HDAC Regulates Transcription at the Outset of Axolotl Tail Regeneration.

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited regeneration through the first 7 days, however after this time, regeneration commenced with variable outgrowth of tailfin tissue and abnormal patterning. Microarray analysis showed that romidepsin altered early, transcriptional responses at 3 and 6-hour post-amputation, especially targeting genes that are implicated in tumor cell death, as well as genes that function in the regulation of transcription, cell differentiation, cell proliferation, pattern specification, and tissue morphogenesis. Our results show that HDAC activity is required at the time of tail amputation to regulate the initial transcriptional response to injury and regeneration.

Do teas rich in antioxidants reduce the physicochemical and peroxidative risk factors for calcium oxalate nephrolithiasis in humans? Pilot studies with Rooibos herbal tea and Japanese green tea.

Several experimental and animal studies have demonstrated that substances rich in antioxidants can reduce the physicochemical and peroxidative risk factors for calcium oxalate (CaOx) renal stone formation in urine and blood. However, there are very few such investigations in humans. In the present pilot study, two varieties of tea, a green one from Japan (JGT) and a herbal one from South Africa (Rooibos) (RT), both rich in antioxidants, were administered to a group of CaOx stone formers (SF) (n = 8) for 30 days. Both teas were analysed for polyphenols by high-performance liquid chromatography and for minerals by plasma atomic and optical emission spectroscopy. 24 h urines (baseline and day 30) were analysed for lithogenic factors. CaOx metastable limits and crystal nucleation and growth kinetics were also determined in each urine sample. Deposited crystals were inspected by scanning electron microscopy. Blood samples were collected (baseline and day 30). Biomarkers of oxidative stress including plasma and urinary thiobarbituric acid reactive substances (TBARS) and urinary N-acetyl-ß-D-glucosaminidase (NAG) were also determined. Urinary physicochemical risk factors were also investigated after ingestion of RT for 30 days in two control groups (CG1 and CG2), the latter one of which consisted of habitual JGT drinkers. Statistical analyses were performed using Wilcoxon signed rank tests and Mann-Whitney tests for paired and independent measurements, respectively. Several flavonoids and catechins were quantified in RT and JGT, respectively, confirming that both teas are rich sources of antioxidants. Mineral content was found to be far below dietary reference intakes. There were no significant changes in any of the urinary physicochemical or peroxidative risk factors in the control groups or in SF, except for the supersaturation (SS) of brushite (Bru) which decreased in the latter group after ingestion of JGT. Crystal morphology showed a tendency to change from mixed CaOx mono- and di-hydrate to monohydrate after ingestion of each tea. Since the latter form has a stronger binding affinity for epithelial cells, this effect is not protective. Analysis of the physicochemical and peroxidative risk factors in CG1 and CG2 did not reveal any evidence of a synergistic effect between the two teas. Paradoxically, baseline risk factors in the habitual JGT control group were significantly raised relative to those in CG1. Our preliminary results suggest that ingestion of RT and JGT does not reduce the risk factors for CaOx stone formation in humans, but these findings need to be tested in further studies involving much larger sample sizes.

Comparison of a morning polypill, evening polypill and individual pills on LDL-cholesterol, ambulatory blood pressure and adherence in high-risk patients; a randomized crossover trial.

AIMS: Cardiovascular polypills are a novel strategy in the prevention of cardiovascular disease. Based on considerations about the effectiveness, the individual pills of a polypill are taken at different times of the day. This study aimed therefore to compare the use of a polypill in the morning, in the evening or the individual components taken at their usual times on cardiovascular risk factors and patient acceptability. METHODS: The study was a randomized three-period crossover trial. Seventy-eight patients with established cardiovascular disease were randomly allocated to the use of polypill (aspirin 75 mg, simvastatin 40 mg, lisinopril 10mg and hydrochlorothiazide 12.5mg) in the morning, in the evening or use of the individual agents taken at different time points (Trial: NCT01506505). RESULTS: Using the polypill in the evening resulted in a 0.2 mmol/L (95%-confidence interval (CI): 0.1 to 0.3) lower fasting LDL-cholesterol compared to the use in the morning, and not statistically significantly different mean 24-hour systolic BP (mean difference: 0.7 mmHg; 95%-CI; -2.1 to 3.4). Compared to the use of the individual agents, the mean LDL-cholesterol was 0.2 mmol/L (95%-CI: 0.1 to 0.3) higher when using the polypill in the morning, but not statistically significantly different when used in the evening (mean difference: -0.1 mmol/L; 95%-CI: -0.1 to 0.0). Furthermore, there were no differences in mean 24-hour systolic BP with morning use (mean difference: 0.4 mmHg; 95%-CI; -1.5 to 2.3) or evening use (mean difference: 1.0mmHg; 95%-CI; -0.8 to 2.8) of the polypill compared to the individual agents. The adherence was 5.2% (95%-CI: 1.4 to 9.1) higher with morning use of the polypill and 5.0% (95%-CI: 1.5 to 8.5) higher with evening use compared to the individual agents. Treatment with the polypill was preferred by 92% of the participants. CONCLUSION: The use of a polypill in the evening was more effective in lowering LDL-cholesterol, and resulted in not statistically significantly different ambulatory BP levels compared to the use of a polypill in the morning. Therapy with a polypill was associated with an increased adherence. The polypill is highly preferred by patients, demonstrating a potential role for the polypill in the prevention of cardiovascular disease.

A randomised controlled trial of a consumer-focused e-health strategy for cardiovascular risk management in primary care: the Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) study protocol.

INTRODUCTION: Fewer than half of all people at highest risk of a cardiovascular event are receiving and adhering to best practice recommendations to lower their risk. In this project, we examine the role of an e-health-assisted consumer-focused strategy as a means of overcoming these gaps between evidence and practice. Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) aims to test whether a consumer-focused e-health strategy provided to Aboriginal and Torres Strait Islander and non-indigenous adults, recruited through primary care, at moderate-to-high risk of a cardiovascular disease event will improve risk factor control when compared with usual care. METHODS AND ANALYSIS: Randomised controlled trial of 2000 participants with an average of 18 months of follow-up to evaluate the effectiveness of an integrated consumer-directed e-health portal on cardiovascular risk compared with usual care in patients with cardiovascular disease or who are at moderate-to-high cardiovascular disease risk. The trial will be augmented by formal economic and process evaluations to assess acceptability, equity and cost-effectiveness of the intervention. The intervention group will participate in a consumer-directed e-health strategy for cardiovascular risk management. The programme is electronically integrated with the primary care provider's software and will include interactive smart phone and Internet platforms. The primary outcome is a composite endpoint of the proportion of people meeting the Australian guideline-recommended blood pressure (BP) and cholesterol targets. Secondary outcomes include change in mean BP and fasting cholesterol levels, proportion meeting BP and cholesterol targets separately, self-efficacy, health literacy, self-reported point prevalence abstinence in smoking, body mass index and waist circumference, self-reported physical activity and self-reported medication adherence. ETHICS AND DISSEMINATION: Primary ethics approval was received from the University of Sydney Human Research Ethics Committee and the Aboriginal Health and Medical Research Council. Results will be disseminated via the usual scientific forums including peer-reviewed publications and presentations at international conferences CLINICAL TRIALS REGISTRATION NUMBER: ACTRN12613000715774.

Optimisation of hepatocellular carcinoma surveillance in patients with viral hepatitis: a quality improvement study.

BACKGROUND: Surveillance for hepatocellular carcinoma (HCC) with 6-monthly ultrasound is a standard of care for higher-risk patients with viral hepatitis. Adherence to screening guidelines is an important quality indicator in hepatology, but multiple studies have demonstrated poor HCC surveillance practices in real-world settings. AIMS: The aim of this project was to audit and then optimise HCC surveillance of viral hepatitis patients, who fulfilled criteria for screening, associated with a large tertiary hospital. METHODS: Clinical practice improvement principles were utilised. A baseline audit of 22 consecutive viral hepatitis patients was performed. Major barriers preventing adequate surveillance were identified and three interventions to improve adherence to guidelines were introduced. These included: improved doctor education, system redesign and improved patient education. The effects of interventions were measured by serial random audits of patients. A final audit occurred over 3 years after the initial baseline audit. RESULTS: At baseline, 46% and 0% of patients had appropriate surveillance performed during the prior 6 months (one surveillance cycle) and 2 years (four surveillance cycles) respectively. Three years after initiation of these strategies, a final audit revealed 92% (vs 46% at baseline) and 64% (vs 0% at baseline) of patients had appropriate HCC surveillance performed during the preceding 6 months and 2 years intervals respectively (P < 0.001 in each case). CONCLUSIONS: Simple and low-cost interventions can considerably improve the clinical effectiveness of HCC screening programmes in real world settings. Clinical practice improvement principles appear to be a valid methodology for achieving this positive change.

Mapping trachoma in Nasarawa and Plateau States, central Nigeria.

OBJECTIVES: The World Health Organization has called upon member states to eliminate blinding trachoma by 2020 using the SAFE strategy. We aimed to determine the prevalence of trachoma and quantify intervention needs for each aspect of the SAFE (surgery, mass administration of antibiotics, promotion of facial cleanliness and environmental improvements) strategy in Nasarawa and Plateau States, Nigeria. METHODS: District-based, household cluster surveys were conducted in all 30 local government areas (LGAs) within the states. RESULTS: A total of 46 960 persons were examined from 7883 selected households. Prevalence estimates of trachomatous inflammation follicular among children 1-9 years of age ranged from 1.7 to 15.8% by LGA. Trichiasis prevalence among adults varied by LGA from 0 to 2.1% and was more common among women (OR = 1.99, 95% CI 1.3 to 3.1). Access to water within a 30 min round trip was reported by 82.3% of households. CONCLUSION: LGA-wide trachoma control interventions are warranted in seven LGAs targeting: 5409 persons for surgery to correct trichiasis, 778 698 persons to receive at least three rounds of mass antibiotic distribution, 855 villages in which to promote face-washing and sanitation, and 102 751 households for latrine construction. These mapping surveys demonstrate an example of evidence-based programme planning necessary for measuring progress towards achieving the GET 2020 objective and can be replicated in other areas yet to be mapped for trachoma.

Use of electronic sales data to tailor nutrition education resources for an ethnically diverse population.

BACKGROUND: Nutrition education may be most effective when personally tailored. Individualised electronic supermarket sales data offer opportunities to tailor nutrition education using shopper's usual food purchases. The present study aimed to use individualised electronic supermarket sales data to tailor nutrition resources for an ethnically diverse population in a large supermarket intervention trial in New Zealand. METHODS: Culturally appropriate nutrition education resources (i.e. messages and shopping lists) were developed with the target population (through two sets of focus groups) and ethnic researchers. A nutrient database of supermarket products was developed using retrospective sales data and linked to participant sales to allow tailoring by usual food purchases. Modified Heart Foundation Tick criteria were used to identify 'healthier' products in the database suitable for promotion in the resources. Rules were developed to create a monthly report listing the tailored and culturally targeted messages to be sent to each participant, and to produce automated, tailored shopping lists. RESULTS: Culturally targeted nutrition messages (n = 864) and shopping lists (n = 3 formats) were developed. The food and nutrient database (n = 3000 top-selling products) was created using 12 months of retrospective sales data, and comprised 60%'healthier' products. Three months of baseline sales data were used to determine usual food purchases. Tailored resources were successfully mailed to 123 Maori, 52 Pacific and 346 non-Maori non-Pacific participants over the 6-month trial intervention period. CONCLUSIONS: Electronic supermarket sales data can be used to tailor nutrition education resources for a large number of ethnically diverse supermarket shoppers.

Txt2stop: a pilot randomised controlled trial of mobile phone-based smoking cessation support.

AIM: To conduct a pilot randomised controlled trial of mobile phone-based smoking cessation support intervention for the UK population. DESIGN: Randomised controlled trial (txt2stop). SETTING: Community. PARTICIPANTS: 200 participants responding to radio, poster and leaflet-based promotions regarding the trial. MAIN OUTCOME MEASURES: The response rate for the outcome measures planned for the main trial. Participants' qualitative responses to open-ended questions about the intervention content. Secondary outcomes were the outcomes planned for the main trial including the point prevalence of self-reported smoking at 4 weeks and pooled effect estimate for the short-term results for the STOMP and txt2stop trials. RESULTS: The response rate at 4 weeks was 96% and at 6 months was 92%. The results at 4 weeks show a doubling of self-reported quitting relative risk (RR) 2.08 (95% CI 1.11 to 3.89), 26% vs 12%. The pooled effect estimate combining txt2stop and a previous New Zealand trial in the short term is RR 2.18 (95% CI 1.79 to 2.65). CONCLUSIONS: Mobile phone-based smoking cessation is an innovative means of delivering smoking cessation support, which doubles the self-reported quit rate in the short term. It could represent an important, but as yet largely unused, medium to deliver age-appropriate public health measures. The long-term effect of this mobile phone-based smoking cessation support will be established by a large randomised controlled trial currently in recruitment.

Randomized clinical trial of honey-impregnated dressings for venous leg ulcers.

BACKGROUND: The efficacy of honey as a treatment for venous ulcers has not been evaluated, despite widespread interest. This trial aimed to evaluate the safety and effectiveness of honey as a dressing for venous ulcers. METHODS: This community-based open-label randomized trial allocated people with a venous ulcer to calcium alginate dressings impregnated with manuka honey or usual care. All participants received compression bandaging. The primary outcome was the proportion of ulcers healed after 12 weeks. Secondary outcomes were: time to healing, change in ulcer area, incidence of infection, costs per healed ulcer, adverse events and quality of life. Analysis was by intention to treat. RESULTS: Of 368 participants, 187 were randomized to honey and 181 to usual care. At 12 weeks, 104 ulcers (55.6 per cent) in the honey-treated group and 90 (49.7 per cent) in the usual care group had healed (absolute increase 5.9 (95 per cent confidence interval (c.i.) -4.3 to 15.7) per cent; P = 0.258). Treatment with honey was probably more expensive and associated with more adverse events (relative risk 1.3 (95 per cent c.i. 1.1 to 1.6); P = 0.013). There were no significant differences between the groups for other outcomes. CONCLUSION: Honey-impregnated dressings did not significantly improve venous ulcer healing at 12 weeks compared with usual care. REGISTRATION NUMBER: ISRCTN 06161544 (http://www.controlled-trials.com).

The role of lifestyle risk factors on mortality from colorectal cancer in populations of the Asia-Pacific region.

Although colorectal cancer is one of the leading malignancies worldwide, there are few data on aetiological relationships from the Asia-Pacific region. Therefore, a collaborative study was conducted involving over half a million subjects from 33 cohort studies in the region. Age-adjusted death rates from colorectal cancer, over an average of 6.8 years follow-up, were 12 and 14 per 100,000 person-years among Asian women and men, respectively; corresponding values in Australasia were 31 and 41. Height was strongly associated with death from colorectal cancer: an extra 5 cm of height was associated with 10% (95%confidence interval, 3% - 18% additional risk, after adjustment for other factors. Smoking increased risk by 43% (9% - 88%), although no significant dose-response relationship was discerned (p>0.05). Other significant (p <0.05) risk factors were body mass index and lack of physical activity. There was no significant effect on colorectal cancer mortality for alcohol consumption, waist circumference, fasting blood glucose or diabetes, although the latter conferred a notable 26% additional risk. Height may be a biomarker for some currently unknown genetic, or environmental, risk factors that are related both to skeletal growth and mutanogenesis. Understanding such mechanisms could provide opportunities for novel preventive and therapeutic intervention.

The impact of modifiable risk factors on mortality from prostate cancer in populations of the Asia-Pacific region.

Mortality from cancer of the prostate is increasing in the Asia-Pacific, when much of this region is undergoing a transition to a Western lifestyle. The role that lifestyle factors play in prostate cancer appears limited, but existing data mainly are from the West. We conducted an individual participant data analysis of 24 cohort studies involving 320,852 men (83% in Asia). Cox proportional hazard models were used to quantify associations between risk factors and mortality from prostate cancer. There were 308 deaths from prostate cancer (14% in Asia) during 2.1 million person-years of follow-up. The age-adjusted hazard ratio (95% confidence interval; CI) for men with body mass index (BMI) 28 kg/m2 or more, compared with below 25, was 1.55 (1.12 - 2.16); no such significant relationship was found for height or waist circumference. The BMI result was unchanged after adjustment for other variables, was consistent between Asia and Australia/New Zealand (ANZ) and did not differ with age. There was no significant relationship with diabetes, glucose or total cholesterol (p > or = 0.18). Smoking, alone, showed different effects in the two regions, possibly due to the relative immaturity of the smoking epidemic in Asia. In ANZ, the multiple-adjusted hazard ratio for an extra 5 cigarettes per day was 1.12 (95%CI: 1.03 - 1.22), whereas in Asia it was 0.77 (0.56 - 1.05). Body size is an apparently important determinant of prostate cancer in the Asia-Pacific. Evidence of an adverse effect of smoking is conclusive only in the predominantly Caucasian parts of the region.

Cardiovascular risk prediction tools for populations in Asia.

BACKGROUND: Cardiovascular risk equations are traditionally derived from the Framingham Study. The accuracy of this approach in Asian populations, where resources for risk factor measurement may be limited, is unclear. OBJECTIVE: To compare "low-information" equations (derived using only age, systolic blood pressure, total cholesterol and smoking status) derived from the Framingham Study with those derived from the Asian cohorts, on the accuracy of cardiovascular risk prediction. DESIGN: Separate equations to predict the 8-year risk of a cardiovascular event were derived from Asian and Framingham cohorts. The performance of these equations, and a subsequently "recalibrated" Framingham equation, were evaluated among participants from independent Chinese cohorts. SETTING: Six cohort studies from Japan, Korea and Singapore (Asian cohorts); six cohort studies from China; the Framingham Study from the US. PARTICIPANTS: 172,077 participants from the Asian cohorts; 25,682 participants from Chinese cohorts and 6053 participants from the Framingham Study. MAIN RESULTS: In the Chinese cohorts, 542 cardiovascular events occurred during 8 years of follow-up. Both the Asian cohorts and the Framingham equations discriminated cardiovascular risk well in the Chinese cohorts; the area under the receiver-operator characteristic curve was at least 0.75 for men and women. However, the Framingham risk equation systematically overestimated risk in the Chinese cohorts by an average of 276% among men and 102% among women. The corresponding average overestimation using the Asian cohorts equation was 11% and 10%, respectively. Recalibrating the Framingham risk equation using cardiovascular disease incidence from the non-Chinese Asian cohorts led to an overestimation of risk by an average of 4% in women and underestimation of risk by an average of 2% in men. INTERPRETATION: A low-information Framingham cardiovascular risk prediction tool, which, when recalibrated with contemporary data, is likely to estimate future cardiovascular risk with similar accuracy in Asian populations as tools developed from data on local cohorts.

Phase II study of pegylated liposomal doxorubicin HCl (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small cell lung cancer.

BACKGROUND: Despite chemotherapy and radiotherapy for small cell lung cancer (SCLC), most patients die within 2 years. Response rates for second-line chemotherapy are 15-25%, with a median survival of 5 months. Caelyx, a pegylated liposomal formulation of doxorubicin, may be better tolerated and has activity in SCLC. PATIENTS AND METHODS: Thirty-two patients were enrolled in a phase II study of intravenous Caelyx (35 mg/m2), cyclophosphamide (750 mg/m2) and vincristine (1.2 mg/m2) every 21 days as second-line therapy in SCLC for up to six cycles. RESULTS: Thirty patients were evaluable for response, with a response rate of 10%. Another two had an unconfirmed response. Stable disease (SD) for >or=2 cycles was seen in an additional 53%. Grade 3 or 4 non-hematologic toxicity was seen in 17 (55%) patients (26 [22%] cycles) and included fatigue, mucositis, plantar-palmar erythrodysesthesia, rash and neuropathy. Twelve patients required transfusions. All patients on study have now expired, with a median survival of 28 weeks (7 months). For patients with SD or partial response, median time to progression was 15 weeks. CONCLUSION: The combination of Caelyx, cyclophosphamide and vincristine, despite cyclophosphamide and Caelyx dose reductions, has modest activity in relapsed SCLC with acceptable toxicity.

Phase II multicenter open-label study of carboplatin and pegylated liposomal doxorubicin in uterine and cervical malignancies.

The results of a multicenter phase II study investigating carboplatin and pegylated liposomal doxorubicin (PLD) in patients with recurrent/metastatic uterine and cervical malignancies (UCM) are presented here. Fifty-three subjects with measurable, untreated, advanced UCM were enrolled. Fifty-one were evaluable for response. Prior combined-modality treatment was permitted if a component of primary therapy. Patients received carboplatin AUC = 5 with PLD 35 mg/m(2) intravenously once every 4 weeks. Overall response rate was 33% (35% stable disease). Overall survival (OS) at six months was 86% (95% CI 76%-96%). Six-month progression-free survival (PFS) was 43% (95% CI 30%-57%). Median PFS was 22.9 weeks (range 16.0-35.3) and median OS was 49.1 weeks (range 41.4-75.1). The most frequent grade 3-4 nonhematological adverse events were: abdominal pain (n = 7), fatigue (4), vomiting (4), nausea (3), and shortness of breath (3). There was 1 report of grade 3 hand-foot syndrome and none of grade 4. Twelve patients had first infusion reactions with only 1 discontinuing treatment. Grade 3-4 neutropenia occurred in 26/230 cycles (11.3%). There were no treatment-related deaths. The combination of carboplatin and PLD is well tolerated with sufficient activity to justify additional evaluation in clinical trials and might be suited to the addition of a taxane.

Do u smoke after txt? Results of a randomised trial of smoking cessation using mobile phone text messaging.

OBJECTIVES: To determine the effectiveness of a mobile phone text messaging smoking cessation programme. DESIGN: Randomised controlled trial SETTING: New Zealand PARTICIPANTS: 1705 smokers from throughout New Zealand who wanted to quit, were aged over 15 years, and owned a mobile phone were randomised to an intervention group that received regular, personalised text messages providing smoking cessation advice, support, and distraction, or to a control group. All participants received a free month of text messaging; starting for the intervention group on their quit day to assist with quitting, and starting for the control group at six months to encourage follow up. Follow up data were available for 1624 (95%) at six weeks and 1265 (74%) at six months. MAIN OUTCOME MEASURES: The main trial outcome was current non-smoking (that is, not smoking in the past week) six weeks after randomisation. Secondary outcomes included current non-smoking at 12 and 26 weeks. RESULTS: More participants had quit at six weeks in the intervention compared to the control group: 239 (28%) v 109 (13%), relative risk 2.20 (95% confidence interval 1.79 to 2.70), p < 0.0001. This treatment effect was consistent across subgroups defined by age, sex, income level, or geographic location (p homogeneity > 0.2). The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests. Reported quit rates remained high at six months, but there was some uncertainty about between group differences because of incomplete follow up. CONCLUSIONS: This programme offers potential for a new way to help young smokers to quit, being affordable, personalised, age appropriate, and not location dependent. Future research should test these findings in different settings, and provide further assessment of long term quit rates.

Smoking, quitting, and the risk of cardiovascular disease among women and men in the Asia-Pacific region.

BACKGROUND: Although smoking is a major risk factor for cardiovascular disease, it has been suggested that Asians may be less susceptible to the adverse effects of smoking than Caucasians. This may have contributed to the high prevalence of smoking, and the low quitting rates, in Asian men. Worldwide, smoking rates are increasing for women, amongst whom cardiovascular awareness is relatively poor. METHODS: An individual participant data analysis of 40 cohort studies was carried out, involving 463 674 Asians (33% female) and 98 664 Australasians (45% female). Cox proportional hazard models, stratified by study and sex where appropriate, were employed. RESULTS: The HR [95% confidence interval (CI)], comparing current smokers with non-smokers, for coronary heart disease (CHD) was 1.60 (1.49-1.72); haemorrhagic stroke 1.19 (1.06-1.33); ischaemic stroke 1.38 (1.24-1.54). There was a clear dose-response relationship between the number of cigarettes smoked per day and both CHD and stroke, with no significant difference (P >/= 0.20) between populations from Asia and Australia/New Zealand. Although there was no sex difference for stroke in the effect of amount smoked (P = 0.16), for CHD, women tended to have higher hazard ratios than men (P = 0.011). Quitting gave a clear benefit, which was not significantly different between the sexes or regions (P > 0.63). The HR (CI) for ex-smokers compared with current smokers was 0.71 (0.64-0.78) for CHD and 0.84 (0.76-0.92) for stroke. CONCLUSIONS: Unless urgent public health measures are put into place, the impact of the smoking epidemic in Asia, and among women, will be enormous. Tobacco control policies that specifically target these populations are essential.

Body mass index and cardiovascular disease in the Asia-Pacific Region: an overview of 33 cohorts involving 310 000 participants.

BACKGROUND: Few prospective data from the Asia-Pacific region are available relating body mass index (BMI) to the risks of stroke and ischaemic heart disease (IHD). Our objective was to assess the age-, sex-, and region-specific associations of BMI with cardiovascular disease using individual participant data from prospective studies in the Asia-Pacific region. METHODS: Studies were identified from literature searches, proceedings of meetings, and personal communication. All studies had at least 5000 person-years of follow-up. Hazard ratios were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk and smoking. The first 3 years of follow-up were excluded in order to reduce confounding due to disease at baseline. RESULTS: A total of 33 cohort studies, including 310 283 participants, contributed 2 148 354 person-years of follow-up, during which 3332 stroke and 2073 IHD events were observed. There were continuous positive associations between baseline BMI and the risks of ischaemic stroke, haemorrhagic stroke, and IHD, with each 2 kg/m(2) lower BMI associated a 12% (95% CI: 9, 15%) lower risk of ischaemic stroke, 8% (95% CI: 4, 12%) lower risk in haemorrhagic stroke, and 11% (95% CI: 9, 13%) lower risk of IHD. The strengths of all associations were strongly age dependent, and there was no significant difference between Asian and Australasian cohorts. CONCLUSIONS: This overview provides the most reliable estimates to date of the associations between BMI and cardiovascular disease in the Asia-Pacific region, and the first direct comparisons within the region. Continuous relationships of approximately equal strength are evident in both Asian and Australasian populations. These results indicate considerable potential for cardiovascular disease reduction with population-wide lowering of BMI.