Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 720
Filtrar
1.
Oncologist ; 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33644953

RESUMO

BACKGROUND: Concomitant use of proton pump inhibitors (PPIs) with capecitabine was suggested to be associated with poor outcomes in gastrointestinal cancers. We analyzed the differential impact of PPI use on capecitabine and fluorouracil using the dataset from the AXEPT trial, a phase III randomized trial that demonstrated the non-inferiority of modified XELIRI (mXELIRI; capecitabine plus irinotecan) with FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Out of the per-protocol set (n=620), patients with information on concomitant medications (n=482) were included in this post-hoc analysis. PPI use was defined as concomitant exposure of capecitabine and the use of any PPI for 20% or more of the study period. The treatment-by-PPI-use interaction was examined after adjusting for stratification factors. RESULTS: Of the 482 patients, 49 (10.1%) used PPI. Among the PPI users, the mXELIRI group tended to have poorer overall survival compared with the FOLFIRI group. In contrast, among the non-users, the overall survival of the mXELIRI group was significantly better than that of the FOLFIRI group. Similarly, a trend of worse progression-free survival with mXELIRI compared with FOLFIRI was observed in PPI users but not in non-users. Treatment-by-PPI-use interaction was significant for overall survival and progression-free survival. CONCLUSION: The significant interaction between PPI use and the type of fluoropyrimidine in terms of overall and progression-free survival suggests that fluorouracil could be a more favourable option than capecitabine for patients with metastatic colorectal cancer using PPIs. IMPLICATIONS FOR PRACTICE: This study showed a significant interaction between the use of proton pump inhibitors (PPIs) and the type of fluoropyrimidines. This interaction mainly comes from the positive impact of PPIs in the survival outcomes in the fluorouracil arm rather than a negative impact of PPIs in the capecitabine arm. The possible drug-drug interaction shown in this study suggests that fluorouracil, rather than capecitabine, could be a more appropriate choice of fluoropyrimidine for patients who are taking PPIs in the treatment of metastatic colorectal cancer.

2.
Environ Health Prev Med ; 26(1): 20, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573606

RESUMO

BACKGROUND: Mounting evidence implicates an association between ambient air pollution and impaired reproductive potential of human. Our study aimed to assess the association between air pollution and ovarian reserve in young, infertile women. METHODS: Our study included 2276 Korean women who attended a single fertility center in 2016-2018. Women's exposure to air pollution was assessed using concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) that had been collected at 269 air quality monitoring sites. Exposure estimates were computed for 1, 3, 6, and 12 months prior to the ovarian reserve tests. Anti-Müllerian hormone (AMH) ratio (defined as an observed-to-expected AMH based on age) and low AMH (defined as < 0.5 ng/mL) were employed as indicators of ovarian reserve. We included a clustering effect of 177 districts in generalized estimating equations approach. A secondary analysis was conducted restricting the analyses to Seoul residents to examine the association in highly urbanized setting. RESULTS: The mean age was 36.6 ± 4.2 years and AMH level was 3.3 ± 3.1 ng/mL in the study population. Average AMH ratio was 0.8 ± 0.7 and low AMH was observed in 10.3% of women (n=235). The average concentration of six air pollutants was not different between the normal ovarian reserve and low AMH groups for all averaging periods. In multivariable models, an interquartile range (IQR)-increase in 1 month-average PM10 was associated with decrease in AMH ratio among total population (ß= -0.06, 95% confidence interval: -0.11, 0.00). When we restrict our analysis to those living in Seoul, IQR-increases in 1 and 12 month-average PM2.5 were associated with 3% (95% CI: -0.07, 0.00) and 10% (95% CI: -0.18, -0.01) decrease in AMH ratio. The ORs per IQR increase in the six air pollutants were close to null in total population and Seoul residents. CONCLUSIONS: In a cohort of infertile Korean women, there was a suggestive evidence of the negative association between ambient PM concentration and ovarian reserve, highlighting the potential adverse impact of air pollution on women's fertility.

3.
Mol Genet Genomic Med ; : e1494, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595912

RESUMO

BACKGROUND: Homozygous or compound heterozygous pathogenic variants in the thromboxane A synthase 1 (TBXAS1) gene are associated with Ghosal hematodiaphyseal dysplasia (GHDD) which is characterized by defective hematopoiesis and increased bone density of long bones. METHODS: Patients 1 and 2 are identical twins, who presented with red blood cell transfusion-dependent normocytic anemia and thrombocytopenia with bone marrow fibrosis and cortical bone thickening of long bones on plain radiograph. To clarify the etiology of their anemia and thrombocytopenia, whole blood was used for the DNA extraction and analyzed using next-generation sequencing (NGS) on an in-house bone marrow failure syndrome panel. RESULTS: The NGS results indicated that these two patients carried two heterozygous variants in TBXAS1, exon7, c.583_584del, p.Ala195Leufs*12, and exon12, c.1420G>T, p.Gly474Trp, which were inherited from their mother and father, respectively. Patients 1 and 2 have been on chronic oral steroids with normalization of hemoglobin and platelet count after steroid initiation. Patient 3 is their sister who has normal blood counts but also has the same variants in TBXAS1 as her brothers. Radiographs showed cortical bone thickening and she has not required any treatment or transfusion. CONCLUSION: We report three Caucasian siblings from non-consanguineous parents with novel compound heterozygous variants of TBXAS1 presenting with the phenotypes of GHDD. These three cases illustrate the variable clinical expressivity of the GHDD from two-compound heterozygous pathogenic variants of TBXAS1.

4.
Diabetes Metab J ; 45(1): 1-10, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33434426

RESUMO

BACKGROUND: This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. METHODS: This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. RESULTS: In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of <6.5%. Moreover, only 11.5% of subjects with diabetes met all three targets of glycosylated hemoglobin, blood pressure, and LDL-C. The percentage of energy intake from carbohydrates was higher in diabetes patients than in those without diabetes, while that from protein and fat was lower in subjects with diabetes. CONCLUSION: The high prevalence and low control rate of diabetes and its comorbidities in Korean adults were confirmed. More stringent efforts are needed to improve the comprehensive management of diabetes to reduce diabetes-related morbidity and mortality.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33340618

RESUMO

We aimed to investigate the associations between genetic variants of the norepinephrine transporter gene (NET, also known as SLC6A2) and diagnosis of bipolar I disorder. In addition, we examined the relationship between the genetic variants and manic and psychotic symptoms in patients with bipolar I disorder. The three SNPs rs28386840, rs2242446, and rs5569 were genotyped in 326 patients: patients with bipolar I disorder (n = 160) and a control group (n = 166). Subsequently, multivariate logistic regression analysis adjusting for age and sex was conducted to identify independent influences of the SNPs on diagnosis of bipolar I disorder. A possible association between manic and psychotic symptoms and variants of SLC6A2 was also investigated in patients with bipolar I disorder. The rs28836840 SNP in the 5'-UTR of SLC6A2 was significantly associated with bipolar I disorder and with severity of manic and psychotic symptoms in this disorder. Individuals carrying a T allele in the rs28836840 SNP were likely to have a lower risk of bipolar I disorder or lower severity of manic and psychotic symptoms in patients with bipolar I disorder (bipolar I disorder diagnosis: OR = 0.643, 95% Cl = 0.468-0.883, p = 0.006; manic symptoms: ß = -2.457, 95% Cl = -4.674 ~ -0.239, p = 0.031; psychotic symptoms: ß = -2.501, 95% Cl = -4.700 ~ -0.301, p = 0.027). For the rs2242446 and rs5569 SNPs, there were no significant differences between patients with bipolar I disorder and those without. Our results revealed associations of the rs28386840 SNP with bipolar I disorder diagnosis and with severity of manic and psychotic symptoms. However, the findings reported here require replication in larger samples and various ethnic groups.

6.
Vaccine ; 39(1): 125-136, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33303180

RESUMO

OBJECTIVES: Using dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions. METHODS: We tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014-2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System. RESULTS: Based on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs. CONCLUSIONS: The same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states.

7.
Vaccine ; 39(1): 147-157, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33303182

RESUMO

OBJECTIVE: This study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model. METHODS: We developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY). RESULTS: The dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90-95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model's time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage. CONCLUSION: A dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90-95%.

8.
Vaccine ; 39(1): 158-166, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33303183

RESUMO

BACKGROUND: This paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile. METHODS: We defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models' different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated. RESULTS: The dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90-95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models' estimates over their different time horizons are compared at infant coverage < 90-95%, their projections fall in the same range. CONCLUSIONS: Static models may serve to explore an intervention's cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally. CLINICAL TRIAL REGISTRY: Clinical Trial registry name and registration number: Not applicable.

9.
BMC Vet Res ; 16(1): 471, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272258

RESUMO

BACKGROUND: Femoral varus deformities complicating the realignment of the quadriceps muscles are frequently associated with medial patellar luxation (MPL) in dogs. Therefore, distal femoral osteotomy (DFO) is recommended in dogs affected with severe MPL and a distal femoral varus deformity. The presence of an anatomic lateral distal femoral angle (aLDFA) of ≥ 102° has been anecdotally recommended as an indication for performing corrective DFO in large-breed dogs. However, the effect of a femoral varus deformity on MPL has not been scientifically evaluated. We aimed to evaluate the influence of a femoral varus deformity on MPL using a finite element method based computer model. Three-dimensionally reconstructed computed tomographic images of a normal femur from a Beagle dog were deformed using meshing software to create distal varus deformities. A total of thirteen aLDFAs, including 95°, 98° and 100°-110°, were simulated. The patellar positions and reaction force between the patella and trochlear grooves were calculated for all finite element models under constant rectus femoris muscle activation. RESULTS: The patella was displaced medially from the trochlear groove at an aLDFA of ≥103°. With an aLDFA of 103° to 110°, the reaction force was equal to zero and then decreased to negative values during the simulation, while other models with aLDFAs of 95°, 98°, and 100°-102° had positive reaction force values. The patella began to luxate at 24.90 seconds (sec) with an aLDFA of 103°, 19.80 sec with an aLDFA of 104°, 21.40 sec with an aLDFA of 105°, 20.10 sec with an aLDFA of 106°, 18.60 sec with an aLDFA of 107°, 15.30 sec with an aLDFA of 108°, 16.60 sec with an aLDFA of 109°, and 11.90 sec with an aLDFA of 110°. CONCLUSION: Severe distal femoral varus with an aLDFA of ≥103° caused MPL when other anatomical factors were controlled. Thissimplified computer model provides complementary information to anecdotal cutoffs for DFO, hence it should be applied to clinical patients with caution.

10.
Nutr Res Pract ; 14(6): 621-636, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33282124

RESUMO

BACKGROUND/OBJECTIVES: The Seoul Metabolic Syndrome Management (SMESY) program is a 1-yr lifestyle modification program targeting metabolic syndrome (MetS) in Seoul residents. This study investigated the associations between adherence to dietary guidelines and MetS among the SMESY program participants. SUBJECTS/METHODS: Data of 54,385 participants aged 20-64 yrs who completed the SMESY program in 2015, had information on adherence to dietary guidelines, and were not medicated for diabetes, hypertension, or dyslipidemia were analyzed. Participants underwent MetS screening and completed a lifestyle questionnaire including adherence to 10 dietary guidelines before and after participation. Participants were classified according to the number of MetS risk factors at baseline (MetS group, ≥ 3; risk group, 1-2; healthy group, none). Adherence to dietary guidelines was determined from the number of "yes" responses regarding the fulfillment of each guideline on ≥ 5 days/week. Multiple logistic regression was used to evaluate associations between newly diagnosed MetS and changes in adherence to dietary guidelines. RESULTS: In the MetS group, MetS prevalence decreased after the SMESY program (men, -41.9%p; women, -48.7%p), and all risk factors were significantly improved (P < 0.0001). All groups exhibited improved adherence to all dietary guidelines after participation (P < 0.0001). In the MetS group with positively changed adherence scores, the MetS prevalence decreased by -44.1%p for men and -49.5%p for women, whereas the prevalence in those with negative changes decreased by -38.1%p for men and -48.6%p for women. In the risk group, those with positively changed adherence scores had significantly decreased odds ratios (ORs) for newly diagnosed MetS compared with those with negative changes (OR, 0.70; 95% confidence interval [CI], 0.61-0.80 for men; OR, 0.88; 95% CI, 0.79-0.99 for women). CONCLUSIONS: The SMESY program may effectively reduce the risk of MetS among adults with risk factors by improving adherence to dietary guidelines.

11.
EMBO Mol Med ; 12(12): e12497, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33258196

RESUMO

The Rv2626c protein of Mycobacterium tuberculosis is a promising vaccine candidate owing to its strong serum antibody response in patients with tuberculosis. However, there is limited information regarding the intracellular response induced by Rv2626c in macrophages. In this study, we demonstrated that Rv2626c interacts with the RING domain of TRAF6 and inhibits lysine (K) 63-linked polyubiquitination of TRAF6 (E3 ubiquitin ligase activity); this results in the suppression of TLR4 inflammatory signaling in macrophages. Furthermore, we showed that the C-terminal 123-131-amino acid Rv2626c motif promotes macrophage recruitment, phagocytosis, M2 macrophage polarization, and subsequent bacterial clearance. We developed rRv2626c-CA, a conjugated peptide containing the C-terminal 123-131-amino acid Rv2626c that targets macrophages, penetrates the cell membrane, and has demonstrated significant therapeutic effects in a mouse model of cecal ligation and puncture-induced sepsis. This multifunctional rRv2626c-CA has considerably improved potency, with an IC50 that is 250-fold (in vitro) or 1,000-fold (in vivo) lower than that of rRv2626c-WT. We provide evidence for new peptide-based drugs with anti-inflammatory and antibacterial properties for the treatment of sepsis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33261243

RESUMO

Ozone is known to cause bronchial inflammation and airway hyper-responsiveness via oxidative injury and inflammation. While other ambient air pollutants such as particulate matter (PM) and NO2 showed decreasing trends of mean annual concentrations, ozone concentration did not decline recently in most countries worldwide. Short-term exposure to high concentration of ozone has been associated with increased mortality and cardiovascular and respiratory morbidity in many regions of the world. However, long-term effects of ozone were less investigated than short-term exposure due to the difficulty of modeling for ozone exposure and linking between individual exposure and health outcome data. Recently developed modeling of ozone exposure enabled investigation of long-term ozone effects on health outcomes. Recent findings suggested that long-term exposure to ozone is associated with an increased risk of cardiovascular and respiratory mortality. Longitudinal studies using large cohorts also revealed that long-term exposure to ozone was associated with a greater decline in lung function and progression of emphysema. Keeping standards for ozone as well as PM is needed to protect respiratory health of the general population and subjects with chronic respiratory diseases.

13.
Patient Prefer Adherence ; 14: 2427-2437, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304097

RESUMO

Purpose: Health-related quality of life (HRQoL) is an important construct in clinical settings, and it is crucial that it should be properly measured. As the EuroQol-5-dimensions-5 levels (EQ-5D-5L) is more effective for such measurement than the 3-level model, data on economic models, clinical studies, and public health evaluations previously collected through the EQ-5D-3L need to be revaluated using the EQ-5D-5L. This study evaluated colorectal cancer (CRC) patients' HRQoL scores using the Vietnamese EQ-5D-5L value set. Patients and Methods: The cross-sectional study included CRC patients treated at a tertiary public hospital. HRQoL was assessed using the EQ-5D-5L, and HRQoL utility scores were calculated using the Vietnamese value set. Tobit regression examined factors associated with HRQoL. Results: The analysis included 197 CRC patients. Ages ranged from 20 to 87 years (M = 57.64, SD = 13.5); 42.2% and 57.8% were diagnosed with cancer of the colon or rectum/anus, respectively. Mean EQ-5D-5L was 0.561 (range, -0.5115 to 1). Most participants experienced anxiety/depression (88%), followed by pain/discomfort (87%), mobility (71%), usual activity (69%), and self-care (67%). Advanced CRC stage (stage II: ß -0.303, se 0.08; stage III: ß -0.305, se 0.07; stage IV: ß -0.456, se 0.07) and surgery (ß -0.113, se 0.05) were negatively associated with EQ-5D-5L scores. Advanced education (high school: ß 0.273, se 0.07); college/vocational: ß 0.134se 0.05; university/higher: Coef 0.213, se 0.08;) and older age (age group 35-44: ß 0.253, se 0.10; 45-54: ß 0.327, se 0.09; 55-64: ß 0.355 se 0.09; 65+ ß 0.204, se 0.09) were positively associated with EQ-5D-5L scores. Conclusion: Patients in advanced CRC stages or undergoing surgery experienced lower HRQoL and higher prevalence of anxiety/depression and pain/discomfort. Older age and high educational attainment predicted high HRQoL. This study provides information on CRC patients' health utility based on various patient characteristics, which can be used in future economic evaluations.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33375113

RESUMO

The incidence and mortality of colorectal cancer (CRC) has increased rapidly in Vietnam, but the economic burden of this disease has never been estimated. We estimate the direct and indirect cost of CRC patients in Vietnam in 2018 using a prevalence-based approach and human capital method. The total economic cost of CRC was VND 3041.88 billion (~$132.9 million), representing 0.055% of the 2018 gross domestic product. Notably, indirect costs comprised 83.58 % of the total cost, 82.61% of which is future income loss, because CRC occurs during productive years. The economic burden of CRC in Vietnam is substantial. The medical cost for CRC diagnosis and treatment is higher for younger patients and for those in advanced stages. Strategies to decrease the economic burden of CRC at the patient and national level, such as screening programs, should be developed and implemented in Vietnam.


Assuntos
Neoplasias Colorretais/economia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Adulto , Idoso , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Vietnã/epidemiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-33223477

RESUMO

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) agents have shown clinical benefits against metastatic colorectal cancer (mCRC) when combined with cytotoxic chemotherapeutic drugs. Because randomized controlled trials have restrictive enrollment criteria, and because the participants typically do not resemble actual patients, we here investigated the efficacy of bevacizumab as part of a combination therapy for mCRC in a Korean real-world practice setting. PATIENTS AND METHODS: We retrospectively evaluated 3748 patients with an initial diagnosis of mCRC or recurrent colorectal cancer with distant metastasis who received first-line chemotherapy in a tertiary cancer center. The primary study endpoint was overall survival. We used multivariate analysis using the Cox regression hazard model and propensity score matching (PSM) methods to adjust for any confounding clinicopathologic factors. Subgroup analysis was also performed for patients who did not receive local treatments for metastatic lesions before receipt of first-line chemotherapy. RESULTS: In an initial crude analysis, patients who received first-line FOLFOX or FOLFIRI showed better survival outcomes if these regimens were combined with bevacizumab (median overall survival, 3.5 vs. 2.3 years; hazard ratio [HR] = 0.66; 95% confidence interval [CI], 0.59-0.73; P < .001). However, Cox regression hazard model adjusted analysis using PSM methods revealed no significant survival differences between these groups (3.0 vs. 2.6 years; HR = 0.92; 95% CI, 0.79-1.07; P = .2612). We performed further survival analysis of 2814 patients with unresectable disease without metastasectomy who received metastatic radiofrequency ablation before chemotherapy. Cox regression and PSM analysis indicated that bevacizumab group showed better survival (HR = 0.82; 95% CI, 0.71-0.94; P = .005; and HR = 0.84; 95% CI, 0.71-0.99; P = .018). CONCLUSION: The addition of bevacizumab to a first-line chemotherapeutic regimen provides survival benefits in a real-world setting for mCRC patients who cannot undergo curative-intent local treatment for metastatic lesions.

16.
Eur Respir J ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184121

RESUMO

Ambient air pollution is associated with prognosis of idiopathic pulmonary fibrosis (IPF) patients. We aimed to identify the impacts of individual exposure to particulate matter with aerodynamic diameter ≤10 µm (PM10) and nitrogen dioxide (NO2) on IPF patients' mortality.Total 1114 patients (mean age, 65.7 years; male, 80.5%) diagnosed with IPF between 1995 and 2016 were included in this study. Individual-level long-term concentrations of PM10 and NO2 at residential addresses of patients were estimated using a national-scale exposure prediction model. The effect of PM10 and NO2 on mortality was estimated using a Cox proportional hazards model adjusted for individual- and area-level covariates.The median follow-up period was 3.8 years, and 69.5% of all the patients died or underwent lung transplantation. When adjusted for individual- and area-level covariates, a 10-ppb increase in NO2 concentration was associated with a 17% increase in mortality (hazard ratio [HR], 1.172 [95% CI: 1.030-1.344, p=0.016]). When IPF patients were stratified by age (≥65 years versus <65 years) or by sex, NO2 was a significant prognostic factor for mortality in the elderly (HR, 1.331 [95% CI: 1.010-1.598, p=0.010]). When stratified by age and sex jointly, NO2 showed the stronger association with mortality in elderly male (HR, 1.305 [95% CI: 1.072-1.598, p=0.008]) than in other groups. PM10 was not associated with IPF mortality in all patients and in subgroups stratified by age or sex.Our findings suggest that increased exposure to NO2 can increase risk of mortality in patients with IPF, specifically in elderly men.

17.
Environ Health ; 19(1): 113, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167999

RESUMO

BACKGROUND: While many studies reported the association between long-term exposure to particulate matter air pollution (PM) and cardiovascular disease (CVD), few studies focused on incidence with relatively high-dose exposure using a nationwide cohort. This study aimed to investigate the association between long-term exposure to PM10 and PM2.5 and incidence of CVD in a nationwide and population-based cohort in South Korea where the annual average concentration of PM2.5 is above 20 µg/m3. METHODS: We selected 196,167 adults in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) constructed based on the entire South Korean population. Incidence of four CVD subtypes including ischemic heart disease (IHD), myocardial infarction, heart failure, and stroke, and total CVD including all four was identified as the first diagnosis for 2007-2015. To assess individual exposures, we used annually-updated district-level residential addresses and district-specific PM concentrations predicted by a previously developed universal kriging prediction model. We computed individual-level long-term PM concentrations for four exposure windows: previous 1, 3, and 5 year(s) and 5 years before baseline. We applied time-dependent Cox proportional hazards models to estimate hazard ratios (HRs) of incident CVDs per 10 µg/m3 increase in PM10 and PM2.5 after adjusting for individual- and area-level characteristics. RESULTS: During 1,578,846 person-year, there were 33,580 cases of total incident CVD. Average PM10 and PM2.5 concentrations for the previous 5 years were 52.3 and 28.1 µg/m3, respectively. A 10 µg/m3 increase in PM2.5 exposed for the previous 5 years was associated with 4 and 10% increases in the incidence of total CVD (95% confidence interval: 0-9%) and IHD (4-16%), respectively. HRs tended to be higher with earlier exposure for IHD and more recent exposure for stroke. The estimated shape of the concentration-response relationship showed non-linear patterns. We did not find evidence of the association for PM10. CONCLUSIONS: Using a population-based nationwide cohort exposed to relatively high PM concentration, this study confirmed the association between PM2.5 and CVD incidence that was reported in previous studies mostly with low-dose environments. The magnitude and the shape of the association were generally consistent with previous findings.

18.
Environ Health Perspect ; 128(11): 117006, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33215932

RESUMO

BACKGROUND: Only a limited number of neuroimaging studies have explored the effects of ambient air pollution in adults. The prior studies have investigated only cortical volume, and they have reported mixed findings, particularly for gray matter. Furthermore, the association between nitrogen dioxide (NO2) and neuroimaging markers has been little studied in adults. OBJECTIVES: We investigated the association between long-term exposure to air pollutants (NO2, particulate matter (PM) with aerodynamic diameters of ≤10µm (PM10) and ≤2.5µm (PM2.5), and neuroimaging markers. METHODS: The study included 427 men and 530 women dwelling in four cities in the Republic of Korea. Long-term concentrations of PM10, NO2, and PM2.5 at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images. A generalized linear model was used, adjusting for potential confounders. RESULTS: A 10-µg/m3 increase in PM10 was associated with reduced thicknesses in the frontal [-0.02mm (95% CI: -0.03, -0.01)] and temporal lobes [-0.06mm (95% CI: -0.07, -0.04)]. A 10-µg/m3 increase in PM2.5 was associated with a thinner temporal cortex [-0.18mm (95% CI: -0.27, -0.08)]. A 10-ppb increase in NO2 was associated with reduced thicknesses in the global [-0.01mm (95% CI: -0.01, 0.00)], frontal [-0.02mm (95% CI: -0.03, -0.01)], parietal [-0.02mm (95% CI: -0.03, -0.01)], temporal [-0.04mm (95% CI: -0.05, -0.03)], and insular lobes [-0.01mm (95% CI: -0.02, 0.00)]. The air pollutants were also associated with increased thicknesses in the occipital and cingulate lobes. Subcortical structures associated with the air pollutants included the thalamus, caudate, pallidum, hippocampus, amygdala, and nucleus accumbens. DISCUSSION: The findings suggest that long-term exposure to high ambient air pollution may lead to cortical thinning and reduced subcortical volume in adults. https://doi.org/10.1289/EHP7133.

19.
Nat Sci Sleep ; 12: 883-894, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177906

RESUMO

Purpose: The mean sleep duration of Koreans is 7 hours 49 minutes, which is the lowest among Organization for Economic Cooperation and Development countries. Although vitamin D deficiency and arthritis are considered modifiable factors influencing restorative sleep, mean vitamin D levels are low (17.33 ng/mL) and arthritis is prevalent among Koreans. This study investigated whether vitamin D deficiency and arthritis increase the risk of short sleep duration. Patients and Methods: The current study used data from the Korean National Health and Nutrition Examination Survey (KNHANES) for 46,405 Korean adults. Vitamin D levels were measured using a radioimmunoassay kit. Sleep duration and arthritis history were assessed using a self-reported questionnaire. Sleep duration was categorized as optimal (7 to <9 hours/day), short (<7 hours/day), and long (≥9 hours/day). Vitamin D levels were grouped as vitamin D sufficiency (≥20 ng/mL), insufficiency (10-19.99 ng/mL), and deficiency (<10 ng/mL). Multiple imputation was used to compensate for missing data. Multinomial logistic regression was used to examine the associations of vitamin D and arthritis status with sleep duration. The regressions were adjusted for covariates, and each model was adjusted for vitamin D and arthritis. Results: Among these participants, 23,078 (49.73%) and 3518 (7.58%) had short and long sleep duration, respectively; 26,724 (57.59%) and 4349 (9.37%) exhibited vitamin D insufficiency and deficiency, respectively; and 4709 (10.15%) were arthritis patients. Compared with vitamin D sufficiency, vitamin D insufficiency and deficiency were associated with short sleep duration (vitamin D insufficiency group: OR = 1.07, 95% CI = 1.01-1.13; vitamin D deficiency group: OR = 1.13, 95% CI = 1.03-1.24). The presence of arthritis was associated with short sleep duration (OR = 1.14, 95% CI = 1.06-1.22) compared with its absence. The interaction between vitamin D deficiency and the presence of arthritis was significantly associated with short sleep duration. However, long sleep duration was not significantly associated with vitamin D levels or arthritis status. Conclusion: Low vitamin D levels and the presence of arthritis were associated with an increased risk of short sleep duration. Additionally, there was a positive interaction effect between vitamin D deficiency and arthritis on short sleep duration.

20.
Biomed Opt Express ; 11(10): 5814-5825, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33149988

RESUMO

Goblet cells (GCs) in the intestine are specialized epithelial cells that secrete mucins to form the protective mucous layer. GCs are important in maintaining intestinal homeostasis, and the alteration of GCs is observed in inflammatory bowel diseases (IBDs) and neoplastic lesions. In the Barrett's esophagus, the presence of GCs is used as a marker of specialized intestinal metaplasia. Various endomicroscopic imaging methods have been used for imaging intestinal GCs, but high-speed and high-contrast GC imaging has been still difficult. In this study, we developed a high-contrast endoscopic GC imaging method: fluorescence endomicroscopy using moxifloxacin as a GC labeling agent. Moxifloxacin based fluorescence imaging of GCs was verified by using two-photon microscopy (TPM) in the normal mouse colon. Label-free TPM, which could visualize GCs in a negative contrast, was used as the reference. High-speed GC imaging was demonstrated by using confocal microscopy and endomicroscopy in the normal mouse colon. Confocal microscopy was applied to dextran sulfate sodium (DSS) induced colitis mouse models for the detection of GC depletion. Moxifloxacin based GC imaging was demonstrated not only by 3D microscopies but also by wide-field fluorescence microscopy, and intestinal GCs in the superficial region were imaged. Moxifloxacin based endomicroscopy has a potential for the application to human subjects by using FDA approved moxifloxacin.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...