The objective of this study was to provide an up-to-date summary of the current evidence that may be useful for updating guidelines. We comprehensively searched the published literatures and ...conferences for studies that compared curative with palliative treatments in colorectal cancer patients with peritoneal metastasis. The primary outcomes considered in this study were three- and five-year overall survival rates. We pooled data across studies and estimated summary effect sizes. Overall, patients who received curative treatments had improved three-year survival (hazard ratio (HR), 2.19 95% CI, 1.83 to 2.62) and five-year survival (HR, 2.22 95% CI, 1.83 to 2.69) compared with those who received palliative treatments. Patients who received curative treatments had an increased risk of treatment-related morbidity (odds ratio (OR), 2.90 95% CI, 2.02 to 4.17), but there was no significant difference in treatment-related mortality between patients who received curative treatments and those who received palliative treatments (OR, 1.46 CI, 0.62 to 3.47). Curative treatments improved overall survival in colorectal cancer patients with peritoneal metastasis and did not increase the risk of treatment-related mortality. Curative treatments were associated with a higher risk of treatment-related morbidity. These data highlight the importance for further investigation aimed at prevention of treatment-associated morbidity.
Adiposity is increasing rapidly in China but little is known about the relevance to it of women's reproductive factors, which differ inter-generationally and from that in the West. We assess ...associations of adiposity with life-course reproductive factors in Chinese women.
In 2004-08, the nationwide China Kadoorie Biobank recruited 303 000 women aged 30-79 (mean 50) years from 10 diverse regions. Multivariable linear regression was used to examine associations of reproductive factors (e.g. age at menarche/first birth/menopause, parity, breastfeeding and reproductive years) with measures of general e.g. body mass index (BMI) and central e.g. waist circumference (WC) adiposity in adulthood.
Overall, the mean BMI was 23.7 (standard deviation 3.3) kg/m 2 , mean age at menarche was 15 (2) years and nearly all had given birth (99%) and breastfed children (98%). Adiposity was associated inversely with age at menarche and at first birth, with 0.19 and 0.05 kg/m 2 lower BMI and 0.38 and 0.12 cm lower WC per 1-year delay respectively ( P < 0.001). Among 128 259 post-menopausal women, adiposity was associated positively with age at menopause and reproductive years, with 0.05 and 0.07 kg/m 2 higher BMI and 0.12 and 0.17 cm higher WC per 1-year increase, respectively ( P < 0.001). The proportion with overweight/obesity had similar associations with these reproductive factors. Adiposity had a non-linear positive association with parity, but no association with breastfeeding duration.
Among Chinese women, earlier age at menarche and at first birth, later age at menopause and longer reproductive years were independently associated with increased adiposity late in life.
Accumulating evidence has shown that poor oral hygiene is associated with increased risk of cardiometabolic diseases in Western populations. However, its relevance about the relationships in Chinese ...adults remains unclear. The China Kadoorie Biobank enrolled 512 715 adults aged 30‐79 years in China during 2004‐2008. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with measures of oral hygiene. Overall 9.3% of the participants reported rarely or never brushing teeth at baseline. Participants who rarely or never brushed teeth had adjusted HR of 1.12 (95% CI: 1.09, 1.15) for MVE, with similar HRs for stroke (1.08, 1.05‐1.12), intracerebral haemorrhage (1.18, 1.11‐1.26) and pulmonary heart disease (1.22, 1.13‐1.32) compared with those who brushed teeth regularly. Those who did not brush teeth also had increased risk of cancer (1.09, 1.04‐1.14), chronic obstructive pulmonary disease (COPD) (1.12, 1.05‐1.20), liver cirrhosis (1.25, 1.09‐1.44) and all‐cause death (1.25, 1.21‐1.28) but not type 2 diabetes (0.94, 0.86‐1.03) and chronic kidney disease (0.98, 0.81‐1.18). Among Chinese adults, we found that poor oral hygiene is associated with higher risks of major vascular disease, cancer, COPD, liver cirrhosis and all‐cause deaths, but not type 2 diabetes and chronic kidney disease.
Little is known about the effects of maintaining healthy sleep patterns on frailty transitions.
Based on 23,847 Chinese adults aged 30-79 in a prospective cohort study, we examined the associations ...between sleep patterns and frailty transitions. Healthy sleep patterns included sleep duration at 7 or 8 h/d, without insomnia disorder, and no snoring. Participants who persisted with a healthy sleep pattern in both surveys were defined as maintaining a healthy sleep pattern and scored one point. We used 27 phenotypes to construct a frailty index and defined three statuses: robust, prefrail, and frail. Frailty transitions were defined as the change of frailty status between the 2 surveys: improved, worsened, and remained. Log-binomial regression was used to calculate the prevalence ratio (PR) to assess the effect of sleep patterns on frailty transitions.
During a median follow-up of 8.0 years among 23,847 adults, 45.5% of robust participants, and 10.8% of prefrail participants worsened their frailty status, while 18.6% of prefrail participants improved. Among robust participants at baseline, individuals who maintained sleep duration of 7 or 8 h/ds, without insomnia disorder, and no-snoring were less likely to worsen their frailty status; the corresponding PRs (95% CIs) were 0.92 (0.89-0.96), 0.76 (0.74-0.77), and 0.85 (0.82-0.88), respectively. Similar results were observed among prefrail participants maintaining healthy sleep patterns. Maintaining healthy sleep duration and without snoring, also raised the probability of improving the frailty status; the corresponding PRs were 1.09 (1.00-1.18) and 1.42 (1.31-1.54), respectively. Besides, a dose-response relationship was observed between constantly healthy sleep scores and the risk of frailty transitions (P for trend < 0.001).
Maintaining a comprehensive healthy sleep pattern was positively associated with a lower risk of worsening frailty status and a higher probability of improving frailty status among Chinese adults.
Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of ...PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition.
In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C PCSK9 genetic score (PCSK9-GS). Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45-0.83); P = 0.0015, major occlusive vascular events n = 15 752; 0.80 (0.67-0.95); P = 0.011, and ischaemic stroke n = 11 467; 0.80 (0.66-0.98); P = 0.029. However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease COPD: n = 6836; 1.38 (1.08-1.76); P = 0.0089 and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD n = 730; 3.61 (1.71-7.60); P = 7.3 × 10-4. We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) pooled OR after meta-analysis of 1.87 (1.38-2.54); P = 5.4 × 10-5 and self-reported asthma pooled OR of 1.17 (1.04-1.30); P = 0.0071. There was no association of a polygenic LDL-C score with COPD hospitalization, COPD exacerbation, or URTI.
The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases. Pharmacovigilance studies may be required to monitor patients treated with therapeutic PCSK9 inhibitors for exacerbations of respiratory diseases or respiratory tract infections.
Genetic analyses of over 100 000 participants of the China Kadoorie Biobank, mimicking the effect of new drugs intended to reduce cholesterol by targeting the PCSK9 protein, have identified potential severe effects of lower PCSK9 activity in patients with existing respiratory disease.PCSK9 genetic variants that are associated with lower cholesterol and reduced rates of cardiovascular disease are also associated with increased risk of a range of respiratory diseases, including asthma, upper respiratory tract infections, and hospitalization with chronic obstructive pulmonary disease (COPD).These genetic variants are not associated with whether or not individuals have COPD; instead, they are specifically associated with an increase in the chance of those who already have COPD being hospitalized and even dying, suggesting that careful monitoring of such patients should be considered during development of and treatment with anti-PCSK9 medication.
In contrast to developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate in the past two decades, lower survival rate, and vast geographic variation. ...However, there is no validated risk prediction model in China to aid early detection yet.
A large nationwide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks of invasive breast cancer. A total of 300,824 women free of any prior cancer were recruited during 2004-2008 and followed up to Dec 31, 2016. Cox models were used to identify breast cancer risk factors and build a relative risk model. Absolute risks were calculated by incorporating national age- and residence-specific breast cancer incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women's Health Study (SWHS), with 73,203 women to externally validate the calibration and discriminating accuracy.
During a median of 10.2 years of follow-up in the CKB, 2287 cases were observed. The final model included age, residence area, education, BMI, height, family history of overall cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed (E/O) ratios of 1.01 (95% confidence interval (CI), 0.94-1.09) and 0.94 (95% CI, 0.89-0.99), respectively. After eliminating the effect of age and residence, the model maintained moderate but comparable discriminating accuracy compared with those of some previous externally validated models. The adjusted areas under the receiver operating curve (AUC) were 0.634 (95% CI, 0.608-0.661) and 0.585 (95% CI, 0.564-0.605) in the CKB and the SWHS, respectively.
Based only on non-laboratory predictors, our model has a good calibration and moderate discriminating capacity. The model may serve as a useful tool to raise individuals' awareness and aid risk-stratified screening and prevention strategies.
Pregnancy and pregnancy loss may be linked to cardiovascular disease (CVD). However, the evidence is still inconsistent, especially in East Asians, whose reproductive patterns differ importantly from ...those in the West. We examined the associations of pregnancy, miscarriage, induced abortion, and stillbirth with CVD incidence among Chinese women.
In 2004-2008, the nationwide China Kadoorie Biobank recruited 302,669 women aged 30-79 years from ten diverse localities. During 7 years of follow-up, 43,968 incident cases of circulatory disease, 14,440 of coronary heart disease, and 19,925 of stroke (including 11,430 ischaemic and 2170 haemorrhagic strokes), were recorded among 289,573 women without prior CVD at baseline. Cox regression yielded multiple adjusted hazard ratios (HRs) for CVD risks associated with pregnancy outcomes.
Overall, 99% of women had been pregnant, and among them 10%, 53%, and 7% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Each additional pregnancy was associated with an adjusted HR of 1.03 (95% confidence interval, CI: 1.02; 1.04) for circulatory disease. A history of miscarriage, induced abortion, and stillbirth, respectively, were associated with adjusted HRs of 1.04 (1.01; 1.07), 1.04 (1.02; 1.07), and 1.07 (1.03; 1.11) for circulatory disease. The relationship was stronger with recurrent pregnancy loss; adjusted HRs for each additional loss being 1.04 (1.00; 1.09) for miscarriage, 1.02 (1.01; 1.04) for induced abortion, and 1.04 (1.00; 1.08) for stillbirth.
Among Chinese women, increases in pregnancy, and a history and recurrence of miscarriage, induced abortion, and stillbirth are each associated with a higher risk of CVD.
Breastfeeding confers substantial benefits to child health and has also been associated with lower risk of maternal cardiovascular diseases (CVDs) in later life. However, the evidence on the effects ...of CVD is still inconsistent, especially in East Asians, in whom the frequency and duration of breastfeeding significantly differ from those in the West.
In 2004-2008, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30 to 79 years from 10 diverse regions across China. During 8 years of follow-up, 16 671 incident cases of coronary heart disease and 23 983 cases of stroke were recorded among 289 573 women without prior CVD at baseline. Cox regression yielded adjusted hazard ratios (HRs) and 95% CIs for incident CVD by breastfeeding. Overall, ≈99% of women had given birth, among whom 97% reported a history of breastfeeding, with a median duration of 12 months per child. Compared with parous women who had never breastfed, ever breastfeeding was associated with a significantly lower risk of CVD, with adjusted HRs of 0.91 (95% CI, 0.84-0.99) for coronary heart disease and 0.92 (95% CI, 0.85-0.99) for stroke. Women who had breastfed for ≥24 months had an 18% (HR, 0.82; 0.77-0.87) lower risk of coronary heart disease and a 17% (HR, 0.83; 0.79-0.87) lower risk of stroke compared with women who had never breastfed. Among women who ever breastfed, each additional 6 months of breastfeeding per child was associated with an adjusted HR of 0.96 (95% CI, 0.94-0.98) for coronary heart disease and 0.97 (95% CI, 0.96-0.98) for stroke.
Among Chinese women, a history of breastfeeding was associated with an ≈10% lower risk of CVD in later life and the magnitude of the inverse association was stronger among those with a longer duration of breastfeeding.
Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health ...records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China.
We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30–79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100–150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10–12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35–84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing.
At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35–84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08–1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 1·42–1·58 vs 1·25 1·20–1·30). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89–2·24) for overall mortality and 1·32 (1·27–1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking.
Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention.
British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.
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