Fenofibrate to prevent amputation and reduce vascular complications in patients with diabetes: FENO-PREVENT.

BACKGROUND: The potential preventive effect of fenofibrate on lower extremity amputation (LEA) and peripheral arterial disease (PAD) in patients with type 2 diabetes (T2D) is not fully elucidated. METHODS: We selected adult patients ≥ 20 years of age with T2D from the Korean National Health Insurance Service Database (2009-2012). The fenofibrate users were matched in a 1:4 ratio with non-users using propensity scores (PS). The outcome variables were a composite of LEA and PAD and the individual components. The risks of outcomes were implemented as hazard ratio (HR) with 95% confidence intervals (CI). For safety issues, the risks of acute kidney injury, rhabdomyolysis and resulting hospitalization were analyzed. RESULTS: A total of 114,920 patients was included in the analysis with a median follow-up duration of 7.6 years (22,984 and 91,936 patients for the fenofibrate user and non-user groups, respectively). After PS matching, both groups were well balanced. The fenofibrate group was associated with significantly lower risks of composite outcome of LEA and PAD (HR 0.81; 95% CI 0.70-0.94), LEA (HR 0.76; 95% CI 0.60-0.96), and PAD (HR 0.81; 95% CI 0.68-0.96). The risk of acute kidney injury, rhabdomyolysis, or hospitalization for these events showed no significant difference between the two groups. Subgroup analyses revealed consistent benefits across age groups, genders, and baseline lipid profiles. CONCLUSIONS: This nationwide population-based retrospective observational study suggests that fenofibrate can prevent LEA and PAD in patients with T2D who are on statin therapy.

Weight change in patients with new-onset type 2 diabetes mellitus and its association with remission: Comprehensive real-world data.

AIMS: We aimed to investigate weight change in patients with new-onset type 2 diabetes mellitus and the association of weight loss on diabetes remission in Korean adults. MATERIALS AND METHODS: We used the health examination database of the Korean National Health Insurance Service. Patients diagnosed with type 2 diabetes mellitus from 2009 to 2012 were enrolled and followed to 2017. The baseline body weight was measured at the health examination closest to the time the patient was enrolled, and the change was calculated by examining the weight measured at the subsequent examination within 2 years. Remission was defined as fasting blood glucose less than 126 mg/dl at two or more consecutive health examinations after stopping medication. RESULTS: In total, 114, 874 patients with new-onset type 2 diabetes mellitus were analysed. Of these, 23 156 (20.2%) lost more than 5% of their body weight, and 2429 (2.1%) achieved remission. The adjusted odds ratio for remission in the weight loss group was 2.56 (95% confidence interval 2.35-2.79) compared with the group with stable body weight. Sensitivity analysis according to the degree of weight change showed that the greater weight loss, the higher the likelihood of remission. In the subgroup analysis, the effects of weight loss on remission were significantly greater in subgroups of age <65 years, male sex and body mass index >25. CONCLUSION: Weight loss within the first 2 years of treating type 2 diabetes mellitus was associated with diabetes remission. Physicians should pay more attention to weight management in new-onset type 2 diabetes mellitus, particularly for young and obese individuals.

Cardiorenal outcomes and mortality after sodium-glucose cotransporter-2 inhibitor initiation in type 2 diabetes patients with percutaneous coronary intervention history.

AIMS: To evaluate the effects of initiating sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiorenal outcomes and mortality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors as active comparators in patients diagnosed with type 2 diabetes with a history of percutaneous coronary intervention (PCI). MATERIALS AND METHODS: We used an active-comparator, new-user design and nationwide data from the National Health Insurance Service in South Korea from 2014 to 2019. Of the 56 392 patients who underwent PCI, 4610 new SGLT2 inhibitor users were paired 1:1 with DPP-4 inhibitor users for analysis using propensity-score matching. RESULTS: During 13 708.59 person-years of follow-up, the initiation of SGLT2 inhibitors, compared with the initiation of DPP-4 inhibitors, was associated with a significantly lower risk of composite repeat revascularization, myocardial infarction, stroke, heart failure (HF), all-cause death and end-stage renal disease (ESRD). The beneficial effects of SGLT2 inhibitor use were consistent with the components of stroke, HF, all-cause death and ESRD. In the cohort that included health examination data, including anthropometric and metabolic factors, new use of SGLT2 inhibitors was associated with a significantly lower risk of HF (hazard ratio [HR] 0.574, 95% confidence interval [CI] 0.36-0.915), all-cause death (HR 0.731, 95% CI 0.567-0.942), and ESRD (HR 0.076, 95% CI 0.018-0.319). The effects of SGLT2 inhibitor use were consistent regardless of the timing of the previous PCI. CONCLUSIONS: The initiation of SGLT2 inhibitors in patients with type 2 diabetes and a history of PCI was significantly associated with a reduced risk of cardiorenal consequences and mortality, irrespective of time since the last PCI.

Risk of Kidney Failure in Patients With Cancer: A South Korean Population-Based Cohort Study.

RATIONALE & OBJECTIVE: Reduced kidney function is associated with an increased risk of cancer; however, it is unclear if cancer increases the risk of kidney failure with replacement therapy (KFRT). We assessed the risk of KFRT among patients with various types of cancer collectively and with specific types of cancer. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: A total of 2,473,095 participants with (n = 824,365) or without (n = 1,648,730) cancer registered in the Korean National Health Insurance Service database. PREDICTORS: Cancer and cancer subtypes defined using International Classification of Diseases, 10th Revision, Clinical Modification, codes. OUTCOMES: Primary outcome was KFRT defined as the initiation of hemodialysis or peritoneal dialysis or kidney transplantation. ANALYTICAL APPROACH: For each patient with cancer, 2 controls matched for age, sex, estimated glomerular filtration rate, diabetes, and hypertension were included. To address the competing risk of death, a competing risk survival analysis was conducted using the Fine and Gray method. RESULTS: Occurrence of KFRT was higher in patients with cancer than in controls without cancer (incidence rates of 1.07 vs 0.51 cases per 1,000 person-years). Competing risk analysis showed that cancer was significantly associated with an increased risk of KFRT after adjusting for other potential predictors (adjusted hazard ratio, 2.29 [95% CI, 2.20-2.39]). Multiple myeloma, leukemia, lymphoma, and kidney, ovarian, and liver cancer were most significantly associated with an increased KFRT risk, with multiple myeloma conferring the highest risk across age and sex groups. All subgroups of patients with cancer (based on age, sex, smoking, alcohol, exercise, obesity, and comorbid conditions) exhibited a higher risk of KFRT. LIMITATIONS: Causal association between cancer and kidney outcomes could not be confirmed. CONCLUSIONS: Patients with cancer, particularly those with multiple myeloma, exhibited an increased risk of KFRT after accounting for the competing risk of death.

Food allergy in early childhood increases the risk of oral allergy syndrome in schoolchildren: A birth cohort study.

BACKGROUND: The level of pollen in Korea has increased over recent decades. Research suggests that oral allergy syndrome (OAS) may be more frequent in childhood than previously recognized. We aimed to investigate the prevalence and characteristics of OAS in children aged 6-10 years from a general-population-based birth cohort. METHODS: We analyzed 930 children from the cohort for childhood origin of asthma and allergic diseases (COCOA). Allergic diseases were diagnosed annually by pediatric allergists. The skin prick tests were performed with 14 common inhalant allergens and four food allergens for the general population of children aged 3 and 7 years. RESULTS: Of the 930 eligible children, 44 (4.7%) aged 6-10 years were diagnosed with OAS. The mean age at onset was 6.74 years. OAS prevalence was 7.2% among children with allergic rhinitis (AR) and 19.1% among those with pollinosis, depending on comorbidity. OAS was more prevalent in schoolchildren with atopic dermatitis, food allergy, and sensitization to food allergens and grass pollen in early childhood. In schoolchildren with AR, only a history of food allergy until the age of 3 years increased the risk of OAS (aOR 2.971, 95% CI: 1.159-7.615). CONCLUSION: Food allergy and food sensitization in early childhood were associated with OAS in schoolchildren with AR. Further study is required to elucidate the mechanism by which food allergy in early childhood affects the development of OAS.

Editor's Choice - Effect of Physical Activity and Tobacco Use on Mortality and Morbidity in Patients with Peripheral Arterial Disease After Revascularisation: A Korean Nationwide Population Based Cohort Study.

OBJECTIVE: To investigate the effects of physical activity (PA) and tobacco use on adverse clinical outcomes after revascularisation for peripheral arterial disease (PAD) in the Western Pacific region, where PAD cases and tobacco use are among the highest in the world. METHODS: This was a retrospective cohort study using the Korean National Health Insurance Service (NHIS) database and included patients who had received revascularisation for PAD between 2010 and 2015. They were categorised as active or inactive based on the number of days per week they engaged in PA and as current or non-tobacco users (self report). The primary outcome was all cause mortality. Secondary outcomes included major adverse outcome (a composite of all cause mortality, myocardial infarction, and stroke) and major adverse limb event (MALE, a composite of amputation and recurrent revascularisation). RESULTS: The relatively healthy cohort comprised 8 324 patients (mean age 64.7 years; 76.9% male) following revascularisation for PAD. Among them, 32.7% were inactive and 26.4% were tobacco users. Active patients had better outcomes than inactive patients (all cause mortality adjusted hazard ratio [adjHR] 0.766; 95% CI 0.685 - 0.855, major adverse outcome adjHR 0.795; 95% CI 0.719 - 0.878, MALE adjHR 0.858; 95% CI 0.773 - 0.953). Tobacco users had poorer outcomes than non-users (all cause mortality adjHR 1.279; 95% CI 1.124 - 1.456, major adverse outcome adjHR 1.263; 95% CI 1.124 - 1.418, MALE adjHR 1.291; 95% CI 1.143 - 1.458). CONCLUSION: Even after receiving revascularisation for PAD, a sizable proportion of patients were physically inactive and used tobacco, leading to adverse clinical outcomes such as death, cardiovascular morbidity, and amputation in Korea. These modifiable risk factors should be addressed systematically, and a comprehensive approach including supervised exercise programmes and tobacco cessation is needed in patients with PAD.

Analysis of national surveillance of respiratory pathogens for community-acquired pneumonia in children and adolescents.

BACKGROUND: Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP. METHODS: The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020. RESULTS: A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports. CONCLUSIONS: This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.

Timed Up and Go Test and the Risk of Parkinson's Disease: A Nation-wide Retrospective Cohort Study.

BACKGROUND: If mild parkinsonian signs can be a marker for Parkinson's disease (PD) development, an impaired Timed Up and Go test (TUG) should also be a marker for prodromal PD. OBJECTIVES: To investigate whether the Timed Up and Go test is associated with PD. METHODS: We included 1,196,614 participants at 66 years of age who underwent the National Screening Program for Transitional Ages for Koreans between 2009 and 2014. Timed Up and Go test times were classified into <10 and ≥10 seconds. Incidence of PD was defined using claims data. RESULTS: During the median follow-up period of 3.5 years, participants with slow Timed Up and Go test time had significantly increased risk of developing PD compared with those with normal Timed Up and Go test time (adjusted hazard ratio: 1.28; 95% confidence interval: 1.20-1.37). Furthermore, participants with an abnormal Timed Up and Go test result, defined as ≥20 seconds, had a significantly increased risk of PD compared with those with a normal Timed Up and Go test result (adjusted hazard ratio: 2.18; 95% confidence interval: 1.63-2.92). CONCLUSION: An indicator of subtle motor deficits, the Timed Up and Go test could be a prodromal marker for the risk of PD development. © 2020 International Parkinson and Movement Disorder Society.

Annual and seasonal patterns in etiologies of pediatric community-acquired pneumonia due to respiratory viruses and Mycoplasma pneumoniae requiring hospitalization in South Korea.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality. Its disease burden varies by age and etiology and is time dependent. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. METHODS: We conducted a retrospective study in 30,994 children (aged 0-18 years) with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified as macrolide-sensitive MP, macrolide-less effective MP (MLEP), and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. RESULTS: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.4% of the total MP pneumonia. In children < 2 years of age, RSV (34.0%) was the most common cause of CAP, followed by MP (9.4%); however, MP was the most common cause of CAP in children aged 2-18 years of age (45.3%). Systemic corticosteroid was most commonly administered for MP pneumonia. The rate of hospitalization in intensive care units was the highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. CONCLUSIONS: The present study provides fundamental data to establish public health policies to decrease the disease burden due to CAP and improve pediatric health.

Modification of additive effect between vitamins and ETS on childhood asthma risk according to GSTP1 polymorphism: a cross -sectional study.

BACKGROUND: Asthma is characterized by airway inflammation, and bronchial airways are particularly susceptible to oxidant-induced tissue damage. OBJECTIVE: To investigate the effect of dietary antioxidant intake and environmental tobacco smoke (ETS) on the risk of childhood asthma according to genotypes susceptible to airway diseases. METHODS: This cross-sectional study included 1124 elementary school children aged 7-12 years old. Asthma symptoms and smoking history were measured using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Intake of vitamin A (including retinol and ß-carotene), C, and E was measured by a semi-quantitative food frequency questionnaire (FFQ). GSTP1 polymorphisms were genotyped from peripheral blood samples. RESULTS: ETS was significantly associated with presence of asthma symptoms (adjusted odds ratio [aOR], 2.48; 95 % confidence interval [CI], 1.29-4.76) and diagnosis (aOR, 1.91; 95 % CI, 1.19-3.06). Dietary antioxidant intake was not associated with asthma symptoms, although ETS plus low vitamin A intake showed a significant positive association with asthma diagnosis (aOR, 2.23; 95 % CI, 1.10-4.54). Children with AA at nucleotide 1695 in GSTP1 who had been exposed to ETS and a low vitamin A intake have an increased risk of asthma diagnosis (aOR, 4.44; 95 % CI,1.58-12.52) compared with children who had not been exposed to the two risk factors. However, ETS exposure and low vitamin A intake did not significantly increase odds of asthma diagnosis in children with AG or GG genotypes. CONCLUSION: Low vitamin A intake and ETS exposure may increase oxidative stress and thereby risk for childhood asthma. These relationships may be modified by gene susceptibility alleles of GSTP1.

Risk of herpes zoster in children with asthma.

BACKGROUND: There is literature that indicates the association of asthma with an increased risk of common and serious microbial infections. We recently reported an increased risk of vaccine-preventable diseases, e.g., herpes zoster (HZ) among children with asthma, defined by predetermined asthma criteria. Little is known about whether this association is persistent if the asthma status is defined by different asthma criteria, e.g., the Asthma Predictive Index, given the heterogeneity of asthma. OBJECTIVE: To assess the consistency of the association between asthma and the risk of HZ in children. METHODS: This is a population-based case-control study based on all pediatric patients with HZ between 1996 and 2001 in Olmsted County, Minnesota, and 1:1 age- and sex-matched controls without a history of HZ who were enrolled in our previous study. The original Asthma Predictive Index criteria was operationalized by two or more wheezing episodes in a year for the first 3 years of life plus one of the major (physician-diagnosed asthma for a parent or physician-diagnosed eczema for a patient) or two of the minor criteria (physician-diagnosed allergic rhinitis for a patient, wheezing apart from cold, or eosinophilia [≥4%]). Data were fit to traditional logistic regression models to calculate odds ratios and 95% confident intervals. RESULTS: Of the original cohort (n = 554), 95 (17%) did not meet the enrollment criteria for this study, which left 459. Of the 221 patients, 53% were female, with a mean (standard deviation) age of 9.7 ± 4.2 years. The risk of HZ was increased in children with asthma defined by the API controlling for a varicella vaccine history and atopic status (adjusted odds ratio 2.56 [95% confidence interval, 1.08-6.56]). CONCLUSIONS: The association between asthma and increased risk of HZ in children and adolescents is consistent, independent of asthma definitions. Asthma might be an important clinical condition to be considered in HZ vaccine studies.

Increased Risk of Fracture after Traumatic Amputation: A Nationwide Retrospective Cohort Study.

The physiological changes and alterations in gait following amputation may increase the risk of fractures. However, there is insufficient research on fracture risk in amputees. Therefore, this study intended to analyze whether the risk of new fractures increases after traumatic amputations. This population-based, retrospective cohort study used data from the Korean National Health Insurance System database. The study included 19,586 participants who had undergone an amputation and 76,645 matched controls. The incidence of any fracture and site-specific fractures (vertebral, hip, and others) according to amputation site(s) and severity of disability due to amputation were evaluated using Cox proportional hazard regression analysis. During the mean follow-up of 4.2 years, amputees had a higher incidence rate (IR) of any fracture (adjusted HR [aHR] 1.47, 95% CI 1.36-1.60), vertebral fracture (aHR 1.63, 95% CI 1.44-1.85), hip fracture (aHR 1.85, 95% CI 1.39-2.46), and other fracture (aHR 1.34, 95% CI 1.20-1.49) compared to that of controls. In the presence of disability, the risks were further increased and were highest among amputees with severe disabilities. All fracture risks were higher in amputees than they were in controls, regardless of lower limb or upper limb amputation. This cohort study demonstrated that traumatic amputees experienced higher incidence of all fractures than did individuals without amputations, and this risk increases with severity of disability. This finding underscores the importance of early screening and lifestyle interventions to address fracture risk in traumatic amputees.

Ten-year incidence of keratoconus in relation to sex, age, and thyroid gland dysfunction: a nationwide population-based cohort study (2009-2018).

Background: Keratoconus is a corneal ectatic disorder that often leads to visual impairment and may require corneal transplantation. However, its age and gender-based incidence and potential association with thyroid gland dysfunction (TGD) remain poorly understood. This study aims to clarify these aspects and investigate the possible connection between keratoconus and TGD. Methods: We conducted a nationwide population-based cohort study using data from the Korean National Health Insurance Service database. A retrospective chart review was conducted on 4,059,021 patients aged over 20 without underlying corneal diseases in 2009. The end of the review period was at ten years, or until the onset of keratoconus. To evaluate the association with TGD, multivariate Cox regression analysis was used with adjustment of confounding variables such as sex and age. Results: During the review period, 2,334 patients developed keratoconus before the 10-year mark. Females exhibited a higher keratoconus incidence (7.101 per 100,000 person-years) compared to males (5.559) (P<0.001). After adjusting for age, the hazard ratio (HR) for keratoconus was 1.295 times higher [95% confidence interval (CI): 1.193-1.406] in females compared to males. Age groups were stratified in 10-year intervals. The highest incidence of keratoconus was observed in the 20 to 29-year age group (10.695 per 100,000 person-years). All other age groups had significantly lower HR values, with the lowest at 50-59 years (0.508, 95% CI: 0.447-0.577). Keratoconus incidence per 100,000 person-years was 6.227 in subjects without TGD, 6.019 in the hypothyroidism group and 8.287 in the hyperthyroidism group, respectively. Although not statistically significant, individuals with hyperthyroidism showed a higher HR (1.290, 95% CI: 0.939-1.771) for keratoconus when compared to those without TGD, after adjusting for age and sex. Conclusions: This study emphasizes a female predominance in keratoconus incidence and suggests a possible connection between hyperthyroidism and keratoconus. Furthermore, it affirms a higher incidence of keratoconus among young individuals.

Risk of fracture among patients with spinal cord injury: A nationwide cohort study in South Korea.

BACKGROUND: Clinical concerns about preventing and managing fractures after spinal cord injury (SCI) have been growing. OBJECTIVE: This study investigates the risk of fractures among SCI patients according to the presence of disability, disease severity, and level of injury. METHODS: We performed a retrospective cohort study using the Korean National Health Insurance Service (KNHIS 2010-2018) database. We included 5190 SCI patients and 1:3 age- and sex-matched control participants. The primary outcome was fracture, and the cohort was followed until December 31, 2019. RESULTS: SCI patients had a higher fracture risk than the matched controls (adjusted hazard ratio [aHR] 1.33, 95 % CI 1.16-1.54). The risk of fracture was higher in the presence of disability (aHR 1.57, 95 % CI 1.19-2.07), especially among patients with severe disability (aHR 1.65, 95 % CI 1.05-2.60). Higher fracture risks were observed among SCI patients regardless of injury level, but statistical significance was found only with cervical-level injury. When we considered site-specific fractures, vertebral (aHR 1.31, 95 % CI 1.04-1.64) and hip fracture risks (aHR 2.04, 95 % CI 1.39-2.98) were both higher among SCI patients than the controls. SCI patients with disability and cervical-level injury showed the highest hip fracture risk (aHR 3.67, 95 % CI 1.90-7.07). CONCLUSIONS: Compared with the controls, SCI patients were at higher risk of any fracture, particularly hip fracture, especially those with disability and cervical-level injury. Clinicians should be aware of the fracture risk among SCI patients to provide proper management.

Association between age-related macular degeneration and risk of incident cancer.

BACKGROUND/AIMS: Age-related macular degeneration (AMD) and cancer may share similar risk factors, indicating possible common pathogenic pathways. We aimed to describe the site-specific cancer risk based on the relationship of AMD with visual disability (VD) status. METHODS: This was a population-based cohort study using data from the Korean National Health Insurance Service database (2009-2019) including patients who participated in a national health screening programme in 2009. The subjects were categorised based on the presence of AMD and VD. The occurrence of cancer was identified using principal diagnosis according to the International Classification of Disease, 10th revision codes in claims data. The Cox regression hazard model was used to compare HRs of site-specific cancer. RESULTS: Among 4 088 814 participants, 51 596 had AMD of which 3683 subjects had VD. The mean follow-up period was 9.6 years. The overall cancer risk was generally null, but the risk of hypervascular cancer such as thyroid cancer (adjusted HR (aHR) 1.10, 95% CI 1.00 to 1.20) and renal cancer (aHR 1.16, 95% CI 1.00 to 1.33) was higher and the risk of stomach cancer (aHR 0.89, 95% CI 0.84 to 0.94) was lower in the AMD group than in the non-AMD group. CONCLUSION: This study demonstrated a possible association between AMD and several cancers. Increased renal and thyroid cancer risk among patients with AMD could indicate that AMD is associated with hypervascular cancer. Further studies in which additional databases are used and the underlying detailed mechanisms evaluated are needed to validate our results.

Increased Risk of Myocardial Infarction, Heart Failure, and Atrial Fibrillation After Spinal Cord Injury.

BACKGROUND: Heart diseases are a growing concern for the spinal cord injury (SCI) population. OBJECTIVES: This study aims to compare the incidence of heart diseases between SCI survivors and the general non-SCI population. METHODS: We identified 5,083 SCI survivors and 1:3 age- and sex-matched non-SCI controls. Study outcomes were myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). The cohort was followed up from the index date (diagnosis date for SCI or corresponding date for matched controls) until 2019. RESULTS: SCI survivors showed a higher risk for MI (adjusted HR [aHR]: 2.41; 95% CI: 1.93-3.00), HF (aHR: 2.24; 95% CI: 1.95-2.56), and AF (aHR: 1.84; 95% CI: 1.49-2.28) compared to controls. The risks were further increased for those who were registered in the National Disability Registry within 1 year from the index date (SCI survivors with disability): SCI survivors with severe disability had the highest risks of MI (aHR: 3.74; 95% CI: 2.43-5.76), HF (aHR: 3.96; 95% CI: 3.05-5.14), and AF (aHR: 3.32; 95% CI: 2.18-5.05). Cervical and lumbar SCI survivors had an increased risk of heart disease regardless of disability compared to matched controls; these risks were slightly higher in those with disability. Thoracic SCI survivors with disability had significantly increased risk of heart disease compared to matched controls. CONCLUSIONS: SCI survivors at all levels were at significantly greater risk for heart disease than non-SCI controls, particularly those with severe disability. Clinicians must be aware of the importance of heart disease in SCI survivors.

Risk of depression in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea.

Depression is frequently reported in amyotrophic lateral sclerosis (ALS) due to the disastrous prognosis of progressive motor impairment, but the risk of depression in ALS is still unclear. Therefore, we investigated the risk of depression in ALS and analyzed the effect of ALS-related physical disability on the risk of developing depression using the Korean National Health Insurance Service (KNHIS) database. A total of 2241 ALS patients, as defined by the International Classification Diseases (ICD, G12.21) and Rare Intractable Disease codes (V123), and 1:10 sex- and age-matched controls were selected from the KNHIS. After applying exclusion criteria (non-participation in national health screening, history of depression, or having missing data), 595 ALS patients and 9896 non-ALS individuals were finally selected. Primary outcome is newly diagnosed depression during follow-up duration defined by ICD code (F32 or F33). A Cox regression model was used to examine the hazard ratios (HRs) after adjustment for potential confounders. During the follow-up period, 283 cases of depression in the ALS group and 1547 in the controls were recorded. The adjusted HR for depression in ALS was 9.1 (95% confidence interval [CI] 7.87-10.60). The risk of depression was slightly higher in the disabled ALS group (aHR 10.1, 95% CI 7.98-12.67) than in the non-disabled ALS group (aHR 8.78, 95% CI 7.42-10.39). The relative risk of depression was higher in younger patients than in older patients, and in obese patients than in non-obese patients. Our study showed that ALS patients have an increased risk of depression compared to non-ALS individuals.

Differing Efficacy of Dapagliflozin Versus Empagliflozin on the Risk of Incident Atrial Fibrillation in Patients With Type 2 Diabetes: A Real-World Observation Using a Nationwide, Population-Based Cohort.

BACKGROUND: Meta-analyses of large clinical trials investigating SGLT2 (sodium-glucose cotransporter-2) inhibitors have suggested their protective effects against atrial fibrillation in patients with type 2 diabetes. However, the results were predominantly driven from trials involving dapagliflozin. METHODS AND RESULTS: We used a nationwide, population-based cohort of patients with type 2 diabetes who initiated either dapagliflozin or empagliflozin between May 2016 and December 2018. An active-comparator, new-user design was used, and the 2 groups of patients were matched using propensity scores. The primary outcome was incident nonvalvular atrial fibrillation, which was analyzed using both the main intention-to-treat and sensitivity analysis that censored patients who skipped their medications for ≥30 days. Men ≥55 years of age and women ≥60 years of age with ≥1 traditional risk factor or those with established cardiovascular disease were categorized as high cardiovascular risk group. Patients not included in the high-risk group were categorized as low risk. After 1:1 propensity-score matching, a total of 137 928 patients (mean age, 55 years; 58% men) were included and followed up for 2.2±0.6 years. The risk of incident atrial fibrillation was significantly lower in the dapagliflozin group in both the main (hazard ratio [HR], 0.885 [95% CI, 0.789-0.992]) and sensitivity analyses (HR, 0.835 [95% CI, 0.719-0.970]). Notably, this was consistent in both the low and high cardiovascular risk groups. There was no effect modification by age, sex, body mass index, duration of diabetes, or renal function. CONCLUSIONS: This real-world, population-based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

Association between types of antihypertensive medication and the risk of atrial fibrillation: a nationwide population study.

Background: Patients with hypertension are at a high risk of atrial fibrillation (AF). Recent research has indicated the varying effects of antihypertensive medications on developing AF. Objectives: We investigated the relationship between different types of antihypertensive medications and the risk of AF occurrence. Methods: We analyzed data from 113,582 subjects with national health screening examinations between 2009 and 2014. The study population was categorized according to antihypertensive medication type. The primary outcome was the incidence of AF. Results: Among 113,582 subjects (mean age 59.4 ± 12.0 years, 46.7% men), 93,557 received monotherapy [angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), beta-blockers, calcium channel blockers (CCB), or diuretics], while 34,590 received combination therapy (ARB/beta-blockers, ARB/CCB, ARB/diuretics, or ARB/CCB/diuretics). During a mean follow-up duration of 7.6 ± 2.1 years, 3.9% of patients were newly diagnosed with AF. In monotherapy, ACEi and CCB had similar AF risks as ARB, while beta-blockers and diuretics showed higher AF risks than ARB. In combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers had the highest compared to ARB/CCB. Among the specific ARBs, the AF risk varied insignificantly, except for telmisartan and candesartan. Conclusions: In hypertensive patients receiving monotherapy, ACEi and CCB showed a similar AF risk as ARBs, while beta-blockers and diuretics were associated with a higher risk. Among those receiving combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers showed the highest risk. Various types of ARBs have different associations with AF risk.

Machine Learning-Based Discrimination of Cardiovascular Outcomes in Patients With Hypertrophic Cardiomyopathy.

Background: Current risk stratification strategies for patients with hypertrophic cardiomyopathy (HCM) are limited to traditional methodologies. Objectives: The authors aimed to establish machine learning (ML)-based models to discriminate major cardiovascular events in patients with HCM. Methods: We enrolled consecutive HCM patients from 2 tertiary referral centers and used 25 clinical and echocardiographic features to discriminate major adverse cardiovascular events (MACE), including all-cause death, admission for heart failure (HF-adm), and stroke. The best model was selected for each outcome using the area under the receiver operating characteristic curve (AUROC) with 20-fold cross-validation. After testing in the external validation cohort, the relative importance of features in discriminating each outcome was determined using the SHapley Additive exPlanations (SHAP) method. Results: In total, 2,111 patients with HCM (age 61.4 ± 13.6 years; 67.6% men) were analyzed. During the median 4.0 years of follow-up, MACE occurred in 341 patients (16.2%). Among the 4 ML models, the logistic regression model achieved the best AUROC of 0.800 (95% CI: 0.760-0.841) for MACE, 0.789 (95% CI: 0.736-0.841) for all-cause death, 0.798 (95% CI: 0.736-0.860) for HF-adm, and 0.807 (95% CI: 0.754-0.859) for stroke. The discriminant ability of the logistic regression model remained excellent when applied to the external validation cohort for MACE (AUROC = 0.768), all-cause death (AUROC = 0.750), and HF-adm (AUROC = 0.806). The SHAP analysis identified left atrial diameter and hypertension as important variables for all outcomes of interest. Conclusions: The proposed ML models incorporating various phenotypes from patients with HCM accurately discriminated adverse cardiovascular events and provided variables with high importance for each outcome.