Estimating effects of whole grain consumption on type 2 diabetes, colorectal cancer and cardiovascular disease: a burden of proof study.

BACKGROUND: Previous studies on whole grain consumption had inconsistent findings and lacked quantitative assessments of evidence quality. Therefore, we aimed to summarize updated findings using the Burden of Proof analysis (BPRF) to investigate the relationship of whole grain consumption on type 2 diabetes (T2D), colorectal cancer (CRC), stroke, and ischemic heart disease (IHD). METHODS: We conducted a literature search in the Medline and Web of Science up to June 12, 2023, to identify related cohort studies and systematic reviews. The mean RR (relative risk) curve and uncertainty intervals (UIs), BPRF function, risk-outcome score (ROS), and the theoretical minimum risk exposure level (TMREL) were estimated to evaluate the level of four risk-outcome pairs. RESULTS: In total, 27 prospective cohorts were included in our analysis. Consuming whole grain at the range of TMREL (118.5-148.1 g per day) was associated with lower risks: T2D (declined by 37.3%, 95% UI: 5.8 to 59.5), CRC (declined by 17.3%, 6.5 to 27.7), stroke (declined by 21.8%, 7.3 to 35.1), and IHD (declined by 36.9%, 7.1 to 58.0). For all outcomes except stroke, we observed a non-linear, monotonic decrease as whole grain consumption increased; For stroke, it followed a J-shaped curve (the greatest decline in the risk of stroke at consuming 100 g whole grain for a day). The relationships between whole grain consumption and four diseases are all two-star pairs (ROS: 0.087, 0.068, 0.062, 0.095 for T2D, CRC, stroke, and IHD, respectively). CONCLUSION: Consuming 100 g of whole grains per day offers broad protective benefits. However, exceeding this threshold may diminish the protective effects against stroke. Our findings endorse replacing refined grains with whole grains as the main source of daily carbohydrates. REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: We have registered our research in PROSPERO, and the identifier of our meta-analyses is CRD42023447345.

Antibiotic use in people and pigs: a One Health survey of rural residents' knowledge, attitudes and practices in Shandong province, China.

Objectives: To evaluate rural residents' knowledge, attitudes and practices (KAP) towards antibiotic use in humans and pigs, among individuals with and without backyard pig farms living in Shandong province, China. Methods: We conducted a cross-sectional questionnaire study among residents in 12 villages, and directly observed medicines stored in households for humans and pigs. Results: In total, 769 residents participated, including 330 backyard pig farmers. Respondents had low levels of knowledge about antibiotics. A quarter of participants had bought one or more antibiotics from a pharmacy without a prescription in the previous year, and this was more common among pig farmers who had bought antibiotics for their pigs without consulting a vet (49% versus 25%, P < 0.001). Stored antibiotics for human use were found in 42% of households, and 70% of participants from these households did not know they were storing antibiotics. Thirty-one percent of backyard pig farmers were storing antibiotics for pig use. Farmers who thought it was good to store leftover antibiotics for their pigs were more likely to have stored antibiotics for pigs (41% versus 20%) and for humans (47% versus 32%; both P < 0.01). A fifth of participants thought their own actions were important for controlling antibiotic resistance. Conclusions: We found differences in the KAP of backyard pig farmers and non-pig farmers to antibiotics, and parallels between pig farmers' attitudes and behaviours towards antibiotic use in pigs and in humans. Our findings reinforce the need for context-adapted multifaceted interventions to improve antibiotic use and provide suggestions for targeting educational approaches.

Antibiotic use in rural China: a cross-sectional survey of knowledge, attitudes and self-reported practices among caregivers in Shandong province.

BACKGROUND: To improve antibiotic use globally, we must deepen our understanding of the public's knowledge, attitudes and practices (KAP) concerning antibiotics. Children are frequent users of antibiotics, and their caregivers play important roles in determining how antibiotics are used. The purpose of this study was to describe caregivers' KAP in a rural province in eastern China, and to identify socio-demographic factors associated with inappropriate antibiotic use. METHODS: A cross-sectional questionnaire based survey was conducted in 12 villages in one county in Shandong Province. A total of 727 individuals who were the primary day-to-day caregiver for a child aged 0-7 years were randomly selected and invited to participate. All caregivers were surveyed face-to-face using a semi-structured questionnaire focusing on the use of antibiotics in children. RESULTS: Almost all invited caregivers (99.3 %) completed the questionnaire in full. Caregivers expressed high levels of over-expectation for antibiotics for common childhood symptoms, stating that antibiotics were always or usually necessary when a child has a fever (46 %) or dry cough (42 %). Most caregivers (93 %) were aware that they should follow the doctor's advice when giving their children antibiotics. Many, however, reported that they had previously deviated from advice; this was most commonly through using antibiotics intermittently rather than regularly, but also by increasing and decreasing doses. Caregivers that were older and that had less formal education had higher levels of self-reported adherence (p < 0.01). A third of caregivers admitted to storing leftover antibiotics at home, and almost all of these caregivers (97 %) had used the antibiotics on a second occasion for their child. CONCLUSION: We have identified important gaps in knowledge, attitudes and practices concerning antibiotics among this rural population of caregivers. There is a clear need for multifaceted interventions that target village doctors, to improve prescribing and communication, as well as the general public, to improve health-seeking behaviours and promote responsible individual use of antibiotics.

The effect of antenatal pelvic floor muscle training on labor and delivery outcomes: a systematic review with meta-analysis.

INTRODUCTION AND HYPOTHESIS: Pelvic floor muscle training (PFMT) has been widely used to prevent and treat urinary incontinence; however, the possible effect of antenatal PFMT on labor and delivery is still not clear. The purpose of the study was to investigate the possible effect of antenatal PFMT on labor and delivery. METHODS: A systematic review of the scientific literature was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Randomized or quasi-randomized controlled studies of an obstetric population who had done antenatal PFMT met the inclusion criteria. Data about labor and delivery outcomes included the first stage of labor, the second stage of labor, episiotomy, instrumental delivery, and perineal laceration. The nine English and four Chinese databases were searched from their inception through November 6, 2014. Fixed or random effects models were selected based on study heterogeneity. The weighted mean differences (WMDs) and odds ratios (ORs) with the corresponding 95 % confidence intervals (CIs) were calculated to assess the association between PFMT and the labor and delivery outcomes. RESULTS: Twelve studies were identified, involving a total of 2,243 women, in which 1,108 were PFMT and 1,135 controls. They indicated that PFMT during pregnancy significantly shortened the first and second stage of labor in the primigravida (WMD = -28.33, 95 % CI: -42.43 to -14.23, I(2) = 0.0 % , and WMD = -10.41, 95 % CI: -18.38 to -2.44, I(2) = 64.0 % respectively). In the subgroup analysis on the second stage of labor, heterogeneity decreased for subgroups of China and European countries (I(2) = 0.0 %, P = 0.768 and I(2) = 0.0 %, P = 0.750 respectively), but statistically significant association only existed in the subgroup of China (WMD = -17.42, 95 % CI: -23.41 to -11.43). When evaluating the effect on the rates of episiotomy, instrumental delivery and perineal laceration, the meta-analysis showed that the results were not significant (OR = 0.75, 95 % CI: 0.54 to 1.02; OR = 0.84, 95 % CI: 0.61 to 1.17 and OR = 0.96, 95 % CI: 0.66 to 1.40 respectively). CONCLUSIONS: Antenatal PFMT might be effective at shortening the first and second stage of labor in the primigravida. The moderate heterogeneity for the second stage of labor data need further study. Antenatal PFMT may not increase the risk of episiotomy, instrumental delivery, and perineal laceration in the primigravida.

Understanding the educational inequalities in suicide attempts and their mediators: a Mendelian randomisation study.

Background: Educational inequalities in suicide have become increasingly prominent over the past decade. Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities. Aims: To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect. Methods: We conducted a two-sample Mendelian randomisation (MR) analysis to estimate the causal effect of educational attainment on suicide attempts, utilising genome-wide association study summary statistics from the Integrative Psychiatric Research (iPSYCH; 6024 cases and 44 240 controls) and FinnGen (8978 cases and 368 299 controls). We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect. Results: In the combined analysis of iPSYCH and FinnGen, each standard deviation (SD) decrease in genetically predicted educational attainment (equating to 3.4 years of education) was associated with a 105% higher risk of suicide attempts (odds ratio (OR): 2.05; 95% confidence interval (CI): 1.81 to 2.31). Of the 42 risk factors analysed, the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts. The respective proportions of mediation were 47% (95% CI: 29% to 66%) for smoking behaviour, 36% (95% CI: 0% to 84%) for chronic pain, 49% (95% CI: 36% to 61%) for depression, 35% (95% CI: 12% to 59%) for anxiety and 26% (95% CI: 18% to 34%) for insomnia. Multivariable MR implicated these five mediators collectively, accounting for 68% (95% CI: 40% to 96%) of the total effect. Conclusions: This study identified smoking, chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.

Determinants of Non-Participation in Population-Based Breast Cancer Screening: A Systematic Review and Meta-Analysis.

Background: Breast cancer (BC) screening can be performed in a screening program (BCSP) or in opportunistic screening. The existing reviews on the determinants of non-participation depend on self-reported data which may be biased. Furthermore, no distinction was made between the probably different determinants of both screening strategies. Objective: To find the determinants of non-participation in BCSP by means of a meta-analysis. Methods: PubMed, Embase, and Web of Science were searched for observational studies which quantified factors associated with non-participation in BCSP in a general population. Studies on opportunistic screening and studies using self-reported data were excluded. A random-effect model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Potential sources of heterogeneity were explored by stratification of the results. Results: Twenty-nine studies with in a total of 20,361,756 women were included. Low income (OR: 1.20, 95% CI: 1.10-1.30), low education (OR: 1.18, 95% CI: 1.05-1.32), living far from an assigned screening unit (OR: 1.15, 95% CI: 1.07-1.24), being immigrant (OR: 2.64, 95% CI: 2.48-2.82), and having a male family doctor (OR: 1.43, 95% CI: 1.20-1.61) was associated with higher non-participation in screening. Reminders sent to non-attenders and estimations of ORs (adjusted or not) partly explained substantial heterogeneity. Conclusion: In this meta-analysis excluding studies on the non-participation in opportunistic screening, or with self-reported data on non-participation, the well-known determinants for non-participation are still significant, but less strong. This analysis only supports the relevance of meta-analysis of studies with registered non-participation in a BCSP. Systematic Review Registration: PROSPERO, CRD42020154016.

Effectiveness of Organized Mammography Screening for Different Breast Cancer Molecular Subtypes.

BACKGROUND: Screening program effectiveness is generally evaluated for breast cancer (BC) as one disease and without considering the regularity of participation, while this might have an impact on detection rate. OBJECTIVES: To evaluate the short-term effectiveness of a mammography screening program for the major molecular subtypes of invasive BC. METHODS: All women who participated in the screening program and were diagnosed with screen-detected or interval BC in Flanders were included in the study (2008-2018). Molecular subtypes considered were luminal and luminal-HER2-positive, human epidermal growth factor receptor 2-positive, and triple-negative BC (TNBC). The relationship between the BC stage at diagnosis (early (I-II) versus advanced (III-IV)) and the method of detection (screen-detected or interval) and the relationship between the method of detection and participation regularity (regular versus irregular) were evaluated by multi-variable logistic regression models. All models were performed for each molecular subtype and adjusted for age. RESULTS: Among the 12,318 included women, BC of luminal and luminal-HER2-positive subtypes accounted for 70.9% and 11.3%, respectively. Screen-detected BC was more likely to be diagnosed at early stages than interval BC with varied effect sizes for luminal, luminal-HER2-positive, and TNBC with OR:2.82 (95% CI: 2.45-3.25), OR:2.39 (95% CI: 1.77-3.24), and OR:2.29 (95% CI: 1.34-4.05), respectively. Regular participation was related to a higher likelihood of screening detection than irregular participation for luminal, luminal-HER2-positive, and TNBC with OR:1.21 (95% CI: 1.09-1.34), OR: 1.79 (95% CI: 1.38-2.33), and OR: 1.62 (95% CI: 1.10-2.41), respectively. CONCLUSIONS: Regular screening as compared to irregular screening is effective for all breast cancers except for the HER2 subtype.

Overdiagnosis of invasive breast cancer in population-based breast cancer screening: A short- and long-term perspective.

BACKGROUND: Overdiagnosis of invasive breast cancer (BC) is a contentious issue. OBJECTIVE: The aim of this paper is to estimate the overdiagnosis rate of invasive BC in an organised BC screening program and to evaluate the impact of age and follow-up time. METHODS: The micro-simulation model SiMRiSc was calibrated and validated for BC screening in Flanders, where women are screened biennially from age 50 to 69. Overdiagnosis rate was defined as the number of invasive BC that would not have been diagnosed in the absence of screening per 100,000 screened women during the screening period plus follow-up time (which was set at 5 years and varied from 2 to 15 years). Overdiagnosis rate was calculated overall and stratified by age. RESULTS: The overall overdiagnosis rate for women screened biennially from 50 to 69 was 20.1 (95%CI: 16.9-23.2) per 100,000 women screened at 5-year follow-up from stopping screening. Overdiagnosis at 5-year follow-up time was 12.9 (95%CI: 4.6-21.1) and 74.2 (95%CI: 50.9-97.5) per 100,000 women screened for women who started screening at age 50 and 68, respectively. At 2- and 15-year follow-up time, overdiagnosis rate was 98.5 (95%CI: 75.8-121.3) and 13.4 (95%CI: 4.9-21.9), respectively, for women starting at age 50, and 297.0 (95%CI: 264.5-329.4) and 34.2 (95%CI: 17.5-50.8), respectively, for those starting at age 68. CONCLUSIONS: Sufficient follow-up time (≥10 years) after screening stops is key to obtaining unbiased estimates of overdiagnosis. Overdiagnosis of invasive BC is a larger problem in older compared to younger women.

Mammographic sensitivity as a function of tumor size: A novel estimation based on population-based screening data.

BACKGROUND: Instead of a single value for mammographic sensitivity, a sensitivity function based on tumor size more realistically reflects mammography's detection capability. Because previous models may have overestimated size-specific sensitivity, we aimed to provide a novel approach to improve sensitivity estimation as a function of tumor size. METHODS: Using aggregated data on interval and screen-detected cancers, observed tumor sizes were back-calculated to the time of screening using an exponential tumor growth model and a follow-up time of 4 years. From the observed number of detected cancers and an estimation of the number of false-negative cancers, a model for the sensitivity as a function of tumor size was determined. A univariate sensitivity analysis was conducted by varying follow-up time and tumor volume doubling time (TVDT). A systematic review was conducted for external validation of the sensitivity model. RESULTS: Aggregated data of 22,915 screen-detected and 10,670 interval breast cancers from the Dutch screening program were used. The model showed that sensitivity increased from 0 to 85% for tumor sizes from 2 to 20 mm. When TVDT was set at the upper and lower limits of the confidence interval, sensitivity for a 20-mm tumor was 74% and 93%, respectively. The estimated sensitivity gave comparable estimates to those from two of three studies identified by our systematic review. CONCLUSION: Derived from aggregated breast screening outcomes data, our model's estimation of sensitivity as a function of tumor size may provide a better representation of data observed in screening programs than other models.

The Role of Socio-Demographic Factors in the Coverage of Breast Cancer Screening: Insights From a Quantile Regression Analysis.

Background: In Flanders, breast cancer (BC) screening is performed in a population-based breast cancer screening program (BCSP), as well as in an opportunistic setting. Women with different socio-demographic characteristics are not equally covered by BC screening. Objective: To evaluate the role of socio-demographic characteristics on the lowest 10th and highest 90th quantile levels of BC screening coverage. Methods: The 2017 neighborhood-level coverage rates of 8,690 neighborhoods with women aged 50-69 and eligible for BCSP and opportunistic screening were linked to socio-demographic data. The association between socio-demographic characteristics and the coverage rates of BCSP and opportunistic screening was evaluated per quantile of coverage using multivariable quantile regression models, with specific attention to the lowest 10th and highest 90th quantiles. Results: The median coverage in the BCSP was 50%, 33.5% in the 10th quantile, and 64.5% in the 90th quantile. The median coverage of the opportunistic screening was 12, 4.2, and 24.8% in the 10th and 90th quantile, respectively. A lower coverage of BCSP was found in neighborhoods with more foreign residents and larger average household size, which were considered indicators for a lower socioeconomic status (SES). However, a higher average personal annual income, which was considered an indicator for a higher SES, was also found in neighborhoods with lower coverage of BCSP. For these neighborhoods, that have a relatively low and high SES, the negative association between the percentage of foreign residents, average household size, and average personal annual income and the coverage in the BCSP had the smallest regression coefficient and 95% confidence interval (CI) values were -0.75 (95% CI: -0.85, -0.65), -13.59 (95% CI: -15.81, -11.37), and -1.05 (95% CI: -1.18, -0.92), respectively, for the 10th quantile. The neighborhoods with higher coverage of opportunistic screening had a relatively higher average personal annual income, with the largest regression coefficient of 1.72 (95% CI: 1.59, 1.85) for the 90th quantile. Conclusions: Women from relatively low and high SES neighborhoods tend to participate less in the BCSP, whereas women with a relatively high SES tend to participate more in opportunistic screening. For women from low SES neighborhoods, tailored interventions are needed to improve the coverage of BCSP.

Knowledge, attitudes and practices relating to antibiotic use and antibiotic resistance among backyard pig farmers in rural Shandong province, China.

China is among the world's largest consumers of antibiotics for livestock, and the demand for meat protein continues to rise. Pig production takes place at a range of facilities, including backyard pig farms. The aim of this study was to describe the knowledge, attitudes and practices of backyard pig farmers concerning antibiotic use and resistance, and to observe household storage of antibiotics for use in pigs. We conducted a cross-sectional questionnaire survey among 271 rural residents with backyard pig farms in 12 villages in one town in Shandong province. The median number of pigs per backyard farm was 14, and 82 % (222/271) of participants reported not having had any training about raising pigs. Eighteen percent of participants (48/271) reported always or often adding antibiotics to feed to keep pigs healthy and prevent diseases, and a third (88/271) of participants believed that pigs should be given antibiotics when they stop eating. Thirty percent (82/271) reported having bought antibiotics in the previous year without having first spoken with a veterinarian. Antibiotics accounted for over half of all medicines stored (55 %, 197/358), and were observed in 31 % of all households (83/271). Less than half of participants (45 %, 37/83) from households in which antibiotics for pig use were found knew that they were storing antibiotics. The most common class of antibiotics stored for use in pigs was (Q)J01C beta-lactam antibiotics, penicillins (19 %, 37/197), followed by (Q)J01F macrolides, lincosamides and streptogramins (14 %, 28/197), and (Q)J01M quinolones (12 %, 25/197). These results provide important insights into how backyard pig farmers are using antibiotics in rural China and suggest potential targets for interventions to reduce unnecessary and inappropriate use.

Study protocol for One Health data collections, analyses and intervention of the Sino-Swedish integrated multisectoral partnership for antibiotic resistance containment (IMPACT).

INTRODUCTION: To effectively minimise the emergence and dissemination of antibiotic resistant bacteria, a holistic One Health approach is called for. The Sino-Swedish Integrated Multisectoral Partnership for Antibiotic Resistance Containment is a cross-sectoral and integrated project on antibiotic resistance, conducted in Shandong Province in China. This paper outlines the overall study protocol for the project. To our knowledge, this is the first research programme aiming to take a true holistic approach across multiple sectors simultaneously in China, and the first to incorporate both antibiotic use and infection prevention and control in addition to antibiotic resistance patterns. The project aims to address gaps in current knowledge and seeks to improve the situation through a system-wide intervention. By using a One Health approach we can address important research questions that individual discipline investigations are unable to. The results obtained should thus more closely reflect the world in which human health, animal health and the environment are inextricably and intimately interlinked. METHODS AND ANALYSIS: Both quantitative and qualitative studies are included for households from 12 villages, their surrounding environment and a tertiary care hospital in a nearby town. The studies include analyses of antibiotic consumption for humans and pigs; qualitative and quantitative data on perceptions, knowledge and attitudes; faecal carriage of extended spectrum ß-lactamase and carbapenemase-producing Enterobacteriaceae from pigs and humans, and occurrence in household drinking water, surface water, waste water and clinical bacterial isolates from the hospital. Carriage of methicillin-resistant Staphylococcus aureus in humans, household pigs and clinical bacterial isolates is also investigated. Furthermore, potential inter-relationships between these sources are analysed. A multifaceted One Health intervention is designed and implemented in 6 of the 12 villages. Repeated and continuous data collections take place over 2 years, where the repeated data collection is performed after 1 year of intervention. Comparisons are made between intervention and control villages, before and after the intervention. ETHICS: Ethics approval was obtained from the first Affiliated Hospital, College of Medicine, Zhejiang University, China, reference number 2015#185 and 2015#283.

Prevalence of the mcr-1 colistin resistance gene in extended-spectrum ß-lactamase-producing Escherichia coli from human faecal samples collected in 2012 in rural villages in Shandong Province, China.

Since its initial discovery in China in 2015, the plasmid-mediated colistin resistance gene mcr-1 has been reported in Escherichia coli isolated from clinical samples, animals and meat worldwide. In this study, 706 extended-spectrum ß-lactamase (ESBL)-producing E. coli from 411 persons were detected in a collection of faecal samples from 1000 rural residents in three counties in Shandong Province, China. These isolates were screened for mcr-1 and phenotypic colistin resistance. The gene was found in 3.5% of the isolates (from 4.9% of persons) from all three counties. All isolates with phenotypic colistin resistance carried mcr-1. These data indicate that commensal carriage of ESBL-producing E. coli with mcr-1 among persons in rural China was already present in 2012 and that mcr-1 was the most important colistin resistance mechanism. Interventions are necessary to minimise further dissemination of mcr-1, which would limit the future usefulness of colistin as a last-resort antibiotic.

Building bridges to operationalise one health - A Sino-Swedish collaboration to tackle antibiotic resistance.

Antibiotic resistance is a complex global health challenge. The recent Global Action Plan on antimicrobial resistance highlights the importance of adopting One Health approaches that can cross traditional disciplinary boundaries. We report on the early experiences of a multisectoral Sino-Swedish research project that aims to address gaps in our current knowledge and seeks to improve the situation through system-wide interventions. Our research project is investigating antibiotic use and resistance in a rural area of China through a combination of epidemiological, health systems and laboratory investigations. We reflect here on the challenges inherent in conducting long distance cross-disciplinary collaborations, having now completed data and sample collection for a baseline situation analysis. In particular, we recognise the importance of investing in aspects such as effective communication, shared conceptual frameworks and leadership. We suggest that our experiences will be instructive to others planning to develop similar international One Health collaborations.