Despite global support, there remain gaps in the integration of early palliative care into cancer care. The methods of implementation whereby evidence of benefits of palliative care is translated into practice deserve attention.To identify implementation frameworks utilised in integrated palliative care in hospital-based oncology services and to describe the associated enablers and barriers to service integration.Systematic review with a narrative synthesis including qualitative, mixed methods, pre-post and quasi experimental designs following the guidance by the Centre for Reviews and Dissemination (PROSPERO registration CRD42021252092).Six databases searched in 2021: EMBASE, EMCARE, APA PsycINFO, CINAHL, Cochrane Library and Ovid MEDLINE searched in 2023. Included were qualitative or quantitative studies, in English language, involving adults >18 years, and implementing hospital-based palliative care into cancer care. Critical appraisal tools were used to assess the quality and rigour.Seven of the 16 studies explicitly cited the use of frameworks including those based on RE-AIM, Medical Research Council evaluation of complex interventions and WHO constructs of health service evaluation. Enablers included an existing supportive culture, clear introduction to the programme across services, adequate funding, human resources and identification of advocates. Barriers included a lack of communication with the patients, caregivers, physicians and palliative care team about programme goals, stigma around the term ‘palliative’, a lack of robust training, or awareness of guidelines and undefined staff roles.Implementation science frameworks provide a method to underpin programme development and evaluation as palliative care is integrated within the oncology setting. What is already known about the topic?The hospital based palliative care services have been ascertained as enabling access to early or timely palliative care. Yet integration of palliative care into existing cancer services remains limited with patients continuing to be referred to palliative care at a late stage, if at all.Implementation science offers an approach to underpin the development of integrated palliative care services.What this paper adds?Just seven studies utilised implementation frameworks to guide service delivery which included RE-AIM, SELFIE model, Medical Research Council framework, and the quality improvement approach of Define, Measure, Analyze and Improve.The main facilitators for palliative care integration included the value of co-design with ‘end users’ of the intervention and the processes of implementation; staff education and training including around processes, communication, and introducing referrals; dedicated communication across the multidisciplinary teams in the hospital. Barriers included lack of time and rapid staff turnover, maintaining fidelity and consistency of the intervention across individual patients and different sites, and a lack of relevant health policy regulations and resources to support palliative care services.Implications for practice, theory, or policyA deeper understanding of the enablers and barriers to the success or failure of the previous palliative care implementation efforts and the opportunities provided by a systematic approach as offered by implementation frameworks will benefit the effective establishment and sustainability of future integrated palliative care programs.The findings from this systematic review may help stakeholders including policy makers and service providers in allocating precious resources towards planning and systematically implementing integrated palliative care programs in hospital-based cancer services. as a core component of oncology care.3 Significant evidence from randomised clinical trials has validated the proven benefits of early palliative care for people with advanced cancer including better symptom management, increased satisfaction with care, and reduced psychological suffering.57 This has led to a strong global consensus supporting the integration of early palliative care in routine cancer practice.8Palliative care is increasingly recognised It includes the identification and response to barriers that block the uptake of proven interventions into care, thereby closing the information gap.11 There is limited literature to guide the implementation of timely palliative care in cancer care services.12 and timely referral to hospital based palliative care services remains challenging. Many clinicians, who oversee the introduction of programs in clinical settings, are unfamiliar with the current implementation science evidence meaning that ‘real-world changes’ do not result.Implementation science is the study of methods and approaches that facilitate the uptake of research into clinical practice. There is also an opportunity for clinical researchers to take a ‘systems’ approach as available in implementation science to the translation of research findings around early palliative care. This systematic review and narrative synthesis aimed to identify the existing utilisation of implementation science frameworks, to describe the barriers and enablers encountered, and strategies adopted to implement integrated palliative care into hospital-based oncology services.There is a need for clinical researchers to consider the acceptability, fidelity, and viability of the intervention that is to be implemented, particularly during the initial phases of its development, when its appraisal and utility may be assessed with iterative checks over time. and followed the guidelines by the Centre for Reviews and Dissemination. This systematic review was registered on the International Prospective Register of Systematic reviews PROSPERO CRD42021252092. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for reporting.A systematic review was conducted with a narrative synthesis approach. Due to the diversity of included study designs  as well as formal randomised controlled trials or implementation studies published in the year 2010 onwards.Exclusion: Publications classified as book reviews or sections, case reports, comments, conference abstracts, posters or oral presentations, conference reviews, dissertations, editorials, lectures, letters or review papers were excluded.Publications were identified through systematic searches of six bibliographic databases, conducted on 12 March 2021: Ovid MEDLINE(R) ALL 1946 to March 10, 2021; Embase 1974 to 2021 March 10 (Ovid); Ovid Emcare 1995 to 2021 Week 08; APA PsycInfo 1806 to March Week 1 2021 (Ovid); CINAHL (EBSCOhost) and Cochrane Library (Wiley). The reference lists of included papers were also searched. An updated additional search was conducted in Medline Ovid from 2021 to 2023 (current) for any pertinent papers published recently. In addition, a hand search was conducted in Google Scholar. using the query:  AND (neoplasms[Majr] OR cancer*[tiab]) AND hospital*[tiab] AND ((implement*[tiab] OR integrat*[tiab]) OR ‘implementation science’[Mesh:NoExp]). Forty publications identified from those results were further analysed using Yale Text Analyser. Search terms retrieved through text mining were extensively tested for usefulness and relevance in Ovid Medline to develop the final search strategy.Search strategies were developed by a medical librarian in consultation with a topic expert. Potential search terms were identified through text mining in PubMed PubReminerSupplemental File 1) and then adapted for other databases adjusting subject headings and syntax as appropriate . Search syntax used in the Ovid databases was adapted for CINAHL (EBSCOhost) and Cochrane (Wiley) using the Polyglot Search Translator.Final search strategies combined the general concepts of Palliative Care AND Cancer AND hospital AND Implementation using a combination of subject headings and text words. Searches were limited to English language publications, but no date limits were applied. An initial search was developed for Ovid Medline , date of publication, participant group, study design. Data were also collected for key findings around descriptions of the implementation process including references to implementation frameworks and models and any barriers and enablers to the implementation. The critical quality appraisal for risk-of-bias was conducted by two authors. is that it adopts a textual approach to the process of synthesis to ‘tell the story’ of the findings from the included studies. The purpose of the narrative synthesis was to organise findings from the included studies in order to provide an assessment of the strength of the evidence for drawing conclusions about the facilitators and/or barriers to implementation identified in the synthesis. The steps towards data synthesis involved two researchers reading the included papers multiple times to facilitate thematic analysis, ascertaining the main, repeating and/or pertinent findings or themes (based on the review question) and/or concepts emerging from the various studies. Thematic analysis provided the researchers with a means of organising and summarising the main ideas and conclusions across the diverse research studies. Patterns were identified in the sections including methods, results and discussion by reviewing the full-text papers and potential themes were extracted in a table and discussed among the two researchers in order to ensure the context of themes, which were later refined under categories. Any inter researcher disagreement about the themes was resolved through consensus and a third senior researcher’s advice. Regular meetings were arranged among all researchers throughout the process to progress discussion and finalisation of findings. The study results were then transformed and summarised into a common rubric. This rubric in A narrative synthesis approach was used to summarise the data. The defining characteristic of narrative synthesis as described by Popay et al.Following removal of duplicates and excluding publication types, 4642 records were screened on title and abstract. An additional update to the search was conducted via Medline Ovid 2021 to 2023 (current) and a further 181 records were screened on title and abstract, leading to a total of 60 records that were subject to full text review. Of these, 16 studies met the inclusion criteria  for mixed methods studies and Joanna Briggs Institute (JBI) tool for pre-and-post  studies. Another risk of bias tool was used for the quantitative cross-sectional studies to assess 10 characteristics of the study. Quality assessment was based on the implementation data provided, rather than the overall study data. Qualitative studies were given a ranking of 1 to 10, cohort studies were given a ranking of 1 to 12 and experimental studies were given a ranking of 0 to 11 based on how many of the CASP questions could be answered positively.27 The Mixed Method Assessment Tool was used with a ranking of 1 to 5 based on how many of the five Mixed Method Assessment Tool questions could be answered positively  toolely see .42 Canada,41 United Kingdom (UK) and Europe including Hungary, Germany and Netherlands and Italy One study was conducted across multiple European countries (The 16 included studies  largely untries .n = 6 out of 16), descriptive/cross-sectional (n = 3), mixed-methods (n = 3), pre-and-post implementation designs (n = 2) and clinical/quasi-experimental studies (n = 2) studies.Studies designs included qualitative studies  and the participating urban and rural oncology services centres .3642  guidance for process evaluation, focusing on context, application of the intervention, mechanism of impact and evaluation phases when establishing hospital based palliative care services33  with few patients completing surveys reporting feedback about palliative care. The stigma surrounding the name ‘palliative’ was reported as a barrier to early palliative care referral that needed to be explicitly addressed within the intervention programme.Patients and caregivers were largely satisfied (84%) with the palliative care intervention• Incorporation into existing workflow Conversely, challenges to implementation included a lack of clinician readiness at the clinical site was observed as an implementation challenge and practices that involved non-palliative care clinicians being tasked with additional clinical responsibilities such as completing symptom assessment tools. Others noted barriers included lack of acceptability and feasibility, with work tools that were considered too specialist focused or not practical, difficult to locate, time consuming and poorly integrated into routine workflows and routines.The integrated palliative care model was most effective when it was implanted into existing workflows and supported by electronic systems.• Administrative barriers  Authors of early palliative care intervention studies described potential cultural or professional conflicts for implementing a complex intervention in clinical settings under the care of multiple specialities.Administrative difficulties included securing optimum space, staff, and sufficient time to launch the implementation programme. and time, funds, education and human resources were dedicated to the implementation programme.38 An important provision is that a balance must be struck between broadening palliative care referral criteria for increasing patient access to palliative care, and taxing limited available palliative care resources including workforce shortages and space constraints. A lack of a standardised Institutional Review Board approach including their hesitancy to approve palliative care research and quality audit activities was encountered by the researchers when undertaking evaluation of outcomes.The integrated palliative care model was most successful if the senior managers and heads of tumour streams provided support,• Rapid staff turnover40 disrupted data collection, clinical relationships and lines of communication.40The rapid turnover of staff in the hospital/clinical settings was reported as having a detrimental impact upon implementing a new service intervention, resulting in delays and funding difficulties with ongoing requirements for staff training,• Organisation culture  was recognised to be pertinent in the delivery of palliative care interventions.41 Considering those studies involving education interventions aimed at increasing clinician ability to recognise palliative care complexity,42 the role of a multidisciplinary team was regarded positively and facilitated earlier access to the palliative care team.Within the organisation, the role of a multidisciplinary team Potential facilitators for palliative care implementation included internal activities such as intercollegiate palliative care training or multidisciplinary team discussions to promote awareness of tools to assist palliative care provision.32Others noted positive organisational change available in early palliative care through the AMBER study which provided a tool to facilitate change to the way care was delivered and also facilitated change to the culture of care delivery.• Recognition of champions To meet the patient and clinician needs, a strong collaboration between palliative care and oncology teams was necessary.The value of clinical advocates and champions was highlighted as supporting a successful palliative care programme implementation.• Communicating42 The importance of ‘timing’ and ‘time’ was emphasised for the palliative care conversations and oncologists involved palliative care clinicians early on in order to establish good communication enabling end-of-life treatment planning for a patient with advanced cancer. However, many haematologists felt the unpredictable nature of hematologic malignancies made it difficult to identify the appropriate time to introduce palliative care consultations. Hence, there were a few missed opportunities where palliative care could not be introduced.The oncologists viewed the role of integrated palliative care as facilitating a comprehensive approach to treating the patient with an advanced cancer, and palliative care consultants were seen as sharing the load. Training in having such discussions was identified as an important aspect of doctor-patient communication.34Physicians conveyed doubts about starting discussions with patients around palliative care as a result of prognostic uncertainty and concerns about destroying patients’ hopes and negatively affecting the physician−patient relationship.2839 A number of authors cited the lack of relevant health policy regulations and financial schemes to support palliative care services. They highlighted the need for distinction on an institutional level between feasibility and ongoing sustainability, which required a more systematic approach.41 Furthermore, the divergent levels of development across services required flexibility in the methods for service engagement and the setting of benchmarks to assess success.40The maintaining of fidelity and consistency of the intervention across individual patients and different sites required ongoing training and education of staff.In order to demonstrate the application of implementation frameworks to this field, the enablers and barriers for palliative care implementation identified through the narrative synthesis are presented in This systematic review supports the need to translate the strong evidence-base supporting integrated palliative care into oncology practice by examining the rigour with which implementation science principles have been employed.i) Main findings/results of the study46 Those studies that clearly utilise implementation frameworks to formally address the issues related to system, staff, patients and intervention have largely been published in recent years, suggesting this is an emerging area in the field.This review indicates that many researchers have hinted at components of implementation frameworks without explicitly using them when establishing integrated palliative care in their hospital settings. This finding is consistent with observations made in the implementation science literature about the paucity of explicitly naming frameworks.42 SELFIE model , MRC  framework to guide complex interventions,38, and the quality improvement approach of Define, Measure, Analyze and Improve. The increase of studies in the recent past which have utilised implementation frameworks may suggest that it is an emerging area in the field of palliative care integration.The few studies in this review which have utilised implementation frameworks to guide service delivery have variously used RE-AIM  framework,ii) What this study adds:2326 The quality appraisal ranking was high for four studies, medium for 11 studies, and low for one study.This review utilises multiple, validated tools for included studies to assess the quality, rigour and risk of bias as part of quality appraisal, with medium scoring allocated to most studies.48While the evidence-base underpinning early integration of palliative care is now mature, it appears that the evidence guiding implementation into practice is less developed. The effective utility of the implementation frameworks for systematically implementing palliative care in hospital clinical settings has been shown in this systematic review with narrative synthesis as well as by previous studies conducted in other settings (such as community settings and aged care facilities) and with other populations such as non-oncology (chronic disease) cohorts and chronic asthma sufferers.We posit the use of an implementation framework such as RE-AIM should be considered going forward to systematically present the barriers and enablers in palliative care implementation programs across hospitals in the oncology units. Having a systematic approach to the implementation of a new service or a new aspect of a service will make explicit not only of those areas which have facilitated the success of the project, but also enable a clearer understanding of reasons underpinning failure to make a change. This in turn may help stakeholders including policy makers and service providers in allocating precious resources towards planning and systematically implementing integrated palliative care programs in the hospital-based cancer services.The systematic approach offered by implementation science frameworks is also key to ensuring the sustainability of those successfully established programs. Importantly, having a common language to report these experiences of service implementation such as those constructs of RE-AIM framework will allow the learning to be available to other services considering establishing integrated palliative care programs.iii) Strengths and weaknesses/limitations of the study:There are few limitations to this review. While care was taken in screening studies, it is possible that some studies were missed, as implementation methodologies were not consistently reported. Only the studies written in English language were selected, and these were conducted in high-income countries, so the implementation strategies presented may not be applicable in the low-to-middle-income countries. Some qualitative studies did not provide adequate details about the interview methodologies, or justification for observing rigour and reflexivity and so were omitted, as was the considerable grey literature and unpublished work in this area. However, the strengths of this review include a robust and systematic screening process, and using multiple, validated risk-of-bias tools for quality appraisal of various study designs, to have a holistic view of the palliative care implementation strategies.The type of Implementation framework that a researcher may want to select could be affected due to the diverse interventions  and settings for the studies. However, using a formal implementation framework prompts comprehensive consideration of the different areas of influence, of activity and evaluation, ensuring a systematic approach to the programme development is available.There is very limited utilisation of implementation frameworks to integrate early palliative care into hospital oncology services. Yet the multidimensional, system-wide approaches within implementation science frameworks offer a structure to guide and evaluate programme development. Key elements of implementation to consider when establishing palliative care service integration in cancer centres include a focus on co-design of the intervention and processes of implementation, staff education and training including around processes, communication and introducing referrals, dedicated resources, recognition of champions and more effective communication across the multidisciplinary teams in the hospital. The opportunities offered by implementation science to guide the effective integration of palliative care into cancer care suggest that the formal use of implementation frameworks should be adopted in future service development initiatives.Click here for additional data file.Supplemental material, sj-pdf-1-pmj-10.1177_02692163231186177 for An evidence-base for the implementation of hospital-based palliative care programs in routine cancer practice: A systematic review by Farwa Rizvi, Helen Elizabeth Wilding, Nicole M Rankin, Roslyn Le Gautier, Lorna Gurren, Vijaya Sundararajan, Kylee Bellingham, Joyce Chua, Gregory B Crawford, Anna K Nowak, Brian Le, Geoff Mitchell, Sue-Anne McLachlan, Tanara Vieira Sousa, Robyn Hudson, Maarten IJzerman, Anna Collins and Jennifer Philip in Palliative MedicineClick here for additional data file.Supplemental material, sj-pdf-2-pmj-10.1177_02692163231186177 for An evidence-base for the implementation of hospital-based palliative care programs in routine cancer practice: A systematic review by Farwa Rizvi, Helen Elizabeth Wilding, Nicole M Rankin, Roslyn Le Gautier, Lorna Gurren, Vijaya Sundararajan, Kylee Bellingham, Joyce Chua, Gregory B Crawford, Anna K Nowak, Brian Le, Geoff Mitchell, Sue-Anne McLachlan, Tanara Vieira Sousa, Robyn Hudson, Maarten IJzerman, Anna Collins and Jennifer Philip in Palliative Medicine


Chronic dysfunction of the nervous system, including autism spectrum disorders and anxiety disorders, is broadly correlated with metabolic dysfunction, such as obesity and diabetes  exercise and examined the effects on the central molecular pathways that respond to metabolic stimuli, namely, AMPK and AKT and their downstream effector, the master regulator, mTOR, which coordinates energetic status and protein synthesis , thereby uncoupling the weight-loss-independent improvement that could stem from the surgery. The 5xFAD mice are transgenic for two human genes (APP and PSEN1), carrying several mutations associated with familial AD, and develop early-onset dementia. While SG did decrease blood glucose and cholesterol levels, it did not affect the number of β-amyloid plaques or cognition in 5xFAD mice. These results suggest that the main effect of bariatric surgery on cognitive function may be attributed to weight loss and improvement in the sequelae of obesity rather than metabolic or other outcomes of the surgery. It is important to consider that in this mouse model, β-amyloid plaques can develop at an early age before the surgery is performed, and reversing an already present condition may be hard to achieve. Additionally, this genetic model for AD may not recapitulate the etiology of the more common non-familial sporadic AD. This study therefore provides crucial insights into the risk the metabolic syndrome plays in AD development, demonstrating that in lean mice improving particular metabolic parameters by sleeve gastrectomy did not directly improve cognitive function.Obesity and hyperglycemia are associated with a higher incidence of cognitive decline and Alzheimer's disease (AD). There is evidence for cognitive benefits in patients with obesity following bariatric surgery  in a longitudinal Finnish population-based twin cohort, with 725 blood plasma samples and accompanying self-reporting data collected in adolescence and young adulthood. Using high-throughput 1H nuclear magnetic resonance spectroscopy (NMR) to profile the metabolites, the study identified a significant negative association of plasma valine and leucine with depression. The same group previously identified ketone body 3-hydroxybutyrate as a biomarker of aggression (Whipp et al., The link between brain dysfunction and metabolism is further evidenced by alterations in the metabolomic profile in the context of mental health problems in human subjects. Chegodayev et al. proposed a hypothetical mechanism tying together a deficiency of ketone bodies with burst suppression in neurons and an abnormal electroencephalographic pattern, which is more prevalent in disorders characterized by corpus callosum abnormalities. Based on existing studies, the authors discussed several pathways through which ketone body metabolism could affect neuronal electrophysiology, including myelination, ATP-sensitive potassium channel signaling, and/or control of neurotransmitter release. The contribution of these mechanisms to the metabolic regulation of neuronal activity may present a potential target for therapeutic intervention and thus warrants further experimental studies.While the mechanisms linking metabolic and neural disorders remain mostly unknown, Together, these studies exemplify and encourage an integrative view of metabolic and neural dysfunction and present recent advances in molecular studies highlighting this link.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


POPs are highly persistent, bioaccumulative and biomagnifying, since they resist chemical, biological, and photolytic degradation. They have been identified in air, water, soil/sediment, and biota all over the world, even in remote regions where they have never been used, not only as a consequence of local contamination sources, but also as a result of efficient long-distance transport by circulation of air masses and waters. POPs enter the aquatic environment through dry and wet atmospheric deposition and attach to soil particles in water runoffs or waste waters. Due to their tendency to sorb to suspended particulate matter, POPs accumulate in aquatic  sediments as one of their main sinks.Persistent organic pollutants (POPs) are a group of 28 toxic compounds of different chemical classes listed in the Stockholm Convention on POPs, which aims to protect the environment and human health. This group includes chemicals used in agriculture (pesticides), industry , as well as unintentional industrial or combustion by-products, such as polychlorinated dibenzo-For the trace determination of POPs in complex environmental and biological matrices, highly selective and sensitive analytical methods are fundamental. Most of these methods are based on selective extraction of target compounds and analysis of purified extracts with high-resolution instrumental techniques, such as gas or liquid chromatography coupled to mass spectrometry.This Special Issue includes six original research articles focused on (a) studies of origin, temporal and spatial distribution, and long-term trends of selected organic pollutants in different environmental compartments; (b) recent advances in analytical methods developed for their identification and quantification in environmental and biological matrices; and (c) prediction of pollutant levels and fate in the environment based on model simulation.In their paper entitled “Distribution and Relationships of Polycyclic Aromatic Hydrocarbons (PAHs) in Soils and Plants near Major Lakes in Eastern China”, a team of Chinese researchers compare the composition and mass fractions of 16 PAHs in soil and plant samples collected close to the shore of nine lakes [10 Particle Fraction and Bulk Deposition” based on toxic equivalence factors and equivalent benzo(a)pyrene (BaP) concentrations for PM10 particle and bulk deposition samples collected in a residential part of the Croatia’s capital Zagreb [A team of Croatian researchers address PAH-related human health and ecological risks in the paper “Carcinogenic Activity and Risk Assessment of PAHs in Ambient Air: PMl Zagreb . The aut10 atmospheric particles, particle-bound benzo(a)pyrene, Pb, As, Cd, Ni, gaseous pollutants NO, NO2, NOx, and SO2) and meteorological parameters. The authors distinguish types of environments characterized by specific interactions between benzo(a)pyrene, other polluting species, and meteorological conditions and explain how advanced artificial intelligence-based modelling can contribute to a better understanding of complex factors that determine the fate of air polluting species in the environment.The article “Potential of Coupling Metaheuristics-Optimized-XGBoost and SHAP in Revealing PAHs Environmental Fate” by a team of Serbian researchers  describeThe fourth article presented in this issue describes in detail a new method for determination of flame retardants polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD) in different types of food and feed, developed by a group of Slovenian researchers (“Simultaneous Method for Selected PBDEs and HBCDDs in Foodstuffs Using Gas Chromatography—Tandem Mass Spectrometry and Liquid Chromatography—Tandem Mass Spectrometry”) . The newThe fifth article, “Emerging Contaminant Imidacloprid in Mediterranean Soils: The Risk of Accumulation Is Greater than the Risk of Leaching”, brings the results of a Croatian-Polish collaboration in researching the behaviour of the neonicotinoid insecticide imidacloprid in Mediterranean soils . AlthougThe last article “Prediction of the Impact of Land Use and Soil Type on Concentrations of Heavy Metals and Phthalates in Soil Based on Model Simulation” by a team of Serbian researchers  looks inWe would like to thank all the authors for their valuable original scientific contributions to this Special Issue and the reviewers for their time and expertise. Our special thanks go to Ms Jessie Zang, the section managing editor, for her valuable suggestions and continuous support and help in promoting this Special Issue.


Despite being acknowledged as a major global health challenge, growing levels of antimicrobial resistance (AMR) in pathogenic and commensal organisms have proven an awkward fit for international health frameworks. This article surveys the history of attempts to coordinate international responses to AMR alongside the origins and evolution of the current international health regulations (IHR). It argues that AMR, which encompasses a vast range of microbial properties and ecological reservoirs, is an awkward fit for the ‘organismal’ philosophies that centre on the rapid control of individual pathogens that have characterised international policy-making since the 19th century. The health challenge of antimicrobial resistance (AMR) is as old as the antimicrobial era, with the first known clinical reports of emerging microbial ‘drug fastness’ in response to prolonged organoarsenic exposure dating back to 1907.Rather than solely trying to make AMR fit into traditional pathogen-focused policy frameworks, we should aim for a new structural mode of international policymaking, and one that moves beyond conceptualizing AMR solely in terms of present overuse and treatment failure and adopts a more long-term conception of stewarding microbial ecosystems.This article examines why AMR has proven so difficult to regulate. Focusing on the period between 1945 and 2015, it contrasts the evolution of AMR stewardship initiatives with the parallel development of international legal frameworks like the International Health Regulations (IHR), which have enjoyed varying levels of success. The article shows that AMR proved an awkward fit for a legal system that was developed around individual pathogens or substances. Traditional contain-and-control strategies developed to stop the spread of well-characterized bacterial and viral entities such as cholera, rinderpest, or influenza.The roots and evolution of our contemporary international health system are intimately tied to the history of pandemics and have consistently focused on containing the spread of individual pathogenic viruses or bacteria across national borders.Office International d’Hygiène Publique  and International Sanitary Conventions (ISCs) .Starting in the 19th century, and building on centuries of more local approaches to quarantine, pandemic events like the repeated waves of cholera and plague prompted imperial powers and emerging nation states to organize a total of 14 International Sanitary Conferences. The goal of these conferences was to develop an internationally standardized way of defining, notifying, and reacting to the spread of pathogenic threats. Despite early tensions, the period around 1900 saw the rise of germ-based explanations of disease and mutual concerns about pandemic events’ impact on trade lead to an initial formalization of international health politics in the form of permanent institutions like the From the 1920s onwards, new permanent international bodies with greater powers like the League of Nations Health Office  and World Health Organisation (WHO 1948-), as well as affiliated national and non-governmental organizations, launched various social medicine-oriented programs  alongside vaccination, environmental control, and disease eradication campaigns. However, all of these non-statutory schemes remained dependent on the often unstable political and financial support of sovereign nation states and imperial powers.In 1951, the International Sanitary Regulations (ISR) consolidated the previous ISC patchwork of reporting regulations for six already quarantinable diseases . Passed in the context of the ‘Hong Kong Flu’ pandemic, the 1969 International Health Regulations (IHR) replaced the ISR but did not include significant new powers. Indeed, reporting requirements were soon limited to three ‘classic’ diseases . Meanwhile, critics bemoaned lack of compliance with ISR/IHR provisions and international legal frameworks’ failure to provide means to react to new or re-emerging pathogens such as HIV/AIDS or multiple drug resistant tuberculosis. In practice, the IHRs were thus increasingly overshadowed by the passage of health-relevant international treaties in the fields of human rights, environmental protection, and trade.Between 1995 and 2005, concerns about pandemic preparedness, bioterrorism, the increasing displacement of international health by trade concerns, and the 2003 SARS outbreak led to sustained attempts to reform the IHRs. Passed in 2005, the revised IHR replaced many classic elements of international disease surveillance with a new concept of integrated biosecurity governance. Although they continued to focus on concerning established pathogens, the 2005 IHR required member states to survey and notify the WHO regarding a far broader range of potential public health risks of urgent international concern — including emergent diseases, intentional bioterrorist releases of disease, and nuclear and chemical hazards. Minimum national surveillance capacities were defined and the WHO could now also use non-governmental data to declare a public health emergency of international concern (PHEIC). In case of a PHEIC, the WHO could issue non-binding recommendations for member states to tackle the emergency, which would theoretically enable a standardized global response.Throughout this long history of trying to contain infectious diseases at the international level, the systemic health threat posed by AMR has been curiously absent from statutory health frameworks. Estimated to have caused over 1.27 million human deaths in 2019,The fact that AMR or ‘drug fastness’ could emerge as a result of exposing organisms to antimicrobial substances was nothing new by the time the first permanent international health institutions emerged. Concerns about the threat it could pose to new generations of antimicrobial treatments emerged soon after the launch and mass-marketing of sulfonamides (1930s) and antibiotics (1940s) and led to repeated calls for ‘rational therapy.’Staphylococcus aureus phage type 80/81, regulators followed a classic ‘organismal’ control approach aimed at stopping the pathogen with hygiene and updated treatment regimes rather than seeking to limit the evolutionary selection pressure being brought to bear on microbial ecosystems.When they did appear, reform responses to emerging AMR were limited. During the 1950s crisis surrounding the pandemic spread of penicillin resistant Despite warnings about the ecological impacts of mass antimicrobial usage by prominent microbiologists like gramicidin-discoverer René Dubos,Statement Regarding Worldwide Antibiotic Misuse that Levy coordinated and had signed by 147 scientists from 27 countries, was multisectoral in its concerns  and was picked up by many press outlets.It was only during the 1980s that sustained calls for wider international efforts to contain AMR emerged. Initially, these calls were voiced not by international organizations but by non-governmental actors. Tufts University clinician-researcher Stuart Levy, especially concerned with resistance-conferring plasmids that respected the boundaries of neither bacterial species nor nation-states, first drew attention to the shared, global nature of AMR. The 1981 Emerging Infections report,Yet despite the inclusion of AMR within the U.S. Institute of Medicine’s influential 1992 Staphylococcus aureus (MRSA), AMR appeared on the policy agendas of powerful nation states and transnational organisations such as the US and the European Union (EU).status quo — were insufficient and tended to follow traditional molds rather than address AMR’s genetic and ecological dimensions. Attempting to fix rather than restructure existing food production and health systems, high-income countries adopted selective usage reductions in human and animal health but mostly neglected the environmental domain whereas new surveillance systems once again focused on resistance in priority pathogens rather than environmental background levels of AMR. Although high-income levels of medical and agricultural usage began to decline by around 2010, interventions’ long-term impact on AMR proved difficult to assess. In some cases, local AMR levels had declined but quickly recovered once drugs were reintroduced; in other cases, interventions came too late to prevent the permanent establishment of AMR in clinical, agricultural, or broader microbial ecologies. Meanwhile, AMR genes and organisms continued to flow freely across borders. As highlighted by reports on New Delhi metallo-betalactamase 1 (2008) and mobilised colistin resistance (2015), addressing AMR required a broader international restructuring of health, food production, and pharmaceutical systems.By the end of the millennium, the ongoing rise of AMR levels was increasingly acknowledged as a severe global health threat that spanned all three domains of human, animal, and ecological health.The systems-dimension of would-be AMR reform efforts went far beyond anything ever attempted within the conservative legal frameworks of international health. Starting with an ill-fated attempt to galvanise AMR action on September 11, 2001, international organizations such as the WHO, the Food and Agriculture Organisation (FAO), and World Organisation for Animal Health (OIE) began to move from simply reporting on AMR to proposing novel surveillance and stewardship frameworks.However, similar to problems regarding the 2005 IHR,In 2000, Lederberg called for a reconsideration of the Manichean “good/bad” mindset regarding bacteria, and for a focus on the broader ecology of the microbial world we inhabit.Amidst the wider reordering of Global Health following COVID-19, a growing number of voices are now calling for an integration of the “silent pandemic”However, there are well-known limitations. At one level, the described measures do not address the upstream forces — from sanitation to the structures of care delivery — that have differentially shaped the worldwide incidence of AMR and disease burdens. New antibiotics will temporarily reduce AMR pressures, and improved surveillance and infection prevention can address the threat posed by individual pathogens. However, addressing the structural drivers of antibiotic dependency and disease will require far broader ‘antibiotic sensitive’ upstream investment in health and food systems resilience.Moreover, the invocation of Lederberg calls to mind a second set of considerations. In 2000, and echoing earlier warnings by René Dubos, Lederberg called for a reconsideration of the Manichean “good/bad” mindset regarding bacteria, and for a focus on the broader ecology of the microbial world we inhabit.If AMR signals an “Anthropocene in the cell,”


Multiple quality metrics have been recommended to ensure consistent, high-quality execution of screening tests for breast, cervical, colorectal, and lung cancers. However, minimal data exist evaluating the evidence base supporting these recommendations and the consistency of definitions and concepts included within and between cancer types.We performed a systematic review for each cancer type using MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 2010 to April 2020 to identify guidelines from screening programs or professional organizations containing quality metrics for tests used in breast, cervical, colorectal, and lung cancer screening. We abstracted metrics’ definitions, target performance levels, and related supporting evidence for test completeness, adequacy , accuracy, and safety.We identified 11 relevant guidelines with 20 suggested quality metrics for breast cancer, 5 guidelines with 9 metrics for cervical cancer, 13 guidelines with 18 metrics for colorectal cancer (CRC), and 3 guidelines with 7 metrics for lung cancer. These included 54 metrics related to adequacy (n = 6), test completeness (n = 3), accuracy (n = 33), and safety (n = 12). Target performance levels were defined for 30 metrics (56%). Ten (19%) were supported by evidence, all from breast and CRC, with no evidence cited to support metrics from cervical and lung cancer screening.Considerably more guideline-recommended test performance metrics exist for breast and CRC screening than cervical or lung cancer. The domains covered are inconsistent among cancers, and few targets are supported by evidence. Clearer evidence-based domains and targets are needed for test performance metrics.PROSPERO 2020 CRD42020179139 Cancer is a leading cause of morbidity and mortality in the United States and around the world . PopulatQuality metrics for cancer screening tests provide several opportunities: aspirational targets for individual programs, feedback to providers performing tests, criteria for competency and certification, and comparisons between different settings. Comparing quality metrics among population subgroups can reveal variation in screening effectiveness, including racial disparities . Useful Despite the widespread use of cancer screening tests and a plethora of guidelines, little work has been done to examine whether test performance quality metrics recommended in existing guidelines are evidence based and consistently defined and used across cancer types. Quality measurement and reporting place substantial burdens on providers and health-care systems . It is iWe conducted a systematic review to 1) identify test performance metrics recommended by professional organizations or governmental organizations for breast, cervical, colon, and lung cancer screening; 2) evaluate conceptual similarities and differences in test performance metrics across cancer types; and 3) describe levels of evidence that current guidelines utilize to support the implementation of test performance metrics. Screening includes specific tests  and processes ; the current evaluation focuses on test performance, defined as the technical completion of screening tests. The quality domains evaluated were created through evaluation of reported quality measures, recommended domains from the Institute of Medicine , and theThis systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (registered in PROSPERO 2020 CRD42020179139). We developed search strategies with a research librarian for Ovid MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Embase (Ovid) databases, using a combination of subject terms and keywords for each of the 4 cancer types: cancer type, quality metrics, and screening tests. These keywords were combined in searches using “AND” to ensure inclusion of all 3 concepts. The search was restricted to literature published in the English language from January 1, 2010, to April 6, 2020. The full search strategy is available in the Articles identified from the search were imported into an electronic database (EndNote X7.8) and systematic review management software (Covidence). Two authors independently reviewed each title and abstract for eligibility for full-text review . Discordant review results were resolved by consensus between the 2 reviewers, with input from KS if needed. Full-text articles of eligible abstracts were retrieved and also independently reviewed for inclusion.Our evaluation addressed quality metrics related to the technical completion of screening tests . Articles reporting cancer screening test performance quality metrics for early detection of cancer or detection of precancer in average-risk, asymptomatic adults were included. We included guidelines from screening programs and professional organizations so as to emphasize consensus guidelines but not the recommendations of individuals. Each quality metric was classified within 1 of 4 domains: completeness of the test ; adequacy of the examination ; accuracy ; and safety . We excluded guidelines primarily intended to standardize the reporting of test results, such as the American College of Radiology Breast Imaging Reporting and Data System Atlas . If multThree authors  abstracted information on guideline identifiers, such as issuing body, year of publication, professional organization or society (if applicable), country of publication, conflicts of interest, funding sources if present, and quality metrics described. All test performance metrics were included from the identified guidelines; guidelines with no relevant metrics were excluded. For each quality metric, information was collected regarding the numerator and denominator definitions as well as the described level of evidence cited, if any, to support the metric. Reference standards with their inclusion and exclusion criteria were noted, when applicable. A second author out of the three  then reviewed abstracted data, and discrepancies were flagged for review and discussion using source documentation and consensus.For each organ type, we summarized the total number of included guidelines, the number of organizations publishing included guidelines, number of guidelines reporting each metric, and each metric’s level of supporting evidence. Metrics were classified according to quality domain  and number of guidelines in which they appeared.The database searches identified 9412 individual records from which review provided 288 relevant full texts for further evaluation by topic matter specialists . The maiEleven guidelines recommended the use of 20 different test performance quality metrics for breast cancer screening of which 2 addressed test adequacy, 15 addressed test accuracy, and 3 addressed test safety Table 1;. MetricsFive guidelines recommended 9 test performance quality metrics for cervical cancer screening of which 7 addressed test accuracy and 2 addressed test adequacy  and adequate ; this suggests routinely measuring and reporting quality metrics in this domain may be of low value, provided excessive radiation doses are not being used to give such high rates of adequate studies . IdentifWhich test accuracy domains will be most important to the balance of risks and benefits of lung cancer screening remains to be determined. A recent initiative of the National Lung Cancer Roundtable has identified quality indicators for lung cancer screening. However, those reaching consensus were process indicators  and not test performance indicators. The proportion of nonsurgical and surgical biopsies with benign results  and the proportion of stage I cancers were identified as highly relevant but eventually not retained because important data were not available at the time in the American College of Radiology Lung Cancer Screening Registry . No guidQuality metrics may require substantial provider and health system effort to measure and to modify, yet few of the quality metrics identified cited supporting evidence for their use. Ideally, readily measurable test performance metrics linked to outcomes of importance should be accurately measured and available for all screening tests. Conversely, quality metrics without a demonstrated impact or utility could be discarded. An example of a successfully developed, readily available, validated, and implemented quality metric is the adenoma detection rate for screening colonoscopy. This measures, at the level of individual providers, the percentage of screening exams that detect at least 1 precancerous  polyp. For example, if a provider performs screening colonoscopies for 100 patients, and 35 of these exams detect at least 1 adenoma, the provider’s adenoma detection rate is 35%. Each 1% decrease in adenoma detection rate has been associated with a 3%-4% increase in postcolonoscopy cancer risk and with increases in risk of cancer-related mortality . It can Previous research has attempted to describe and prioritize quality metrics, primarily for individual cancer screening tests . To our Strengths of this review include the comprehensive searches performed simultaneously across multiple cancers, efforts to search the grey literature, and the participation of topic experts in all included cancer types. There are also some weaknesses. We may have underascertained the evidence available to support the included quality metrics as we assumed that guidelines would cite available evidence supporting the metric. Quality metrics for screening programs are sometimes published uniquely in the local language, such that some from non-English guidelines may have been missed. Most quality metrics came from organized national screening programs and may not be generalizable to the US context of primarily opportunistic screening. Finally, some relevant guidelines may have been published prior to 2010 and thus missed by our database search. However, we searched bibliographies of included literature and the grey literature; presumably these guidelines, if still used, would have been cited by more recent literature. We included some guidance documents, such as the Bethesda System, that primarily standardized the reporting of test results, for their relevant sections that addressed concepts regarding specimen adequacy .In conclusion, in this comprehensive, cross-cancer, systematic evaluation of quality metrics for cancer screening test performance, we identified substantial gaps in the existence of quality metrics, notably for cervical and lung cancers, in the evidence available to support use of existing metrics for performance monitoring and quality improvement, and in conceptual consistency of quality domains across cancer types. Further work is needed to determine which test performance quality domains can best be used to monitor and improve cancer screening and which existing performance metrics can be safely discarded.djad028_Supplementary_DataClick here for additional data file.


Background: Ovarian malignant tumours are rarely diagnosed in adolescents but may have a significant impact on their survival, future fertility and quality of life. The management of such cases is rather complex and requires expertise and careful planning according to scarce existing evidence and recommendations. Objective: The aim of this study was to review and compare recommendations from published guidelines regarding the diagnosis, prognosis and treatment of malignant ovarian tumours in adolescents. Evidence acquisition: A comparative descriptive/narrative review of guidelines issued by L’Observatoire des Tumeurs Malignes Rares Gynécologiques, the British Society for Paediatric & Adolescent Gynaecology, the European Society for Medical Oncology, the European Society of Gynecological Oncology-European Society for Paediatric Oncology and the European Cooperative Study Group for Pediatric Rare Tumors was conducted. Results: All guidelines recommend a thorough diagnostic work-up, consisting of both imaging tests and serum tumour marker measurement, as well as the use of immunohistochemical methods to confirm the diagnosis and complete surgical staging prior to constructing the treatment plan. There is a lack of recommendations regarding the assessment of prognostic factors, with only one guideline providing detailed information. Treatment strategies, as suggested by the majority of guidelines and with only a few discrepancies between them, should include both surgery and adjuvant therapies, mainly chemotherapy, with great emphasis on fertility preservation when it is considered oncologically safe and on the significance of regular and long-term follow-up. Conclusions: There is a significant degree of agreement among recommendations of existing guidelines. The reported differences, although limited, highlight the need for the adoption of an international consensus in order to further improve the management of adolescent ovarian cancer. Ovarian tumours are the most common neoplasms affecting the reproductive system in adolescents ,2. They The diagnosis of ovarian cancer in the adolescent population can pose challenges in clinical practice, considering the low suspicion of the disease due to young age, the heterogenous and often subtle clinical presentation and the potential limitations in diagnostic imaging in an effort to reduce radiation exposure ,16. OvarThe aim of this descriptive review is to compare and synthesise recommendations from published international guidelines regarding the diagnosis, prognosis and treatment of malignant ovarian tumours in adolescents.The main objective of the present narrative review was to identify existing guidelines or recommendations issued by official medical organisations, colleges, associations, societies, committees and study groups regarding the management of ovarian malignant tumours in pediatric and adolescent populations. A search of the literature was conducted in September 2022 through PubMed, Scopus and Web of Science databases. The literature search was performed regarding the period 1990–2022. Electronic search was conducted by using combinations of terms “ovarian cancer” [tiab] OR “ovarian mass”[tiab] AND “adolescent” [tiab] OR “children” [tiab] OR “pediatric” OR “paediatric” [tiab] AND “guidelines” [tiab] OR “recommendations” [tiab]. Additionally, the websites of internationally recognised medical organisations and societies with scientific interest on gynecologic and pediatric oncology were also searched in order to identify official published guidelines relevant to the objective of the present review. Namely, American College of Obstetrics and Gynaecology (ACOG), American Academy of Pediatrics (AAP), American Pediatric Surgical Association (APSA), Society of Obstetricians and Gynaecologists of Canada (SOGC), International Federation of Gynecology and Obstetrics (FIGO), Royal College of Obstetricians and Gynaecologists (RCOG), British Society for Paediatric and Adolescent Gynaecology (BritSPAG), National Institute for Health and Care Excellence (NICE), French Society of Gynaecologic Oncology (SFOG), L’observatoire des tumeurs rares malignes gynécologiques (IMAGYN), European Society of Gynaecologic Oncology (ESGO), European Society of Paediatric Oncology (SIOPE), European Society of Medical Oncology (ESMO), Paediatric Rare Tumours Network-European Registry (PARTNER), Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) and Chinese Society of Obstetrics and Gynaecology (CSOG) were reviewed.Exclusion criteria included all other types of studies, except for official guidelines and recommendations, as well as guidelines written in any language except for English and French. The main outcomes of interest to identify in the included guidelines/recommendations were the most common types of ovarian cancer in non-adult population, staging and therapeutic management of each type of ovarian cancer in adolescents, as well as suggested follow-up.Systematic search revealed 96 items with potential for inclusion in our narrative review, of which 12 were duplicated and another 74 were excluded based on title/abstract. There were finally twelve items reviewed as potentially eligible for our review, of which three were excluded because of not reporting guidelines/recommendations, two items were excluded because of not reporting guidelines for paediatric/adolescent population, one item was excluded for reporting only on population with hereditary cancer and one item was excluded because of reporting on population with cancer in pregnancy.There were finally five published guidelines/official recommendations regarding the management of ovarian tumours in children and adolescents that were retrieved and included in the present descriptive/narrative review. In particular, two national guidelines were identified, issued by L’Observatoire des Tumeurs Malignes Rares Gynécologiques   and by tIn order to ensure optimal management and due to the rarity of these cases, paediatric and adolescent patients with suspected ovarian malignancies should be referred to a specialised center with a multidisciplinary team composed of trained gynaecological and paediatric oncologists with experience in such cases  ,26,29,30The preoperative diagnostic work-up should include a combination of tests and modalities, performed to further evaluate suspicious ovarian masses and confirm the diagnosis of ovarian cancer, as well as for staging purposes and the assessment of prognostic factors  ,26,27. AThere is a consensus among all guidelines that serum tumour markers, especially β-human chorionic gonadotropin (β-hCG), alpha-fetoprotein (AFP), lactate dehydrogenase (LDH) and cancer antigen 125 (CA125), should be measured in all ovarian masses with suspicious features  ,27,35. AA preoperative diagnostic biopsy can definitively provide a histological confirmation of ovarian malignancy, but it should be avoided if a cystic component is identified within the suspicious mass and it is formally indicated only in the case of extraovarian spread of the disease  ,27. TissAlthough different factors define the prognosis among the various histological types of ovarian cancer in adolescents, the treatment of patients in large specified cancer centers is considered a favourable prognostic factor that applies to all cases (ESMO 2018) . For patPatients should be staged according to the FIGO 2014 staging system  ,27. SurgAlthough the therapeutic management of ovarian malignances in adolescents is tailored according to the histological type, the stage of the disease and the individual characteristics and needs of each patient, there are some general principles that apply in all cases. Adolescents with non-epithelial ovarian cancer should preferably be treated, when feasible, in the setting of clinical trials (ESGO-SIOPE 2020) . The choOncofertility counselling should be provided to all adolescent patients with ovarian cancer before receiving treatment (ESGO-SIOPE 2020) . Even ifYoung premenopausal patients with GCTs or SCSTs treated with chemotherapy are also eligible for hormone replacement therapy (HRT) in order to relieve the symptoms of potential oestrogen deficiency and iatrogenic menopause, which are often more pronounced compared to those following naturally occurring menopause. HRT can be safely administered to patients with GCTs and SCCOHT, but it should generally be avoided in cases of SCSTs, with the exception of stage IA and IB granulosa-type tumours, where it might be considered upon approval of a multidisciplinary board  ,24. For Regular, targeted and long-term follow-up is essential to monitor the response to treatment and to early diagnose a potential recurrence. As already mentioned, the postoperative measurement of serum tumour markers  is used to assess tumour response during chemotherapy, in addition to imaging by pelvic ultrasound and CT scan of the abdomen, pelvis and chest, when lung metastases are suspected, while an abdominal MRI could also be useful in case of equivocal findings and patients with poor visibility on ultrasound  ,26,27. RSpecific recommendations for the therapeutic management of germ-cell tumours, sex cord stromal tumours and small cell carcinomas of the ovary will be presented in the following respective sections of the article.Preoperative MRI is necessary in patients with suspected malignant GTCs with a solid or partially solid mass on ultrasound and if a solid component is also present on MRI; then, surgery is the suggested initial treatment (ESGO-SIOPE 2020) . When plThe need for adjuvant chemotherapy in patients with early-stage GCTs is determined according to the histological type and the stage of the disease. The most used combination is the 5-day bleomycin/etoposide/cisplatin (BEP) regimen  ,24. In sActive surveillance can be applied for stage IA   pure dysFertility-sparing surgery should be considered even in patients with advanced-stage disease due to the high chemosensitivity of malignant GCTs. For the same reason and given the fact that adjuvant chemotherapy is indicated for all patients with advanced stage GTCs, extensive cytoreductive surgery, which may pose delays in the commencement of postoperative chemotherapy and significantly increase long-term morbidity, should be avoided during initial surgical management  ,24,26.Platinum-based chemotherapy agents, mainly the 5-day BEP regimen, remain the treatment of choice for adolescent as well as adult patients. In general, the regimen is administered for three cycles in patients with complete surgical resection and for four cycles in case of macroscopical residual disease, with bleomycin omitted after cycle three to reduce the risk of lung toxicity  ,26. OtheA second surgical resection is not always necessary after the completion of chemotherapy. It is recommended in all patients with residual disease  and normal serum cancer markers after chemotherapy, as well as in cases of embryonal carcinomas or non-secreting mixed germ-cell tumours with post-chemotherapy residual lesions. The same applies for immature teratomas, in order to avoid the growing teratoma syndrome  ,24,26. HWhen a recurrence of the disease is suspected, a biopsy is necessary to obtain histological confirmation before deciding on additional treatment. It is important to thoroughly examine retrieved specimens in order to identify or rule out the presence of immature tissues. In patients with recurrent disease, normal serum cancer markers and histopathology indicative of an immature teratoma or a mixed tumour with a component of immature teratoma, growing teratoma syndrome should always be included in differential diagnosis. If confirmed, it should be exclusively treated with surgical resection, on the condition of the absence of immature tissues on histological examination (ESGO-SIOPE 2020) . The rolComplete surgical staging is imperative in patients with SCSTs, including peritoneal fluid sampling or peritoneal washings, unilateral adnexectomy, examination of contralateral ovary, large omental biopsy or infracolic omentectomy, endometrial curettage for older patients, random blind peritoneal sampling and resection of any suspicious lesions  ,26,27. TRegarding juvenile granulosa cell tumours, patients with stage IA-IC1 disease and complete surgical resection may avoid chemotherapy, which is otherwise required for stages IC2-IC3  ,24,26,27Debulking surgery is considered the most effective course of treatment for advanced stage granulosa cell tumours  ,24, althThe treatment plan for patients with recurrent SCSTs should be discussed in a multidisciplinary board setting and tailored according to the site of recurrence, histological subtype, dissemination, tumour-free interval and previous therapeutic management. Cytoreductive surgery is the treatment of choice for relapsed patients (ESGO-SIOPE 2020) , followeConfirmation of diagnosis by an expert pathologist and discussion of therapeutic management in a specialised tumour board is suggested due to the rarity of these tumours (ESMO 2018) . ConsideDebulking surgery, either initially or after an interval of three–six cycles of chemotherapy, including omentectomy, systematic pelvic and para-aortic lymph node dissection and complete removal of peritoneal disease is the optional treatment for advanced stage SCCOHT  ,24,26. CCurrently, there are no official guidelines about the treatment of patients with recurrent SCCOHT. However, close follow-up is recommended due to the aggressive course and rapid progression of the disease (ESGO-SIOPE 2020) .Ovarian cancer is rarely diagnosed in children and adolescents, whose diagnostic and therapeutic management can pose great challenges and requires expertise and experience. There is a significant degree of agreement in the recommendations of the existing reviewed guidelines, which generally overlap or complement each other, with only a few areas of dispute. All guidelines suggest that diagnostic work should include both imaging tests (at least ultrasound of abdomen and pelvis) and the measurement of a basic panel of serum tumour markers, while there is debate around the necessity of MRI and the diagnostic value of PET scan. There is a consensus among guidelines about the significant role of molecular biology and immunohistochemistry in confirming the diagnosis, as well as about the procedures that a complete surgical staging should include. On the other hand, only ESMO guidelines provide suggestions about the prognostic factors that should be taken into consideration for adolescent patients with ovarian malignancies. Finally, considering basic therapeutic principles and treatment strategies, recommendations from existing guidelines are mostly identical, suggesting that a combination of fertility-preserving surgery  and adjuvant therapy is effective in most cases of ovarian cancer in adolescents, with a few discrepancies, mainly detected in proposed time intervals between follow-up appointments. The differences in the reviewed guidelines, although they are limited, highlight the need for the adoption of an international consensus in order to further improve the management of ovarian malignant tumours in the adolescent population.


The interplay between human psychology and the natural environment has gained significant global attention in recent years. Green psychology, such as ecopsychology, is part of environmental psychology and investigates the psychological, emotional, and cognitive effects of nature on individuals and society. It explores the intricate relationship between human beings and nature, emphasizing the psychological benefits and behaviors associated with nature engagement and sustainability outcomes. Extant research has consistently shown that a stronger “human nature connection” is associated with pro-environmental attitudes, conservation and ecological awareness, adoption of sustainable lifestyle choices, and the development of an environmental identity  “The articles included in this RT cover a wide variety of fields outside the specific application of theoretical concepts in many areas related to sustainability outcomes. These articles have contributed to the overall understanding of the subject matter and have advanced our knowledge in the fields of human psychology and its interface with the environment and sustainability. The call for articles has resulted in the receipt of a wide range of submissions, with a final selection of eleven original research articles prompting discussions on defining the concept of green psychology, developing models, theories, and frameworks on its influence on human behavior toward sustainability. This RT is a result of the collaboration between researchers from different parts of the world and focuses on sustainability through farmer behavior in agriculture (8 articles), citizen behavior in climate control (1 article), patient behavior in healthcare (1 article), and consumer behavior in green retail (1 article). The articles are the outcomes of research focused on many countries, such as China, Korea, Malaysia, Germany, and Iran.Kam and Yoo documents a design practice method to satisfy customer sensibility and individual taste in the fashion industry. The agricultural sector faces many sustainability challenges, and farmers are the most important stakeholder group willing to adopt sustainable farming methods, which are well understood as climate-resilient or climate-smart agricultural practices. In this regard, many articles in this RT address different aspects of farmer perspectives on the adoption of practices that develop sustainable outcomes. This included new technology adoption , straw returning technology (Ren and Zhong), sustainable certification , low-carbon agricultural technologies , green control technology adoption , livestock manure resource utilization behavior , and rangeland conservation (Savari).As emerges from the articles, understanding the multiple stakeholder perspectives is crucial as they determine green adoption behavior. Stakeholders in a specific sustainable practice need to be motivated and educated to understand the importance of green practices and how they can contribute to sustainability. It can be related to sustainable product design or green prevention and control techniques. Sustainable design includes responsibly using materials that are recyclable or biodegradable, thus minimizing waste. Mostly, ambiguity about stakeholder or end-user emotions and tastes significantly poses challenges to sustainable design practices. The original research included in this RT by Ren and Zhong; Jiang et al.), rational-choice theory , rational behavior theory , new economic sociology theory , information-motivation behavior , unified theory of acceptance and use of technology , and the value-belief norm (Savari). A few observations documented in this RT have policy implications. First, they suggest a cognitive process in sustainability adoptions referred to as a “prospective benefit and drawback evaluation,” which involves perceived value, the level of social capital, and the level of subjective cognition . Second, increasing the social capital of farmers could encourage them to embrace innovative practices . Effective communication and responsible leadership are beneficial in developing a higher level of participation by smallholder farmers in sustainable practices . Third, the cognitive deficiencies of farmers are an important barrier to the adoption of sustainable practices, and government assistance is essential to overcome such challenges (Ren and Zhong).The empirical studies that looked at stakeholder behavior in the adoption of sustainable practices explored several theoretical perspectives and found them relevant in the context of the studies. These include the theory of planned behavior -based perception of the natural environment and observed that blue and green hospital environments are more beneficial to psychological health compared to gray. The study established that human wellbeing is positively affected by natural environments, even among cancer patients. Similarly, Blöbaum et al. observed substantial similarities between nature conservation beliefs grounded in a biospheric value orientation (protecting biodiversity) and climate protection values and norms; there did not seem to be value-based conflicts between nature conservation and climate protection.The research by As regards the emerging research direction, more recent policy articles and scientific studies indicate a trend toward new topics and technologies, such as carbon capture and storage (CCS), carbon capture and use (CCU), bioenergy with carbon capture and storage (BECCS), direct air carbon capture and storage (DACCS), use of hydrogen, and negative emission technologies (NETs) (Antonini et al., From policy perspectives, integrating green psychology into policies and practices is essential across various sectors for promoting sustainability and enhancing individuals' connection with nature. By incorporating principles of green psychology in healthcare, education, urban planning, and organizational management, it may be possible to leverage psychological insights to support pro-environmental behavior change and foster a deeper appreciation for the natural world. Such policy integrations can contribute to a more sustainable future where policies and practices prioritize the wellbeing of both individuals and the environment.MV: Writing—review and editing. VK: Writing—review and editing. GR: Writing—review and editing.


The burden of non-communicable diseases (NCDs) is increasing. Risk perception of NCDs is an important factor towards the uptake of preventive health interventions. There are various questionnaires assessing risk perception of NCDs, but no internationally standardized questionnaire has been available. Identification of factors associated with risk perception of NCDs may facilitate the development of targeted interventions. This systematic review aims to identify available questionnaire assessing risk perception of NCDs and the factors associated with risk perception of NCDs.The reporting of this systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We carried out a literature search through three databases  and targeted original article published in English between 2012 and 2021. Quality appraisal of the eligible articles was conducted using the Mixed Methods Appraisal Tool. Findings were synthesized using content analysis.A total of 86 studies were included. We found a variety of questionnaires assessing risk perception of NCDs, with many differences in their development, domains, items and validity. We also identified several personal, sociopsychological and structural factors associated with risk perception of NCDs.Most of the included studies were of cross-sectional design, and therefore the quality of evidence was considered low and exhibit a high risk of bias. The role of publication bias within this systematic review should be acknowledged as we did not include grey literature. Additionally, language bias must be considered as we only included English-language publications.Further development and testing of available questionnaire is warranted to ensure their robustness and validity in measuring risk perception of NCDs. All the identified factors deserve further exploration in longitudinal and experimental studies. According to the World Health Organization (WHO), non-communicable diseases (NCDs) are chronic diseases which tend to have long duration. The main types of NCD include cardiovascular diseases (CVDs), cancers, chronic respiratory diseases and diabetes (DM) . NCDs kiIn general, NCDs occur due to the combination of several factors, including genetic, physiological, environment and behavioural factors . BehavioAccording to the HBM, there are four types of risk perception, including perceived susceptibility, perceived severity, perceived benefits and perceived barriers. Perceived susceptibility refers to the subjective risk of contracting a health condition, while perceived severity is the judgement on degree of seriousness of a given health condition. In addition, perceived benefits refers to an individual’s estimate that a given behaviour will be effective in reducing the threat of disease, while perceived barrier refers to the barriers that must be overcome to follow the health recommendation , 9. An iMany studies have been conducted to assess the perceived risk of developing NCDs. The use of questionnaire as an instrument to measure an individual’s risk perception of NCDs has been widely adopted , 11. TheTo better understand risk perception of NCDs, identification of its associated factors is essential. Literatures have highlighted several factors associated with risk perception of certain disease, including personal factor variables  , 12–14 sDespite the potential usefulness of the available questionnaires for assessing risk perception of NCDs, to our knowledge, there are no systematic reviews that summarize these instruments and assess their validity. Previous systematic review also focused on factors that specifically influence risk perception of certain disease, such as cancer , while lThe reporting of this systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement  S1 Appe. The outThe review question was developed using the PEO  concept . The PICThe literature search was conducted in December 2021, including three databases: Scopus, PubMed and Web of Science. In addition, hand searching of the reference lists of included studies was undertaken to identify further relevant references. The keywords used for the searching of related articles are provided in The inclusion criteria were: (1) publication from 2012–2021; (2) publication in English language; (3) original article (4) described questionnaire that explicitly assessed risk perception of non-communicable diseases or questionnaire that contained at least five items measuring risk perception of non-communicable diseases, and 5) described associated factors of risk perception of non-communicable diseases. We limited the publication date to 2012 and 2021 (articles published in the past 10 years) so that we can build our systematic review on the recent literature considering the dynamic pattern of risk perception , 20. NonTwo authors (JLMY and NA) screened the titles and abstracts independently based on the review questions. A total of 915 articles were removed during the screening. For the remaining 91 articles, 90 full-text were retrieved for assessment of eligibility, while the remaining one article was inaccessible due to post-publication correction . DisagreQuality appraisal was conducted by JLMY and ANA on all studies using the Mixed Methods Appraisal Tool (MMAT) . The MMAJLMY and NA extracted the data independently using a standardized data extraction form which is organized using Microsoft Excel. Information collected in the form include: (1) author, (2) publication year, (3) reference, (4) country, (5) study design, (6) statistical analysis and (7) results. A total of 86 studies were included in this systematic review Tables  and 3. SMajority of the included studies were quantitative studies , while one study was of mixed methods design. Most of the studies (n = 72) explored the associated factors of risk perception of NCDs, while 11 studies described the questionnaire for assessing risk perception of NCDs. Three studies describe both the questionnaire used to assess risk perception of NCDs, as well as the associated factors of risk perception of NCDs.A total of six questionnaires were developed to measure risk perception of a group of NCDs, including CVDs, DM, cancer, chronic respiratory diseases, stroke, hypertension and cancer –37, 40. Of all the questionnaires, five were developed based on established theory or model such as the Health Belief Model and/or Transtheoretical Model , 36, 37.All except four questionnaires , 34, 37 In terms of validation, five questionnaires were only evaluated for either content validity and/or face validity , 38, 41.Most of the studies (n = 72) reported associations between personal factors with risk perception of NCDs, including hypertension, DM, CVDs, CKD, cancers, stroke, osteoporosis and severe depression . A totalPersonal factors including demographic, lifestyle and health history factors  were fouOnly one study each reported association between religion and marital status with NCD risk perception. A total of 11 studies reported associations between education level and NCD risk perception, while five studies found associations between income and risk perception of NCDs.Several lifestyle factors were identified, including physical activity, smoking, alcohol consumption, sweet consumption, number of sexual partner and age at sexual debut. A total of five and ten studies reported associations between physical activity and smoking with NCD risk perception. Three and two studies reported associations between alcohol intake and sexual behaviour with NCD risk perception. Only one study reported association between sweets consumption and risk perception of DM.The health history factors found to be associated with risk perception of NCDs include BMI, waist circumference, 2-hour glucose level, cholesterol level, blood pressure level, underlying NCD, underlying sexually transmitted disease, history of gestational DM, HIV status, use of oral pill/ injectable contraception, prior screening for NCD, family history of NCD and number of relative with NCD.A total of 17 and two studies reported associations between BMI and waist circumference with NCD risk perception, respectively. Several studies (n = 14) reported associations between underlying comorbidities such as high blood pressure, high cholesterol, underlying NCDs, history of gestational DM, history of sexually transmitted disease and HIV positivity with risk perception of NCDs.Only one study reported association between the use of hormonal contraception with risk perception of breast cancer. Three studies reported associations between prior screening of NCD with risk perception of NCD. A total of 31 studies reported associations between family history of NCD and/or number of relative with NCD with risk perception of NCDs.Several sociopsychological factors were found to be associated with risk perception of NCDs, namely social exposure to NCD, perceived stigma by others, insured status, worry, distress, personal control, conscientiousness, emotional stability, optimistic bias, belief in the genetic cause of NCD, perceived oneself as overweight, believing overweight is a personal health problem, perceived risk of HPV exposure and perception of own health status.Only one study reported association between social exposure to NCD and perception of stigma by other with risk perception of NCDs, while three studies found association between insured status and risk perception of NCDs. Emotional status such as worry and distress have been associated with risk perception of NCDs in five and one study, respectively.Only one study found that greater personal control was associated with higher DM risk perception. Personality traits such as conscientiousness, emotional stability and optimistic were also found to be associated with risk perception of NCDs in three studies. Previous studies (n = 2) have occasionally examined health beliefs, while 11 studies reported associations between perception regarding own health and risk perception of NCDs.In addition to personal and sociopsychological factors that may influence NCD risk perception, structural factors were also identified. Under structural factors, several knowledge-related factors were identified, such as knowledge of NCD (n = 7), history of genetic counselling (n = 1), either discussed with or informed by healthcare professional about risk of NCD (n = 4), received recommendation for NCD screening by healthcare professional (n = 1) and discussion on NCD risk in the family (n = 1).The studies were appraised using the Mixed Methods Appraisal Tool (MMAT) . The autAn individual’s risk perception of developing a disease is an important factor towards adopting healthy lifestyles and the uptake of preventive health interventions. To date, there has been no systematic review which has summarized the questionnaires assessing risk perception of NCDs and evaluated the evidence of factors influencing the risk perception of several major NCDs. Therefore, the purpose of this systematic review was to identify the best available evidence on questionnaire assessing risk perception of NCDs and factors associated with risk perception of NCDs. In this systematic review of 86 studies, we summarized the available questionnaire assessing risk perception of NCDs. We also identified several key personal, sociopsychological and structural factors associated with risk perception of NCDs.This review has identified questionnaires that explicitly assessed risk perception of NCDs or included at least five items assessing risk perception of NCDs. These questionnaires that assessed risk perception of NCDs pose very different questions, as they were developed based on different model, theory or adapted from different studies. Nevertheless, most of these questionnaires comprehensively measure various dimensions of risk perception of NCDs given the multi-dimensional nature of the concept.For example, questionnaire developed by Mya et al included five domains of risk perception, namely perceived susceptibility, perceived benefit, perceived barrier, self-efficacy and behavioural change intention , while aThe strength of the questionnaires included in this review is their comprehensiveness within a relatively short questionnaire. For example, the 48-item questionnaire by Agarwal et al can be completed within 20 minutes which is acceptable without overloading the respondents . AdditioRegarding the validity, only a few of the included questionnaires tested construct validity using confirmatory factor analysis. The lack of construct validity assessment is also commonly seen in questionnaires assessing other constructs such as empowerment in cancer patients and parenting style , 113. HeDemographic factors including gender, age, ethnicity, religion, education level, income and marital status play a role in risk perception of NCDs. Even though many studies reported that women were more likely to perceived themselves to be at risk of NCDs , 80, 82,Ample evidence exists regarding the association between age and risk perception of NCDs. The higher risk perception of NCDs among those of older age is explainable, as NCDs are often associated with older age due to the higher prevalence of NCDs in the older age group , 115. NeThe association between ethnicity and risk perception of NCDs has been shown in the literature. The difference of risk perception between different ethnicities may be attributable to cultural salient factors such as wishful thinking, fatalistic beliefs and medical mistrust . This fiThe concerns of high socioeconomic status people about NCDs may be related to health literacy exposure, shaped by messages and media, as well as communication of health care professional . HoweverLifestyle factors associated with risk perception of NCDs included physical activity, smoking, alcohol consumption, sweet consumption and sexual behaviour. The knowledge regarding the benefit of physical activity in preventing NCDs might lead to lower risk perception among those who are physically active . HoweverThe higher risk perception of NCDs among smokers might be expected, as the adverse health effects of smoking is well known, particularly risk of cancers, CVD and respiratory diseases –121. SimWe also observed reported association between sexual behaviour and risk perception of NCDs. The higher risk perception of cervical cancer among those who had more sex partners is not surprising, as those who had more lifetime sexual partners and those practicing risky sexual lifestyle were more likely to be diagnosed with human papillomavirus infection which increases their risk of cervical cancer .Health history factors associated with NCD risk perception included BMI, waist circumference, 2-hour glucose level, cholesterol level, blood pressure level, underlying NCD, underlying sexually transmitted disease, history of gestational DM, HIV status, use of oral pill/ injectable contraception, prior screening for NCD, family history of NCD and number of relative with NCD. The positive relationship between anthropometric values such as BMI and waist circumference with risk perception of NCD indicate that people seem to associate those readily visible factors with the risk of NCDs.In addition to prior screening for NCD, underlying comorbidities such as high blood pressure, high cholesterol level, and pre-existing communicable and non-communicable diseases have also been associated with risk perception of NCDs. Those who had prior screening for NCD and underlying comorbidity may have more opportunity of receiving health counselling or advice from health care provider and therefore more likely to perceive risk for NCDs , 101.The higher risk perception of breast cancer among those using hormonal contraception is possibly due to the established fact that hormonal contraception increases the risk of breast cancer . There iSociopsychological factors including social exposure to NCD, perceived stigma by others, insured status, worry, distress, personal control, conscientiousness, emotional stability, optimistic bias, belief in the genetic cause of NCD, perceived oneself as overweight, believing overweight is a personal health problem, perceived risk of HPV exposure and perception of own health status may also play a role in NCD risk perception. The association between social exposure to NCD and personality traits  with risk perception of NCD is well supported by the Health Belief Model which suggested that prior contact of certain disease and personality can influence an individual’s risk perception of the disease .The relationship between perception of stigmatized by other with risk perception of NCDs may be explained by the greater awareness of chronic disease among those who perceived stigma from others . StudiesEmotional status such as worry and distress have been found to be associated with risk perception of NCDs. In view of these findings, future health interventions need to address NCD-related worry and distress to motivate health-related behaviours. Greater personal control was associated with higher risk perception of DM. However, this finding is contrary to the findings by Kim et al, which may be attributed to differences in the nature and composition of study sample . Based oLiterature also consistently reported association between perception regarding own health with risk perception of NCDs. The greater risk perception of DM among those who perceived themselves as overweight is possibly due to the higher health literacy, making them understand and aware that being overweight increases their risk for DM . The lowStructural factors associated with NCD risk perception included several knowledge-related factors, namely knowledge of NCD, history of genetic counselling, either discussed with or informed by healthcare professional about risk of NCD, received recommendation for NCD screening by healthcare professional and discussion on NCD risk in the family. In general, it is not surprising that, those who were more knowledgeable about certain NCD had high risk perception of NCD. Furthermore the Health Belief Model also identified knowledge as a factor that can influence risk perception towards certain disease .As with any research, this systematic review is not without limitations. Most of the included studies were of cross-sectional design, and therefore the quality of evidence was considered to be low and exhibit a high risk of bias. Another limitation relates to the measurement of risk perception of NCDs. Many studies assessed risk perception of NCDs using only a single item , 58, 82,The role of publication bias within this systematic review should be acknowledged as we did not include grey literature. We acknowledge the value of grey literature in systematic reviews. However, this systematic review did not include grey literature, in part due to the difficulty in searching and retrieving these documents, as well as time constraints. Another limitation is that we did not consult experts for source recommendations. Additionally, language bias must be considered as we only included English-language publications. Nevertheless, our search strategy has resulted in literature sourced from various countries where English is not the first language . One of the strengths of this review is that we have included both questionnaires that explicitly assessed risk perception of NCDs, as well as questionnaires that included at least five items related to risk perception of NCDs. This process increased the chances of identifying items related to risk perception of NCDs for future research. Additionally, to the best of our knowledge, this is the first systematic review synthetizing research evidence on risk perception of several major NCDs, highlighting the available questionnaire assessing NCD risk perception and the correlates of perceived risk of acquiring NCDs.This systematic review may serve as a guideline for researchers who intend to measure risk perception of NCDs, as the results provide an overview of the components included in those questionnaires, which can provide guidance in the choice of questionnaire. Nevertheless, further evidence is needed to support the validity of these questionnaires. In view of this limitation, researchers should pay attention in assessing validity in future questionnaire development work.This systematic review also highlighted several key factors related to the risk perception of NCDs. All these key factors deserve further exploration in longitudinal and experimental studies. Based on the synthesized evidence, health interventions addressing risk perception of NCDs should not only focus on facts about personal factors , but also on the sociopsychological and structural factors that may influence the risk perception of NCDs particularly among those at risk of NCDs.S1 Appendix(DOCX)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.S1 Table(XLSX)Click here for additional data file.