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1.
Sci Rep ; 14(1): 7189, 2024 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-38531925

RESUMEN

Our study aimed to conduct a comparative evaluation of various noninvasive tests (NITs) for risk stratification in at-risk population for non-alcoholic fatty liver disease (NAFLD), focusing on cardiovascular and liver-related mortality. A total of 21,715 adults aged 40 years and older were enrolled at baseline. The mean follow-up period was 12.39 years. Three types of NITs (fibrosis-4 index [FIB-4], NAFLD fibrosis score [NFS], and steatosis-associated fibrosis estimator [SAFE] score) were used. When using the low cut-off as a 'rule-out' strategy, there were no significant differences in cardiovascular mortality between the 'rule-out' (low-risk) group and the 'rule-in' (intermediate- or high-risk) group based on FIB-4 (aHR = 1.029, P = 0.845) or NFS (aHR = 0.839, P = 0.271) classification. However, the SAFE score exhibited higher sensitivity in predicting cardiovascular mortality compared to FIB-4 or NFS (73.3% in SAFE score vs. 29.6% in FIB-4 or 21.3% in NFS). Only the SAFE score could effectively differentiate the risk between low- and intermediate- or high-risk groups for all types of mortality (all P values for aHR < 0.001). The low cutoff value of the SAFE score discriminated not only liver-related mortality but also identified the cardiovascular high-risk group in the community cohort.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedad del Hígado Graso no Alcohólico , Adulto , Humanos , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Causas de Muerte , Cirrosis Hepática/etiología , Índice de Severidad de la Enfermedad , Biopsia/efectos adversos , Medición de Riesgo , Enfermedades Cardiovasculares/complicaciones , Fibrosis
2.
Liver Int ; 44(4): 944-954, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38291809

RESUMEN

BACKGROUND & AIMS: The cost-effectiveness to screen hepatic fibrosis in at-risk population as recommended by several professional societies has been limited. This study aimed to investigate the cost-effectiveness of this screening strategy in the expanded at-risk population recently proposed by several societies. METHODS: A combined model of the decision tree and Markov models was developed to compare expected costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) between screening and no screening groups. The model included liver disease-related health states and cardiovascular disease (CVD) states as a base-case analysis. Screening strategy consisted of fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE) and intensive lifestyle intervention (ILI) as a treatment for diagnosed patients. RESULTS: Cost-effectiveness analysis showed that screening the at-risk population entailed $298 incremental costs and an additional 0.0199 QALY per patient compared to no screening (ICER $14 949/QALY). Screening was cost-effective based on the implicit ICER threshold of $25 000/QALY in Korea. When the effects of ILI on CVD and extrahepatic malignancy were incorporated into the cost-effectiveness model, the ICER decreased by 0.85 times from the base-case analysis (ICER $12 749/QALY). In contrast, when only the effects of liver disease were considered in the model, excluding cardiovascular disease effects, ICER increased from the baseline case analysis to $16 305. Even when replacing with medical costs in Japan and U.S., it remained cost-effective with the estimate below the countries' ICER threshold. CONCLUSIONS: Our study provides compelling evidence supporting the cost-effectiveness of FIB-4-based screening the at-risk population for advanced hepatic fibrosis.


Asunto(s)
Enfermedades Cardiovasculares , Diagnóstico por Imagen de Elasticidad , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/terapia , Análisis Costo-Beneficio , Análisis de Costo-Efectividad , Cirrosis Hepática/diagnóstico por imagen
3.
J Biomed Sci ; 30(1): 95, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38110948

RESUMEN

BACKGROUND: Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), and its pathogenicity is associated with its ability to evade the host defense system. The secretory form of the chorismate mutase of M. tuberculosis (TBCM, encoded by Rv1885c) is assumed to play a key role in the pathogenesis of TB; however, the mechanism remains unknown. METHODS: A tbcm deletion mutant (B∆tbcm) was generated by targeted gene knockout in BCG to investigate the pathogenic role of TBCM in mice or macrophages. We compared the pathogenesis of B∆tbcm and wild-type BCG in vivo by measuring the bacterial clearance rate and the degree of apoptosis. Promotion of the intrinsic apoptotic pathway was evaluated in infected bone marrow-derived macrophages (BMDMs) by measuring apoptotic cell death, loss of mitochondrial membrane potential and translocation of pore-forming proteins. Immunocytochemistry, western blotting and real-time PCR were also performed to assess the related protein expression levels after infection. Furthermore, these findings were validated by complementation of tbcm in BCG. RESULTS: Deletion of the tbcm gene in BCG leads to reduced pathogenesis in a mouse model, compared to wild type BCG, by promoting apoptotic cell death and bacterial clearance. Based on these findings, we found that intrinsic apoptosis and mitochondrial impairment were promoted in B∆tbcm-infected BMDMs. B∆tbcm down-regulates the expression of Bcl-2, which leads to mitochondrial outer membrane permeabilization (MOMP), culminating in cytochrome c release from mitochondria. Consistent with this, transcriptome profiling also indicated that B∆tbcm infection is more closely related to altered mitochondrial-related gene expression than wild-type BCG infection, suggesting an inhibitory role of TBCM in mitochondrial dysfunction. Moreover, genetic complementation of B∆tbcm (C∆tbcm) restored its capacity to inhibit mitochondria-mediated apoptotic cell death. CONCLUSIONS: Our findings demonstrate the contribution of TBCM to bacterial survival, inhibiting intrinsic apoptotic cell death of macrophages as a virulence factor of M. tuberculosis complex (MTBC) strains, which could be a potential target for the development of TB therapy.


Asunto(s)
Corismato Mutasa , Mycobacterium bovis , Mycobacterium tuberculosis , Tuberculosis , Animales , Ratones , Apoptosis/genética , Corismato Mutasa/metabolismo , Macrófagos/metabolismo , Macrófagos/microbiología , Mitocondrias/genética , Mitocondrias/metabolismo , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculosis/genética , Tuberculosis/microbiología
4.
Hepatol Commun ; 7(10)2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37738414

RESUMEN

BACKGROUND: The fibrosis-4 index (FIB-4) and the NAFLD fibrosis score (NFS) have been used as noninvasive screening methods for advanced fibrosis in patients with NAFLD. However, their diagnostic performance has not been evaluated in at-risk individuals regardless of hepatic steatosis. This study evaluated the performance of the FIB-4 and NFS in at-risk groups of health check-up examinees at mass screening centers. METHODS: This retrospective, cross-sectional study included 8545 participants who underwent voluntary magnetic resonance elastography at a discounted fee during their regular health check-ups at 13 mass screening centers nationwide. The at-risk group was defined as those with any of the following conditions: NAFLD, 2 or more metabolic abnormalities, diabetes mellitus, or abnormal aminotransferase levels. A magnetic resonance elastography cutoff of ≥3.6 kPa was used to define conventional advanced fibrosis. RESULTS: According to the proposed criteria, the proportion of at-risk individuals was 67.4%-80.2% in the health check-up cohort without viral or alcohol-associated liver disease. The prevalence of individuals with advanced hepatic fibrosis in each at-risk group was ~2.3%-2.8% according to various criteria. It was higher in patients without NAFLD than in those with NAFLD. A total of 28.2%-39.6% of those in each at-risk group did not show hepatic steatosis on ultrasonography. The performance of FIB-4 for advanced fibrosis in the at-risk group was comparable with that in the NAFLD group. FIB-4 showed a better area under the receiver operating characteristic curve and sensitivity than NFS in the at-risk group. CONCLUSIONS: FIB-4 demonstrated superior performance compared with the NFS, and its performance in at-risk individuals was similar to that observed for patients with NAFLD.


Asunto(s)
Hepatopatías Alcohólicas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estudios Transversales , Estudios Retrospectivos , Tamizaje Masivo , Cirrosis Hepática/diagnóstico por imagen
5.
JAMA Netw Open ; 6(8): e2329568, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37589973

RESUMEN

IMPORTANCE: The diagnostic performance of the fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for advanced fibrosis in lean patients with NAFLD is limited. OBJECTIVE: To evaluate the diagnostic performance of the FIB-4 and NFS in lean individuals with NAFLD. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study included adults with biopsy-proven NAFLD from 6 referral centers in Asia from 1995 to 2019. Cohorts were matched by age and sex between the lean and nonlean groups. All statistical analyses were executed from October 2022 to March 2023. MAIN OUTCOMES AND MEASURES: The diagnostic performance of the FIB-4 and NFS at the current cutoff for advanced hepatic fibrosis in lean (body mass index [BMI] below 23 [calculated as weight in kilograms divided by height in meters squared]) and nonlean (BMI above 23) patients were evaluated. RESULTS: A total of 1501 patients were included in analysis (mean [SD] age, 46.1 [16.4] years); 788 male (52.5%), 115 lean (7.7%), 472 (30.2%) Korean, 821 (48.7%) Japanese, and 341 (21.3%) Taiwanese. Among the age- and sex-matched cohort, the mean (SD) age was 52.3 (15.1) years and 41.2% (47 of 114) were male. The diagnostic performance and areas under the operating characteristic curve of the FIB-4 (lean, 0.807 vs nonlean, 0.743; P = .28) and NFS (lean, 0.790 vs nonlean, 0.755; P = .54) between the 2 groups were comparable in the age- and sex-matched cohort. The sensitivity and specificity of the NFS showed increasing and decreasing tendency according to the BMI quartiles (P for trend < .001), while those of the FIB-4 did not (P for trend = .05 and P = .20, respectively). Additionally, although the areas under the operating characteristic curve of the FIB-4 and NFS were not significantly different in the lean group (0.807 vs 0.790; P = .09), the sensitivity of the current NFS cutoff values was lower in the lean group than in that of FIB-4 (54.4% vs 81.8%; P = .03). CONCLUSIONS AND RELEVANCE: In this cohort study, the performance of the FIB-4 and NFS in diagnosing advanced fibrosis did not differ significantly between the 2 groups overall. However, in lean NAFLD, while the sensitivity for diagnosing advanced hepatic fibrosis remained reasonable at the current cutoff level, the sensitivity of NFS at the current cutoff was too low to be an adequate screening tool.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Humanos , Adulto , Masculino , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Asia , Pueblo Asiatico , Cirrosis Hepática/diagnóstico
6.
Clin Mol Hepatol ; 29(3): 779-793, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37188331

RESUMEN

BACKGROUND/AIMS: To eliminate hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the World Health Organization (WHO) criteria in 2021, this study investigated the national core indicators representing the current status of viral hepatitis B and C in South Korea. METHODS: We analyzed the incidence, linkage-to-care, treatment, and mortality rates of HBV and HCV infection using the integrated nationwide big data of South Korea. RESULTS: According to data from 2018-2020, the incidence of acute HBV infection in South Korea was 0.71 cases per 100,000 population; tthe linkage-to-care rate was only 39.4%. Among those who need hepatitis B treatment, the treatment rate was 67.3%, which was less than 80% reported in the WHO program index. The annual liver-related mortality due to HBV was 18.85 cases per 100,000 population, exceeding the WHO target of four; the most frequent cause of death was liver cancer (54.1%). The annual incidence of newly diagnosed HCV infection was 11.9 cases per 100,000 population, which was higher than the WHO impact target of five. Among HCV-infected patients, the linkage-to-care rate was 65.5% while the treatment rate was 56.8%, which were below the targets of 90% and 80%, respectively. The liver-related annual mortality rate due to HCV infection was 2.02 cases per 100,000 population. CONCLUSION: Many of the current indicators identified in the Korean population did not satisfy the WHO criteria for validation of viral hepatitis elimination. Hence, a comprehensive national strategy should be urgently developed with continuous monitoring of the targets in South Korea.


Asunto(s)
Hepatitis B , Hepatitis C , Hepatitis Viral Humana , Neoplasias Hepáticas , Humanos , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Hepacivirus , República de Corea/epidemiología , Virus de la Hepatitis B
7.
Orphanet J Rare Dis ; 17(1): 262, 2022 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-35840997

RESUMEN

BACKGROUND: Transthyretin cardiac amyloidosis, also known as transthyretin cardiomyopathy (ATTR-CM) is a poorly-recognized disease with delayed diagnosis and poor prognosis. This nationwide population-based study aimed to identify disease manifestations, economic burden, and mortality of patients with ATTR-CM. METHODS: Data of newly diagnosed patients with ATTR-CM between 2013 and 2018 from the Korean National Health Insurance Service were used, covering the entire population. Patient characteristics included comorbidities, medical procedures, and medication. Healthcare resource utilization and medical costs were observed as measures of the economic burden. The Kaplan-Meier survival curve and years of potential life lost (YPLL) from the general population were estimated for disease burden with ATTR CM. RESULTS: A total of 175 newly diagnosed patients with ATTR-CM were identified. The most common cardiac manifestation was hypertension (51.3%), while the most common non-cardiac manifestation was musculoskeletal disease (68.0%). Mean medical costs at the post-cohort entry date were significantly higher than those at the pre-cohort entry date ($1,864 vs. $400 per patient per month (PPPM), p < 0.001). Of the total medical costs during the study period, the proportion of inpatients cost was 12.9 times higher than the outpatients cost ($1,730 and $134 PPPM, respectively). The median survival time was 3.53 years from the first diagnosis of ATTR-CM, and the mean (SD) YPLL was 13.0 (7.7). CONCLUSIONS: Patients with ATTR-CM had short survival and high medical costs. To reduce the clinical and economic burdens, carefully examining manifestations of disease in patients can help with early diagnosis and treatment.


Asunto(s)
Neuropatías Amiloides Familiares , Cardiomiopatías , Neuropatías Amiloides Familiares/diagnóstico , Cardiomiopatías/diagnóstico , Estrés Financiero , Corazón , Humanos , Prealbúmina
8.
Nutrients ; 14(14)2022 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-35889886

RESUMEN

Sunbanghwalmyung-eum (SBH) is a traditional herbal medicine that exhibits various pharmacological properties, such as antioxidant, anti-inflammatory, and anticancer activities. In this study, we investigated the systemic anti-obesity effects of an aqueous extract of SBH in the liver, adipose, and muscle tissue from high-fat and high-cholesterol diet (HFHCD)-induced obese C57BL/6J mice. After 6 weeks of an HFHCD, the mice were continuously fed HFHC with oral administration of SBH (100 mg/kg/day), Sim (simvastatin, 5 mg/kg/day, positive control), or water (HFHC only) for another 6 weeks. Our results showed that SBH attenuated the HFHCD-induced body weight gain and fat accumulation in the liver, and improved plasma lipid levels, such as those of triglycerides (TGs), blood total cholesterol (TC), and low-density lipoprotein (LDL-c). SBH and Sim inhibited the inflammation accompanied by obesity via decreasing inflammatory cytokine interleukin (IL)-1ß, tumor necrosis factor α (TNFα), and monocyte chemoattractant protein 1 (MCP1). Moreover, SBH downregulated the expression of protein levels of adipogenic-related factors, including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), in the liver, adipose, and muscle tissue. The SBH and Sim treatment also significantly upregulated the phosphorylation of AMP-activated protein kinase α (AMPKα) in the liver and hormone-sensitive lipase (HSL) in the adipose tissue. Overall, the effects of SBH on HFHCD-induced obesity were similar to or more potent than those of simvastatin. These results indicated that SBH has great potential as a therapeutic herbal medicine for obesity.


Asunto(s)
Fármacos Antiobesidad , Hiperlipidemias , Proteínas Quinasas Activadas por AMP/metabolismo , Adipogénesis , Tejido Adiposo/metabolismo , Animales , Fármacos Antiobesidad/uso terapéutico , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Colesterol/metabolismo , Dieta Alta en Grasa , Hiperlipidemias/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/metabolismo , PPAR gamma/metabolismo , Extractos Vegetales/uso terapéutico , Simvastatina/farmacología , Agua/metabolismo
9.
Front Oncol ; 11: 728740, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34926248

RESUMEN

BACKGROUND: Studies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain. METHODS: We constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses. RESULTS: Based on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER. CONCLUSION: We showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice.

10.
Appl Health Econ Health Policy ; 19(3): 439-450, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32789657

RESUMEN

OBJECTIVES: To assess price reductions of anticancer drugs in South Korea over 12 years and analyze the association between price reduction, drug characteristics, and repricing mechanisms. METHODS: We constructed a dataset based on the Health Insurance Review and Assessment Service (HIRA) price log of anticancer drugs from January 2007 to June 2019. We investigated each mechanism that resulted in a price reduction, including actual transaction price (ATP), voluntary reduction by a manufacturer, price-volume agreement, expansion of indication or reimbursement scope, price cut at generic entry, lump price cut in April 2012, and re-evaluation. The price reduction rate per year was estimated by dividing the total number of price reduction events by the total period for which the products were on the market. A Poisson regression model was used to estimate the characteristics-adjusted incidence rate ratio of the price reduction. Price reduction per event was also determined across originator and generic products. Data analysis was performed using R (version 3.5.1). RESULTS: Five hundred price reductions occurred in 439 new anticancer drugs, with a reduction rate per 100 product-years of 23. ATP was the most frequent cause (39.2%) but had minimal impact (average reduction per event of 3%), followed by lump price cut (19.2%) and voluntary reduction (10.2%). Generic entries and lump price cut had the greatest impact (16-29% reduction per event). ATP was the most frequently occurring mechanism, followed by generic entry, voluntary reduction, and the lump price-cut in April 2012. CONCLUSIONS: The incidence of price reduction of anticancer drugs increased gradually due to various repricing mechanisms. Although these mechanisms are effective, improvements can be made. Well-designed mechanisms that actively regulate price adjustment are needed to establish repricing policies that adequately reflect changes in the value of drugs over their entire life cycle.


Asunto(s)
Antineoplásicos , Costos de los Medicamentos , Medicamentos Genéricos , Humanos , Políticas , República de Corea
11.
Gut ; 70(11): 2172-2182, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33239344

RESUMEN

OBJECTIVE: The cost-effectiveness of antiviral treatment in adult immune-tolerant (IT) phase chronic hepatitis B (CHB) patients is uncertain. DESIGN: We designed a Markov model to compare expected costs and quality-adjusted life-years (QALYs) of starting antiviral treatment at IT-phase ('treat-IT') vs delaying the therapy until active hepatitis phase ('untreat-IT') in CHB patients over a 20-year horizon. A cohort of 10 000 non-cirrhotic 35-year-old patients in IT-phase CHB (hepatitis B e antigen-positive, mean serum hepatitis B virus (HBV) DNA levels 7.6 log10 IU/mL, and normal alanine aminotransferase levels) was simulated. Input parameters were obtained from previous studies at Asan Medical Center, Korea. The incremental cost-effectiveness ratio (ICER) between the treat-IT and untreat-IT strategies was calculated. RESULTS: From a healthcare system perspective, the treat-IT strategy with entecavir or tenofovir had an ICER of US$16 516/QALY, with an annual hepatocellular carcinoma (HCC) incidence of 0.73% in the untreat-IT group. With the annual HCC risk ≥0.54%, the treat-IT strategy was cost-effective at a willingness-to-pay threshold of US$20 000/QALY. From a societal perspective considering productivity loss by premature death, the treat-IT strategy was extremely cost-effective, and was dominant (ICER <0) if the HCC risk was ≥0.43%, suggesting that the treat-IT strategy incurs less costs than the untreat-IT strategy. The most influential parameters on cost-effectiveness of the treat-IT strategy were those related with HCC risk (HBV DNA levels, platelet counts and age) and drug cost. CONCLUSION: Starting antiviral therapy in IT phase is cost-effective compared with delaying the treatment until the active hepatitis phase in CHB patients, especially with increasing HCC risk, decreasing drug costs and consideration of productivity loss.


Asunto(s)
Antivirales/economía , Antivirales/uso terapéutico , Análisis Costo-Beneficio , Hepatitis B Crónica/tratamiento farmacológico , Años de Vida Ajustados por Calidad de Vida , Adulto , Femenino , Hepatitis B Crónica/inmunología , Humanos , Pruebas de Función Hepática , Masculino , Cadenas de Markov
12.
Artículo en Inglés | MEDLINE | ID: mdl-33376113

RESUMEN

OBJECTIVE: To explore differences in end-of-life healthcare utilisation and medication costs between patients with haematological malignancies and patients with solid tumours. METHODS: Data on deceased patients with cancer were selected from the sample cohort data of health insurance claims from 2008 to 2015 in South Korea. They were categorised into two groups: patients with haematological malignancies and patients with solid tumours. Longitudinal data comprised the patient-month unit and aggregated healthcare utilisation and medication cost for 1 year before death. Healthcare utilisation included emergency room visits, hospitalisation and blood transfusions. Medication costs were subdivided into anticancer drugs, antibiotics, opioids, sedatives and blood preparation. Generalised linear mixed models were used to evaluate differences between the two groups and time trends. RESULTS: Of the 8719 deceased patients with cancer, 349 died from haematological malignancies. Compared with solid tumours, patients with haematological malignancies were more likely to visit the emergency room (OR=1.36, 95% CI 1.10 to 1.69) and receive blood transfusions (OR=5.44, 95% CI 4.29 to 6.90). The length of hospitalisation of patients was significantly different (difference=2.49 days, 95% CI 1.75 to 3.22). Medication costs, except for anticancer treatment, increased as death approached. The costs of antibiotics and blood preparations were higher in patients with haematological malignancies than in those with solid tumours: 3.24 (95% CI 2.14 to 4.90) and 4.10 (95% CI 2.77 to 6.09) times higher, respectively. CONCLUSIONS: Patients with haematological malignancies are at a higher risk for aggressive care and economic burden at the end of life compared with those with solid tumours. Detailed attention is required when developing care plans for end-of-life care of haematological patients.

13.
Nutr Res Pract ; 14(2): 109-116, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32256985

RESUMEN

BACKGROUND/OBJECTIVES: Excessive intake of simple sugars induces obesity and increases the risk of inflammation. Thus, interest in alternative sweeteners as a sugar substitute is increasing. The purpose of this study was to determine the effect of saccharin on inflammation in 3T3-L1 adipocytes. MATERIALS/METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes. The adipocytes were treated with saccharin (0, 50, 100, and 200 µg/mL) for 24 h. Inflammation was induced by exposure of treated adipocytes to lipopolysaccharide (LPS) for 18 h and cell proliferation was measured. The concentration of nitric oxide (NO) was measured by using Griess reagent. Protein expressions of nuclear factor kappa B (NF-κB) and inhibitor κB (IκB) were determined by western blot analysis. The mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1ß (IL-1ß), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) were determined by real-time PCR. RESULTS: Compared with the control group, the amount of NO and the mRNA expression of iNOS in the LPS-treated group were increased by about 17.6% and 46.9%, respectively, (P < 0.05), and those parameter levels were significantly decreased by saccharin treatment (P < 0.05). Protein expression of NF-κB was decreased and that of IκB was increased by saccharin treatment (P < 0.05). Saccharin decreased the mRNA expression of COX-2 and the inflammation cytokines (IL-1ß, IL-6, MCP-1, and TNF-α) (P < 0.05). CONCLUSIONS: The results of this study suggest that saccharin can inhibit LPS-induced inflammatory responses in 3T3-L1 adipocytes via the NF-κB pathway.

14.
Clin Otolaryngol ; 44(6): 997-1003, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31468673

RESUMEN

OBJECTIVES: The aim of the current study was to investigate the effectiveness and clinical feasibility of Biyeom-go for the treatment of nasal symptoms associated with rhinitis. DESIGN: Prospective observational study. SETTING: This study was conducted at the Woosuk Korean Medicine Medical Center in South Korea. PARTICIPANTS: Fifty-eight patients with rhinitis participated in this study. All patients received Biyeom-go treatment >3 times daily for a total of 4 weeks. MAIN OUTCOME MEASURES: The primary outcome was the total nasal symptom score. Mini-rhinoconjunctivitis quality of life questionnaire, nasal endoscopy index, total serum immunoglobulin E levels and immunologic factors in nasal lavage fluid were also measured. RESULTS: Biyeom-go administration was associated with significant improvements in total nasal symptoms scores (P < .0001) and mini-rhinoconjunctivitis quality of life questionnaire scores (P < .0001) in a time-dependent manner. The nasal endoscopy index also significantly improved at weeks 2 (P = .0049), 3 (P < .0001) and 4 (P = .0001) after Biyeom-go treatment. Significantly, increased interleukin-2 levels (P = .005) and decreased interleukin-8, chemokine (C-C motif) ligand (CCL) 5, chemokine (C-X-C motif) ligand (CXCL) 9, CCL2 and CXCL10 levels were observed in the nasal lavage fluid. CONCLUSIONS: The present findings suggest that Biyeom-go may be beneficial for the management of rhinitis symptoms and rhinitis-associated quality of life. Further well-designed randomised controlled trials are needed to evaluate the effectiveness of Biyeom-go for rhinitis.


Asunto(s)
Antialérgicos/uso terapéutico , Fitoterapia , Extractos Vegetales , Rinitis/complicaciones , Rinitis/terapia , Administración Intranasal , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rociadores Nasales , Pomadas , Estudios Prospectivos , Adulto Joven
15.
Ultrasound Med Biol ; 45(10): 2672-2678, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31262524

RESUMEN

This study evaluated the diagnostic performance of a commercially available computer-aided diagnosis (CAD) system (S-Detect 1 and S-Detect 2 for thyroid) for detecting thyroid cancers. Among 218 thyroid nodules in 106 patients, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the CAD systems were 80.2%, 82.6%, 75.0%, 86.3% and 81.7%, respectively, for the S-Detect 1 and 81.4%, 68.2%, 62.5%, 84.9% and 73.4%, respectively, for the S-Detect 2. The inter-observer agreement between the CAD system and radiologist for the description of calcifications was fair (kappa = 0.336), while the final diagnosis and each ultrasonographic descriptor showed moderate to substantial agreement for the S-Detect 2. To conclude, the current CAD systems had limited specificity in the diagnosis of thyroid cancer. One of the main limitations of the S-Detect 2 was its inaccuracy in recognizing calcifications, which meant that differentiation had to be undertaken by the radiologist.


Asunto(s)
Interpretación de Imagen Asistida por Computador/métodos , Nódulo Tiroideo/diagnóstico por imagen , Ultrasonografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico por Computador , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Glándula Tiroides/diagnóstico por imagen , Adulto Joven
16.
Phytomedicine ; 52: 254-263, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30599906

RESUMEN

BACKGROUND: Platycodi Radix (root of Platycodon grandiflorum) and its active compound platycodin D (PD) has been previously shown to possess anti-obesity properties, but the underlying mechanisms remain poorly understood. PURPOSE: The present study was aimed to evaluate the anti-obese effect of PD and reveal its mechanism of action. STUDY DESIGN/METHODS: Genetically obese db/db mice were orally treated with PD for 4 weeks, and body weight gain, adipose tissue weight, serum parameters were measured. Then, assays on adipogenic factors, thermogenic factors, and AMP-activated protein kinase (AMPK) pathway were performed in PD-treated 3T3-L1 murine adipocytes, human adipose-derived mesenchymal stem cells (hAMSCs), and primary cultured brown adipocytes. RESULTS: PD treatment attenuated body weight gain, suppressed white adipose tissue weight and improved obesity-related serum parameters in db/db mice. Two major adipogenic factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) were decreased by PD treatment in WAT of db/db mice, 3T3-L1 adipocytes and hAMSCs. In BAT of db/db mice and primary cultured brown adipocytes, PD treatment elevated the expressions of uncoupled protein 1 (UCP1) and peroxisome proliferator-activated receptor γ coactivator 1 α (PCG1α), the key regulators of BAT-associated thermogenesis. In addition, PD activated AMPKα both in vivo and in vitro. However, when AMPK was inhibited by compound C, PD treatment failed to suppress adipogenic factors and increase thermogenic factors. CONCLUSIONS: PD improved obesity in db/db mice by AMPK-associated decrease of adipogenic markers including PPARγ and C/EBPα. PD increased thermogenic factors such as UCP1 and PGC1α in db/db mice and primary cultured brown adipocytes. AMPK inhibition nullified the effects of PD, suggesting its anti-adipogenic and thermogenic actions were dependent on AMPK pathway activation.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Adipocitos Marrones/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Obesidad/tratamiento farmacológico , Saponinas/farmacología , Termogénesis/efectos de los fármacos , Triterpenos/farmacología , Células 3T3-L1 , Tejido Adiposo Pardo/citología , Tejido Adiposo Blanco/citología , Animales , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Humanos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Ratones Noqueados , PPAR gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Platycodon/química , Proteína Desacopladora 1/metabolismo
17.
Eur Radiol ; 29(4): 1978-1985, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30350161

RESUMEN

PURPOSE: To evaluate the diagnostic performance and reproducibility of a computer-aided diagnosis (CAD) system for thyroid cancer diagnosis using ultrasonography (US) based on the operator's experience. MATERIALS AND METHODS: Between July 2016 and October 2016, 76 consecutive patients with 100 thyroid nodules (≥ 1.0 cm) were prospectively included. An experienced radiologist performed the US examinations with a real-time CAD system integrated into the US machine, and three operators with different levels of US experience (0-5 years) independently applied the CAD system. We compared the diagnostic performance of the CAD system based on the operators' experience and calculated the interobserver agreement for cancer diagnosis and in terms of each US descriptor. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the CAD system were 88.6, 83.9, 81.3, 90.4, and 86.0%, respectively. The sensitivity and accuracy of the CAD system were not significantly different from those of the radiologist (p > 0.05), while the specificity was higher for the experienced radiologist (p = 0.016). For the less-experienced operators, the sensitivity was 68.8-73.8%, specificity 74.1-88.5%, PPV 68.9-73.3%, NPV 72.7-80.0%, and accuracy 71.0-75.0%. The less-experienced operators showed lower sensitivity and accuracy than those for the experienced radiologist. The interobserver agreement was substantial for the final diagnosis and each US descriptor, and moderate for the margin and composition. CONCLUSIONS: The CAD system may have a potential role in the thyroid cancer diagnosis. However, operator dependency still remains and needs improvement. KEY POINTS: • The sensitivity and accuracy of the CAD system did not differ significantly from those of the experienced radiologist (88.6% vs. 84.1%, p = 0.687; 86.0% vs. 91.0%, p = 0.267) while the specificity was significantly higher for the experienced radiologist (83.9% vs. 96.4%, p = 0.016). • However, the diagnostic performance varied according to the operator's experience (sensitivity 70.5-88.6%, accuracy 72.0-86.0%) and they were lower for the less-experienced operators than for the experienced radiologist. • The interobserver agreement was substantial for the final diagnosis and each US descriptor and moderate for the margin and composition.


Asunto(s)
Nódulo Tiroideo/diagnóstico por imagen , Adolescente , Adulto , Anciano , Sistemas de Computación , Diagnóstico por Computador/normas , Femenino , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Variaciones Dependientes del Observador , Examen Físico/normas , Estudios Prospectivos , Radiólogos/normas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Neoplasias de la Tiroides/diagnóstico por imagen , Ultrasonografía
18.
Hepatology ; 69(4): 1599-1613, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30365164

RESUMEN

Ultrasonography (US) is generally recommended for the surveillance of hepatocellular carcinoma (HCC) in patients at risk. However, in patients with cirrhosis who have sufficiently high HCC incidence, surveillance using magnetic resonance imaging (MRI) with liver-specific contrast showed markedly higher sensitivity in detecting early-stage HCC than US. This study aimed to compare the cost-effectiveness of semiannual surveillance using MRI versus US in patients with compensated cirrhosis and to identify the population that would gain optimal cost-effectiveness through MRI surveillance. We designed a Markov model to compare the expected costs and quality-adjusted life-years (QALYs), between MRI and US, with a 20-year time horizon, from the health care system perspective. The starting age of the cohort was 50 years, and 71% had hepatitis B virus-associated cirrhosis. The cycle length was 6 months. Transition probabilities and costs were obtained mainly from a prospective cohort study (the PRIUS study, NCT01446666). Cost and effectiveness were discounted at 5%. An incremental cost-effectiveness ratio (ICER) was calculated and tested using sensitivity analyses. The cost-effectiveness analysis indicated that the use of MRI incurred $5,562 incremental costs, 0.384 incremental life-years (LYs), and 0.221 incremental QALYs compared to US. The annual HCC incidence was the most influential factor on the ICER. The ICERs were $14,474/LY and $25,202/QALY at an annual HCC incidence of 3%. When the HCC incidence rate was >1.81%, the ICER was below $50,000/QALY. With increased HCC incidence, MRI surveillance was acceptable as a cost-effective option, even with an increased MRI/US cost ratio. Conclusion: Semiannual surveillance using MRI with liver-specific contrast may be more cost-effective than US in patients with virus-associated compensated cirrhosis at sufficiently high HCC risk despite the higher test cost of MRI.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética/economía , Vigilancia de la Población , Adulto , Anciano , Carcinoma Hepatocelular/economía , Carcinoma Hepatocelular/etiología , Femenino , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/economía , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad
19.
Front Pharmacol ; 9: 773, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30061836

RESUMEN

Benign prostate hyperplasia (BPH) is a common disease in elderly men, characterized by proliferated prostate and urinary tract symptoms. The hormonal cascade starting by the action of 5-alpha-reductase (5AR) is known to be one of the pathways responsible for the pathogenesis of BPH. Present investigation evaluated the capacity of berberine (BBR), a nature-derived compound abundant in Coptis japonica, in testosterone-induced BPH rats. Experimental BPH was induced by inguinal injection with testosterone propionate (TP) for 4 weeks. BBR or finasteride, a 5AR inhibitor as positive control, was treated for 4 weeks during BPH. BPH induced by TP evoked weight gaining and histological changes of prostate and BBR treatment improved all the detrimental effects not only weight reduction and histological changes but also suppression of prostate-specific antigen (PSA), which is elevated during BPH. Additionally, BBR suppressed TP-associated increase of 5AR, androgen receptor (AR) and steroid coactivator-1 (SRC-1), the key factors in the pathogenesis of BPH. To evaluate the underlying molecular mechanisms responsible for beneficial effects of BBR, we investigated whether these effects were associated with the mitogen-activated protein kinase pathway. BPH induced by TP showed increased phosphorylation of extracellular signal-regulated kinase (ERK), whereas this was suppressed by BBR treatment. On the other hand, c-jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase was not changed in BPH rats. In in vitro study using RWPE-1 cells, a human prostate epithelial cell line. TP increased cell proliferation and BPH-related key factors such as PSA, AR, and 5AR in RWPE-1 cells, and those factors were significantly decreased in the presence of BBR. Furthermore, these proliferative effects in RWPE-1cells were attenuated by treatment with U0126, an ERK inhibitor, confirming BBR can relieve overgrowth of prostate via ERK-dependent signaling. The cotreatment of U0126 and BBR did not affect the change of 5AR nor proliferation compared with U0126 alone, suggesting that the effect of BBR was dependent on the action of ERK. In conclusion, this study shows that BBR can be used as a therapeutic agent for BPH by controlling hyperplasia of prostate through suppression of ERK mechanism.

20.
Korean J Radiol ; 19(4): 665-672, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29962872

RESUMEN

Objective: To prospectively evaluate the diagnostic performance of computer-aided diagnosis (CAD) for detection of thyroid cancers via ultrasonography (US). Materials and Methods: This study included 50 consecutive patients with 117 thyroid nodules on US during the period between June 2016 and July 2016. A radiologist performed US examinations using real-time CAD integrated into a US scanner. We compared the diagnostic performance of radiologist, the CAD system, and the CAD-assisted radiologist for the detection of thyroid cancers. Results: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the CAD system were 80.0, 88.1, 83.3, 85.5, and 84.6%, respectively, and were not significantly different from those of the radiologist (p > 0.05). The CAD-assisted radiologist showed improved diagnostic sensitivity compared with the radiologist alone (92.0% vs. 84.0%, p = 0.037), while the specificity and PPV were reduced (85.1% vs. 95.5%, p = 0.005 and 82.1% vs. 93.3%, p = 0.008). The radiologist assisted by the CAD system exhibited better diagnostic sensitivity and NPV than the CAD system alone (92.0% vs. 80.0%, p = 0.009 and 93.4% vs. 88.9%, p = 0.013), while the specificities and PPVs were not significantly different (88.1% vs. 85.1%, p = 0.151 and 83.3% vs. 82.1%, p = 0.613, respectively). Conclusion: The CAD system may be an adjunct to radiological intervention in the diagnosis of thyroid cancer.


Asunto(s)
Nódulo Tiroideo/diagnóstico , Ultrasonografía , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Diagnóstico por Computador , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Nódulo Tiroideo/diagnóstico por imagen , Adulto Joven
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