Psychiatry has witnessed a new wave of approaches to clinical phenotyping and the study of psychopathology, including the National Institute of Mental Health’s Research Domain Criteria, clinical staging, network approaches, the Hierarchical Taxonomy of Psychopathology, and the general psychopathology factor, as well as a revival of interest in phenomenological psychopathology. The question naturally emerges as to what the relationship between these new approaches is – are they mutually exclusive, competing approaches, or can they be integrated in some (...) way and used to enrich each other? In this opinion piece, we propose a possible integration between clinical staging and phenomenological psychopathology. Domains identified in phenomenological psychopathology, such as selfhood, embodiment, affectivity, etc., can be overlaid on clinical stages in order to enrich and deepen the phenotypes captured in clinical staging (‘high resolution’ clinical phenotypes). This approach may be useful both ideographically and nomothetically, in that it could complement diagnosis, enrich clinical formulation, and inform treatment of individual patients, as well as help guide aetiological, prediction, and treatment research. The overlaying of phenomenological domains on clinical stages may require that these domains are reformulated in dimensional rather than categorial terms. This integrative project requires assessment tools, some of which are already available, that are sensitive and thorough enough to pick up on the range of relevant psychopathology. The proposed approach offers opportunities for mutual enrichment: clinical staging may be enriched by introducing greater depth to phenotypes; phenomenological psychopathology may be enriched by introducing stages of severity and disorder progression to phenomenological analysis. (shrink)

Recent editions of diagnostic manuals in psychiatry have focused on providing quick and efficient operationalized criteria. Notwithstanding the genuine value of these classifications, many psychiatrists have argued that the operationalization approach does not sufficiently accommodate the rich and complex domain of patients’ experiences that is crucial for clinical reasoning in psychiatry. How can we increase the role of phenomenology in the process of diagnostic reasoning in psychiatry? I argue that this could be done by adopting a clinical (...) class='Hi'>staging approach in diagnostic reasoning in psychiatry. The approach has the resources to include the progressive nature of patients’ experiences to a much greater degree than is currently practiced. It can address the recent plea for increasing the role of phenomenology in psychiatric diagnosis by offering a model for clinical reasoning that goes beyond the operationalized, static criteria of diagnostic manuals, without depriving us of their benefits. (shrink)

Staging and stratification are two diagnostic approaches that have introduced a more dynamic outlook on the development of diseases, thus participating in blurring the line between the normal and the pathological. First, diagnostic staging, aiming to capture how diseases evolve in time and/or space through identifiable and gradually more severe stages, may be said to lean on an underlying assumption of “temporal determinism”. Stratification, on the other hand, allows for the identification of various prognostic or predictive subgroups based (...) on specific markers, relying on a more “mechanistic” or “statistical” form of determinism. There are two medical fields in which these developments have played a significant role and have given rise to sometimes profound nosological transformations: oncology and psychiatry. Drawing on examples from these two fields, this paper aims to provide much needed conceptual clarifications on both staging and stratification in order to outline how several epistemological and ethical issues may, in turn, arise. We argue that diagnostic staging ought to be detached from the assumption of temporal determinism, though it should still play an essential role in adapting interventions to stage. In doing so, it would help counterbalance stratification’s own epistemological and ethical shortcomings. In this sense, the reflections and propositions developed in psychiatry can offer invaluable insights regarding how adopting a more transdiagnostic and cross-cutting perspective on temporality and disease dynamics may help combine both staging and stratification in clinical practice. (shrink)

BackgroundThe high incidence of post-stroke depression during rehabilitation exerts a negative effect on the treatment and functional recovery of patients with stroke and increases the risk of mortality. It is necessary to screen PSD in the rehabilitation stage and thus provide effective intervention strategies. However, existing measurements used to assess PSD in the rehabilitation stage in patients with stroke lack specificity. This study aimed to develop a clinical measure to assess symptoms of PSD in the rehabilitation stage.MethodsThe research team (...) created the initial items through a literature review and semi-structured interviews of patients with stroke. Then, the symptom-related items were estimated by three panels: healthcare professionals, Delphi experts, and patients with stroke in the rehabilitation stage.ResultsThe literature review and semi-structured interview produced 51 symptom-related items including six domains, and the items were reduced to 47 by the healthcare professionals. The symptom-related items were further reduced to 33 items by a two-round Delphi consultation. The initiative coefficients of the two Delphi rounds were 71.4 and 100%, the expert authority coefficients were both 0.85, Kendall’s W were 0.152 and 0.408, and the coefficient of variation were 0.05–0.32 and 0.00–0.18, respectively. The item-level content validity index was 0.53–1.00, the scale-level CVI/universal agreement was 0.26, and the S-CVI/average was 0.85 for the first found Delphi consultation; the I-CVI was 0.67–1.00, the S-CVI/UA was 0.61, and the S-CVI/Ave was 0.97 for the second round Delphi consultation. All content validity indicators have been significantly improved compared with the first round. Using mean ≥ 4 and full score ≥ 0.5, combined with CV ≤ 0.16 as the item criteria, a clinical measure of PSD with 33 items and 6 dimensions was finally formed after two rounds. The patients with stroke made no further revisions after evaluation.ConclusionThe research team developed a specific tool with good content validity to assess the symptoms of PSD in the rehabilitation stage. (shrink)

The history of drug/vaccine development has included major advances guided primarily by risk/benefit analyses concerning the innovative agent, not by evidence-based clinical trials (Phase I–IV). Because the approval for new drugs is hindered under the present process, the system requires restructuring. The Phase I/II study period should be more flexible, using the “environment of knowledge” about the new agent, plus risk/benefit assessments. Phase III, as presently constructed, does not add new adverse events data, it provides a narrower profile of (...) drug efficacy than properly done Phase II studies, and placebo-controlled trials continue to raise unresolved ethical and social issues. Phase III studies should be abandoned for most drugs, and substituted with properly powered Phase II doseranging studies plus careful post-marketing surveillance. Phase III should be a penalty for poor drug development, not a regulatory requirement. (shrink)

Optogenetics is being optimistically presented in contemporary media for its unprecedented capacity to control cell behavior through the application of light to genetically modified target cells. As such, optogenetics holds obvious potential for application in a new generation of invasive medical devices by which to potentially provide treatment for neurological and psychiatric conditions such as Parkinson's disease, addiction, schizophrenia, autism and depression. Design of a first-in-human optogenetics experimental trial has already begun for the treatment of blindness. Optogenetics trials involve a (...) combination of highly invasive genetic and electronic interventions that results in irreversible and permanent modifications of an individual's nervous system. Given its novelty, its uncertain benefit to patients, and its unique risk profile of irreversible physiological alteration, optogenetics requires a reassessment of the ethical challenges for protecting human participants in clinical trials, particularly at formative stages of clinical evaluation. This study explores the evolving ethical issues surrounding optogenetics’ potential harm to participants within trial design, especially focusing on whether Phase 1 trials should incorporate efficacy as well as safety endpoints in ways that are fair and respectful to research trial participants. (shrink)

The nature of the relationship between clinical investigator and research participant continues to be contested. The related discussions have largely focused on the doctor-researcher dichotomy thought to permeate the work of a clinical investigator with research participants, whom in turn occupy two corresponding roles: patient and subject. This paper contributes to current debates on the topic by providing a voice to research participants, whose perspectives have been largely invisible. It draws on 42 in-depth interviews conducted in Ghana and (...) South Africa with respondents at different stages of involvement in clinical research, ranging from no experience in clinical research to enrollment in several clinical trials. The perspectives of all respondents were largely congruent and rooted in the common view that clinical research contributed to the improvement of local health. They went beyond the researcher/participant versus doctor/patient dichotomy, long established in research ethics, and preferred to view participants and investigators as partners working together to find ways to address local health needs. The conceptualization of investigator-participant relations as a partnership reinforced expectations of care, transparency and accountability, which were viewed as necessary expressions of mutuality and respect within equal collaborations. It is important to engage with these views in order to avoid antagonizing societal expectations and to build up long-term public trust, crucial for the continuous operation of clinical research. (shrink)

Clinical research under the usual regulatory constraints may be difficult or even impossible in a public health emergency. Regulators must seek to strike a good balance in granting as wide therapeutic access to new drugs as possible at the same time as gathering sound evidence of safety and effectiveness. To inform current policy, I reexamine the philosophical rationale for restricting new medicines to clinical trials, at any stage and for any population of patients (which resides in the precautionary (...) principle), to show that its objective to protect public health, now or in the future, could soon be defeated in a pandemic. Providing wider therapeutic access and coordinating observations and natural experiments, including service delivery by cluster (wedged cluster trials), may provide such a balance. However, there are important questions of fairness to resolve before any such research can proceed. (shrink)

BackgroundThe present study aimed at assessing the diagnostic properties of the Montreal Cognitive Assessment in non-demented ALS patients and at exploring the MoCA administrability according to motor-functional status.MaterialsN = 348 patients were administered the MoCA and Edinburgh Cognitive and Behavioural ALS Screen. Administrability rates and prevalence of defective MoCA scores were compared across King’s and Milano-Torino clinical stages. Regression models were run to test whether the non-administrability of the MoCA and a defective score on it were predicted, net of (...) the ECAS-Total, by disease duration, ALS Functional Rating Scale-Revised and progression rate, computed as /disease duration. Intrinsic and post-test diagnostics were tested against a below-cut-off ECAS-total score.ResultsThe 79.9% of patients successfully underwent the MoCA, whose administrability rates decreased with advanced clinical stages, at variance with its defective score prevalence. The probability of the FAB not being administrable was predicted only by lower ALSFRS-R-bulbar and-upper-limb scores; no motor features, but the ECAS-Total, predicted a defective MoCA performance. The MoCA showed high accuracy and good intrinsic and post-test properties—being slightly more specific than sensitive.DiscussionIn non-demented ALS patients, the MoCA is featured by optimal diagnostics as a screener for cognitive impairment, especially for ruling-out its occurrence, as long as patients are in the early stages of the disease and have sufficiently spared bulbar and upper-limb functions. (shrink)

The concept of selecting for a disability, and deafness in particular, has triggered a controversial and sometimes acrimonious debate between key stakeholders. Previous studies have concentrated on the views of the deaf and hard of hearing, health professionals and ethicists towards reproductive selection for deafness. This study, however, is the first of its kind examining the views of hearing children of deaf adults towards preimplantation genetic diagnosis and prenatal diagnosis to select for or against deafness. Hearing children of deaf adults (...) straddle both the deaf and hearing worlds, and this dual perspective makes them ideally placed to add to the academic discourse concerning the use of genetic selection for or against deafness. The study incorporated two complementary stages, using initial, semistructured interviews with key informants as a means to guide the subsequent development of an electronic survey, completed anonymously by 66 individuals. The participants shared many of the same views as deaf individuals in the D/deaf community. The similarities extended to their opinions regarding deafness not being a disability, their ambivalence towards having hearing or deaf children and their general disapproval of the use of genetic technologies to select either for or against deafness. (shrink)

Metastasis is one of the clinical parameters that has a strong negative influence on the prognosis of cancer patients. In recent years, significant advances have furthered our understanding of this process at the molecular and biological levels. This paper will discuss recent discoveries relating to the earliest, intra‐tumoral stages of metastasis in cancer cells, specifically focusing on: (i) the development of metastatic traits during primary tumorigenesis; (ii) intrinsic and extrinsic cancer cell programs associated with malignant traits; (iii) the intra‐tumoral (...) migration patterns of cancer cells and the dynamic roles played by the Rho/Rac GTPases and epithelial‐mesenchymal transitions in this process; and (iv) the genetic strategies used by metastatic cancer cells to promote intra‐tumoral cell migration and their subsequent escape to peripheral tissues. Finally, the therapeutic and diagnostic relevance of this information will be discussed, as well as potential future developments. (shrink)

Ethical dilemmas are part of medicine, but the type of challenges, the frequency of their occurrence and the nuances in the difficulties have not been systematically studied in low-income settings. The objective of this paper was to map out the ethical dilemmas from the perspective of Ethiopian physicians working in public hospitals. A national survey of physicians from 49 public hospitals using stratified, multi-stage sampling was conducted in six of the 11 regions in Ethiopia. Descriptive statistics were used and the (...) responses to the open-ended question “If you have experienced any ethical dilemma, can you please describe a dilemma you have encountered in your own words?” were analyzed using a template analysis process. A total of 587 physicians responded, and 565 met the inclusion criteria. Twelve of 24 specified ethically challenging situations were reported to be experienced often or sometimes by more than 50% of the physicians. The most frequently reported challenge concerned resource distribution: 93% agreed that they often or sometimes had to make difficult choices due to resource limitation, and 83% often or sometimes encountered difficulties because patients were unable to pay for the preferred course of treatment. Other frequently reported difficulties were doubts about doing good or harming the patient, relating to conflicting views, concern for family welfare, disclosure issues and caring for patients not able to consent. Few reported dilemmas related to end-of-life issues. The 200 responses to the open-ended question mirrored the quantitative results. Ethiopian physicians report ethical challenges related more to bedside rationing and fairness concerns than futility discussions and conflicts about autonomy as described in studies from high-income countries. In addition to the high report of experienced challenges, gravity of the dilemmas that are present in their narratives are striking. Recognition of the everyday experiences of physicians in low-income settings should prompt the development of ethics teaching and support mechanisms, discussion of ethical guidelines as well as increase our focus on how to improve the grave resource scarcity they describe. (shrink)

Relatively little has been written about the ethics of conducting early phase clinical trials involving subjects from the developing world. Below, I analyze ethical issues surrounding one of gene transfer’s most widely praised studies conducted to date: in this study, Italian investigators recruited two subjects from the developing world who were ineligible for standard of care because of economic considerations. Though the study seems to have rendered a cure in these two subjects, it does not appear to have complied (...) with various international guidelines that require that clinical trials conducted in the developing world be responsive to their populations’ health needs. Nevertheless, policies devised to address large scale, late stage trials, such as the AZT short‐course placebo trials, map somewhat awkwardly to early phase studies. I argue that interest in conducting translational research in the developing world, particularly in the context of hemophilia trials, should motivate more rigorous ethical thinking around clinical trials involving economically disadvantaged populations. (shrink)

Headache disorders can be considered as the predominant neurological condition. In the field of neurological diseases, migraine was estimated to cost a total of €27 billion per year for the loss through reduced work productivity in the European Community. Medical data and information in turn provide knowledge based on which physicians make scientific decisions for diagnosis and treatments. It is, therefore, very useful to create diagnostic tools to help physicians make better decisions. This paper is focused on a new hybrid (...) clustering system combining analytic hierarchy process and weighted fuzzy c-means clustering method for diagnosing children with primary headache disorder. The proposed three-stage hybrid diagnosing system is tested on data set collected from hospitalized children in the Clinical Centre of Vojvodina, Novi Sad, Serbia. (shrink)

ABSTRACTRelatively little has been written about the ethics of conducting early phase clinical trials involving subjects from the developing world. Below, I analyze ethical issues surrounding one of gene transfer’s most widely praised studies conducted to date: in this study, Italian investigators recruited two subjects from the developing world who were ineligible for standard of care because of economic considerations. Though the study seems to have rendered a cure in these two subjects, it does not appear to have complied (...) with various international guidelines that require that clinical trials conducted in the developing world be responsive to their populations’ health needs. Nevertheless, policies devised to address large scale, late stage trials, such as the AZT short‐course placebo trials, map somewhat awkwardly to early phase studies. I argue that interest in conducting translational research in the developing world, particularly in the context of hemophilia trials, should motivate more rigorous ethical thinking around clinical trials involving economically disadvantaged populations. (shrink)

During a pandemic, where there is widespread human infection, various and varying measures are taken that are targeted at public health objectives. During the early stages of a pandemic, these objectives may focus on containing the disease and minimizing its spread, but they may switch to mitigation as the emergent infectious disease takes hold in a population. There has been considerable debate and elucidation of the ethical principles and framework for the various responses including the need to fast track research (...) and vaccine development. However, the measures imposed during a pandemic would have unintended and untoward effect on ongoing clinical research. For example, precautionary measures, such as social distancing, may hamper ongoing clinical research, because recruitment and participation of patients and healthy volunteers is a potential source of virus spread. In this paper, we argue that a framework is needed to ensure the continuity of such research. Such a framework that considers the pertinent issues would need the ‘buy in’ of the key stakeholders (policy makers, funding agencies, institutional authorities, researchers and subjects) to ensure that the issues that are ethically relevant to pandemic planning would not be neglected or overlooked. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Clinical CommentarySim Kang, Associate ProfessorRegarding the question of whether to disclose the incidental finding or not to the 72-year-old subject, one needs to consider several issues pertaining to the elderly subject, investigator team, informed consent process, illness under examination and wider societal and cultural context. First, in terms of the subject, would keeping the incidental finding secret in the context of the informed consent be respectful of the (...) wishes of the subject? One needs to bear in mind that consent was taken with the understanding that assessments will not be further shared with the subject as the assessments were done in the research study to generate new data and were not part of clinical evaluation or treatment. In one sense, autonomy of the subject in agreeing and consenting to the study investigations must be respected and the subject is comfortable that no results of the extensive assessments (blood tests and brain scans which are performed at baseline and annually for three years prospectively) will be proffered in the course of the project. At a more personal level, it may also be that the subject prefers not to know of any incidental findings even if present, which in some cases may be related to cultural notions of abnormal findings and ill health.Second, from the standpoint of the research team, would awareness of the space-occupying lesion but not informing the subject constitute a breach of ethical principles of beneficence and non maleficence? When the subject is enrolled in a research study, it is understood that the balance between research risks and benefits should have been evaluated in favour of the latter. Although more needs to be clarified to determine the clinical significance of the lesion, there is a possibility that the lesion may be malignant which would pose [End Page 289] further challenges. If the lesion is detected early, there may be a likelihood of early intervention, including surgical or non-surgical options. If the lesion of undetermined stage at present is not treated expediently and expeditiously, is there a possibility of it progressing to a stage when delayed treatment may be less effective? In this aspect, the welfare of the subject needs to be kept in mind. Even if nondisclosure is opted, is it just to allow the subject to continue in the longitudinal study if the small intracerebral lesion turns out to be malignant or that treatment may be rendered less effective over time?Third, with regard to the informed consent procedure, does the patient fully appreciate the details and implications of the study including not sharing laboratory or neuroimaging evaluations? For the process of informed consent to be meaningful, there are three elements that need to be present, namely adequate and appropriate disclosure of details about the study, demonstration of understanding of the information presented, as well as voluntariness in participation. Pertaining to adequate disclosure, was there appropriate disclosure and discussion of some of the key aspects of the study, including prospective nature lasting three years, repeated measurements and no sharing of details of assessments? The subject needs to have an appreciation of the impact of the information beyond intellectual comprehension. Was he or she cognisant of the number of visits over the entire course of the study as well as the amount of time involved for each visit? What was the response of the subject when it was made known that additional information obtained from the study evaluations will not be revealed or disclosed?Factors that may influence the understanding in this case include older age with possible easier fatigability and shorter attention span, severity of illness with related level of cognitive impairment, educational level, and familiarity with research procedures, all of which are unclear in this case at this point. With respect to voluntariness, was there any undue coercion or influence that may compromise the respect for autonomy of the research subject? It is noteworthy that the team has painstakingly committed to retake the consent before each follow up (thrice over three years) and that the subject can withdraw from the participation in the study at any point in time. Were there factors that may affect the willingness of the subject... (shrink)

Psychoanalysis is sometimes thought to rely on a “pragmatic theory of truth,” whose chief assumption should be that the effectiveness of a treatment counts as evidence for the truth of the interpretations provided during each treatment, and/or the psychoanalytic ontology of mind itself. While there is some support for this claim in psychoanalytic views both on the nature of psychic reality and on clinical practice, it needs qualification. It should not be taken to imply that the theory is true (...) because or insofar as it (clinically) works. What I mean to show is, rather, that psychoanalysis is a distinctive illustration of the pragmatist concept that effective explanations are, in Dewey’s words, “experimental,” and adjust themselves to real processes while changing reality, and indeed by changing reality. Truth enjoys, in psychoanalysis, a peculiar status, being what one might call an emergent property of a relational process. But not just any relational process, even if it “works,” will produce truth. The key of psychoanalytic treatment is transference, and the main pragmatic character of transference is what one may call its theatrical quality. I try to clarify this through a comparison of Freud’s and Pierre Janet’s clinical approaches. (shrink)

While a significant literature has appeared discussing theoretical ethical concerns regarding COVID-19, particularly regarding resource prioritization, as well as a number of personal reflections on providing patient care during the early stages of the pandemic, systematic analysis of the actual ethical issues involving patient care during this time is limited. This single-center retrospective cohort mixed methods study of ethics consultations during the first surge of the COVID 19 pandemic in Massachusetts between March 15, 2020 through June 15, 2020 aim to (...) fill this gap. Results indicate that there was no significant difference in the median number of monthly consultation cases during the first COVID-19 surge compared to the same period the year prior and that the characteristics of the ethics consults during the COVID-19 surge and same period the year prior were also similar. Through inductive analysis, we identified four themes related to ethics consults during the first COVID-19 surge including (1) prognostic difficulty for COVID-19 positive patients, (2) challenges related to visitor restrictions, (3) end of life scenarios, and (4) family members who were also positive for COVID-19. Cases were complex and often aligned with multiple themes. These patient case-related sources of ethical issues were managed against the backdrop of intense systemic ethical issues and a near lockdown of daily life. Healthcare ethics consultants can learn from this experience to enhance training to be ready for future disasters. (shrink)

Background Protecting the privacy of research participants is widely recognized as one of the standard ethical requirements for clinical research. It is unknown, however, how research professionals regard concepts of privacy as well as the situations in the research setting that require privacy protections. The aim of this study was to explore the views of research professionals from Arab countries regarding concepts and scope of privacy that occur in clinical research. Methods We adopted an exploratory qualitative approach by (...) the use of focus group discussions. We recruited individuals involved in research from Egypt and Morocco. We analyzed focus group data via a constant comparison approach, which consisted of close reading of the transcribed interviews followed by coding and then determining themes and subthemes. Results Between August 2016 and July 2018, we conducted nine focus group discussions. Respondents discussed several privacy issues that occurred before the research began ; during research, and after the research. Respondents revealed their perspectives of patients towards privacy in the clinical and research settings and mentioned that patients are more likely to permit access to their privacy in the clinical setting compared with research setting due to the existence of benefits and trust in clinical care. Respondents also recommended training regarding data protections for individuals involved in research. Conclusions Our study shows that research professionals discussed a range of privacy issues that are present during the different stages of research. We recommend 1) development of standards regarding privacy protections during recruitment efforts; 2) additional training for individuals involved in research regarding best practices with data security in secondary research; 3) a quantitative study involving investigators and REC members to determine their knowledge, attitudes and practices regarding privacy issues that occur in research; and 4) a quantitative study involving patients to elicit their views regarding their privacy concerns in research. (shrink)

The past decade has witnessed a shift in the ambitions of pharmacists away from the core role of dispensing medicines towards more interesting and rewarding relationships and responsibilities with other healthcare providers and patients. The patient-centred role of pharmacists has allowed ethical issues experienced in medical practice to surface in pharmacy practice, resulting in an increase in the number and variety of ethical dilemmas that pharmacists face in their routine pharmacy practice. Pharmacy education prepares pharmacy students for practice and must (...) be in tune with the professional dynamics. Many countries that provide patient-centered pharmacy services have redesigned pharmacy ethics education while others are in various stages of revision of their curriculum in order to adequately equip future pharmacists with the rudiments required to handle ethical issues in clinical pharmacy practice. In contrast, in Nigeria, little or no pharmacy ethics is taught to pharmacy students and the challenge lies with the curriculum design and method of teaching. (shrink)

Discusses concepts of agency and free will from the perspective of clinical practice and feminism. Following a definition of agency that locates it in a relational context , the problematized nature of subjective experience is explored from both a feminist and a psychoanalytic perspective. These considerations set the stage for examining the contradictions and dilemmas of clinical practice devoted to individual change and improving lives as well as political values and ideology devoted to social change, suggesting the history (...) of incest in Western culture and practice as an example. The need to act/practice despite uncertainty is acknowledged, relating the position of the practitioner to the responsibilities of being a parent. 2012 APA, all rights reserved). (shrink)

IntroductionOne of the most important duties of hospital ethics committees is to provide medical ethics consultation to the staff and patients. This study was conducted with the aim of the needs assessment of the staff for optimal provision of medical ethics consultation services.Materials and methodsThe data collection tool was a self-administered questionnaire. Hospital managers, chief nursing officers, ward managers, and head nurses of all hospitals affiliated with Tehran and Iran University of Medical Sciences entered the study. The questionnaire together with (...) an invitation letter was sent to the samples. In the next stage, telephone follow-up of the incomplete forms was performed by the research team.ResultsA total of 448 persons participated in this study (response rate: 54.2%). The mean frequency of the need for ethics consultation in each ward was 5.2 times in the last 3 months with a median of 3. The highest needs for consultation, which were common in all wards, were observed in treatment rejection by the patient, providing necessary information to obtain informed consent and obtaining consent to high risk procedures, conflict between the decisions made by the patient and the family members, decision making for the high risk patient, request for futile or inappropriate treatments, giving bad news, and decision making for the incompetent patient.ConclusionThe prevalence of ethical issues in clinical wards is variably high. The ethical issues in the clinical setting are mainly related to respect for the patient’s autonomy and competency for decision making. (shrink)

This article historicizes a single stage in how the contemporary obsessive–compulsive disorder (OCD) category was built. Starting from the position that the two central components which make up OCD are ‘obsessions’ and ‘compulsions’, it illustrates how these concepts were taken apart by a small group of clinical psychologists working at the Institute of Psychiatry and the Maudsley psychiatric hospital in south London in the early 1970s, and why compulsions were investigated whilst obsessions were ignored. The decision to distinguish the (...) previously undifferentiated symptoms is attributed to the commitment amongst psychologists at the Maudsley, most notably Stanley Rachman, to an empirical conception of science which emphasized observability. Two aspects of this are discussed. First, compulsions were deemed ‘visible’ through their correspondence with animal behaviour. Second, the symptom was seen as open to an experimental modification procedure which privileged visible outcomes. Ultimately, the article concludes that the historical division between ‘obsessions’ and ‘compulsions’, and the extensive investigation of the latter, has had substantial implications for the development of OCD as a category centred on visible behaviours and treated through behavioural means. (shrink)

Now in its fourth edition, Rational Diagnosis and Treatment: Evidence-Based Clinical Decision - Making is a unique book to look at evidence-based medicine and the difficulty of applying evidence from group studies to individual patients._ The book analyses the successive stages of the decision process and deals with topics such as the examination of the patient,_the reliability of clinical data, the logic of diagnosis, the fallacies of uncontrolled therapeutic experience and the need for randomised clinical trials and (...) meta-analyses. It is the main theme of the book that, whenever possible, clinical decisions must be based on the evidence from clinical research, but the authors also explain the pitfalls of such research and the problems involved in applying evidence from groups of patients to the individual patient._ For this new edition, the sections on placebo and meta-analysis and on alternative medicine have been thoroughly updated, and there is more focus on insufficient reporting of harms of interventions. The sections on different research designs describe advantages and limitations, and the increased medicalisation and the effects of cancer screening on health people are noted. A section on academic freedom when clinicians collaborate with industry and ghost authors is added._ This essential reference work integrates the science and statistical approach of evidence-based medicine with the art and humanism of medical practice; distinguishing between data, sets of data, knowledge and wisdom, and their application. Such an intellectually challenging book is ideal for both medical students and doctors who require theoretical and practical clinical skills to help ensure that they apply theory in practice. (shrink)

All investigators funded by the National Institutes of Health are now required to receive training about the ethics of clinical research. Based on a course taught by the editors at NIH, Ethical and Regulatory Aspects of Clinical Research is the first book designed to help investigators meet this new requirement. The book begins with the history of human subjects research and guidelines instituted since World War II. It then covers various stages and components of the clinical trial (...) process: designing the trial, recruiting participants, ensuring informed consent, studying special populations, and conducting international research. Concluding chapters address conflicts of interest, scientific misconduct, and challenges to the IRB system. The appendix provides sample informed consent forms. This book will be used in undergraduate courses on research ethics and in schools of medicine and public health by students who are or will be carrying out clinical research. Professionals in need of such training and bioethicists also will be interested. (shrink)

Tumor‐infiltrating lymphocyte (TIL) therapy is a promising approach for treating refractory or advanced solid cancers by using autologous TILs harvested from cancer tissues. Despite the heterogeneity of cancer, TIL therapy can potentially produce a positive therapeutic response, including complete remission.After decades of research on lymphocyte functions, culture/expansion methods, therapeutic protocols, and multiple clinical trials, TIL therapy has finally reached a stage where it can be formally approved for clinical use.TIL therapy is expected to hold a unique position among (...) anti‐cancer therapeutic options as a standard intervention. To successfully introduce TIL therapy into clinical settings, there is a need to expand therapeutic indications and set up the best protocols for cancer tissue sampling and manufacturing, and related clinical trials. Moreover, studies on next‐generation TIL therapy have already begun, and post‐approval real‐world data will promote and support further research. (shrink)

Issues of race have traditionally been addressed in medical school curricula in a didactic manner. However, medical school curricula often lack adequate opportunity for the application of learning material relating to race and culture. When confronted with acts of racism in clinical settings, students are left unprepared to respond appropriately and effectively. Forum Theatre offers a dynamic platform by which participants are empowered to actively engage with and become part of the performance. When used in an educational context, Forum (...) Theatre can be a powerful tool for students to interact with a wide variety of social issues. This paper describes the process by which one medical school designed a workshop in the Forum Theatre style to equip students to respond to racism observed in clinical settings. Based on real student experiences, the Responding to Racism in the Clinical Setting workshop was designed to give students an opportunity to combine cultural humility, communication theory and conflict resolution skills in order to prepare for interactions in clinical stages of medical education. As a result of workshop evaluations, surveys, and written reflections, the authors propose that Forum Theatre is a novel teaching modality for incorporating issues of race and culture into medical curriculum. (shrink)

Nicolas Philibert's 1997 documentary, La moindre des choses, depicts the daily lives of residents and staff at the private psychiatric clinic La Borde, and their production of Witold Gombrowicz's play Operetka. This paper will analyse the aesthetic and ethical implications of La Borde's production of Gombrowicz's play by mapping the documentary, text and production's collective expressions. The film's capacities to reconfigure audience subjectivities through a filmic and intensive entanglement will be explored at length by framing the documentary's cinematography in Félix (...) Guattari's theories of the ethico-aesthetic paradigm and minor cinema. (shrink)

IntroductionDespite the need for trained physician ethicists, fellowships in clinical ethics are limited and primarily offered to thosewho have completed a graduate degree. The standardization of credentialing for clinical ethics consultants (CECs) and the restructuring of undergraduate medical education allow innovative models to train CECs that can provide an expanded opportunity for formal ethics training at an earlier stage.MethodsAt the University of Michigan Medical School we developed, implemented, and evaluated a pre-doctoral clinical ethics fellowship program from 2017 (...) to 2019 for senior medical students, designed to meet established competencies for CECs. Consultation notes from the beginning and end of the fellowship program were randomly selected for each fellow and independently rated by two faculty ethicists who used the validated Ethics Consultation Quality Assessment Tool (ECQAT).1 Inter rater reliability and trends in scores over time were calculated.ResultsThree students successfully completed the fellowship at the University of Michigan Medical School, conducted at least 50 formal ethics consultations, and spent approximately 40 hours a week on service for a minimum of six months. All students finished the fellowship with teaching and policy development experience, first-authored peer-reviewed manuscripts, and national presentations. The fellows demonstrated improvement in their ECQAT overall holistic rating score; all ended their fellowship with a holistic score of adequate or above. There was 92 percent agreement between raters withrespect to the acceptability of the fellows’ ethics consult notes. Two fellows have taken and passed the Healthcare Ethics Consultant-Certification (HEC-C) exam offered by the American Society for Bioethics and Humanities (ASBH).ConclusionsIntegration of a pre-doctoral fellowship model that meets professional certification standards for clinical ethics consultation creates an opportunity for medical students to become trained CECs early in their career. (shrink)

Se propone una reflexión sobre el método clínico y sus etapas, la relación médico-paciente y la presencia tecnológica en la Cardiología Pediátrica. La ecocardiografía transtorácica no puede sustituir el pensamiento médico, la anamnesis, ni el examen físico. Como medio diagnóstico realizado e interpretado por humanos, está sujeto a error, el cual se minimiza según la calidad de los datos clínicos aportados por el médico que lo solicita. El presente trabajo tiene como objetivo analizar los aspectos éticos del método clínico en (...) relación con la utilización de la ecocardiografía transtorácica en niños con cardiopatías congénitas. It is proposed a reflexion about the clinical method and its stages, the doctor-patient relation and the presence of technology in paediatric cardiology. The transthoracic echocardiography can4t substitute medical thought, neither the anamnesis nor the physical examination. As a diagnostic medium carried out and interpreted by humans, it is subject to error, which it is minimized according to the quality of the clinical data provided by the doctor who requests them. The present work has the objective to analyse the Ethical foundations of the clinical method in connection with the use of transthoracic echocardiography in children with congenital cardiopathies. (shrink)

Clinical trials aim to minimise participant risk and generate new clinical knowledge for the wider population. Many military agencies are now investing efforts in pushing towards developing new treatments involving Brain-Computer Interfaces, Gene Therapy and Stem Cells interventions. These trials are targeting smaller disease groups, as such they give rise to novel participant risks of harms that are largely not accommodated by existing practice. This is of most concern with irreversible harms at early trial stages, where participants may (...) forfeit any future therapy, and in personalised medicine, where the individual participant assumes all of the trial risk. Given these new experimental interventions involve high risk of irreversible harms, how much risk should patients be exposed to when participating in experimental testing of innovative technologies? Designing clinical trials which better balance risk/benefit ratios for participants is crucial. The aim of this book chapter is to suggest a new stratified risk framework aimed at minimising the risk-benefit ratio to participants in clinical trials associated with high risk of irrevocable harms. We will argue it demands a higher-level of clinical data capture at earlier trial stages than predicated by current trial doctrine; it also requires publication of all trial data to minimise risk to participants of any future trial. (shrink)

Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and healthy volunteers participating (...) in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research. (shrink)

The purpose of this study was to explore how one person experienced the early years of dementia as she was living through the pre-clinical and earlyclinical stages of Alzheimer’s disease. Interviews were held onfour occasions over a period of three years. The data were analyzed usingthe descriptive phenomenological psychological method, in which theresearcher approached the data from a caring perspective. The livedexperience of early-stage Alzheimer’s disease showed to be acomplex transitional phenomenon that involves a dynamic process of personaladjustment. The (...) process is set in motion as the participant receives thediagnosis and will eventually lead her towards a state of increased opennessand receptiveness toward the disease. The results describe this process asit unfolds in the context of the overall experience, and the variousadjustments that the participant undertakes. Some reflections concerning theplausible needs of patients with early-stage Alzheimer’s diseaseare included in the discussion. (shrink)

Background If trials of therapeutic interventions are to serve society's interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical - trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world's nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative entities of (...) the 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial's stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research. (shrink)

In this paper, our goal is to survey some of the legal contexts within which violence risk assessment already plays a prominent role, explore whether developments in neuroscience could potentially be used to improve our ability to predict violence, and discuss whether neuropredictive models of violence create any unique legal or moral problems above and beyond the well worn problems already associated with prediction more generally. In Violence Risk Assessment and the Law, we briefly examine the role currently played by (...) predictions of violence in three high stakes legal contexts: capital sentencing, civil commitment hearings, and sexual predator statutes. In Clinical vs. Actuarial Violence Risk Assessment, we briefly examine the distinction between traditional clinical methods of predicting violence and more recently developed actuarial methods, exemplified by the Classification of Violence Risk software created by John Monahan and colleagues as part of the MacArthur Study of Mental Disorder and Violence [1]. In The Neural Correlates of Psychopathy, we explore what neuroscience currently tells us about the neural correlates of violence, using the recent neuroscientific research on psychopathy as our focus. We also discuss some recent advances in both data collection and data analysis that we believe will play an important role when it comes to future neuroscientific research on violence. In The Potential Promise of Neuroprediction, we discuss whether neuroscience could potentially be used to improve our ability to predict future violence. Finally, in The Potential Perils of Neuroprediction, we explore some potential evidentiary, constitutional, and moral issues that may arise in the context of the neuroprediction of violence. (shrink)

BackgroundCommunity Advisory Boards (CAB) have become essential organs of involving communities in HIV clinical trials especially in developing countries. However, limited empirical evidence exists on the role of CABs in low and middle-income countries including Tanzania. This study aims at exploring the role of CABs in community-based HIV clinical trials conducted in Tanzania.MethodologyWe adopted a phenomenological approach to purposefully select HIV clinical trial stakeholders. These included CAB members, researchers and Institutional Review Board (IRB) members in Tanzania. We (...) conducted In-depth Interviews (IDIs) with ten participants and three Focus Group Discussions (FGDs) with eighteen participants. The data were thematically analyzed with the aid of MAXQDA software version 20.2.1.ResultsThe findings indicate that at every stage of implementation of a community-based HIV clinical trial, a functioning CAB is important for its success. This importance is based on contextualization of the informed consent process and protocol, managing rumours in the community, weighing trial risks and benefits, sensitizing the community, assisting participant recruitment, tracing and retention. However, being perceived as financial beneficiaries than community representatives emerged as a challenge to CAB members. ConclusionThe study empirically indicates the need for functioning CABs in every stage of implementation of community-based HIV clinical trials. The roles of which are interwoven in serving research goals and protecting the interests of the community and that of trial participants. (shrink)

Regulating clinical trials for testing new drugs is fraught with risk. Misregulation can slow development of innovative and useful new drugs, but in other ways misregulation can foster trials that are inefficient and unethical, driven by commercial rather than scientific ends, and that can harm patients. In this paper, we argue not for more but for better regulation, based on the goal of rapidly producing innovative and safe products that represent significant advances in medical care. Data on industry-funded, late-stage (...) clinical trials demonstrate an urgent need for dramatic changes in how these trials are designed, conducted, and analyzed. On the one hand, current patent rules can dissuade development of innovative new products with smaller markets and press trial designers to create positive results too rapidly. But at the same time, numerous studies show that when the pharmaceutical industry sponsors clinical trials, the results are systematically biased in favor of the sponsor's product, often to the detriment of patients and the public. The reasons for this bias are both complex and unavoidable, and the ways in which clinical trial design, conduct, and reporting can be inappropriately influenced are so varied and nuanced, that efforts to manage this conflict of interest and prevent harms are inevitably unsuccessful. Instead, we conclude such conflict should be avoided and a strong firewall should exist between drug developers and the final stages of clinical testing in humans. All financial support for phase III clinical trials should pass through a public-private partnership organization — perhaps tied to a broader clinical effectiveness research enterprise — which would be charged with designing, funding, and monitoring late-stage human clinical trials of new pharmaceutical products. (shrink)

BackgroundThe terminal illness of late-stage Alzheimer’s and related dementias is progressively cruel, burdensome, and can last years if caregivers assist oral feeding and hydrating. Options to avoid prolonged dying are limited since advanced dementia patients cannot qualify for Medical Aid in Dying. Physicians and judges can insist on clear and convincing evidence that the patient wants to die—which many advance directives cannot provide. Proxies/agents’ substituted judgment may not be concordant with patients’ requests. While advance directives can be patients’ last resort (...) to attain a peaceful and timely dying consistent with their lifelong values, success depends on their being effective and acceptable. A single flaw can provide opponents justification to refuse the directive’s requests to cease assisted feeding.AimThis article considers 24 common advance directive flaws in four categories. Process flaws focus on how patients express their end-of-life wishes. Content flaws reflect drafters’ selection of conditions and interventions, and how they are described. Inherent flaws can make advance directives unacceptable to authorities concerned about premature dying. Strategies are needed to compel physicians to write needed orders and to prevent third parties from sabotaging these orders after they are implemented. The article includes excerpts from “dementia-specific” directives or supplements that exemplify each flaw—mostly from the US and Europe. No directive critiqued here included an effective strategy to resolve this long-debated bioethical conflict: the past directive requests “Cease assisted feeding” but the incapacitated patient apparently expresses the desire to “Continue assisted feeding.” Some opponents to the controversial request, cease assisted feeding, use this conflict as a conceptual wedge to practice hard paternalism. This article proposes a protocol to prevent this conflict from emerging. These strategies may prevent authorities from requiring patients to fulfill authorities’ additional clinical criteria as a prerequisite to honor the requests in patients directives.ConclusionThis critique of flaws may serve as a guide to drafting and to selecting effective and acceptable advance directives for dementia. It also poses several bioethical and clinical questions to those in authority: Does your paternalistic refusal to honor patients’ wishes respect their self-determination? Protect vulnerable patients from harm? Force patients to endure prolonged suffering? Violate the principles of bioethics? Violate the very foundation of patient-centered care? (shrink)

There are a number of existing classifications and staging schemes for carcinomas, one of the most frequently used being the TNM classification. Such classifications represent classes of entities which exist at various anatomical levels of granularity. We argue that in order to apply such representations to the Electronic Health Records one needs sound ontologies which take into consideration the diversity of the domains which are involved in clinical bioinformatics. Here we outline a formal theory for addressing these issues (...) in a way that the ontologies can be used to support inferences relating to entities which exist at different anatomical levels of granularity. Our case study is the colon carcinoma, one of the most common carcinomas prevalent within the European population. (shrink)

The 2012 Varsity Medical Debate between Oxford University and Cambridge University provided a stage for representatives from these famous institutions to debate the motion “This house believes that trainee doctors should be able to use the developing world to gain clinical experience.” This article brings together many of the arguments put forward during the debate, centring around three major points of contention: the potential intrinsic wrong of ‘using’ patients in developing countries; the effects on the elective participant; and the (...) effects on the host community. The article goes on to critically appraise overseas elective programmes, offering a number of solutions that would help optimise their effectiveness in the developing world. (shrink)

Flawed clinical practice guidelines may compromise patient care. Commercial conflicts of interest on panels that write treatment guidelines are particularly problematic, because panelists may have conflicting agendas that influence guideline recommendations. Historically, there has been no legal remedy for conflicts of interest on guidelines panels. However, in May 2008, the Attorney General of Connecticut concluded a ground-breaking antitrust investigation into the development of Lyme disease treatment guidelines by one of the largest medical societies in the United States, the Infectious (...) Diseases Society of America (IDSA). Although the investigation found significant flaws in the IDSA guidelines development process, the subsequent review of the guidelines mandated by the settlement was compromised by a lack of impartiality at various stages of the IDSA review process. This article will examine the interplay between the recent calls for guidelines reform, the ethical canons of medicine, and due process considerations under antitrust laws as they apply to the formulation of the IDSA Lyme disease treatment guidelines. The article will also discuss pitfalls in the implementation of the IDSA antitrust settlement that should be avoided in the future. (shrink)

Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children’s consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children’s competence to consent to clinical research and to what extent they explain the variation (...) in competence judgments. (shrink)