Tuberculosis and osteoporotic fracture risk: development of individualized fracture risk estimation prediction model using a nationwide cohort study.

Purpose: Tuberculosis (TB) is linked to sustained inflammation even after treatment, and fracture risk is higher in TB survivors than in the general population. However, no individualized fracture risk prediction model exists for TB survivors. We aimed to estimate fracture risk, identify fracture-related factors, and develop an individualized risk prediction model for TB survivors. Methods: TB survivors (n = 44,453) between 2010 and 2017 and 1:1 age- and sex-matched controls were enrolled. One year after TB diagnosis, the participants were followed-up until the date of fracture, death, or end of the study period (December 2018). Cox proportional hazard regression analyses were performed to compare the fracture risk between TB survivors and controls and to identify fracture-related factors among TB survivors. Results: During median 3.4 (interquartile range, 1.6-5.3) follow-up years, the incident fracture rate was significantly higher in TB survivors than in the matched controls (19.3 vs. 14.6 per 1,000 person-years, p < 0.001). Even after adjusting for potential confounders, TB survivors had a higher risk for all fractures (adjusted hazard ratio 1.27 [95% confidence interval 1.20-1.34]), including hip (1.65 [1.39-1.96]) and vertebral (1.35 [1.25-1.46]) fractures, than matched controls. Fracture-related factors included pulmonary TB, female sex, older age, heavy alcohol consumption, reduced exercise, and a higher Charlson Comorbidity Index (p < 0.05). The individualized fracture risk model showed good discrimination (concordance statistic = 0.678). Conclusion: TB survivors have a higher fracture risk than matched controls. An individualized prediction model may help prevent fractures in TB survivors, especially in high-risk groups.

Tuberculosis and the Risk of Ischemic Heart Disease: A Nationwide Cohort Study.

BACKGROUND: Little is known about the risk of ischemic heart disease (IHD) in tuberculosis (TB) survivors. METHODS: We performed a population-based retrospective cohort study using the Korean National Health Insurance Service database. TB survivors (n = 60 602) and their 1:1 age- and sex-matched controls (n = 60 602) were enrolled. Eligible participants were followed up from 1 year after their TB diagnosis to the date of an IHD event, date of death, or the end of the study period (31 December 2018), whichever came first. The risk of IHD was estimated using a Cox proportional hazards regression, and stratified analyses were performed for related factors. Among IHD events, we additionally analyzed for myocardial infarction (MI). RESULTS: During a median of 3.9 years of follow-up, 2.7% of TB survivors (1633/60 602) and 2.0% of the matched controls (1228/60 602) developed IHD, and 0.6% of TB patients (341/60 602) and 0.4% of the matched controls (223/60 602) developed MI. The overall risk of developing IHD and MI was higher in TB patients (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI]: 1.12-1.32 for IHD and aHR 1.48, 95% CI: 1.23-1.78 for MI) than in the matched controls. Stratified analyses showed that TB survivors have an increased risk of IHD and MI regardless of income, place of residence, smoking status, alcohol consumption, physical activity, body mass index, and Charlson comorbidity index. CONCLUSIONS: TB survivors have a higher risk of IHD than matched controls. Strategies are needed to reduce the burden of IHD in TB survivors.

Tuberculosis and Risk of Ischemic Stroke: A Nationwide Cohort Study.

BACKGROUND: Conflicting results exist regarding the risk of ischemic stroke in tuberculosis survivors. We aimed to estimate the risk of ischemic stroke using a nationwide population-based retrospective cohort. METHODS: We gathered data from the Korean National Health Insurance Service on tuberculosis survivors and 1:1 age- and sex-matched non-tuberculosis cases. Eligible participants were followed up from 1 year after tuberculosis diagnosis to the date of ischemic stroke event, date of death, or until the end of the study period (December 31, 2018), whichever came first. Cox proportional hazard regression and stratified analyses were performed to identify any related factors. RESULTS: During follow-up periods of 3.8 years for patients with tuberculosis and matched non-tuberculosis cases, 1.3% of patients with tuberculosis (941/72 863) and 1.0% of matched non-tuberculosis cases (707/72 863) developed ischemic stroke. The overall risk of ischemic stroke was higher in tuberculosis patients (adjusted hazard ratio: 1.22 [95% CI, 1.10-1.36]) compared with the matched non-tuberculosis cases. A stratified analysis showed that patients with tuberculosis had increased risk of ischemic stroke regardless of age, sex, smoking status, alcohol consumption, physical activity, body mass index, and Charlson Comorbidity Index score. CONCLUSIONS: Tuberculosis survivors had a higher risk of ischemic stroke than their matched non-tuberculosis cases. The results of this study suggest that tuberculosis is a crucial infectious factor associated with increased incidence of ischemic stroke.

Association of Change in Alcohol Consumption With Risk of Ischemic Stroke.

BACKGROUND: The effect of serial change in alcohol consumption on stroke risk has been limitedly evaluated. We investigated the association of change in alcohol consumption with risk of stroke. METHODS: This study is a population-based retrospective cohort study from National Health Insurance Service database of all Koreans. Four lakh five hundred thirteen thousand seven hundred forty-six participants aged ≥40 years who underwent 2 subsequent national health examinations in both 2009 and 2011. Alcohol consumption was assessed by average alcohol intake (g/day) based on self-questionnaires and categorized into non-, mild, moderate, and heavy drinking. Change in alcohol consumption was defined by shift of category from baseline. Cox proportional hazards model was used with adjustment for age, sex, smoking status, regular exercise, socioeconomic information, and comorbidities, Charlson Comorbidity Index, systolic blood pressure, and laboratory results. Subgroup analysis among those with the third examination was conducted to reflect further change in alcohol consumption. RESULTS: During 28 424 497 person-years of follow-up, 74 923 ischemic stroke events were identified. Sustained mild drinking was associated with a decreased risk of ischemic stroke (adjusted hazard ratio, 0.88 [95% CI, 0.86-0.90]) compared with sustained nondrinking, whereas sustained heavy drinking was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.06 [95% CI, 1.02-1.10]). Increasing alcohol consumption was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.11 [95% CI, 1.06-1.17] from mild to moderate; adjusted hazard ratio, 1.28 [95% CI, 1.19-1.38] from mild to heavy) compared with sustained mild drinkers. Reduction of alcohol consumption from heavy to mild level was associated with 17% decreased risk of ischemic stroke through 3× of examinations. CONCLUSIONS: Light-to-moderate alcohol consumption is associated with a decreased risk of ischemic stroke, although it might be not causal and could be impacted by sick people abstaining from drinking. Reduction of alcohol consumption from heavy drinking is associated with a decreased risk of ischemic stroke.

Non-Alcoholic Fatty Liver Disease and the Risk of Diabetes Mellitus by Menopausal Status: A Nationwide Cohort Study.

Background: Non-alcoholic fatty liver disease (NAFLD) is regarded as a risk factor for type 2 diabetes mellitus (DM). Menopausal status also influences T2DM risk, where estrogen is presumed to play a protective role by decreasing insulin resistance. As such, we investigated the association between NAFLD and DM risk according to menopausal status. Objectives: We sought to examine the association between NAFLD and DM incidence in pre- and post-menopausal women. Methods: A total of 842,772 pre-menopausal and 1,074,767 post-menopausal women who underwent health examinations between 2009 and 2014 were included from the Korean National Health Insurance Service database. Multivariate Cox proportional hazard analyses were performed to evaluate the association between the risk of DM according to menopausal status and NAFLD, defined by a fatty liver index >60. Results: During the mean follow-up period (7.8 years), DM was diagnosed in 33,461 (4.0%) of pre-menopausal women and 121,102 (9.4%) post-menopausal women. A stronger association between NAFLD and the risk of DM was found in pre-menopausal women (multivariable-adjusted hazard ratio [aHR], 3.60; 95% confidence interval [CI], 3.48−3.71) than in post-menopausal women (aHR, 2.24; 95% CI, 2.21−2.28) (P-interaction < 0.01). Subgroup analyses among women aged 45 to 55 years also showed a stronger association in pre-menopausal (aHR, 3.35; 95% CI, 3.21−3.49) than in post-menopausal women (aHR, 2.83; 95% CI, 2.68−2.98) (P-interaction < 0.01). Conclusions: The association between NAFLD and DM was stronger in pre-menopausal women than in post-menopausal women. This might be due to the protective effect of estrogen, which is possibly in higher production in the peripheral fat tissue of post-menopausal women with NAFLD.

Obesity and Risk of Diabetes Mellitus by Menopausal Status: A Nationwide Cohort Study.

Although both obesity and menopause are associated with increased risk of diabetes mellitus (DM), the association between obesity and DM according to menopausal status remains uncertain. Therefore, we conducted a study to examine the relationship between obesity and incidence of diabetes mellitus (DM) in premenopausal and postmenopausal women. Total of 926,196 premenopausal and 1,193,881 postmenopausal women who underwent health examinations from 2009 to 2014 were identified using the database of the Korean National Health Insurance Service. We compared the incidence and risk of DM according to body mass index (BMI) and waist circumference (WC) in the two groups of women. Cox proportional hazards analyses were performed to evaluate the association between the presence of obesity and risk of DM according to menopausal state. During the 7.8-year follow-up period, 37,736 (4.1%) premenopausal women and 121,102 (10.1%) postmenopausal women were diagnosed with DM. Compared to the reference group (BMI 18.5-23), a stronger association between obesity and risk of DM was observed in both pre- and postmenopausal women: multivariable-adjusted hazard ratios and 95% confidence intervals for BMI subgroups <18.5, 23-25, 25-30, and >30 were 0.62 (0.54, 0.70), 1.91 (1.85, 1.97), 3.38 (3.28, 3.47), and 6.25 (6.02, 6.48), respectively (p trend < 0.001) in premenopausal women and 0.87 (0.82, 0.92), 1.44 (1.41, 1.46), 2.00 (1.97, 2.03), and 2.96 (2.89, 3.02) in postmenopausal women (p trend < 0.001, p-interaction < 0.001). A similar trend was observed for WC. Subgroup analyses of women aged 45 to 55 also showed a stronger association with DM in premenopausal than in postmenopausal women. In conclusion, the association between obesity and DM was stronger in premenopausal women than in postmenopausal women. As estrogens are synthesized in adipose tissue by aromatization of androgens after menopause, increased estrogen levels in obese postmenopausal might have a protective effect against DM.

Sex differences in the association between nonalcoholic fatty liver disease and Parkinson's disease.

BACKGROUND: The association between nonalcoholic fatty liver disease (NAFLD) and Parkinson's disease (PD) remains uncertain. This study sought to assess the sex-specific association between NAFLD and PD risk considering that sex is an important factor in both conditions. METHODS: We included 2,651,169 men and 2,998,904 women (≥40 years of age) who underwent health examinations in 2009 using database of the Korean National Health Insurance Service. To define NAFLD, the Fatty Liver Index (FLI) was used and a score of at least 60 points was regarded as suggesting the presence of NAFLD. Cox proportional hazards analyses were performed to evaluate the association between the presence of NAFLD/each component of FLI and the risk of PD. All analyses were stratified by sex. RESULTS: The median follow-up duration was 7.3 years in both men and women. Of the total study population, 23,233 patients with PD (10,578 men and 12,655 women) were identified. Among men, a decreased risk of PD was observed in those with NAFLD [adjusted hazard ratio (aHR): 0.86, 95% confidence interval (CI): 0.82-0.91]. In contrast, among women, an increased risk of PD was observed in those with NAFLD (aHR: 1.09, 95% CI: 1.02-1.16). This different association according to sex was more prominent among younger participants but was not significant in the old age group. CONCLUSIONS: NAFLD defined by FLI is differently associated with the risk of PD by sex (i.e., low risk of PD in men with NAFLD vs. high risk of PD in women with NAFLD).

The Association between the Use of Dietary Supplement and Psychological Status of Cancer Survivors in Korea: A Cross-Sectional Study.

BACKGROUND: Dietary supplements (DS) use is known to be common among cancer survivors. However, detailed information on the factors influencing DS use seems insufficient, including cancer-related and psychological factors. METHODS: Study subjects were 1,852 Korean adult cancer survivors recruited from cancer survivor clinic of two university-affiliated hospitals. Data were collected retrospectively through review of medical records and self-administered questionnaires. Psychological factors were assessed using Hospital Anxiety and Depression Scale (HADS) and Fear of Cancer Recurrence Inventory-Short Form. Factors associated the DS use were evaluated by multiple logistic regression analysis after adjusting for covariates. RESULTS: The prevalence of long-term DS use was 15.7% in overall (17.5% in female and 11.6% in male). Female survivors were 3.14 times (95% confidence interval [CI], 1.89-5.22) more likely to use DS than male. In male cancer survivors, ever-smoking and previous radiotherapy were positively associated with DS use. In females, breast cancer survivors were 0.32 times less likely to use DS compared with stomach cancer survivors, and survivors with family history of cancer were 1.39 times more likely to use DS than those without. After adjusting for sociodemographic, clinical, and lifestyle factors, survivors with anxiety (HADS ≥8) used DS 1.38 times (95% CI, 1.01-1.91) more frequently, compared with those without anxiety. CONCLUSION: Diverse factors such as female sex, cancer treatment modality, smoking history, family history and anxiety status were associated with DS use in Korean cancer survivors. Targeted strategies with consideration of these factors are needed for counseling DS use for cancer survivors.

Thermal and fast neutron detection through high-purity single-crystal CVD diamonds.

We developed neutron detectors for detecting thermal and fast neutrons. The sensing element of the neutron detector uses a high-purity chemical-vapor-deposited (CVD) diamond plate, with a size of 3 mm × 3 mm × 0.5 mm, and the ø5 mm detector is sealed for use in the reactor as a small tube by using laser micro welding. The electrodes of the fast and thermal neutron detectors are made up of Ag and Gd with approximately 100-nm and 5 µm thicknesses, respectively. The deposition method of the electrode uses the RF plasma sputtering system. The developed neutron detectors were tested on a 30-MeV cyclotron, which generates fast neutrons and gamma rays. High-density polyethylene plates, Cd plates, and Pb bricks were used for the moderator and shielding. The Ag electrode detector measured the current generated by fast neutrons and gamma rays. Although the sensitivity of the Gd electrode detector is smaller than that of the Ag electrode detector, it measured the current generated by thermal neutrons as well as fast neutrons and gamma rays.

Development of array-type prompt gamma measurement system for in vivo range verification in proton therapy.

PURPOSE: In vivo range verification is one of the most important parts of proton therapy to fully utilize its benefits delivering high radiation dose to tumor, while sparing the normal tissue with the so-called Bragg peak. Currently, however, range verification method is not used in clinics. The purpose of the present study is to optimize and evaluate the configuration of an array-type prompt gamma measurement system on determining distal dose edge for in vivo range verification of proton therapy. METHODS: To effectively measure the prompt gammas against the background gammas, the Monte Carlo simulations with the MCNPX code were employed in optimizing the configuration of the measurement system, and the Monte Carlo method was also used to understand the effect of the background gammas, mainly neutron capture gammas, in the measured gamma distribution. To reduce the effect of the background gammas, the optimized energy window of 4-10 MeV in measuring the prompt gammas was employed. A parameterized source was used to maximize computation speed in the optimization study. A simplified test measurement system, using only one detector moving from one measurement location to the next, was constructed and applied to therapeutic proton beams of 80-220 MeV. For accurate determination of the distal dose edge, the sigmoidal curve-fitting method was applied to the measured distributions of the prompt gammas, and then, the location of the half-value between the maximum and minimum value in the curve-fitting was determined as the distal dose edge and compared with the beam range assessed by the proton dose distribution. RESULTS: The parameterized source term employed in optimization process improved the calculation speed by up to ∼300 times. The optimization study indicates that an array-type measurement system with 3, 2, 2, and 150 mm for scintillator thickness, slit width, septal thickness, and slit length, respectively, can effectively measure the prompt gamma distributions minimizing the contribution of background gammas. The present results show that a few hundred counts of prompt gammas can be easily obtained by measuring 10 s at each measurement location for proton beams of ∼4 nA. The distal dose edges determined by the prompt gamma distribution are 5.45, 14.73, and 27.74 cm for proton beams of 5.17 (80 MeV), 14.99 (150 MeV), and 27.38 (220 MeV) cm, respectively. CONCLUSIONS: The results show that the array-type measurement system can measure prompt gamma distributions from a therapeutic proton beam within a short measurement time, and that the distal dose edge can be determined within a few millimeters of error without using any sophisticated analysis.