Summary Background Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of ...AKI and assess the availability of diagnosis and treatment in China. Methods We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and National Bureau of Statistics. Findings Of 2 223 230 patients admitted to the 44 hospitals screened in 2013, 154 950 (7·0%) were suspected of having AKI by electronic screening, of whom 26 086 patients (from 374 286 total admissions) were reviewed with medical records to confirm the diagnosis of AKI. The detection rate of AKI was 0·99% (3687 of 374 286) by KDIGO criteria and 2·03% (7604 of 374 286) by expanded criteria, from which we estimate that 1·4–2·9 million people with AKI were admitted to hospital in China in 2013. The non-recognition rate of AKI was 74·2% (5608 of 7555 with available data). Renal referral was done in 21·4% (1625 of 7604) of the AKI cases, and renal replacement therapy was done in 59·3% (531 of 896) of those who had the indications. Delayed AKI recognition was an independent risk factor for in-hospital mortality, and renal referral was an independent protective factor for AKI under-recognition and mortality Interpretation AKI has become a huge medical burden in China, with substantial underdiagnosis and undertreatment. Nephrologists should take the responsibility for leading the battle against AKI. Funding National 985 Project of China, National Natural Science Foundation of China, Beijing Training Program for Talents, International Society of Nephrology Research Committee, and Bethune Fund Management Committee.
Summary Background The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated ...glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. Methods We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1·73 m2 or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. Findings 50 550 people were invited to participate, of whom 47 204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1·73 m2 was 1·7% (95% CI 1·5–1·9) and of albuminuria was 9·4% (8·9–10·0). The overall prevalence of chronic kidney disease was 10·8% (10·2–11·3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119·5 million (112·9–125·0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16·9% 15·1–18·7) and southwest (18·3% 16·4–20·4) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. Interpretation Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. Funding The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation.
Summary Background MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma. Methods ...We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival. Findings 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues. A signature of five miRNAs, each significantly associated with DFS, was identified in the training set. We calculated a risk score from the signature and classified patients as high risk or low risk. Compared with patients with low-risk scores, patients with high risk scores in the training set had shorter DFS (hazard ratio HR 2·73, 95% CI 1·46–5·11; p=0·0019), DMFS (3·48, 1·57–7·75; p=0·0020), and overall survival (2·48, 1·24–4·96; p=0·010). We noted equivalent findings in the internal validation set for DFS (2·47, 1·32–4·61; p=0·0052), DMFS (2·28, 1·09–4·80; p=0·030), and overall survival (2·87, 1·38–5·96; p=0·0051) and in the independent set for DFS (3·16, 1·65–6·04; p=0·0011), DMFS (2·39, 1·05–5·42; p=0·037), and overall survival (3·07, 1·34–7·01; p=0·0082). The five-miRNA signature was an independent prognostic factor. A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set (area under receiver operating characteristics 0·68 95% CI 0·60–0·76 vs 0·60 0·52–0·67; p=0·013), the internal validation set (0·70 0·61–0·78 vs 0·61 0·54–0·68; p=0·012), and the independent set (0·70 0·62–0·78 vs 0·63 0·56–0·69; p=0·032). Interpretation Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression. Funding Science Foundation of Chinese Ministry of Health, National Natural Science Foundation of China, Pearl River Scholar Funded Scheme, Guangdong Key Scientific and Technological Innovation Program, Guangdong Natural Science Foundation, Fundamental Research Funds for the Central Universities.
Summary Background Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy ...and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC. Methods We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according to EGFR mutation type, histological subtype (adenocarcinoma vs non-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov , number NCT00874419 , and has completed enrolment; patients are still in follow-up. Findings 83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 95% CI 10.58–16.53 vs 4.6 4.21–5.42 months; hazard ratio 0.16, 95% CI 0.10–0.26; p<0.0001). Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib (including neutropenia in 30 42% of 72 patients and thrombocytopenia in 29 40% patients on chemotherapy vs no patients with either event on erlotinib); the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (three 4% of 83 patients) and skin rash (two 2% patients). Chemotherapy was also associated with increased treatment-related serious adverse events (ten 14% of 72 patients decreased platelet count, n=8; decreased neutrophil count, n=1; hepatic dysfunction, n=1 vs two 2% of 83 patients both hepatic dysfunction). Interpretation Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability. These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC. Funding F Hoffmann-La Roche Ltd (China); Science and Technology Commission of Shanghai Municipality.
Objective To investigate the efficacy and safety of selective head cooling with mild systemic hypothermia in hypoxic-ischemic encephalopathy (HIE) in newborn infants. Study design Infants with HIE ...were randomly assigned to the selective head cooling or control group. Selective head cooling was initiated within 6 hours after birth to a nasopharyngeal temperature of 34° ± 0.2°C and rectal temperature of 34.5° to 35.0°C for 72 hours. Rectal temperature was maintained at 36.0° to 37.5°C in the control group. Neurodevelopmental outcome was assessed at 18 months of age. The primary outcome was a combined end point of death and severe disability. Results One hundred ninety-four infants were available for analysis (100 and 94 infants in the selective head cooling and control group, respectively). For the selective head cooling and control groups, respectively, the combined outcome of death and severe disability was 31% and 49% (OR: 0.47; 95% CI: 0.26-0.84; P = .01), the mortality rate was 20% and 29% (OR:0.62; 95% CI: 0.32-1.20; P = .16), and the severe disability rate was 14% (11/80) and 28% (19/67) (OR: 0.40; 95% CI: 0.17-0.92; P = .01). Conclusions Selective head cooling combined with mild systemic hypothermia for 72 hours may significantly decrease the combined outcome of severe disability and death, as well as severe disability.
Summary Background Platinum chemotherapy has a role in the treatment of metastatic triple-negative breast cancer but its full potential has probably not yet been reached. We assessed whether a ...cisplatin plus gemcitabine regimen was non-inferior to or superior to paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer. Methods For this open-label, randomised, phase 3, hybrid-designed trial undertaken at 12 institutions or hospitals in China, we included Chinese patients aged 18–70 years with previously untreated, histologically confirmed metastatic triple-negative breast cancer, and an ECOG performance status of 0–1. These patients were randomly assigned (1:1) to receive either cisplatin plus gemcitabine (cisplatin 75 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8) or paclitaxel plus gemcitabine (paclitaxel 175 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8) given intravenously every 3 weeks for a maximum of eight cycles. Randomisation was done centrally via an interactive web response system using block randomisation with a size of eight, with no stratification factors. Patients and investigator were aware of group assignments. The primary endpoint was progression-free survival and analyses were based on all patients who received at least one dose of assigned treatment. The margin used to establish non-inferiority was 1·2. If non-inferiority of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine was achieved, we would then test for superiority. The trial is registered with ClinicalTrials.gov , number NCT01287624. Findings From Jan 14, 2011, to Nov 14, 2013, 240 patients were assessed for eligibility and randomly assigned to treatment (120 in the cisplatin plus gemcitabine group and 120 in the paclitaxel plus gemcitabine group). 236 patients received at least one dose of assigned chemotherapy and were included in the modified intention-to-treat analysis (118 per group). After a median follow-up of 16·3 months (IQR 14·4–26·8) in the cisplatin plus gemcitabine group and 15·9 months (10·7–25·4) in the paclitaxel plus gemcitabine group, the hazard ratio for progression-free survival was 0·692 (95% CI 0·523–0·915; pnon-inferiority <0·0001, psuperiority =0·009, thus cisplatin plus gemcitabine was both non-inferior to and superior to paclitaxel plus gemcitabine. Median progression-free survival was 7·73 months (95% CI 6·16–9·30) in the cisplatin plus gemcitabine group and 6·47 months (5·76–7·18) in the paclitaxel plus gemcitabine group. Grade 3 or 4 adverse events that differed significantly between the two groups included nausea (eight 7% vs one <1%), vomiting (13 11% vs one <1%), musculoskeletal pain (none vs ten 8%), anaemia (39 33% vs six 5%), and thrombocytopenia (38 32% vs three 3%), for the cisplatin plus gemcitabine compared with the paclitaxel plus gemcitabine groups, respectively. In addition, patients in the cisplatin plus gemcitabine group had significantly fewer events of grade 1–4 alopecia (12 10% vs 42 36%) and peripheral neuropathy (27 23% vs 60 51%), but more grade 1–4 anorexia (33 28% vs 10 8%), constipation (29 25% vs 11 9%), hypomagnesaemia (27 23% vs five 4%), and hypokalaemia (10 8% vs two 2%). Serious drug-related adverse events were seen in three patients in the paclitaxel plus gemcitabine group (interstitial pneumonia, anaphylaxis, and severe neutropenia) and four in the cisplatin plus gemcitabine group (pathological bone fracture, thrombocytopenia with subcutaneous haemorrhage, severe anaemia, and cardiogenic syncope). There were no treatment-related deaths. Interpretation Cisplatin plus gemcitabine could be an alternative or even the preferred first-line chemotherapy strategy for patients with metastatic triple-negative breast cancer. Funding Shanghai Natural Science Foundation.
Summary Background Nanoliposomal irinotecan showed activity in a phase 2 study in patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapies. We ...assessed the effect of nanoliposomal irinotecan alone or combined with fluorouracil and folinic acid in a phase 3 trial in this population. Methods We did a global, phase 3, randomised, open-label trial at 76 sites in 14 countries. Eligible patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy were randomly assigned (1:1) using an interactive web response system at a central location to receive either nanoliposomal irinotecan monotherapy (120 mg/m2 every 3 weeks, equivalent to 100 mg/m2 of irinotecan base) or fluorouracil and folinic acid. A third arm consisting of nanoliposomal irinotecan (80 mg/m2 , equivalent to 70 mg/m2 of irinotecan base) with fluorouracil and folinic acid every 2 weeks was added later (1:1:1), in a protocol amendment. Randomisation was stratified by baseline albumin, Karnofsky performance status, and ethnic origin. Treatment was continued until disease progression or intolerable toxic effects. The primary endpoint was overall survival, assessed in the intention-to-treat population. The primary analysis was planned after 305 events. Safety was assessed in all patients who had received study drug. This trial is registered at ClinicalTrials.gov , number NCT01494506. Findings Between Jan 11, 2012, and Sept 11, 2013, 417 patients were randomly assigned either nanoliposomal irinotecan plus fluorouracil and folinic acid (n=117), nanoliposomal irinotecan monotherapy (n=151), or fluorouracil and folinic acid (n=149). After 313 events, median overall survival in patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid was 6·1 months (95% CI 4·8–8·9) vs 4·2 months (3·3–5·3) with fluorouracil and folinic acid (hazard ratio 0·67, 95% CI 0·49–0·92; p=0·012). Median overall survival did not differ between patients assigned nanoliposomal irinotecan monotherapy and those allocated fluorouracil and folinic acid (4·9 months 4·2–5·6 vs 4·2 months 3·6–4·9; 0·99, 0·77–1·28; p=0·94). The grade 3 or 4 adverse events that occurred most frequently in the 117 patients assigned nanoliposomal irinotecan plus fluorouracil and folinic acid were neutropenia (32 27%), diarrhoea (15 13%), vomiting (13 11%), and fatigue (16 14%). Interpretation Nanoliposomal irinotecan in combination with fluorouracil and folinic acid extends survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma who previously received gemcitabine-based therapy. This agent represents a new treatment option for this population. Funding Merrimack Pharmaceuticals.
Abstract Background Partial reimbursement of antivirals for hepatitis B virus (HBV) was implemented in Beijing, China, on July 1, 2011. In previous studies, we found that partial reimbursement ...significantly improved antiviral drug use among insured patients with chronic HBV infection but not among patients who paid out-of-pocket. Also, after the new policy entecavir, a suggested first-line agene have replaced with adefivor, a predominantly used agents before reimbursement and become the most widely used drug. The aim of this study was to assess the effectiveness and cost-effectiveness of the reimbursement among patients with chronic HBV infection. Methods This retrospective cohort was based on electronic claims from Beijing You'an Hospital between Jan 14, 2008, and Dec 30, 2012. Age, sex, insurance status, antiviral drug claims, and on-study laboratory test of a retrospective cohort of 92 776 outpatients and 2774 inpatients with non-cirrhotic chronic HBV infection of Beijing residents were retrieved. We enrolled patients with chronic HBV infection who received adefovir, which was the most common used for patients with chronic HBV infection before the reimbursement, or entecavir, which was the most frequently used among insured patients after the reimbursement. Patients were not included if they were coinfected with other virus infection or severe diseases. The antiviral drug use data during an 18 month period prior to the enrollment were used to define naive patients. Medication possession ratio (MPR) was used to assess adherence, defined as the proportion of days within an observation period for which antiviral drugs were supplied. We used naive patients and applied the Markov model to assess cost-effectiveness for specific antivirals with different adherence rates. The study was approved by the Ethical Review Committee of the Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Beijing You'an Hospital of Capital Medical University. Findings Between Jan 1, 2009 and Dec 31, 2012, we enrolled 7665 outpatients who received adefivor and 5439 patients who received entecavir. MPR of adefivor remained constant in insured patients (84·4% SD 23·1% before reimbursement vs 85·8% 20.8% after reimbursement), whereas the MPR of entecavir increased greatly from 79·7% (28·7%) before reimbursement to 89·1% (20·9%) after reimbursement among insured patients. The policy significantly improved adherence among insured patients compared with patients who paid out-of-pocket (odds ratio 1·6 95% CI 1·2–2·4), even after adjusting for age, sex, disease severity, and antiviral drugs. Compared with MPR less than 0·5, naive patients with MPR of 0·8 or more had the highest HBV DNA response rate, with hazard ratio of 2·0 (95% CI 1·4–2·9) for HB e antigen positive patients and 1·6 (95% CI 1·2–2·1) for HB e antigen negative patients. Patients who adhered to entecavir treatment gained the longest quality-adjusted life years, and entecavir treatment was identified as the most cost-effectiveness option. Compared with patients who received adefovir or patients who adhered poorly to entecavir treatment, treatment among patients who adhered well to entecavir treatment had an incremental cost-effectiveness ratio, which was less than the common reference thresholds based on GDP per person (¥87 091). Interpretation For patients with chronic HBV infection, the partial reimbursement of drugs to an acceptable cost might effectively improve antiviral treatment outcomes by increasing antiviral use, especially the use of first-line drugs, as well as adherence. Funding Ministry of National Science and Technology of China (2012ZX10004904, 2013ZX10002002006002).
Summary Background Outcomes are poor for patients with recurrent or metastatic nasopharyngeal carcinoma and no well established first-line chemotherapy is available for the disease. We compared the ...efficacy and safety of gemcitabine plus cisplatin versus fluorouracil plus cisplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. Methods In this multicentre, randomised, open-label, phase 3 trial, patients with recurrent or metastatic nasopharyngeal carcinoma were recruited from 22 hospitals in China. Key inclusion criteria were Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function, and measurable lesions according to Response Evaluation Criteria in Solid Tumors version 1.1. Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine (1 g/m2 intravenously on days 1 and 8) and cisplatin (80 mg/m2 intravenously on day 1), or fluorouracil (4 g/m2 in continuous intravenous infusion over 96 h) and cisplatin (80 mg/m2 on day 1 given intravenously) once every 3 weeks for a maximum of six cycles. The randomisation was done centrally via an interactive phone response system using block randomisation with a size of six. The primary endpoint was progression-free survival assessed by the independent image committee in the intention-to-treat population. Safety analyses were done in patients who received at least one cycle of study drug. This study is ongoing and is registered with ClinicalTrials.gov , number NCT01528618. Findings Between Feb 20, 2012, and Oct 30, 2015, 362 patients were randomly assigned to a group (181 to the gemcitabine plus cisplatin group and 181 to the fluorouracil plus cisplatin group). Median follow-up time for progression-free survival was 19·4 months (IQR 12·1–35·6). The median progression-free survival was 7·0 months (4·4–10·9) in the gemcitabine group and 5·6 months (3·0–7·0) in the fluorouracil group (hazard ratio HR 0·55 95% CI 0·44–0·68; p<0·0001). A total of 180 patients in the gemcitabine group and 173 patients in the fluorouracil group were included in the safety analysis. Significantly different treatment-related grade 3 or 4 adverse events between the gemcitabine and fluorouracil groups were leucopenia (52 29% vs 15 9%; <0·0001), neutropenia (41 23% vs 23 13%; p=0·0251), thrombocytopenia (24 13% vs three 2%; p=0·0007), and mucosal inflammation (0 vs 25 14%; <0·0001). Serious treatment-related adverse events occurred in seven (4%) patients in the gemcitabine group and ten (6%) in the fluorouracil group. Six (3%) patients in the gemcitabine group and 14 (8%) patients in the fluorouracil group discontinued treatment because of drug-related adverse events. No treatment-related deaths occurred in either group. Interpretation Gemcitabine plus cisplatin prolongs progression-free survival in patients with recurrent or metastatic nasopharyngeal carcinoma. The results establish gemcitabine plus cisplatin as the standard first-line treatment option for this population. Funding The 5010 Clinical Research Foundation of Sun Yat-sen University.
We present a new method for remote sensing image segmentation, which utilizes both spectral and texture information. Linear filters are used to provide enhanced spatial patterns. For each pixel ...location, we compute combined spectral and texture features using local spectral histograms, which concatenate local histograms of all input bands. We regard each feature as a linear combination of several representative features, each of which corresponds to a segment. Segmentation is given by estimating combination weights, which indicate segment ownership of pixels. We present segmentation solutions where representative features are either known or unknown. We also show that feature dimensions can be greatly reduced via subspace projection. The scale issue is investigated, and an algorithm is presented to automatically select proper scales, which does not require segmentation at multiple-scale levels. Experimental results demonstrate the promise of the proposed method.
