Impact of linkage level on inferences from big data analyses in health and medical research: an empirical study.

BACKGROUND: Linkage errors that occur according to linkage levels can adversely affect the accuracy and reliability of analysis results. This study aimed to identify the differences in results according to personally identifiable information linkage level, sample size, and analysis methods through empirical analysis. METHODS: The difference between the results of linkage in directly identifiable information (DII) and indirectly identifiable information (III) linkage levels was set as III linkage based on name, date of birth, and sex and DII linkage based on resident registration number. The datasets linked at each level were named as databaseIII (DBIII) and databaseDII (DBDII), respectively. Considering the analysis results of the DII-linked dataset as the gold standard, descriptive statistics, group comparison, incidence estimation, treatment effect, and moderation effect analysis results were assessed. RESULTS: The linkage rates for DBDII and DBIII were 71.1% and 99.7%, respectively. Regarding descriptive statistics and group comparison analysis, the difference in effect in most cases was "none" to "very little." With respect to cervical cancer that had a relatively small sample size, analysis of DBIII resulted in an underestimation of the incidence in the control group and an overestimation of the incidence in the treatment group (hazard ratio [HR] = 2.62 [95% confidence interval (CI): 1.63-4.23] in DBIII vs. 1.80 [95% CI: 1.18-2.73] in DBDII). Regarding prostate cancer, there was a conflicting tendency with the treatment effect being over or underestimated according to the surveillance, epidemiology, and end results summary staging (HR = 2.27 [95% CI: 1.91-2.70] in DBIII vs. 1.92 [95% CI: 1.70-2.17] in DBDII for the localized stage; HR = 1.80 [95% CI: 1.37-2.36] in DBIII vs. 2.05 [95% CI: 1.67-2.52] in DBDII for the regional stage). CONCLUSIONS: To prevent distortion of the analyses results in health and medical research, it is important to check that the patient population and sample size by each factor of interest (FOI) are sufficient when different data are linked using DBDII. In cases involving a rare disease or with a small sample size for FOI, there is a high likelihood that a DII linkage is unavoidable.

Association of Androgen Deprivation Therapy with Osteoporotic Fracture in Patients with Prostate Cancer with Low Tumor Burden Using a Retrospective Population-Based Propensity-Score-Matched Cohort.

This study evaluated the effect of androgen deprivation therapy (ADT) on osteoporotic fractures (OF) and its prognostic effect on overall survival in patients with localized or regional prostate cancer (PC) using the Korean National Insurance Dataset. A total of 8883 pairs of 1:1 propensity-score-matched patients with localized or regional PC were retrospectively enrolled between 2007 and 2016. All patients underwent at least 1 year of follow-up to evaluate therapeutic outcomes. Multivariate analysis was performed to determine the prognostic effect of ADT on OF. During a mean follow-up of 47.7 months, 977 (3.43%) patients developed OF, and the incidences of hip, spine, and wrist fractures were significantly different between ADT and non-ADT groups (p < 0.05). The ADT group had a significantly higher incidence of OF (hazard ratio 2.055, 95% confidence interval 1.747-2.417) than the non-ADT group (p < 0.05), and the incidence of spine/hip/wrist OF was significantly higher in the ADT group regardless of the PC stage (p < 0.05). Multivariate analysis failed to show any significant difference in overall survival between the two groups (p > 0.05). ADT resulted in a significantly higher incidence of OF among patients with localized and regional PC, but the overall survival did not differ between ADT and non-ADT groups.

Risk of Fractures in Thyroid Cancer Patients With Postoperative Hypoparathyroidism: A Nationwide Cohort Study in Korea.

Postoperative hypoparathyroidism (PO-hypoPT) is an uncommon complication of total thyroidectomy in thyroid cancer patients. Although long-term hypoPT causes characteristic changes in bone metabolism, the risk of fractures in hypoPT remains inconclusive. We investigated the risk of fractures in Korean thyroid cancer patients with PO-hypoPT. This was a retrospective cohort study using data from the Korea Central Cancer Registry and Korean National Health Insurance Service. We analyzed 115,821 thyroid cancer patients aged ≥18 years, who underwent total thyroidectomy between 2008 and 2016. The risk of any fractures, including vertebral, hip, humerus, and wrist fractures, according to parathyroid function after total thyroidectomy, was analyzed using the multivariable Cox proportional hazard model. The PO-hypoPT and preserved parathyroid function groups included 8789 (7.6%) and 107,032 (92.4%) patients, respectively. Over a mean follow-up duration of 4.8 years, 159 (1.8%) and 2390 (2.2%) fractures occurred in the PO-hypoPT and preserved parathyroid function groups, respectively. The risk of any fractures was significantly lower in the PO-hypoPT group than in the preserved parathyroid function group (hazard ratio [HR] = 0.83; 95% confidence interval [CI] 0.70-0.98; p = 0.037) after adjusting for confounders. Regarding the fracture site, only the risk of vertebral fractures was significantly lower in the PO-hypoPT group compared with the preserved parathyroid function group (HR = 0.67; 95% CI 0.47-0.96; p = 0.028) after adjusting for confounders. Subgroup analyses showed that bone mineral density measurements and calcium supplementation interacted with the relationship between PO-hypoPT and the risk of any fractures (p for interactions = 0.010 and 0.017, respectively). PO-hypoPT was associated with a lower risk of fractures in thyroid cancer patients, especially at the vertebra. The relatively low bone turnover caused by PO-hypoPT and appropriate management for PO-hypoPT with active vitamin D and calcium may prevent the deterioration of skeletal health in thyroid cancer patients who can easily be exposed to long-term overtreatment with levothyroxine. © 2023 American Society for Bone and Mineral Research (ASBMR).

The risk of osteoporotic fracture in gastric cancer survivors: total gastrectomy versus subtotal gastrectomy versus endoscopic treatment.

PURPOSES: Previous studies have suggested that there is an increased risk of osteoporotic fracture in gastric cancer survivors. However, the data was not classified according to surgery type. This study investigated the cumulative incidence osteoporotic fracture (OF) in gastric cancer survivors according to treatment modality. METHODS: A total of 85,124 gastric cancer survivors during 2008-2016 were included. The type of surgery was classified as total gastrectomy (TG, n = 14,428)/subtotal gastrectomy (SG, n = 52,572)/endoscopic mucosal dissection and endoscopic mucosal resection (ESD/EMR, n = 18,125). The site of osteoporotic fractures included the spine, hip, wrist, and humerus. We examined cumulative incidence using Kaplan-Meier survivor analysis and cox proportional hazards regression analysis to determine the risk factor of OF. RESULTS: The incidence of OF per 100,000 patient year was 2.6, 2.1, 1.8 in TG, SG, ESD/EMR group. The cumulative incidence rate was 2.3% at 3 years, 4.0% at 5 years, and 5.8% at 7 years in gastrectomy group, and 1.8% at 3 years, 3.3% at 5 years in the SG group, and 4.9% at 7 years postoperatively in ESD/EMR group. TG increased the risk of OF compared to patients who underwent SG (HR 1.75, 95% confidence interval [CI] 1.57-1.94), and ESD/EMR (hazard ratio [HR] 2.23, 95% CI 2.14-2.32). CONCLUSION: Gastric cancer survivors who underwent TG had an increased osteoporotic fracture risk than did SG or ESD/EMR in these patients. The amount of gastric resection and accompanying metabolic changes seemed to mediate such risk. Additional research is needed to establish an optimal strategy for each type of surgery.

Long-term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort.

BACKGROUND/AIMS: This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. METHODS: The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. RESULTS: The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. CONCLUSION: This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Comparison of the efficiency between electrocardiogram and echocardiogram for left ventricular hypertrophy evaluation in patients with hypertension: Insight from the Korean Hypertension Cohort Study.

In patients with hypertension, left ventricular hypertrophy (LVH) represents a risk factor for cardiovascular disease and asymptomatic organ damage. Currently, electrocardiography (ECG) and two-dimensional echocardiography (Echo) are the most widely used methods for LVH evaluation. This study aimed to compare the long-term outcomes of LVH, as evaluated by ECG and Echo, in patients with hypertension. Patients diagnosed with hypertension as a primary disease between 2006 and 2011 were enrolled in the Korean Hypertension Cohort study. The study finally included 1743 patients who underwent both ECG and Echo. The primary endpoint was defined as the composite of major adverse cardiovascular events (MACEs) or death. Overall, LVH was identified in 747 patients. The patients were categorized into four groups according to the detection of LVH by ECG or Echo: No LVH (n = 996), LVH diagnosed by ECG alone (n = 181), LVH diagnosed by Echo alone (n = 415), LVH diagnosed by both ECG and Echo (n = 151). After adjusting for variables, the incidence of MACEs or death was significantly greater in patients with LVH diagnosed by ECG alone (hazards ratio [HR]: 1.69; 95% confidence interval [CI]: 1.22-2.35; P = .001), LVH diagnosed by Echo alone (HR: 1.54; 95% CI: 1.16-2.05; P = .002), and LVH diagnosed by both ECG and Echo (HR: 1.87; 95% CI: 1.18-2.94; P = .002) than in those with no LVH. Both ECG and Echo are efficient diagnostic tools for LVH and useful for long-term risk stratification. Additional Echo evaluation for LVH is helpful for predicting long-term outcomes only in patients without LVH diagnosis by ECG.

Discrepancy between the Status Quo and Adjusted Risk of First-Onset Suicidal Ideation in Older Adults: A Longitudinal Study Based on the Korean Welfare Panel Study (2011-2021).

Whether older adults can more likely commit suicide than those in other age groups, after adjusting for other possible causes, remains unknown. We aimed to examine why elderly individuals are more likely to develop first-onset suicidal ideation than individuals in other age groups. We identified 2018 young, 3329 middle-aged, and 2714 elderly individuals without a history of suicidal ideation, from the Korean Welfare Panel Study 2011-2021. To determine key stressors that can induce suicidal ideation, selected groups of variables were adjusted progressively in a generalized estimating equation (GEE) model. Incidence rates of the elderly, middle-aged, and young individuals were 15.9, 22.0, and 11.3 per 1000 person-years, respectively. In GEE analysis, a positive association was not noted between age group and suicidal ideation after adjusting for stressor variables. Furthermore, the overly adjusted model (Full model) showed a strong negative association with aging; young [odds ratio (OR): 1.68, 95% confidence interval (CI): 1.35-2.11] and middle-aged (OR: 1.94, 95% CI: 1.38-2.73) individuals were more likely to develop first-onset suicidal ideation than the elderly. We found that full models, particularly assessing wealth rather than income, can explain why the elderly have higher suicide rates than those in other age groups.

The Korean Hypertension Cohort study: design and baseline characteristics.

BACKGROUND/AIMS: Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients. METHODS: The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data. RESULTS: This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively. CONCLUSION: The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.

[Entecavir therapy for patients with hepatitis B virus-related decompensated cirrhosis].

BACKGROUND/AIMS: Entecavie (ETV) has a potent antiviral effect and low rates of resistance in hepatitis B virus (HBV) and is the first-line monotherapy in patients with HBV-related decompensated cirrhosis. We evaluated the efficacy of 12 months treatment with ETV and tried to determine predictive factors of response. METHODS: Forty-five consecutive decompensated cirrhotic patients who received ETV (0.5 mg/day) for more than six months were included. All patients were positive for HBV DNA, and the Child-Turcotte-Pugh (CTP) scores were over 8 point. Seventeen patients were HBeAg-positive. CTP score, model for end-stage liver disease (MELD) score, serum markers of liver function and HBV DNA were assessed every 3 months. RESULTS: ETV treatment for 12 months resulted in improvement of CTP and MELD scores. Pre-treatment mean CTP and MELD score were decreased from 10.1 (±2.0) and 13.48 (±4.05) to 7.24 (±2.0) and 9.68 (±4.85) at 12 months, respectively. The 1-year cumulative rates of HBV DNA negativity and HBeAg loss were 88.9% and 52.9%, respectively, by intention-to-treat analysis. Thirty-two (71.1%) showed improvement in CTP score. Eleven patients did not show change, and 2 patients got worse. The AST/ALT, albumin, bilrubin, prothrombin time were significantly normalized within six months. The good responder group had high level of prothrombin time than the poor responder group (p=0.004). CONCLUSIONS: Our result shows that entecavir can improve liver function in about 70% of patients with HBV related decompensated liver cirrhosis. INR may be a predictive factor of good response with entecavir in these patients.