Documentation of structured community engagement initiatives and real-time monitoring of community engagement activities during large-scale epidemics is limited. To inform such initiatives, this paper analyses the Community Led Ebola Action (CLEA) approach implemented through the Social Mobilization Action Consortium (SMAC) during the 2014–2016 Ebola epidemic in Sierra Leone. The SMAC initiative consisted of a network of 2466 community mobilisers, >6000 religious leaders and 42 local radio stations across all 14 districts of Sierra Leone. Community mobilisers were active in nearly 70% of all communities across the country using the CLEA approach to facilitate community analysis, trigger collective action planning and maintain community action plans over time. CLEA was complemented by interactive radio programming and intensified religious leader engagement.Community mobilisers trained in the CLEA approach used participatory methods, comprised of an initial community ‘triggering’ event, action plan development and weekly follow-ups to monitor progress on identified action items. Mobilisers collected operational and behavioural data on a weekly basis as part of CLEA. We conducted a retrospective analysis of >50 000 weekly reports from approximately 12 000 communities from December 2014 to September 2015. The data showed that 100% of the communities that were engaged had one or more action plans in place. Out of the 63 110 cumulative action points monitored by community mobilisers, 92% were marked as ‘in-progress’ (85%) or ‘achieved’ (7%) within 9 months. A qualitative examination of action points revealed that the in-progress status was indicative of the long-term sustainability of most action points  versus one-off action items that were marked as achieved . Analysis of behavioural outcomes of the intervention indicate an increase over time in the fraction of reported safe burials and fraction of reported cases referred for medical care within 24 hours of symptom onset in the communities that were engaged.Through CLEA, we have demonstrated how large-scale, coordinated community engagement interventions can be achieved and monitored in real-time during future Ebola epidemics and other similar epidemics. The SMAC initiative provides a practical model for the design, implementation and monitoring of community engagement, integration and coordination of community engagement interventions with other health emergency response pillars, and adaptive strategies for large-scale community-based operational data collection. Reviews of the 2014–2016 Ebola epidemic in West Africa identified community engagement and social mobilisation programmes as a critical component of the response and important contributing factor to ending transmission.The Social Mobilization Action Consortium (SMAC) was the largest coordinated community engagement initiative during the Sierra Leone Ebola outbreak, reaching more than 12 000 communities through 2466 trained community mobilisers, a network of 2000 mosques and churches and 42 local radio stations.We present the SMAC’s Community Led Ebola Action (CLEA) data set and undertake a retrospective analysis of the CLEA triggering and community action planning process and reported behavioural outcomes in engaged communities.The findings demonstrate that large-scale participatory community engagement and real-time data collection, including community-generated surveillance data on Ebola-safe behaviours, sickness and death, are achievable in the context of a health emergency if adequately structured, managed, coordinated and resourced.The findings suggest lessons and innovations for large-scale community engagement that should be considered in future epidemics and other health emergencies. These include the need for: (1) recognition of community agency, two-way communications and active roles for communities in epidemic response; (2) prioritisation of community engagement interventions as a critical pillar of epidemic preparedness and response; (3) a supportive infrastructure for mobilisers and front-line workers; (4) standards of practice to guide quality and coordination of community engagement interventions; (5) integration of community engagement activities and data with other bio-medical pillars of disease response, in particular surveillance; (6) prioritisation of real-time community data collection and analysis to inform response decision-making; and (7) taking into account the imperatives of emergency response when defining ‘community’.Community engagement and other community-centred approaches during public health emergencies are increasingly recognised as important components of health emergency preparedness and response, in order to foster enabling and reinforcing conditions for behaviour change to reduce the spread of disease.6–9The importance of community engagement was exemplified during the 2014–2016 outbreak of Ebola Virus Disease (Ebola) in West Africa.12Early messaging overly emphasised Ebola as a ‘killer disease’ but fell short in providing actionable information on prevention, treatment, and possible survival.11It is within this context that five partner organisations—GOAL , Restless Development Sierra Leone , FOCUS 1000 , BBC Media Action , and the US Centers for Disease Control and Prevention—developed an integrated, community-led, data-driven approach to Ebola social mobilisation, with its core component consisting of a large-scale community engagement to support outbreak containment. The Social Mobilization Action Consortium (SMAC) was established in September 2014 and became operational in October 2014 in support of the Sierra Leone Ministry of Health and Sanitation’s Social Mobilization Pillar.Previous research on community behaviour and practice in West Africa during the Ebola outbreak has found that communities have the capacity to rapidly acquire new knowledge and make change, but that effective behaviour change or adoption of safe practices can only occur when practical or realistic actions are in place to facilitate them.In this paper, we describe SMAC’s approach to community engagement within the Sierra Leone outbreak response. We analyse over 50 000 semi-structured weekly reports from the network of SMAC community mobilisers (mobilisers). We draw upon this extensive data, and collective implementation experience, to identify key lessons and make recommendations for future design, implementation and research of community engagement activities within epidemic response and other health emergencies.Restless Development and GOAL trained and supported nearly 2500 mobilisers who worked with communities to design and implement community action planning. FOCUS 1000 trained, engaged and supported over 6000 religious leaders from over 2000 mosques and churches to promote key messages and role model promoted behaviours, especially around safe burials. BBC Media Action supported 42 local radio station in all 14 districts to improve the quality and synchronisation of radio programming. Mobilisers were deployed in approximately 70% of communities in Sierra Leone across all 14 districts. Community engagement activities were complemented by near universal radio coverage and religious leader engagement .10.1136/bmjgh-2019-002145.supp1Supplementary dataMobilisers were recruited from an existing cohort of community health workers, former Restless Development youth volunteers and trusted people nominated by communities. Ebola survivors were also actively recruited as mobilisers, bringing with them first-hand experience of engaging with response mechanisms. This strategy of recruiting Ebola survivors also responded to the need for providing survivors with much-needed employment.19Community engagement was facilitated through the Community-led Ebola Action (CLEA) approach see .20 CLEA 13Mobilisers completed a 1 week hands-on training programme, and subsequent refresher trainings, action-learning and other capacity building activities as part of their preparation for implementing the CLEA approach.11 25A critique of the Ebola response in West Africa, especially in the early stages, was the emphasis on one-way, health communication messaging focussed on the disease itself.The aim of CLEA triggering events was to create a sense of urgency, a desire to act and local ownership. In each community, an initial triggering event was held using a set of six tailored PLA tools and facilitated by trained mobilisers. Communities received no payments for attendance and participation; however, community leaders received a comprehensive briefing on the programmes and its activities ahead of engagement. The participatory triggering activities consisted of: (i) Body Mapping; (ii) Danger Discussion; (iii) Burial Roleplay; (iv) Personal Protective Equipment Demonstration; (v) Ebola Survivor Stories; (vi) Ebola Spread Exercise. These are detailed in the CLEA manual.community identification of priority actions for action plans once an ‘ignition moment’ had been achieved and communities were receptive and prepared to develop an action plan. Mobilisers were trained with a set of indicative actions covering focus areas such as burials, reporting symptoms/deaths, reintegration of survivors and child protection, but also to anticipate that community priorities for action may include a combination of both Ebola-specific actions and non-Ebola-specific community priorities  using Open Data Kit (opendatakit.com). Starting in April 2015, digital data reporting was extended to also document the activities of religious groups and radio stations in the five aforementioned districts. Using these data, weekly community engagement situation reports were developed. These included qualitative reports from communities, actions of national and district pillars, numbers of community visits, mobiliser meetings and alerts, religious leader and radio activities see ref. .Through the CLEA approach, mobilisers worked with more than 12 000 communities nationally. Mobilisers using the standardised paper forms engaged 2 113 902 community members, of which 50.2% were women while 49.8% were men, and 46% were young people under 18 years while 54% were adults. This number of individual engagements includes multiple interactions with community members who met with mobilisers over multiple visits. During triggering events, the average number of participants per community was 48; in follow-up visits however, the number more than doubled to 113 participants, on average, engaging in community discussions. Distributions of sex and age among participants at triggering versus follow-up visits were not significantly different.In parallel, using digital reports, mobilisers collected data from both community-level visits and, predominantly in urban areas, house-to-house visits. Mobilisers had 3 129 380 individual engagements with community members across multiple visits. Similar to the visits recorded in the paper-based data, 52% of these were women and 48% men. The average visit consisted of an interaction with 57 community members with most around 25 people, but some as high as hundreds.The main behavioural outcomes measured during triggering and follow-up visits were (i) timely referrals of sick household members for medical care and (ii) timely requests of safe burials for deceased family members . In our Monitoring data revealed that 100% of communities developed community action plans; action plans contained, on average, three action points. Between April and September 2015, when monitoring was fully operational including through the digital system, mobilisers followed-up on 63 110 cumulative action points. Of these collective action points, 85% were assessed as ‘in-progress’ while 7% were marked as ‘achieved’ and another 7% were ‘not achieved’. Summary statistics from our data on action points and bylaws collected through the paper forms are presented in The data show shifts in action points prioritised and implemented by community members during the intervention period . For insThese data were collected to inform an operational response during an ongoing outbreak. Approval for the SMAC initiative, including community-level data collection, was obtained from the Government of Sierra Leone. Further, the University of Vermont Institutional Review Board (IRB) deemed the work exempt from requiring IRB approval. The data were collected anonymously at the community level. No individual-level data were collected, therefore personal identifiers are not included in the aggregated data set. Mobilisers were trained to obtain verbal informed consent from community members—including community leaders—before completing monitoring data forms during all community visits. Use of the data is subject to terms and conditions outlined in a data-sharing agreement between the Institute for Disease Modeling (in USA) and FOCUS 1000 (in Sierra Leone), the latter being custodian of the SMAC data set.Monitoring data show that between November 2014 and December 2015 SMAC mobilisers, community champions and religious leaders made more than 4500 alerts to response authorities at district level, through the Ebola 117 hotline as well as directly to district-level alerts desks, which were often manned by SMAC mobilisers.These factors essentially established a de facto community surveillance system and closed feedback loop that resulted in mobilisers becoming a primary source of new alerts in some districts. It took some time for response authorities to recognise the need for closer integration of community engagement with other biomedical pillars of the response. These findings indicate the benefits  of creating strong operational linkages between community-level prevention and other aspects of the response, particularly surveillance. For example, the development of SOPs for community engagement that are integrated with biomedical pillars and afford closer integration is integral within an effective Ebola response.11 24Programmatic data demonstrate that it is possible not only to deliver a large-scale national participatory community engagement intervention in a health emergency context, but also that such participatory methodologies can support the collection of real-time data at scale. The monitoring, follow-up and data collection efforts themselves were able to establish meaningful feedback loops for exchange of information between response authorities and affected communities. This was demonstrated by the increased reliance of district authorities on mobilisers for new alerts, as well as the use of data on community perceptions to inform changes to other response services. Previous studies have shown that digital data collection can be successfully implemented by community health workers with little experience if adequately trained and supervised.The SMAC model also suggests that behaviour change interventions are most likely to be effective when a combination of communication channels and platforms are used, including community-level interpersonal communication and mass media, and working within an overarching government strategy. This approach is more likely to achieve consistent information and messaging supporting community-led responses that are repeated and reinforced via multiple channels (such as religious leaders and radio), thereby increasing information credibility and reducing confusion caused by mixed messaging.CLEA demonstrates that communities are not passive recipients of health messages and services. Communities can—and must—be seen as critical agents and equal partners in an emergency response, as they are often best-placed to assess risk and identify mitigation steps in their contexts through collective action planning. Communities are willing to adopt new and sometimes difficult changes to deep-rooted, socio-cultural practices such as funerals and burials, and are capable of arriving at locally-appropriate and acceptable modifications to such practices in response to disease threat.18Analysis of the CLEA approach and other SMAC interventions indicate that it is feasible to support communities to plan for and monitor their own actions in a quantifiable way during an epidemic, provided the right enabling and reinforcing operational structures are in place. Community action plans are more durable and flexible than universal or standardised communications messaging. Participatory action planning methodologies can enable community benchmarking, tracking and adaptation of agreed actions and behaviours over time and as an epidemic evolves. The data on community action plans, as well as the role modeling done by religious leaders as trusted influencers, illustrate how community engagement can facilitate behaviour changes to stop disease spread, especially when targeted in geographical regions of high transmission. Analysis of population-based trends in Sierra Leone show a sixfold increase in intention to wait for safe burial teams and twofold increase in self-reported avoidance of unsafe burials in high transmission regions when comparing before and after the peak of the outbreak.32Community engagement, when guided by standardised, but flexible, operational processes can be effectively monitored, sustained and adjusted within the context of an epidemic response. Undertaking community engagement at scale requires clear protocols and guidelines that facilitate a sustained relationship between response authorities, front-line workers and communities. Such protocols include: collection of strong baseline data identifying key behavioural determinants of disease transmission; regular and timely systems for capturing and reporting community monitoring data; systematic and consistent community engagement approaches emphasising two-way communication and feedback loops; established and clear lines of responsibility from response management to front-line mobilisers; iterative mapping of mobilisation activities and systematic identification of emergent issues, cases and trends in localised geographies; continuous supervision and ongoing peer-to-peer support for community mobilisers and front-line support staff; and adequate logistical and communication support.Community health approaches that depend on what are often termed ‘volunteers’, such as Community Health Workers and other community mobilisers, can be marked by high levels of attrition.Since the Sierra Leone Ebola outbreak, the WHO has published the WHO guideline on health policy and system support to optimise community health worker programmes,35Given its decentralised nature, community engagement in epidemic response can sometimes suffer from poor coordination, resulting in confusing or conflicting messages, as well as inconsistent coverage whereby some communities are neglected or underserved, while others are oversaturated and fatigued. To address this, roles, responsibilities and accountability mechanisms should be clearly outlined for implementing agencies undertaking community engagement activities. Coordination between stakeholders can be greatly advanced through a shared set of protocols or standards guiding practice. Shared standards informing community engagement approaches, communications messaging, training and monitoring systems across implementing agencies can enable consistency, quality interventions from which relevant data can be collected to inform other aspects of the operational response. For example, in Sierra Leone the development of Standard Operating Procedures for Ebola Social Mobilisation, which drew significantly on the CLEA model, significantly improved the operational response in relation to rapid response teams and the district-level coordination.The SMAC consortium model also suggests that behaviour change interventions are most likely to be effective when a combination of communication channels and platforms are coordinated, combining community-based interpersonal communication such as CLEA with mass media and working in support of government policies. This approach is more likely to achieve rapid behaviour change in an outbreak setting, as consistent information and messaging that support community-led responses are repeated and reinforced via multiple channels, thereby increasing information credibility and reducing confusion caused by mixed messaging.Community engagement approaches are focussed on improving the effectiveness of the biomedical response. It spans both demand generation for response services and ensuring that the supply of essential services meets increased demand. This is increasingly relevant as new pharmaceutical tools become available for treating or preventing transmission, yet uncertainty or distrust in communities may avert their uptake. By establishing two-way communication platforms between response actors and communities, community engagement informs decision-making across all aspects of the response. Therefore, response actors should place more emphasis on creating strong functional linkages between community-level prevention and other aspects of the response. Separation of community-based activities from other technical areas that are inherently interconnected risk undermining response effectiveness.In Sierra Leone, the SOPs were developed by the Social Mobilization Pillar in conjunction with representatives from other response pillars.Community engagement can be monitored at scale in an epidemic response context. Where possible, it should be consistently and rigorously measured during health emergencies of all sizes. Real-time data collection of both behavioural and operational data allows for the findings to inform response decision-making and programming in real time. The granularity of community engagement data collected in real-time at the level of individual communities allows for responses to be localised and responsive to the specific local challenges and opportunities. While existing models for community engagement have developed mechanisms for gathering considerable amounts of social science and behavioural data during the most recent outbreak in the Democratic Republic of the Congo (for example, issues such as rumours and knowledge, attitudes and practices related directly to the disease itself37Modelling of the impacts of social interventions on disease transmission in an epidemic is limited by a lack of reliable, at-scale field data collection on social and behavioural indicators, along with indicators that measure the process of community engagement. Tracking a few key community engagement indicators, aligned to a national, government-led monitoring and evaluation framework, should be included in national Situation Reports and mandated for collection and collation by primary implementing agencies.Placing tools for collection and analysis in the hands of communities, whereby mobilisers or front-line workers are provided with the training, tools and support structures to collect data on community engagement, ensure that the analysis flows back to communities, so they understand how response authorities are using it. Developing a digital data collection system also proved invaluable in ensuring information on behaviours in communities was immediately available. Digital data collection overcomes the limitations of paper-based data collection, including collection, transportation and onerous data entry, as well as inconsistencies in spelling and large degrees of missing information on handwritten forms. Donors and governments should increase investment in digital data collection in order to help generate robust, large-scale, real-time data from communities on health and other social issues affecting quality of life.It should be acknowledged that the imperatives of structured community engagement initiatives in humanitarian response can risk undervaluing the complexity of communities and their contexts.Despite efforts in design and implementation of the CLEA approach to address issues of participation, inclusion and empowerment, the concept of ‘community’ underpinning the SMAC initiative remained relatively homogeneous. However, for the purpose of rapidly establishing a mechanism for two-way communication at scale, it was found that the framing of ‘community’ focussed on a geographical function, as well as representation of shared values, customs and assets, was effective in garnering sufficient levels of community participation. In Freetown and other urban centres, where ‘communities’ are even more ill-defined, it was found that specific challenges such as lack of community cohesion, high density, informal urban settlement conditions and high mobility required adaptations to the CLEA methodology, including house-to-house visits. There is considerable scope for research on the impacts of community engagement itself on the power dynamics within communities and the effectiveness of models of intervention.One of the main shortcomings of the SMAC data set is that data from November 2014 through December 2015 were collected through paper reports, while a subset of data from April through September 2015 were collected through digital reports. Direct merging of these data sets proved problematic due to differences in data collection. For instance, some questions that had been open-ended in the paper form entry were included with categorised, multiple-choice type options in the digital form entry. Quantitative epidemiological data were consistently entered across all data collection platforms.It should be noted that data were self-reported by communities and collected by community mobilisers which may have resulted in positive reporting bias. As such, issues of latent non-compliance cannot be discounted in some communities overreporting based on expectations of Ebola-safe practice.The CLEA approach demonstrated that communities are able to plan for and monitor their own actions in a quantifiable way during an epidemic provided the right enabling and reinforcing structures are in place. Evidence for the approach included: strong baseline data identifying key behavioural determinants; systematic and consistent community engagement approaches emphasising two-way communication and feedback loops; regular and timely system for capturing and reporting monitoring data; continuous supervision, top-up training and ongoing peer-to-peer support for community mobilisers; and adequate logistical and communication support, including communications support to communities. Furthermore, the data suggest that communities are capable of engaging in localised surveillance and referral if given the right tools, support and linkages to the formal health structures and systems. Finally, the experience of the SMAC initiative and broader community engagement response in Sierra Leone suggests mechanisms for improving community engagement quality, coordination, integration and monitoring across response actors.


Dear Editor in Chief,1 Environmental and cultural factors, as well as lifestyle preferences, play important roles in the rising prevalence of childhood obesity worldwide.2 Evidence implies the increasing trend of childhood obesity globally, especially in developing countries.3, 4 Studies in developing countries are more concentrated on nutritional deficiencies. Deficiencies in nutrition, notwithstanding, childhood obesity and its complications should be focused upon for appropriate practice of evidence-based health promotion.5 Accordingly, we sought to collect evidence on the prevalence and trends of obesity among children and adolescents in Iran and compare our findings with the other regions of the World Health Organization (WHO) using the WHO data. 6Childhood obesity is an important predisposing factor for most noncommunicable diseases, namely diabetes, high blood pressure, asthma and other respiratory problems, sleep disorders, and liver disease in the future.As is shown in The high prevalence and increasing trend of obesity among children and adolescents must be deemed alarming by health policymakers, who should devise interventional preventive programs aimed at these sensitive age groups. The high prevalence of obesity in adults in many countries renders weight reduction a tremendous challenge; it is, therefore, advisable that children be considered the priority population for such intervention strategies as enhanced physical activity and improved diet. Preschool institutions and schools are appropriate places for the implementation of these interventions.


Anesthetic care in patients undergoing thoracic surgery presents specific challenges that necessitate standardized, multidisciplionary, and continuously updated guidelines for perioperative care.A multidisciplinary expert group, the Perioperative Anesthesia in Thoracic Surgery (PACTS) group, comprising 24 members from 19 Italian centers, was established to develop recommendations for anesthesia practice in patients undergoing thoracic surgery . The project focused on preoperative patient assessment and preparation, intraoperative management , and postoperative care and discharge. A series of clinical questions was developed, and PubMed and Embase literature searches were performed to inform discussions around these areas, leading to the development of 69 recommendations. The quality of evidence and strength of recommendations were graded using the United States Preventative Services Task Force criteria.Recommendations for preoperative care focus on risk assessment, patient preparation (prehabilitation), and the choice of procedure (open thoracotomy vs. video-assisted thoracic surgery).These recommendations should help pulmonologists to improve preoperative management in thoracic surgery patients. Further refinement of the recommendations can be anticipated as the literature continues to evolve.The online version contains supplementary material available at 10.1186/s13741-020-00168-y. It has become increasingly clear that thoracic surgical procedures should be considered as a single step in a long journey, the perioperative care pathway, in which the collaboration of multiple healthcare professionals is crucial. Evidence-based perioperative care protocols, known as the enhanced recovery after surgery (ERAS®) “philosophy,” have been developed in many surgical settings, including lung surgery  group, was convened to review the evidence supporting different preoperative, intraoperative, and postoperative interventions in thoracic surgery patients.The PACTS group is a joint task force of the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care ; the Italian Society of Thoracic Surgery ; the Italian Society of Thoracic Endoscopy ; the Italian Society of Surgery ; the Italian Association of Hospital Pneumologists ; and the Italian Society of Pneumology . The group comprised 13 anesthetists, 3 pneumologists, 8 thoracic surgeons, a clinical epidemiologist, and management staff. Clinical centers were chosen from the participating Societies according to their expertise in thoracic surgery (primarily in cancer patients) in Italy.A Delphi consensus method was used to achieve consensus. Two preparatory meetings, three Delphi rounds, and a final consensus conference took place between June 2018 and March 2019. In the preparatory meetings, decisions were made on the final scope and structure of the project, composition of the expert panel, methods , definitions, authorship criteria, and management of potential conflicts of interest. It was decided that the principal focus of the project would be on elective lung resection for lung cancer in adults, and that the project would address three main areas: preoperative patient assessment and preparation, intraoperative management , and postoperative procedures and discharge. Surgery for mediastinal masses, esophagectomy, diagnostic procedures, and lung transplantation were not included in the project. An experienced medical librarian performed PubMed and Embase literature searches before the Delphi rounds, and updated them regularly; additional evidence was identified by manually scanning the reference lists in retrieved papers. A shared online folder was used to make evidence available to all group members. The search strategies are available in the Additional file The panel was divided into groups, covering preadmission, preoperative, intraoperative, and postoperative care. Each group comprised anesthesiologists, thoracic surgeons, and a pulmonologist. In the preliminary Delphi round, each group was assigned a specific subgroup of questions for each area, and drafted preliminary recommendations in response to each question, supported by appropriate references. In addition, a preliminary assessment of the overall quality of the evidence for each question was made at this time. In subsequent Delphi rounds, the whole panel had the opportunity to suggest modifications to any of the questions and recommendations.The panel adopted the United States Preventative Services Task Force (USPFTF) system for grading the quality of evidence Table  and streAfter the consensus meeting, a draft report was prepared and distributed via email to supervisors and the steering committee for modification and comment. Based on this feedback, a second draft was prepared and distributed to the expert panel and external consultants. Each author approved the final version prior to submission. This paper summarizes the final recommendations for preadmission and preoperative care, and the supporting evidence for these Table . The recWe recommend fully evaluating patients with lung cancer who are potential candidates for curative surgical resection, regardless of age. However, age itself is a risk factor included in two mortality risk scores after thoracic surgery, and should be taken into account to estimate the perioperative risk.Recommendation 1: Level of evidence: FairStrength of recommendation: AThe prevalence of lung cancer increases with age, and it is estimated that approximately 30–35% of candidates for pulmonary resection for lung cancer are over 70 years of age   class > 2 is a significant risk factor for death, prolonged hospitalization, or major cardiopulmonary complications in patients undergoing lung resection  by means of validated questionnaires is suggested in high-risk obese patients, with the aim of implementing strategies to reduce perioperative and postoperative complications. The perioperative team should focus on strategies to reduce the risk of complications for patients with body mass index ≥ 30 kg/m2.Recommendation 3: Level of evidence: GoodStrength of recommendation: AObesity is a growing problem in developed countries, and the perioperative respiratory management of obese surgical patients poses a number of challenges.2) is actually associated with a decreased risk of prolonged LOS following lung resection, compared with being within normal weight ranges  occurs in approximately 5–10% of thoracic surgery patients, and is associated with prolonged hospitalization and increased rates of complications such as tracheal reintubation, postoperative mechanical ventilation, and ICU admission; it has also been associated with increased mortality  Anemia Workgroup Evidence from small patient series shows that pulmonary resection for non-small cell lung cancer in patients receiving hemodialysis is associated with high rates of morbidity and mortality  .Recommendation 5: Level of evidence: FairStrength of recommendation: ACurrent smoking is a risk factor for postoperative complications, prolonged LOS, and mortality in patients undergoing thoracic surgery .Recommendation 6: Level of evidence: FairStrength of recommendation: ASeveral studies have shown that alcohol abuse in patients undergoing surgery for lung cancer is associated with increased rates of postoperative pulmonary complications and reduced long-term survival ; patients with VO2max > 20 mL/kg/min, 10–15 mL/kg/min, and < 10 mL/kg/min may be considered as being at low, intermediate, and high risk, respectively  where a lower threshold (ppoFEV1and ppoDLCO = 30%) may be considered. Because ppoFEV1and ppoDLCO are not always accurate predictors of postoperative function and outcome, we recommend the use of a larger panel of exercise tests in patients with values < 40% to evaluate risk according to guidelines for the preoperative evaluation of lung resection patients.Recommendation 8: Level of evidence: FairStrength of recommendation: A1) and predicted postoperative FEV1 (ppoFEV1) has traditionally been a key component of the preoperative evaluation of lung cancer patients, and decreases in these measures are associated with increased morbidity and mortality Recommendation 9: Level of evidence: FairStrength of recommendation: A2max > 20 mL/kg/min are at low risk of postoperative pulmonary complications, and these patients are deemed to be suitable candidates for all types of resection, including pneumonectomy ; a VE/VCO2 ratio > 35% indicates an intermediate or high risk of pulmonary complications , rather than major pneumonectomy  or lobectomy   and carbon dioxide (PaCO2) should be performed as part of the preoperative evaluation in all patients scheduled for elective pulmonary resection  to estimate the surgical risk of patients undergoing thoracic surgery.Recommendation 11: Level of evidence: Fair ; Good Strength of recommendation: AP = 0.04) , but not on multivariate analysis  . In these patients, multidisciplinary assessment is useful to consider different treatment options and select the best therapeutic approach.Recommendation 12: Level of evidence: PoorStrength of recommendation: AThe preoperative evaluation and perioperative management of patients undergoing thoracic surgery requires a multidisciplinary approach to assess the relative risks and benefits of surgery, optimize perioperative conditions, and plan the treatment regimen. This approach is endorsed in multiple management guidelines  in candidates for curative surgical intervention for lung cancer as it may reduce postoperative pulmonary complications. Since prehabilitation may reduce length of stay and postoperative pulmonary complications, it may be useful in COPD patients with mild to severe airway obstruction. Multimodal prehabilitation  is more effective than unimodal prehabilitation. It is advisable to schedule a preoperative prehabilitation program of 3 weeks.Recommendation 13: Level of evidence: PoorStrength of recommendation: A1, forced vital capacity, and performance in the 6-min walk test  model to monitor patients’ engagement and psychological needs and expectations.Recommendation 14: Level of evidence: FairStrength of recommendation: BThere is evidence that involving the patient in their care by the provision of preoperative counseling may reduce fear and postoperative fatigue and pain, enhance recovery, and facilitate early discharge from hospital , a shorter LOS , and a higher 4-year survival rate  , reintubation , blood transfusion , LOS , and chest tube duration   should be established during the preoperative evaluation, and shared with all members of the care team ahead of surgery.We do not recommend preoperative mechanical bowel preparation in patients undergoing lung surgery.Recommendation 16: Level of evidence: PoorStrength of recommendation: DA retrospective study of 560 thoracic surgery patients showed that preoperative mechanical bowel preparation did not reduce postoperative complications or length of stay   reduction in median recovery time, from 72 min (interquartile range [IQR] 50–102) to 62 min (IQR 44–90)  guideline on postoperative delirium discourages the use of benzodiazepine premedication, except for patients with severe anxiety , it is important to recognize that open thoracotomy is by no means an obsolete procedure, and may be more appropriate for certain patients than VATS. Our literature reviews and discussions highlighted that a comprehensive risk assessment prior to surgery is essential in candidates for lung resection, as this will help to determine the optimal surgical approach  in the individual patient. It is hoped that this approach will contribute to achieving optimal postoperative outcomes in the greatest number of thoracic surgery patients.The ERAS lung surgery guidelines (Batchelor et al. The management of thoracic surgery patients is a rapidly changing field, in which strongly evidence-based recommendations have hitherto been lacking. Further refinement of our recommendations can be anticipated as the literature continues to evolve.Additional file 1. Search strategy and keywords.


The brain is the most complex organ of human body composed of several highly specialised and heterogeneous population of cells, represented by neurones, neuroglia  and cells of brain vasculature. Neurones and neuroglia form neural circuits; different types of glial cells contribute to shaping and maintaining synaptic connections, plasticity, homeostasis, and network level activity through dynamic monitoring and alteration of central nervous system (CNS) functional architecture . Microgl12 purinoceptor is of a particular relevance for microglia. First and foremost, the expression of this receptor distinguishes CNS resident microglia from peripheral macrophages , which in the periphery acts as a major instigator of platelet aggregation and granule secretion thus supporting thrombogenesis -containing secretory vesicles: disruption of either impairs the microglia-somatic junction  last for tens of minutes and even up to 1 h, which is much longer compared to microglia-dendritic or microglia-synaptic contacts which usually last for several minutes only . Neuronajunction . To summMicroglial processes establish intimate contacts with axon initial segments early in development and these contacts are maintained through adulthood probably supporting axonal structure . Increas12 receptors that detect the source of ATP/ADP as a potential damage signal  remains; these cells arguably participate in defensive, safeguarding responses against neuropathology.The P2YConceptualisation: S-SL and AV; writing—original draft preparation: S-SL and AV; literature review, writing—review and editing: S-SL, YT, PI, and AV.Our work was supported by National Key R&D Program of China (2019YFC1709101), the Project First-Class Disciplines Development of Chengdu University of Traditional Chinese Medicine (CZYHW1901), the National Natural Science Foundation of China (81774437 and 81973969), and Science and Technology Program of Sichuan Province, China (2019YFH0108).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Probabilistic programming is an approach to reasoning under uncertainty by encoding inference problems as programs. In order to solve these inference problems, probabilistic programming languages (PPLs) employ different inference algorithms, such as sequential Monte Carlo (SMC), Markov chain Monte Carlo (MCMC), or variational methods. Existing research on such algorithms mainly concerns their implementation and efficiency, rather than the correctness of the algorithms themselves when applied in the context of expressive PPLs. To remedy this, we give a correctness proof for SMC methods in the context of an expressive PPL calculus, representative of popular PPLs such as WebPPL, Anglican, and Birch. Previous work have studied correctness of MCMC using an operational semantics, and correctness of SMC and MCMC in a denotational setting without term recursion. However, for SMC inference—one of the most commonly used algorithms in PPLs as of today—no formal correctness proof exists in an operational setting. In particular, an open question is if the resample locations in a probabilistic program affects the correctness of SMC. We solve this fundamental problem, and make four novel contributions: (i) we extend an untyped PPL lambda calculus and operational semantics to include explicit resample terms, expressing synchronization points in SMC inference; (ii) we prove, for the first time, that subject to mild restrictions, any placement of the explicit resample terms is valid for a generic form of SMC inference; (iii) as a result of (ii), our calculus benefits from classic results from the SMC literature: a law of large numbers and an unbiased estimate of the model evidence; and (iv) we formalize the bootstrap particle filter for the calculus and discuss how our results can be further extended to other SMC algorithms.


In 2013, Kenya fully and rapidly devolved health services to 47 county governments under its new constitution. It soon became evident that the coordination mechanism to manage the health workforce at a county level was inadequate. This case study describes how Kenya created an inter-county, multi-stakeholder human resources for health (HRH) coordination framework that promotes consensus, commitment, and cooperation in devolved HR management.Through USAID funding, IntraHealth International built the health workforce management capacity of county governments by strengthening coordination mechanisms at the national and county levels. Informed by stakeholder mapping, Kenya’s 47 counties were grouped into nine clusters with similar geographic contexts and HRH challenges. Inter-county cluster HRH stakeholder coordination forums are hosted by a rotating county-led secretariat and meet quarterly to address gaps, share successes and challenges, and track implementation of action plans. They link to the national level for capacity building, policy formulation, HRH regulation, and provision of standards. Counties have assumed ownership of the forums and contributed about US$85000 to date toward expenses.As a mechanism for transforming Kenya’s national HRH agenda into action at the county level, the HRH coordination framework has been instrumental in (1) expediting development, customization, and dissemination of policies, (2) enabling national HRH officers to mentor their county counterparts, and (3) providing collaborative platforms for multiple stakeholders to resolve HRH challenges and harmonize HR practices nationwide. Successes catalyzed through the inter-county forums include hiring over 20 000 health workers to address shortages; expanding the national HR information system to all 47 counties; developing guidelines for sharing specialist providers; and establishing professionalized HRH units in all 47 counties.Kenya has made great strides in strengthening its health system through the HRH coordination framework, which supports standardization of county health operations with national goals while enabling national policy to address HRH gaps in the counties. Transitioning to fully local funding of inter-county forums is important for sustaining progress. The First Global Forum on Human Resources for Health (HRH) in 2008 raised concerns about inadequate inter-sectoral coordination for HRH planning and governance. Participating countries were asked to adopt the World Health Organization’s Country Coordination and Facilitation (CCF)  approachThe HRH-ICC, with technical assistance from IntraHealth International through funding from USAID, expanded its mandate to focus on the implementation of the first National HRH Strategic Plan 2009–2012. The committee established three technical working groups (TWGs)—HR management, HR development, and HR information systems—to provide input on HRH technical issues, and assigned a secretariat supported by IntraHealth. The HRH-ICC monitored implementation of the HRH strategic plan and conducted an end-term evaluation that concluded the plan’s design suitably targeted the country’s HRH needs and that it had substantially achieved its intended outcomes.Aligned with the Country Coordination and Facilitation approach, the HRH-ICC provided a platform for developing and sustaining synergy, minimizing duplication of interventions, ensuring the focus remained on the critical HRH priorities envisioned in the national strategic plan, and leading in the coordination of a sector-wide HRH reform agenda. The HR Development TWG established a platform for coordination of pre- and in-service health training programs, contributing to completion of the first national health workforce forecast, which led to structuring of an HR development plan. The HRH-ICC also supported the MOH to map partners involved in hiring contract health workers in the public sector to harmonize their HR practices. The HRH-ICC and its partners were instrumental in developing Kenya’s 2013 HRH commitments declared during the Third Global Forum on HRH [Under the Constitution of Kenya 2010, the country transitioned from a centralized system to a decentralized system in 2013, with health services fully devolved to the 47 counties. The transition took place within 6 months instead of the 3 years recommended by the MOH’s HRH transition plan [An HR management rapid situation analysis conducted by IntraHealth in 2014 highlighted the lack of a smooth transition to devolved workforce management, including inadequate HR guidelines, structures, and procedures; delays in salary payment, third party and statutory deductions; and pension issues, giving rise to industrial unrest. Lack of coordinated communications strained relationships between county departments of health and the national MOH. In terms of HRH capacity at the county level, the analysis found insufficient HR management within health departments; limited access to HR policies and guidelines and lack of a repository to host the policies; a weak HR regulatory framework with HR functions being managed by non-HR professionals; weak coordination mechanisms within the departments responsible for HR functions; and inadequate HR practices in areas including recruitment, performance management, disciplinary and grievance procedures, and employee relations. Undefined reporting structures led to conflicts related to roles among the various levels of leadership in the county health departments [Through USAID funding, IntraHealth built the HR management capacity of county public service boards and county health departments by strengthening coordination mechanisms at national and county levels, interfacing with the Council of Governors and other constitutional bodies. The national HRH-ICC framework was cascaded to the counties beginning in 2014 through forming inter-county cluster HRH stakeholder coordination forums to address the HRH coordination gaps and to create a link to the national level for capacity building, policy formulation, HRH regulation, and provision of standards. Informed by stakeholder mapping conducted by IntraHealth and based on former administrative structures, the 47 counties were grouped into nine clusters with similar geographic contexts and HRH challenges: Central, Coast, Lake Basin, Nairobi Metropolitan, North Eastern, North Rift Valley, South Rift Valley, Upper Eastern, and Western  and meet quarterly to deliberate HRH issues ; validate and disseminate policies; share successes and challenges and track implementation of action plans; receive outcomes of HRH-ICC meetings; and share county issues with the national level. The counties also publish and share quarterly bulletins on their successes in HRH and service delivery.Participants in the inter-county forums include county departments of health, public service boards, and directorates of HR; medical training institutions; regulatory bodies and their local branches; health workforce trade union leaders and local chapters; national training and referral hospitals; and implementing partners involved in HRH, service delivery, and training.The key roles of these participants are based on each stakeholder’s specific mandate and thus influence the nature of the promising practices and challenges that they bring to the forums as part of the overall coordination process. County departments of health have the mandate of managing the health workforce and improving HRH systems in the devolved setup. Public service boards and directorates of HR have the responsibility for HR management and development at the county level . As part of their role in training health workers, medical training institutions also need to understand the labor market for their trainees. Regulatory bodies share standards of practice as well as regulatory requirements. Trade unions bring the voice of their members in representing health workers’ welfare. Implementing partners support carrying out health and HRH strengthening action plans emerging from the forum.The forums also have TWGs for HR management and information systems and HR development that discuss key challenges and make recommendations for implementation by the cluster counties Fig. . ThroughWhile the implementation of the HRH coordination framework has been led by IntraHealth with USAID funding, the framework provided from the onset a co-funding mechanism that allows counties to meet certain costs of the forums . The rotating secretariat function ensures individual counties are not at a disadvantage cost-wise. This hosting structure has gained momentum with counties taking over the ownership and management of the forums, funding/co-funding meetings, coordinating partner support, and chairing the sessions. To date, counties have contributed about US$85000 toward hosting the forums and meeting participants’ logistical and allowance expenses.Another coordination mechanism that has emerged from the inter-county forums is the county Chief Officers of Health Forum, which meets quarterly and is institutionalized through the Council of Governors. Deliberations of the Chief Officers of Health Forum are processed through the inter-governmental forum that brings county ministers of health and county executive committee members for health together with the Cabinet Secretary for Health  and other national stakeholders. The inter-governmental forum then shares resolutions with the summit chaired by the President of Kenya that brings county governors together to resolve matters arising from the lower-level decision-making structures.As a mechanism for transforming Kenya’s national HRH agenda into action at the county level, the HRH coordination framework has been instrumental in (1) expediting the development, customization, and dissemination of policies, especially at the county level, (2) enabling national HRH officers to mentor and coach their county counterparts to provide the required stewardship at the subnational levels, and (3) providing vibrant and effective collaborative platforms for multiple stakeholders to resolve HRH challenges and harmonize HR practices nationwide.The linkage between the national HRH-ICC and county governments has cultivated more consultation and collaboration in addressing HRH challenges. This has led to exchange of knowledge and experiences across interdependent departments, enhancing the efficiency of the health system. Peer-to-peer learning has catalyzed change and promoted harmonized understanding of policies across counties and implementation of HRH priorities including performance management for quality service provision.The inter-county HRH forums have served to effectively engage counties to identify and discuss solutions to key HRH challenges in the context of devolution. Some of the successes supported through these forums include the following:Counties have hired 21 481 health workers (46% growth) over the past 6 years to address shortages and bridge gaps. In addition, 764 (98%) of contract health workers have been transitioned from partner support to counties. The forums contributed to these gains by analyzing data on workforce gaps, advocating for budgets through the county health departments and county assemblies, and developing plans to hire priority health workers.IntraHealth, through USAID projects, has directly supported 27 priority high HIV-burden counties to implement its open source HR information system (iHRIS) to manage data needed to make informed HRH decisions. More than 63 000 public health worker records are now automated nationwide and each county has an iHRIS dashboard with visual workforce reports.TWGs have developed concept notes to address key HRH issues affecting counties such as the lack of specialized health workers like oncologists, family health physicians, radiologists, and other medical consultants, leading to “bottom up” policy development resulting in a guideline on sharing of specialist providers in the health sector. The guideline provides a framework for accessing specialists from other counties, national government, teaching and referral hospitals, the private sector, and faith-based organizations.An inter-county HR management capacity building plan has been implemented through training and mentorship. This has resulted in 1136 health sector managers and leaders with an HR mandate trained in HR management skills; 612 mentored, including 77 HR officers; and 47 county HRH units established, with 121 HR officers deployed to provide professional HR support to county health workers; 130 health sector leaders and 96 trade union leaders have also received training in leadership, management, and governance.The inter-county forums and information system TWG have been catalysts for peer mentorship and training to expand iHRIS to the remaining 22 counties.The incorporation of trade union leaders in the inter-county forums has provided an avenue for joint problem-solving and amicable resolution of disputes to avert health worker unrest.County stakeholders have participated in national HRH policy and guideline development through a defined process that allows customization at the county level for adoption and implementation. The forums have disseminated at least 104 policies and guidelines, including schemes of service, to all 47 counties, and over 35 policy guidelines have been developed.Key challenges have included (1) high turnover of leadership in county and national government, requiring regular orientation of new leaders to the coordination structure; (2) county public service boards lack of full understanding of the needs of the health sector, and especially HRH, even though health makes up 60–70% of the workforce in the counties and a similarly large budget; and (3) unavailability of funders besides USAID to support the coordination mechanism, resulting in unequal attention to arid and semi-arid land counties. Donor changes in geographic scope in 2015 slowed progress toward sustainability; however, this challenge also became an opportunity for counties’ greater self-reliance in convening and co-funding meetings.Kenya has made great strides in strengthening its health system through the HRH coordination framework. Through enhanced linkages between the national MOH and county health departments, the national Public Service Commission and county public service boards, and between the county public service boards and county health departments, it supports standardization of county health operations with national HRH goals while enabling national policy to address existing HRH gaps in the counties. Sustaining the inter-county cluster HRH stakeholders’ forums is critical if counties are to continue collaborating to effectively address the myriad of challenges that emerge in the devolved county health departments regarding health workforce management. Hence, it is key to maintain progress in establishing a county-led HRH stakeholders’ strategy with a secretariat that will manage it, and in transitioning from fully donor-supported funding to a donor/county cost-sharing structure to purely county-supported funding.Kenya’s HRH coordination framework presents a model for creating a multi-stakeholder platform that fosters open dialog and promotes consensus, commitment, and cooperation on HRH priorities in devolved health system management. It also provides a platform for discussions on HRH strategies for implementation of the journey to self-reliance. While many solutions and recommendations have been successfully integrated into on-going HRH interventions with commendable results, the endeavor needs to be sustained over the long-term to significantly impact health care service delivery in Kenya.


Aspergillus mycotoxins  during pregnancy may impair intrauterine fetal growth and promote neonatal jaundice. Findings were inconclusive concerning the influence of aflatoxin exposure on perinatal death and preterm birth. Only two studies assessed effects of maternal exposure to Fusarium mycotoxins  on adverse pregnancy outcomes. These studies found that maternal fumonisin exposure may be associated with hypertensive emergencies in pregnancy and with neural tube defects. Studies using grain farming and weather conditions as a proxy measure for mycotoxin exposure found that such exposure was associated with an increased risk of preterm birth and late-term miscarriage. In conclusion, there is already some evidence to suggest that exposure to mycotoxins during pregnancy may have detrimental effects on pregnancy outcomes. However, given the limited number of studies, especially on effects of Fusarium mycotoxins, more studies are needed for a more comprehensive understanding of the effects of different mycotoxins on maternal and fetal health and to guide public health policies and interventions.Mycotoxin exposure from food occurs globally but is more common in hot humid environments, especially in low-income settings, and might affect pregnancy outcomes. This study aimed to synthesize the evidence from epidemiological studies on the relationship between maternal or fetal exposure to different mycotoxins and the occurrence of adverse pregnancy outcomes. Multiple databases were systematically searched up to December 2018 to identify studies that assessed the association between mycotoxin exposure in pregnant women or fetuses and at least one pregnancy outcome. Studies were appraised and results were synthesized using standard methods for conducting systematic reviews. This review identified and included 17 relevant studies. There is some evidence to suggest that exposure to various  Aspergillus mold strains produce AFs and OTA, while Fusarium mold strains produce FBs, DON, and ZEN , and birth small-for-gestational-age (SGA), is multifactorial and not fully understood. Besides parity, maternal infection, hypertensive disease in pregnancy, and smoking as well-known risk factors Kramer , insuffiGlobally, mycotoxins contaminate an estimated 25% of cereal crops CAST  and due Chronic exposure to AFs, the most widely studied mycotoxins, is a known risk factor for liver cancer  AND ) AND .A systematic literature search was conducted in six major databases including PubMed, Web of Science, Ovid-Medline(R), Ovid-EMBASE, Ovid-MIDIRS (Maternity and Infant Care), and Ovid-AMED (Allied and Complementary Medicine), without language restrictions, to identify relevant studies up to December 8, 2018. The review question was defined using the PECO  framework  was conducted using the same search terms as above. For the Ovid database searches, a search was conducted using the same search terms as above combined with appropriate Boolean logic operators, incorporating the multiple field search (MP) and explosion (XM) function, as required. Additional searches for gray literature with the Google Scholar search engine, as well as cross-referencing, were conducted by manually searching bibliographies of the included articles for additional eligible studies. Finally, the search strategies for PubMed and Web of Science were saved and set up to receive automatic updates of new results. This systematic review was conducted in accordance with PRISMA guidelines  were published original observational studies or trials that assessed the effects of maternal  exposure to mycotoxins  on pregnancy outcomes  and (b) reported the association between maternal mycotoxin exposure and adverse pregnancy outcome(s) with an appropriate quantitative effect measure. Two reviewers  screened the titles and abstracts of identified articles to assess their eligibility for inclusion using the aforementioned criteria. Full texts of potentially relevant studies were obtained for further assessment. Studies that examined the prevalence of mycotoxins or of pregnancy outcomes only but not their association were excluded, as well as studies on the effects of mycotoxins more generally without a specific focus on maternal exposures and pregnancy outcomes. Relevant articles published as abstracts or posters only were also excluded because the amount of information was not sufficient for quality assessment.Two investigators  extracted data from eligible studies independently from each other, using a pre-coded data extraction form. This included the basic characteristics of the included studies and information on methodological quality assessment, as reported in Table A modified Newcastle-Ottawa Scale for observational studies , the remaining 204 studies were screened and 17 studies were then retained for full text review  quantitatively measured mycotoxin exposure; 11 of these used high-performance liquid chromatography (HPLC) often with fluorescence detection. Over half of the studies (9/17) assessed mycotoxins from maternal blood samples: four on the first antenatal visit (between 18 and 24 weeks of gestation) and five during the postnatal period. About half (5/9) of these studies also assessed mycotoxins from cord or infant blood samples. The remaining four studies that quantitatively measured mycotoxin exposure assessed mycotoxins either from cord blood or infant blood samples.The median detection frequency of mycotoxins in maternal blood samples was 87%, with detection levels ranging between 17% and 100%. The median reported detection frequency of mycotoxins in infant blood samples was 48%, with reported levels ranging from 15% to 91%. The adverse pregnancy outcomes investigated were intrauterine growth restriction (10 studies), neonatal jaundice (4 studies), miscarriage, stillbirth or perinatal death (3 studies), pre-eclampsia (2 studies), spontaneous preterm birth (1 study), and birth defects (1 study).Overall, ten studies were identified that evaluated the effects of maternal or fetal exposure to AFs on the occurrence of intrauterine growth restriction, which was mainly operationalized as lower mean birth weight (7 out of 10) and LBW  between AF exposure and birth weight  between AF exposure and incidence of LBW babies  in jaundiced neonates compared to non-jaundiced neonates   among children of grain farmers who were exposed to two or more fungal warnings in the season of conception compared to those exposed to one or no warnings, but findings were also consistent with no difference between groups  such as spina bifida up to a threshold of sa:so ratio of 0.35, beyond which fetal death was more likely , with only three studies published in the last decade. Despite the wide geographic distribution of the included studies covering four of the six WHO world regions , it is noteworthy that no study was from the Southeast Asia region despite a large number of human mycotoxin biomonitoring studies in this region  did not describe the population from which the study participants were selected or the criteria for selecting the analytic sample. Furthermore, because all the included studies were observational and many did not adjust for important factors such as maternal age and socioeconomic status, the possibility of residual confounding cannot be excluded. Nonetheless, all the included studies used an objective and reliable method for assessing adverse pregnancy outcomes and the majority (13 out of 17) also used standard quantitative methods for measuring mycotoxin exposure. The blood biomarkers used for AFs, for example, do not only provide an objective estimate of mycotoxin exposure but also provide an estimate of prior recent exposure , rather than the effect of exposure to multiple mycotoxins as occurs in reality, which may be reflected by the proxy measures.In Norway, where the proxy exposure studies were conducted, a recent study applying a semi-quantitative multimycotoxin analysis of grain grown in favorable fungal climatic conditions confirmed a high prevalence of multimycotoxin contamination  maternal exposure to AFs on intrauterine growth, potentially more so in girls, (b) fetal AF exposure on the development of neonatal jaundice, (c) maternal exposure to FBs on the development of hypertensive disease in pregnancy and neural tube defects, and (d) exposure to mycotoxins as measured through grain farming and weather conditions on preterm birth and late-term miscarriage.More prospective studies, using pregnancy and birth surveillance systems or using linked databases, are still needed to firmly establish the effects of mycotoxin exposure on adverse pregnancy outcomes in humans. In particular, studies should take advantage of recent development in biomarker analysis, enabling relatively easy and objective measurement of multiple different mycotoxins that constitute real-life exposure.


Background: The double burden of both under- and overnutrition during the first 1000 days is highly prevalent in Southeast Asia (SEA), with major implications for lifelong health. Tackling this burden requires healthcare professionals (HCPs) to acquire evidence-based current knowledge and counselling skills. We assessed the needs of HCPs in SEA and developed a continuing medical education/professional development (CME/CPD) program using an e-learning platform to reduce existing gaps. Methods: European, Thai and Malaysian universities collaborated with SEA national nutrition associations in the Early Nutrition eAcademy Southeast Asia (ENeA SEA) project. We assessed HCPs’ needs using questionnaires and mapped CME/CPD programmes and regulations through stakeholder questionnaires. Using a co-creation approach, we established an e-learning platform. Evaluation in users was undertaken using questionnaires. Results: HCPs in SEA reported major training gaps relating to the first 1000 days of nutrition and limited impact of existing face-to-face training. Existing pre/postgraduate, residency and CME/CPD programmes did not adequately address the topic. To address these gaps, we produced a targeted e-learning platform with six modules and CME-tests. National ministries, Thai and Malaysian universities, and professional associations endorsed the training platform. To date, over 2600 HCPs have registered. Evaluation shows high acceptance and a very positive assessment. Conclusions: Dedicated e-learning can reduce major gaps in HCP training in SEA regarding nutrition during the first 1000 days of life at scale and is highly valued by both users and key stakeholders. Despite encouraging economic development, considerable nutritional challenges remain across Southeast Asia (SEA). In children and adults, obesity prevalence has rapidly increased, while underweight in young children, high rates of stunting and of micronutrient deficiencies continue to exist, resulting in a double or even triple burden of malnutrition ,2. The bEarly life nutrition during preconception, pregnancy, infancy and early childhood is a significant contributor to the lifelong NCD burden, through a “programming” effect on the later risk of NCD. Research in the field of early nutrition and lifestyle during the first 1000 days of life after conception demonstrated that optimised nutrition and lifestyle during this critical phase of early development provides a window of opportunity to promote life-long health and wellbeing ,7.An important measure to tackle the double burden of malnutrition is providing health care professionals (HCPs) with current, evidence-based knowledge on early nutrition and lifestyle recommendations that enables effective counselling of (pre-) pregnant women and of families with infants and young children. Nutrition-related health problems including low birth weight, protein-energy malnutrition, iron deficiency anaemia and common deficiencies of micronutrients such as iron, iodine and vitamins A and D can be addressed through targeted advice from HCPs with appropriate knowledge and skills. Every encounter a HCP has with their patient is a window of opportunity for positive change. The World Health Organisation (WHO) has set SEA region guidelines for continuing medical education/professional development (CME/CPD) , but lacE-learning is a convenient and cost-efficient learning strategy, particularly in an era of social distancing in pandemic circumstances. It is easily accessible from various locations and devices and allows studying at the user’s own pace and time availability, with no time and cost investment for travel to a learning site. Therefore, we chose to establish e-learning on early nutrition and lifestyle for HCPs in SEA. Here we report on the approach used, the assessment of needs, and the experience with the established e-learning platform.The ENeA SEA project started on 15 October, 2016, co-funded by the European Union (EU) Erasmus + Capacity-Building for Higher Education (CBHE) Programme with a contribution of nearly 1 Million EUR for 3.5 years. The ENeA SEA consortium consists of leading experts in the field of early nutrition and e-learning from nine institutions: three universities from Europe, four universities from Thailand and Malaysia, the Nutrition Association in Thailand and the Nutrition Society in Malaysia . The goaMedical doctors that provide care for women who may get pregnant or are pregnant and for families with infants and young children were the primary target HCP group in the project, because they act as “multipliers” to set standards in the counselling process among HCPs at different levels. We anticipated that establishing knowledge among these professionals would create interest among other HCP groups, including nurses, midwives and nutritionists. Therefore, e-learning content was written at the level required for medical doctors, serving as the basis for subsequent adaptation for other HCP groups.Identifying specific topics and their prioritisation to develop a targeted ENeA SEA curriculum and e-learning modulesCreating appropriate, effective educational and technical formats optimally matching the needs of target groupsEnsuring that the content was of high practical relevance and could be directly translated into clinical practice and counselling, and into CME/CPD programmes, complementing existing training activities.Analysing the situation and assessing the needs of HCPs in SEA, with a focus on Thailand and Malaysia, was a prerequisite for achieving the project outputs, includingUnderstanding the needs of Thai and Malaysian HCPs related to early nutrition and lifestyle and analysing the CME/CPD structures were achieved through desktop research combined with online surveys containing closed and open questionnaire elements. The focus was to identify the underlying gaps in the transfer of knowledge in doctor’s practice to (pre-) pregnant and lactating women, infants and children , and the reasons for these gaps. Alongside identifying gaps in knowledge in relation to early nutrition and lifestyle healthcare counselling, the questionnaires sought to examine outdated knowledge and practices.Desktop research was performed to study and understand the present landscape of CME/CPD systems in Thailand and Malaysia, and more broadly in the SEA region. Using the Google search engine, the terminologies searched comprised: CME/CPD in Southeast Asia, Medical Association of Thailand, Medical Council of Thailand, Medical Association of Malaysia, WHO Guidelines, ASEAN Recommendations. The documents and websites analysed are listed in The content for questions of the online surveys was discussed among consortium partners, doctors in practice and nutritionists/dieticians working in the field of early nutrition, leaders of regional nutrition and medical societies. A survey containing three questionnaires was set up, discussed and approved by the EU and SEA partners. The questionnaires contained questions of different types, including dichotomous closed questions (Yes/No), Likert response scale (bipolar rating 1 to 5), nominal questions (multiple selection options) and open questions (text fields). All three questionnaires contained consent to terms and conditions of participation, collection of sociodemographic data, closed and/or open question, and agreement to publish anonymised survey results.The questionnaires were administered to HCPs for assessment of their needs (bottom-up approach), leaders of professional associations and key stakeholders holding leadership positions at SEA universities and in governmental bodies (top-down approach). Closed questions were quantitatively analysed based on automatically generated reports provided by the survey software. Open questions were analysed thematically and manually by two researchers after the raw data was downloaded from the online survey.https://www.surveymonkey.com/; SurveyMonkey Europe UC, Dublin, Ireland). The questionnaires were beta-tested by SEA project partners, resulting in further optimisation of the questions. The questionnaire links together with an accompanying introduction of the study’s context and aims, and detailed consent to terms and conditions of participation were provided to all SEA project partners who distributed the information to their personal and professional networks in spring 2017 to target HCPs in the field of early nutrition. Inclusion criteria for being eligible to fill-in the online questionnaires were set by the mandatory selection of a health care profession from a drop down menu. In addition, only HCPs from the SEA region were included in the analysis. There were no further inclusion restrictions to allow for a higher number of participation and to retrieve a broader spectrum of answers.To efficiently distribute, collect and analyse the responses to the questionnaires, the online tool “Surveymonkey” was chosen  platform of LMU Munich served as the basis for generating adapted and needs driven targeted content of the ENeA SEA modules, along with an established e-learning programme on malnutrition of the University of Southampton. By comparative analysis of the needs assessment and existing content of the ENeA Global platform, topics for e-learning modules and relevant content adaptations for SEA were determined. Guided by a “scientific content panel” and through an iterative regular review process, six e-learning modules were identified. A “Distance Learning Expert Panel” guided platform design using open source learning management software Moodle based on the existing ENeA Global Moodle infrastructure. Instructional design elements comprised videos, animated characters representing SEA regional healthcare staff and clients, case-based scenarios and interactive elements using H5P, a free and open-source content collaboration framework based on JavaScript. H5P is an abbreviation for HTML5 Package, and enables for everyone to create, share and reuse interactive HTML5 content. Innovation of the e-learning platform and its modules is reflected by an interactive and culturally sensitive design approach. It is based on constructivism, supporting the learner to construct knowledge based on their existing knowledge through situated learning and authentic tasks. A narrative counselling situation of a client and a HCP shown through a 3D video is such an example. Scenario-based cases and culturally appealing visual presentation motivate and actively engage the learner in their learning process, which is very important for effective learning. Furthermore, to achieve a high level of identification of the learner, great care was taken to design characters representative of SEA and to reflect real life situations. This facilitates the learner to build concrete knowledge through experiencing relevant case scenarios, which in turn makes it possible for the learner to apply their gained knowledge in practice.Conceptualising, generating and implementing the e-learning platform with targeted curriculum and e-modules required a carefully steered process of co-creation, with close collaboration of experts from different disciplines and cultural backgrounds. Supported by a project steering committee, two panels comprising experts in the field of early nutrition and lifestyle and e-learning experts, respectively, guided the development and implementation of the e-learning platform, curriculum, contents and instructional design formats. Dedicated face-to-face working sessions and training weeks for co-creating contents and formats along with online meetings, feedback and review characterised the collaboration. Regular evaluation within the project consortium was undertaken to optimise collaboration.In addition to a standard learning curriculum of modules with a structured learning pathway, a customised learning route was developed, enabling the user to generate their own curricula. This is based on actively selecting topics and automatic semantic analysis of an open text field where users can indicate their areas of interest. The software ReaderBench allows comparing and matching this information with all e-learning contents (78 lessons) offered on the platform in less than a few seconds, providing the user with individualised curriculum recommendations ,10,11. FA year after the launch of the e-learning platform and first modules, the descriptive user statistics (April 2020) and explorative evaluation questionnaires were analysed (January 2020) using Moodle inherent statistical and report generation plugins on the ENeA SEA e-learning platform. We obtained information on the number of registered users and country of origin, the number of users enrolled into each module, and the number of CME tests completed per module and their pass-rates. An explorative evaluation questionnaire to collect user feedback was generated and implemented at the end of each module as a mandatory element for the user to access the subsequent CME test and Certificate. The questionnaire contained 11 closed questions in addition to the collection of sociodemographic data .n = 42), nutritionists (n = 44), dieticians (n = 14), other medical doctors (n = 12), scientists (n = 6), pharmacists (n = 3), nurses (n = 3) and other health care professionals (n = 18). Most participants (92%) were from Thailand and Malaysia. The most commonly requested topics for receiving CME were “nutrition and lifestyle during pregnancy”, “breastfeeding” and “nutritional care of preterm infants”. 85–91% of HCPs reported regular internet use. English language proficiency was higher among doctors than other HCP groups. 57% indicated a preference for e-learning over face-to-face training, preferably using a mobile device rather than a desktop computer. About 80% of HCPs were part of a CME CPD system, and 58% rated the importance of CME/CPD credits as high or very high, with national credits reported as more important than European or credits. The questionnaire and its full results are presented in The first online questionnaire containing mainly closed questions was completed by 142 respondents. The respondent sample comprised pediatricians (n = 30), nutritionists (n = 30), other medical doctors (n = 13), dieticians (n = 11) and lecturers (n = 8). Themes of highest interest to users were “nutrition in pregnancy”, “infant nutrition and feeding”, “breastfeeding” and “best practice/guidelines/latest research findings on early nutrition and lifestyle”.The second survey with open text fields to questions was completed by 105 participants. Some 64% of participants were from Thailand and 28% from Malaysia; 90% practised in urban areas. Participants comprised pediatricians (n = 7) and Malaysia (n = 4), with eight participants holding responsibility for setting the standards for HCP professional specialisation, training or CME accreditation in the College of Obstetrics and Gynaecology, Academy of Medicine of Malaysia, the Medical Deans Council of the Malaysian Public Universities, the Malaysian College of Paediatrics, the Academy of Medicine of Malaysia, the Royal College of Pediatricians of Thailand, the Medical Council of Thailand, the Allergy, Asthma and Immunology Association of Thailand and the Royal College of Orthopaedic Surgeons of Thailand.The third questionnaire addressed to governing bodies and stakeholders influencing or determining CME/CPD was conducted in May 2017 and was completed by 11 participants; full results are presented in There were wide variations in CME/CPD assessment in different SEA countries and healthcare systems. Centralised recertification examinations were often perceived as threatening and difficult to tailor to the needs of individual practitioners. Most systems are currently based on an hour-related credit system. There are common features of content and process that allow for international recognition of CME/CPD activities. Some countries in SEA have systems of mandatory periodic recertification. However, efforts to make CME/CPD programmes mandatory with an hours-based credit system for recertification have not yet been successful, mostly because of lack of a needs-based accredited CME/CPD programmes, incentives and a regulatory framework. Despite these limitations, different professional bodies, academic institutes and medical councils in many SEA countries have organised CME/CPD programmes and encourage doctors to actively participate in these. The SEA Regional Network of Medical Councils adopted a concept paper on “Continuing medical education” and developed Guidelines for CME for the SEA region in 2008 [The included modules address nutrition and lifestyle in pregnancy, breastfeeding, breastmilk substitutes, complementary feeding, nutritional care of preterm infants and malnutrition . The bren = 636), followed by the modules nutrition and lifestyle in pregnancy (n = 421), complementary feeding (n = 293), breastmilk substitutes (n = 266) and nutritional care of preterm infants (n = 216). The highest completion rate of a module was 72%. Comprehensive results are shown in By April 2020, 2688 users had registered on the ENeA SEA Moodle platform, with the highest number enrolled in the breastfeeding module  and 10 being the maximum score (excellent)) and by 38% of users with 7 to 8 out of 10. Some 7% of users rated the module overall with 5 or 6 out of 10.n = 53 up to 87), but all showed a similar pattern of responses to the “breastfeeding” module. While the collection of feedback from evaluation questionnaires is a valuable information source for further improving the ENeA SEA modules and programme, knowledge acquisition by the user is evaluated by the embedded CME tests with multiple-choice questions. Moreover, passing the CME tests with a threshold of 70% of correct answers is a pre-requisite to obtain the CME certificates of completion.The results of the evaluation questionnaires of the other three modules were completed by fewer participants  and question banks, as well as concrete case studies which are accessible for tutors after registration and verification by the SEA lead partners.However, the practical skills training, interactive case discussion and personal guidance element which would be needed for a comprehensive qualification programme cannot be met by an e-learning approach alone. Recognising this as one of the major shortcomings of the ENeA SEA programme as it has been developed up to date, partners seek to further implement a strong complementing face-to-face case based training part of the programme. The developed tutor area and its materials described earlier will serve as a starting point for these ambitions. A currently planned roll-out of ENeA SEA in Indonesia will additionally develop and execute a concept for evaluating the actual public health impact mediated by such an educational programme for HCPs on the ultimate target groups ((pre-)pregnant women, infants, young children and their families).We conclude that the ENeA SEA e-learning programme contributes successfully to improving practical counselling competencies targeting (pre-) pregnant women and families of infants and young children. This meets national and regional ambitions to reduce early nutrition and lifestyle-related health problems and subsequent risks of suboptimal development and physical and cognitive abilities, and of NCD risk. The launch of the ENeA SEA platform customised curriculum also allows targeted e-learning for effective and efficient knowledge acquisition within limited time availabilities. Exploitation and sustainability actions with key stakeholders should ensure updates of e-modules and their integration into pre-and postgraduate study programmes. Inclusion in CME/CPD systems in Thailand and Malaysia will be fostered by local language versions of the modules. We aim at further expansion into other SEA countries, such as Indonesia. We anticipate that these actions will support reducing the double burden of malnutrition and obesity that arises through suboptimal early nutrition and are a major public health concern.


The American Indian (AI) population experiences significant diet-related health disparities including diabetes and cardiovascular disease (CVD). Owing to the relatively small sample size of AIs, the population is rarely included in large national surveys such as the NHANES. This exclusion hinders efforts to characterize potentially important differences between AI men and women, track the costs of these disparities, and effectively treat and prevent these conditions.We examined the sex differences in diabetes prevalence, comorbidity experience, health care utilization, and treatment costs among AIs within a Northern Plains Indian Health Service (IHS) service unit.n = 7299) on prevalence of diabetes by age and sex. We described sex differences in comorbidities, health care utilization, and treatment costs among the adults with diabetes.We assessed data from a sample of 11,144 persons using an IHS service unit in the Northern Plains region of the United States. Detailed analyses were conducted for adults . The prevalence of CVD among men and women with diabetes was 45.7% and 34.0%, respectively. Among adults with diabetes, men had a statistically higher prevalence of hypertension and substance use disorders than women. The men were statistically less likely to have a non–substance use mental health disorder. Although men had higher utilization and costs for hospital inpatient services than women, the differences were not statistically significant.In this AI population, there were differences in comorbidity profiles between adult men and women with diabetes, which have differential mortality and cost consequences. Appropriate diabetes management addressing gender-specific comorbidities, such as substance use disorders for men and non–substance use mental health disorders for women, may help reduce additional comorbidities or complications to diabetes. American Indian and Alaska Native peoples (AI/ANs) are more than twice as likely to experience diet-related health disparities  as the general US population , 2. FromAlthough there are documented sex differences in health status and health care utilization patterns in the US general population, the literature on sex differences among AI/ANs is still developing , 11. TheTo contribute to this understanding, we examine the sex differences in diabetes prevalence, comorbidity experience, health care utilization, and treatment costs within a Northern Plains Indian Health Service (IHS) service area—the IHS is an agency within the Department of Health and Human Services and the principal federal health care provider for AI/ANs .1) the National Patient Information Reporting System (NPIRS), which includes utilization data for IHS services; 2) Purchased/Referred Care (PRC), which includes information on specialty inpatient and outpatient services obtained from non-IHS providers and paid for by the IHS; 3) Centers for Medicare & Medicaid Services (CMS) Cost Reports (Cost Reports); and 4) IHS procurement data for prescribed medication costs. The data used in this analysis are from Phase 1 of the Data Project and include FY2010 measures. The FY2010 Northern Plains service area population includes 11,144 persons.The data for the Northern Plains IHS Service Unit for fiscal year 2010 (FY2010) come from the IHS Improving Healthcare Delivery Data Project (Data Project), which was created to provide a longitudinal data infrastructure of sufficient size and scope that it may be used for program planning and evaluation with a specific focus on chronic diseases. The data infrastructure includes 4 existing types of IHS electronic data: The project is based at the Centers for American Indian and Alaska Native Health (CAIANH), Colorado School of Public Health, University of Colorado Anschutz Medical Campus. The protocol was reviewed by the IHS National Institutional Review Board (IRB), the Colorado Multiple IRB , 1 regional IHS IRB, and 6 Tribal IRBs. Tribal Councils have provided approvals though resolutions and letters for project involvement. In addition, a data agreement was put in place with the IHS and 1 Tribal organization.NPIRS demographic information includes age, gender, and geographic information.We used Sightlines DxCG Risk Solutions software to identify diagnosed conditions a patient may have . This soNPIRS and PRC inpatient service measures include the number of admissions and inpatient days.NPIRS includes >120 outpatient clinic codes. We used clinic and provider codes to categorize outpatient services into service categories to report IHS outpatient utilization of these. They included emergency, urgent, primary, specialty , dental, eye care , foot care , behavioral health, physical therapy and other rehabilitative services, public health nurse, and home services. Five of the service categories were designated as education, case management, and advanced practice pharmacy services (ECP). Education services include those for diabetes, nutrition, and other types of education. Outpatient services for gynecology, obstetrics, and women's health screening were excluded to facilitate comparisons by sex in outpatient service use. Procedure codes were used in addition to clinic and provider codes to identify ECP services.During Phase 1, we developed algorithms to use FY2010 Cost Report data, NPIRS utilization data for all persons who used services, and local data for the Service Unit to estimate site-specific costs for the provision of different types of IHS-provided services . The site-specific service cost estimates for each type of visit included costs associated with ancillary services . The expert opinions of IHS/Tribal fiscal and medical personnel and CAIANH were used to guide allocations of some costs  across service types when data were not available.Treatment costs for IHS-provided services for each person were estimated based on his/her utilization of inpatient and outpatient services  and the estimated average costs of providing those services in the Service Unit where he/she lived. IHS-paid amounts for PRC services were used to estimate his/her costs of inpatient and outpatient services that occurred at non-IHS providers. Total IHS treatment costs for each person were calculated by summing his/her estimated costs for IHS- and non-IHS-provided services. It is important to note that IHS treatment costs do not include costs for services obtained at non-IHS providers and not paid for by IHS. For example, the costs exclude the majority of costs associated with renal dialysis.We used SAS statistical software version 9.4   to conduAmong all persons, the prevalence of diabetes was 10.5%. The overall prevalence of diabetes did not differ by gender, nor were sex differences found for any age group , followed by CVD (39.5%), non–substance use mental health disorders (25.3%), and tobacco use disorders (21.1%)  that provides resources for preventive services and early detection . SDPI prIn addition, across AI/AN communities in the United States there are a growing number of programs that aim to improve AI community food environments to prevent diet-related conditions for future generations. For example, the THRIVE study, funded by the National Heart, Lung, and Blood Institute, supported Oklahoma AI communities in improving access to healthy foods in Tribally owned convenience stores, resulting in increased healthy food purchases among AIs in these communities . There aThis study has several limitations. We highlight 2 main ones. Our analysis was limited by the size of the study population, which reduced our statistical power, and the findings are only generalizable to the active users of the Northern Plains IHS Service Unit. Health care utilization and treatment cost estimates are for IHS services and services paid for by IHS through PRC; they exclude utilization and costs for services obtained at non-IHS providers and not paid for by PRC. Nevertheless, the treatment cost estimates reflect the costs of providing services within the IHS service system. Given the limited knowledge of sex differences in diabetes prevalence, and of comorbidities, health care utilization, and treatment costs among AI/ANs, our study contributes to this understanding.Our study examined data from a Northern Plains IHS Service Unit to understand sex differences in diabetes prevalence, comorbidities, health care utilization, and treatment costs. Unlike the national trends where men have a slightly higher prevalence of diabetes than women, we found similar prevalence of diabetes by age and sex . However