The molecular bases of training adaptation

Skeletal muscle is a malleable tissue capable of altering the type and amount of protein in response to disruptions to cellular homeostasis. The process of exercise-induced adaptation in skeletal muscle involves a multitude of signalling mechanisms initiating replication of specific DNA genetic sequences, enabling subsequent translation of the genetic message and ultimately generating a series of amino acids that form new proteins. The functional consequences of these adaptations are determined by training volume, intensity and frequency, and the half-life of the protein. Moreover, many features of the training adaptation are specific to the type of stimulus, such as the mode of exercise. Prolonged endurance training elicits a variety of metabolic and morphological changes, including mitochondrial biogenesis, fast-to-slow fibre-type transformation and substrate metabolism. In contrast, heavy resistance exercise stimulates synthesis of contractile proteins responsible for muscle hypertrophy and increases in maximal contractile force output. Concomitant with the vastly different functional outcomes induced by these diverse exercise modes, the genetic and molecular mechanisms of adaptation are distinct. With recent advances in technology, it is now possible to study the effects of various training interventions on a variety of signalling proteins and early-response genes in skeletal muscle. Although it cannot presently be claimed that such scientific endeavours have influenced the training practices of elite athletes, these new and exciting technologies have provided insight into how current training techniques result in specific muscular adaptations, and may ultimately provide clues for future and novel training methodologies. Greater knowledge of the mechanisms and interaction of exercise-induced adaptive pathways in skeletal muscle is important for our understanding of the aetiology of disease, maintenance of metabolic and functional capacity with aging, and training for athletic performance. This article highlights the effects of exercise on molecular and genetic mechanisms of training adaptation in skeletal muscle.

The health effects of temperature : current estimates, future projections, and adaptation strategies

Climate change is expected to be one of the biggest global health threats in the 21st century. In response to changes in climate and associated extreme events, public health adaptation has become imperative. This thesis examined several key issues in this emerging research field. The thesis aimed to identify the climate-health (particularly temperature-health) relationships, then develop quantitative models that can be used to project future health impacts of climate change, and therefore help formulate adaptation strategies for dealing with climate-related health risks and reducing vulnerability. The research questions addressed by this thesis were: (1) What are the barriers to public health adaptation to climate change? What are the research priorities in this emerging field? (2) What models and frameworks can be used to project future temperature-related mortality under different climate change scenarios? (3) What is the actual burden of temperature-related mortality? What are the impacts of climate change on future burden of disease? and (4) Can we develop public health adaptation strategies to manage the health effects of temperature in response to climate change? Using a literature review, I discussed how public health organisations should implement and manage the process of planned adaptation. This review showed that public health adaptation can operate at two levels: building adaptive capacity and implementing adaptation actions. However, there are constraints and barriers to adaptation arising from uncertainty, cost, technologic limits, institutional arrangements, deficits of social capital, and individual perception of risks. The opportunities for planning and implementing public health adaptation are reliant on effective strategies to overcome likely barriers. I proposed that high priorities should be given to multidisciplinary research on the assessment of potential health effects of climate change, projections of future health impacts under different climate and socio-economic scenarios, identification of health cobenefits of climate change policies, and evaluation of cost-effective public health adaptation options. Heat-related mortality is the most direct and highly-significant potential climate change impact on human health. I thus conducted a systematic review of research and methods for projecting future heat-related mortality under different climate change scenarios. The review showed that climate change is likely to result in a substantial increase in heatrelated mortality. Projecting heat-related mortality requires understanding of historical temperature-mortality relationships, and consideration of future changes in climate, population and acclimatisation. Further research is needed to provide a stronger theoretical framework for mortality projections, including a better understanding of socioeconomic development, adaptation strategies, land-use patterns, air pollution and mortality displacement. Most previous studies were designed to examine temperature-related excess deaths or mortality risks. However, if most temperature-related deaths occur in the very elderly who had only a short life expectancy, then the burden of temperature on mortality would have less public health importance. To guide policy decisions and resource allocation, it is desirable to know the actual burden of temperature-related mortality. To achieve this, I used years of life lost to provide a new measure of health effects of temperature. I conducted a time-series analysis to estimate years of life lost associated with changes in season and temperature in Brisbane, Australia. I also projected the future temperaturerelated years of life lost attributable to climate change. This study showed that the association between temperature and years of life lost was U-shaped, with increased years of life lost on cold and hot days. The temperature-related years of life lost will worsen greatly if future climate change goes beyond a 2 °C increase and without any adaptation to higher temperatures. The excess mortality during prolonged extreme temperatures is often greater than the predicted using smoothed temperature-mortality association. This is because sustained period of extreme temperatures produce an extra effect beyond that predicted by daily temperatures. To better estimate the burden of extreme temperatures, I estimated their effects on years of life lost due to cardiovascular disease using data from Brisbane, Australia. The results showed that the association between daily mean temperature and years of life lost due to cardiovascular disease was U-shaped, with the lowest years of life lost at 24 °C (the 75th percentile of daily mean temperature in Brisbane), rising progressively as temperatures become hotter or colder. There were significant added effects of heat waves, but no added effects of cold spells. Finally, public health adaptation to hot weather is necessary and pressing. I discussed how to manage the health effects of temperature, especially with the context of climate change. Strategies to minimise the health effects of high temperatures and climate change can fall into two categories: reducing the heat exposure and managing the health effects of high temperatures. However, policy decisions need information on specific adaptations, together with their expected costs and benefits. Therefore, more research is needed to evaluate cost-effective adaptation options. In summary, this thesis adds to the large body of literature on the impacts of temperature and climate change on human health. It improves our understanding of the temperaturehealth relationship, and how this relationship will change as temperatures increase. Although the research is limited to one city, which restricts the generalisability of the findings, the methods and approaches developed in this thesis will be useful to other researchers studying temperature-health relationships and climate change impacts. The results may be helpful for decision-makers who develop public health adaptation strategies to minimise the health effects of extreme temperatures and climate change.

Malnutrition and its impact on cost of hospitalization, length of stay, readmission and 3-year mortality

Background & aims The confounding effect of disease on the outcomes of malnutrition using diagnosis-related groups (DRG) has never been studied in a multidisciplinary setting. This study aims to determine the impact of malnutrition on hospitalisation outcomes, controlling for DRG. Methods Subjective Global Assessment was used to assess the nutritional status of 818 patients within 48 hours of admission. Prospective data were collected on cost of hospitalisation, length of stay (LOS), readmission and mortality up to 3 years post-discharged using National Death Register data. Mixed model analysis and conditional logistic regression matching by DRG were carried out to evaluate the association between nutritional status and outcomes, with the results adjusted for gender, age and race. Results Malnourished patients (29%) had longer hospital stays (6.9±7.3 days vs. 4.6±5.6 days, p<0.001) and were more likely to be readmitted within 15 days (adjusted relative risk = 1.9, 95%CI 1.1–3.2, p=0.025). Within a DRG, the mean difference between actual cost of hospitalisation and the average cost for malnourished patients was greater than well-nourished patients (p=0.014). Mortality was higher in malnourished patients at 1 year (34% vs. 4.1 %), 2 years (42.6% vs. 6.7%) and 3 years (48.5% vs. 9.9%); p<0.001 for all. Overall, malnutrition was a significant predictor of mortality (adjusted hazard ratio = 4.4, 95%CI 3.3-6.0, p<0.001). Conclusions Malnutrition was evident in up to one third of inpatients and led to poor hospitalisation outcomes, even after matching for DRG. Strategies to prevent and treat malnutrition in the hospital and post-discharge are needed.

Estimating the Burden of Malignant Neoplasm in Shandong Province [山东省恶性肿瘤疾病负担研究]

Objective To make a comprehensive estimation of the burden of malignant neoplasm in Shandong province by the means of disability- adjusted life year (DALY) for the first time. Methods DALYs were calculated following the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability. We measured YLLs using the cancer mortality data of 19 Disease Surveillance Points (DSPs) in Shandong Province during 2000 and 2005. YLDs were estimated based on the cancer morbidity data of 6 Cancer Incidence Surveillance Points in Shandong Province in 2005. Results All cancers were responsible for 20.60 DALYs for every thousand population in Shandong Province (25.30 for men and 15.74 for women) . 94.3% of the losses were due to premature death and 5.7% to disability. 31.9% of the DALYs happened among 45~59 age group. The top 10 cancers for DALYs were lung cancer, liver cancer, stomach cancer, oesophagus cancer, colon/rectum cancer, breast cancer, leukemia, brain cancer, pancreas cancer and cervix uteri cancer in turn. The burden of major cancers such as lung cancer and liver cancer in Shandong were heavier than the global and national level. Conclusions he burden of disease of malignant neoplasm is mainly because of premature death. Lung cancer, liver cancer, stomach cancer and oesophagus cancer are the major cancers in Shandong Province and should be paid more attention to their prevention and control. Abstract in Chinese 目的 首次应用伤残调整寿命年(DALY)对山东省居民恶性肿瘤疾病负担进行综合评价. 方法 以2000-2005年山东省疾病监测系统的恶性肿瘤死亡资料和2005年山东省恶性肿瘤发病监测系统的发病资料为基础,利用世界卫生组织提供的专门公式,计算恶性肿瘤的YLLs、YLDs和DALYs,以此评价恶性肿瘤的疾病负担. 结果 山东省每千人每年因恶性肿瘤造成20.60个DALYs损失(男性25.30,女性15.74),其中,9413%为早死所致,5.7%因残疾所致:恶性肿瘤主要导致45～59岁人群的DALYs损失,占31.93%;恶性肿瘤疾病负担前10位依次为肺癌、肝癌、胃癌、食道癌、肠癌、乳腺癌、白血病、脑癌、胰腺癌和宫颈癌;山东省肺癌、肝癌等主要癌症疾病负担高于全球和全国水平. 结论 恶性肿瘤疾病负担主要由早死所致,肺癌、肝癌、胃癌和食道癌等主要癌症的防制地位十分突出.

Estimating the burden of malignant neoplasm on village residents in a mountainous area [山区农村居民恶性肿瘤疾病负担的估计]

Objective To make a comprehensive estimation of the burden of malignant neoplasm on village residents in Linqu County by the means of DALY (Disability-adjusted life year). Methods DALYs, YLLs and YLDs were calculated following the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability, based on the cancer registration data of Linqu villages during 1998-2004, in order to measure the burden of various caners. Results All cancers were responsible for 20.00 DALYs for every thousand population in Linqu County (24.82 for men and 14.96 for women). 92.5% of the losses were due to premature death and 7.5% to disability. 31.5% of the DALYs happened among 45-59 age group. The top 10 cancers for DALYs were stomach cancer, lung cancer, liver cancer, oesophagus cancer, leukemia,colon/rectum cancer, brain cancer, pancreas cancer, breast cancer and bone cancer in turn. Only stomach cancer, lung cancer and liver cancer together account for 69.3% of total DALYs due to malignant neoplasm. The burden of malignant neoplasm was on rising recent years. Conclusions The burden of disease of malignant neoplasm is mainly because of premature death. Stomach cancer, lung cancer and liver cancer lead to heavier burden than the global and national levels. Abstract in Chinese 目的 应用伤残调整寿命年(DALY)对临朐县农村恶性肿瘤疾病负担进行评价. 方法 以1998～2004年临朐县农村肿瘤登记资料为基础,利用全球疾病负担研究中使用的专门公式计算恶性肿瘤的YLLs、YLDs和DALYs,以此评价各类恶性肿瘤的疾病负担. 结果 临朐农村每千人每年因恶性肿瘤造成20.0个DALYs损失(男性24.82,女性14.96),其中92.5%为早死所致,7.5%因残疾所致;恶性肿瘤主要导致45～59岁人群的DALYs损失,占31.5%;恶性肿瘤疾病负担前10位依次为胃癌、肺癌、肝癌、食道癌、白血病、肠癌、脑癌、胰腺癌、乳腺癌和骨癌,其中仅胃癌、肺癌和肝癌三大肿瘤DALYs就占全部肿瘤的69.3%;临朐县农村恶性肿瘤疾病负担有进一步上升的趋势. 结论 恶性肿瘤疾病负担主要由早死所致,胃癌、肺癌、肝癌等主要癌症疾病负担高于全球和中国区水平.

Economic burden of malignant neoplasms in Shandong province [山东省恶性肿瘤经济负担分析]

Objective: To evaluate the economic burden of malignant neoplasms in Shandong province in order to provide scientific evidence for policy-making. Methods: The main sources for this study were the data from the third sampling survey of death cause in 2006 and cancer prevalence survey in 2007 in Shandong province. The direct medical cost was calculated based on the survey data. The indirect cost due to mortality and morbidity were estimated with human capital approach based on the data of disability-adjusted life years derived from the two surveys and gross domestic product (GDP) data. The total economic burden was the sum of direct medical cost and indirect cost. The uncertainty analysis was conducted according to the methodology in global burden of disease study. Results: The total cost of cancer in Shandong province in 2006 estimated was 18 057 million Yuan RMB (95% confidence interval:16 817 － 19 393 million), which accounted for 0. 83% of the total GDP. The direct medical cost，indirect mortality cost and indirect morbidity cost accounted for 17.28%, 78.53%, and 4.20% of total economic burden of malignant neoplasms, respectively. Liver，lung and stomach cancer were the top three tumors with heavier economic burden, with accounted for more than one half (57. 83%) of the total economic burden of all cancers. The uncertainty of total burden estimated was around ± 7%, which mainly derived from the uncertainty of indirect economic burden. Conclusion: The influence of cancers on social economy is dominated by the loss of productivity, especially by the productivity loss due to premature death. Liver, lung and stomach cancer are the major cancers for disease control and prevention in Shandong province. Abstract in Chinese 目的 评价山东省恶性肿瘤经济负担,为卫生决策提供科学依据. 方法 以2006年山东省第3次死因回顾抽样凋查资料和2007年山东省恶性肿瘤现患状况抽样调查资料为基础,测算全省直接医疗成本;采用人力资本法测算死亡间接负担和伤残间接负担;参考全球疾病负担研究的方法对测算结果的不确定性进行分析. 结果 2006年山东省因恶性肿瘤导致的总经济负担为180.57亿元(95%CI=16 817～19 393),占全省GDP总量的0.83%,其中直接医疗成本占总负担的17.28%,死亡造成的间接经济负担占78.53%,伤残所致间接经济负担占4.20%;肝癌、肺癌和胃癌为山东省经济负担最重的3种恶性肿瘤,总经济负担合计占全部恶性肿瘤的57.83%;总经济负担估计结果的不确定性范围在±7%左右,主要取决于间接经济负担的不确定性. 结论 恶性肿瘤对社会经济的影响主要通过生产力的损失产生作用,并以死亡所致生产力损失为主;肝癌、肺癌和胃癌应是山东省恶性肿瘤预防控制的重点.

Rates of radiologically confirmed pneumonia as defined by the World Health Organization in Northern Territory Indigenous children

Objective To determine the burden of hospitalised, radiologically confirmed pneumonia (World Health Organization protocol) in Northern Territory Indigenous children. Design, setting and participants Historical, observational study of all hospital admissions for any diagnosis of NT resident Indigenous children, aged between >= 29 days and < 5 years, 1 April 1997 to 31 March 2005. Intervention All chest radiographs taken during these admissions, regardless of diagnosis, were assessed for pneumonia in accordance with the WHO protocol. Main outcome measure The primary outcome was endpoint consolidation (dense fluffy consolidation [alveolar infiltrate] of a portion of a lobe or the entire lung) present on a chest radiograph within 3 days of hospitalisation. Results We analysed data on 24 115 hospitalised episodes of care for 9492 children and 13 683 chest radiographs. The average annual cumulative incidence of endpoint consolidation was 26.6 per 1000 population per year (95% Cl, 25.3-27.9); 57.5 per 1000 per year in infants aged 1-11 months, 38.3 per 1000 per year in those aged 12-23 months, and 13.3 per 1000 per year in those aged 24-59 months. In all age groups, rates of endpoint consolidation in children in the arid southern region of NT were about twice that of children in the tropical northern region. Conclusion The rates of severe pneumonia in hospitalised NT Indigenous children are among the highest reported in the world. Reducing this unacceptable burden of disease should be a national health priority.

Hospitalisation of Indigenous children in the Northern Territory for lower respiratory illness in the first year of life

Objective To describe the epidemiology of acute lower respiratory infection (ALRI) and bronchiectasis in Northern Territory Indigenous infants hospitalised in the first year of life. Design A historical cohort study constructed from the NT Hospital Discharge Dataset and the NT Imm(u)nisation Register. Participants and setting All NT resident Indigenous infants, born 1 January 1999 to 31 December 2004, admitted to NT public hospitals and followed up to 12 months of age. Main outcome measures Incidence of ALRI and bronchiectasis (ICD-10-AM codes) and radiologically confirmed pneumonia (World Health Organization protocol). Results Data on 9295 infants, 8498 child-years of observation and 15 948 hospitalised episodes of care were analysed. ALRI incidence was 426.7 episodes per 1000 child-years (95% Cl, 416.2-437.2). Incidence rates were two times higher (relative risk, 2.12; 95% Cl, 1.98-2.27) for infants in Central Australia compared with those in the Top End. The median age at first admission for an ALRI was 4.6 months (interquartile range, 2.6-7.3). Bronchiolitis accounted for most of the disease burden, with a rate of 227 per 1000 child-years. The incidence of first diagnosis of bronchiectasis was 1.18 per 1000 child-years (95% Cl, 0.60-2.16). One or more key comorbidities were present in 1445 of the 3227 (44.8%) episodes of care for ALRI. Conclusions Rates of ALRI and bronchiectasis in NT Indigenous infants are excessive, with early onset, frequent repeat episodes, and a high prevalence of comorbidities. These high rates of disease demand urgent attention.

Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia

Objective To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia. Methods We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence. Findings There were 526 pneumonia events among 10 600 children - an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses. Conclusion There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.

Usefulness of a self-reported history of chickenpox in adult women in the Top End

Early determination of immune status is essential for the prevention and/or amelioration of disease following exposure to chickenpox. This is of particular significance for pregnant women because of the additional risks to the foetus or newborn.1 To determine the usefulness of a self-reported history of chickenpox in adult women in the Top End, we compared it with serological evidence of immunity.

The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer

Prostacyclin synthase and thromboxane synthase signaling via arachidonic acid metabolism affects a number of tumor cell survival pathways such as cell proliferation, apoptosis, tumor cell invasion and metastasis, and angiogenesis. However, the effects of these respective synthases differ considerably with respect to the pathways described. While prostacyclin synthase is generally believed to be anti-tumor, a pro-carcinogenic role for thromboxane synthase has been demonstrated in a variety of cancers. The balance of oppositely-acting COX-derived prostanoids influences many processes throughout the body, such as blood pressure regulation, clotting, and inflammation. The PGI2/TXA2 ratio is of particular interest in-vivo, with the corresponding synthases shown to be differentially regulated in a variety of disease states. Pharmacological inhibition of thromboxane synthase has been shown to significantly inhibit tumor cell growth, invasion, metastasis and angiogenesis in a range of experimental models. In direct contrast, prostacyclin synthase overexpression has been shown to be chemopreventive in a murine model of the disease, suggesting that the expression and activity of this enzyme may protect against tumor development. In this review, we discuss the aberrant expression and known functions of both prostacyclin synthase and thromboxane synthase in cancer. We discuss the effects of these enzymes on a range of tumor cell survival pathways, such as tumor cell proliferation, induction of apoptosis, invasion and metastasis, and tumor cell angiogenesis. As downstream signaling pathways of these enzymes have also been implicated in cancer states, we examine the role of downstream effectors of PGIS and TXS activity in tumor growth and progression. Finally, we discuss current therapeutic strategies aimed at targeting these enzymes for the prevention/treatment of cancer. © 2010 Elsevier B.V. All rights reserved.

Utilising hospital data to inform product safety prioritisation : the application of RAPEX severity rankings in ICD-coded burn data

Background The implementation of the Australian Consumer Law in 2011 highlighted the need for better use of injury data to improve the effectiveness and responsiveness of product safety (PS) initiatives. In the PS system, resources are allocated to different priority issues using risk assessment tools. The rapid exchange of information (RAPEX) tool to prioritise hazards, developed by the European Commission, is currently being adopted in Australia. Injury data is required as a basic input to the RAPEX tool in the risk assessment process. One of the challenges in utilising injury data in the PS system is the complexity of translating detailed clinical coded data into broad categories such as those used in the RAPEX tool. Aims This study aims to translate hospital burns data into a simplified format by mapping the International Statistical Classification of Disease and Related Health Problems (Tenth Revision) Australian Modification (ICD-10-AM) burn codes into RAPEX severity rankings, using these rankings to identify priority areas in childhood product-related burns data. Methods ICD-10-AM burn codes were mapped into four levels of severity using the RAPEX guide table by assigning rankings from 1-4, in order of increasing severity. RAPEX rankings were determined by the thickness and surface area of the burn (BSA) with information extracted from the fourth character of T20-T30 codes for burn thickness, and the fourth and fifth characters of T31 codes for the BSA. Following the mapping process, secondary data analysis of 2008-2010 Queensland Hospital Admitted Patient Data Collection (QHAPDC) paediatric data was conducted to identify priority areas in product-related burns. Results The application of RAPEX rankings in QHAPDC burn data showed approximately 70% of paediatric burns in Queensland hospitals were categorised under RAPEX levels 1 and 2, 25% under RAPEX 3 and 4, with the remaining 5% unclassifiable. In the PS system, prioritisations are made to issues categorised under RAPEX levels 3 and 4. Analysis of external cause codes within these levels showed that flammable materials (for children aged 10-15yo) and hot substances (for children aged <2yo) were the most frequently identified products. Discussion and conclusions The mapping of ICD-10-AM burn codes into RAPEX rankings showed a favourable degree of compatibility between both classification systems, suggesting that ICD-10-AM coded burn data can be simplified to more effectively support PS initiatives. Additionally, the secondary data analysis showed that only 25% of all admitted burn cases in Queensland were severe enough to trigger a PS response.

In arrayed ranks array technology in the study of mesothelioma steven

Mesothelioma is a rare malignancy arising from mesothelial cells lining the pleura and peritoneum. Advances in modern technology have allowed the development of array based approaches to the study of disease allowing researchers the opportunity to study many genes or proteins in a high-throughput fashion. This review describes the current knowledge surrounding array based approaches with respect to mesothelioma research. © 2009 by the International Association for the Study of Lung Cancer.

Estimation of the burden of malignant neoplasms by DALYs in Shandong Province [应用伤残调整寿命年测量山东省恶性肿瘤疾病负担的研究]

Objective: To evaluate the burden of malignant neoplasms in Shandong Province in order to provide scientific evidence for policy-making. Methods: The main data for this study were from Shandong third cause of death sampling survey in 2006 and Shandong 2007 cancer prevalence survey. YLLs, YLDs, DALYs and disability weights of each type of cancers were calculated according to the global burdens of disease （GBD） methodology. The direct method was used to estimate YLDs. The uncertainty analysis was conducted following the methodology in GBD study. Results: The total cancers burden in Shandong population was 1 383 thousands DALYs. Lung cancer, liver cancer, stomach cancer and esophagus cancer were the top four cancers with the highest health burden. The burden of the four major cancers together accounted for 71.45% of the total burden of all cancers. 95% of the total burden of malignant tumors was caused by premature death, and only 5.26% of the total cancer burden was due to disability. The uncertainty of total burden estimate was around±11%， the uncertainty of YLDs was bigger than that of YLLs. Conclusion: The health burden due to cancers in Shandong population is heavier than that of the national average level. Liver cancer, lung cancer and stomach cancer should be the major cancers for disease control and prevention in Shandong.

Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group

Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.