University Research Ethics Committee Research Articles

Observational cohort study investigating cognitive outcomes, social networks and well-being in older adults: a study protocol

IntroductionSocial networks play a role in slowing the development of dementia. However, there is a need for further investigation of the effects of improving social networks on health-related quality of...

Characterization of Goal-Directed and Habitual Behavior in Children with Attention-Deficit/Hyperactivity Disorder

Background: Children with attention-deficit/hyperactivity disorder (ADHD) exhibit cognitive impairments that affect their daily life functioning. These impairments may reflect a deficit in action-control, i.e., an inability to flexibly adapt behavior to changing consequences. Action-control is modulated by balancing goal-directed (reflective) and habitual (reflexive) behaviors. Studying action-control as a cognitive mechanism will further our understanding of the nature of ADHD in terms of varying degrees of dysfunction at the individual level. Here, we aimed to characterize action-control patterns in children with ADHD as an endophenotype with diagnostic value. Our central hypothesis was that children with ADHD have a higher dominance of habitual response compared to healthy children (HC). Methods: We tested 18 medication-free children with ADHD and 12 HC. Participants were 6-10 years old and were group matched for age and gender. We tested action-control using a computer-based task of the outcome-devaluation paradigm. We used a Q-learning computational model to fit cognitive data and examine individual mechanisms of response. Findings: Compared to HC, children with ADHD demonstrated a predominance of habitual behavior, and a higher level of random choice exploration regardless of feedback. Habitual behavior scores differentiated HC from children with ADHD with a 90% specificity and sensitivity, and correlated with different ADHD symptoms. Interpretation: These findings suggest that studying goal-directed/habitual behavior in children with ADHD can serve as a cognitive endophenotype with a potential diagnostic value. Funding: Hikma Pharmaceuticals LLC., Mr. Saad Mouasher, and Mr. Fadi Ghandour. Declaration of Interest: All authors report no financial disclosures or conflict of interests. Ethical Approval: All research was conducted according to the Declaration of Helsinki and approved by Al-Quds University Research Ethics Committee.

Does exercise impact gut microbiota composition in men receiving androgen deprivation therapy for prostate cancer? A single-blinded, two-armed, randomised controlled trial

IntroductionA potential link exists between prostate cancer (PCa) disease and treatment and increased inflammatory levels from gut dysbiosis. This study aims to examine if exercise favourably alters gut microbiota in...

NOD2 Inhibits Tumorigenesis and Increases Chemosensitivity of Hepatocellular Carcinoma by Targeting LKB1/AMPK/mTORC1 Axis

Background: NOD2 is a recognized innate immune sensor which can initiate potent immune response against pathogens. However its role in cancer remains to be clarified. Methods: DEN/CCL4 induced HCC mice model and xenograft tumor model were constructed to define the function of NOD2 in HCC progression. CCK-8, transwell and colony formation assay were performed to detect the malignant behaviors of HCC cells. Immunohistochemical staining, western blot and qRT-PCR were performed to detect the relative expression of NOD2 in clinical HCC specimen. Signaling transduction of HCC cells was defined by western blot. Co-Immunoprecipitation and immunofluorescence were performed to verify the binding between NOD2 and AMPK-LKB1 complex. Findings: NOD2 deficiency promoted hepatocarcinogenesis both in vivo and in vitro. Absent expression of NOD2 in clinical HCC tissues was significantly correlated with advanced disease stages. Further investigation showed that NOD2 inhibited malignant behaviors and enhanced chemosensitivity of HCC cells through activating LKB1/AMPK/mTORC1 signaling pathway by directly binding with AMPK-LKB1 complex. Interpretation: This study showed that NOD2 acted as a tumor suppressor as well as a chemotherapeutic regulator in HCC cells, which indicated a potential therapeutic strategy for HCC treatment by regulating NOD2/LKB1/AMPK/mTORC1 signaling axis. Funding: This study was supported by the National Natural Science Foundation of China (No.81672391 and No.81472269) and the Major Innovation Project of Shandong Province (No.2018CXGC1217). Declaration of Interest: The authors declare no conflict of interests. Ethical Approval: All of the protocols carried out to mice were followed the guidelines of the Institutional Animal Care and Use Committee, and approved by the Medical Ethics Committee of Shandong University. Written informed consents were obtained from all patients before participation. All protocols were in accordance with the Helsinki Declaration and were approved by Shandong University Research Ethics Committee.

Biochemical effects and safety of Gum arabic (Acacia Senegal) supplementation in patients with sickle cell anemia.

BackgroundSickle cell anemia (SCA) is a hereditary chronic hemolytic anemia with several clinical consequences. Intravascular sickling of red blood cells leads to multi-organ dysfunction. Moreover, several biochemical abnormalities have been associated with SCA. Gum arabic (GA) is an edible dried gummy exudate obtained from Acacia Senegal tree. GA showed antioxidant and cytoprotective activities and demonstrated protection against hepatic, renal, and cardiac toxicities in experimental rats. We hypothesized that regular intake of GA improves renal and liver functions in patients with SCA.MethodsForty-seven patients (5–42 yr) carrying hemoglobin SS were recruited. The patients received 30 g/day GA for 12 weeks. Blood samples were collected before administering GA and then after 4, 8, and 12 weeks. Liver enzymes, total protein, albumin, electrolytes, urea, creatinine, and uric acid were determined in the serum. The study was approved by the Al Neelain University Institutional Review Board and Research Ethics Committee Ministry of Health. The trial was registered at ClinicalTrials.gov (identifier: NCT02467257).ResultsGA significantly decreased direct bilirubin level [statistical significance (P-value)=0.04]. It also significantly decreased serum alanine transaminase level after 4 weeks, which was sustained till the 8th week. GA, however, had no effect on serum aspartate transaminase level. In terms of renal function, GA decreased serum urea level but the effect was not sustained after the first month.ConclusionGA may alter the disease severity in SCA as demonstrated by its ability to decrease direct bilirubin and urea levels in the serum.

Blood Pressure Changes Have a More Strong Impact on Short- than Long-Term Outcomes of Major Adverse Cardiovascular Events

Background: Whether blood pressure (BP) changes have a different impact on short- and long-term outcomes of major adverse cardiovascular events (MACE) remains unclear. Therefore, we aimed to investigate and compare the effects of BP changes on short- and long-term outcomes of MACE. Methods: We conducted a prospective cohort study, which consisted of four examinations: baseline, 2008, 2010, and 2017 follow-up. BP changes were measured from baseline to 2008, short- and long-term outcomes were defined by incident events occurred from 2008 to 2010 and 2008 to 2017, respectively. The final analysis was restricted to 24,495 and 27,522 participants in short- and long-term analysis. Adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). The difference of β coefficients between short- and long-term outcomes were examined using Fisher Z test. Findings: During a median follow-up of 12·5-years, 451 (216 stroke, 33 myocardial infarction, 219 CVD deaths) and 2,025 (1,532 stroke, 371 myocardial infarction, 991 CVD deaths) MACE were identified during short- and longterms, respectively. For prehypertension to hypertension, the HR (95% CI) were 1·36 (1·00-1·84) for short-term MACE, 1·19 (1·01-1·40) for long-term stroke. For hypertension to prehypertension, 0·66 (0·49-0·91) for short-term MACE, 0·46 (0·27-0·78) for short-term stroke, 0·82 (0·69-0·97) for long-term stroke. Furthermore, short-term outcomes conferred a stronger impact than long-terms (measured as β coefficients, all P<0·05). Interpretation: BP changes were significantly associated with MACE and its subtypes for the short- and long-terms, and short-term outcomes conferred a strong impact than long-terms. Funding Statement: This research was partly supported by funds from National Nature Science Foundation of China (No. 81773510), Nature Science Foundation of Liaoning Province (No. 20170541048), National Key R&D Program of China (Grant #2017YFC1307600), and National Key R&D Program of China (Grant #2018YFC1311600). Declaration of Interests: The authors state: none. Ethics Approval Statement: The research protocol was approved by the China Medical University Research Ethics Committee, and written informed consent was formally obtained from all the participants or their guardians

Assessment of burnout in medical undergraduate students in Riyadh, Saudi Arabia

BackgroundTo assess the prevalence of burnout symptoms among preclinical and clinical medical students studying at AlFaisal University in Riyadh, Saudi Arabia.MethodsA cross-sectional study was conducted using Maslach Burnout Inventory questionnaire on 276 medical students from Alfaisal University, Riyadh, Saudi Arabia. The study was approved by Alfaisal University research ethics committee. Chi-square test was used to identify statistically significant differences, and binary logistic regression was used to identify predictors of burnout.Results276 entered into final data analysis with a mean age 20.62 ± 1.58, of whom 54% were males, and 46% were females. The overall burnout prevalence was 13.4%, of which PA was the most prevalent domain of burnout with 64.9%. Female gender was a significant predictor of EE and DP [OR = 4.34; 95% Cl 1.86–10.13; P-value 0.001] and [OR = 2.01; 95% Cl 1.07–3.79; P-value 0.030] respectively as per multivariate analysis for demographic characteristics. Regarding the total level of burnout, females (75.7%) had significantly higher levels of burnout compared to males (41.4%); (P-value < 0.001).ConclusionBurnout is prevalent among medical student. Gender was found to exhibits effect on the burnout. Mutual proactive strategies and reactive coping mechanisms between the students and the universities are encouraged to prevent and reduce burnout among medical students.

Reducing Expectations for Antibiotics in Primary Care: A Randomised Experiment to Test the Response to Fear-Based Messages About Antimicrobial Resistance

Background: Public health campaigns often provide fear-based information about antibiotic-use and antimicrobial-resistance (AMR). This study aimed to test the likely impact of fear-based messages on patient consultations/antibiotic-requests for influenza-like-illnesses. Methods: We hypothesised that fear-based messages containing empowering information about self-management without antibiotics would be more effective, particularly in a pre-specified subgroup with low AMR awareness. Respondents from an online research panel, representative of United Kingdom adults, were randomised to receive three different messages about antibiotic-use and AMR, designed to induce fear about AMR to varying degrees. Two messages (one 'strong-fear', one 'mild-fear') also contained empowering information regarding influenza-like-symptoms being easily self-managed without antibiotics. The main outcome measures were self-reported effect of information on likelihood of visiting a doctor, and requesting antibiotics, for influenza-like-illness; analysed separately according to whether the AMR information was very/somewhat new to respondents, pre-specified based on a previous non-randomised survey. Findings: The 'fear-only' message was very/somewhat new to 285/1,000(28·5%) respondents; 'mild-fear-plus-empowerment' to 336/1,500(22·4%); and 'strong-fear-plus-empowerment' to 388/1,500(25·9%) (p=0·002). Of those for whom the respective information was very/somewhat new, only those given the 'strong-fear-plus-empowerment' message said they would be less likely to request antibiotics if they visited a doctor for an influenza-like-illness (p<0·0001; 182/388(46·9%) 'much less likely'/'less likely', versus 116/336(34·5%) with 'mild-fear-plus-empowerment' versus 85/285(29·8%) with 'fear-alone'). Those for whom the respective information was not very/somewhat new said they would be less likely to request antibiotics for influenza-like-illness (p<0·0001) across all messages (interaction p<0·0001 versus very/somewhat new subgroup). The three messages had analogous self-reported effects on likelihood of visiting a doctor, and in subgroups defined by believing antibiotics would definitely/probably help an influenza-like-illness. Interpretation: Fear could be effective in public campaigns aimed at reducing antibiotic-use, but should be combined with messages empowering patients to self-manage symptoms effectively without antibiotics. Funding Statement: The research was funded by the National Institute for Health Research Health Protection Research Units (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford [grant number HPRU-2012-10041] and at Imperial College London [grant number HPRU-2012–10047], and the NIHR HPRU in Evaluation of Interventions at the University of Bristol [grant number HPRU-2012-10026], all in partnership with Public Health England (PHE). Michele Peters is an Associate Professor supported by the Department of Health funded Policy Research Unit on Quality and Outcomes of Person Centred Care (QORU), a collaboration between the London School of Economics and Political Science (LSE) and the Universities of Kent and Oxford. Tim Peto and A. Sarah Walker are NIHR Senior Investigators. Enrique Castro-Sanchez was supported by a Wellcome ISSF Faculty Fellowship at Imperial College London. Laurence S.J. Roope, Derrick Crook, Tim Peto, A. Sarah Walker, and Sarah Wordsworth are supported by funding from the NIHR Oxford Biomedical Research Centre (BRC). Declaration of Interests: All authors declare: no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could have influenced the submitted work. Ethical Approval Statement: This study is based on data from three surveys. The first survey data existed prior to this study, having been developed separately,24 on attitudes to antibiotics and awareness of AMR. This and the second survey (first wave of this study) were not submitted for ethical approval based on previous similar surveys, since they were undertaken outside the NHS setting and did not request personal health information, only views about health. Respondents had volunteered to receive information about such surveys from SSI. Completion of the survey was considered as indicating consent and respondents were able to refuse to participate in the survey at any stage in the process. The third survey (second wave of this study), which is identical to the second survey (first wave of this study), was approved by the University of Oxford’s Central University Research Ethics Committee – reference number R49463/RE001. Following approval of the third survey, the original and second survey were retrospectively considered by the same committee (reference number R57213/RE001) who deemed that “it is probable that, had the documentation and a full application been submitted for ethical opinion at the correct time, the committee would have granted ethical approval (perhaps subject to some amendments of the documentation).” Respondents gave informed consent before taking part. We attest that we have obtained appropriate permissions and paid any required fees for use of copyright protected materials.

The Relationship between Psychotic Experiences, Nightmares and Emotion Dysregulation: Results from a Student Population

Background: Sleep-disruption is commonly associated with psychotic experiences. Whilst sparse, the literature to date highlights nightmares and related distress as prominent risk factors for psychosis in students. We aimed to further explore the relationship between specific nightmare symptoms and psychotic experiences in university students whilst examining the mediating role of emotion dysregulation. Method: A sample (N=1273) of students respondents from UK Universities completed measures of psychotic experiences, nightmare disorder symptomology, and emotion dysregulation. Findings: Hierarchical linear regression analysis showed that psychotic experiences were significantly associated (Adjusted R2 = 32.4%) with perceived nightmare intensity, consequences and resulting awakenings, and with emotion regulation difficulties. Furthermore, multiple mediation analysis showed that the association between psychotic experiences and nightmare factors was mediated by emotion regulation difficulties. Interpretation: Adaptive regulation of dream content during rapid eye-movement sleep has previously been demonstrated to attenuate surges in affective arousal by controlling the intensity and variability of emotional content. Deficits in emotion regulation may partially explain the experience of more intense and disruptive nightmares amongst individuals with psychotic experiences. Emotion regulation may represent an important control mechanism that safeguards dream content and sleep quality. Funding Statement: The authors stated: funding received. Declaration of Interests: No conflicts of interest declared in relation to this paper. Ethics Approval Statement: The study was approved by the Sheffield Hallam University Research Ethics Committee, and all participants provided online informed consent.

Evaluating the impact of a community-based social prescribing intervention on people with type 2 diabetes in North East England: mixed-methods study protocol

IntroductionSocial prescribing enables healthcare professionals to use voluntary and community sector resources to improve support for people with long-term conditions. It is widely promoted in the UK as a way...

Contemporary Update of Overall Prognosis and Nomogram to Predict Individualized Survival for Chinese Patients with Eyelid Sebaceous Carcinoma

Background: The prognosis of Chinese patients with eyelid sebaceous gland carcinoma (SC) has not been updated for more than 3 decades. The predictors for the prognoses are multifactorial, there is no validated prognostic model for eyelid SC. Methods: The study included 238 consecutive patients with eyelid SC. All patients were followed up for metastasis and mortality. The predictors of tumor-related survival were explored by Cox analyses. A prognostic nomogram was developed and validated using bootstrap resampling. The predictive accuracy and discriminative ability were compared between nomogram and Tumor, Node, Metastasis (TNM) staging system. Findings: After a median follow-up period of 55.5 months, 27 (11.3%) patients died of the metastatic SC, with a median survival time of 48.0 months. The 5-year and 10-year tumor-related survival rate was 88.1% and 77.9%, respectively. Prior radiation therapy (HR:5.63, p=0.003), tumor with orbital involvement (HR:4.64, p=0.001), greatest tumor basal diameter (HR:1.07, p<0.001), the presence of pagetoid spread (HR:3.12, p=0.012) were the independent risk factors for tumor-related death. Nomogram integrating these 4 factors was developed with a C-index of 0.875, which is significantly better than that of TNM staging system (p=0.038). The risk groups stratified by nomogram scores (p=0.042 (low vs intermediate risk); p<0.001 (intermediate vs high risk)) displayed better discrimination ability than TNM staging (T1vsT2: p=0.358; T2vsT3: p=0.171; T3vsT4: p<0.001) in patients at an early stage. Interpretation: The prognosis of Chinese patients of eyelid SC has been improved for the last 3 decades, and it is comparable to the patients from other countries. This nomogram provides more-accurate individualized estimates of survival for eyelid SC patients, and may guide clinicians in their therapeutic decisions. Funding Statement: This work was supported by the Scientific Research Program of the National Health and Family Planning Commission of China (201402014). Declaration of Interests: The authors declare no conflict of interest in this paper. Ethics Approval Statement: This study adhered to the tenets of the Declaration of Helsinki and was approved by the Shanghai Jiaotong University research ethics committee.

Repercussions of the prevalence of metabolic syndrome on adults and elderly people in the context of primary health care

To identify the prevalence of metabolic syndrome in users of the hypertension and diabetes mellitus program at a Health Center in Jequié City, Bahia, Brazil. This is a descriptive cross-sectional study. The sample consisted of 100 patients enrolled in HIPERDIA. This study was approved by the Research Ethics Committee of the State University of Southwest of Bahia (Minutes no. 013/2011). The prevalence of metabolic syndrome in these users was 43%. Regarding sex, the prevalence was 35% among men and 47% among women, considering that in 23% of the medical records there were insufficient data for classification. It was evidenced that the metabolic syndrome reaches proportionately more women than men, whereas, in relation to age, a higher prevalence of the disease was verified in individuals older than 60 years.

An Investigation into the Association of Pre- and Post-Migration Experiences on the Self-Rated Health Status Among New Resettled Adult Humanitarian Refugees to Australia: A Longitudinal Study

Background: Refugees are potentially at an increased risk for health problems due to their past and current migration experiences. How migration factors shape refugee health is not well understood. We examined the association between migration factors and the self-rated health of adult humanitarian refugees living in Australia. Methods: We analysed the first three waves of data from the 'Building A New Life in Australia' survey of 2399 humanitarian refugees resettled in Australia. Outcomes were self-rated health measured by the 36-Item Short Form Health Survey; the Kessler Psychological Distress Scale and Posttraumatic Stress Disorder-8 items. Predictors were migration process and resettlement factors. We used generalized linear mixed models to investigate the relationship between predictor and outcome variables. Findings: Poor health persisted among this refugee population at high levels throughout the three-year follow-up. Pre-migration trauma predicted serious mental illness and PTSD. Increasing number of financial difficulties and loneliness were positively associated with all study outcomes. Serious mental illness and poorer general health were associated with offshore immigration detainment in a seemingly protective fashion and lower language proficiency. Language barrier stress and unemployment were significantly associated with poorer general health. Interpretation: Pre-migration trauma, financial difficulties and social isolation appear particularly problematic for the health of humanitarian refugees in Australia. There is also a high prevalence of ill-health throughout the early years of resettlement. Our findings highlight opportunities for intervention as a way of alleviating the health burden of resettling refugees. Funding Statement: The authors declare No funding was secured for this study. The BNLA is funded by the Australian Government’s Department of Social Services and had no involvement in the preparation of this manuscript. Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: De-identified BNLA data is accessible by authorized researchers who have obtained permission from the Australian Department of Social Services. This permission was obtained by study authors AD, JE and GR. Ethics exemption to use the data was granted by the Monash University Research Ethics Committee.

Causas de recusa familiar na doação de órgãos e tecidos

INTRODUÇÃO: A taxa de doações de órgãos e tecidos vem crescendo durante os anos. Porém, a não efetivação das doações ainda é alta, sendo o principal fator a recusa familiar. OBJETIVO: Descrever os motivos de recusa familiar para doação de órgãos e tecidos. MÉTODOS: Estudo quantitativo, descritivo, retrospectivo, transversal e exploratório, realizado com 350 prontuários de pacientes potenciais doadores de órgãos nos hospitais de Petrolina-PE, entre os anos de 2013 a 2017. Para coleta de dados utilizou-se um formulário de pesquisa elaborado pelas autoras. Os dados foram tabulados e armazenados no programa Excel for Windows/2013, compondo o banco de dados da pesquisa. Projeto aprovado pelo Comitê de Ética em Pesquisa da Universidade do Estado da Bahia sob nº 65496017.3.0000.0057. RESULTADOS: Foram analisados 350 prontuários de potenciais doadores os quais a entrevista familiar foi realizada. Para este estudo, foram utilizados apenas os prontuários em que houve a recusa familiar para a doação dos órgãos e tecidos, totalizando 147. As causas mais frequentes foram: corpo íntegro (36,0%), desconfiança do processo de doação (32,6%), doador contrário em vida (16,3%), revolta com atendimento da equipe hospitalar (4,7%), demora do processo de doação (2,7%), motivos religiosos e não compreensão da morte encefálica (1,3%). CONCLUSÃO: Percebe-se que os fatores de recusa remetem à falta de informação e divulgação sobre o processo de doação, sendo necessário que campanhas educativas sejam realizadas com o objetivo de esclarecer a população sobre esta temática, visando diminuir as negativas devido à recusa familiar.

The Impact at Scale of the Ghana School Feeding Programme on Primary School-Age Children's Anthropometry: A Cluster Randomised Trial

Background: Attention to nutrition during all phases of child and adolescent development is necessary to ensure healthy physical growth and to protect investments made earlier in life. Leveraging school feeding programmes as platforms to scale-up nutrition interventions is relevant as programmes function in nearly every country in the world. This study is aimed at evaluating the impact of the national school feeding programme in Ghana on school-age children's anthropometry indicators. Methods: A longitudinal cluster randomized control trial was implemented across the 10 regions of Ghana, covering 2,869 school age children (aged 5-15y). Communities were randomized to 1) control group without intervention; or 2) treatment group providing the reformed national school feeding programme. Primary outcomes included height-for-age (HAZ) and BMI-for-age (BAZ) scores. The analysis followed an intention to treat approach as per the published protocol for the study population and sub-group analysis by age (i.e. mid-childhood for children 5-8y and early adolescence for children 9-15y), gender, poverty and region of residence. We used single difference ANCOVA with mixed-effect regression models to assess programme impacts. Findings: School feeding had no effect on HAZ and BAZ in children aged 5-15 years. However, in per protocol subgroup analysis, the school feeding intervention improved HAZ in 5-8y old children (effect size 0.12 SDs), in girls (effect size 0.12 SDs), particularly girls aged 5-8y living in the northern regions, and in children aged 5-8 in households living below the poverty line (effect size 0.22 SDs). There was also evidence that the intervention influenced food allocation and sharing at the household level. Interpretation: Schools feeding can provide a platform to scale-up nutrition interventions in the early primary school years, with important benefits accruing for more disadvantaged children. Trial Number: Trial registered on the ISRCTN Registry as ISRCTN66918874 Funding Statement: This trial was funded by the Bill and Melinda Gates Foundation and Dubai Cares. Declaration of Interests: Aulo Gelli received support from the CGIAR Research Program on Agriculture for Nutrition and Health (A4NH), led by the International Food Policy Research Institute. Ethics Approval Statement: Ethical clearance was obtained from the Institutional Review Board of the Noguchi Memorial Medical Research Institute of the University of Ghana and sought at the Imperial College Research Ethics Committee. Meetings were held from early stages in the study development with relevant government ministries both at central and decentralised levels to discuss the purpose, procedures and risks involved in the study. Informed consent was obtained from parents/guardians of children through written and verbal information provided before interviews.

Efficacy of photobiomodulation on oral lichen planus: a protocol study for a double-blind, randomised controlled clinical trial

IntroductionOral lichen planus (OLP) is an idiopathic chronic mucocutaneous disease with a wide range of clinical manifestations, including white reticular patches, erosive/ulcerative and atrophic lesions, both associated with intense symptomatology....

Ease of access to antibiotics without prescription in Chinese pharmacies: a nationwide cross-sectional study

BackgroundThe acquisition of antibiotics without a prescription is recognised as a major cause of misuse of antibiotics, and a contributor to anti-microbial resistance (AMR) globally. Levels of AMR in China are among the highest in the world. The aim of this study was to assess ease of access to antibiotics without prescription across the three regions of mainland China. MethodsUsing the simulated patient method, we did a cross-sectional survey using purposive sampling, in retail pharmacies in urban and rural areas of 13 provinces in China from July to September, 2017. The simulated patients were medical students who described very mild upper respiratory tract symptoms, following a standardised protocol. They recorded the details of the pharmacy and their experience. This included whether they were given an antibiotic and at what stage in the protocol, whether the pharmacy was part of a chain or independent, whether the attending pharmacist attending them had a licence, and whether there was a sign stating prescriptions were required for antibiotic. We used χ2 tests to compare categorical variables. Ethical approval was obtained from Zhejiang University Research Ethics Committee. FindingsComplete data were obtained from 1106 pharmacies. Antibiotics were obtained in 925 pharmacies (83·6%, 95% CI 81·5–85·8). There were differences between provinces, ranging from 57% in Zhejiang to 98·8% in Guizhou There were no significant differences in access to antibiotics by level of city, county, or township (p=0·25), whether the pharmacy was part of a chain or independent (p=0·23), whether a licensed pharmacist was attending (p=0·82), or whether there was a standard sign saying that prescriptions were required for antibiotics (p=0·19). Pharmacists overall provided a poor standard of service, with very little questioning about the students' symptoms or no explanation about correct use of antibiotics. InterpretationIt is very easy to obtain antibiotics without a prescription in retail pharmacies in China. Given that effective anti-microbial stewardship programmes have been introduced in many hospital settings in China, especially at tertiary level, the failure of the government to enforce the existing law on prohibition of antibiotic sales without prescription is all the more concerning. Such enforcement should be addressed as a matter of urgency, alongside a targeted public education campaign. FundingThis work was supported by Zhejiang University Explorative Research Programme (Number GW-17–04).

Hepcidin Attenuates the Secondary Neuronal Injury after Intracerebral Hemorrhage in Rats

Iron plays a key role in secondary neuronal injury after intracerebral hemorrhage (ICH), and hepcidin is able to reduce brain iron in iron-overloaded rats by down-regulating iron transport proteins. These led us to hypothesize that hepcidin might reduce iron-mediated neurotoxicity by inhibiting iron accumulation in ICH brain. Here, we tested our hypothesis in 510 rats and demonstrated for the first time that hepcidin could significantly suppress the ICH-induced increase in iron and ferritin in brain tissues and cerebrospinal fluid by inhibiting expression of iron transport proteins, increase neuronal survival by attenuating ICH-induced apoptosis, neurodegeneration and brain edema, as well as effectively improve ICH-induced behavioral and cognitive deficit in rats. We concluded that hepcidin could effectively attenuate iron-mediated secondary neuronal injury after ICH in rats. This naturally existing protein which is biodegradable, nontoxic, and non-immunogenic can potentially be developed into a therapeutic drug for the treatment of ICH patients. Funding: The studies were supported by the National Natural Science Foundation of China (NSFC31330035-ZMQ, NSFC31571195-ZMQ), the Competitive Earmarked Grants of The Hong Kong Research Grants Council (GRF14111815-KY, GRF 14167817-KY, GRF14107616-KY), Hong Kong Health & Medical Research Fund (HMRF: 03141436-KY), Hong Kong Innovation and Technology Fund (ITS/163/16-KY), and the National 973 Programs (2014CB541604-ZMQ). Conflict of interest: The authors declare that they have no conflict of interest. Ethical Approval Statement: The Health Department of Hong Kong and Shanghai Government and the Animal Research Ethics Committee of The Chinese University of Hong Kong and Fudan University approved the experimental procedures of this study and the care and handling of the animals were in accord with National Institutes of Health guidelines.

Caracterização do trabalho de enfermeiros e profissionais do Núcleo de Apoio à Saúde da Família na Atenção Primária

Introdução: Avaliar o trabalho dos profissionais de saúde da atenção básica pode revelar informações importantes relacionadas à forma de produção de cuidado, essenciais para sua qualificação e atendimento das necessidades de saúde da população. Objetivo: Este estudo se propôs caracterizar o trabalho de enfermeiros da Estratégia Saúde da Família e profissionais de saúde de Núcleos de Apoio à Saúde da Família em um município da Paraíba, Brasil. Métodos: Trata-se de um estudo transversal no qual foram incluídos enfermeiros da Estratégia Saúde da Família e profissionais de saúde dos Núcleos de Apoio à Saúde da Família da cidade de Campina Grande, totalizando 52 profissionais, 20 enfermeiros e 32 de outras formações da área de saúde. Utilizou-se um questionário estruturado com informações sobre formação profissional, características do trabalho e satisfação profissional. O projeto teve aprovação pelo Comitê de Ética em Pesquisa da Universidade Estadual da Paraíba. Resultados: Os enfermeiros destacaram falta de solidariedade no trabalho e de reconhecimento. A maioria dos profissionais dos Núcleos de Apoio à Saúde da Família mostrou insegurança decorrente de instabilidade laboral e medo de ficar sem trabalho. Ambos os grupos de profissionais indicaram baixa satisfação com a estrutura física, o atendimento individual à demanda e as reuniões com a comunidade. Conclusão: Os profissionais da Atenção Primária à Saúde do município têm que lidar com limitações impostas por um cenário estrutural pouco favorável das unidades de saúde e vínculos trabalhistas marcados por insegurança, falta de solidariedade e baixo reconhecimento.

Bone Marrow-Derived Macrophage Contributes to Fibrosing Steatohepatitis Through Activating Hepatic Stellate Cells

Background & Aims: The role of macrophages in fibrosing steatohepatitis is largely unclear. We characterized the origin and molecular mechanisms of macrophages and its targeted therapy in fibrosing steatohepatitis. Methods: Fibrosing steatohepatitis was established in Alms1 mutant (foz/foz) and C57BL/6 wildtype mice fed high-fat/high-cholesterol (HFHC) or methionine-and choline-deficient (MCD) diet. Bone marrow transplantation (BMT) was performed to track the macrophage origin in fibrosing steatohepatitis. Macrophages were depleted by liposomal clodronate. Primary macrophages were isolated from bone marrow for adoptive transfer into mice. Results: Macrophage infiltration is significantly induced in two mouse models of fibrosing steatohepatitis and human NASH-fibrosis patients. Bone marrow-derived macrophages (BMMs) contribute to the hepatic macrophage accumulation in experimental fibrosing steatohepatitis. Hepatic BMMs depletion by liposomal clodronate significantly attenuated fibrosing steatohepatitis. This effect was associated with reduced hepatic stellate cell (HSC) activation, collagen deposition and hepatic expression of key pro-fibrotic factors (TIMP1, TIMP2 and TGFβ1) and endoplasmic reticulum (ER) stress markers (GRP78, IRE1α and PDI). Conversely, adoptive transfer of BMMs significantly aggravated fibrosing steatohepatitis. Moreover, macrophage conditioned medium directly promoted the phenotypic transition of primary quiescent HSCs to activated HSCs; enhanced activation and proliferation (P<0.01) but decreased apoptosis (P<0.001) of HSC cell lines (LX-2 and HSC-T6). The effect of BMMs in promoting fibrosing steatohepatitis was mediated by inducing key pro-fibrosis factors and signaling pathways including cytokine/chemokine, TGF-β, and complement cascade by cDNA expression array. Complement 3a receptor (C3aR1) was a predominant effector of macrophage mediated fibrosing steatohepatitis. Knockout C3aR1 in mice blunted the development of fibrosing steatohepatitis. Conclusions: Macrophages recruited from bone marrow promote the progression of fibrosing steatohepatitis through directly activating HSCs. BMMs targeted therapy is a promising approach for fibrosing steatohepatitis. Funding: The project was supported by the RGC-GRF Hong Kong (14106415, 14111216, 14163817); Science and Technology Program Grant Shenzhen (JCYJ20170413161534162); Vice-Chancellor's Discretionary Fund CUHK; Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute; CUHK Direct grant. The human liver specimens were provided by Prof. Vincent WS Wong in the Prince of Wales Hospital, the Chinese University of Hong Kong and Prof. Kwan Man in the Queen Mary Hospital, University of Hong Kong, Hong Kong. Competing interests: All authors declare that they have no competing interests. Ethics Approval Statement: All subjects were given written informed consent prior to sample collection and the study protocol was approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong.