The impact of circadian rhythms on the immune response to influenza vaccination in middle-aged and older adults (IMPROVE): a randomised controlled trial.

BACKGROUND: Vaccination is important in influenza prevention but the immune response wanes with age. The circadian nature of the immune system suggests that adjusting the time of vaccination may provide an opportunity to improve immunogenicity. Our previous cluster trial in Birmingham suggested differences between morning and afternoon vaccination for some strains in the influenza vaccine in older adults. Whether this effect is also seen in a younger age group with less likelihood of compromised immunity is unknown. We therefore conducted an individual-based randomized controlled trial in Guangzhou to test the hypothesis that influenza vaccination in the morning induces a stronger immune response in older adults than afternoon vaccination. We included adults in middle age to determine if the effect was also seen in younger age groups. RESULTS: Of the 418 participants randomised, 389 (93.1%, 191 middle-aged adults aged 50-60 years and 198 older adults aged 65-75 years) were followed up. Overall, there was no significant difference between the antibody titers (geometric mean /95% CI) after morning vs afternoon vaccination (A/H1N1: 39.9 (32.4, 49.1) vs. 33.0 (26.7, 40.7), p = 0.178; A/H3N2: 92.2 (82.8, 102.7) vs. 82.0 (73.8, 91.2), p = 0.091; B: 15.8 (13.9, 17.9) vs. 14.4 (12.8, 16.3), p = 0.092), respectively. However, in pre-specified subgroup analyses, post-vaccination titers for morning versus afternoon vaccination in the 65-75 years subgroup were (A/H1N1): 49.5 (36.7, 66.6) vs. 32.9 (24.7, 43.9), p = 0.050; (A/H3N2): 93.5 (80.6, 108.5) vs. 73.1 (62.9, 84.9), p = 0.021; (B): 16.6 (13.8, 20.1) vs. 14.4 (12.3, 17.0), p = 0.095, respectively. Among females, antibody titers for morning versus afternoon vaccination were (A/H1N1): 46.9 (35.6, 61.8) vs. 31.1 (23.8, 40.7), p = 0.030; (A/H3N2): 96.0 (83.5, 110.3) vs. 84.7 (74.4, 96.5), p = 0.176; (B): 14.8 (12.7, 17.3) vs. 13.0 (11.3, 14.9), p = 0.061, respectively. In the 50-60 years old subgroup and males, there were no significant differences between morning and afternoon vaccination. CONCLUSIONS: Morning vaccination may enhance the immunogenicity to influenza vaccine in adults aged over 65 and women. An intervention to modify vaccination programs to vaccinate older individuals in the morning is simple, cost free and feasible in most health systems.

Mendelian Randomization Focused Analysis of Vitamin D on the Secondary Prevention of Ischemic Stroke.

BACKGROUND AND PURPOSE: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. METHODS: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study-identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. RESULTS: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48-0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35-0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42-0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30-0.81]). CONCLUSIONS: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI.

Screening and the epidemic of thyroid cancer in China: An analysis of national representative inpatient and commercial insurance databases.

Reasons behind the rapid increase of thyroid cancer (TC) in China are uncertain. We assessed the burden of TC and the role of access to screening and salt iodization. We analyzed two national databases in China: Hospital Quality Monitoring System (HQMS) and China Reinsurance Company (CRC) database. HQMS covered 1037 (44.3%) Class 3 hospitals and 76 263 617 Class 3 hospital inpatients in 2013 to 2017 and CRC covered 93 123 018 clients in 2000 to 2016. The proportion of TC inpatients among inpatients in HQMS and TC incidence in critical illness insurance buyers were used to evaluate the association with screening and iodine status. Between 2013 and 2017, the proportion of TC patients in HQMS with urban employee medical insurance and good access to screening increased sharply while there was little change among those with the other two forms of medical insurance. Across provinces, the proportion of TC inpatients in HQMS was positively correlated with per capita disposable income but not with median urinary iodine. Similar findings were observed in the CRC database. In 2017, approximately 1000 individuals were overdiagnosed with TC daily. We conservatively forecast that 5.1 million healthy individuals would become TC patients unnecessarily between 2019 and 2030. Our findings suggested the epidemic of TC in China was substantially underestimated. It was associated with screening but not with salt iodization.

Higher total white blood cell and neutrophil counts are associated with an increased risk of fatal stroke occurrence: the Guangzhou biobank cohort study.

BACKGROUND: Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population. METHODS: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke. RESULTS: (i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16-2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10-2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10-1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10-2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (- 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07-2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02-2.05, P = 0.04) increased risk of fatal all stroke occurrence. CONCLUSIONS: The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population.

Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.

AIMS/HYPOTHESIS: Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. METHODS: An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. RESULTS: In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery < 6.45 × 10-7). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta] = 3.74 × 10-15) in the combined analysis. CONCLUSIONS/INTERPRETATION: We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.

The effect of physician's 30 s smoking cessation intervention for male medical outpatients: a pilot randomized controlled trial.

OBJECTIVE: To study the effectiveness of a very brief advice (<30 s) on smoking cessation. DESIGN: A 'proof-of-principle' single-blind, randomized controlled trial (RCT). SETTING: Medical outpatient clinics of a general hospital in Guangzhou, China. PARTICIPANTS: One hundred and twenty-six male current smokers randomly allocated into an intervention (n = 74) and a control group (n = 52). Intervention A health warning by physicians that half of all smokers would be killed by smoking, an advice to quit immediately and referral to a cessation clinic. The control group received none. OUTCOMES: Primary: seven-day quitting point prevalence at 6 months. Secondary: 7-day point prevalence at 1, 3 and 12 months, sustained abstinence at 3, 6 and 12 months, smoking reduction by half and cessation clinic attendance. RESULTS: By intention-to-treat analysis, 7-day quitting point prevalence rates at four follow-ups were 27.0, 23.0, 21.6 and 18.9% in the intervention group, compared with 5.8, 3.8, 5.8 and 5.8% in the control group (first three P < 0.05). At 3, 6 and 12 months, sustained abstinence prevalence rates were 18.9, 17.6 and 14.9% versus 3.8, 3.8 and 3.8% (P = 0.035, 0.046, 0.074). More smokers in the intervention group had reduced smoking. Almost no participants attended the cessation clinic. CONCLUSION: Our findings support the need for large RCTs on minimal interventions with the 'one in two' warning.

Study protocol for "Moving Bright, Eating Smart"- A phase 2 clinical trial on the acceptability and feasibility of a diet and physical activity intervention to prevent recurrence in colorectal cancer survivors.

BACKGROUND: Colorectal cancer is the second most common cancer and cancer-killer in Hong Kong with an alarming increasing incidence in recent years. The latest World Cancer Research Fund report concluded that foods low in fibre, and high in red and processed meat cause colorectal cancer whereas physical activity protects against colon cancer. Yet, the influence of these lifestyle factors on cancer outcome is largely unknown even though cancer survivors are eager for lifestyle modifications. Observational studies suggested that low intake of a Western-pattern diet and high physical activity level reduced colorectal cancer mortality. The Theory of Planned Behaviour and the Health Action Process Approach have guided the design of intervention models targeting a wide range of health-related behaviours. METHODS/DESIGN: We aim to demonstrate the feasibility of two behavioural interventions intended to improve colorectal cancer outcome and which are designed to increase physical activity level and reduce consumption of a Western-pattern diet. This three year study will be a multicentre, randomised controlled trial in a 2x2 factorial design comparing the "Moving Bright, Eating Smart" (physical activity and diet) programme against usual care. Subjects will be recruited over a 12-month period, undertake intervention for 12 months and followed up for a further 12 months. Baseline, interim and three post-intervention assessments will be conducted.Two hundred and twenty-two colorectal cancer patients who completed curative treatment without evidence of recurrence will be recruited into the study. Primary outcome measure will be whether physical activity and dietary targets are met at the end of the 12-month intervention. Secondary outcome measures include the magnitude and mechanism of behavioural change, the degree and determinants of compliance, and the additional health benefits and side effects of the intervention. DISCUSSION: The results of this study will establish the feasibility of targeting the two behaviours (diet and physical activity) and demonstrate the magnitude of behaviour change. The information will facilitate the design of a further larger phase III randomised controlled trial with colorectal cancer outcome as the study endpoint to determine whether this intervention model would reduce colorectal cancer recurrence and mortality. TRIAL REGISTRATION: ClinicalTrials.gov No: NCT01708824.

Parity and incident type 2 diabetes in older Chinese women: Guangzhou Biobank Cohort Study.

This study examined the association between parity and incident type 2 diabetes in older Chinese women and estimated the mediation effect of adiposity indicators. A total of 11,473 women without diabetes at baseline from 2003 to 2008 were followed up until 2012. We used Cox proportional hazards regression to assess the association between parity and incident type 2 diabetes, and mediation analysis to estimate the mediation effect of adiposity indicators. Compared to women with one parity, the hazard ratio (HR) (95% confidence interval (CI)) for incident type 2 diabetes was 0.85 (0.44-1.63), 1.20 (1.11-1.30), 1.28 (1.16-1.41) and 1.27 (1.14-1.42) for women with parity of 0, 2, 3, and ≥ 4, respectively. The proportion of indirect effect (95% CI) mediated by body mass index, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage was 26.5% (19.2-52.2%), 54.5% (39.4-108.7%), 25.1% (18.2-49.1%), 35.9% (25.6-74.1%), 50.3% (36.5-98.6%) and 15.1% (- 66.4 to 112.3%), respectively. Compared to women with one parity, women with multiparity (≥ 2) had a higher risk of incident type 2 diabetes and up to half of the association was mediated by abdominal obesity.

Designing an intervention to help people with colorectal adenomas reduce their intake of red and processed meat and increase their levels of physical activity: a qualitative study.

BACKGROUND: Most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients' preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial. METHODS: Patients aged 60-74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared. RESULTS: Two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population. CONCLUSIONS: This study has confirmed and amplified recently published factors involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to individuals, the lack of knowledge about the aetiology of colon cancer and the lack of motivation to change behaviour are critical factors. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03320951.

Low-Carbohydrate Diets and Mortality in Older Asian People: A 15-Year Follow-Up from a Prospective Cohort Study.

The long-term effects of a low-carbohydrate diet (LCD) on mortality, accounting for the quality and source of the carbohydrate, are unclear. Hence, we examined the associations of LCDs with all-cause and cause-specific mortality in a prospective cohort study. A total of 20,206 participants (13.8% diabetes) aged 50+ years were included. Overall, vegetable-based and meat-based LCD scores were calculated based on the percentage of energy as total and subtypes of carbohydrates, fat, and protein. Cox regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). During 294,848 person-years of follow-up, 4624 deaths occurred, including 3661 and 963 deaths in participants without and with diabetes, respectively. In all participants, overall LCD score was not associated with all-cause and cause-specific mortality, after multivariable adjustment. However, for the highest versus the lowest quartiles of vegetable-based LCD, the adjusted HRs (95%CIs) of all-cause and CVD mortality were 1.16 (1.05-1.27) and 1.39 (1.19-1.62), respectively. The corresponding values for highest versus lowest quartiles of meat-based LCD for all-cause and CVD mortality were 0.89 (0.81-0.97) and 0.81 (0.70-0.93), respectively. Similar associations were found in participants without diabetes. In patients with diabetes, the adjusted HR (95%CI) of CVD mortality for the highest versus the lowest quartiles of vegetable-based LCD was 1.54 (1.11-2.14). Although there were no significant associations with overall LCD score, we found that the vegetable-based LCD score was positively, whereas the meat-based LCD score was negatively, associated with all-cause and CVD mortality in older Asian people.

Mendelian randomization analysis of vitamin D in the secondary prevention of hypertensive-diabetic subjects: role of facilitating blood pressure control.

BACKGROUND: Vitamin D (Vit-D) promotes vascular repair and its deficiency is closely linked to the development of type 2 diabetes mellitus (T2DM) and hypertension. Whether genetially predicted vitamin D status (serological 25-hydroxyvitamin D [25(OH)D]) confers secondary protection against cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was unknown. METHODS: This is a prospective, individual-data, two-sample Mendelian randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive Vit-D mechanistic pathways using high-throughput exome chip analyses in a derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of comprehensive CVD hard clinical endpoints in an independent sample of hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and serological 25(OH)D deficiency [< 20 ng/mL] 45%. RESULTS: After 55.6 ± 28.9 months, 561 (15%) combined CVD events including myocardial infarction, unstable angina, ischemic stroke, congestive heart failure, peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier analysis showed that genetically predicted reduced vitamin D status was associated with reduced event-free survival from combined CVD events (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). Mendelian randomization indicates that increased Vit-D exposure, leveraged through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects against combined CVD events (Wald's estimate: OR = 0.86 [95%CI 0.75 to 0.95]), and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, genetically predicted increase in Vit-D status ameliorates risk of deviation from achieving guideline-directed hypertension control (JNC-8: systolic target < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]). CONCLUSIONS: Genetically predicted increase in Vit-D status [25(OH)D] may confer secondary protection against incident combined CVD events and myocardial infarction in a hypertensive-diabetic population where serological 25(OH)D deficiency is common, through facilitating blood pressure control.

Natural menopausal age and cardiovascular disease risk factors in older Chinese women: Guangzhou Biobank Cohort Study.

OBJECTIVE: To examine the associations of natural menopausal age with cardiovascular disease risk factors and whether the associations varied by parity in older Chinese women. METHODS: Information of demographic characteristics, lifestyles, and reproductive factors was collected by face-to-face interview. Framingham Risk Score was used as an indicator of cardiovascular disease risk, with a score ≥ 10% considered as high cardiovascular disease risk (vs low, dichotomous). Multivariable logistic and linear regressions were used to examine the associations of menopausal age with cardiovascular disease risk factors. RESULTS: Of 18,339 women aged 50+ years, the average (standard deviation) age was 61.8 (6.9) years. Compared with women with menopausal age of 45 to 54 years, after adjustment for multiple potential confounders, women with menopausal age <45 years or ≥55 years had higher Framingham Risk Score (0.93%, 95% confidence interval: 0.40-1.46, and 0.69%, 95% confidence interval: 0.18-1.20, respectively). Women with menopausal age <45 or ≥55 years had higher odds of high cardiovascular disease risk (vs low) (odds ratio [95% confidence interval]:1.26 (1.10-1.44) and 1.17 (1.02-1.33), respectively). The associations of menopausal age with the Framingham Risk Score varied by parity (P for interaction ≤0.001). The Framingham Risk Score was higher in those with one to three parity (<45 y: 1.01 [0.43-1.59]; ≥55 y: 1.14 [0.60-1.68]) and lower for parity ≥4 (<45 y: -0.33 [-1.84 to 1.18]; ≥55 y: -2.02 [-3.82 to -0.22]). In nulliparous women, the Framingham Risk Score was highest in menopausal age <45 years (3.97 [1.67-6.26]), but the differences were nonsignificant in menopausal age ≥55 years (0.66 [-1.38 to 2.71]). CONCLUSIONS: Both early and late natural menopausal ages were associated with a higher cardiovascular disease risk, and the associations were stronger in those with lower parity.

Video Summary:http://links.lww.com/MENO/A813 .

Effects of dietary and physical activity interventions on generic and cancer-specific health-related quality of life, anxiety, and depression in colorectal cancer survivors: a randomized controlled trial.

PURPOSE: To assess the effects of dietary and physical activity (PA) interventions on generic and cancer-specific quality of life (QoL), anxiety, and depression levels among adult Chinese colorectal cancer (CRC) survivors. METHODS: Two-hundred twenty-three adult CRC survivors within 1 year of completion of primary cancer treatment were randomized to receive dietary, PA or combined intervention, or usual care for a 12 monthduration, under a 2 (diet vs usual care) × 2 (PA vs usual care) factorial design. Generic and cancer-specific QoL was assessed using a Chinese version 12-Item Short Form Health Survey (SF-12) and the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) scale, respectively. Anxiety and depression was assessed using the Hospital Anxiety and Depression Scale at baseline, 6, 12, 18, and 24 months. Linear mixed models were used for examining the intervention effects. RESULTS: Participants receiving dietary intervention experienced a significant improvement in the generic measure of QoL (SF-6D utility scores, mean difference 0.042, 95%CI 0.03 to 0.081) at 12 months, the cancer-specific QoL scores (mean difference 3.09, 95%CI 0.13 to 6.04), and levels of depression (P = 0.015) at both 12 and 24 months follow-up. Participants receiving PA intervention only demonstrated a significant improvement in SF-6D utility index (mean difference 0.039, 95%CI 0.002 to 0.077) and physical functioning (mean difference 2.85, 95%CI 1.00 to 4.70) at 6 months. CONCLUSIONS: Dietary intervention improved the generic and cancer-specific QoL and depression in CRC survivors. TRIAL REGISTRATION: The study was prospectively registered on 17 October 2012 at ClinicalTrials.gov (NCT01708824). IMPLICATIONS FOR CANCER SURVIVORS: CRC survivors can benefit from dietary interventions in alleviating depression and improving overall health-related QoL.

Systemic Corticosteroids and Mortality in Severe and Critical COVID-19 Patients in Wuhan, China.

BACKGROUND: Systemic corticosteroids are now recommended in many treatment guidelines, although supporting evidence is limited to 1 randomized controlled clinical trial (RECOVERY). OBJECTIVE: To identify whether corticosteroids were beneficial to COVID-19 patients. METHODS: A total of 1514 severe and 249 critical hospitalized COVID-19 patients from 2 medical centers in Wuhan, China. Multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]) were used to estimate the association of corticosteroid use with risk of in-hospital mortality in severe and critical cases. RESULTS: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to the non-corticosteroid group, systemic corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality in either severe cases (HR = 1.77; 95% CI, 1.08-2.89; P = 0.023), or critical cases (HR = 2.07; 95% CI, 1.08-3.98; P = 0.028). Findings were similar in time-varying Cox analysis. For patients with severe COVID-19 at admission, corticosteroid use was not associated with improved or harmful outcome in either PSM or IPTW analysis. For critical COVID-19 patients at admission, results were consistent with multivariable Cox model analysis. CONCLUSION: Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan. Absence of the beneficial effect in our study in contrast to that observed in the RECOVERY clinical trial may be due to biases in observational data, in particular prescription by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, timing of initiation of treatment, and duration of treatment.

Tar, nicotine and carbon monoxide yield of UK cigarettes and the risk of non-muscle-invasive and muscle-invasive bladder cancer.

Cigarette smoking is a major risk factor for bladder cancer (BC); however, the impact of cigarette content remains unclear. This study aims to investigate tar, nicotine and carbon monoxide (TNCO) yields of different filtered cigarettes in relation to BC risk. From the Bladder Cancer Prognosis Programme 575 non-muscle-invasive bladder cancer (NMIBC) cases, 139 muscle-invasive bladder cancer (MIBC) cases and 130 BC-free controls with retrospective data on smoking behaviour and cigarette brand were identified. Independently measured TNCO yields of cigarettes sold in the UK were obtained through the UK Department of Health and merged with the Bladder Cancer Prognosis Programme dataset to estimate the daily intake of TNCO. BC risk increased by TNCO intake category for NMIBC cases (P <0.050 in all multivariate models), but only for the daily intake of tar for MIBC cases (P=0.046) in multivariate models. No difference in risk was observed between smokers of low-tar/low-nicotine and high-tar/high-nicotine cigarettes compared with never smokers, either for NMIBC (P=0.544) or MIBC (P=0.449). High daily intake of TNCO additionally increases the risk of both NMIBC and MIBC compared with low daily intake. However, as there is no difference in BC risk between low-tar/low-nicotine and high-tar/high-nicotine cigarette smokers, it remains unclear whether smoking behaviour or TNCO yield of cigarettes explains this association.

[A cross-sectional study on self-reported health and intention of quitting smoking of smokers in Guangzhou factory workers].

OBJECTIVE: To investigate the health status and intention of quitting smoking in factory workers, so as to provide scientific evidence for smoking control. METHODS: A cross-sectional survey was carried out on smoking behavior, self-reported health status (SRHS), and intention of quitting smoking in 668 Guangzhou factory workers with different job types. Fagerstrom Test for Nicotine Dependence (FTND) was used on current smokers. Logistic regression model was used to analyze the association of SRHS, difficulty of quitting smoking (DQS) with some risk factors. RESULTS: (1) 65.0% (n = 348) male and 3.0% (n = 4) female workers were ever-smokers. 90.6% of male smokers usually smoked when getting together with friends or smokers, staying at home, or at leisure time, or just after a meal. (2) 10.7% of the daily smokers and ex-smokers had a worse SRHS than the general same-age people, which is significantly higher than 5.1% of the occasional smokers and those who were never smoking. The OR was 2.22 (95% CI 1.08 approximately 4.59) after adjusting age and education. (3) Of male daily smokers, 50.5% ever thought of quitting smoking. The proportions of ever-thought of quitting smoking were 73.3%, 50.0% and 37.2% respectively in those with better, pretty the same and worse SRHS than the general same-age people (P = 0.009). The proportions of DQS self-scored 30 or less, 31 to 60 and 60 or more were 26.9%, 24.9% and 48.2% respectively in male daily smokers. The OR for DQS (self-scored > 30 vs < or =30) increased with increasing number of colleague smoked and worked around, and with nicotine dependence. CONCLUSION: Daily smokers and former smokers have worse SRHS than those who are occasional smokers or never smokers in male workers, and most of those with worse SRHS who ever thought of quitting smoking. The DQS is mainly significantly associated with number of colleague smoking and working around, and with nicotine dependence.

The role of social support in family socio-economic disparities in depressive symptoms during early pregnancy: Evidence from a Chinese birth cohort.

BACKGROUND: Few studies have examined the association between a composite measure of family socio-economic position (SEP)2 and depressive symptoms among Chinese pregnant women, nor any potential underlying mechanisms which may be amenable to preventative interventions. METHODS: We investigated the association between a composite SEP measure and depressive symptoms during early pregnancy, and tested for mediation by social support and moderation by parity in the Born in Guangzhou Cohort Study (n = 12,382) using adjusted logistic regression and causal mediation analysis. RESULTS: In this population, 18.4% of women experienced depressive symptoms before the 20th gestational week. Compared with the highest quartile, the lowest SEP score quartile was associated with a higher risk of depressive symptoms (OR 1.50, 95% CI 1.31-1.71), which was more pronounced among multiparous women than nulliparous women (P for interaction <0.001). Social support mediated the association between SEP and depressive symptoms, with greater proportion mediated in nulliparous women (73.4% for the lowest SEP score quartile) than multiparous women (30.5%). LIMITATIONS: Depressive symptoms were measured by Self-rated Depression Scale, which is not designed as a clinical diagnosis tool for depression. We only had information on perceived social support but not actual social support, although these two parameters were modestly correlated. CONCLUSION: Lower SEP was associated with higher risk of depressive symptoms in pregnant women, driven by social support. And the association between SEP and depressive symptoms and mediation by social support were modified by parity. Whether this association extends to the post pregnancy period or is amenable to cost-effective interventions should be investigated in further studies.

Dietary and Physical Activity Interventions for Colorectal Cancer Survivors: A Randomized Controlled Trial.

There has been evidence on the protective effects of diets high in fiber and low in red and processed meat (RPM), and physical activity (PA) against colorectal cancer (CRC) development, but that against CRC recurrence has been limited. This study evaluated the efficacy of a behavioral program comprising dietary and PA interventions in improving Chinese CRC survivors' lifestyle. A 2 × 2 factorial randomized controlled trial of 223 CRC patients (82 females, mean age 65), randomly assigned to receive dietary, PA or both interventions, or usual care for 12 months, and assessed every 6 months for 24 months. Primary outcomes included two dietary and two PA targets. Secondary outcomes included changes in dietary consumptions and PA levels. Dietary interventions significantly increased the odds of achieving the targets of consuming less RPM at all time-points (OR 3.22-4.57, all p < 0.01) and refined grain (RG) at months 6 (OR 3.13, p = 0.002) and 24 (OR 2.19, p = 0.039), and reduced RPM (2.49-3.48 servings/week, all p < 0.01) and RG (0.31-0.5 servings/day, all p < 0.01) consumptions. Patients receiving PA interventions potentially spent more time on moderate-to-vigorous PA. This study demonstrated the efficacy of a behavioral program in improving dietary habits of Chinese CRC survivors.

Differences in perceived causes of childhood obesity between migrant and local communities in China: A qualitative study.

In developing countries, obesity traditionally affectsmore affluent children, butis spreading to a wider social group. Understanding the perceivedcontributors can provide valuable insights to plan preventive interventions. We exploreddifferences in the perceived causes of childhood obesity between local and migrant communities in a major Chinese city. We conducted 20 focus groups (137 parents, grandparents, school teachers) and 11semi-structured interviews with school Principals from migrant and local communities in Guangzhou. Data were transcribed and analysed using a thematic approach. We found that Lack of influence from grandparents, who were perceived to promote obesogenic behaviorin local children, fewer opportunities for unhealthy snacking and less pressure for academic attainment leading to moreactive play were interpreted as potential "protective" factors among migrant children. Nevertheless, two perceived causes of obesity were more pronounced in migrant than local children: lack of parental monitoring after-school andunsafe neighborhoods limiting physical-activity. Two barriers that restricted child physical activity were only found in the migrant community: limited home space, and cultural differences, inhabitinginteractive play with local children. Future interventions should consider uniquedeterminants of obesity in children from different social backgrounds, with tailored strategies to prevent further rise of the epidemic.

[Determination of cotinine in human urine with gas chromatograph-mass spectrometry].

OBJECTIVE: To establish the method of gas chromatograph-mass spectrometry (GC-MS) for the determination of the cotinine (COT) in human urine. METHODS: The conjugated trans-3'-hydroxycotinine (THOC) and COT were hydrolyzed in human urine with beta-glucuronidase. The composition of COT was extracted with the mixture of dichloromethane and n-butyl acetate (2:1) and was separated with HP-5MS fused-silica capillary column. The GC-MS was used for determining its content. RESULTS: The monitoring limit of this method was 0.02 microg/L. Its recovery rate was higher than 90%, Its accuracy rate was 4.30%. It was used for the determination of the cotinine in human urine in Guangzhou Biological Bank the Elderly Cohort. CONCLUSION: The GC-MS method is a good microanalysis for monitoring the cotinine in human urine rapidly and accurately with little background disturbance. It has been applied in our Guangzhou Cohort Study for determining cotinine in human urine.