buckling); retinal ablation (laser photocoagulation, cryotherapy)] were evaluated. We identified 141,964 premature infants, 42,300 of whom had ROP, with a nationwide incidence of 29.8%. The incidence of ROP in GA28 group was 4.3 times higher than in GA28-37 group (63.6% [2240/3522] vs 28.9% [40,060/138,442], p < 0.001). As for the 12-year trends, the incidence of ROP decreased from 39.5% (3308/8366) in 2007 to 23.5% (2943/12,539) in 2018. 3.0% of ROP infants underwent treatment (25.0% in GA28; 1.7% in GA28-37); 0.2% (84/42,300) and 2.9% (1214/42,300) underwent surgery and retinal ablation, respectively. The overall percentage of ROP infants who underwent treatment has decreased from 4.7% in 2007 to 1.8% in 2018. This first Korean nationwide epidemiological study of ROP revealed a decreased incidence of ROP and a decreased percentage of ROP infants undergoing conventional treatment during a 12-year period.

Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea.

OBJECTIVES: Concerns have been expressed that some drugs may increase susceptibility to SARS-CoV-2 infection. In contrast, other drugs have generated interest as potential therapeutic agents. METHODS: All adults aged ≥18 years who were tested for COVID-19 were included. Exposure was defined as a prescription of study drugs which would have been continued until 7 days prior to test for COVID-19 or later. The outcome measures were the diagnosis of COVID-19 and severe COVID-19. Disease risk score matching and multiple logistic regression was used. RESULTS: Matched claims and testing results were available for 219,961 subjects, of whom 7,341 (3.34%) were diagnosed with COVID-19. Patients were matched to 36,705 controls, and the subset of 878 patients of severe COVID-19 also matched with 1,927 mild-to-moderate patients. Angiotensin receptor blockers were not associated with either the diagnosis of COVID-19 (adjusted OR [aOR], 1.02; 95% confidence interval [CI], 0.90-1.15) or severe disease (aOR, 1.11; 95% CI, 0.87-1.42). The use of hydroxychloroquine was not associated with a lower risk for COVID-19 (aOR, 0.94; 95% CI, 0.53-1.66) or severe disease (aOR, 3.51; 95% CI, 0.76-16.22). CONCLUSIONS: In this national claims data-based case-control study, no commonly prescribed medications were associated with risk of COVID-19 infection or COVID-19 severity.

Effect of Underlying Comorbidities on the Infection and Severity of COVID-19 in Korea: a Nationwide Case-Control Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is an emerging threat worldwide. It remains unclear how comorbidities affect the risk of infection and severity of COVID-19. METHODS: This is a nationwide retrospective case-control study of 219,961 individuals, aged 18 years or older, whose medical costs for COVID-19 testing were claimed until May 15, 2020. COVID-19 diagnosis and infection severity were identified from reimbursement data using diagnosis codes and on the basis of respiratory support use, respectively. Odds ratios (ORs) were estimated using multiple logistic regression, after adjusting for age, sex, region, healthcare utilization, and insurance status. RESULTS: The COVID-19 group (7,341 of 219,961) was young and had a high proportion of female. Overall, 13.0% (954 of 7,341) of the cases were severe. The severe COVID-19 group had older patients and a proportion of male ratio than did the non-severe group. Diabetes (odds ratio range [ORR], 1.206-1.254), osteoporosis (ORR, 1.128-1.157), rheumatoid arthritis (ORR, 1.207-1.244), substance use (ORR, 1.321-1.381), and schizophrenia (ORR, 1.614-1.721) showed significant association with COVID-19. In terms of severity, diabetes (OR, 1.247; 95% confidential interval, 1.009-1.543), hypertension (ORR, 1.245-1.317), chronic lower respiratory disease (ORR, 1.216-1.233), chronic renal failure, and end-stage renal disease (ORR, 2.052-2.178) were associated with severe COVID-19. CONCLUSION: We identified several comorbidities associated with COVID-19. Health care workers should be more careful while diagnosing and treating COVID-19 when patients have the abovementioned comorbidities.

Statins and All-Cause Mortality in Patients Undergoing Hemodialysis.

Background Recommendations have not yet been established for statin therapy in patients on maintenance dialysis. In this study, we aimed to evaluate the effects of statin therapy on all-cause mortality in patients undergoing maintenance hemodialysis. Methods and Results This retrospective cohort study analyzed data from adults, aged ≥30 years, who were on maintenance hemodialysis for end-stage renal disease. Data on statin use, along with other clinical information between 2007 and 2017, were extracted from the Health Insurance Review and Assessment Service database in Korea. In total, 65 404 patients were included, and 41 549 (73.2%) patients had received statin therapy for a mean duration of 3.6±2.6 years. Compared with statin nonusers before and after the initiation of hemodialysis (entry), patients who initiated statin therapy after entry and patients who continued statins from the pre-end-stage renal disease to post-end-stage renal disease period had a lower risk of all-cause mortality; the adjusted hazard ratios (95% CIs) were 0.48 (0.47-0.50; P<0.001) for post-end-stage renal disease only statin users and 0.59 (0.57-0.60; P<0.001) for continuous statin users. However, those discontinuing statins before or at entry showed a higher risk of all-cause mortality. Statin-ezetimibe combinations were associated with better survival benefits than fixed patterns of statin therapy. These results were consistent across various subgroups, including elderly patients aged >75 years, and were maintained even after propensity score matching. Conclusions Our results showed that in adult patients undergoing maintenance hemodialysis, statin therapy, preferably combined with ezetimibe, was associated with a lower risk of all-cause mortality.

Redefining the role of etoposide in first-line treatment of peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCLs) have an aggressive biological course and poor clinical outcomes. Despite producing somewhat less-than-satisfactory results, the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remains the de facto standard in PTCL treatment. Addition of etoposide to CHOP backbone to overcome such unsatisfactory results has yielded contradictory information. We aimed to thoroughly analyze the impact of incorporating etoposide into first-line treatment. Using merged data from the Korean National Health Insurance Service and National Cancer Registry, a total of 1933 patients (median age, 58 years) were evaluated for clinical characteristics and treatment outcomes. Thirty-eight percent (n = 748) of the 1933 patients received CHOP or CHOP-like regimen, 35.1% (n = 678) received CHOP-like regimen plus etoposide, 5.9% (n = 113) received other backbone chemotherapy plus etoposide, and 20.3% (394) received other treatments in the first-line setting. When we divided the patients into 3 groups according to regimen (group 1, CHOP or CHOP-like regimen; group 2, CHOP or CHOP-like regimen plus etoposide; group 3, all others), group 1 was associated with longest progression-free survival (PFS; P < .001) and overall survival (OS; P < .001). This lack of benefit with etoposide addition was observed across different PTCL subtypes and age groups. Adding etoposide led to longer hospitalizations and cytopenias requiring more transfusion. Upfront hematopoietic stem-cell transplantation led to better OS. Addition of etoposide to CHOP-like regimens does not result in better PFS or OS for patients with PTCL. Overall, Asian patients with PTCL do not benefit from chemotherapy intensification of first-line treatment. We hereby provide crucial information on establishing standardized PTCL treatment.