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.

Association of Fibrate use with clinical expression of hypertrophic cardiomyopathy.

AIMS: An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM. METHODS: We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate-user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate-naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years. RESULTS: During a median follow-up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630-0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553-0.934) and 0.655 (0.492-0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591-0.929) and 0.750 (0.609-0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities. CONCLUSION: The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours.

Association between changes in renal function and clinical outcomes in anticoagulated atrial fibrillation patients with marginal renal function. A nationwide observational cohort study.

Background: Renal function is one of the crucial components for determining the dose and type of oral anticoagulants in atrial fibrillation (AF) patients, and is also closely associated with the risks of stroke and bleeding. This study aimed to assess renal function changes and their impact on clinical outcomes in anticoagulated AF patients with marginal renal function. Methods: From a Korean claims database, patients with AF on anticoagulants and a baseline eGFR of 45 to <60 ml/min/1.73 m2 were studied. Patients were grouped by changes in renal function over two years-maintained, improved (eGFR >60 ml/min/1.73 m2), or worsened (eGFR <45 ml/min/1.73 m2)-the study analyzed outcomes including ischemic stroke, major bleeding, end-stage renal disease (ESRD), all-cause death, and a composite of clinical outcomes. Results: A total of 5,126 patients were included in the study: 2,170 (42.3%) in the maintained group, 2,276 (44.4%) in the improved group, and 680 (13.1%) in the group with worsened renal function. The worsened group was older and had more prevalent comorbidities than other groups. After multivariable adjustment, the worsened group was associated with significantly higher risks of major bleeding (adjusted hazard ratio, 95% confidence interval; 1.46, 1.03-2.07, p = 0.035), ESRD (1.49, 1.24-1.80, p < 0.001), all-cause death (9.29, 4.92-17.6, p < 0.001), and the composite outcome (1.57, 1.36-1.83, p < 0.001). Conclusions: In anticoagulated AF patients with marginal renal function, a substantial proportion of patients experienced renal function decline below eGFR 45 ml/min/1.73 m2 within 2 years. Renal function decline was associated with higher risks of major bleeding, ESRD, all-cause death, and the composite outcome compared to those who maintained their baseline renal function.

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.

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.

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.

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.

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.

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.

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.

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.