CTONG0806 assessed the efficacy of pemetrexed versus gefitinib as second-line treatment in advanced nonsquamous nonsmall-cell lung cancer (NSCLC) harboring wild-type epidermal growth factor receptor ...(EGFR).
Patients with locally advanced or metastatic nonsquamous NSCLC harboring wild-type EGFR, detected by direct sequencing, and previously treated with platinum-based chemotherapy were randomized to receive gefitinib (250 mg/day) orally or pemetrexed (500 mg/m2) i.v. on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS). The Independent Review Committee (IRC) evaluated all pictorial data.
From February 2009 to August 2012, 161 patients were enrolled, and 157 were assessable (81 in the gefitinib arm, 76 in the pemetrexed arm). Baseline characteristics were balanced between the two arms. The median PFSs were 4.8 versus 1.6 months in the pemetrexed and gefitinib arms, respectively hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.40–0.75, P < 0.001 as confirmed by IRC evaluation (5.6versus 1.7 months, HR 0.53, 95% CI 0.38–0.75, P < 0.001). The median overall survival (OS) showed a trend of superiority in the pemetrexed arm (12.4 versus 9.6 months, HR 0.72, 95% CI 0.49–1.04, P = 0.077). Quality-of-life assessment showed no marked difference between the arms. No unexpected adverse events were found. Of 108 patients with sufficient DNA samples, EGFR mutation status was re-tested by Scorpion amplification refractory mutation system (ARMS); 32 (29.6%) tested positive (19 in the pemetrexed arm, 13 in the gefitinib arm; median PFS: 8.1 versus 7.0 months, HR 0.94, 95% CI 0.43–2.08, P = 0.877).
CTONG0806 is the first trial to show significant improvement in PFS and an improved OS trend with pemetrexed compared with gefitinib as second-line setting treatment of EGFR wild-type advanced nonsquamous NSCLC. ARMS is superior to direct sequencing in excluding false-negative patients.
NCT00891579.
The impact of the urban heat island (UHI) effect on environmental and regional climate has been receiving wide attention in recent decades. Taiwan, especially Taipei (located in northern Taiwan), is ...experiencing a significant UHI effect due to its high population density and the uniqueness of the geographic structure. In order to evaluate the impacts of urbanization and UHI effect over northern Taiwan, a next generation mesoscale model, Weather Research and Forecasting (WRF) model coupled with the Noah land surface model and Urban Canopy model (UCM), was used to study this issue.
By using the WRF–Noah–UCM model, it has significantly improved our simulation results for the prediction of the UHI effect, boundary layer development, and land sea breeze. Observations of weather stations and Lidar showed that the near surface air temperature was nearly 34–35
°C and the boundary layer height was nearly 1500
m around noon in Taipei on 17 June 2006. Around midnight, the air temperature ranged from 26 to 28
°C. Our model can predict well for boundary layer development during the daytime and the UHI effect in northern Taiwan. Sensitivity tests indicate that the anthropogenic heat (AH) plays an important role for the boundary layer development and UHI intensity in the Taipei area, especially during nighttime and early morning. When we increase AH by 100
W
m
−2 in the model, the average surface temperature could increase nearly 0.3
°C in Taipei. Furthermore, we found the UHI effect also has a significant impact on land sea circulation. It could enhance the sea breeze in the daytime and weaken the land breeze during the nighttime and hence had a significant impact on the air pollution diffusion in northern Taiwan.
This study investigated seasonal variations in the mass concentration and chemical composition of ambient aerosols observed at three stations (coastal, mountainous, and downtown sites) in northern ...Taiwan from March 2009 to February 2012. The results show that the major aerosol components include ammonium, sulfate, nitrate, sea salt, dust, organic carbon, and elemental carbon, whereas the mass fraction of each species depends on the sampling location and season. A significant correlation (r = 0.7–0.8) was observed in aerosol concentrations measured at the respective stations, indicating that aerosol concentrations were dominated by regional‐scale factors. Ammonium, sulfate, and nitrate consistently reached respective peak values in the spring in conjunction with dust particle levels. This shows that the transport of dust and particulate air pollutants from the Asian continent has affected the atmospheric environment in this area. Distinct seasonality was observed for sea salt and secondary organic carbon (SOC): sea salt levels peaked in the autumn, whereas SOC levels peaked in the summer, implying that their sources were regulated by independent seasonal factors. Correlation between sea salt concentration and surface wind speed was derived from coastal measurements and showed a high value for the wind speed sensitivity parameter of around 0.37 for our location. In addition, it was revealed that the SOC concentration in aerosols was positively correlated with oxidant photolysis index (Ox × UVB), suggesting that the SOC seasonality was dominated by hydroxyl radical production.
Key Points
Inorganic particulate pollutants and dust consistently peaked in the spring due to Asian outflow effects
Ambient concentrations of sea salt particles were exponentially correlated with surface wind speeds
The production of secondary organic aerosols was dominated by the photolysis of total oxidants
Talaromyces marneffei
(
T. marneffei
) can cause talaromycosis, a fatal systemic mycosis, in patients with AIDS. With the increasing number of talaromycosis cases in Guangdong, China, we aimed to ...investigate the susceptibility of 189
T. marneffei
clinical strains to eight antifungal agents, including three echinocandins (anidulafungin, micafungin, and caspofungin), four azoles (posaconazole, itraconazole, voriconazole, and fluconazole), and amphotericin B, with determining minimal inhibition concentrations (MIC) by Sensititre YeastOne™ YO10 assay in the yeast phase. The MICs of anidulafungin, micafungin, caspofungin, posaconazole, itraconazole, voriconazole, fluconazole, and amphotericin B were 2 to > 8 μg/ml, >8 μg/ml, 2 to > 8 μg/ml, ≤ 0.008 to 0.06 μg/ml, ≤ 0.015 to 0.03 μg/ml, ≤ 0.008 to 0.06 μg/ml, 1 to 32 μg/ml, and ≤ 0.12 to 1 μg/ml, respectively. The MICs of all echinocandins were very high, while the MICs of posaconazole, itraconazole, and voriconazole, as well as amphotericin B were comparatively low. Notably, fluconazole was found to have a higher MIC than other azoles, and exhibited particularly weak activity against some isolates with MICs over 8 μg/ml. Our data in vitro support the use of amphotericin B, itraconazole, voriconazole, and posaconazole in management of talaromycosis and suggest potential resistance to fluconazole.
Summary
A growing elderly population is expected worldwide, and the burden of hip fractures on health care system will continue to increase. By 2035, there will be a 2.7-fold increase in the number ...of hip fractures in Taiwan. The study provides quantitative basis for the future distribution of medical resources.
Introduction
Hip fractures have long been recognized as a major public health concern. The study aimed to determine time trends in the incidence of hip fractures and to forecast the number of hip fractures expected in Taiwan up to 2035.
Methods
A nationwide survey was conducted using data from the Taiwan National Health Insurance Research Database from 2004 to 2011. A total of 141,397 hip fractures were identified, with a mean of 17,675 fractures/year. Annual incidences of hip fractures were calculated and tested for trends. Projections of the incidence rates of hip fractures and bed days associated with hip fractures were calculated using Poisson regression on the historical incidence rates in combination with population projections from 2012 to 2035.
Results
The incidence rates of hip fracture during 2004–2011 were 317 and 211 per 100,000 person-years among women and men, respectively. Over this 8-year period, the age-standardized incidence of hip fracture decreased by 13.4 % among women and 12.2 % among men. Despite the decline in the age-standardized incidence, the absolute number of hip fractures increased owing to the aging population. The number of hip fractures is expected to increase from 18,338 in 2010 to 50,421 in 2035—a 2.7-fold increase. The number of bed days for 2010 and 2035 was estimated at 161,248 and 501,995, respectively, representing a 3.1-fold increase.
Conclusions
The socioeconomic impact of hip fractures will be high in the near future. This study provides a quantitative basis for future policy decisions to serve this need.
The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. ...This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients’ 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.
ABSTRACT Hot dust-obscured galaxies (hot DOGs), selected from Wide-Field Infrared Survey Explorer's all-sky infrared survey, host some of the most powerful active galactic nuclei known and may ...represent an important stage in the evolution of galaxies. Most known hot DOGs are located at , due in part to a strong bias against identifying them at lower redshift related to the selection criteria. We present a new selection method that identifies 153 hot DOG candidates at , where they are significantly brighter and easier to study. We validate this approach by measuring a redshift z = 1.009 and finding a spectral energy distribution similar to that of higher-redshift hot DOGs for one of these objects, WISE J1036+0449 ( ). We find evidence of a broadened component in Mg ii, which would imply a black hole mass of and an Eddington ratio of . WISE J1036+0449 is the first hot DOG detected by the Nuclear Spectroscopic Telescope Array, and observations show that the source is heavily obscured, with a column density of . The source has an intrinsic 2-10 keV luminosity of , a value significantly lower than that expected from the mid-infrared/X-ray correlation. We also find that other hot DOGs observed by X-ray facilities show a similar deficiency of X-ray flux. We discuss the origin of the X-ray weakness and the absorption properties of hot DOGs. Hot DOGs at could be excellent laboratories to probe the characteristics of the accretion flow and of the X-ray emitting plasma at extreme values of the Eddington ratio.
The high rate of neuropsychologic sequelae in CM survivors indicates that initial antifungal therapy is far from being satisfactory. This prospective cross-sectional study applied DTI on HIV-negative ...CM patients to determine whether microstructural changes in brain tissue are associated with subsequent cognitive symptoms.
Fifteen patients with HIV-negative CM and 15 sex- and age-matched healthy volunteers were evaluated and compared. All underwent complete medical and neurologic examinations and neuropsychologic testing. Brain DTI was obtained to derive the FA and ADC of several brain regions. Correlations among DTI parameters, neuropsychologic rating scores, and cryptococcal-antigen titer in CSF were analyzed.
Significant ADC values increased and FA values decreased in HIV-negative CM patients in multiple selected regions of interest, including the genus of the corpus callosum and the frontal, parietal, orbito-frontal, and periventricular white matter and lentiform nucleus. Higher CSF cryptococcal-antigen titer on admission was associated with poorer DTI parameters (r = -0.666, P = .018), which were linearly related to worse cognitive performance during follow-up.
The decline in brain DTI parameters in the associated brain areas indicates an HIV-negative CM microstructural pathology that is related to neuropsychologic consequences.
Essentials
Perioperative blood loss and inflammatory response can significantly affect recovery after surgery.
We studied the effects of multiple‐dose oral tranexamic acid on blood loss and ...inflammatory response.
A postoperative four‐dose regimen brought about maximum reduction in postoperative blood loss.
A postoperative four‐dose regimen reduced inflammatory response and promoted early rehabilitation.
Summary
Background
Tranexamic acid (TXA) can reduce blood loss and the inflammatory response at multiple doses in total knee arthroplasty patients. However, the optimal regimen has not been determined.
Objectives
To identify the most effective regimen for achieving maximum reductions in blood loss and the inflammatory response.
Patients/Methods
Two hundred and seventy‐five patients were randomized to receive a placebo (group A), a single 2‐g oral dose of TXA 2 h preoperatively followed by 1 g of oral TXA 3 h postoperatively (group B), a single dose followed by 1 g of oral TXA 3 h and 7 h postoperatively (group C), a single dose followed by 1 g of oral TXA 3 h, 7 h and 11 h postoperatively (group D), or a single dose followed by 1 g of oral TXA 3 h, 7 h, 11 h and 15 h postoperatively (group E). The primary outcome was total blood loss on postoperative day (POD) 3. Secondary outcomes included a decrease in the hemoglobin level, coagulation parameters, inflammatory marker levels, and thromboembolic complications.
Results
Groups D and E had significantly lower blood loss and smaller decreases in hemoglobin level than groups A, B, and C, with no significant difference on POD 3 between groups D and E. Significantly enhanced coagulation was identified for the four multiple‐dose regimens; however, all thromboelastographic parameters remained within normal ranges. Group E had the lowest inflammatory marker levels and pain, and the greatest range of motion. No thromboembolic complications were identified.
Conclusion
The four‐dose regimen yielded the maximum reductions in blood loss and inflammatory response, improved analgesia, and promoted early rehabilitation. Further studies are required to ensure that these findings are reproducible.
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