The promise of protein glycosylation for personalised medicine

BackgroundComplex diseases such as cancer are a consequence of numerous causes. State of the art personalised medicine approaches are mostly based on evaluating patients' individual genetic background. Despite the advances of genomics it fails to take individual dynamic influences into account that contribute to the individual and unique glycomic and glycoproteomic “configurations” of every living being.Scope of reviewGlycomic and glycoproteomic-based personalised medicine diagnostics are still in their infancies, however some initial success stories indicate that these fields are highly promising to mediate novel early diagnosis and disease stratification markers, subsequently resulting in improved patient well-being and reduced treatment costs. In this review we not only summarise current protein glycosylation based examples that substantially improve or possess great potential for personalised medicine, but also describe current limitations as well as future perspectives and challenges associated with establishing protein glycosylation aspects for this purpose.Major conclusionsMany protein biomarkers currently in clinical use are glycoproteins, however, their glycosylation status is seldom evaluated in a clinical context. To date just few examples have already been successfully translated into clinical practice, making protein glycosylation a highly promising diagnostic target with humongous potential for personalised medicine.General significanceThere is an urgent need for markers that enable the establishment of an individualised and optimised patient treatment at the earliest disease stage possible. The glycosylation status of a patient and/or specific marker proteins can provide important clues that result in improved patient management. This article is part of a Special Issue entitled “Glycans in personalised medicine” Guest Editor: Professor Gordan Lauc.     

On being “actionable”: clinical sequencing and the emerging contours of a regime of genomic medicine in oncology

This article explores commercial, academic, and national initiatives aimed at using sequencing technologies to generate “actionable” genomic results that can be applied to the clinical management of oncology patients. We argue that the term “actionable” is not merely a buzzword, but signals the emergence of a distinctive sociotechnical regime of genomic medicine in oncology. Unlike other regimes of genomic medicine that are organized around assessing and managing inherited risk for developing cancer (e.g. BRCA testing), actionable regimes aim to generate predictive relationships between genetic information and drug therapies, thereby generating new kinds of clinical actions. We explore how these genomic results are made actionable by articulating them with existing clinical routines, clinical trials, regulatory regimes, and health care systems; and in turn, how clinical sequencing programs have begun to reconfigure knowledge and practices in oncology. Actionability regimes confirm the emergence of bio-clinical decision-making in oncology, whereby the articulation of molecular hypotheses and experimental therapeutics become central to patient care.     

The politics of recognition in culturally appropriate care

Over the last 20 years, the concept of culturally appropriate health care has been gradually gaining popularity in medicine and public health. In calling for health care that is culturally appropriate, minority groups seek political recognition of often racialized constructions of cultural difference as they intervene in health care planning and organization. Based on interview narratives from people involved in community organizing to establish a federally funded community health center in a mid-size New England city, I chart the emergence of a language of "culturally appropriate health care" in language used to justify the need for a health center. An identity model of recognition underlies the call for ethnic resemblance between patient and provider seen in many culturally appropriate care programs. I contrast this model of health care with earlier calls for community access and control by activists in the 1970s and explore the practical and theoretical implications of each approach.     

Quantification Methodology of “Health Human Resources” Related to “Health Technologies” Based on Indicators “RhSan”, “TechSan” and “RhTech”: Application to Senegal

ObjectivesAfter a century of spectacular advances, healthcare systems are facing unprecedented crisis, linked to shortage of health human resources and health technologies. In fact, availability of care depends on both technological and human resources of health. The objective of this study is to develop indicators that can measure qualitatively human resources and technologies of health in healthcare facilities, in order to assess availability of care in sub-Saharan African countries.Materials and MethodsRegarding “health technology” related to “medical devices”, an indicator called “TechSan” for “Technologies de Santé” was previously developed and published (Ndione FB et al. (2019) [6]). To address the deficiencies in usual indicators related to health human resources, a second indicator called “RhSan” for “Ressources humaines de santé” in French is proposed. This indicator assigns a weight to each health worker taking into account his specific “level of medical knowledge” and “experience”. In order to correlate “RhSan” with “TechSan”, a third indicator called “RhTech” is also developed to assess matches between “health technologies” and “health human resources” and establish realistic availability of care. These indicators have the advantage to be consolidated by specialty such as laboratory, imaging, surgery, and “mother and child care”.ResultsThe application of TechSan, RhSan and RhTech to data collected in Senegal in 2016, enabled to assess the distribution of “health technology” and “health human resources” in this country. They also permit the mapping of care availability per specialty in Senegal. The results show a strong oversupply of Dakar in terms of both human resources and technologies of health compared to other Senegalese regions. Oppositely, Sedhiou, Kaffrine, Matam and Kédougou are poorly endowed showing limits of the Senegalese health pyramid system.ConclusionTechSan, RhSan and RhTech can provide reliable decision-making tools in order to elaborate health policies in sub-Saharan African countries on more rigorous basis.     

The Practical Application of Narrative Medicine at Mayo Clinic: Imagining the Scaffold of a Worthy House

American health care institutions increasingly recognize narrative medicine as a means to developing quality patient care. More commonly applied in health care professional development settings, narrative medicine is less overtly employed with patient populations. In this article, we describe the application of various narrative practices in the patient care and medical education programs of a major health care center in Minnesota. We discuss the impact of these programs on their participants in relation to the evidence based in current scholarship. Further, we examine narrative externalization of illness in Katherine Butler Hathaway’s disability memoir “The Little Locksmith,” a text which implicates the work of metaphor-making as a transformative step in healing. While several reports demonstrate that patients can find creative writing during times of illness to be therapeutic, there are many for whom the practice is problematic or unattractive, obstacles to practice implementation that the authors discuss. However, based on the experience of our institution, for health care institutions seeking to build a legacy of leadership in empathic patient care, narrative—employed in mentoring physicians in training and in establishing strong, dialogic relationships with patients and colleagues—should serve as a central strategy, or scaffold.     

Nutrigenomics-based personalised nutritional advice: in search of a business model?

Nutritional advice has mainly focused on population-level recommendations. Recent developments in nutrition, communication, and marketing sciences have enabled potential deviations from this dominant business model in the direction of personalisation of nutrition advice. Such personalisation efforts can take on many forms, but these have in common that they can only be effective if they are supported by a viable business model. The present paper takes an inventory of approaches to personalised nutrition currently available in the market place as its starting point to arrive at an identification of their underlying business models. This analysis is presented as a unifying framework against which the potential of nutrigenomics-based personalised advice can be assessed. It has uncovered nine archetypical approaches to personalised nutrition advice in terms of their dominant underlying business models. Differentiating features among such business models are the type of information that is used as a basis for personalisation, the definition of the target group, the communication channels that are being adopted, and the partnerships that are built as a part of the business model. Future research should explore the consumer responses to the diversity of “archetypical” business models for personalised nutrition advice as a source of market information on which the delivery of nutrigenomics-based personalised nutrition advice may further build.     

Clinicians’ views and expectations of human microbiome science on asthma and its translations

Human microbiome science examines the microbiota that live in and on the human body and their role in human health. This paper examines clinicians’ views and expectations of microbiome science in asthma care. Drawing on qualitative interviews with 10 clinicians in Canada, we explore their perspectives for insights into translation of human microbiome science. The emphasis on novelty in much microbiome scholarship, we suggest, does not account fully for the ways in which microbiome science translations may be taken up in multiple ways that are both disruptive to and continuous with contemporary biomedicine. We suggest that clinicians drew on scientific discourses of “evidence” and “facts” as a form of boundary work to re-establish a separation between western biomedicine and alternative health practitioners, and clinical expertise and lay knowledge. We conclude with a discussion of human microbiome science and the emergence of post-Pasteurian modes of health in western biomedicine.     

Dysglycemia-Based Chronic Disease: An American Association of Clinical Endocrinologists Position Statement

The American Association of Clinical Endocrinologists (AACE) has created a dysglycemia-based chronic disease (DBCD) multimorbidity care model consisting of four distinct stages along the insulin resistance-prediabetes-type 2 diabetes (T2D) spectrum that are actionable in a preventive care paradigm to reduce the potential impact of T2D, cardiometabolic risk, and cardiovascular events. The controversy of whether there is value, cost-effectiveness, or clinical benefit of diagnosing and/or managing the prediabetes state is resolved by regarding the problem, not in isolation, but as an intermediate stage in the continuum of a progressive chronic disease with opportunities for multiple concurrent prevention strategies. In this context, stage 1 represents “insulin resistance,” stage 2 “prediabetes,” stage 3 “type 2 diabetes,” and stage 4 “vascular complications.” This model encourages earliest intervention focusing on structured lifestyle change. Further scientific research may eventually reclassify stage 2 DBCD prediabetes from a predisease to a true disease state. This position statement is consistent with a portfolio of AACE endocrine disease care models, including adiposity-based chronic disease, that prioritize patient-centered care, evidence-based medicine, complexity, multimorbid chronic disease, the current health care environment, and a societal mandate for a higher value attributed to good health. Ultimately, transformative changes in diagnostic coding and reimbursement structures for prediabetes and T2D can provide improvements in population-based endocrine health care.Abbreviations: A1C = hemoglobin A1c; AACE = American Association of Clinical Endocrinologists; ABCD = adiposity-based chronic disease; CVD = cardiovascular disease; DBCD = dysglycemia-based chronic disease; FPG = fasting plasma glucose; GLP-1 = glucagon-like peptide-1; MetS = metabolic syndrome; T2D = type 2 diabetes     

From Exceptional to Liminal Subjects: Reconciling Tensions in the Politics of Tuberculosis and Migration

Controlling the movement of potentially infectious bodies has been central to Australian immigration law. Nowhere is this more evident than in relation to tuberculosis (TB), which is named as a ground for refusal of a visa in the Australian context. In this paper, I critically examine the “will to knowledge” that this gives rise to. Drawing on a critical analysis of texts, including interviews with migrants diagnosed with TB and healthcare professionals engaged in their care (n=19), I argue that this focus on border policing, rather than resettlement and the broader social determinants of health that drive current rates of TB, paradoxically renders migrants diagnosed with TB as liminal subjects in the post-arrival phase. This raises ethical issues about who “matters,” as well as dilemmas about what constitutes adequate care for the “Other,” both of which go to the heart of the political economy of migration.     

From evidence-based medicine to genomic medicine

The concept of ‘evidence-based medicine’ dates back to mid-19th century or even earlier. It remains pivotal in planning, funding and in delivering the health care. Clinicians, public health practitioners, health commissioners/purchasers, health planners, politicians and public seek formal ‘evidence’ in approving any form of health care provision. Essentially ‘evidence-based medicine’ aims at the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients. It is in fact the ‘personalised medicine’ in practice. Since the completion of the human genome project and the rapid accumulation of huge amount of data, scientists and physicians alike are excited on the prospect of ‘personalised health care’ based on individual’s genotype and phenotype. The first decade of the new millennium now witnesses the transition from ‘evidence-based medicine’ to the ‘genomic medicine’. The practice of medicine, including health promotion and prevention of disease, stands now at a wide-open road as the scientific and medical community embraces itself with the rapidly expanding and revolutionising field of genomic medicine. This article reviews the rapid transformation of modern medicine from the ‘evidence-based medicine’ to ‘genomic medicine’.     

Addressing the conflict between partner notification and patient confidentiality in serodiscordant relationships: How can Ubuntu help?

This study evaluates the conflict between patient confidentiality and partner notification in sero‐discordant relationships, and argues the thesis that based on a theoretical formulation of Ubuntu, a health provider is obliged to facilitate friendly relationships in which individuals are true subjects and/or objects of communal friendship. In serodiscordant relationships, the health professional can fulfil this obligation by notifying “others” (particularly a partner with whom an HIV positive patient has a “present” and “actual relationship”) of their spouse's HIV seroconversion, since without such relevant information a partner (subject) of an HIV positive patient cannot “appropriately” care for the patient's condition (object). There is a need to move away from the medical traditional emphasis that has for so long put primacy on doctor‐patient confidentiality as is the case with the Health Professions Council of South Africa Guidelines (Booklet 12) which favours patient confidentiality over partner notification. Given empirical evidence to support effectiveness of partner notification amongst sero‐discordant couples, there is thus, a need to focus emphasis on latter. This shift is necessary for achieving the United Nations’ Sustainable Development of Goal of ending HIV/AIDS epidemic by 2030. I proposed in this study that African ethics, specifically Ubuntu, will do a better job than current ethical frameworks at ensuring that partner notification receives more emphasis in the care of serodiscordant couples. If this framework is integrated into ethical guidelines and codes, it would significantly enhance the care of serodiscordant couples, as well as further boost global effort at ending HIV/AIDS epidemic by 2030.     

How primary health care professionals and residents assess issues related to the oral health of older persons?

doi: 10.1111/j.1741‐2358.2009.00355.x
How primary health care professionals and residents assess issues related to the oral health of older persons? Background and objectives: It is known that older persons need integrated primary health care. However, oral health may not be a frequent concern of multi‐professional teams taking care of older persons. The aim of the present study was to evaluate knowledge and practices related to oral health care, as reported by professionals and residents in a primary health care service. Material and methods: One hundred and seventy‐three health professionals and residents were assessed in this cross‐sectional study by means of a structured questionnaire containing questions pertaining to oral health practices and beliefs. Participants were grouped based on their professions into “primary health care dentists” or “other primary health care professionals” and based on their working status into “permanent team” or “residents”. Results: Permanent team members (other professionals) assessed and recommended dental care more frequently than residents. Permanent team members (other professionals) also reported that they felt they were able to inform older patients in respect to oral health‐related issues more frequently than did residents (68.7% vs. 31.3%, respectively). Conclusion: Oral health‐related knowledge and beliefs were frequent among non‐dentists primary health care workers, suggesting that primary health care which integrates oral health represents an attainable goal.     

Extending experimentation: oncology’s fading boundary between research and care

Historians and social scientists view the distinction between research and care as diachronically and synchronically contingent, rather than transcendental, as is often the case in bioethics. Comparing how the notion of total care was used in the 1950s with present-day use of that same term by genomically informed oncology programs, the paper argues that the distinction between research and care needs: to be historicized, by examining its repeated emergence and re-definition, and the shifting relations between these two “ideal-typical” components; and to be problematized, by paying attention to the entities, practices, and institutions that are constitutive of the successive regimens that have punctuated oncology’s development. Shifting to contemporary activities, the paper examines how the recent massive injection of molecular biology and high-throughput genomic technologies in the field of oncology has been accompanied by a reshuffling of the research/care distinction, a process that is leading to new forms of “experimental care”.     

Market Liberalism in Health Care: A Dysfunctional View of Respecting “Consumer” Autonomy

The unfortunately vast history of paternalism in both medicine and clinical research has resulted in perpetually increasing respect for patient autonomy and free choice in Western health care systems. Beginning with the negative right to informed consent, the principle of respect for autonomy has for many patients evolved into a positive right to request treatments and expect accommodation. This evolution of patient autonomy has mirrored a more general social attitude of market liberalism where increasing numbers of patients have come to embody the role of the “consumer.” This paper explores this transformation and critiques the current way in which respect for patient autonomy is put into practice. Ultimately, this paper concludes that the consumer view of patient autonomy is dysfunctional. Moreover, this paper argues that, based on the inherent goals of medicine, some form of paternalism is required in any meaningfully therapeutic relationship.     

WEIGHTING HEALTH STATES AND STRONG EVALUATION*

The problem of public consultation over the allocation of health care resources is addressed by considering the role that quality of life measures, such as QALYs and the Nottingham Health Profile, could play. Such measures are typically grounded in social surveys, and as such may reflect public preferences for health care priorities. Using Charles Taylor's concepts of “weak” and “strong” evaluation, it is suggested that current quality of life measures are inadequate, insofar as they typically presuppose that survey respondents are mere “weak evaluators”, who express only inarticulate preferences. Respondents may, conversely, be understood as strong evaluators, with deeper visions of human nature and the good life informing their health preferences. Space is then created for such respondents to be asked to defend their preferences, and so be encouraged to reflect critically and publicly on the beliefs and prejudices that ground their view of health care priorities.     

Ecopharmacognosy and the responsibilities of natural product research to sustainability

The recently developed term “ecopharmacognosy” is defined as the study of sustainable, biologically active, natural resources. As a philosophical approach, it provides a conceptual framework for developing new strategies and new scientific perspectives which may improve future global food and health care product accessibility and assure beneficial outcomes. In this brief article some facets of how the precepts of ecopharmacognosy may apply in developing new medicinal products may be developed, based on sustainability and the use of integrated technologies.Although from a medicinal agent perspective, plants remain a primary source of global health care, these resources are not being pursued by major pharmaceutical companies as sources of new agents, and essentially all tropical diseases, as well as most microbially based diseases, remain outside the scope of their drug discovery programs. Countries and regions therefore must address their own drug discovery needs for “local” and some global diseases. In addition, the cost of drug importation is so high that development of local resources, i.e. traditional medicines, may be the only rational alternative approach. At the same time, network pharmacology is exploring the many diverse effects of both individual and complex natural products at the gene level, and this is offering new opportunities to rethink and restructure the core, long-standing, Western, magic bullet philosophy to drug discovery. Other ecopharmacognosy changes underway include the computer-aided design of natural product derivatives, based on molecular docking, which is providing targetable enzyme substrates, and remote sensing technologies which can assess natural materials non-invasively for critical constituents as a part of rethinking quality control strategies in the field. Furthermore, there are the hyphenated chromatographic and spectroscopic procedures to quantitatively analyze single and multicomponent plant mixtures for bioactive markers to enhance quality control and, thereby, patient care. The relationship of these evolving approaches will serve as practical examples to the philosophies of ecopharmacognosy. In summary, with respect to health care, ecopharmacognosy poses the long-term practical question for drugs, “How Green is Your Medicine?”     

Who Will Manage American Patients With Diabetes? Residents’ Career Preferences and Perceptions of Diabetes Care

ObjectiveTo identify the factors that encourage or discourage internal medicine and pediatric residents regarding specializing in endocrinology with a focus on diabetes.MethodsWe conducted an electronic survey of internal medicine and pediatric residents using a $10 participation incentive. A total of 653 residents responded to the survey (estimated response rate of 9.2%)—626 from residency programs that were contacted for our survey and 27 from referrals.ResultsAmong internal medicine and pediatric residents surveyed, 39 respondents (6.0%) planned to specialize in endocrinology, and 27 of these (4.1% of total respondents) planned to focus on diabetes. “Intellectual satisfaction, ” “emotional satisfaction, ” and “work-life balance” were identified by respondents as the most important factors in their choice of a specialty, with ratings of 5.5, 5.4, and 5.3 on a 6-point Likert scale. Among these factors identified as most important to a medical career, endocrinology with a focus on diabetes scored poorly with regard to intellectual and emotional satisfaction but received high ranking with regard to lifestyle. With regard to other factors, endocrinology was rated negatively on “compensation, ” “number of procedures, ” and “patient adherence to prescribed treatment.” Exposure to diabetes during training had no major influence on the decision to enter endocrinology.ConclusionEndocrinology with a focus on diabetes care is not an attractive specialty for most internal medicine and pediatric residents. Therefore, new strategies to attract residents to the field of diabetes care are needed. (Endocr Pract. 2011;17:235-239)     

Sample Size Considerations for GEE Analyses of Three‐Level Cluster Randomized Trials

Summary Cluster randomized trials in health care may involve three instead of two levels, for instance, in trials where different interventions to improve quality of care are compared. In such trials, the intervention is implemented in health care units (“clusters”) and aims at changing the behavior of health care professionals working in this unit (“subjects”), while the effects are measured at the patient level (“evaluations”). Within the generalized estimating equations approach, we derive a sample size formula that accounts for two levels of clustering: that of subjects within clusters and that of evaluations within subjects. The formula reveals that sample size is inflated, relative to a design with completely independent evaluations, by a multiplicative term that can be expressed as a product of two variance inflation factors, one that quantifies the impact of within‐subject correlation of evaluations on the variance of subject‐level means and the other that quantifies the impact of the correlation between subject‐level means on the variance of the cluster means. Power levels as predicted by the sample size formula agreed well with the simulated power for more than 10 clusters in total, when data were analyzed using bias‐corrected estimating equations for the correlation parameters in combination with the model‐based covariance estimator or the sandwich estimator with a finite sample correction.     

Challenges of Work–Life Balance for Women Physicians/Mothers Working in Leadership Positions

BackgroundFemale leadership in medicine is still disproportionately small, which might be due to the barriers of combining work and family.ObjectivesThe aim of this study was, first, to perform a strengths, weakness, opportunities, and threats (SWOT) analysis and, second, to create a strategic concept for career development.MethodsIn this study, all women in leadership positions in the health care system in Vienna, Austria, with at least 1 child (n = 8), were interviewed about the advantages and disadvantages of gender with regard to career development, the strengths and weaknesses of female leadership, and their work–life balance. Different factors that influenced the work–life balance were specified, and career strategies to realize adequate solutions were developed.ResultsThe sporadic focus on career advancement, time-consuming child care, responsibility for family life, and a woman's tendency toward understatement were barriers to career development. Work–family enrichment has a positive spillover effect that spreads positive energy and helps to balance the work–life relationship. For each individual, the allocation and interaction of different resources such as time, money, scope of decision making, and physical, emotional, and social resources, were essential to maintain the individual work–life balance.ConclusionsIn addition to the existing “glass ceiling,” the predominant responsibility for child care is still borne by the woman. However, mentoring programs, coaching, networking, and support of the partner or of other people help to strengthen female “soft” skills and achieve a work–life balance.