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The commercial determinants of health (CDoH) are attracting increased interest and are of great importance when discussing how trade affects health. Through a citation analysis of recent foundational CDoH documents (a Lancet paper series and an Oxford University textbook), we find that fully 71% of all citations reference the health sciences. The health sciences may be well suited to documenting the specific pathways of how commercial (by)products and practices harm human health. However, to operationalize upstream solutions for mitigating these harms, our citation analysis suggests that the field can engage political scientists, economists, sociologists, the trade law and business, as well as advocates in civil society and journalism, more so than it currently does. With CDoH explicitly referring to the interaction between commerce and health, CDoH researchers might be uniquely positioned to get health on the agenda of others, which requires that CDoH methods, datasets, evidence reviews, and proposed interventions are drawn from the widest possible range of sources. [ABSTRACT FROM AUTHOR]

Over the years, the Bio-Ontologies SIG at ISMB has provided a forum for discussion of the latest and most innovative research in the application of ontologies and more generally the organisation, presentation and dissemination of knowledge in biomedicine and the life sciences. The ten papers selected for this supplement are extended versions of the original papers presented at the 2010 SIG. The papers span a wide range of topics including practical solutions for data and knowledge integration for translational medicine, hypothesis based querying , understanding kidney and urinary pathways, mining the pharmacogenomics literature; theoretical research into the orthogonality of biomedical ontologies, the representation of diseases, the representation of research hypotheses, the combination of ontologies and natural language processing for an annotation framework, the generation of textual definitions, and the discovery of gene interaction networks. [ABSTRACT FROM AUTHOR]

Over the 15 years, the Bio-Ontologies SIG at ISMB has provided a forum for discussion of the latest and most innovative research in the bio-ontologies development, its applications to biomedicine and more generally the organisation, presentation and dissemination of knowledge in biomedicine and the life sciences. The seven papers and the commentary selected for this supplement span a wide range of topics including: web-based querying over multiple ontologies, integration of data, annotating patent records, NCBO Web services, ontology developments for probabilistic reasoning and for physiological processes, and analysis of the progress of annotation and structural GO changes. [ABSTRACT FROM AUTHOR]

Over the 14 years, the Bio-Ontologies SIG at ISMB has provided a forum for discussion of the latest and most innovative research in the bio-ontologies development, its applications to biomedicine and more generally the organisation, presentation and dissemination of knowledge in biomedicine and the life sciences. The seven papers selected for this supplement span a wide range of topics including: web-based querying over multiple ontologies, integration of data from wikis, innovative methods of annotating and mining electronic health records, advances in annotating web documents and biomedical literature, quality control of ontology alignments, and the ontology support for predictive models about toxicity and open access to the toxicity data. [ABSTRACT FROM AUTHOR]

Background: Across the care economy there are major shortages in the health and care workforce, as well as high rates of attrition and ill-defined career pathways. The aim of this study was to evaluate current evidence regarding methods to improve care worker recruitment, retention, safety, and education, for the professional care workforce. Methods: A rapid review of comparative interventions designed to recruit, retain, educate and care for the professional workforce in the following sectors: disability, aged care, health, mental health, family and youth services, and early childhood education and care was conducted. Embase and MEDLINE databases were searched, and studies published between January 2015 and November 2022 were included. We used the Quality Assessment tool for Quantitative Studies and the PEDro tools to evaluate study quality. Results: 5594 articles were initially screened and after applying the inclusion and exclusion criteria, 30 studies were included in the rapid review. Studies most frequently reported on the professional nursing, medical and allied health workforces. Some studies focused on the single domain of care worker education (n = 11) while most focused on multiple domains that combined education with recruitment strategies, retention strategies or a focus on worker safety. Study quality was comparatively low with a median PEDro score of 5/10, and 77% received a weak rating on the Quality Assessment tool for Quantitative Studies. Four new workforce strategies emerged; early career rural recruitment supports rural retention; workload management is essential for workforce well-being; learning must be contextually relevant; and there is a need to differentiate recruitment, retention, and education strategies for different professional health and care workforce categories as needs vary. Conclusions: Given the critical importance of recruiting and retaining a strong health and care workforce, there is an immediate need to develop a cohesive strategy to address workforce shortfalls. This paper presents initial evidence on different interventions to address this need, and to inform care workforce recruitment and retention. Rapid Review registration PROSPERO 2022 CRD42022371721 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022371721 [ABSTRACT FROM AUTHOR]

Background: Maintaining a health professional workforce in rural and remote areas poses a significant challenge internationally. A range of recruitment and retention strategies have had varying success and these are  generally developed from the collective experience of all health professions, rather than targeted to professional groups with differing educational and support contexts. This review explores, compares and synthesises the evidence examining the experience of early career rural and remote allied health professionals and doctors to better understand both the profession specific, and common factors that influence their experience.Methods: Qualitative studies that include early career allied health professionals' or doctors' experiences of working in rural or remote areas and the personal and professional factors that impact on this experience were considered. A systematic search was completed across five databases and three grey literature repositories to identify published and unpublished studies. Studies published since 2000 in English were considered. Studies were screened for inclusion and critically appraised by two independent reviewers. Data was extracted and assigned a level of credibility. Data synthesis adhered to the JBI meta-aggregative approach.Results: Of the 1408 identified articles, 30 papers were eligible for inclusion, with one rated as low in quality and all others moderate or high quality. A total of 23 categories, 334 findings and illustrations were aggregated into three synthesised findings for both professional groups including: making a difference through professional and organisational factors, working in rural areas can offer unique and rewarding opportunities for early career allied health professionals and doctors, and personal and community influences make a difference. A rich dataset was obtained and findings illustrate similarities including the need to consider personal factors, and differences, including discipline specific supervision for allied health professionals and local supervision for doctors.Conclusions: Strategies to enhance the experience of both allied health professionals and doctors in rural and remote areas include enabling career paths through structured training programs, hands on learning opportunities, quality supervision and community immersion.Systematic Review Registration Number: PROSPERO CRD42021223187. [ABSTRACT FROM AUTHOR]

Background: The pharmacoepidemiology of the long-term benefits and harms of medicines in pregnancy and breastfeeding has received little attention. The impact of maternal medicines on children is increasingly recognised as a source of avoidable harm. The focus of attention has expanded from congenital anomalies to include less visible, but equally important, outcomes, including cognition, neurodevelopmental disorders, educational performance, and childhood ill-health. Breastfeeding, whether as a source of medicine exposure, a mitigator of adverse effects or as an outcome, has been all but ignored in pharmacoepidemiology and pharmacovigilance: a significant 'blind spot'. Whole-population data on breastfeeding: why we need them Optimal child development and maternal health necessitate breastfeeding, yet little information exists to guide families regarding the safety of medicine use during lactation. Breastfeeding initiation or success may be altered by medicine use, and breastfeeding may obscure the true relationship between medicine exposure during pregnancy and developmental outcomes. Absent or poorly standardised recording of breastfeeding in most population databases hampers analysis and understanding of the complex relationships between medicine, pregnancy, breastfeeding and infant and maternal health. The purpose of this paper is to present the arguments for breastfeeding to be included alongside medicine use and neurodevelopmental outcomes in whole-population database investigations of the harms and benefits of medicines during pregnancy, the puerperium and postnatal period. We review: 1) the current situation, 2) how these complexities might be accommodated in pharmacoepidemiological models, using antidepressants and antiepileptics as examples; 3) the challenges in obtaining comprehensive data. Conclusions: The scarcity of whole-population data and the complexities of the inter-relationships between breastfeeding, medicines, co-exposures and infant outcomes are significant barriers to full characterisation of the benefits and harms of medicines during pregnancy and breastfeeding. This makes it difficult to answer the questions: 'is it safe to breastfeed whilst taking this medicine', and 'will this medicine interfere with breastfeeding and/ or infants' development'? [ABSTRACT FROM AUTHOR]

Background: Maintaining a health professional workforce in rural and remote areas poses a significant challenge internationally. A range of recruitment and retention strategies have had varying success and these are generally developed from the collective experience of all health professions, rather than targeted to professional groups with differing educational and support contexts. This review explores, compares and synthesises the evidence examining the experience of early career rural and remote allied health professionals and doctors to better understand both the profession specific, and common factors that influence their experience. Methods: Qualitative studies that include early career allied health professionals' or doctors' experiences of working in rural or remote areas and the personal and professional factors that impact on this experience were considered. A systematic search was completed across five databases and three grey literature repositories to identify published and unpublished studies. Studies published since 2000 in English were considered. Studies were screened for inclusion and critically appraised by two independent reviewers. Data was extracted and assigned a level of credibility. Data synthesis adhered to the JBI meta-aggregative approach. Results: Of the 1408 identified articles, 30 papers were eligible for inclusion, with one rated as low in quality and all others moderate or high quality. A total of 23 categories, 334 findings and illustrations were aggregated into three synthesised findings for both professional groups including: making a difference through professional and organisational factors, working in rural areas can offer unique and rewarding opportunities for early career allied health professionals and doctors, and personal and community influences make a difference. A rich dataset was obtained and findings illustrate similarities including the need to consider personal factors, and differences, including discipline specific supervision for allied health professionals and local supervision for doctors. Conclusions: Strategies to enhance the experience of both allied health professionals and doctors in rural and remote areas include enabling career paths through structured training programs, hands on learning opportunities, quality supervision and community immersion. Systematic review registration number: PROSPERO CRD42021223187. [ABSTRACT FROM AUTHOR]

Background: The objective of this paper is to outline and compare the regulation of paid healthcare professions and associated support workers in international context, bringing out the lessons to be learned as appropriate. Modern neo-liberal societies have sought to enhance healthcare through greater professional regulation, albeit in different ways and at variable pace. This general trend is illustrated with reference to medicine in the UK. However, although such reforms have helpfully cascaded to other health professions, government policy in high-income countries has not yet adequately regulated the interrelated group of non-professionalised health support workers who form the largest and least recognised part of the workforce. Nonetheless, in low- and middle-income (LMIC) countries-aside from the greater need for regulation of health professions-there is even more of an imperative to regulate the disparate, largely invisible support workforce.Methods: With reference to existing studies of the medical and wider health professions in the UK and selected other higher income societies, the importance of health professional regulation to the public is underlined in the Global North. The larger gap in the regulation of support workers in modern neo-liberal countries is also emphasised on a similar basis, with an increasingly ageing population and advances in healthcare. It is argued from the very limited patchwork of secondary literature, though, that policy-makers may want to focus even more on enhancing regulation of both the professional and non-professional workforce in LMIC societies centred mainly in the Global South, drawing on lessons from the Global North.Results/conclusions: Efforts to reform health professional regulatory approaches in more economically developed countries, while needing refinement, are likely to have had a positive effect. However, even in these societies there are still substantial shortfalls in the regulation of health support workers. There are even larger gaps in LMICs where there are fewer health professional staff and a greater dependence on support workers. With higher rates of morbidity and mortality, there is much more scope here for reforming health regulation in the public interest to extend standards and mitigate risk, following the pattern for healthcare professions in the Global North. [ABSTRACT FROM AUTHOR]

Background: Attacks on health care in armed conflict, including those on health workers, facilities, patients and transports, represent serious violations of human rights and international humanitarian law. Information about these incidents and their characteristics are available in myriad forms: as published research or commentary, investigative reports, and within online data collection initiatives. We review the research on attacks on health to understand what data they rely on, what subjects they cover and what gaps exist in order to develop a research agenda going forward. Methods and findings: This study utilizes a systematic review of peer-reviewed to identify and understand relevant data about attacks on health in situations of conflict. We identified 1479 papers published before January 1, 2020 using systematic and hand-searching and chose 45 articles for review that matched our inclusion criteria. We extracted data on geographical and conflict foci, methodology, objectives and major themes. Among the included articles, 26 focused on assessment of evidence of attacks, 15 on analyzing their impacts, three on the legal and human rights principles and one on the methods of documentation. We analyzed article data to answer questions about where and when attacks occur and are investigated, what types of attacks occur, who is perpetrating them, and how and why they are studied. We synthesized cross-cutting themes on the impacts of these attacks, mitigation efforts, and gaps in existing data. Conclusion: Recognizing limitations in the review, we find there have been comparatively few studies over the past four decades but the literature is growing. To deepen the discussions of the scope of attacks and to enable cross-context comparisons, documentation of attacks on health must be enhanced to make the data more consistent, more thorough, more accessible, include diverse perspectives, and clarify taxonomy. As the research on attacks on health expands, practical questions on how the data is utilized for advocacy, protection and accountability must be prioritized. [ABSTRACT FROM AUTHOR]

Background: The role of Artificial intelligence (AI) which is defined as the ability of computers to perform tasks that normally require human intelligence is constantly expanding. Medicine was slow to embrace AI. However, the role of AI in medicine is rapidly expanding and promises to revolutionize patient care in the coming years. In addition, it has the ability to democratize high level medical care and make it accessible to all parts of the world. Main text: Among specialties of medicine, some like radiology were relatively quick to adopt AI whereas others especially pathology (and surgical pathology in particular) are only just beginning to utilize AI. AI promises to play a major role in accurate diagnosis, prognosis and treatment of cancers. In this paper, the general principles of AI are defined first followed by a detailed discussion of its current role in medicine. In the second half of this comprehensive review, the current and future role of AI in surgical pathology is discussed in detail including an account of the practical difficulties involved and the fear of pathologists of being replaced by computer algorithms. A number of recent studies which demonstrate the usefulness of AI in the practice of surgical pathology are highlighted. Conclusion: AI has the potential to transform the practice of surgical pathology by ensuring rapid and accurate results and enabling pathologists to focus on higher level diagnostic and consultative tasks such as integrating molecular, morphologic and clinical information to make accurate diagnosis in difficult cases, determine prognosis objectively and in this way contribute to personalized care. [ABSTRACT FROM AUTHOR]

Background: Creation and use of ontologies has become a mainstream activity in many disciplines, in particular, the biomedical domain. Ontology developers often disseminate information about these ontologies in peer-reviewed ontology description reports. There appears to be, however, a high degree of variability in the content of these reports. Often, important details are omitted such that it is difficult to gain a sufficient understanding of the ontology, its content and method of creation. Results: We propose the Minimum Information for Reporting an Ontology (MIRO) guidelines as a means to facilitate a higher degree of completeness and consistency between ontology documentation, including published papers, and ultimately a higher standard of report quality. A draft of the MIRO guidelines was circulated for public comment in the form of a questionnaire, and we subsequently collected 110 responses from ontology authors, developers, users and reviewers. We report on the feedback of this consultation, including comments on each guideline, and present our analysis on the relative importance of each MIRO information item. These results were used to update the MIRO guidelines, mainly by providing more detailed operational definitions of the individual items and assigning degrees of importance. Based on our revised version of MIRO, we conducted a review of 15 recently published ontology description reports from three important journals in the Semantic Web and Biomedical domain and analysed them for compliance with the MIRO guidelines. We found that only 41.38% of the information items were covered by the majority of the papers (and deemed important by the survey respondents) and a large number of important items are not covered at all, like those related to testing and versioning policies. Conclusions: We believe that the community-reviewed MIRO guidelines can contribute to improving significantly the quality of ontology description reports and other documentation, in particular by increasing consistent reporting of important ontology features that are otherwise often neglected. [ABSTRACT FROM AUTHOR]

Background: Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. Results: This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network. Supplementary data is available online and our code in Macaulay2 and Matlab are available via http://www.ms.uky.edu/~dmu228/ControlAlg. Conclusions: This paper presents a novel method for the identification of intervention targets in Boolean network models. The results in this paper show that the proposed methods are useful and efficient for moderately large networks. [ABSTRACT FROM AUTHOR]

Background: There is growing enthusiasm for the application of machine learning (ML) and artificial intelligence (AI) techniques to clinical research and practice. However, instructions on how to develop robust high-quality ML and AI in medicine are scarce. In this paper, we provide a practical example of techniques that facilitate the development of high-quality ML systems including data pre-processing, hyperparameter tuning, and model comparison using open-source software and data.Methods: We used open-source software and a publicly available dataset to train and validate multiple ML models to classify breast masses into benign or malignant using mammography image features and patient age. We compared algorithm predictions to the ground truth of histopathologic evaluation. We provide step-by-step instructions with accompanying code lines.Findings: Performance of the five algorithms at classifying breast masses as benign or malignant based on mammography image features and patient age was statistically equivalent (P > 0.05). Area under the receiver operating characteristics curve (AUROC) for the logistic regression with elastic net penalty was 0.89 (95% CI 0.85 - 0.94), for the Extreme Gradient Boosting Tree 0.88 (95% CI 0.83 - 0.93), for the Multivariate Adaptive Regression Spline algorithm 0.88 (95% CI 0.83 - 0.93), for the Support Vector Machine 0.89 (95% CI 0.84 - 0.93), and for the neural network 0.89 (95% CI 0.84 - 0.93).Interpretation: Our paper allows clinicians and medical researchers who are interested in using ML algorithms to understand and recreate the elements of a comprehensive ML analysis. Following our instructions may help to improve model generalizability and reproducibility in medical ML studies. [ABSTRACT FROM AUTHOR]

Background: Hospital governance is broadening its orientation from cost and production controls towards 'improving performance on clinical outcomes'. Given this new focus one might assume that doctors are drawn into hospital management across OECD countries. Hospital performance in terms of patient health, quality of care and efficiency outcomes is supposed to benefit from their involvement. However, international comparative evidence supporting this idea is limited. Just a few studies indicate that there may be a positive relationship between medical doctors being part of hospital boards, and overall hospital performance. More importantly, the assumed relationship between these so-called doctor managers and hospital performance has remained a 'black-box' thus far. However, there is an increasing literature on the implementation of quality management systems in hospitals and their relation with improved performance. It seems therefore fair to assume that the relation between the involvement of doctors in hospital management and improved hospital performance is partly mediated via quality management systems. The threefold aim of this paper is to 1) perform a quick scan of the current situation with regard to doctor managers in hospital management in 19 OECD countries, 2) explore the phenomenon of doctor managers in depth in 7 OECD countries, and 3) investigate whether doctor involvement in hospital management is associated with more advanced implementation of quality management systems.Methods: This study draws both on a quick scan amongst country coordinators in OECD's Health Care Quality Indicator program, and on the DUQuE project which focused on the implementation of quality management systems in European hospitals.Results: This paper reports two main findings. First, medical doctors fulfil a broad scope of managerial roles at departmental and hospital level but only partly accompanied by formal decision making responsibilities. Second, doctor managers having more formal decision making responsibilities in strategic hospital management areas is positively associated with the level of implementation of quality management systems.Conclusions: Our findings suggest that doctors are increasingly involved in hospital management in OECD countries, and that this may lead to better implemented quality management systems, when doctors take up managerial roles and are involved in strategic management decision making. [ABSTRACT FROM AUTHOR]

Background: "Neglected Tropical Diseases" (NTDs) affect millions of people in Africa, Asia and South America. The two primary ways of strategic interventions are "preventive chemotherapy and transmission control" (PCT), and "innovative and intensified disease management" (IDM). In the last 5 years, phenomenal progress has been achieved. However, it is crucial to intensify research effort into NTDs, because of the emerging drug resistance. According to the World Health Organization (WHO), the term NTDs covers 17 diseases, namely buruli ulcer, Chagas disease, dengue, dracunculiasis, echinococcosis, trematodiasis, human African trypanosomiasis, leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, rabies, schistosomiasis, soil-transmitted helminthes, taeniasis, trachoma, and yaws. The aim of this study is to map out research and development (R&D) landscape through patent analysis of these identified NTDs. To achieve this, analysis and evaluation have been conducted on patenting trends, current legal status of patent families, priority countries by earliest priority years and their assignee types, technological fields of patent families over time, and original and current patent assignees.Main Body: Patent families were extracted from Patseer, an international database of patents from over 100 patent issuing authorities worldwide. Evaluation of the patents was carried out using the combination of different search terms related to each identified NTD. In this paper, a total number of 12,350 patent families were analyzed. The main countries with sources of inventions were identified to be the United States (US) and China. The main technological fields covered by NTDs patent landscape are pharmaceuticals, biotechnology, organic fine chemistry, analysis of biological materials, basic materials chemistry, and medical technology. Governmental institutions and universities are the primary original assignees. Among the NTDs, leishmaniasis, dengue, and rabies received the highest number of patent families, while human African trypanosomiasis (sleeping sickness), taeniasis, and dracunciliasis received the least. The overall trend of patent families shows an increase between 1985 and 2008, and followed by at least 6 years of stagnation.Conclusion: The filing pattern of patent families analyzed undoubtedly reveals slow progress on research and development of NTDs. Involving new players, such as non-governmental organizations may help to mitigate and reduce the burden of NTDs. [ABSTRACT FROM AUTHOR]

Background: Debate is intensifying about how to assess the full range of impacts from medical research. Complexity increases when assessing the diverse funding streams of funders such as Asthma UK, a charitable patient organisation supporting medical research to benefit people with asthma. This paper aims to describe the various impacts identified from a range of Asthma UK research, and explore how Asthma UK utilised the characteristics of successful funding approaches to inform future research strategies. Methods: We adapted the Payback Framework, using it both in a survey and to help structure interviews, documentary analysis, and case studies. We sent surveys to 153 lead researchers of projects, plus 10 past research fellows, and also conducted 14 detailed case studies. These covered nine projects and two fellowships, in addition to the innovative case studies on the professorial chairs (funded since 1988) and the MRC-Asthma UK Centre in Allergic Mechanisms of Asthma (the 'Centre') which together facilitated a comprehensive analysis of the whole funding portfolio. We organised each case study to capture whatever academic and wider societal impacts (or payback) might have arisen given the diverse timescales, size of funding involved, and extent to which Asthma UK funding contributed to the impacts. Results: Projects recorded an average of four peer-reviewed journal articles. Together the chairs reported over 500 papers. All streams of funding attracted follow-on funding. Each of the various categories of societal impacts arose from only a minority of individual projects and fellowships. Some of the research portfolio is influencing asthmarelated clinical guidelines, and some contributing to product development. The latter includes potentially major breakthroughs in asthma therapies (in immunotherapy, and new inhaled drugs) trialled by university spin-out companies. Such research-informed guidelines and medicines can, in turn, contribute to health improvements. The role of the chairs and the pioneering collaborative Centre is shown as being particularly important. Conclusions: We systematically demonstrate that all types of Asthma UK's research funding assessed are making impacts at different levels, but the main societal impacts from projects and fellowships come from a minority of those funded. Asthma UK used the study's findings, especially in relation to the Centre, to inform research funding strategies to promote the achievement of impact. [ABSTRACT FROM AUTHOR]

Background: In recent years an increasing number of public investments and policy changes have been made to improve the availability, affordability and quality of medicines available to consumers in developing countries, including anti-malarials. It is important to monitor the extent to which these interventions are successful in achieving their aims using quantitative data on the supply side of the market. There are a number of challenges related to studying supply, including outlet sampling, gaining provider cooperation and collecting accurate data on medicines. This paper provides guidance on key steps to address these issues when conducting a medicine outlet survey in a developing country context. While the basic principles of good survey design and implementation are important for all surveys, there are a set of specific issues that should be considered when conducting a medicine outlet survey. Methods: This paper draws on the authors' experience of designing and implementing outlet surveys, including the lessons learnt from ACTwatch outlet surveys on anti-malarial retail supply, and other key studies in the field. Key lessons and points of debate are distilled around the following areas: selecting a sample of outlets; techniques for collecting and analysing data on medicine availability, price and sales volumes; and methods for ensuring high quality data in general Results and conclusions: The authors first consider the inclusion criteria for outlets, contrasting comprehensive versus more focused approaches. Methods for developing a reliable sampling frame of outlets are then presented, including use of existing lists, key informants and an outlet census. Specific issues in the collection of data on medicine prices and sales volumes are discussed; and approaches for generating comparable price and sales volume data across products using the adult equivalent treatment dose (AETD) are explored. The paper concludes with advice on practical considerations, including questionnaire design, field worker training, and data collection. Survey materials developed by ACTwatch for investigating anti-malarial markets in sub-Saharan Africa and Asia provide a helpful resource for future studies in this area. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials (RCTs) form the foundational background of modern medical practice. They are considered the highest quality of evidence, and their results help inform decisions concerning drug development and use, preventive therapies, and screening programs. However, the inputs that justify an RCT to be conducted have not been studied.Methods: We reviewed the MEDLINE and EMBASE databases across six specialties (Ophthalmology, Otorhinolaryngology (ENT), General Surgery, Psychiatry, Obstetrics-Gynecology (OB-GYN), and Internal Medicine) and randomly chose 25 RCTs from each specialty except for Otorhinolaryngology (20 studies) and Internal Medicine (28 studies). For each RCT, we recorded information relating to the justification for conducting RCTs such as average study size cited, number of studies cited, and types of studies cited. The justification varied widely both within and between specialties.Results: For Ophthalmology and OB-GYN, the average study sizes cited were around 1100 patients, whereas they were around 500 patients for Psychiatry and General Surgery. Between specialties, the average number of studies cited ranged from around 4.5 for ENT to around 10 for Ophthalmology, but the standard deviations were large, indicating that there was even more discrepancy within each specialty. When standardizing by the sample size of the RCT, some of the discrepancies between and within specialties can be explained, but not all. On average, Ophthalmology papers cited review articles the most (2.96 studies per RCT) compared to less than 1.5 studies per RCT for all other specialties.Conclusions: The justifications for RCTs vary widely both within and between specialties, and the justification for conducting RCTs is not standardized. [ABSTRACT FROM AUTHOR]

Background: There are interwoven personal, professional and organisational relationships to be navigated in maternity in all regions. In rural regions relationships are integral to safe maternity care. Yet there is a paucity of research on how relationships influence safety and nurture satisfying experiences for rural maternity care providers and mothers and families in these regions. This paper draws attention to how these relationships matter. Methods: This research is informed by hermeneutic phenomenology drawing on Heidegger and Gadamer. Thirteen participants were recruited via purposeful sampling and asked to share their experiences of rural maternity care in recorded unstructured in-depth interviews. Participants were women and health care providers living and working in rural regions. Recordings were transcribed and data interpretively analysed until a plausible and trustworthy thematic pattern emerged. Results: Throughout the data the relational nature of rural living surfaced as an interweaving tapestry of connectivity. Relationships in rural maternity are revealed in myriad ways: for some optimal relationships, for others feeling isolated, living with discord and professional disharmony. Professional misunderstandings undermine relationships. Rural maternity can become unsustainable and unsettling when relationships break down leading to unsafeness. Conclusions: This study reveals how relationships are an important and vital aspect to the lived-experience of rural maternity care. Relationships are founded on mutual understanding and attuned to trust matter. These relationships are forged over time and keep childbirth safe and enable maternity care providers to work sustainably. Yet hidden unspoken pre-understandings of individuals and groups build tension in relationships leading to discord. Trust builds healthy rural communities of practice within which everyone can flourish, feel accepted, supported and safe. This is facilitated by collaborative learning activities and open respectful communication founded on what matters most (safe positive childbirth) whilst appreciating and acknowledging professional and personal differences. [ABSTRACT FROM AUTHOR]

Background: Redundant hierarchical relations refer to such patterns as two paths from one concept to another, one with length one (direct) and the other with length greater than one (indirect). Each redundant relation represents a possibly unintended defect that needs to be corrected in the ontology quality assurance process. Detecting and eliminating redundant relations would help improve the results of all methods relying on the relevant ontological systems as knowledge source, such as the computation of semantic distance between concepts and for ontology matching and alignment. Results: This paper introduces a novel and scalable approach, called FEDRR - Fast, Exhaustive Detection of Redundant Relations - for quality assurance work during ontological evolution. FEDRR combines the algorithm ideas of Dynamic Programming with Topological Sort, for exhaustive mining of all redundant hierarchical relations in ontological hierarchies, in O(c · ∣V∣ + ∣E∣) time, where ∣V∣ is the number of concepts, ∣E∣ is the number of the relations, and c is a constant in practice. Using FEDRR, we performed exhaustive search of all redundant is-a relations in two of the largest ontological systems in biomedicine: SNOMED CT and Gene Ontology (GO). 372 and 1609 redundant is-a relations were found in the 2015-09-01 version of SNOMED CT and 2015-05-01 version of GO, respectively. We have also performed FEDRR on over 190 source vocabularies in the UMLS - a large integrated repository of biomedical ontologies, and identified six sources containing redundant is-a relations. Randomly generated ontologies have also been used to further validate the efficiency of FEDRR. Conclusions: FEDRR provides a generally applicable, effective tool for systematic detecting redundant relations in large ontological systems for quality improvement. [ABSTRACT FROM AUTHOR]

Background: Gout is the most common form of inflammatory arthritis. It is associated with substantial co-morbidity and often managed in primary care. A greater understanding of the communication process between patients and healthcare professionals provides one way of improving the management of this condition. This paper describes communication about gout medicines and treatment between patients and primary care health professionals during routine consultations. Methods: Video-recordings of 31 individual healthcare consultations between patients and a range of primary care practitioners (general practitioners, practice nurses, podiatrists, dietitians) from an archived database were reviewed. Consultations that encompassed any discussion about gout medicines and treatment were included (n = 27) and were not solely restricted to those where gout was the presenting complaint. Themes were derived from an inductive qualitative analysis, from clinical and linguistic perspectives, based on the conversation between patients and practitioners about medicines and visual observation of these interactions. Results: A number of factors were identified that had the potential to impact on the optimal management of gout in primary care. These included level of patient knowledge, patient attitudes to medicines, and the attributes of practitioner communication with patients. The latter related to the style of delivery and content of the information provided, and the ability of practitioners to make use of opportunities that arose to discuss these issues. Conclusions: Patients with gout communicate at varying levels of complexity with a diverse range of primary care healthcare professionals about the treatment of their condition. It is important that all practitioners engaging with gout patients in this setting are knowledgeable about the current management of gout, provide clear, consistent and accurate messages, remain aware that these messages may need repeating over time, and are supportive of patients’ medicine-taking preferences. [ABSTRACT FROM AUTHOR]

Background: The overall goal of the BioCreative Workshops is to promote the development of text mining and text processing tools which are useful to the communities of researchers and database curators in the biological sciences. To this end BioCreative I was held in 2004, BioCreative II in 2007, and BioCreative II.5 in 2009. Each of these workshops involved humanly annotated test data for several basic tasks in text mining applied to the biomedical literature. Participants in the workshops were invited to compete in the tasks by constructing software systems to perform the tasks automatically and were given scores based on their performance. The results of these workshops have benefited the community in several ways. They have 1) provided evidence for the most effective methods currently available to solve specific problems; 2) revealed the current state of the art for performance on those problems; 3) and provided gold standard data and results on that data by which future advances can be gauged. This special issue contains overview papers for the three tasks of BioCreative III. Results: The BioCreative III Workshop was held in September of 2010 and continued the tradition of a challenge evaluation on several tasks judged basic to effective text mining in biology, including a gene normalization (GN) task and two protein-protein interaction (PPI) tasks. In total the Workshop involved the work of twenty-three teams. Thirteen teams participated in the GN task which required the assignment of EntrezGene IDs to all named genes in full text papers without any species information being provided to a system. Ten teams participated in the PPI article classification task (ACT) requiring a system to classify and rank a PubMed® record as belonging to an article either having or not having "PPI relevant" information. Eight teams participated in the PPI interaction method task (IMT) where systems were given full text documents and were required to extract the experimental methods used to establish PPIs and a text segment supporting each such method. Gold standard data was compiled for each of these tasks and participants competed in developing systems to perform the tasks automatically. BioCreative III also introduced a new interactive task (IAT), run as a demonstration task. The goal was to develop an interactive system to facilitate a user's annotation of the unique database identifiers for all the genes appearing in an article. This task included ranking genes by importance (based preferably on the amount of described experimental information regarding genes). There was also an optional task to assist the user in finding the most relevant articles about a given gene. For BioCreative III, a user advisory group (UAG) was assembled and played an important role 1) in producing some of the gold standard annotations for the GN task, 2) in critiquing IAT systems,. 3) in providing guidance for a future more rigorous evaluation of IAT systems. Six teams participated in the IAT demonstration task and received feedback on their systems from the UAG group. Besides innovations in the GN and PPI tasks making them more realistic and practical and the introduction of the IAT task, discussions were begun on community data standards to promote interoperability and on user requirements and evaluation metrics to address utility and usability of systems. Conclusions: In this paper we give a brief history of the BioCreative Workshops and how they relate to other text mining competitions in biology. This is followed by a synopsis of the three tasks GN, PPI, and IAT in BioCreative III with figures for best participant performance on the GN and PPI tasks. These results are discussed and compared with results from previous BioCreative Workshops and we conclude that the best performing systems for GN, PPIACT and PPI-IMT in realistic settings are not sufficient for fully automatic use. This provides evidence for the importance of interactive systems and we present our vision of how best to construct an interactive system for a GN or PPI like task in the remainder of the paper. [ABSTRACT FROM AUTHOR]

Background: This paper presents a novel approach to the problem of hedge detection, which involves identifying so-called hedge cues for labeling sentences as certain or uncertain. This is the classification problem for Task 1 of the CoNLL-2010 Shared Task, which focuses on hedging in the biomedical domain. We here propose to view hedge detection as a simple disambiguation problem, restricted to words that have previously been observed as hedge cues. As the feature space for the classifier is still very large, we also perform experiments with dimensionality reduction using the method of random indexing. Results: The SVM-based classifiers developed in this paper achieves the best published results so far for sentence-level uncertainty prediction on the CoNLL-2010 Shared Task test data. We also show that the technique of random indexing can be successfully applied for reducing the dimensionality of the original feature space by several orders of magnitude, without sacrificing classifier performance. Conclusions: This paper introduces a simplified approach to detecting speculation or uncertainty in text, focusing on the biomedical domain. Evaluated at the sentence-level, our SVM-based classifiers achieve the best published results so far. We also show that the feature space can be aggressively compressed using random indexing while still maintaining comparable classifier performance. [ABSTRACT FROM AUTHOR]

Background: This paper provides a summary of a Keynote lecture delivered at the 2009 Australasian Podiatry Conference. The aim of the paper is to review recent research that has adopted dynamic cadaver and invasive kinematics research approaches to better understand foot and ankle kinematics during gait. It is not intended to systematically cover all literature related to foot and ankle kinematics (such as research using surface mounted markers). Since the paper is based on a keynote presentation its focuses on the authors own experiences and work in the main, drawing on the work of others where appropriate Methods: Two approaches to the problem of accessing and measuring the kinematics of individual anatomical structures in the foot have been taken, (i) static and dynamic cadaver models, and (ii) invasive in-vivo research. Cadaver models offer the advantage that there is complete access to all the tissues of the foot, but the cadaver must be manipulated and loaded in a manner which replicates how the foot would have performed when in-vivo. The key value of invasive in-vivo foot kinematics research is the validity of the description of foot kinematics, but the key difficulty is how generalisable this data is to the wider population. Results: Through these techniques a great deal has been learnt. We better understand the valuable contribution mid and forefoot joints make to foot biomechanics, and how the ankle and subtalar joints can have almost comparable roles. Variation between people in foot kinematics is high and normal. This includes variation in how specific joints move and how combinations of joints move. The foot continues to demonstrate its flexibility in enabling us to get from A to B via a large number of different kinematic solutions. Conclusion: Rather than continue to apply a poorly founded model of foot type whose basis is to make all feet meet criteria for the mechanical 'ideal' or 'normal' foot, we should embrace variation between feet and identify it as an opportunity to develop patient-specific clinical models of foot function. [ABSTRACT FROM AUTHOR]

Background: There is a health crisis in Turkmenistan similar to, but more severe than, in other Central Asian countries. This paper asks whether the health crisis in Turkmenistan is attributable to the consequences of the dictatorship under president Niyazov, who died in 2006. Methods: The basis for this paper was a series of semi-structured in-depth interviews with key informants complemented by an iterative search of internet sites, initially published as a report in April 2005, and subsequently updated with feedback on the report as well as a comprehensive search of secondary information sources and databases. Results: This paper describes in depth three areas in which the dictatorship in Turkmenistan had a negative impact on population health: the regime's policy of secrecy and denial, which sees the "solution" to health care problems in concealment rather than prevention; its complicity in the trafficking of drugs from Afghanistan; and the neglect of its health care system. Conclusion: The paper concludes that dictatorship has contributed to the health crisis facing Turkmenistan. One of the first tests of the new regime will be whether it can address this crisis. [ABSTRACT FROM AUTHOR]

Background: Viewed through the micro focus of an interpretive lens, medical anthropology remains mystified because interpretivist explanations seriously downplay the given context in which individual health seeking-behaviours occur. This paper draws upon both the interpretivist and political economy perspectives to reflect on the ethno medical practices within the Korean-Australian community in Sydney. Methods: We draw on research data collected between 1995 and 1997 for an earlier study of the use of biomedical and traditional medicine by Korean-Australians in Sydney. A total of 120 interviews were conducted with a range of participants, including biomedical doctors, traditional health professionals, Korean community leaders and Korean migrants representing a range of socio-economic backgrounds and migration patterns. Results and Discussion: First, the paper highlights the extent to which the social location of migrants in a host society alters or restructures their initial cultural practices they bring with them. Second, taking hanbang medicine in the Korean-Australian community as an illustrative case, the paper explores the transformation of the dominant biomedicine in Australia as a result of the influx of ethnomedicine in the era of global capitalism and global movement. Conclusion: In seeking to explain the popularity and supply of alternative health care, it is important to go beyond the culture of each kind of health care itself and to take into consideration the changes occurring at societal, national and global levels as well as consequential individual response to the changes. New social conditions influence the choice of health care methods, including herbal/alternative medicine, health foods and what are often called New Age therapies. [ABSTRACT FROM AUTHOR]

Background: Uganda introduced a multipronged intervention, the supervision, performance assessment, and recognition strategy (SPARS), to improve medicines management (MM) in public and not-for-profit health facilities. This paper, the first in a series, describes the SPARS intervention and reports on the MM situation in Uganda before SPARS (baseline). Methods: To build MM capacity at health facilities, health workers were trained as MM supervisors to visit health facilities, assess MM performance, and use the findings to provide support and standardize MM practices. Performance is assessed based on 25 MM indicators covering five domains: dispensing quality (7 indicators), prescribing quality (5), stock management (4), storage management (5) and ordering and reporting (4). From the end of 2010 to 2013, MM supervisors assessed baseline MM performance of 1384 government (85 %) and private not-for-profit facilities at all levels of care in about half of Uganda's districts. Results: The overall MM baseline median score was 10.3 out of a maximum of 25 with inter-quartile range (IQR) of 8.7-11. 7. Facility domain scores (out of a maximum of 5) were as follows: storage management, median score of 2.9 (IQR 2.3-3.4); stock management 2.3 (IQR 2.0-2.8), ordering and reporting 2.2 (IQR 1.3-2.5), and dispensing quality 2.1 (IQR 1.7-2.7). Performance in prescribing quality was 0.9 (IQR 0.4-1.4). Significant regional differences were found: overall scores were highest in the Northern region (10.7; IQR 9.2-12.4) and lowest in the Eastern region (9.6; (IQR 7.8-11.2) (p<0.001). Overall scores did not differ by facility ownership; however, government facilities scored lower in dispensing and storage and higher in ordering and reporting. Hospitals scored higher overall and in domains other than prescribing and stock management. Districts classified a priori as having high capacity for implementing SPARS had higher scores at baseline compared to lower-capacity districts. Conclusion: Assessing and building national capacity in MM is needed in both private not-for-profit and government facilities at all levels of care. The indicator-based, multipronged SPARS assessment has been described here, while the strategy's impact has yet to be documented. [ABSTRACT FROM AUTHOR]

Background: Involving doctors in management has been intended as one of the strategies to spread organizational principles in healthcare settings. However, professionals often resist taking on relevant managerial responsibility, and the question concerning by which means to engage doctors in management in a manner that best fit the challenges encountered by different health systems remains open to debate.Methods: This paper analyzes the different forms of medical management experienced over time in the Italian NHS, a relevant "lab" to study the evolution of the involvement of doctors in management, and provides a framework for disentangling different dimensions of medical management.Results: We show how new means to engage frontline professionals in management spread, without deliberate planning, as a consequence of the innovations in service provision that are introduced to respond to the changes in the healthcare sector.Conclusions: This trend is promising because such means of performing medical management appear to be more easily compatible with professional logics; therefore, this could facilitate the engagement of a large proportion of professionals rather than the currently limited number of doctors who are "forced" or willing to take formal management roles. [ABSTRACT FROM AUTHOR]

Background: Since the early 1980s all European countries have given priority to reforming the management of health services. A distinctive feature of these reforms has also been the drive to co-opt professionals themselves into the management of services, taking on full time or part time (hybrid) management or leadership roles. However, although these trends are well documented in the literature, our understanding of the nature and impact of reforms and how they are re-shaping the relationship between medicine and management remains limited. Most studies have tended to be nationally specific, located within a single discipline and focused primarily on describing new management practices. This article serves as an Introduction to a special issue of BMC Health Services Research which seeks to address these concerns. It builds on the work of a European Union funded COST Action (ISO903) which ran between 2009 and 2013, focusing specifically on the changing relationship between medicine and management in a European context.Main Text: Prior to describing the contributions to the special issue, this Introduction sets the scene by exploring four main questions which have characterised much of the recent literature on medicine and management. First is the question of what we understand by the changing relationship between medicine and management and in particular which this means for the emergence of so called 'hybrid' clinical leader roles? A second question concerns the forces that have driven change, in particular those relating to the wider project of management reforms. Third, we raise questions of how medical professionals have responded to these changes and what factors have shaped their responses. Lastly we consider what some of the outcomes of greater medical involvement in management and leadership might be, both in terms of intended and unintended outcomes.Conclusions: The paper concludes by summarising the contributions to the special issue and highlighting the need to extend research in this area by focusing more on comparative dimensions of change. It is argued that future research would also benefit theoretically by drawing together insights from health policy and management literatures. [ABSTRACT FROM AUTHOR]

Background: Older youth in out-of-home care often live in restrictive settings and face psychiatric issues without sufficient family support. This paper reports on the development and piloting of a manualized treatment foster care program designed to step down older youth with high psychiatric needs from residential programs to treatment foster care homes. Methods: A team of researchers and agency partners set out to develop a treatment foster care model for older youth based on Multi-dimensional Treatment Foster Care (MTFC). After matching youth by mental health condition and determining for whom randomization would be allowed, 14 youth were randomized to treatment as usual or a treatment foster home intervention. Stakeholders were interviewed qualitatively at multiple time points. Quantitative measures assessed mental health symptoms, days in locked facilities, employment and educational outcomes. Results: Development efforts led to substantial variations from the MTFC model and a new model, Treatment Foster Care for Older Youth was piloted. Feasibility monitoring suggested that it was difficult, but possible to recruit and randomize youth from and out of residential homes and that foster parents could be recruited to serve them. Qualitative data pointed to some qualified clinical successes. Stakeholders viewed two team roles -- that of psychiatric nurse and skills coaches -- very highly. However, results also suggested that foster parents and some staff did not tolerate the intervention well and struggled to address the emotion dysregulation issues of the young people they served. Quantitative data demonstrated that the intervention was not keeping youth out of locked facilities. Conclusions: The intervention needed further refinement prior to a broader trial. Intervention development work continued until components were developed to help address emotion regulation problems among fostered youth. Psychiatric nurses and skills coaches who work with youth in community settings hold promise as important supports for older youth with psychiatric needs. [ABSTRACT FROM AUTHOR]

Introduction: This paper assesses both patients' perspectives on the differences in primary care quality between traditional Tibetan medicine (TTM) hospitals and western medicine (WM) hospitals and the efficacy of the government's investment in these two Prefecture-level primary care structures in Tibet. Method: A validated Tibetan version of the Primary Care Assessment Tool (PCAT-T) was used to collect data on 692 patients aged over 18 years old, who reported the sampling site was their regular source of health care. T-tests were performed to compare the separate and total primary care attributes between WM hospitals and TTM hospitals. Multiple linear regression analysis was conducted to examine the association of the health care setting with primary care attributes while controlling for socio-demographic, health service use and health status characteristics. Results: Compared to WM hospitals, the results showed that TTM hospitals had patients who were older (15.8 % versus 8.4 % over 60 years); with lower education levels (66.0 % versus 35.8 % with below junior high school ) and income levels (46.9 % versus 26.5 % with annual household income below 30,000RMB); more likely to be married (79.2 % versus 60.5 %); made less frequent health care visits; and had higher self-rated health status. Overall, patients assessed the primary care performance in TTM hospitals significantly higher (80.0) than WM hospitals (74.63). There were no differences in health care assessment by patient gender, age, income, education, marital status and occupation. Conclusions: TTM patients reported better primary care experiences than patients using WM hospitals, which validated the government's investment in traditional Tibetan medicine. [ABSTRACT FROM AUTHOR]

The European Orphan Medicinal Products (OMP) Regulation has successfully encouraged research to develop treatments for rare diseases resulting in the authorisation of new OMPs in Europe. While decisions on OMP designation and marketing authorisation are made at the European Union level, reimbursement decisions are made at the national level. OMP value and affordability are high priority issues for policymakers and decisions regarding their pricing and funding are highly complex. There is currently no European consensus on how OMP value should be assessed and inequalities of access to OMPs have previously been observed. Against this background, policy makers in many countries are considering reforms to improve access to OMPs. This paper proposes ten principles to be considered when undertaking such reforms, from the perspective of an OMP manufacturer. We recommend the continued prioritisation of rare diseases by policymakers, an increased alignment between payer and regulatory frameworks, pricing centred on OMP value, and mechanisms to ensure long-term financial sustainability allowing a continuous and virtuous development of OMPs. Our recommendations support the development of more consistent frameworks and encourage collaboration between all stakeholders, including research-based industry, payers, clinicians, and patients. [ABSTRACT FROM AUTHOR]

Background: Cloud computing is a recent and fast growing area of development in healthcare. Ubiquitous, on-demand access to virtually endless resources in combination with a pay-per-use model allow for new ways of developing, delivering and using services. Cloud computing is often used in an "OMICS-context", e.g. for computing in genomics, proteomics and molecular medicine, while other field of application still seem to be underrepresented. Thus, the objective of this scoping review was to identify the current state and hot topics in research on cloud computing in healthcare beyond this traditional domain. Methods: MEDLINE was searched in July 2013 and in December 2014 for publications containing the terms "cloud computing" and "cloud-based". Each journal and conference article was categorized and summarized independently by two researchers who consolidated their findings. Results: 102 publications have been analyzed and 6 main topics have been found: telemedicine/teleconsultation, medical imaging, public health and patient self-management, hospital management and information systems, therapy, and secondary use of data. Commonly used features are broad network access for sharing and accessing data and rapid elasticity to dynamically adapt to computing demands. Eight articles favor the pay-for-use characteristics of cloud-based services avoiding upfront investments. Nevertheless, while 22 articles present very general potentials of cloud computing in the medical domain and 66 articles describe conceptual or prototypic projects, only 14 articles report from successful implementations. Further, in many articles cloud computing is seen as an analogy to internet-/web-based data sharing and the characteristics of the particular cloud computing approach are unfortunately not really illustrated. Conclusions: Even though cloud computing in healthcare is of growing interest only few successful implementations yet exist and many papers just use the term "cloud" synonymously for "using virtual machines" or "web-based" with no described benefit of the cloud paradigm. The biggest threat to the adoption in the healthcare domain is caused by involving external cloud partners: many issues of data safety and security are still to be solved. Until then, cloud computing is favored more for singular, individual features such as elasticity, pay-per-use and broad network access, rather than as cloud paradigm on its own. [ABSTRACT FROM AUTHOR]

Canadian reports have recommended that health as a human right must be Canada's overarching global commitment and that the primacy of human rights should be prioritized over other elements of international law including international trade and investment law as it applies to access to pharmaceuticals. This paper uses a series of case reports to examine Canada's commitment to this goal. Specifically it examines cases where improved access has been in conflict with increased intellectual property rights. The 6 cases are: Canada's position when 39 pharmaceutical companies took South Africa to court in 1998 over its legislation to allow parallel importation of patented medicines and to regulate the price of medications; the stance that Canada took in the negotiations around the Doha Declaration in 2001; the passage of Canada's Access to Medicines Regime in 2004 and subsequent attempts to amend the legislation in 2011 and 2012; Canada's involvement in the final declaration at the United Nations High-Level meeting on non-communicable diseases in 2012; Canada's views about the terms in the Anti-Counterfeiting Trade Agreement as expressed in 2009; and Canada's 2013 position on the extension of the exemption for least developed countries from having to comply with the terms of the Trade Related Aspects of Intellectual Property Rights Agreement. In the first case Canada was neutral but in the remaining 5 cases Canada prioritized intellectual property rights over access. This position is consistent with how Canada has acted around domestic issues involving intellectual property rights for pharmaceutical products. Canada has supported strengthened rights despite the fact that their touted benefits have not been realized either domestically or in developing countries. As a result Canada has failed in its humanitarian duty to protect the human right to health in the form of safe and low cost medicines for the people in developing countries. [ABSTRACT FROM AUTHOR]

Background: There is a growing interest in high income countries to control expenditure on medicines by improving the rationale for their selection. However, in middle income countries with differing priorities and needs, little attention has been paid to this issue. In this paper we explore the policies and processes for the selection and use of medicines in a group of hospitals in Chile, a middle income country which has recently joined the OECD. Methods: A combination of qualitative and quantitative methods was used. A national survey questionnaire was distributed to investigate the role and operation of PTCs (Pharmacy and Therapeutics Committees). Interviews were conducted with key actors in the selection of medicines in large urban public hospitals. Results: The national survey had an overall response rate of 42% (83 out of 196), whilst 7 out of 14 hospitals participated in the qualitative study. High complexity hospitals are large urban hospitals; all of which claim to have a working PTC. The pharmacy offices are mainly involved in dispensing medicines with little involvement in clinical duties. The interviews conducted suggest that the formulary of all the hospitals visited is no more than a stock list. PTCs are unable to influence the prescribing practices of doctors. Members do not feel prepared to challenge the opinions of specialists requesting a certain drug, and decisions are based primarily on costs. The inclusion of medicines in the clinical practice of hospitals is as a result of doctors bypassing the PTC and requesting the purchase of exceptional items, some of which are included in the formulary if they are widely used. Conclusions: There is an urgent need to develop medicine policies in hospitals in Chile. The procedures used to purchase medicines need to be revised. Central guidance for PTCs could help ensure a more rational use of medicines. PTCs need to be empowered to design formularies which cover all the clinical needs of doctors, training members in the analysis of scientific evidence beyond their own specialities. An influential PTC can take the appropriate measures and design workable policies to enforce a cost effective-use of resources. [ABSTRACT FROM AUTHOR]

Background: The United Kingdom has led the world in the development of children's palliative care. Over the past two decades, the illness trajectories of children with life-limiting conditions have extended with new treatments and better home-based care. Future planning is a critically under-researched aspect of children's palliative care globally. This paper describes the development, implementation and evaluation of innovative child and parent-held palliative care planning resources. The resources were designed to facilitate parent and child thinking and engagement in future planning, and to determine care preferences and preferred locations of care for children with life-limiting conditions from diagnosis onwards. These resources fill a significant gap in palliative care planning before the end-of-life phase. Methods: Drawing on contemporaneous research on producing evidence-based children's health information, we collaborated with leading children's not-for-profit organisations, parents, children, and professionals. A set of resources (My Choices booklets) were developed for parents and children and evaluated using interviews (parents, children, professionals) and questionnaires (professionals) and an open web-based consultation. Results: Parents and children responded in three ways: Some used the booklets to produce detailed written plans with clear outcomes and ideas about how best to achieve desired outcomes. Others preferred to use the booklet to help them think about potential options. Remaining parents found it difficult to think about the future and felt there was no point because they perceived there to be no suitable local services. Professionals varied in confidence in their ability to engage with families to plan ahead and identified many challenges that prevented them from doing so. Few families shared their plans with professionals. Parents and children have far stronger preferences for home-care than professionals. Conclusion: The My Choices booklets were revised in light of findings, have been endorsed by Together for Short Lives, and are free to download in English and Welsh for use by parents and young people globally. More work needs to be done to support families who are not yet receptive to planning ahead. Professionals would benefit from more training in person-centred approaches to future planning and additional communications skills to increase confidence and ability to engage with families to deliver sensitive palliative care planning. [ABSTRACT FROM AUTHOR]

Background: Crisis resolution and home treatment (CRHT) is an emerging mode of delivering acute mental health care in the community. There is a paucity of knowledge regarding the workings of CRHT in the literature. This is the first paper in a series of three from the longitudinal survey of patients of a CRHT team in Norway, which was aimed at describing the characteristics of patients served, professional services provided, and clinical outcomes. This report focuses on describing the characteristics of the patients at admission. Methods: The study was a descriptive, quantitative study based on the patient data from a longitudinal survey of one CRHT team in Norway. The participants of the survey, a total of 363 patients, were the complete registration of patients of this team in the period from February 2008 to July 2009. Results: Although diverse in their characteristics, the patients were over represented by females, young to middle aged, and people on public support. The patients were mostly referred to the team by self/family members and primary care physicians. At admission, depression was the most prevalent symptom, the overall intensity level of mental health problems was low, and most of the patients had long-standing mental health problems. Conclusions: Self/family referral seems to be a critical route to receive services by CRTH teams as shown in our study, suggesting a need to examine policies that disallow this form of referral in some communities. The findings from our study show that the patients of the CRHT team, while mostly having long-standing mental health problems and had been receiving healthcare for them, did not have severe mental health problems at admission, although could have been in crises. There is a need for further studies to examine how people with severe mental health problems obtain services in time of crises, and to address the need to gain a greater understanding of the role of CRHT. [ABSTRACT FROM AUTHOR]

Background: There are several humanly defined ontologies relevant to Medline. However, Medline is a fast growing collection of biomedical documents which creates difficulties in updating and expanding these humanly defined ontologies. Automatically identifying meaningful categories of entities in a large text corpus is useful for information extraction, construction of machine learning features, and development of semantic representations. In this paper we describe and compare two methods for automatically learning meaningful biomedical categories in Medline. The first approach is a simple statistical method that uses part-of-speech and frequency information to extract a list of frequent nouns from Medline. The second method implements an alignment-based technique to learn frequent generic patterns that indicate a hyponymy/hypernymy relationship between a pair of noun phrases. We then apply these patterns to Medline to collect frequent hypernyms as potential biomedical categories. Results: We study and compare these two alternative sets of terms to identify semantic categories in Medline. We find that both approaches produce reasonable terms as potential categories. We also find that there is a significant agreement between the two sets of terms. The overlap between the two methods improves our confidence regarding categories predicted by these independent methods. Conclusions: This study is an initial attempt to extract categories that are discussed in Medline. Rather than imposing external ontologies on Medline, our methods allow categories to emerge from the text. [ABSTRACT FROM AUTHOR]

Background: Biomedical ontologies usually encode knowledge that applies always or at least most of the time, that is in normal circumstances. But for some applications like phenotype ontologies it is becoming increasingly important to represent information about aberrations from a norm. These aberrations may be modifications of physiological structures, but also modifications of biological processes. Methods: To facilitate precise definitions of process-related phenotypes, such as delayed eruption of the primary teeth or disrupted ocular pursuit movements, I introduce a modeling approach that draws inspiration from the use of continuations in the analysis of programming languages and apply a similar idea to ontological modeling. This approach characterises processes by describing their outcome up to a certain point and the way they will continue in the canonical case. Definitions of process types are then given in terms of their continuations and anomalous phenotypes are defined by their differences to the canonical definitions. Results: The resulting model is capable of accurately representing structural process anomalies. It allows distinguishing between different anomaly kinds (delays, interruptions), gives identity criteria for interrupted processes, and explains why normal and anomalous process instances can be subsumed under a common type, thus establishing the connection between canonical and anomalous process-related phenotypes. Conclusion: This paper shows how to to give semantically rich definitions of process-related phenotypes. These allow to expand the application areas of phenotype ontologies beyond literature annotation and establishment of genotypephenotype associations to the detection of anomalies in suitably encoded datasets [ABSTRACT FROM AUTHOR]

Background: Manually annotated corpora are critical for the training and evaluation of automated methods to identify concepts in biomedical text. Results: This paper presents the concept annotations of the Colorado Richly Annotated Full-Text (CRAFT) Corpus, a collection of 97 full-length, open-access biomedical journal articles that have been annotated both semantically and syntactically to serve as a research resource for the biomedical natural-language-processing (NLP) community. CRAFT identifies all mentions of nearly all concepts from nine prominent biomedical ontologies and terminologies: the Cell Type Ontology, the Chemical Entities of Biological Interest ontology, the NCBI Taxonomy, the Protein Ontology, the Sequence Ontology, the entries of the Entrez Gene database, and the three subontologies of the Gene Ontology. The first public release includes the annotations for 67 of the 97 articles, reserving two sets of 15 articles for future text-mining competitions (after which these too will be released). Concept annotations were created based on a single set of guidelines, which has enabled us to achieve consistently high interannotator agreement. Conclusions: As the initial 67-article release contains more than 560,000 tokens (and the full set more than 790,000 tokens), our corpus is among the largest gold-standard annotated biomedical corpora. Unlike most others, the journal articles that comprise the corpus are drawn from diverse biomedical disciplines and are marked up in their entirety. Additionally, with a concept-annotation count of nearly 100,000 in the 67-article subset (and more than 140,000 in the full collection), the scale of conceptual markup is also among the largest of comparable corpora. The concept annotations of the CRAFT Corpus have the potential to significantly advance biomedical text mining by providing a high-quality gold standard for NLP systems. The corpus, annotation guidelines, and other associated resources are freely available at http://bionlp-orpora.sourceforge.net/CRAFT/index.shtml. [ABSTRACT FROM AUTHOR]

Background: Healthcare accreditation standards are advocated as an important means of improving clinical practice and organisational performance. Standard development agencies have documented methodologies to promote open, transparent, inclusive development processes where standards are developed by members. They assert that their methodologies are effective and efficient at producing standards appropriate for the health industry. However, the evidence to support these claims requires scrutiny. The study's purpose was to examine the empirical research that grounds the development methods and application of healthcare accreditation standards. Methods: A multi-method strategy was employed over the period March 2010 to August 2011. Five academic health research databases (Medline, Psych INFO, Embase, Social work abstracts, and CINAHL) were interrogated, the websites of 36 agencies associated with the study topic were investigated, and a snowball search was undertaken. Search criteria included accreditation research studies, in English, addressing standards and their impact. Searching in stage 1 initially selected 9386 abstracts. In stage 2, this selection was refined against the inclusion criteria; empirical studies (n = 2111) were identified and refined to a selection of 140 papers with the exclusion of clinical or biomedical and commentary pieces. These were independently reviewed by two researchers and reduced to 13 articles that met the study criteria. Results: The 13 articles were analysed according to four categories: overall findings; standards development; implementation issues; and impact of standards. Studies have only occurred in the acute care setting, predominately in 2003 (n = 5) and 2009 (n = 4), and in the United States (n = 8). A multidisciplinary focus (n = 9) and mixed method approach (n = 11) are common characteristics. Three interventional studies were identified, with the remaining 10 studies having research designs to investigate clinical or organisational impacts. No study directly examined standards development or other issues associated with their progression. Only one study noted implementation issues, identifying several enablers and barriers. Standards were reported to improve organisational efficiency and staff circumstances. However, the impact on clinical quality was mixed, with both improvements and a lack of measurable effects recorded. Conclusion: Standards are ubiquitous within healthcare and are generally considered to be an important means by which to improve clinical practice and organisational performance. However, there is a lack of robust empirical evidence examining the development, writing, implementation and impacts of healthcare accreditation standards. [ABSTRACT FROM AUTHOR]

Background: Excessive alcohol use is a significant problem in rural and remote Australia. The factors contributing to patterns of alcohol use have not been adequately explained, yet the geographic variation in rates suggests a potential contribution of district-level factors, such as socio-economic disadvantage, rates of population change, environmental adversity, and remoteness from services/population centres. This paper aims to investigate individual-level and district-level predictors of alcohol use in a sample of rural adults. Methods: Using baseline survey data (N = 1,981) from the population-based Australian Rural Mental Health Study of community dwelling residents randomly selected from the Australia electoral roll, hierarchal logistic regression models were fitted for three outcomes: 1) at-risk alcohol use, indicated by Alcohol Use Disorders Identification Test scores ≥8; 2) high alcohol consumption (> 40 drinks per month); and 3) lifetime consequences of alcohol use. Predictor variables included demographic factors, pre-dispositional factors, recent difficulties and support, mental health, rural exposure and district-level contextual factors. Results: Gender, age, marital status, and personality made the largest contribution to at-risk alcohol use. Five or more adverse life events in the past 12 months were also independently associated with at-risk alcohol use (Adjusted Odds Ratio [AOR] 3.3, 99%CI 1.2, 8.9). When these individual-level factors were controlled for, at-risk alcohol use was associated with having spent a lower proportion of time living in a rural district (AOR 1.7, 99%CI 1.3, 2.9). Higher alcohol consumption per month was associated with higher district-level socio-economic ranking, indicating less disadvantage (AOR 1.2, 99%CI 1.02, 1.4). Rural exposure and district-level contextual factors were not significantly associated with lifetime consequences of alcohol use. Conclusions: Although recent attention has been directed towards the potential adverse health effects of district or community level adversity across rural regions, our study found relatively few district-level factors contributing to at-risk alcohol consumption after controlling for individual-level factors. Population-based prevention strategies may be most beneficial in rural areas with a higher socio-economic ranking, while individual attention should be focused towards rural residents with multiple recent adverse life events, and people who have spent less time residing in a rural area. [ABSTRACT FROM AUTHOR]

Background: The treatment of negation and hedging in natural language processing has received much interest recently, especially in the biomedical domain. However, open access corpora annotated for negation and/or speculation are hardly available for training and testing applications, and even if they are, they sometimes follow different design principles. In this paper, the annotation principles of the two largest corpora containing annotation for negation and speculation - BioScope and Genia Event - are compared. BioScope marks linguistic cues and their scopes for negation and hedging while in Genia biological events are marked for uncertainty and/or negation. Results: Differences among the annotations of the two corpora are thematically categorized and the frequency of each category is estimated. We found that the largest amount of differences is due to the issue that scopes - which cover text spans - deal with the key events and each argument (including events within events) of these events is under the scope as well. In contrast, Genia deals with the modality of events within events independently. Conclusions: The analysis of multiple layers of annotation (linguistic scopes and biological events) showed that the detection of negation/hedge keywords and their scopes can contribute to determining the modality of key events (denoted by the main predicate). On the other hand, for the detection of the negation and speculation status of events within events, additional syntax-based rules investigating the dependency path between the modality cue and the event cue have to be employed. [ABSTRACT FROM AUTHOR]

Background: Efficient identification of drug targets is one of major challenges for drug discovery and drug development. Traditional approaches to drug target identification include literature search-based target prioritization and in vitro binding assays which are both time-consuming and labor intensive. Computational integration of different knowledge sources is a more effective alternative. Wealth of omics data generated from genomic, proteomic and metabolomic techniques changes the way researchers view drug targets and provides unprecedent opportunities for drug target identification. Results: In this paper, we develop a method based on flux balance analysis (FBA) of metabolic networks to identify potential drug targets. This method consists of two linear programming (LP) models, which first finds the steady optimal fluxes of reactions and the mass flows of metabolites in the pathologic state and then determines the fluxes and mass flows in the medication state with the minimal side effect caused by the medication. Drug targets are identified by comparing the fluxes of reactions in both states and examining the change of reaction fluxes. We give an illustrative example to show that the drug target identification problem can be solved effectively by our method, then apply it to a hyperuricemia-related purine metabolic pathway. Known drug targets for hyperuricemia are correctly identified by our two-stage FBA method, and the side effects of these targets are also taken into account. A number of other promising drug targets are found to be both effective and safe. Conclusions: Our method is an efficient procedure for drug target identification through flux balance analysis of large-scale metabolic networks. It can generate testable predictions, provide insights into drug action mechanisms and guide experimental design of drug discovery. [ABSTRACT FROM AUTHOR]

Background: In the past forty years, many gains have been made in our understanding of the concept of research utilization. While numerous studies exist on professional nurses' use of research in practice, no attempt has been made to systematically evaluate and synthesize this body of literature with respect to the extent to which nurses use research in their clinical practice. The objective of this study was to systematically identify and analyze the available evidence related to the extent to which nurses use research findings in practice. Methods: This study was a systematic review of published and grey literature. The search strategy included 13 online bibliographic databases: Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE, HAPI, Web of Science, SCOPUS, OCLC Papers First, OCLC WorldCat, ABI Inform, Sociological Abstracts, and Dissertation Abstracts. The inclusion criteria consisted of primary research reports that assess professional nurses' use of research in practice, written in the English or Scandinavian languages. Extent of research use was determined by assigning research use scores reported in each article to one of four quartiles: low, moderate-low, moderate-high, or high. Results: Following removal of duplicate citations, a total of 12,418 titles were identified through database searches, of which 133 articles were retrieved. Of the articles retrieved, 55 satisfied the inclusion criteria. The 55 final reports included cross-sectional/survey (n = 51) and quasi-experimental (n = 4) designs. A sensitivity analysis, comparing findings from all reports with those rated moderate (moderate-weak and moderate-strong) and strong quality, did not show significant differences. In a majority of the articles identified (n = 38, 69%), nurses reported moderate-high research use. Conclusions: According to this review, nurses' reported use of research is moderate-high and has remained relatively consistent over time until the early 2000's. This finding, however, may paint an overly optimistic picture of the extent to which nurses use research in their practice given the methodological problems inherent in the majority of studies. There is a clear need for the development of standard measures of research use and robust well-designed studies examining nurses' use of research and its impact on patient outcomes. The relatively unchanged self-reports of moderate-high research use by nurses is troubling given that over 40 years have elapsed since the first studies in this review were conducted and the increasing emphasis in the past 15 years on evidence-based practice. More troubling is the absence of studies in which attempts are made to assess the effects of varying levels of research use on patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Applications of Natural Language Processing (NLP) technology to biomedical texts have generated significant interest in recent years. In this paper we identify and investigate the phenomenon of linguistic subdomain variation within the biomedical domain, i.e., the extent to which different subject areas of biomedicine are characterised by different linguistic behaviour. While variation at a coarser domain level such as between newswire and biomedical text is well-studied and known to affect the portability of NLP systems, we are the first to conduct an extensive investigation into more fine-grained levels of variation. Results: Using the large OpenPMC text corpus, which spans the many subdomains of biomedicine, we investigate variation across a number of lexical, syntactic, semantic and discourse-related dimensions. These dimensions are chosen for their relevance to the performance of NLP systems. We use clustering techniques to analyse commonalities and distinctions among the subdomains. Conclusions: We find that while patterns of inter-subdomain variation differ somewhat from one feature set to another, robust clusters can be identified that correspond to intuitive distinctions such as that between clinical and laboratory subjects. In particular, subdomains relating to genetics and molecular biology, which are the most common sources of material for training and evaluating biomedical NLP tools, are not representative of all biomedical subdomains. We conclude that an awareness of subdomain variation is important when considering the practical use of language processing applications by biomedical researchers. [ABSTRACT FROM AUTHOR]

Background: A quantitative measurement of inequality in geographic accessibility to pediatric care as well as that of mean distance or travel time is very important for priority setting to ensure fair access to pediatric facilities. However, conventional techniques for measuring inequality is inappropriate in geographic settings. Since inequality measures of access distance or travel time is strongly influenced by the background geographic distribution patterns, they cannot be directly used for regional comparisons of geographic accessibility. The objective of this study is to resolve this issue by using a standardization approach. Methods: Travel times to the nearest pediatric care were calculated for all children in Oita Prefecture, Japan. Relative mean differences were considered as the inequality measure for secondary medical service areas, and were standardized with an expected value estimated from a Monte Carlo simulation based on complete spatial randomness. Results: The observed mean travel times in the area considered averaged 4.50 minutes, ranging from 1.83 to 7.02 minutes. The mean of the observed inequality measure was 1.1, ranging from 0.9 to 1.3. The expected values of the inequality measure varied according to the background geographic distribution pattern of children, which ranged from 0.3 to 0.7. After standardizing the observed inequality measure with the expected one, we found that the ranks of the inequality measure were reversed for the observed areas. Conclusions: Using the indicator proposed in this paper, it is possible to compare the inequality in geographic accessibility among regions. Such a comparison may facilitate priority setting in health policy and planning. [ABSTRACT FROM AUTHOR]

Background: Across the globe the emphasis on roles and responsibilities of primary care teams is under scrutiny. This paper begins with a review of general practice financing in Australia, and how nurses are currently funded. We then examine the influence on funding structures on the role of the nurse. We set out three dilemmas for policymakers in this area: lack of an evidence base for incentives, possible untoward impacts on interdisciplinary functioning, and the substitution/enhancement debate. Methods: This three year, multimethod study undertook rapid appraisal of 25 general practices and year-long studies in seven practices where a change was introduced to the role of the nurse. Data collected included interviews with nurses (n = 36), doctors (n = 24), and managers (n = 22), structured observation of the practice nurse (51 hours of observation), and detailed case studies of the change process in the seven year-long studies. Results: Despite specific fee-for-service funding being available, only 6% of nurse activities generated such a fee. Yet the influence of the funding was to focus nurse activity on areas that they perceived were peripheral to their roles within the practice. Conclusions: Interprofessional relationships and organisational climate in general practices are highly influential in terms of nursing role and the ability of practices to respond to and utilise funding mechanisms. These factors need to be considered, and the development of optimal teamwork supported in the design and implementation of further initiatives that financially support nursing in general practice. [ABSTRACT FROM AUTHOR]

Background: Recent development of high-resolution single nucleotide polymorphism (SNP) arrays allows detailed assessment of genome-wide human genome variations. There is increasing recognition of the importance of SNPs for medicine and developmental biology. However, SNP data set typically has a large number of SNPs (e.g., 400 thousand SNPs in genome-wide Parkinson disease data set) and a few hundred of samples. Conventional classification methods may not be effective when applied to such genome-wide SNP data. Results: In this paper, we use shrunken dissimilarity measure to analyze and select relevant SNPs for classification problems. Examples of HapMap data and Parkinson disease (PD) data are given to demonstrate the effectiveness of the proposed method, and illustrate it has a potential to become a useful analysis tool for SNP data sets. We use Parkinson disease data as an example, and perform a whole genome analysis. For the 367440 SNPs with less than 1% missing percentage from all 22 chromosomes, we can select 357 SNPs from this data set. For the unique genes that those SNPs are located in, a gene-gene similarity value is computed using GOSemSim and gene pairs that has a similarity value being greater than a threshold are selected to construct several groups of genes. For the SNPs that involved in these groups of genes, a statistical software PLINK is employed to compute the pair-wise SNP-SNP interactions, and SNPs with significance of P < 0.01 are chosen to identify SNPs networks based on their P values. Here SNPs networks are constructed based on Gene Ontology knowledge, and therefore each SNP network plays a role in the biological process. An analysis shows that such networks have relationships directly or indirectly to Parkinson disease. Conclusions: Experimental results show that our approach is suitable to handle genetic variations, and provide useful knowledge in a genome-wide SNP study. [ABSTRACT FROM AUTHOR]