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New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that are resistant to first-line therapeutics. Here we report the exploration of MMV692140 (2) from the Pathogen Box, a collection of 400 compounds that was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 was profiled in in vitro models of malaria and was found to be active against multiple life-cycle stages of Plasmodium parasites. The mode of resistance, and putatively its mode of action, was identified as Plasmodium falciparum translation elongation factor 2 (PfeEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA. The compound maintains activity against a series of drug-resistant parasite strains. The structural motif of the tetrahydroquinoline (2) was explored in a chemistry program with its structure-activity relationships examined, resulting in the identification of an analog with 30-fold improvement of antimalarial asexual blood stage potency.

Background Health checks can detect risk factors and initiate prevention of cardiovascular diseases but there is no consensus on how to communicate the results. The aim of this study was to investigate the preferences of the general population for communicating health check results. Methods A randomly selected sample of the Swedish population aged 40–70 years completed a discrete choice experiment survey that included questions on sociodemographics, lifestyle and health and 15 choice questions consisting of six attributes (written results, notification method, consultation time, waiting time, lifestyle recommendation and cost). Data were analyzed with a latent class analysis (LCA). Relative importance of the attributes and predicted uptake for several scenarios were estimated. Results In the analysis, 432 individuals were included (response rate 29.6%). A three-class LCA model best fit the data. Cost was the most important attribute in all classes. Preferences heterogeneity was found for the other attributes; in Class 1, receiving consultation time and the written results were important, respondents in Class 2 dominated on costs and respondents in Class 3 found consultation time, waiting time and lifestyle recommendations to be important. Health literate respondents were more likely to belong to Class 3. The predicted uptake rates ranged from 7 to 88% for different health checks with large differences across the classes. Conclusion Cost was most important when deciding whether to participate in a health check. Although cost was the most important factor, it is not sufficient to offer health checks free-of-charge if other requirements regarding how the test results are communicated are not in place; participants need to be able to understand their results. Supplementary Information The online version contains supplementary material available at 10.1007/s40271-021-00512-4.

GDPR is currently being implemented across Europe and researchers, ethical review boards and national authorities are waiting for guidance on how to do the ethical balancing of the interests of privacy and the interest of conducting effective scientific, e.g. biomedical research, in practice. In order to reach this one must both understand the specific challenges that are related to new developments within the field of personalised medicine where massive uses of personal data are foreseen and what it really means to protect someone’s privacy. In this chapter I will suggest how a balance may be reached between personalised medicine and privacy protection based on the premises of genetic science, ethics and the GDPR.

Objectives There is an increased interest in patient preferences informing the development and authorisation of medical products. A requirement for robust and meaningful results of such studies is that patients adequately understand the risks and benefits associated with treatments for which their preferences are elicited. This study aims to determine the influence of an educational tool, compared with traditional written information on patient preferences elicited in a discrete choice experiment (DCE). Methods Treatment preferences of Swedish patients with rheumatoid arthritis (RA) were assessed using a DCE. Patients were recruited via clinics, a research panel, and the Swedish Rheumatism Association. Respondents received training materials either as plain written text or as an online educational tool. The educational tool was designed to enhance understanding of the written text by using graphics, pictograms, icon arrays, spoken text, and click-on functions. Data were analysed using random parameter logit models. Results 675 patients with RA were included in the analysis. The patients received either a written information (n = 358) or information via an educational tool (n = 317). Respondents receiving the educational tool placed relatively more importance on all included side effects in their decision making, compared to respondents receiving the written text, who placed greater importance on treatment effectiveness and administration methods. Conclusion Compared to the respondents receiving the written text, the decisions of respondents receiving the educational tool were more influenced by medication side effects. Further research is needed to provide guidance on how and when to use educational tools to inform and elicit patients’ preferences. Practice implications The ways in which attributes are presented to patients significantly impacts preferences measured in a DCE.

The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally. This work was supported by the U.S. Department of Health and Human Services National Institutes of Health (5r24od011883), National Institutes of Health (NIH) Office of the Director (OD); the Monarch Initiative (1R24OD011883) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54 HD079123). Sí

Contains fulltext : 207092.pdf (Publisher’s version ) (Closed access) In the era of patient-centered medicine, shared decision-making (SDM) - in which healthcare professionals and patients exchange information and preferences and jointly reach a decision - has emerged as the gold standard model for the provision of formal healthcare. Indeed, in many geographical settings, patients are frequently invited to participate in choices concerning the design and delivery of their medical management. From a clinical perspective, benefits of this type of patient involvement encompass, for example, enhanced treatment satisfaction, improved medical compliance, better health outcomes, and maintained or promoted quality of life. Yet, although the theory and enactment of SDM in healthcare are well-described in the literature [1-3], comparatively less attention has been devoted to contextualizing questions relating to if, when, and how to include patients in decisions within medical research. In this context, patient involvement would be expected to be potentially relevant for and applicable to a wide range of activities and processes, from the identification of research priorities and development of grant applications, to the design of patient information and consent procedures, formulation of interventions, identification and recruitment of study sample populations, feasibility of a clinical trial, identification, selection, and specification of endpoints and outcomes in clinical trials and observational studies, data collection and analysis, and dissemination of results. To this end, 45 clinicians, healthcare professionals, researchers, patients, caregivers, and representatives from regulatory authorities and pharmaceutical companies from 15 different countries met to discuss the level of involvement of patients with neuromuscular diseases, specifically in the following settings of medical research for neuromuscular diseases: i) registries and biobanks; ii) clinical trials; and iii) regulatory processes. In this report, we present summaries of the talks that were given during the workshop, as well as discussion outcomes from the three topic areas listed above.

Background There is increasing interest in involving patient preferences for benefits and risks in regulatory decision making. Therefore, it is essential to identify patient perspectives regarding the value of patient preference information (PPI). Objectives The aim of this study was to explore how patients with rheumatoid arthritis (RA) value the use of PPI in regulatory decision making regarding medical products. Methods Regulators and patients with RA were interviewed to gather initial insights into opinions on the use of PPI in regulatory decisions regarding medical products. The interviews were used to draft and validate the interview guide for focus groups with patients with RA. Participants were purposively sampled in collaboration with the Swedish Rheumatism Association in Stockholm and Uppsala. Each focus group consisted of three to six patients (18 in total). All interviews were audio-recorded, transcribed verbatim, and analysed using content analysis. Results According to the participants, PPI could lead to regulators considering patients’ needs, lifestyles and well-being when making decisions. PPI was important in all stages of the medical product lifecycle. Participants reported that, when participating in a preference study, it is important to be well-informed about the use of the study and the development, components, administration, and risks related to the medical products. Conclusions Patients thought PPI could be valuable to consider in regulatory decisions. It is essential for patients to be well-informed when asked for their preferences. Research on information materials to inform patients in preference studies is needed to increase the value of PPI in regulatory decision making. Electronic supplementary material The online version of this article (10.1007/s40271-018-0344-2) contains supplementary material, which is available to authorized users.

Background Preference assessments of patients with rheumatoid arthritis can support clinical therapeutic decisions for including biologic and targeted synthetic medicines to use. This study assesses patient preferences for attributes of second-line therapies and heterogeneity within these preferences to estimate the relative importance of treatment characteristics and to calculate the minimum benefit levels patients require to accept higher levels of side effects. Methods Between November 2018 to August 2019, patients with rheumatoid arthritis were recruited to a survey containing demographic and disease-related questions as well as a discrete choice experiment to measure their preferences for second-line therapies using biologics or Janus kinases inhibitors. Treatment characteristics included were route of administration, frequency of use, probability of mild short-term side effects, probability of side effects changing appearance, probability of psychological side effects, probability of severe side effects and effectiveness of treatment. Results A total of 358 patients were included in the analysis. A latent class analysis revealed three preference patterns: (1) treatment effectiveness as the single most important attribute, (2) route of administration as the most important attribute, closely followed by frequency of use and psychological side effects and (3) severe side effects as the most important attribute followed by psychological side effects. In addition, disease duration and mild side effects influenced the patients’ choices. Conclusion Respondents found either effectiveness, route of administration or severe side effects as the most important attribute. Patients noting effectiveness as most important were more willing than other patients to accept higher risks of side effects.

[Image: see text] The further optimization of a recently disclosed series of inverse agonists of the nuclear receptor RORC2 is described. Investigations into the left-hand side of compound 1, guided by X-ray crystal structures, led to the substitution of the 4-aryl-thiophenyl residue with the hexafluoro-2-phenyl-propan-2-ol moiety. This change resulted in to compound 28, which combined improved drug-like properties with good cell potency and a significantly lower dose, using an early dose to man prediction. Target engagement in vivo was demonstrated in the thymus of mice by a reduction in the number of double positive T cells after oral dosing.

Giving Patients’ Preferences a Voice in Medical Treatment Life Cycle : The PREFER Public–Private Project

To improve healthcare policymaking, commentators have recommended the use of evidence, health technology assessment, priority setting, and public engagement in the process of policymaking. Preconception expanded carrier screening, according to the World Health Organization's definition, is a novel health technology and therefore warrants assessment, part of which involves evaluating ethical and social implications. We examined ten Swedish policymakers' perspectives on ethical and social aspects of preconception expanded screening through in-depth expert interviewing, using a semi-structured questionnaire. Respondents were affiliated to governmental and non-governmental institutions that directly influence healthcare policymaking in Sweden. The interviews were recorded, transcribed verbatim, and analyzed via inductive thematic analysis method, which generated seven themes and several subthemes. Policymakers harbored concerns regarding the economics, Swedish and international political respects, implementation procedures, and societal effects, which included long-term ones. Moreover, participants detailed the role of public engagement, research, and responsibility in regard to preconception expanded carrier screening implementation. Since this is a qualitative study, with a small non-random sample, the results may not be generalizable to all policymakers in Sweden. However, the results give a profound insight into the process and interpretative knowledge of experts, in the Swedish milieu and the extent of readiness of Sweden to implement a preconception expanded carrier screening program.

Purpose: This study aims to determine research participants’ preferences for receiving genetic risk information when participating in a scientific study that uses genome sequencing. Methods: A discrete choice experiment questionnaire was sent to 650 research participants (response rate 60.5%). Four attributes were selected for the questionnaire: type of disease, disease penetrance probability, preventive opportunity, and effectiveness of the preventive measure. Panel mixed logit models were used to determine attribute level estimates and the heterogeneity in preferences. Relative importance of the attribute and the predicted uptake for different information scenarios were calculated from the estimates. In addition, this study estimates predicted uptake for receiving genetic risk information in different scenarios. Results: All characteristics influenced research participants’ willingness to receive genetic risk information. The most important characteristic was the effectiveness of the preventive opportunity. Predicted uptake ranged between 28% and 98% depending on what preventive opportunities and levels of effectiveness were presented. Conclusion: Information about an effective preventive measure was most important for participants. They valued that attribute twice as much as the other attributes. Therefore, when there is an effective preventive measure, risk communication can be less concerned with the magnitude of the probability of developing disease.

The development of mental disorders constitutes a complex phenomenon driven by unique social, psychological and biological factors such as genetics and epigenetics, throughout an individual's life course. Both environmental and genetic factors have an impact on mental health phenotypes and act simultaneously to induce changes in brain and behavior. Here, we describe and critically evaluate the current literature on gene-environment interactions and epigenetics on mental health by highlighting recent human and animal studies. We furthermore review some of the main ethical and social implications concerning gene-environment interactions and epigenetics and provide explanations and suggestions on how to move from statistical and epigenetic associations to biological and psychological explanations within a multi-disciplinary and integrative approach of understanding mental health.

Different types of consent are used to obtain human biospecimens for future research. This variation has resulted in confusion regarding what research is permitted, inadvertent constraints on future research, and research proceeding without consent. The National Institutes of Health (NIH) Clinical Center's Department of Bioethics held a workshop to consider the ethical acceptability of addressing these concerns by using broad consent for future research on stored biospecimens. Multiple bioethics scholars, who have written on these issues, discussed the reasons for consent, the range of consent strategies, and gaps in our understanding, and concluded with a proposal for broad initial consent coupled with oversight and, when feasible, ongoing provision of information to donors. This article describes areas of agreement and areas that need more research and dialogue. Given recent proposed changes to the Common Rule, and new guidance regarding storing and sharing data and samples, this is an important and timely topic.

Ethicists, regulators and researchers have struggled with the question of whether incidental findings in genomics studies should be disclosed to participants. In the ethical debate, a general conse ...

The development of mental disorders constitutes a complex phenomenon driven by unique social, psychological and biological factors such as genetics and epigenetics, throughout an individual's life course. Both environmental and genetic factors have an impact on mental health phenotypes and act simultaneously to induce changes in brain and behavior. Here, we describe and critically evaluate the current literature on gene-environment interactions and epigenetics on mental health by highlighting recent human and animal studies. We furthermore review some of the main ethical and social implications concerning gene-environment interactions and epigenetics and provide explanations and suggestions on how to move from statistical and epigenetic associations to biological and psychological explanations within a multi-disciplinary and integrative approach of understanding mental health.

Background: The availability of tests to predict the risk of developing chronic diseases is increasing. The identification of individuals at high risk of disease can trigger early intervention to reduce the risk of disease and its severity. In order for predictive tests to be accepted and used by those at risk, there is a need to understand people's perceptions of predictive testing. Method: A meta-synthesis of qualitative research that explored patient and public perceptions of predictive testing for chronic inflammatory diseases was conducted. Studies were coded by researchers and patient research partners, and then organised into common themes associated with the acceptability or use of predictive testing. Results: Perceived barriers to predictive testing were identified, including a concern about a lack of confidentiality around the use of risk information; a lack of motivation for change; poor communication of information; and a possible impact on emotional well-being. In order to reduce these barriers, the literature shows that a patient-centred approach is required at each stage of the testing process. This includes the consideration of individual needs, such as accessibility and building motivation for change; readily available and easy to understand pre and post-test information; support for patients on how to deal with the implications of their results; and the development of condition specific lifestyle intervention programmes to facilitate sustainable lifestyle changes. Conclusion: Patients and members of the public had some concerns about predictive testing; however, a number of strategies to reduce barriers and increase acceptability are available. Further research is required to inform the development of a resource that supports the individual to make an informed decision about whether to engage in a predictive test, what test results mean, and how to access post-test support.

Aims The pharmacokinetic (PK) similarity between PF-05280014, a proposed trastuzumab biosimilar, trastuzumab sourced from European Union (trastuzumab-EU) or from United States (trastuzumab-US) was evaluated. Safety and immunogenicity were also assessed.

In medical research, patients are increasingly recognized with ‘lay knowledge’ but their views are poorly researched. The study objective was to investigate patients’ attitudes to medical research. This is in comparison to lay and expert members on ethical review boards (ERB), as their task is to evaluate the risk−benefits of research, which are ultimately grounded in attitudes and values. From focus-group interviews with patients suffering from chronic inflammatory diseases, a postal questionnaire was developed and sent to patient members of the Swedish Rheumatism Association ( n = 1195) and to all ERB board members in Sweden ( N = 583). Response rates were 65 percent and the surveys were conducted in Jan−May 2011. Agreement across the groups included priority for medical research on diagnostic and early detection of disease. A key difference was expert and lay ERB members giving higher priority to basic research/research on lifestyle and prevention (primarily benefiting future patients), whereas patients prioritized research on daily function. On this significant point, lay members did not share the opinion of this patient group, indicating that they may be poor representatives for patients’ views. These results call for further research: how can patient perspectives be included in ERB discussions and in what way should patients’ values influence the research agenda.

Research ethics, once a platform for declaring intent, discussing moral issues and providing advice and guidance to researchers, has developed over time into an extra-legal regulatory system, complete with steering documents (ethics guidelines), overseeing bodies (research ethics committees) and formal procedures (informed consent). The process of institutionalizing distrust is usually motivated by reference to past atrocities committed in the name of research and the need to secure the trustworthiness of the research system. This article examines some limitations of this approach. First, past atrocities cannot provide the necessary justification unless institutionalized distrust is a necessary or efficient means to prevent future ones – and there are several reasons to doubt this. Second, the efficacy of ethics review in safeguarding morally acceptable research depends on the moral competence and integrity of individual researchers – the very qualities that institutionalized distrust calls into question. Third, ethics guidelines cannot, as is sometimes assumed, educate or guide researchers in moral behaviour unless they already possess considerable capacity for moral judgment. Fourth, institutionalized distrust is a potential threat to the moral competence and integrity of researchers by encouraging a blinkered view of ethical issues, inducing moral heteronomy through incentives, and alienating them to research ethics. We conclude that the moral problem posed by inappropriate short-term behaviour on behalf of researchers is dwarfed by the potential long-term consequences if their moral competence is allowed to deteriorate. Measures must therefore be taken to ensure that researchers are equipped to take their individual responsibility and are not obstructed from so doing.

It is necessary to carry out randomised clinical cancer trials (RCTs) in order to evaluate new, potentially useful treatments for future cancer patients. Participation in clinical trials plays an important role in determining whether a new treatment is the best therapy or not. Therefore, it is important to understand on what basis patients decide to participate in clinical trials and to investigate the implications of this understanding for optimising the information process related to study participation. The aims of this study were to (1) describe motives associated with participation in RCTs, (2) assess if patients comprehend the information related to trial enrolment, and (3) describe patient experiences of trial participation. Questionnaires were sent to 96 cancer patients participating in one of nine ongoing clinical phase 3 trials at the Department of Oncology, Uppsala University Hospital in Sweden. Eighty-eight patients completed the questionnaire (response rate 92%); 95% of these were patients in adjuvant therapy and 5% participated in clinical trials on palliative care. Two main reasons for participation were identified: personal hope for a cure and altruism. Patients show adequate understanding of the information provided to them in the consent process and participation entails high patient satisfaction.

One of the most common arguments in the discussion on doping is that it represents a form of cheating. In this paper it is argued that common doping-is-cheating arguments based on notions of rule-violation and unfair advantage are inadequate, since they treat cheating as distinct from the structure and the logic of competitive sport. An alternative approach to cheating in sport as regards performance enhancement will be offered based on the ethics of participation in interpersonal relationships. This participatory perspective points towards the need to broaden our conception of agency and moral responsibility in relation to doping, beyond the notion of the individual “drug-cheat” who acts in a vacuum.

It is well known that research participants want to receive genetic risk information that is about high risks, serious diseases and potential preventive measures. The aim of this study was to explore, by qualitative means, something less well known: how do healthy research participants themselves make sense of genetic risk information?A phenomenographic approach was chosen to explore research participants' understanding and assessment of genetic risk. We conducted four focus-group (N=16) interviews with participants in a research programme designed to identify biomarkers for cardiopulmonary disease.Among the research participants, we found four ways of understanding genetic risk: as a binary concept, as an explanation, as revealing who I am (knowledge of oneself) and as affecting life ahead.Research participants tend to understand genetic risk as a binary concept. This does not necessarily imply a misunderstanding of, or an irrational approach to, genetic risk. Rather, it may have a heuristic function in decision-making.Risk communication may be enhanced by tailoring the communication to the participants' own lay conceptions. For example, researchers and counselors should address risk in binary terms, maybe looking out for how individual participants search for threshold figures.

Our starting point in this article is the debate between John Harris and Iain Brassington on whether or not there is a duty to take part in scientific research. We consider the arguments that have been put forward based on fairness and a duty to rescue, and suggest an alternative justification grounded in a hypothetical agreement: that is, because effective healthcare cannot be taken for granted, but requires continuous medical research, and nobody knows what kind of healthcare they will need, participating in research should be viewed from the perspective of a social contract, based on our mutual need for medical advances.

This study determined the pharmacokinetics (PK) of figitumumab and its effects on insulin-like growth factor (IGF) axis-related biomarkers, following a single intravenous dose (10 [n = 16] and 20 [n = 12] mg/kg) in healthy adults. Serial blood sampling for PK and biomarkers was conducted up to 84 days postdose. A dose increase from 10 to 20 mg/kg led to 1.9- and 2.4-fold increases in mean C(max) and AUC∞, respectively. Median disposition half-life was 21.1 and 27.8 days at 10 and 20 mg/kg, respectively. At 10 and 20 mg/kg, figitumumab increased total IGF-1, free IGF-1, IGF binding protein (IGFBP)-3, and insulin by 4.1- and 4.8-, 8.3- and 12.1-, 2.4- and 2.9-, and 7.3- and 9.8-fold, respectively; increases were sustained throughout the 84-day period. There was a slight and transient elevation in IGF-2. Mean plasma glucose increased by 18% and 16% at 10 and 20 mg/kg, respectively. Most treatment-related adverse events were mild in severity; the most common included dry eye (n = 9) and ocular hyperemia (n = 9) in the 20-mg/kg group. No antidrug antibodies were detected. Overall, figitumumab (10 or 20 mg/kg) demonstrated PK properties typical of IgG2 antibodies and produced substantial and sustained increases in IGF-1 (total and free), IGFBP-3, and insulin.

To investigate pharmacokinetic interactions associated with coadministration of lersivirine with zidovudine, tenofovir disoproxil fumarate (DF)/emtricitabine (Truvada(®)) or abacavir/lamivudine (Epzicom(®)/Kivexa(®)).Three Phase I, open, crossover studies with two (studies 1 and 3) or three (study 2) treatment periods were conducted in healthy individuals. In study 1, individuals received zidovudine and placebo or zidovudine and lersivirine on days 1-14. In study 2, individuals received lersivirine and tenofovir DF/emtricitabine, lersivirine and placebo or tenofovir DF/emtricitabine and placebo on days 1-10. In study 3, individuals received abacavir/lamivudine only in period 1 (5 days) and abacavir/lamivudine and lersivirine in period 2 (10 days). Blood samples were taken on days 1-14 (study 1) or day of final dose (studies 2 and 3) and analysed using high performance liquid chromatography/dual mass spectrometry. Pharmacokinetic parameters were calculated by standard non-compartmental methods.When coadministered with lersivirine, zidovudine exposure increased by 35%, and exposure of its metabolite zidovudine-glucuronide decreased by 19%. Following coadministration of lersivirine and tenofovir DF/emtricitabine, tenofovir exposure increased by 30%, and lersivirine exposure decreased by 12%. Coadministration of lersivirine and abacavir/lamivudine increased abacavir exposure by 27% and decreased lamivudine exposure by 8%. Adverse events were predominantly mild in these Phase I studies.Coadministration of lersivirine with zidovudine, tenofovir DF/emtricitabine or abacavir/lamivudine influenced the systemic exposure of all nucleoside reverse transcriptase inhibitor agents investigated (except for lamivudine; emtricitabine pharmacokinetics were not assessed). Changes were not considered clinically meaningful for zidovudine and abacavir. The clinical relevance of the effect on tenofovir pharmacokinetics is currently unknown.

There is a growing concern in the ethics literature and among policy makers that de-identification or coding of personal data and biospecimens is not sufficient for protecting research subjects from privacy invasions and possible breaches of confidentiality due to the possibility of unauthorized re-identification. At the same time, there is a need in medical science to be able to identify individual patients. In particular for rare disease research there is a special and well-documented need for research collaboration so that data and biosamples from multiple independent studies can be shared across borders. In this article, we identify the needs and arguments related to de-identification and re-identification of patients and research subjects and suggest how the different needs may be balanced within a framework of using unique encrypted identifiers. Funding for this research was received by the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 305444 (RD-Connect) and 305121 (Neuromics). Hansson also received funding by the Innovative Medicines Initiative project BT-Cure (grant agreement number 115142-1), the BioBanking and Molecular Resource Infrastructure of Sweden project (financed by the Swedish Research Council), and the European Union Seventh Framework Programmes Euro-TEAM, BiobankCloud and BBMRI-LPC. Dawkins acknowledges support-in-part from the Australian National Health and Medical Research Council RD-Connect project APP1055319 under the NHMRC–European Union Collaborative Research Grants scheme. Sí

Today, certain rule-violating behaviours, such as doping, are considered to be an issue of concern for the sport community. This paper underlines and examines the affective dimensions involved in m ...

We investigated 60 patients (89 feet) with a mean age of 64 years (61 to 67) treated for congenital clubfoot deformity, using standardised weight-bearing radiographs of both feet and ankles together with a functional evaluation. Talocalcaneal and talonavicular relationships were measured and the degree of osteo-arthritic change in the ankle and talonavicular joints was assessed. The functional results were evaluated using a modified Laaveg-Ponseti score. The talocalcaneal (TC) angles in the clubfeet were significantly lower in both anteroposterior (AP) and lateral projections than in the unaffected feet (p < 0.001 for both views). There was significant medial subluxation of the navicular in the clubfeet compared with the unaffected feet (p < 0.001). Severe osteoarthritis in the ankle joint was seen in seven feet (8%) and in the talonavicular joint in 11 feet (12%). The functional result was excellent or good (≥ 80 points) in 29 patients (48%), and fair or poor (< 80 points) in 31 patients (52%). Patients who had undergone few (0 to 1) surgical procedures had better functional outcomes than those who had undergone two or more procedures (p < 0.001). There was a significant correlation between the functional result and the degree of medial subluxation of the navicular (p < 0.001, r2= 0.164), the talocalcaneal angle on AP projection (p < 0.02, r2 = 0.025) and extent of osteoarthritis in the ankle joint (p < 0.001).We conclude that poor functional outcome in patients with congenital clubfoot occurs more frequently in those with medial displacement of the navicular, osteoarthritis of the talonavicular and ankle joints, and a low talocalcaneal angle on the AP projection, and in patients who have undergone two or more surgical procedures. However, the ankle joint in these patients appeared relatively resistant to the development of osteoarthritis.

In Sweden, most patients are recruited into biobank research by non-researcher doctors. Patients' trust in doctors may therefore be important to their willingness to participate. We suggest a model of trust that makes sense of such transitions of trust between domains and distinguishes adequate trust from mistaken trust. The unique position of doctors implies, we argue, a Kantian imperfect duty to compensate for patients' mistaken trust. There are at least three kinds of mistaken trust, each of which requires a different set of countermeasures. First, trust is mistaken when necessary competence is lacking; the competence must be developed or the illusion dispelled. Second, trust is irrational whenever the patient is mistaken about his actual reasons for trusting. Care must therefore be taken to support the patient's reasoning and moral agency. Third, some patients inappropriately trust doctors to recommend only research that will benefit them directly. Such trust should be counteracted by nurturing a culture where patients expect to be asked occasionally to contribute to the common good.

In the majority of patients with slipped upper femoral epiphysis only one hip is involved at primary diagnosis. However, the contralateral hip often becomes involved over time. There are no reliable factors predicting a contralateral slip. Whether or not the contralateral hip should undergo prophylactic fixation is a matter of controversy. We present a number of essential points that have to be considered both when choosing to fix the contralateral hip prophylactically as well as when refraining from surgery and instead following the patients with repeat radiographs.

The participation of children in medical research raises many ethical issues, in particular regarding assent. However, little is known about children's own views on participation. This study presents results from interviews with children 10–12 years old with and without experience in a large-scale longitudinal screening study. We identified five themes: (1) knowledge about research, (2) a sense of altruism, (3) shared decision-making and right to dissent, (4) notions of integrity, privacy, and access, and (5) understanding of disease risk and personal responsibilities. We conclude that the children feel positive towards medical research, and want to take an active part in decisions and have their integrity respected. However, the study also indicates that children who had participated in longitudinal screening had a limited understanding, suggesting the vital importance of providing information appropriate to their age and maturity. This information should be provided out of respect for the children as persons, but also to promote their willingness to continue participating in longitudinal studies.

In this paper we will argue: (1) that scholars, regardless of their normative stand against or for genetic enhancement indeed have a moral/professional obligation to hold on to a realistic and up-to-date conception of genetic enhancement; (2) that there is an unwarranted hype surrounding the issue of genetic enhancement in general, and gene doping in particular; and (3) that this hype is, at least partly, created due to a simplistic and reductionist conception of genetics often adopted by bioethicists.

Elective surgery can be cancelled when resources are overwhelmed by emergency cases. We hypothesized that such cancellations, on psychological grounds, are followed also by inferior clinical results and we conducted a retrospective survey of patients following joint replacement surgery. Sixty patients having suffered from administrative cancellation prior to their operation during an 18-month period and with six months follow-up were identified and compared with another 60 matched patients after having the same type of surgery but without prior cancellation. All patients received questionnaires on complications and on visual analogue scale (VAS) assessment on subjective wellbeing and quality of life (QoL) at follow-up. The study group reported 50 complications versus 33 for controls ( P < 0.03). A borderline significant difference was found for myocardial infarction, 4 versus 0 ( P < 0.05). There was no difference in VAS registration and QoL measurements did not quite reach statistical significance ( P = 0.06). Cancellations (postponements) of elective surgery for administrative reasons may be followed by inferior clinical results, and this merits further prospective study.

With the advanced methods of analysing old biological material, it is pressing to discuss what should be allowed to be done with human remains, particularly for well documented historical individuals. We argue that Queen Christina of Sweden, who challenged the traditional gender roles, has an interest in maintaining her privacy when there are continued attempts to reveal her 'true' gender. In the long-running philosophical debate on posthumous wronging, the fundamental question is: Who is wronged? Our aim is to find this 'missing subject' using narrative theory. Narrative identity emphasises the fact that no person is alone in knowing or telling their life story. People's lives are entangled and parts of the life story of a deceased person can remain in the living realm. Since the narrative identity of a person does not necessarily end upon their death, and this narrative continues to relate directly to the person who once existed, it is the narrative subject that can continue to be posthumously wronged. Queen Christina can no longer maintain her own identity, but we maintain it by our research into her life. We propose three duties relevant for posthumous wronging: the duty of truthfulness, the duty of recognition and the duty to respect privacy.

The objective of the present paper is to explore parents' views on safety and confidentiality, information and consent, the importance of different kinds of research, and their responsibilities regarding children's participation. A questionnaire was distributed to 2500 families in south-east Sweden with children born during the years 1997–1999; 1302 responded. The sample was chosen to include views of families with and without earlier research experience. A clear majority of responding parents stated that parents have a moral responsibility to let their children participate in research that is considered important, safe and moderately time-consuming. Respondents stressed the importance of thorough review and control of research involving children. Respondents also found it important that parents are guaranteed the right to decide about their children's participation and that they are thoroughly informed on central aspects of the study.

From the perspective of current and future patients, the development of the field of pharmacogenetics is of immense interest. The encouraging vision that is now being established is that we may move from trial and error therapies to evidence-based personalized medicine in clinical practice. However, research and the application of pharmacogenetics to clinical practice are believed to raise a host of controversial ethical issues. Some of these are related to the research process, for example, confidentiality and informed consent in association with human tissue sampling. Other issues arise on a societal level, for example, issues regarding justice and the use of race or ethnicity as proxies for genotyping. In this perspective, I comment on this debate and also suggest what we may learn from previous discussions regarding DNA testing and gene transfer methods. Arguably, the most important ethical perspective in medical research and drug development is related to the interests of patients wanting medical treatment that is both effective and carries low risks of adverse effects. Risk:benefit ratios must always be compared with existing alternatives, and while the risk of adverse effects may be tolerable for some individuals, owing to genetic reasons, this may not be relevant for others. This will have consequences for regulatory policies regarding drug development. In the future, personalized medicine will also need to take epigenetic and environmental factors into consideration.