To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC).
In all, ...185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).
EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio HR 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020).
Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.
Abstract Background China is reshaping its health-care system to orient towards primary care. We developed a short instrument on the basis of the Primary Care Assessment Tool-Adult Edition (PCAT-AE) ...to assess patients' experiences of primary-care delivery in community health centres, the major primary-care provider in urban areas. Methods A multistage cluster sampling method was used to select seven geographical regions in southern China where the population's ageing and gender structure is similar to that of China's overall population. A validated PCAT-AE (Mandarin Chinese short version) with 33 PCAT items on a four-point Likert-type scale was used, with higher scores representing better primary-care experiences. This study was approved by the Ethics Committee of Guangzhou Medical University, Guangzhou, China, and the Survey and Behaviour Research Ethics Committee of The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China (TB106179/MD10606). All study participants provided written consent. Findings The overall response rate of adult subjects interviewed at community health centres was 85·8% (3360 of 3916). Both frequent (2237) and less-frequent service users (1123) were surveyed, among which 1122 (33%) patients had an optimum PCAT score (higher than the third quantile of the score range—ie, above 99 of 132). The proportion of subjects with optimum scores in individual primary-care domains ranged from 62·1% (95%CI 59·8–64·3) in the comprehensiveness of service attribute to only 16·6% (14·7–18·7) in the community orientation attribute. Among all subjects, those with social medical insurance were more likely to report optimum primary care experience (adjusted odds ratio 2·30, 95% CI 1·92–2·75) than those uninsured. In the stratified analysis among subjects who were uninsured, those attending community health centres owned and managed by the government as their usual source of primary care had the highest PCAT scores compared with other models of community health centres owned and managed by secondary or tertiary hospitals (95·16 vs 90·18; p=0·0001) or by private investors (95·16 vs 87·80; p<0·0001), as a result of better first-contact care and coordination of care. Interpretation The study suggests an urgent need to understand and address how social medical insurance coverage could affect patients' experiences. The community health centre model with a government-dominant top-down approach seems to be most effective in solving conundrums for China's health-care reform. Funding This study was funded by the Bauhinia Foundation Research Centre; Department of Health, Guangdong province (C2009006/2009–2013); Department of Education, Guangdong province (BKZZ2011047/2010–2013); Medical Research Fund, Chinese Medical Association (2010-08-05); and Community Health Research Fund, Community Health Association of China (2012-2-91). HHXW was supported by a postdoctoral research fellowship in the Hong Kong–Scotland Partners in Post Doctoral Research programme, Research Grants Council of Hong Kong and the Scottish Government (S-CUHK402/12). JJW is supported by Guangdong Exemplary Centres for Exploratory Teaching in Higher Education Institutions—General Practice Exploratory Teaching Centre (GDJG-2010-N38-35, Guangdong Department of Education) and The Ninth Round of Guangdong Key Disciplines—General Practice (GDJY-2012-N13-85, Guangdong Department of Education), both of which he leads.
Abstract Purpose Current health care reforms in China have an overall goal of strengthening primary care through the establishment and expansion of primary care networks based on community health ...centers (CHCs). Implementation in urban areas has led to the emergence of different models of ownership and management. The objective of this study was to evaluate the primary care experiences of patients in the Pearl River Delta as measured by the Primary Care Assessment Tool (PCAT) and the relationships with ownership and management in the 3 different models we describe. Methods This cross-sectional study was conducted on-site at CHCs in 3 cities within the Pearl River Delta, China, using a multistage cluster sampling method. A validated Mandarin Chinese version of the PCAT–Adult Edition (short version) was adopted to collect information from adult patients regarding their experiences with primary care sources. PCAT scores for individual primary care attributes and total primary care assessment scores were assessed with respect to sociodemographic characteristics, health characteristics, and health care service utilization across 3 primary care models. Results One thousand four hundred forty (1,440) primary care patients responded to the survey, for an overall response rate of 86.1%. Respondents gave government-owned and -managed CHCs the highest overall PCAT scores when compared with CHCs either managed by hospitals (95.18 vs 90.81; P = .005) or owned by private and social entities (95.18 vs 90.69; P = .007) as a result of better first-contact care (better first-contact utilization) and coordination of care (better service coordination and information system). Factors that were positively and significantly associated with higher overall assessment scores included the presence of a chronic condition ( P <.001), having medical insurance (P = .006), and a self-reported good health status ( P <.001). Conclusions This study suggests that government-owned and -managed CHCs may be able to provide better first-contact care in terms of utilization and coordination of care, and may be better at solving the problem of underutilization of the CHCs as the first-contact point of care, one key problem facing the reforms in China.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary Background The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is ...unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. Methods We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III–IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18–59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov , number NCT01245959. Findings Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38–49), 3-year failure-free survival was 80% (95% CI 75–85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66–78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48–0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 42% vs 17 7%), leucopenia (98 41% vs 41 17%), and stomatitis (98 41% vs 84 35%). Interpretation Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. Funding Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).
Summary Background Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence ...of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. Methods Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON QFT) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. Findings 21 022 (90%) of 23 483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend <0·0001). Rates of latent tuberculosis infection were higher for men than women (p<0·0001). Overall agreement between the tuberculin skin test and the QFT test was moderate (81·06%; kappa coefficient 0·485), with skin-test-only positive results associated with the presence of BCG scar, male sex, and ages of 60 years and older, and QFT-only positive results associated with male sex and ages of 60 years and older. Interpretation On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. Funding The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.
Presbyopia, age-related decline in near vision, is the most common cause of vision impairment globally, but no trials have assessed its workplace effects. We aimed to study the effect of near glasses ...on the productivity of tea workers with presbyopia.
This randomised trial was done in tea pickers aged 40 years or older in Assam, India, with unaided near visual acuity (NVA) lower than 6/12 in both eyes, correctable to 6/7·5 with near glasses; unaided distance vision 6/7·5 or greater; and no eye disease. Participants were randomly assigned (1:1) to receive free glasses optimising NVA at working distance (cost including delivery US$10·20 per person), either immediately (intervention group) or at closeout (control group). Participants were stratified by age, sex, and productivity. The primary outcome (investigator-masked) was the difference between groups in the change in mean daily weight of tea picked (productivity), between the 4-week baseline period (June, 2017) and the 11-week evaluation period (July 24, 2017, to Oct 7, 2017). Workers' income was tied to their productivity. Compliance with study glasses was assessed at seven unannounced visits. Results were analysed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT03228199.
Between July 3, 2017, and July 15, 2017, 1297 (48·1%) of 2699 permanent workers met the age criteria and consented for eye examinations. 751 (57·9%) fulfilled vision criteria and were randomly assigned to the intervention (n=376) or control (n=375) groups. Groups did not differ substantially in baseline characteristics. No participants owned glasses at baseline, 707 (94·1%) received the allocated intervention, and all were followed up and analysed. Between the baseline and evaluation periods, mean productivity in the intervention group increased from 25·0 kg per day to 34·8 kg per day (an increase of 9·84 kg per day), a significantly higher increase than in the control group (from 26·0 kg per day to 30·6 kg per day; an increase of 4·59 kg per day), corresponding to a between-group difference of 5·25 kg per day (95% CI 4·50–5·99; 21·7% relative productivity increase; effect size 1·01 95% CI 0·86–1·16; p<0·0001). Intervention-group compliance with study glasses reached 84·5% by closeout. Regression model predictors of greater productivity increase included intervention group membership (5·25 kg per day 95% CI 4·60–5·91, p<0·0001) and, among intervention participants, older age (p=0·039) and better compliance with the intervention (p<0·0001).
A substantial productivity increase was achieved in this rural cohort by providing glasses to correct presbyopia, with little cost and high intervention uptake.
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...ED visits and unplanned hospital readmissions result from complications of cancer or its treatment, other comorbidities, or symptoms near the end of life 7-9. ...some visits that were cancer ...related may have been missed, and some visits that were not cancer related may have been included.
Improved markers for predicting recurrence are needed to stratify patients with localised (stage I–III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel ...assay integrating three modalities—clinical, genomic, and histopathological—to improve the predictive accuracy for localised renal cell carcinoma recurrence.
In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI).
The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825–0·876 vs 0·608–0·793; p<0·05). The RFI of patients with low stage or grade is usually better than that of patients with high stage or grade; however, the RFI in the multimodal recurrence score-defined high-risk stage I and II group was shorter than in the low-risk stage III group (hazard ratio HR 4·57, 95% CI 2·49–8·40; p<0·0001), and the RFI of the high-risk grade 1 and 2 group was shorter than in the low-risk grade 3 and 4 group (HR 4·58, 3·19–6·59; p<0·0001).
Our multimodal recurrence score is a practical and reliable predictor that can add value to the current staging system for predicting localised renal cell carcinoma recurrence after surgery, and this combined approach more precisely informs treatment decisions about adjuvant therapy.
National Natural Science Foundation of China, and National Key Research and Development Program of China.
Abstract Background: S -adenosylmethionine (SAMe) is an endogenous molecule that plays an important role in cellular metabolism. Despite being widely used as a dietary supplement with claimed ...benefits for numerous conditions, there is little information about the pharmacokinetic properties of exogenous SAMe. Objectives: One aim of this study was to characterize the pharmacokinetic properties of SAMe after administration of single and multiple doses of orally and intravenously administered SAMe tosylate disulfate (STD) in healthy male and female Chinese volunteers. Because men have higher erythrocyte levels of endogenous SAMe than do women, we also assessed the effects of sex on the disposition of SAMe. Methods: A simple and sensitive assay for SAMe based on liquid chromatography-mass spectrometry using selected-ion monitoring of analyte and acyclovir as internal standard was developed and validated. The assay was used to study the pharmacokinetic properties of SAMe. STD was administered as single and multiple doses of enteric-coated tablets and IV infusion of STD to groups of healthy native Chinese volunteers. After an overnight fast, male and female Chinese volunteers were assigned to receive STD 1000 mg for 5 days, either in enteric-coated tablet formulation or as a 250-mL IV infusion. Blood samples were collected 24 hours after the first and last dose and used for determining plasma SAMe concentrations and pharmacokinetic parameters. For the oral formulation, SAMe concentrations were corrected for concentrations of endogenous SAMe. Pharmacokinetic parameters were calculated for men and women separately and for the total group of volunteers. Adverse events were monitored using a physician during blood collection and by spontaneous reporting. Results: Twenty healthy volunteers were enrolled (oral formulation: 5 men, 5 women; mean SD age, 24.1 4.7 years range, 21–37 years; mean SD weight, 59.9 4.8 kg range, 54–70 kg; IV formulation: 5 men, 5 women; mean SD age, 22.6 1.8 years range, 21–27 years; mean SD weight, 59.5 5.4 kg range, 53–67 kg). None of the between-sex differences in SAMe pharmacokinetic properties were significant. The (mean SD) pharmacokinetic properties of singledose oral SAMe in men and women, respectively, were as follows: Cmax , 2.37 (1.58) and 2.50 (1.83) μmol/L; Tmax , 5.40 (1.14) and 5.20 (1.48) hours; AUC0-24 , 8.56 (5.16) and 10.3 (8.0) μmol/L/h; and t1/2β , 6.06 (1.80) and 6.28 (2.60) hours. Corresponding values with the single-dose IV formulation were: Cmax , 127 (49) and 211 (94) μmol/L; Tmax , 1.90 (0.22) and 1.60 (0.22) hours; AUC0-24 , 329 (84) and 480 (176) μmol/L/h; and t1/2β , 4.34 (0.57) and 3.83 (0.78) hours. The single-dose oral:IV ratios of AUC0-24 in men and women, respectively, were 2.60% and 2.14% (degrees of fluctuation: 4.96 1.77 and 9.49 0.91). The pharmacokinetic properties of multiple-dose oral and IV SAMe were not significantly different from those with single-dose administration. None of the volunteers reported any adverse events during the study. Conclusions: In this small study in healthy Chinese volunteers, there were no significant differences in the pharmacokinetic parameters of SAMe between men and women or between single- and multiple-dose administration of STD 1000 mg administered orally or intravenously. No evidence of accumulation of SAMe in plasma was found on multiple dosing. Both enteric-coated tablets and the IV infusion were well tolerated in these volunteers.
Background Intracranial arterial stenosis is a common cause of ischemic stroke in Asians. We therefore sought to explore the relationship of brachial-ankle pulse wave velocity and intracranial ...arterial stenosis in 834 stroke-free hypertensive patients. Methods Intracranial arterial stenosis was evaluated through computerized tomographic angiography. Brachial-ankle pulse wave velocity was measured by an automated cuff device. Results The top decile of brachial-ankle pulse wave velocity was significantly associated with intracranial arterial stenosis ( P = .027, odds ratio = 1.82; 95% confidence interval: 1.07-3.10). The patients with the top decile of brachial-ankle pulse wave velocity showed 56% higher risk for the presence of intracranial arterial stenosis to the whole population, which was more significant in patients younger than 65 years old. We also found that brachial-ankle pulse wave velocity related to both intracranial arterial stenosis and homocysteine. Conclusion Our study showed the association of brachial-ankle pulse wave velocity with asymptomatic intracranial arterial stenosis in hypertension patients, especially in relative younger subjects. Brachial-ankle pulse wave velocity might be a relatively simple and repeatable measurement to detect hypertension patients in high risk of intracranial arterial stenosis.
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