Multiple factors can directly influence frozen food quality, during processing and post-processing, in the cold chain. There is a great interest in investigating, understanding, and ultimately quantitatively expressing the effect of the quality determining factors with regards freezing method applied, ice crystal morphology, food microstructure, glass transition phenomena, temperature and temperature fluctuations during distribution and storage. This can contribute to the improvement of the freezing process and the subsequent handling, aiming at optimum frozen product quality from process to final use or consumption. In this context, this Special Issue “Changes during Food Freezing and Frozen Storage” comprises research papers and review articles focused on the different phenomena observed during food freezing and subsequent storage.Roos 2021) [ [1] authNeri et al. 2020) [020 [2] cGiannakourou et al. (2020)  reviewedBy implementation of kinetics on quality degradation and shelf life prediction of frozen foods, Tsironi et al. (2021)  developeThe subject of shelf life estimation of frozen meat products was studied by Leygonie et al. (2020) . The intThe reliable prediction of frozen food shelf life, at any point in the actual cold chain, was addressed by Giannakourou and Taoukis (2020) . A holisIn summary, the Special Issue “Changes during Food Freezing and Frozen Storage” evidences the great importance of investigating the impact of the freezing process and frozen storage conditions on food quality and shelf life and building this knowledge into effective mathematical tools that can lead into a quantitative assessment of process and post-process quality determining parameters. This will ultimately support the optimized management of the cold chain from production to use.


For more than 20 years, family caregivers have been supported through the National Family Caregiver Support Program (NFCSP) of the Older Americans Act (Title IIIE). The NFCSP provides information to caregivers about available services; assistance in gaining access to services; counseling, support groups and caregiver training; respite care; and supplemental services. In the 2019 National Survey of Older Americans Act Participants, 1,909 NFCSP caregivers were asked “What recommendations do you have for improving the service?” The resulting 748 open-ended responses were thematically coded. The thematic analysis yielded six major themes: Additional Resources, Staffing, Communication, Care Coordination, Quality of Services, and Eligibility. Sub-themes were identified for Additional Resources and Staffing. The most common sub-themes for Additional Resources were requests for more help or services , increased funding or financial assistance, and more service hours . The most common sub-theme for Staffing was the need for consistent staffing due to high turnover of staff. Chi-Squared tests and Fisher’s Exact tests indicated that there were no significant associations between any of the recommendation themes and the gender of the caregiver, employment status of the caregiver, or whether the care recipient has Alzheimer’s or dementia. Many of the themes align with results from a recent RAISE Family Caregiving Advisory Council Report. Recommendations from both sets of findings indicate ways that programs, services, and policies can be enhanced to support the needs of care recipients and caregivers.


COVID-19 has highlighted once more the need for urgent attention to the quality of health care globally.As health systems plan recovery from COVID-19, there will be opportunities to systematically address quality of care.By focusing on quality in COVID-19 recovery, health systems can not only improve population health outcomes but also improve their resilience against future crises.Practical steps to address quality of care in COVID-19 recovery include considering quality in formal recovery planning; strengthening national strategic direction on quality, built around a set of quality interventions; monitoring and publicly reporting on quality of care; and leveraging existing assets and expertise on quality of care.Coronavirus disease-2019 (COVID-19) has shocked health systems globally, overwhelming rich and poor countries and highlighting both the need for and risks to quality care. Massive and persistent problems have been encountered in providing public health interventions as well as acute and chronic care for COVID-19 and in maintaining reliable provision of essential health services, already daunting for much of the world in so-called ordinary times. A survey from mid-2020 highlighted that 90% of the included countries had disruptions to their essential health services, with low and middle income settings worst affected .Even without the increased pressures of COVID-19, poor quality care is responsible for between 5.7 and 8.4 million deaths each year in low- and middle-income settings [‘Health systems recovery’ is a term used to describe the process of restoring and improving the functions of a health system that have been exposed to a shock or public health emergency, such as natural disaster, conflict, or a disease outbreak. The World Health Organization has proposed that ‘the goal of health systems recovery is to design a system that is able to respond to the demands and health needs of the population; perform its functions effectively, efficiently, and sustainably; increase health systems resilience; and mitigate the risk of future health emergencies’ . The criSo what should a focus on quality in recovery look like? While context-specific approaches will be required, particularly in settings of extreme adversity, we propose here four main components applicable across most settings.Firstly, there is a need for systematic consideration of quality within formal recovery planning, requiring intentional efforts to analyse quality challenges, identify opportunities for action within emerging recovery plans and programmes, and allocate adequate resource.Secondly, recovery post-COVID-19 presents an opportunity to strengthen national strategic direction on quality, based on published global recommendations , 11, 12 Box 1.Illustrative quality interventions to support health systems recoveryEnsure basic infrastructure and essential inputsAssess facility capacity for delivery of safe and effective health servicesStrengthen infection prevention and controlUse context-appropriate guidelines, standards, and protocolsPerform clinical audit and feedbackProvide training and supportive supervision of workforceUse electronic/digital health technologies and programsFormally engage and empower local communitiesOptimize procurement and supply chain systemsStrengthen public performance reporting of process and outcomes measuresThirdly, efforts to monitor health systems performance through COVID-19 response and recovery should systematically measure and publicly report quality of care data to allow problems to be identified, progress tracked, and accountability enforced.Fourthly, those leading health systems’ recovery efforts should identify and leverage existing quality assets across health systems. In many countries, vast experience on quality of care already exists that can be of value in recovery, from facility-level expertise in areas such as infection prevention and control or quality improvement processes, through to national quality directorates with experience in diverse areas like standards development and community engagement. This workforce should be engaged and strengthened throughout health systems recovery.


The exponential growth of health information technology has the potential to facilitate community engagement in research. However, little is known about the use of health information technology in community-engaged research, such as which types of health information technology are used, which populations are engaged, and what are the research outcomes.The objectives of this scoping review were to examine studies that used health information technology for community engagement and to assess (1) the types of populations, (2) community engagement strategies, (3) types of health information technology tools, and (4) outcomes of interest.We searched PubMed and PCORI Literature Explorer using terms related to health information technology, health informatics, community engagement, and stakeholder involvement. This search process yielded 967 papers for screening. After inclusion and exclusion criteria were applied, a total of 37 papers were analyzed for key themes and for approaches relevant to health information technology and community engagement research.This analysis revealed that the communities engaged were generally underrepresented populations in health-related research, including racial or ethnic minority communities such as Black/African American, American Indian/Alaska Native, Latino ethnicity, and communities from low socioeconomic backgrounds. The studies focused on various age groups, ranging from preschoolers to older adults. The studies were also geographically spread across the United States and the world. Community engagement strategies included collaborative development of health information technology tools and partnerships to promote use  and use of health information technology to engage communities in research . The types of technology varied across studies, with mobile or tablet-based apps being the most common platform. Outcomes measured included eliciting user needs and requirements, assessing health information technology tools and prototypes with participants, measuring knowledge, and advocating for community change.This study illustrates the current landscape at the intersection of health information technology tools and community-engaged research approaches. It highlights studies in which various community-engaged research approaches were used to design culturally centered health information technology tools, to promote health information technology uptake, or for engagement in health research and advocacy. Our findings can serve as a platform for generating future research upon which to expand the scope of health information technology tools and their use for meaningful stakeholder engagement. Studies that incorporate community context and needs have a greater chance of cocreating culturally centered health information technology tools and better knowledge to promote action and improve health outcomes. The field of health informatics is defined as “the science of how to use data, information, and knowledge to improve human health and the delivery of health care services .” HealthA key opportunity lies in using health information technology to engage communities and stakeholders from multiple sectors in health-related research as a potentially powerful method of involving traditionally underrepresented groups in research and promoting health equity. The importance of involving patients and other stakeholders in research is underscored by program initiatives such as the Patient-Centered Outcomes Research Institute (PCORI) . A growiCommunity engagement presents a key opportunity to bring additional knowledge and lived experience to social determinants of health, or the conditions in which we live, work, and play (including internet access), which are increasingly recognized as key drivers of health outcomes . CommuniCurrent health information technology literature is predominantly focused on individual patient engagement strategies in health care . HoweverWe followed the 5-step framework developed by Arksey and O’Malley  and updaThe literature review was conducted to answer the following 4 research questions about health information technology and community-engaged research: (1) What types of populations were included in these studies? (2) What community engagement strategies were utilized? (3) What types of health information technology tools were used? and (4) What outcomes of interest were measured?A search strategy was developed with the following inclusion criteria: (1) English-language papers; (2) published between 2010 and 2019; (3) peer-reviewed papers only; (4) any geographic location; and (5) search term found in title or abstract. We searched 2 key databases in summer 2019: PubMed and PCORI Engagement in Health Research Literature Explorer. The searches were conducted using various combinations of the following words and phrases: “health information technology,” “technology,” “health informatics,” “informatics,” “eHealth,” “mHealth,” “health,” “community engagement,” “community participation,” “community involvement,” “community-engaged research,” “stakeholder involvement,” and “citizen science.” Note that search terms were intentionally kept broad to capture any work being done in this space; specific types of communities engaged  were included as long as the studies involved some form of health information technology and community-engaged research.After screening papers for duplicates, titles and abstracts were screened for relevance to the topic . Examples of papers excluded for lack of topic alignment were studies with key words about community participation but that did not entail community engagement . The next largest exclusion category was studies that used a citizen science approaches, but without a human health or health information technology focus . After this step, full texts were further screened to assess for eligibility.The final papers were analyzed and coded using following criteria: (1) the population of interest ; (2) research objective or stated project aims; (3) health information technology tools used ; (4) methods for community engagement ; and (5) outcomes of interest . A few papers were initially reviewed by all authors to establish a model for data extraction and to discuss any relevant issues. Data extraction was then conducted primarily by the first author (GR), using Excel (Microsoft Office 365) and Word (Microsoft Office 365) software, and any cases that lacked clarity were resolved with input from coauthors (PRE or LGR). All analyses were double checked by coauthors before interpretation.Extracted data were summarized. Findings were synthesized to address the research questions, and figures and tables are used to present the results. The key takeaway messages from this review are presented below, along with identified gaps to be addressed in future research.A PRISMA  diagramThe communities engaged were generally populations that have been underrepresented in health-related research, including racial or ethnic minority communities, such as Black/African American, American Indian/Alaska Native, Latino ethnicity, and communities with low socioeconomic status . The stuTwo approaches to community engagement emerged. First, some researchers employed community engagement in studies for collaborative health information technology development and promotion. These included collaborative development and partnerships to promote health information technology use; health information technology engagement through community advisory boards and other techniques; and focus groups to assess community health information needs. The next approach involved using health information technology to engage communities in participatory research related to questions beyond the use or development of the health technology. One key example of this participatory approach is the “citizen science” method whereby citizens  participate as scientists and use health information technology tools for specific data collection and advocacy efforts.Collaborative development of health information technology and partnerships to promote health information technology use was the largest category of community engagement ,15,18-25Several of the studies -33 in thFocus groups were also employed to solicit community input in the development of health information technology ,16,34-39The second set of studies ,40-49 emStudies were classified  in the fThe types of technology used varied across different studies , with moOverall, 4 main categories of outcomes emerged : (1) eliThis scoping literature review showcases the current state of community and stakeholder engagement in health-related research that uses health information technology and how these 2 fields currently intersect. Collaborative development of health information technology tools and partnerships to promote use  were the most frequent intersection between health information technology and community engagement. This was followed by use of health information technology to engage diverse communities in research . Overall, most studies targeted underrepresented communities, including racial or ethnic minority groups, and many included informational community and patient-facing tools, such as websites or educational apps. Mobile- and tablet-based apps were by far the largest category of health information technology tools used across studies, followed by websites. For most studies in this review, the concurrent use of community engagement and technology enhanced the cultural appropriateness of information or interventions regarding chronic diseases and other conditions that disproportionately affect underserved and underresourced communities.This scoping review revealed that the number of research studies that utilize health information technology alongside community-engaged research is relatively limited, although increasing. This suggests room for expansion of future research involving various technologies for improving outcomes beyond the individual level  and for meaningful engagement of communities and stakeholders from multiple sectors. This is particularly relevant as existing evidence indicates the presence of a digital divide, with racial or ethnic and other underserved communities having less access and familiarity with health information technology ,52. Our Our findings also highlight the power of using community-engaged research and health information technology to design interventions relevant to the specific populations of interest and their health priorities including: designing websites with chronic illness content tailored to racial minorities , investiThis study furthers existing knowledge based on published literature reviews on patient engagement approaches in the health-related research context  and on iFinally, the intersection of community-engaged research and health information technology might look different today, given the COVID-19 pandemic and its impact on digital health technology. Since the conclusion of our search, we have seen a significant uptake in telehealth tools and virtual forms of engaging communities and stakeholders in response to the COVID-19 pandemic. For example, Peeters et al  created This review makes a unique contribution to the literature, with a focus on health information technology and community-engaged research, given that the majority of health information technology engagement strategies focus on individuals as end users rather than on patients as research partners and community engagement. We reviewed the body of literature in the last decade during which the field of health information technology–related research has been growing; hence, this review focuses on an important timeframe. By presenting research to-date and covering a breadth of information, this review also highlights gaps and points to opportunities, which can be utilized to shape future directions of community-engaged research supported by health information technology.The search process was designed to be comprehensive, but it is possible that some search terms were omitted . Additionally, it is possible that a wider range of results may have been obtained by searching additional databases. However, during our development of the search strategy we found significant overlap between PubMed and other databases . Finally, selection criteria were rigorous; therefore, some relevant papers may have been excluded. Inclusion and exclusion criteria were determined through discussions by study authors, by reviewing best practices in scoping reviews. Search terms and inclusion criteria were designed to address our conceptualization of health information technology and community engagement previously described. However, other conceptualizations  are possible and could be explored in future studies.This study addresses the gap in the literature regarding the extent to which health information technology and community-engaged research are utilized concurrently, types of health information technology tools used, the various community engagement strategies utilized, and key outcomes assessed. Our results create a current assessment of the literature from which to promote further ideas for expanding the breadth and depth of technology utilization along with community and stakeholder engagement in health-related research to create more relevant and culturally centered outcomes and health information technology tools.Furthermore, this scoping review showcases the types of health information technology interventions and tools that are currently utilized and presents successful examples of community engagement across the health information technology research spectrum. Thus, it provides researchers with starting points for expanding community engagement and the use of health information technology in health-related research. Many studies included in this review highlight the opportunity and efficacy of community engagement to drive change and to ensure sustainability. Utilization of health information technology offers great potential for promoting diverse stakeholder engagement and for establishing long-term and equitable research partnerships.


Low/middle-income countries (LMICs) face triple burden of malnutrition associated with infectious diseases, and non-communicable diseases. This review aims to synthesise the available data on the delivery, coverage, and effectiveness of the nutrition programmes for conflict affected women and children living in LMICs.We searched MEDLINE, Embase, CINAHL, and PsycINFO databases and grey literature using terms related to conflict, population, and nutrition. We searched studies on women and children receiving nutrition-specific interventions during or within five years of a conflict in LMICs. We extracted information on population, intervention, and delivery characteristics, as well as delivery barriers and facilitators. Data on intervention coverage and effectiveness were tabulated, but no meta-analysis was conducted.Ninety-one pubblications met our inclusion criteria. Nearly half of the publications (n=43) included population of sub-Saharan Africa (n=31) followed by Middle East and North African region. Most publications (n=58) reported on interventions targeting children under 5 years of age, and pregnant and lactating women (n=27). General food distribution (n=34), micronutrient supplementation (n=27) and nutrition assessment (n=26) were the most frequently reported interventions, with most reporting on intervention delivery to refugee populations in camp settings (n=63) and using community-based approaches. Only eight studies reported on coverage and effectiveness of intervention. Key delivery facilitators included community advocacy and social mobilisation, effective monitoring and the integration of nutrition, and other sectoral interventions and services, and barriers included insufficient resources, nutritional commodity shortages, security concerns, poor reporting, limited cooperation, and difficulty accessing and following-up of beneficiaries.Despite the focus on nutrition in conflict settings, our review highlights important information gaps. Moreover, there is very little information on coverage or effectiveness of nutrition interventions; more rigorous evaluation of effectiveness and delivery approaches is needed, including outside of camps and for preventive as well as curative nutrition interventions.CRD42019125221. Women and children affected by conflict suffer from high burden of malnutrition and poor nutritional outcomes.In recent decades, conflict related deaths resulting from malnutrition and other health problems have increased significantly to the extent where they are now being considered a public health problem.General food distribution was the most common intervention provided in the included studies.Most of the intervention were delivered to refugee populations in camp settings and through community-based approaches.Very few studies reported on coverage and effectiveness of the nutritional interventions.Key delivery facilitators included community advocacy and social mobilisation, effective monitoring and the integration of nutrition and other sectoral interventions and services.Key delivery barriers included insufficient resources, nutritional commodity shortages, security concerns, poor outcome reporting, limited cooperation and difficulty accessing and following-up of beneficiaries.Studies and research should be conducted to generate and strengthen evidence on coverage, access and improvement in delivery of nutritional interventions in context to conflict setting with rigorous and improved assessment methods.Studies should also study on multi-sectoral programming approach and its integration with early childhood development and mental health, which is an emerging issue.Armed conflict is defined as ‘a political conflict in which armed combat involves the armed forces of at least one state , and in which people have been killed by the fighting during the course of the conflict’.2Globally, 136 million people are in need of assistance due to conflict, while 52 million children suffer from acute malnutrition where disease epidemics are a global threat.6et al,According to a recent systematic review by Blanchet In this review we aimed to synthesise the data and information currently available on how nutrition interventions for women and children have been delivered in conflict settings, and the reported barriers and facilitators of programme delivery. We also aimed to synthesise the available data on the coverage of nutrition programmes for women and children in such settings and their effectiveness.www.crd.york.ac.uk/prospero/).This systematic review on nutritional interventions is a part of series of reviews in conflict settings which includes delivery of mental health, sexual and reproductive health and other interventions in conflict settings.10.1136/bmjgh-2020-004897.supp1Supplementary dataWe systematically searched MEDLINE, Embase, CINAHL and PsycINFO online databases for indexed journal articles published between 1 January 1990 and 31 March 2018 using search terms relating to women, children or adolescents accessing or receiving nutrition-specific interventions in conflict or post-conflict settings in LMICs . In addiWe deduplicated all retrieved indexed records using Endnote X7 software,For both indexed and grey literature, we excluded case reports of single patients; studies reporting on military personnel, refugee populations in high-income countries, surgical techniques or economic or mathematical modelling; editorials and opinion pieces; guidelines; and reviews.We extracted relevant qualitative and quantitative information from eligible publications using a structured, pilot tested data abstraction tool in REDCap software in duplicate.Sphere HandbookWe descriptively analysed the key characteristics of the included publications, focal populations and reported interventions, including their delivery characteristics, and we tabulated reported estimates of intervention coverage and effectiveness. We compared reported nutrition treatment intervention coverage and effectiveness estimates with key indicators outlined in the We retrieved a total of 7817 unique citations from our indexed database search, and ultimately assessed 55Nearly half of the included publications  reported on nutrition interventions delivered in conflict-affected countries in sub-Saharan Africa and about one-third  in the Middle East and North African region . The couWe classified the individual interventions reported in the literature into broader categories, and we synthesise their components and delivery characteristics below.Twenty-six publications reported on mass screening for malnutrition as a component of other nutrition interventions.We found 22 publications reporting on the delivery of interventions to promote or support breast feeding or other infant and young child feeding (IYCF) interventions.80Twenty publications reported on the delivery of interventions to either prevent and/or manage communicable disease among children under 5 years of age.26 49 107Food fortification in conflict settings was not very commonly reported in the included literature. Only three publications reported on food fortification of which two were published between 2001 and 2010,36Twenty-seven publications reported on the delivery of micronutrient supplementation interventions to women or children in conflict settings.72Vitamin A supplementation for non-displaced/IDP/refugee children under-five living in West Bank and Gaza,83Thirty-four publications reported on GFD in conflict settings either through take home rations or hot cooked meal provision, or through cash or vouchers for food.In publications describing those GFD interventions where food rations were provided to households, the delivery personnel involved were either NGO staff33The provision of food through cash or voucher distribution was reported in 10 publications.A total of 19 publications reported on interventions to treat acute malnutrition on an inpatient basis.102Twenty publications reported on supplementary feeding of which three were published between years 1990 and 2000,99Thirteen included publications reported on targeted supplementary feeding (TSF) interventions, aimed at treating MAM and preventing SAM.The majority of both blanket and TSF interventions were delivered either in supplementary feeding centre (SFC), in health centres or at distribution points in markets,74 80 93 99 101 109Twenty two publications reported on nutrition-focused education delivered alone or as a component of other nutrition interventions in conflict settings.Only eight publications89Specific delivery barriers that we identified from the literature are presented in Effective social mobilisation, monitoring and surveillance, and integration of nutrition services into other sectors were key delivery facilitators . Local cWe identified 91 publications from 1990 and 2018 that described the delivery of nutrition interventions to women and children affected by armed conflict in LMICs, mostly reported in African region. Less than half of the included publications reported on research findings, and nearly 40% were sourced from the grey literature. Studies published between year 1990 and 2000, majorly focused on GFD and disease prevention and management. Studies published between year 2001 and 2010 also focused on disease prevention and management and on micronutrient supplementation, and studies published after 2011 focused on nutrition assessment, GFD and SAM/MAM treatment. GFD, micronutrient supplementation and nutrition assessment were the most frequently reported interventions, with most publications reporting on intervention delivery to refugee populations in camp settings and using community-based approaches .114 LimiOur results yield important insights about the nutrition delivery and important gaps. It is evident that much of the documentation of nutrition interventions and programmes implemented in conflict and likely in emergency settings more generally, exists in the grey literature generated by UN agencies, NGOs and other humanitarian implementers actively working in the field rather than from government reports and indexed literature. Second, the limited number of included studies and variation in population behaviour and in context such as country, underlying health system, disease outbreak, and type and severity of conflict has curtailed us from studying the impact of nutrition intervention on women in conflict setting in greater depth.In addition, much of the literature focused on nutrition interventions delivered to camp-based refugees, with relatively little reported on populations displaced or non-displaced populations. It is difficult to know whether the lack of reporting on non-camp and non-displaced populations reflects actual nutrition intervention delivery patterns on the ground, or rather a failure to document.With respect to the types of interventions, the relatively higher frequency of reporting on food distribution and the management of acute malnutrition is understandable, given the high prevalence of food insecurity and the high morbidity and mortality burden of malnutrition. It was somewhat surprising to find relatively little on the delivery of IYCF interventions, though there were some examples of innovative practices to provide safe spaces for women to breast feed. Moreover, we captured just as many publications reporting on infant formula distribution as on breastfeeding promotion interventions.We also found that many publications reported on nutrition intervention delivery at household level or through outreach approaches. We also note that the CMAM has been adopted as national policy by several governments including Ethiopia, Jordan and Sudan. Given these experiences, the humanitarian nutrition sector may be particularly well-placed to further innovate and test community-based approaches that might overcome or circumvent the specific implementation challenges across sectors.In context to barriers of delivery; destruction of health facilities, targeted attacks on facilities and health workers, as well as disruption of supply chains were key issues, which further added to the existing weak governance and healthcare system infrastructure. Thus, the actors should identify effective strategies for delivering interventions through planning which must addresses the security concerns of health service providers and beneficiaries. Moreover, gathering support and acceptance from local influencers and communities, including local authorities, appears to be critical, while maintaining the perception of their impartiality and neutrality.Finally, literature reports on multi-sectoral programming approach with the nutrition cluster collaborating with the health and WASH clusters, but has failed to report its integration with early childhood development and mental health, which is an emerging issue. Moreover, there is no data on gender equality and social inclusion. Thus, future studies should untake gender analyses, to investigate the gendered differences in access, needs and uptake of healthcare services.This systematic review of the literature is the first, to our knowledge, to focus on the delivery of nutrition interventions in armed conflict settings, and thus makes a novel and important contribution to the field. However, in addition to the limitations inherent in the existing literature itself, discussed above, we must also acknowledge that by restricting our review only to publications published in English, and by undertaking a comprehensive but not exhaustive search of the grey literature, we have inevitably excluded other relevant publications that may have provided different information from what we have captured presently.There is very little information on achieved coverage or effectiveness of nutrition interventions delivered in conflict settings; more (and more rigorous) evaluation of different delivery approaches is needed, including outside of camps and for preventive as well as curative nutrition interventions. The humanitarian nutrition sector may be particularly well-placed to advance the field with respect to community-based intervention delivery in conflict contexts, and has effective, existing networks to widely disseminate the important evidence that it could generate.


Many indigenous people have died or been harmed because of inadequately monitored research. Strong regulations in Human Research Ethics (HRE) are required to address these injustices and to ensure that peoples’ participation in health research is safe. Indigenous peoples advocate that research that respects indigenous principles can contribute to addressing their health inequities. This scoping literature review aims to analyze existing peer reviewed and grey literature to explore how indigenous values and principles from countries of Oceania are incorporated into HRE and the governance of research involving human participants.A scoping literature review framework was used for this study. A search for peer reviewed and grey literature from Google, bibliographies, and electronic databases such as SCOPUS, SPRINGER, Medline (Ovid) and JBI Database of Systematic Reviews was conducted, limited to the years 2002–2020. Sixty (60) documents that focused on indigenous knowledge from Oceania region and HRE were included, from which key findings and themes were synthesized.Charting the data showed that more than half the eligible documents were peer-reviewed journal articles (54%). Other sources included: International Declarations on Human Research (8%); book chapters (8%); government documents (8%); HRE Guidelines or protocols (13%); news articles (7%) and PhD thesis (2%). The literature was from Australia, Cook Islands, Guam, New Zealand, Fiji, Samoa, Tonga and Vanuatu, some of which focused specifically on HREs in the Pacific Region. Issues emerging from the literature were grouped into five themes (i) indigenous and cultural principles of HRE; (ii) informed consent in indigenous settings in Oceania; (iii) vulnerability and minority status of indigenous populations exploited for research; (iv) research ethics governance for Oceania indigenous peoples; and (v) research ethics committees in Oceania. Respect, relationship building, and trust were priority indigenous HRE principles that encompass the principles of partnership, capacity building, reciprocity, and equality. Relationship building and trust imply the equal distribution of benefits for indigenous population and researchers.Indigenous principles of HRE identified were interconnected and interdependent. Recommendations were to incorporate indigenous principles of research in HRE regulations and processes of all countries with indigenous populations. This is especially pertinent for emerging national research committees in LMIC countries, including Fiji and Tonga. Relationship building among researchers and indigenous populations is key to successful research with indigenous populations. HRE principles important for relationship building include respect that is reciprocal among researchers and indigenous people. Elements of the principle of respect highlighted are empathy, collaboration, sharing of benefits, reciprocity, appreciation, empowerment, protection, safety and awareness of culture and languages. Indigenous ontology from the Oceania region involves spirituality, connectedness to land, religious beliefs and a participatory approach to HRE and should be respected in research. An ethical governance mechanism of HRE is one that incorporates indigenous principles and applications for the purpose of maximizing the protection of the dignity and rights of indigenous peoples of Oceania. Human Research Ethics aims to ensure that research is conducted to the highest ethical standard and that human participants in research are protected . ImportaThousands of people have lost their lives , 68 and These deficiencies prompted calls for strong regulations in health research ethics to ensure that people participating in health research are not harmed , 83, 98.Table Indigenous is defined as “people who are descendants from populations that inhabited the region before the time of conquest and colonization, and who, independently of their legal status, have preserved all or part of their social, economic, cultural and political institutions, and that, at the same time, self-recognize themselves as such” .The Oceania Region is divided into four major sub-regions; (i) Australia and New Zealand sub-region include Australia, Christmas Island, Cocos Islands, Heard Island, New Zealand and Norfolk Island, (ii) Melanesia sub-region include Fiji, New Caledonia, Papua New Guinea, Solomon Islands, and Vanuatu, (iii) Micronesia include Guam, Kiribati, Marshall Islands, Nauru, Northern Mariana Islands and Palau, (iv) Polynesia sub-region include Pitcairn Islands, Samoa, Tokelau, Tonga, Tuvalu and Wallis and Futuna , 88.Indigenous people of the Pacific Islands are divided into three main groups, Melanesia, Micronesia and Polynesia . MelanesA scoping literature review framework defined by Arksey and O’Malley  was usedThe research questions for this scoping review were: (i) what are the existing underlying theoretical principles that inform indigenous ethical approaches of HRE? and (ii) how are indigenous principles applied in the governance of human research? The literature search process is shown in the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analysis’ (PRISMA) diagram Fig.  72] and and72] aThe first author (EL) collated the data, read and summarized all documents according to the following characteristics and recorded the following in a table; profile of document, study location, study population, aim, research ethics/bioethics principles or theories, methodology (only research articles), important results and outcomes. A framework was developed for a consistent approach to the analysis of the findings from the gathered literature. Based on the aim, the framework consisted of two categories: (i) the indigenous knowledge incorporated into HRE; and (ii) the regulations of HRE in indigenous populations.The search strategy is presented in Table The PRISMA Identification stage involved a database search in SCOPUS, Springer, MEDLINE (Ovid), JBI Database for Systematic Review and it was decided that the search will be filtered by years, 2002–2020. English search words were utilized for the search and this search yielded a total of 1154 documents. Google search was used to search for the French translation of the English search words. Then the names of the French nations in the Oceania region Tahiti, New Caledonia and Wallis and Futuna were added to the search words and a search was conducted in the databases. This search did not yield any results.Further search for documents that may not have been found in the databases was also conducted in Google Scholar, EJournals, Bibliographic Search and in relevant Organizational webpages and 82 documents were found and the total was 1223 documents. The duplicates were removed and 954 documents remained. The next stage was the screening stage which is the strategic selection of documents to be included or excluded. Inclusion criteria strategy was to include all documents that were about research, bioethics and indigenous research ethics knowledge in countries of Oceania and exclude documents about biomedical ethics, health care ethics, about non-indigenous contexts and HRE in countries outside of Oceania region. Six hundred fifty-six documents were excluded and 298 documents remained that met the inclusion criteria. A further screening exercise was conducted where an exclusion criteria was set to exclude documents that was about Biomedical ethics in health care, Research Bioethics in general, books and book chapters difficult to find. This screening exercise resulted in the exclusion of 238 documents. The next stage required the screening of documents for eligibility. Only documents that included research bioethics and indigenous knowledge of Human research ethics were included. Documents that were excluded were about biomedical ethics in health care, research bioethics in general, books and book chapters that were difficult to find. Sixty documents remained and were included in the scoping literature review. The search process is presented as a PRISMA flow chart; Fig. The scoping literature review found that although high income countries such as Australia and New Zealand have HRE regulations that engage indigenous HRE knowledge, many low and middle income countries like Fiji and Tonga have not yet developed HRE regulations that incorporate their cultural values or indigenous values. The English search yielded results while the French search did not yield any results. Some books and book chapters could not be located or accessed, so they were not included.Charting the data showed that more than half the eligible documents were peer-reviewed journal articles (54%). Other sources included: International Declarations on Human Research (8%); book chapters (8%); government documents (8%); HRE Guidelines or protocols (13%); news articles (7%) and PhD thesis (2%).The geographical distribution of the literature from Oceania region were as follows; Australia 12%, Cook Islands 2%, Fiji 6%, Guam 2%, General 22%, New Zealand 18%, Pacific Islands 18%, Samoa 6% and Tonga 8%, Vanuatu 6%.The themes that emerged were divided into five main categories: (i) indigenous and cultural principles of HRE; (ii) informed consent (IC) in indigenous settings in Oceania; (iii) vulnerability and minority status of indigenous populations exploited for research; (iv) research ethics governance for indigenous peoples; and (v) research ethics committees in Oceania. Indigenous from here onwards means indigenous knowledge from the Oceania region only. Each theme is summarized and presented in Table This section discusses a critical analysis of indigenous principles expressed in literature, including relationship building, and the ontology of indigenous populations in Oceania. Indigenous research principles include respect for relationships, knowledge and reciprocity, and participation among other principles , 71, 92.Relationship building with community leaders and prospective participants in cross cultural research is very important  [94 [9442] , 73.In the Pacific Region, AutogenIndigenous epistemologies have been long subjugated, while the application of Western ideologies in indigenous settings seem to have been the norm for many years, for example, the attempt by Autogen to apply an individualistic approach to informed consent in an indigenous communitarian setting like Tonga was a mistake. The outcome of making such a mistake is that the proposed Autogen genetic research in Tonga was cancelled. The Australia Broadcasting Commission (ABC) Pacific Beat reported an American company Phoenix Life Sciences had chosen the Melanesian country of Vanuatu despite its dormant ethics committee, to trial cannabis-derived drugs. ABC reported that Phoenix Life Sciences was forced to move to Vanuatu because of strict drugs legislations in the USA and Vanuatu was attractive because of “the ability to work through the Dangerous Drug Act”. Phoenix Life Sciences move was strongly opposed by the Vanuatu Medical Association , 16, 37.Isevusevu’, which is a presentation of ‘yaqona’  by the research team as a request for entry into a Vanua  in Fijian communities [Isevusevu is not conducted the people of the Vanua will feel disrespected and will not welcome the research team.Western paradigms are associated with expert knowledge while indigenous paradigms are associated with “lay knowledge” . Westernmunities , 60. If The practical advice offered about the ethical conduct of research in indigenous populations involves the inclusion of internationally accepted ethical principles such as beneficence, non-maleficence, tolerance for ambiguity, patience, adaptiveness, an open mind and courtesy. Risk and benefit analyses and research projects that maximize benefits for indigenous populations should be conducted , 48. AdvResearchers are to immerse themselves in the culture of indigenous populations to develop an in-depth and accurate comprehension of the indigenous populations’ culture , 73, 94.Statements for the governance of human research in indigenous populations have been developed in some countries of Oceania region. Some of the statements identified in this scoping literature review were from Australia, Fiji, New Zealand; Pacific statements issued by New Zealand Universities and Tonga. The title and the citation for these statements are presented in Table The cases of the Fiji and Tonga HRE governance mechanisms need elaboration. Although there are existing documents about Fijian and Tongan cultural standards and frameworks of human research developed by indigenous Fijians , 60 and National Statement on Ethical Conduct in Human Research: 2007 (Updated 2018)” in Australia [, the “Te Ara Tika: Guidelines for Māori research ethics” [An interesting variation was identified in the lists of references of the national guidelines of human research in indigenous populations of high-income countries compared to low and middle income countries. The “ustralia , the “Te ethics”  and the  ethics”  made ref ethics” . This isResearch Ethics Committees (RECs) or Ethics Committee (EC) , 41 or RHRECs were established worldwide in the early 1980s with stewardship roles within health research systems. HRECs are well developed and strong in Australia, New Zealand for indigenous people but not so in other countries of Oceania like Fiji. LMICs which includes some countries in Oceania lack resources, have limited legal systems and little expertise in bioethics . Online In a time of increasing health inequity around the world, (HRECs) must provide oversight of human research such as review and approval of human research proposals , 36. A cCapacity building and institutional support for HRECs is needed yet lacking. HRECs cannot function on altruistic grounds only where members’ contributions are for the benefits of others only, but HRECs need funding and support in the form of human resources in order to function effectively . The HREThe aim of this scoping literature review is to explore how Oceania regional countries’ indigenous knowledge of HRE is engaged in the governance of research involving human participants. The findings demonstrate significant development in the governance of HRE in developed countries like Australia and New Zealand, for the protection of Australian Aboriginal and Torres Strait Islander indigenous peoples and Maori of Aotearoa . There are existing regulations, policies or guidelines developed solely for the protection of indigenous people in human research in Australia and New Zealand. The guidelines inform researchers of indigenous principles and methods appropriate for the conduct of research with indigenous people. By contrast, this is not the case in countries like Fiji, Tonga, Vanuatu and other PICs. For researchers to achieve integrity in research that involves indigenous people, they need to gain extensive knowledge of indigenous history, socio-cultural and religious backgrounds before starting a research project. Distinctive HRE principles and values identified in this review that are common threads in research settings with Oceania indigenous populations are mapped in the flow diagram Fig. .Fig. 2DiThe engagement of indigenous principles in HRE regulations and guidelines ensures the achievement of research integrity. Two HRE guidelines, (i) Values and ethics: Guidelines for ethical conduct in Aboriginal and Torres Strait Islander health research  and (ii)It is interesting to note the portrayal of the indigenous principles of ‘respect’ in literature reviewed. Respect described by authors as encompassing the values of mutual care, humility, empathy, collaboration, generosity and sharing of benefits, reciprocity, appreciation, awareness of culture and languages, protection, safety, survival and spirituality. Respect and its core values are highlighted in the literature thus respect is established as one of the foundational pillars of relationship building and trust in research with integrity involving indigenous populations. Indigenous peoples demand the application of respect through various methods in research to uphold their dignity and right.The notion of ‘participation’ encompasses partnership, benefits, capacity building, empowerment, equality, integrity, mutual care, partnership, reciprocity, respect, responsibility, responsiveness, spirituality, survival and protection. Empowerment of all stakeholders in research emerges via ‘participation’. Capacity building involves indigenous people’s involvement in the conduct of research projects with a goal of increased knowledge of conducting research. Capacity building can also be a two-way learning experience where everyone learns and teaches. Reciprocity in research involving indigenous people applies to respect, sharing of knowledge among all stakeholders, being generous and equal distribution of benefits among all stakeholders and capacity building.An interesting reciprocal angle of empowerment via ‘participation’ emerges. Where there is participation of indigenous people in research, ‘doors’ into indigenous knowledge and societal etiquettes will open to research stakeholders through indigenous participation. This reciprocity in participation enables a successful research endeavour, which will bring benefits to all parties involved. The notion of “reciprocity” further emphasizes equality in the distribution of benefits of research. Benefits that are both tangible and intangible should be shared equally among research stakeholders and be enforced via HRE regulations.This scoping literature review has significant findings. Relationship building between researchers and indigenous populations is key to a successful research in indigenous populations. HRE principles and their elements important for relationship building include respect that is reciprocal between researchers and indigenous people. Elements of the principle of respect are highlighted, including empathy, collaboration, sharing of benefits, reciprocity, appreciation, empowerment, protection for safety and survival, respect for spirituality, and awareness of culture and languages. The ontology of indigenous people is different from the ontology of Western thoughts. Indigenous ontology as understood for research includes spirituality, connectedness to land, religious beliefs and a participatory approach to HRE. The participatory approach comprises the ethical principles of reciprocity, respect, equality, responsibility, survival and protection or safety, spirit and integrity, partnership, responsiveness and benefit. Western paradigms adopted in research methodologies can create challenges in indigenous settings because of the differences in paradigms. Indigenous paradigms and applications methods are fundamental to research involving indigenous populations. A participatory approach in an informed consent process would be first step to build a trusting relationship between researcher and research participants.The findings indicated the need to make recommendations for successful research involving indigenous populations in Oceania. Indigenous HRE principles and applications methods should be part of HRE governance mechanisms. Informed consent processes in indigenous settings should be informed by both individualistic approach and a communitarian approach. The existing research frameworks in countries of Oceania could be linked and highlighted in HRE governance mechanisms. Capacity building and institutional support for the establishment of Research Ethics Committees is needed. Governance mechanisms of RECs, once established, must incorporate indigenous principles and applications in order to maximize the protection of the dignity and rights of indigenous peoples of Oceania.


The aim of this review was to assess relevant global literature on capped-fee (CF) and fee-for-service (FFS) payment models as used by public dental services. Research data were assessed through the PRISMA check list and sourced from MEDLINE, PubMed, ProQuest, Cochrane Library, and other methods. The inclusion criteria were peer reviewed articles published between 2004 and 2020 and (i) other countries’ health systems that were evaluated in contrast to Australia; (ii) care provided to individuals; (iii) payment models for private services that were the same as Australian government policy (CF and FFS); and (iv) care provided by dentists. We used a mixed methodology for data collection. A total of 262 references were reviewed with 10 references meeting the inclusion criteria with the quality rating being: three—strong, six—moderate, and one—weak. The literature included studies from Sweden (three references), Ireland (three references), United Kingdom (six references), United States of America (two references), and Norway (one reference). Four references included studies within multiple countries. The sample size varied between 20 and 106,874 participants. The two payment systems can impact on individual outcomes, such as by overtreatment in an FFS system and undertreatment in a CF system. The implementation of cost containment tools dates to 1970 but its universal use in Organization for Economic Cooperation and Development (OECD) countries has only been apparent since 1990 . Both feGlobal discussions about priority settings have focused on addressing efficiency and equity, targeting marginalised populations, and integrating oral health into other general medical services ,4. TheseCurrently the most successful OECD countries in implementing FFS are France, Germany, and Japan for medical practices . PaymentThe aim of this systematic literature review is to assess the relevant literature on payment models for public dental services focused on FFS and CF that are designed to target dental practitioners/facilities and specific consumer high-risk target cohorts. Thus, the analysis required multiple aspects to be considered: (i) cost–benefit analysis; (ii) practitioner/facility participation and views on pricing; (iii) patient views on participation and quality of care; and (iv) relevance to Australia’s government policy on utilising private services to deliver public dental care.The study used the PRISMA method as the basis for assessing the review findings  and the The EPHPP Global rating tool was evaluated by Thomas  to assesWe restricted publication time to the last 16 years as literature debating FFS and CF goes back to 1990. We decided to focus on more recent papers (2004–2020) to ensure that the systematic literature review would be relevant to today’s issues of procuring private practitioners/facilities to provide public dental care.The systematic process applied the PICO Framework  to obtaiThis systematic review searched 4 electronic databases, websites, and organisations using key terms and citation searching. The databases were MEDLINE, PubMed, ProQuest, and Cochrane Library. The inclusion criteria were: (i) other countries’ health systems evaluated in contrast to Australia; (ii) care provided to individuals; (iii) payment models for private services that were the same as Australian government policy (CF and FFS); (iv) care provided by dentists. We used a mixed methodology for data collection, which included only those titles published in the last 16 years (2004–2020). Only English language papers were included because of cost, time, funding, and language resource constraints.The key terms used were capitation (CF), procured services, dental, dental services, oral health, payment types, practitioner type, practitioner options of CF, and patient options of CF.There were no restrictions on the clinical setting or location of the study. However, “grey” literature from government and non-government organisations was excluded, as it consisted of reports, strategic planning, policy statements, and discussion/issue papers.The general characteristics of each article including participants, details of the payment model(s) being tested, along with the study measures and outcomes were extracted.The references that met the inclusion criteria were reviewed with the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies and allocated a global quality rating . This inThe EPHPP Dictionary was used to clarify the objective of each of the assessment domains.The total number of references that were assessed for eligibility was 15 . HoweverA total of 237 records were identified from the 4 databases and 25 records via websites, organisations, and citation searching. Two duplicates were removed, and the remainder assessed by their titles and abstracts. The exclusion criteria were: publications older than 2004, topics not relevant to the aim of the paper, articles without sufficient information regarding methodology and not able to be assessed with the EPHPP tool, and data not from a recognised source. This resulted in 141 selected with a further 131 removed upon reading the references in full. Therefore, a total of 10 (eight studies and two reports) passed the EPHPP assessment . Data weReference designs included a quasi-experimental study , a longiThere were variances within the study designs. The systematic review by Brocklehurst et al.  containeUsing the EPHPP Global rating, the 10 references were rated as either strong, moderate, or weak. Three were classified as strong, seven were moderate and one weak . Two of It was challenging to assess bias due to the different types of methodology, e.g., systemic review. This risk of bias was particularly evident in and due to the quasi-experimental study design. References with notable risk of bias are discussed below.Andäs and Hakeberg’s article (2014)  acknowleIn comparison, the Andäs and Hakeberg article (2016)  found twIn references where questionnaires were used, a response bias may be expected. For example, responses are more likely to come from more enthusiastic and passionate participants and practitioners. This risk cannot be accounted for or measured accurately. In Woods , questioThe 10 references included studies within the following counties: Sweden (three refences), Ireland (three references), UK (six references), USA (two references), and Norway (one reference). Four references included studies within multiple countries . The samn = 2) there was an equal proportion of male and female participants. All 10 references covered both rural and urban areas in their analysis. The adult age groups in some references were presented in groupings. In the Andäs and Hakeberg [In the studies where sex was reported  and participants were aware of the data collection methods (questionnaires) and the interventions that were measured. However, the research question was not revealed to the participants in any of the references.Four out of the 10 selected references suggested that the participants favoured CF. Those who selected CF reported being healthier and more engaged in health-promoting behaviours. The study by Andäs and Hakeberg  noted thThe current study reviewed the existing evidence regarding the complexities of the payment systems (CF and FFS) used in the private sector to support the service delivery for dental care.Schneider et al.  reportedIn Australia 87% of dental services are provided privately . The difImportant arguments were raised within the selected references to improve the payment systems, such as better communication concerning the contract and risk assessment . AdditioA limitation of this systematic review is in comparing the different cohorts within the selected references as they often did not analyse the same criteria such as age groups, e.g., adults starting at 16 years or at 20 years of age. This was also the case with various aspects of treatment within the payment schemes. However, this did not weaken the findings that there is a variance in quality of care between CF and FFS and that public health services will remain dependent on the private dentist to help meet demand.The two payment systems (FFS and CF) can have impacts on individual outcomes, such as overtreatment in an FFS system and undertreatment in a CF system. Population health strategies targeting marginalised populations need a consistent approach to address oral health inequalities, encourage skill mix, and promote and facilitate the dental professionals to deliver appropriate and high-quality care irrespective of the payment system.


Leptin is a non-glycosylated 16 kDa protein synthesized mainly in adipose cells. The main function of leptin is to regulate energy homeostasis and weight control in a central manner. There is increasing evidence that leptin also has systemic effects, acting as a link between innate and acquired immune responses. The expression of leptin and its receptor in human dental pulp and periradicular tissues have already been described, as well as several stimulatory effects of leptin protein expression in dental and periodontal tissues. The aim of this paper was to review and to compile the reported scientific literature on the role and effects of leptin in the dental pulp and periapical tissues. Twelve articles accomplished the inclusion criteria, and a comprehensive narrative review was carried out. Review of the available scientific literature concluded that leptin has the following effects on pulpal and periapical physiology: 1) Stimulates odontogenic differentiation of dental pulp stem cells (DPSCs), 2) Increases the expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1), odontoblastic proteins involved in odontoblastic differentiation and dentin mineralization, 3) Stimulates vascular endothelial growth factor (VEGF) expression in human dental pulp tissue and primary cultured cells of human dental pulp (hDPCs), 4) Stimulates angiogenesis in rat dental pulp cells, and 5) Induces the expression of interleucinas 6 and 8 in human periodontal ligament cells (hPDLCs). There is evidence which suggests that leptin is implicated in the dentin mineralization process and in pulpal and periapical inflammatory and reparative responses.  At present, the possible association between oral inflammatory processes caused by infection and systemic health is an interesting aspect that the medical and dental community focuses its research on to improve the health of patients . In spitPulpitis and apical periodontitis are oral inflammatory processes caused by infection, and these diseases may help the scientific community as they are ideal models to explore the pathways or mechanisms by which oral local infections can harm systemic health. The dental pulp is a connective tissue that is located inside of the tooth and is limited by dentin, a hard, calcified and continuous formation tissue. The dental pulp and dentin are two tissues with different histological characteristics, but due to their similar embryological origin and structural implications are considered a functional unit. To establish a correct knowledge of dental pulp biology, it is necessary to also know the tissues that surround it; both dentin and periapical tissues are intimately involved in pathophysiology of the dental pulp . When etThe inflammation of the tissue around the tooth root, usually around the root apex, caused by infection of the dental pulp, is known as apical periodontitis . The preThe link between pulp/apical inflammation and pulp/apical repair is still not fully understood. The prerequisite for tissue repair is the host’s inflammatory response, which includes the production of antimicrobial peptides and cytokines and the activation of migratory immune cells . Leptin,The aim of this review is to analyze the available scientific evidence about the expression and effects of leptin in dental pulp and periapical tissues in order to clarify and summarize the role of leptin in pulpal and periapical physiology.An electronic search of PubMed, Web of Science, and Scopus was conducted using appropriate keywords, as follows: (leptin OR leptin receptor OR LEPR OR OBR OR OB-R OR Ob-Rb) AND . All studies which carried out investigations of the expression of leptin or LEPR, as well as leptin effects, in dental pulp tissue or in periapical tissues were included. Fifteen articles were applicable to these inclusion criteria. Taking into account the scope of this search and the type of studies found, a comprehensive narrative review was carried out.Leptin, whose first functional role is the control of appetite and hunger , is a noLeptin acts as a link between obesity and inflammation . The linperoxisome proliferator- activated receptor gamma two (PPARγ2) and lipoprotein lipase (LPL), two adipocyte-specific transcripts [El Karim et al. (2009)  were thenscripts . TherefoProposing that leptin has biological functions in the dental pulp requires demonstrating that LEPR, the specific receptor for leptin, is expressed in pulpal cells. The expression of LEPR in human dental pulp was first described by Martín-González et al.  Table 1Table 1. The effects of leptin on dental pulp have been investigated. The results of the studies carried out suggest that leptin is involved in the odontogenic differentiation of DPSCs, dentin matrix mineralization, and angiogenesis .Leptin acts as a modulator of pulpal mesenchymal stem cell differentiation, promoting odontoblastic and suppressing adipogenic differentiation ,58. On tLeptin also stimulates the expression of dentin matrix protein-1 (DMP-1) in human dental pulp ,61. DMP-The stimulatory effect of leptin on DSPP and DMP-1 expression in human dental pulp, two critical proteins for proper mineralization of dentin and odontoblast differentiation , suggestAnother effect of leptin on pulp physiology is angiogenesis stimulation  by increThe first studies that linked leptin with periradicular tissues focused on their possible relationship with periodontal disease. Johnson and Serio  describeRegarding the presence of leptin and its receptor in periapical tissues, the expression of both leptin and LEPR in human chronic periapical lesions was first described by Kangarlou et al.  Table 1Table 1. About the possible role of leptin in periradicular tissues, few data are available. Leptin and LEPR increase substantially in inflammatory periradicular tissues, inducing the expression of mRNA and the proteins IL-6 and IL-8 in human periodontal ligament cells (hPDLCs); these effects correlate with the extent of inflammatory infiltration  Table 2Table 2. This is comparable to what happens in obesity , where iThe functional effects mediated by the interaction of leptin with its specific receptor LEPR in dental pulp and periradicular tissues, described in this review, suggest that leptin is involved in the biomineralization process and in pulpal and periapical inflammatory and reparative responses. However, the biological significance of the link between pulpal and periapical physiology and an adipokine, such as leptin, mainly released by adipose tissue and whose first functional role is the control of appetite and hunger ,16, needThe fact that leptin and LEPR are expressed in pulpal and periapical tissues could be interpreted as evidence supporting the relationship between obesity, inflammation, and endodontic infections. Several possible pathways involving the host response and bacterial challenge have been proposed to explain the association between obesity and inflammation . ObesitySeveral important effects of leptin in pulpal and periapical physiology have been described: (1) Stimulates odontogenic differentiation of DPSCs, (2) Increases the expression of DSPP and DMP-1, odontoblastic proteins involved in dentin mineralization and odontoblastic differentiation, (3) Stimulates VEGF expression in human dental pulp tissue and primary cultured cells of human dental pulp (hDPCs), (4) Stimulates angiogenesis in rat dental pulp cells, and (5) Induces the expression of IL-6 and IL-8 in human periodontal ligament cells (hPDLCs).The data provided identify that there is evidence regarding the role of leptin in the dentin mineralization process and/or in pulpal and periapical inflammatory and reparative responses. The information is relevant and potentially contributes to this field of study; however, the little information that exists to date in this line of research may prove a limitation. Further research is needed to fully discern the possible connection between obesity, inflammation and endodontic infections and should be investigated.


The 2014 Ebola outbreak reminded us of the importance of preparedness for addressing health security threats. Learning from this experience, we aim to (1) enhance the understanding of preparedness by policy and decision makers, (2) discuss opportunities for Africa to invest in the prevention of health security threats, (3) highlight the value of investing in preventing health security threats, and (4) propose innovations to enhance investments for the prevention or containment of health security threats at the source.We used observations of governments' attitudes towards investing in preparedness for health security prevention or containment at the source. We conducted a literature review through PubMed, the World Wide Web, and Mendeley using the keywords: “health emergency financing”, “investing in health threats prevention”, and “stopping outbreaks at the source”.Countries in sub-Saharan Africa invest inadequately towards building and maintaining critical capacities for preventing, detecting, and containing outbreaks at the source. Global health security emergency funding schemes target responses to outbreaks but neglect their prevention. Governments are not absorbing and maintaining adequately capacity built through GHS, World Bank, and development aid projects – a lost opportunity for building and retaining outbreak prevention capacity.Governments should (1) allocate adequate national budgets for health honouring the Abuja and related commitments; (2) own and maintain capacities developed through International Development Aids, OH networks, research consortia and projects; (3) establish a regional health security threats prevention fund. The global community and scientists should (1) consider broadening existing health emergency funds to finance the prevention and containment outbreaks at the source and (2) Strengthen economic analyses and case studies as incentives for governments' budget allocations to prevent health security threats. It exposed major health systems weaknesses, common to sub-Saharan African countries, including severe shortages of skilled health workers and gross systems unpreparedness to prevent, detect, and contain outbreaks at the source. Fear and panic due to unpreparedness were compounded by superstition, perceptions and practices among affected populations impeded effective disease containment policies including safe burial.We have observed that major huddles to systems strengthening arise from misconceptions and insufficient understanding of the full spectrum of activities necessary for effective preparedness against health threats among policy and decision makers, and unappreciation of the value of investing in long-term systems strengthening rather than short term interventions with immediate results.We provide this opinion piece to provoke rethinking and encourage Policy and decision makers to value and invest in preparedness for health threats.7 Failure to rapidly and adequately detect and respond to such spilllover can lead to pathogen amplification in animal and human populations, resulting in uncontainable epidemics or pandemics. This spectrum can be categorised as “before”, “during”, and “after” outbreak periods. Natural or human environmental disturbances may trigger spillover of pathogens from the wild to domestic life and eventually to human beings.9The “before-outbreak” period is a peaceful time, which makes it optimal for strengthening capacities and collaborations among the human, animal, and environmental health systems to prepare to prevent or contain any outbreak at the source as provided by International Health Regulations (IHR) and World Organization for Animal Health (OIE) Standards on the performance of veterinary services (PVS).2 This is the best period for multisectoral coordination and collaboration to assess, build, and maintain a vibrant mixed disciplines and skills workforce, enhance syndromic surveillance capacity for real-time reporting, and establish joint activities among animal and human health workers teams, hence strengthening multisectoral coordination and collaboration.12 It offers the opportunity to engage communities  and anthropologists to build community trust and strengthen community participation to avoid the kind of mistrust, beliefs and practices fueling outbreaks as evidenced during the 2014 Ebola outbreak.11Essential capacities, as summarised in 15It is optimal for engaging the private sector to learn from their best practices, including regular simulation exercises in order to prevent or minimise the negative economic consequences of outbreaks on business, like what happened with Ebola, SARS and previous pandemics.19Engaging national finance ministries and departments responsible for national budget allocations, to identify needs, and generate or revise annual national preparedness plans and strategies during this period will enhance their appreciation of the value of prevention before an outbreak especially if presented with economic analyses that highlight the size of potential savings is essential.Usually, human case reporting to national health authorities and the World Health Organization (WHO), triggers national and global response and allows access to global emergency funds, while wildlife events are often neglected.23A well-prepared workforce (sufficient in skills and numbers), updated response plan, standard operating procedures (SOPs) and protocols for field epidemiology and laboratory investigations, case identification, management, and contact tracing are necessary during this period. A functional Emergency Operations Centers (EOC) is required to provide responsible leadership with clear lines of command and daily reporting of actions and behaviour of the outbreak. There is growing evidence that good multisectoral coordination optimises mobilisation and use of resources; enhance efficiency, transparency, accountability and the application of effective national and regional policies that minimise negative economic impact.The “after-outbreak” period is for conducting thorough multisectoral After-Action Reviews (AAR) to determine the strengths of the response and identify related capacity gaps. Findings and lessons learnt are useful for reviewing the preparedness and response plans, response protocols, SOPs and strengthening the operational systems, for future responses. AAR further identifies important research gaps and informs on the effects of existing national and regional policies, guiding their revision.24 Vacci-nation programmes have provided cost-effective disease prevention, eradication and significantly reduced related death and disabilities.28 Unfortunately, African governments invest inadequately towards building preventative capacities and implementing preventive interventions during the “before-outbreak” period since the results of this investment are not immediate and visible. Achieving the Abuja declaration goal of 15% allocation for health has been slow.31 Consequently, infrastructure for disease prevention, including laboratories, epidemiological surveillance and research receive inadequate African financial support and heavily rely on external financing. Routine disease prevention receives negligible budgets, and there are far too few health workers in Africa to efficiently and adequately manage the collective burden of illness and injury.31There is unequivocal evidence in human and veterinary medicine that prevention is better than cure/response and strategies for disease prevention have been defined.Effective surveillance and early warning systems operating routinely during the “before event” period (th October - 8th December 2017). The others appeared singly and sporadically always contained at the source. Expenditure data, only available for the Marburg outbreak, indicates that Uganda spent Shillings 5.2 billion equivalent to $ 1.0 million . Uganda has stopped and contained human trypanosomiasis outbreaks, previous Ebola outbreaks and these other recent outbreaks at the source by applying a multi sectoral One Health (OH) approach with limited funding.22 Okello and others have also shown the efficiency and effectiveness of multisectoral coordination mechanisms in preventing and controlling health threats in Nigeria, Tanzania and Uganda.23 The Uganda Emergency Operations Center (EOC) estimates that a multisectoral OH rapid response team, comprising a veterinary officer, case management physician, social mobiliser, wildlife officer, environmental health officer and epidemiologist using 2 vehicles and drivers to respond to an outbreak within.Uganda is exemplary in that it has suffered 4 outbreaks between January and December 2017, which could have amplified into epidemic levels threatening the East African region. Two large epidemics were stopped and declared as ended (Highly Pathogenic Avian Influenza (HPAI) 15 January to 19 August 2017; Marburg 1922  in 199222 .A 3-pronged multisectoral strategy of (1) controlling the vector using both traps and spraying of animals , (2) reducing pathogen density by identifying and treating infected animals, and (3) identifying and treating human cases (human interventions) was applied. Trypanosomiasis is on the verge of elimination in Uganda 27 years after introducing the preventive strategy. Policy and decision makers can learn from the long-term investment (27 years) and long-term maintenance of routine activities for prevention, surveillance, case detection and treatment, with community engagement.31At the global level, major achievements in preventive efforts against human and animal diseases have been the eradication of small-pox and rinderpest, respectively.The global community  need to work with the WHO and OIE to urge African countries to honour their commitments to invest in health systems strengthening, with stronger ownership and leadership reducing dependency on foreign aids. Allocating 15% of their budget for health and 1% of their GDP for research would allow institutionalisation of capacities built by projects and networks and boost efforts addressing gaps identified through the Joint External Evaluation (JEE) and highlighted by the 2014 Ebola outbreak.Regional governments facing common threats like the East African community under threat from hemorrhagic syndromes like Ebola, Riff valley fever, Marburg and Crimean Congo Hemorrhagic fevers bear responsibility and motivation to create a regional Prevention Fund aimed at containing disease outbreaks at the source. Ebola should also motivate African countries as a region to create such a fund. An RHEPF has the potential of reducing substantially the overall cost of response, as demonstrated by the case of Uganda.National multisectoral coordination and collaboration mechanisms provide opportunities to monitor and thoroughly document the results and how funds are utilised. Mechanisms for servicing the fund should be explored, including member states contributions. This is an opportunity to build the essential backbone of the Africa CDC. Donors and development aid agents may set complementary levels supporting governments' contributions as part of strengthening One Health approach institutionalisation for transparency and accountability. The fund will invigorate Africa CDC's activities and strengthen its role of providing technical assistance and leadership on innovative strategies for preventing and controlling diseases in Africa. The regional fund may operate through open competitive calls, with clear eligibility criteria in order to maintain quality, strengthen national preparedness capacity, ownership and allow monitoring and documenting achievements over time.We recommend expanding the scope of the existing global health emergency funds including the UN Central Emergency Response Fund (CERF-2006), The World Bank Pandemic Emergency Financing Facility (PEF), and the WHO's Contingency Fund for Emergencies (CFE) to include financing preparedness capacity building. Their current scope is limited to financing countries in crisis and does not catalyze investing in routine preparedness capacity building.32 Africa awaken!African governments bear the responsibility of protecting their populations from health threats and, therefore, cannot afford to wait for another Ebola-like event or to neglect the looming threat of antimicrobial resistance. Realising a new public health order for African health security requires investing in preparedness to shield Africa from the catastrophic consequences of uncontrolled health threats.


The ideal prostate cancer diagnostic test should identify clinically significant prostate cancer that would benefit from treatment, avoid diagnosis of insignificant cancer that does not benefit from treatment, and have a low side-effect profile.Systematic transrectal ultrasound-guided (TRUS) biopsy, the mainstay of prostate cancer diagnosis for the past 30 yr, is associated with errors leading to clinically significant cancers being missed and overdetection of clinically insignificant cancer that might not benefit from treatment but can lead to overtreatment-related harms. This may contribute to why randomised treatment trials such as PROTECT and PIVOT, which used systematic TRUS biopsy as the method for cancer diagnosis, have shown limited benefit of radical treatment in improving prostate cancer-specific mortality Systematic TRUS biopsy alone should no longer be carried out as the primary diagnostic test in men with suspected prostate cancer. The PRECISION study demonstrated that a pathway involving magnetic resonance imaging (MRI) first followed by MRI-targeted biopsy (MRI-TB) in men with an MRI-visible lesion leads to more significant cancer being identified, fewer insignificant cancers being diagnosed, and nearly a third of men avoiding biopsy altogether An additional question is whether one should add systematic biopsies to MRI-targeted biopsies or perform MRI-TB alone. A well-conducted prospective clinical trial showed that an additional 5% of Gleason 3 + 4 cancer cases would be detected on addition of systematic biopsies, although only 1% of these were Gleason 4 + 3 or worse Even if some low-volume Gleason 3 + 4 disease is missed by an MRI-TB–alone strategy and is “MRI-invisible”, there are data showing that nonvisible Gleason 3 + 4 disease has a different biology to MRI-visible, clinically significant detected cancer. MRI-visible prostate cancer has upregulation of a number of genes associated with cancer aggressiveness, progression free-survival, and metastasis What is an undisputed limitation of the addition of systematic biopsies to MRI-TB is the 34% higher odds of having insignificant cancer detected Avoiding the addition of systematic biopsies leads to a quicker procedure time; a lower burden on the pathologist, who can thus spend more time on producing higher-quality analysis of fewer specimens; greater capacity in the urology service in a hospital; and, putatively, fewer side effects. When one considers that approximately 1 million biopsies are performed in Europe every year, these advantages accumulate.There are a number of other considerations commonly cited for adding systematic biopsy in treatment decision planning such as the suitability of focal therapy and nerve-sparing decisions for radical prostatectomy. The mere presence of cancer on the contralateral side of the prostate, which is typically the information that proponents of systematic biopsy look for, does not preclude the patient from having nerve-sparing or focal therapy. It is more important to understand the location of that disease in relation to key anatomic structures such as the neurovascular bundle and urethral sphincter, which is information best gleaned from MRI. It has been demonstrated that the use of dedicated uroradiology MRI planning meetings before radical prostatectomy can improve patients’ functional outcomes and would not necessitate the addition of systematic biopsy In summary, systematic biopsies have a limited role in prostate cancer diagnosis. The cancer that is typically identified by systematic biopsies is not of the nature that is likely to benefit from treatment but can lead to expensive monitoring strategies and harmful patient side effects if overtreated.Conflicts of interest: Caroline M. Moore receives funding from Prostate Cancer UK, Movember, the Medical Research Council, Cancer Research UK, and the National Institute of Health Research (NIHR); receives fees for proctoring from SonaCare; has received speaker fees from Astellas and Janssen; and receives research support from Spectracure. Mark Emberton serves as a consultant/educator/trainer for Sonacare, Exact Imaging, Angiodynamics, and Profound Medical; and receives research support from the NIHR UCLH/UCL Biomedical Research Centre. Veeru Kasivisvanathan has nothing to disclose.Acknowledegments: Veeru Kasivisvanathan is an academic clinical lecturer and Caroline M. Moore is a research professor funded by the UK National Institute for Health Research (NIHR). Mark Emberton is an NIHR senior investigator (2015) and receives research support from the UCLH/UCL NIHR Biomedical Research Centre. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health.