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Objective: Short midline catheter use in paediatric populations appears to be increasing, however data on success rates and efficacy are sparse. This study aims to describe the success rate when midline venous catheters are employed as a single device for intravenous antibiotic therapy in paediatric patients with cystic fibrosis. Methods: A retrospective cohort study was performed in a single institution, retrieving electronic medical record data from July 2017 through March 2020. The primary outcome was device success, defined as a catheter that remained functional until the end of antibiotic therapy. Reasons for device failure were categorized in a standard fashion. Results: Primary outcome data were available for 116 catheter insertions, involving 49 patients and 55 proceduralists. The success rate was 84% ( n = 98). Median age at insertion was 15 years (range 4–19) and median weight 52 kg (13–81). Soft, polyether block amide, Arrow® Seldinger Arterial Catheters were employed. Only 16 patients (14%) required general anaesthesia. Median time to failure was 6 days, and median time to successful completion of treatment was 13 days. Six of 18 failures occurred within 48 h and were likely insertion complications. The most common reasons for device failure were occlusion, extravasation, phlebitis and dislodgement. More than half of patients (56%) received antibiotic therapy at home. Conclusion: There is a high single device success rate when inserting short midlines for 13-day intravenous pulmonary antibiotic therapy in children with cystic fibrosis. These results should be confirmed with a prospective study.

Although excess adiposity has been linked with various cancers, association between body composition and some cancers remains unclear, like lung and prostate cancers. We investigated associations of body composition with risk of overall cancer and major site-specific cancers in a prospective cohort of 454,079 cancer-free participants from UK-Biobank. Body composition was measured with bioimpedance analysis. We evaluated hazard ratio (HR) and 95% confidence interval (CI) with multivariate Cox linear and nonlinear models in men and women separately. We identified 27,794 cancers over 7.6 years of follow-up. Multivariable adjusted models including fat-free mass (FFM) and fat mass (FM) showed that FFM was positively associated with overall cancer risk in men and women (HR 1.03, 95% CI 1.01-1.04 and 1.07, 1.04-1.10, respectively); while the association between FM and overall cancer disappeared after adjusting for FFM. FFM was associated with higher risks of obesity-related cancers combined, stomach (women only), malignant melanoma, postmenopausal breast, corpus uteri, prostate, kidney (men only), and blood cancers, and lower risk of lung cancer. FM was associated with higher risks of obesity-related cancers combined, esophageal, colon, lung (men only), postmenopausal breast (at the lower end of FM range), and corpus uteri cancers, and lower risks of rectal, malignant melanoma (women only), prostate and blood cancers. FFM and FM seemed to have different effects on cancer risk, and the effects varied substantially by cancer type, in both direction and size. Higher FM/FFM ratio was also associated with some cancers risk, and might be a useful predictor of cancer risk. This article is protected by copyright. All rights reserved.

While birth cohorts are shaped by underpinning life course frameworks, few if any report how they select them. This review aimed to (1) summarise publicly available frameworks relevant to planning and communicating large new early-life cohorts and (2) help select frameworks to guide and communicate Generation Victoria (GenV), a whole-of-state birth and parent cohort in planning in the state of Victoria, Australia. We identified potential frameworks from prior knowledge, networks and a pragmatic literature search in 2019. We considered for inclusion only frameworks with an existing visual graphic. We summarised each framework’s concept, then judged it on a seven-item matrix (Scope, Dimensions, Outcomes, Life course, Mechanisms, Multi-age, and Visual Clarity) to be of high, intermediate or low relevance to GenV. We presented and evaluated 14 life course frameworks across research and policy. Two, nine and three frameworks, respectively, were ranked as high, intermediate and low relevance to GenV, although none totally communicated its scope and intent. Shonkoff’s biodevelopmental framework was selected as GenV’s primary framework, adapted to include ongoing feedback loops through the life course and influence of an individual’s outcomes on the next generation. Because conceptual simplicity precluded the primary framework from capturing the wide range of relevant exposures, we selected the Australian Institute of Health and Welfare’s person-centred model as a secondary framework. This summary of existing life course frameworks may prove helpful to other cohorts in planning. Our transparent process and focus on visual communication are already assisting in explaining and selecting measures for GenV. The feasibility, comprehension and validity of these frameworks could be further tested at implementation.

HIV disclosure to spouses can promote HIV prevention and facilitate support from those spouses; it can also cause mental health challenges for the spouses. We conducted a qualitative study of the mental health status and potential contributing factors of mental health challenges of spouses of men living with HIV in Sichuan, China. We interviewed 31 spouses whose husbands were living with HIV. Qualitative data were analyzed using content and thematic analyses. We found that mental health challenges were common among the spouses; leading challenges were themed as hopelessness, depression, and anxiety. Greater HIV knowledge, close relationship with husband, and psychological support may protect spouses from mental health challenges, whereas HIV-related stigma, heavy caregiving burden, and an unsupportive environment might be detrimental to mental health. Spouses of men living with HIV need mental health services, which should take into account a wide spectrum of contributors at individual, couple, and social levels.

Focus and outcomes for participants “Children are our future” - the wellbeing of our future adults will influence the future of the world. However, this generation of children and mid-life adults face increasing rates of complex health and development problems, and many of them are preventable. Traditional research approaches are not keeping pace with need. Discovery and testing of solutions is blocked by the lack of fast, cheap, large-scale, low burden and effective ways to conduct research for the population and its many subgroups. Innovation in epidemiological methods is required to deliver large scale studies of unprecedented scale and scope. These will support research that enables better prevention, prediction and treatment – all of which are needed to solve today’s pressing child and adult health problems. This 90-minute symposium will draw on the forthcoming Generation Victoria (GenV) to illustrate innovative epidemiological methods established in its foundation phase to enable large-scale studies. GenV is designed to address physical, mental and social issues experienced during childhood and mid-adulthood, as well as the antecedents of a wide range of diseases of ageing. Parents of all newborns (estimated. 170,000) in the state of Victoria (population 6.5 million), Australia, will be approached from 2021 for two full years. Following consent, GenV proposes to bank biosamples collected during routine care, link to administrative and clinical data, and directly collect parent and child data using interactive electronic interfaces with the potential for face-to-face assessment during the school years. Encompassing clinical trials, registries, health services and geospatial as well as discovery research, GenV’s initial focus will be on pregnancy and newborns, reaching into regional and rural communities and traditionally hard-to-reach groups in sizeable numbers. Permission will be sought to link trials, registries, and health services research with existing pre- and post-birth administrative and electronic health record datasets, and also to bank biospecimens collected during routine care. We will discuss why innovation is essential to the next wave of large-scale studies such as GenV, and share practical examples of method innovations being developed within GenV. We will forecast the opportunities and challenges of large-scale studies for improving wellbeing and reducing the disease burden with children and adults. Focus: Outcomes: Rationale for the symposium, including for its inclusion in the Congress The future wellbeing and productivity of our societies depend on wellbeing and good health of our children and adults. However, today’s children and mid-life adults are facing both old and new challenges. Traditional research approaches have largely failed to deliver progress towards solving these challenges. For example, most existing cohorts only allow for observational follow up, and children are greatly under-represented in gold-standard clinical trials, which leads to less evidence to children’s treatment and prevention. Multi-purpose, low burden, high up-take innovative large studies are required to address these gaps. GenV seeks to generate translatable evidence (prediction, prevention, treatments, and services) to improve future wellbeing and reduce the future disease burden of children and adults. It will allow researchers, clinicians and policy makers to better understand the issues affecting Victorian children and their families with greater speed and precision, and therefore outcomes be translated more quickly into practice. Also it will help facilitate an environment where researchers, clinicians, policy makers, and other organisations can come together to enact change for future generations’ wellbeing. With this symposium, we intend to share our reflections on how the scale of cohort studies is changing, and showcase new trends in research design. The GenV team will then show how we practically achieve innovation in large-study methodology and design, with the aim of encouraging others to think ambitiously at large-scale. We will share our intentions and rationale for these innovations as well as the challenges. The symposium is designed to spark a discussion with the audience, seeking their reflections and suggestions on shaping our innovations. Finally, we aim to encourage researchers (especially early career researchers) to exchange their vision and views on innovations and methods for cohort studies. Presentation program (90 minutes) Names of presenters Prof Melissa Wake, Dr Susan Clifford, Dr Yanhong Jessika Hu, A/Prof Jo Said, Dr Joan Leong, Dr Suzanne Mavoa.

Background We sought to understand the epidemiology and characteristics of antimicrobial resistance (AMR) and the impact of the National Action Plan (NAP) on AMR. This information will be critical to develop interventions and strengthen antibiotic stewardship in hospital settings in China. Methods Cross-sectional data collection from the hospital information management system from 1 January 2015 to 30 August 2018. Variables included patient age, sex, diagnosis, hospital department and antibiotic sensitivity test. T-test for two samples method was applied to compare the results before and after NAP implementation. Multivariate analysis with binary logistic regression was conducted to examine the associations of risk factors for antimicrobial resistance. Results In total there were 352,238 isolates in the final analysis after excluding contamination strains and isolates with incomplete information. More than 50% of patients were > 66 years old. 62% were male. 40% of the total samples were sputum. Among the total sample, the total resistance rate was 42% among all isolates. The rate of resistance to all antibiotics declined by 5.3% (95% CI 4.96–5.64%, p 65 years, ICU department, diagnosed with certain diseases were more likely to be associated with antimicrobial resistance. Conclusions Antibiotic resistance rates were high in this teaching hospital. However, the introduction of the China NAP since 2016 followed by hospital policy emphasis was associated with a declining AMR trend. Policies will need to incorporate antimicrobial stewardship with a focus on certain departments, with infection control practices and with increases in vaccination coverage among elderly.

Health registries are critical to understanding, benchmarking and improving quality of care for specific diseases and conditions, but face hurdles including funding, bias towards clinical rather than population samples, lack of pre-morbid and outcomes data, and absent cross-registry harmonisation and coordination. Children are particularly under-represented in registry research. This paper lays out novel principles, methods and governance to integrate diverse registries within or alongside a planned children’s mega-cohort to rapidly generate translatable evidence. GenV (Generation Victoria) will approach for recruitment parents of all newborns (estimated 150,000) over two years from mid-2021 in the state of Victoria (population 6.5 million), Australia. Its sample size and population denominator mean it will contain almost all children with uncommon or co-morbid conditions as they emerge over time. By design, it will include linked datasets, biosamples (including from pregnancy), phenotypes and participant-reported measures, all of which will span pre-morbid to long-term outcomes. We provide a vignette of a planned new registry for high-risk pregnancies to illustrate the possibilities. To our knowledge, this is the first paper to describe such a methodology designed prospectively to enhance both the clinical relevance of a large multipurpose cohort and the value and inclusivity of registries in a population.

Aim Most prescribed medicines during pregnancy are antibiotics, with unknown effects on a fetus and on the infant's acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections. Methods Design and participants: The Longitudinal Study of Australian Children birth cohort recruited a nationally-representative sample of 5107 infants in 2004. Measures Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1-6). Analysis Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. Results A total of 4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: 'consistently low' (86.2%), 'moderate to low' (5.6%), 'low to moderate' (6.7%) and 'consistently high' (1.4%). Antibiotic use in pregnancy was associated with children following 'consistently high' (adjusted odds ratio 2.04, 95% confidence interval 1.08-3.88, P = 0.03) and 'moderate to low' (adjusted odds ratio 1.78, 95% confidence interval 1.25-2.53, P = 0.001) trajectories. Conclusions Antibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for the study of potential mechanisms underlying these associations.

BackgroundAlthough rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomised, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea.MethodsAdults with acute uncomplicated diarrhoea aged 18 to 70 were randomised to 4 groups: (A) loperamide; (B) loperamide and berberine; (C) loperamide and turmeric; (D) loperamide, berberine and turmeric. All participants were given rescue ciprofloxacin for use after 48 h if symptoms worsened or were unimproved. Primary endpoints were feasibility and ciprofloxacin use during the 2-week follow-up period. Semi-structured interviews were conducted following recruitment and were analysed thematically. Recruiting doctors, delivery pharmacists and research assistants were blinded to treatment allocation.ResultsOnly 21.5% (278/1295) of patients screened were deemed eligible, and 49% (136/278) of these consented and were entered into the final analysis. Most participants had mild symptoms, because most patients with moderate or severe symptoms wanted to be given antibiotics. Follow-up was good (94% at 2 weeks). Only three participants used rescue antibiotics compared to 67% of acute diarrhoea patients in the hospital during the recruitment period. The median symptom duration was 14 h in group B (interquartile range (IQR) 10-22), 16 h in group D (IQR 10-22), 18 h in group A (IQR 10-33) and 20 h in group C (IQR 16-54). Re-consultation rates were low. There were no serious treatment-related adverse events. Most interviewed participants said that although they had believed antibiotics to be effective for diarrhoea, they were surprised by their quick recovery without antibiotics in this trial.ConclusionAlthough recruitment was challenging because of widespread expectations for antibiotics, patients with mild diarrhoea accepted trying an alternative. The three nutraceuticals therapy require further evaluation in a fully powered, randomised controlled trial among a broader sample.Trial registrationChiCTR-IPR-17014107

Background: Although rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomized, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea. Methods: Adults with acute uncomplicated diarrhoea were randomized to 4 groups: (A) loperamide; (B) loperamide and berberine; (C) loperamide and turmeric; (D) loperamide, berberine and turmeric. All participants were given rescue ciprofloxacin for use after 48 hours if symptoms worsened or were unimproved. Primary endpoints were feasibility and ciprofloxacin use during the 2 week follow-up period. Semi-structured interviews were conducted following recruitment. Results: Only 21.5% (278/1295) of patients screened were deemed eligible, and 49% (136/278) of these consented and entered into the final analysis. Most participants had mild symptoms, because most patients with moderate or severe symptoms wanted to be given antibiotics. Follow-up was good (94% at 2 weeks). Only two participants used rescue antibiotics compared to 65% of acute diarrhoea patients in the hospital during the recruitment period. The median symptom duration was: 14 hours in group B (IQR 10-22), 16 hours in group D (IQR 10-22), 18 hours in group A (IQR 10-33), 20 hours in group C (IQR 16-54). Re-consultation rates were low. There were no serious treatment-related adverse events. Most interviewed participants said the treatment was effective. Conclusion: Although recruitment was challenging because of widespread expectations for antibiotics, patients with mild diarrhoea accepted to try an alternative. This therapy requires further evaluation in a fully powered, randomised controlled trial among a broader sample.

BackgroundMost prescribed medicines during pregnancy are antibiotics, with unknown effects on a foetus and on the infant’s acquired microbiome. This study investigates associations between in utero antibiotic exposure and ear infection trajectories over the first decade of life, hypothesising effects on early or persistent, rather than later-developing, ear infections.MethodsDesign & Participants: The Longitudinal Study of Australian Children (LSAC) birth cohort recruited a nationally-representative sample of 5107 infants in 2004. Measures: Mothers reported antibiotic use in pregnancy when a child was 3-21 months old (wave 1), and ongoing problems with ear infection every 2 years spanning ages 0-1 to 10-11 years (waves 1 to 6). Analysis: Latent class models identified ear infection trajectories, and univariable and multivariable multinomial logistic regression determined odds of adverse trajectories by antibiotic exposure. Results4500 (88.1% of original sample) children contributed (mean baseline age 0.7 years; 51.3% boys); 10.4% of mothers reported antibiotic use in pregnancy. Four probability trajectories for ear infection emerged: “consistently low” (86.2%), “moderate to low” (5.6%), “low to moderate” (6.7%) and “consistently high” (1.4%). Antibiotic use in pregnancy was associated with children following “consistently high” (aOR 2.06, 95% CI 1.09 to 3.91, p=0.03) and “moderate to low” (aOR 1.78, 95% CI 1.25 to 2.53, p=0.001) trajectories.ConclusionsAntibiotic use in pregnancy is associated with an increased risk of persistent and early childhood ear infections. This highlights the wisdom of cautious antibiotic use during pregnancy, and the need for study of potential mechanisms underlying these associations.

Background Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities. Methods Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years. Results For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian’s agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day. Conclusions Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years.

Background Accumulating evidence suggested that long-term antibiotic use may alter the gut microbiome, which has, in turn, been linked to type 2 diabetes. We undertook this study to investigate whether antibiotic use was associated with increased risk of type 2 diabetes. Methods This prospective cohort study included women free of diabetes, cardiovascular disease and cancer in the Nurses’ Health Study (NHS 2008–2014) and NHS II (2009–2017). We evaluated the overall duration of antibiotics use in the past 4 years and subsequent diabetes risk with Cox proportional-hazards regression adjusting for demography, family history of diabetes and lifestyle factors. Results Pooled analyses of NHS and NHS II (2837 cases, 703 934 person-years) revealed that a longer duration of antibiotic use in the past 4 years was associated with higher risk of diabetes [Trend-coefficient = 0.09, 95% confidence interval (CI) 0.04 to 0.13]. Participants who received antibiotics treatment for a medium duration of 15 days to 2 months [hazard ratio (HR) 1.23, 95% CI 1.10 to 1.39] or long duration of >2 months (HR 1.20, 95% CI 1.02 to 1.38) had higher risk of type 2 diabetes as compared with non-users. Subgroup analyses suggested that the associations were unlikely to be modified by age, family history of diabetes, obesity, smoking, alcohol drinking, physical activity and overall diet quality. Conclusions A longer duration of antibiotic use in recent years was associated with increased risk of type 2 diabetes in women. Physicians should exercise caution when prescribing antibiotics, particularly for long-term use.

Background There is a lack of studies comparing hypertension and comorbidities in rural and urban older people in China. This study aimed to investigate the prevalence of hypertension and comorbidities in older people and to describe differences between patients from rural and urban areas in China. Methods A cross-sectional study on global AGEing and adult health (SAGE) was conducted from 2007 to 2010 across 8 provinces in China. The current study included a nationally representative subsample of 7,403 respondents aged 60 years and above. Hypertension was either self-reported diagnosed hypertension or 1 elevated measured blood pressure measurement (≥140/90 mm Hg). Comorbidities were self-reported and included angina, arthritis, asthma, stroke, diabetes, depression, and chronic lung disease. Results The prevalence of hypertension was 66.1%. Hypertension associated with 1 comorbidity was recorded in 35.9% of all participants. A large majority (73.6%) of participants with hypertension reported “good” or “very good” general health status. The prevalence of hypertension and the number of comorbidities increased with age. The prevalence rates of multiple comorbidities were higher for urban participants than their rural counterparts (27.8 vs. 42.4% for 1 morbidity; 7.7 vs. 16.4% for 2 comorbidities; 1.4 vs. 4.7% for 3 comorbidities; 0.4 vs. 1.2% for ≥4 comorbidities) after adjustment for sociodemographic factors. However, urban participants reported better general health status, irrespective of the number of comorbidities. Conclusions Our study implies that health promotion policies targeting older people should be developed. Rural areas should be a priority, and investment in the quality of health care in rural areas is urgently needed.

Supplemental material, Appendix for Berberine for diarrhea in children and adults: a systematic review and meta-analysis by Mingkun Yu, Xuejing Jin, Changhao Liang, Fanlong Bu, Deng Pan, Qian He, Yang Ming, Paul Little, Hongbo Du, Shibing Liang, Ruixue Hu, Chengze Li, Yanhong Jessika Hu, Huijuan Cao, Jianping Liu and Yutong Fei in Therapeutic Advances in Gastroenterology

Additional file 1. SPIRIT Checklist (Microsoft Word Document (.docx)). Completed SPIRIT guideline to indicate on what page trialists would find SPIRIT-related information to consider in their trial design. However, the completed form does not apply to any actual trial or group of trials.

Additional file 2. Example Working Together Agreement (Microsoft Word Document (.docx)). An example Working Together Agreement (WTA) developed for the GenV Trials Working Group following GenV’s rapid evidence review of large research-led partnerships. The WTA focuses on good communication, transparency and agreement. We have included to indicate considerations for GenV and trials in developing their own WTA.

ObjectivesTo investigate leftover antibiotics and their influence on self-medication with antibiotics (SMA) for Chinese children, and further explore the different influences of leftovers from two main sources: previous prescriptions and pharmaceutical purchases.DesignA cross-sectional questionnaire study.SettingThe participants were approached through kindergartens and primary schools as well as in vaccination clinics.ParticipantsA total of 9526 parents from three Chinese provinces whose children were aged 0–13 years completed the survey.Outcome measuresThe prevalence of keeping antibiotics at home for children and the proportion of leftover antibiotics from two main sources were measured by a self-administrated questionnaire. Logistic regression models were established to examine the association between keeping antibiotics at home and SMA for children, specifically the risks of leftovers from two main sources.ResultsOverall, 4580 (48.1%) reported keeping antibiotics at home for children. Among those who had leftovers, 2891 (63.1%) reported that their leftovers came from previous prescriptions and 1619 (35.3%) reported that their leftovers came from pharmaceutical purchases. Mothers, older age of child, higher household income, higher education level and medical background were significantly associated with keeping antibiotics at home. Keeping antibiotics at home was significantly associated with SMA for children (adjusted OR=4.91, 95% CI 3.84 to 6.28). Particularly, compared with parents who did not keep antibiotics at home, parents who kept leftover antibiotics from previous prescriptions and those whose leftovers came from pharmaceutical purchases were 3.80 (95% CI 2.89 to 5.00) and 6.45 (95% CI 4.89 to 8.51) times more likely to engage in SMA for children, respectively.ConclusionsKeeping antibiotics at home for children was pervasive in China. Most leftovers came from previous prescriptions, while those from pharmacies had a higher risk of SMA for children.

Objectives: This study aims to explore how changes in external factors caused by migration impact antibiotic use behaviors among Chinese university students in comparison to their peers from host areas and origin areas. Migration status was determined by host universities and origin areas, which were broadly defined as eastern vs. western regions in China. Methods: This study analyzed secondary data from a cross-sectional study conducted in China about the antibiotic use behaviors of university students in 2015. Students were divided into four groups: eastern local students (E-Es), western local students (W-Ws), eastern&ndash, western migrant students (E-Ws), and western&ndash, eastern migrant students (W-Es). Results: After controlling for gender, grade, major, hometown (rural or urban), and parents&rsquo, education, E-Ws reported a significantly higher odds of asking for antibiotics (OR = 2.13, 95% CI = 1.54&ndash, 3.03, p &lt, 0.001) and taking antibiotics prophylactically (OR = 1.85, 95% CI = 1.32&ndash, 2.56, 0.001) compared with E-Es, W-Es reported a significantly lower odds of asking for antibiotics (OR = 0.56, 95% CI = 0.37&ndash, 0.83, 0.01) and taking antibiotics prophylactically (OR = 0.57, 95% CI = 0.41&ndash, 0.81, 0.01) compared with W-Ws. Discussion: Regional differences likely interacted with students&rsquo, migration status in forming different antibiotic use behaviors. Factors including financial incentives and loose regulations of antibiotic over-prescription by health providers and peer influence may contribute to worsened antibiotic use behaviors among E-Ws.

Introduction: Antimicrobial resistance is a global health crisis and primarily caused by antibiotic misuse. Antibiotic misuse among children is particularly concerning, and its prevalence may vary from region to region in China with different development levels. Methodology: Zhejiang and Shaanxi were selected to represent developed and less developed provinces in China, respectively. Data of 2924 parents in Zhejiang and 3355 parents in Shaanxi whose children were 0-13 years old were collected through multi-stage stratified cluster random sampling and a self-administrated questionnaire. Chi-square tests and logistic regression models were used for statistical analysis. Results: Compared to parents in Zhejiang, those in Shaanxi were more likely to keep antibiotics for children at home, to engage in self-medication with antibiotics for children, and to make their children take antibiotics prophylactically. While there were no significant provincial differences between parents’ requests for antibiotics during pediatric consultations, parents in Shaanxi province were more likely to receive prescribed antibiotics. Conclusions: Children in less developed provinces face higher risks of antibiotic misuse at home as well as when attending medical practitioners. Comprehensive educational interventions are required to improve antibiotic use for children all over China but particularly in less developed provinces such as Shaanxi. Furthermore, non-prescription sales and over-prescribing of antibiotics should be reduced by targeted strategies.

Background: There is accumulating evidence suggesting that long-term antibiotic use may alter the gut microbiome which has, in turn, been linked to type 2 diabetes. We undertake this study to investigate whether antibiotic use was associated with increased risk of type 2 diabetes. Methods: This prospective cohort study included U.S. women free of diabetes, cardiovascular disease and cancer in the Nurses' Health Study (NHS 2004-2012) and NHS II (2005-2013). We evaluated the overall duration of antibiotics use in the past four years and at different ages (NHS: age 20-39, 40-59, and 60+; NHS II: age 20-39, 40-49, and 50+) and subsequent diabetes risk with a time-dependent COX proportional hazards model. Findings: Pooled analyses of NHS and NHS II (1 476 cases, 379 143 person-years) revealed that a longer duration of antibiotic use in the past 4 years was significantly associated with higher risk of diabetes (Ptrend = 0·002). As compared with non-users, participants who received antibiotics treatment for a medium duration of 15 days to 2 months (HR 1.29, 95% CI 1·11 to 1·51) or long duration of over 2 months (HR 1·27, 95% CI 1·12 to 1·58) had significantly higher risk. We also noted significant positive associations between antibiotic use duration at age 40-49 and the diabetes risk in NHS II (Ptrend < 0·0001) and between antibiotic use at age 60+ and diabetes risk in NHS (Ptrend = 0·01). Interpretation: A longer duration of antibiotic use in recent years and in middle or older age was associated with increased risk of type 2 diabetes in women. Funding Statement: This study was supported by the startup grant for the 100 Top Talents Program, The Seventh Affiliated Hospital, Sun Yat-sen University (392012). The NHS and NHS II were supported by the National Cancer Institute (UM1 CA176726, and UM1 CA186107), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK58845, DK112940). Declaration of Interests: The authors declared that there was no potential conflicts of interest relevant to this article. Ethics Approval Statement: The NHS and NHS II were approved by the Human Research Committee at the Brigham and Women’s Hospital, Boston, MA. All participants provided written informed consent.

Massive misuse of antibiotics is one of the most important reasons for antimicrobial resistance (AMR). Misconceptions of antibiotics contribute to antibiotic misuse behaviors. This study aims to examine whether university students hold the misconception that Antibiotic is a Xiaoyanyao (literally means anti-inflammatory drug in Chinese), and association between this misconception and antibiotic misuse behaviors. A cross-sectional study was conducted among university students using the cluster random sampling method in six universities of six regions in China (one university per region). The Chi-square test was used to assess the relationship between the misconception and antibiotic misuse behaviors. Logistic regression was conducted to identify the risk factors for antibiotic misuse behaviors. 11,192 of university students completed the entire questionnaire. There were 3882 (34.7%) students who were considered to have the misconception. Female students were more likely to have the misconception compared with males (36.7% vs. 32.6%, P &lt, 0.001). Those students with a background of social science/humanities were more likely to have the misconception compared with those from science and medicine (44.1% vs. 30.3% vs. 20.1%, P &lt, 0.001). Students came from rural areas compared with those from urban areas (37.5% vs. 32.5%, P &lt, 0.001) were more likely to have the misconception. Students who had the misconception were 1.51 (95% CI 1.21&ndash, 1.89, P &lt, 0.001) times, 1.34 (95% CI 1.21&ndash, 1.48, P &lt, 0.001) times, and 1.36 (95% CI 1.24&ndash, 1.50, P &lt, 0.001) times more likely to report self-medication, request to obtain antibiotics, and take antibiotics prophylactically than those who did not have this misconception, respectively. The high proportion of university students' misconception on Antibiotic is a Xiaoyanyao is worth more attention. Effective health education and interventions need to be promoted among university students and the whole population.

Background: Diarrhea is a ubiquitous digestive system disease, leading to loss of fluid and electrolytes, and may be life-threatening, especially in children and adults who are immunosuppressed or malnourished. Berberine has a broad-spectrum antibiotic activity and is very widely used to treat diarrhea in China. No systematic review has been carried out to evaluate the evidence presented in clinical trials. The aim of this study was to assess the effectiveness and safety of berberine in diarrhea treatment among children and adults. Methods: Seven databases and two clinical trial registries were searched on 1 September 2019. Randomized controlled trials were included, where participants were diagnosed (first diagnosed) as having diarrhea according to clear diagnostic criteria. Berberine alone or in combination with Western medication as intervention were included. Subgroup analyses were conducted based on children or adults, acute or persistent diarrhea, infectious or noninfectious and treatment courses. Primary outcomes were clinical cure rate and duration of diarrhea. The GRADE tool was used to assess the quality of evidence. Results: A total of 38 randomized controlled trials were included involving 3948 participants (including 27 trials on 2702 children) were included. Compared with antibiotics, berberine plus antibiotics showed better results in both adults and in children in general, especially when given for 7 days or 3 days in acute infectious diarrhea of children. Compared with the control groups, using berberine alone or in combination with montmorillonite, probiotics, and vitamin B increased the clinical cure rate of diarrhea. The use of berberine alone or berberine combined with montmorillonite reduced the duration of hospitalization. Using berberine had significantly better laboratory indicators (isoenzyme, inflammatory factors, myocardial enzyme, and fecal trait) and fewer systemic symptoms than the no berberine groups. Overall, 22 of 27 trials on children used berberine as an enema. No deaths and serious adverse events were reported. The quality of evidence of included trials was moderate to low or very low. The impact of different dosages, frequencies and treatment durations on the outcomes was not evaluated due to insufficient number of trials. Conclusion: This review demonstrated that berberine was generally effective in improving clinical cure rates and shortening the duration of diarrhea compared with control groups. No severe adverse event was reported. However, there is still a lack of high-quality evidence for evaluating the efficacy and safety of berberine. Trial registration: PROSPERO CRD42020151001 (available from http://www.crd.york.ac.uk/PROSPERO/ ).

Objective To make a systematic review of risk factors, outcomes and prevalence of extended-spectrum β-lactamase-associated infection in children and young adults in South-East Asia and the Western Pacific. Methods Up to June 2018 we searched online databases for published studies of infection with extended-spectrum β-lactamase-producing Enterobacteriaceae in individuals aged 0-21 years. We included case-control, cohort, cross-sectional and observational studies reporting patients positive and negative for these organisms. For the meta-analysis we used random-effects modelling of risk factors and outcomes for infection, and meta-regression for analysis of subgroups. We mapped the prevalence of these infections in 20 countries and areas using available surveillance data. Findings Of 6665 articles scanned, we included 40 studies from 11 countries and areas in the meta-analysis. The pooled studies included 2411 samples testing positive and 2874 negative. A higher risk of infection with extended-spectrum β-lactamase-producing bacteria was associated with previous hospital care, notably intensive care unit stays (pooled odds ratio, OR: 6.5; 95% confidence interval, CI: 3.04 to 13.73); antibiotic exposure (OR: 4.8; 95% CI: 2.25 to 10.27); and certain co-existing conditions. Empirical antibiotic therapy was protective against infection (OR: 0.29; 95% CI: 0.11 to 0.79). Infected patients had longer hospital stays (26 days; 95% CI: 12.81 to 38.89) and higher risk of death (OR: 3.2; 95% CI: 1.82 to 5.80). The population prevalence of infection was high in these regions and surveillance data for children were scarce. Conclusion Antibiotic stewardship policies to prevent infection and encourage appropriate treatment are needed in South-East Asia and the Western Pacific.

Effective health care models to scale up combination antiretroviral therapy (ART) are needed in rural southwestern China. We aimed to evaluate the ART treatment outcomes and their associations with patients' demographic characteristics and pre-treatment clinical features in a scaled-up provincial ART program serving eight heavily HIV-affected prefectures in Yunnan Province. We abstracted information from a computerized database for adults initiating ART between July 2007 and September 2008. Survival functions of mortality and treatment failure were calculated by age group, gender, transmission mode, and baseline CD4 count. Multivariable Cox regression analyses were conducted to find independent associations of various demographic and baseline clinical features with outcome variables. Of the 1967 patients in the mortality analysis, there were 110 deaths, of which 16 were coded as accidents or suicides. Adjusted hazard ratios (AHR) associated with mortality were greater for patients with baseline CD4 counts100 cells/µl vs. patients with CD4 counts ≥200 cells/µl, for male vs. female, for single vs. married, and for those acquired HIV through injection drug use (IDU) vs. other modes of transmission. Successful treatment was 81.3% at six months after treatment started. Immunologic treatment failure was associated with baseline CD4 counts but not with demographic characteristics. Overall loss to follow-up rate was 2.1%. Collaboration between clinics and community networks are distinctive features of Yunnan's model for scaling up ART across a diverse, poor, and rural population. This study finds that the strategy can succeed even if 40% of the patients have a history of IDU.