The eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage classification (TNM) for nasopharyngeal carcinoma (NPC) was launched. It ...remains unknown if incorporation of nonanatomic factors into the stage classification would better predict survival. We prospectively recruited 518 patients with nonmetastatic NPC treated with radical intensity‐modulated radiation therapy ± chemotherapy based on the eighth edition TNM. Recursive partitioning analysis (RPA) incorporating pretreatment plasma Epstein–Barr virus (EBV) DNA derived new stage groups. Multivariable analyses to calculate adjusted hazard ratios (AHRs) derived another set of stage groups. Five‐year progression‐free survival (PFS), overall survival (OS) and cancer‐specific survival (CSS) were: Stage I (PFS 100%, OS 90%, CSS 100%), II (PFS 88%, OS 84%, CSS 95%), III (PFS 84%, OS 84%, CSS 90%) and IVA (PFS 71%, OS 75%, CSS 80%) (p < 0.001, p = 0.066 and p = 0.002, respectively). RPA derived four new stages: RPA‐I (T1–T4 N0–N2 & EBV DNA <500 copies per mL; PFS 94%, OS 89%, CSS 96%), RPA‐II (T1–T4 N0–N2 & EBV DNA ≥500 copies per mL; PFS 80%, OS 83%, CSS 89%), RPA‐III (T1–T2 N3; PFS 64%, OS 83%, CSS 83%) and RPA‐IVA (T3–T4 N3; PFS 63%, OS 60% and CSS 68%) (all with p < 0.001). AHR using covariate adjustment also yielded a valid classification (I: T1–T2 N0–N2; II: T3–T4 N0–N2 or T1–T2 N3 and III: T3–T4 N3) (all with p < 0.001). However, RPA stages better predicted survival for PS and CSS after bootstrapping replications. Our RPA‐based stage groups revealed better survival prediction compared to the eighth edition TNM and the AHR stage groups.
What's new?
The AJCC/UICC TNM stage classification is the most widely accepted common language to describe the magnitude and spread of cancer. However, a new pretreatment staging system comprising both anatomic and non‐anatomic factors is warranted to improve survival prediction. Here, the authors propose new stage groups incorporating pretreatment plasma Epstein–Barr virus (EBV) DNA for non‐metastatic nasopharyngeal carcinoma (NPC). Their prospective study measuring pretreatment plasma EBV DNA in 518 completely staged non‐metastatic NPC patients who were later treated with intensity‐modulated radiation therapy with/without adjunct chemotherapy demonstrates significantly better survival prediction with the newly proposed stages as compared to the current edition TNM.
A raft of concessions for business aimed at not only keeping companies viable, but positioning them for future economic recovery has been outlined by the Singapore government in its 2009 budget. ...Finance minister Tharman Shanmugaratnam outlined a S$20.5 billion resilience package aimed at helping Singapore through the crisis. Here are the highlights of the tax measures: The current Singapore corporate tax rate of 18% will drop to 17% with effect from year of assessment (YA) 2010. A 40% property tax rebate for industrial and commercial properties will be provided for 2009. The writing down period in respect of capital expenditure incurred by a media and digital entertainment company or partnership acquiring IPRs will be reduced and accelerated from five years to two years, subject to conditions. A property tax rebate of 40% for owner-occupied residential properties for 2009 will be granted.
Patients with chronic hepatitis B (CHB) are aging because of improved survival under better health care. This has an important implication on the choice of antiviral treatment (AVT), given that ...long‐term safety would be a concern in the presence of multiple comorbidities. We aimed to determine the prevalence of key comorbidities and concomitant medications in a territory‐wide CHB cohort in Hong Kong in 2000‐2017. CHB patients who have been under the care at primary, secondary, and tertiary medical centers in the public sector were identified through the Clinical Data Analysis and Reporting System of the Hospital Authority, Hong Kong. The demographics and prevalence of key comorbidities, including diabetes mellitus, hypertension, chronic kidney disease, osteopenia/osteoporosis based on diagnosis codes, relevant medications, and/or laboratory parameters, were determined according to CHB patients’ first appearance in four time periods: 2000‐2004, 2005‐2009, 2010‐2013, and 2014‐2017. In the final analysis, 135,395 CHB patients were included; the mean age increased with time: 41 ± 15 years in 2000‐2004; 46 ± 17 years in 2005‐2009; 51 ± 16 years in 2010‐2013; and 55 ± 15 years in 2014‐2017. There was a trend of increasing prevalence of several common comorbidities over the four periods: hypertension 25.5%, 23.8%, 27.2%, and 28.6%; diabetes mellitus 10.6%, 12.5%, 16.1%, and 20.1%; cardiovascular disease 12.5%, 16.9%, 20.9%, and 22.2%; and malignancy 7.0%, 13.2%, 17.3%, and 23.6%, respectively (all P < 0.001). Conclusion: CHB patients are getting older with increasing prevalence of common comorbidities. These comorbidities should be taken into account when choosing AVT.
This dissertation investigates the contextual and institutional factors that affects the growth of Chinese baby boomer churches in Toronto. Boomer churches are churches whose target audiences are ...people born between 1946-1964. The Chinese boomers in our study were born overseas in Hong Kong or China and they immigrated to Canada in the past twenty years. The traditional Chinese culture, the boomer Chinese culture and the North American boomers culture are compared and contrasted and a cultural relevant strategy for the Chinese boomer churches is developed. The first part of the dissertation examines the contextual growth factor. Basic Chinese worldview is studied and its effects on the development of the character of Chinese people are explored. The historical development of the Chinese boomer culture in Canada is traced and a sociological and culturally relevant strategy for a Chinese boomer church is proposed by analyzing and synthesizing current research findings on Caucasian and Chinese church growth. The second part of the dissertation explores the biblical principles of the true nature reality, priority and purpose of life for the boomer generation. A case study from the Richmond Hill Chinese Community Church illustrates how this church incorporates cultural and biblical principles into the philosophy of ministry and the growth and non-growth of this church is analyzed. A number of key growth factors for the Chinese boomer churches are then developed. Finally future plans and evaluation for the next five years are suggested for the effective growth of this church.
ABSTRACT
BACKGROUND
Insufficient sleep among students is a major school health problem. School‐based sleep education programs tailored to reach large number of students may be one of the solutions. A ...systematic review and meta‐analysis was conducted to summarize the programs' effectiveness and current status.
METHODS
Electronic databases were searched up until May 2015. Randomized controlled trials of school‐based sleep intervention among 10‐ to 19‐year‐old students with outcome on total sleep duration were included. Methodological quality of the studies was assessed using the Cochrane's risk of bias assessment.
RESULTS
Seven studies were included, involving 1876 students receiving sleep education programs and 2483 attending classes‐as‐usual. Four weekly 50‐minute sleep education classes were most commonly provided. Methodological quality was only moderate, with a high or an uncertain risk of bias in several domains. Compared to classes‐as‐usual, sleep education programs produced significantly longer weekday and weekend total sleep time and better mood among students at immediate post‐treatment, but the improvements were not maintained at follow‐up.
CONCLUSIONS
Limited by the small number of studies and methodological limitations, the preliminary data showed that school‐based sleep education programs produced short‐term benefits. Future studies should explore integrating sleep education with delayed school start time or other more effective approaches.
Background & Aims Little is known about the validity of hepatocellular carcinoma (HCC) risk scores derived from treatment-naïve patients with chronic hepatitis B for patients treated with entecavir. ...Methods We performed a retrospective-prospective cohort study of 1531 patients with chronic hepatitis B (age, 51 ± 12 years; 1099 male; 332 with clinical cirrhosis) who were treated with entecavir 0.5 mg daily for at least 12 months at Prince of Wales Hospital in Hong Kong from December 2005 to August 2012. The patients were assessed once every 3 to 6 months for symptoms, drug history, and adherence; blood samples were collected for biochemical analyses. We validated 3 HCC risk scores (CU-HCC, GAG-HCC, and REACH-B scores) based on data collected when patients began treatment with entecavir and 2 years later. Results After 42 ± 13 months of follow-up, 47 patients (2.9%) developed HCC. The 5-year cumulative incidence of HCC was 4.3% (95% confidence interval CI, 3.6%–5.0%). Older age, presence of cirrhosis, and virologic remission after 24 months or more of therapy were independently associated with HCC in the entire cohort; advanced age and hypoalbuminemia were associated with HCC in patients without cirrhosis. The area under the receiver operating characteristic curves (AUCs) for baseline CU-HCC, GAG-HCC, and REACH-B scores for HCC were 0.80 (95% CI, 0.75–0.86), 0.76 (95% CI, 0.70–0.82), and 0.71 (95% CI, 0.62–0.81), respectively; the time-dependent AUCs 1 to 4 years after patients started treatment were comparable to those at baseline. The cutoff value of the baseline CU-HCC score identified patients who would develop HCC with 93.6% sensitivity and 47.8% specificity, the baseline GAG-HCC score with 55.3% sensitivity and 78.9% specificity, and the baseline REACH-B score with 95.2% sensitivity and 16.5% specificity. Compared with patients with CU-HCC scores <5 at baseline, those with CU-HCC scores that either decreased from ≥5 to <5 or remained ≥5 had a higher risk of HCC (5-year cumulative incidences, 0% vs 3.9% and 7.3%; P = .002 and P < .001, respectively). Conclusions The CU-HCC, GAG-HCC, and REACH-B HCC risk scores accurately predict which patients with chronic hepatitis B treated with entecavir will develop HCC.
Hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels are members of the voltage‐gated cation channel family known to be expressed in the heart and central nervous system. Ivabradine, a ...small molecule HCN channel‐blocker, is FDA‐approved for clinical use as a heart rate‐reducing agent. We found that HCN2 and HCN3 are overexpressed in breast cancer cells compared with normal breast epithelia, and the high expression of HCN2 and HCN3 is associated with poorer survival in breast cancer patients. Inhibition of HCN by Ivabradine or by RNAi, aborted breast cancer cell proliferation in vitro and suppressed tumour growth in patient‐derived tumour xenograft models established from triple‐negative breast cancer (TNBC) tissues, with no evident side‐effects on the mice. Transcriptome‐wide analysis showed enrichment for cholesterol metabolism and biosynthesis as well as lipid metabolism pathways associated with ER‐stress following Ivabradine treatment. Mechanistic studies confirmed that HCN inhibition leads to ER‐stress, in part due to disturbed Ca2+ homeostasis, which subsequently triggered the apoptosis cascade. More importantly, we investigated the synergistic effect of Ivabradine and paclitaxel on TNBC and confirmed that both drugs acted synergistically in vitro through ER‐stress to amplify signals for caspase activation. Combination therapy could suppress tumour growth of xenografts at much lower doses for both drugs. In summary, our study identified a new molecular target with potential for being developed into targeted therapy, providing scientific grounds for initiating clinical trials for a new treatment regimen of combining HCN inhibition with chemotherapy.
Overexpression of HCN provides advantages for the survival and proliferation of cancer cells. The addition of Ivabradine blocks HCN channels and affects intracellular homeostasis of Ca2+. Subsequently, this induces ER‐stress and triggers apoptosis. Also, it makes the cancer cells become more sensitive to other chemotherapeutic agents.
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