Empirical research in clinical ethics: The 'committed researcher' approach.

After the 'empirical turn' in bioethics, few specific approaches have been developed for doing clinical ethics research in close connection with clinical decision-making on a daily basis. In this paper we describe the 'committed researcher' approach to research in clinical ethics that we have developed over the years. After comparing it to two similar research methodological approaches, the 'embedded researcher' and 'deliberative engagement', we highlight its main features: it is patient-oriented, it is implemented by collegial and multidisciplinary teams, it uses an ethical grid to build the interview guide, and it is geared towards bringing the results to bear on the public debate surrounding the issue at stake. Finally, we position our methodological approach with respect to the 'is vs. ought' distinction. We argue that our 'commitment researcher' approach to clinical ethics research takes concerned people's life-building values as the main data, and compares them to the larger normative framework underlying the medical practice at stake.

"Futility" as in English or "Futilities" as in French: A Valuable Semantic Misunderstanding?

This article offers a comparative perspective of the controversy about the use of the term futility as presented by Schneiderman and colleagues (2017). The English concept of "medical futility" has no semantic equivalent in the French language. The traditional term used to translate it was "therapeutic obstinacy," which changed to "unreasonable obstinacy" when the first end-of-life law was adopted in 2005. The change was done in order to demedicalize the concept and make it less objective and less scientific. As such, the intention of the French legislature may have been equivalent to the intention behind the recent U.S. policy statement that proposed replacing the term futile with inappropriate (Bosslet et al. 2015). The semantic change towards "unreasonable obstinacy" pushed practitioners in France to the same conclusion formalized some years ago by Helft and colleagues (2000), who said that pronouncing the term futility can't be enough by itself to convince patients or their proxies that the treatments should be ceased. Instead, it should initiate the difficult task of negotiating until they will accept that there is no other issue for the patient but the withdrawal of all aggressive and invasive treatments. The best way to enter this cruel negotiation remains unresolved. Is it in using the term futility, which involves a notion of medical undisputable objectivity, as well as an ending dimension that is difficult for people to be confronted with? Or is it in choosing a less definitive word, which leaves room for something else to happen and to be positively constructed, in order to escape the dimension of hopelessness included in the announcement of futility?

Withdrawal of artificial nutrition and hydration in neonatal intensive care: parents' and healthcare practitioners' views.

Withdrawing Artificial Nutrition and Hydration (WANH) in the neonatal intensive care units (NICUs) has long been controversial. In France, the practice has become a legal option since 2005. But even though, the question remains as to what the stakeholders' experience is, and whether they consider it ethically appropriate. In order to contribute to the debate, we initiated a study in 2009 to evaluate parental and health care professionals (HCP) perspectives, after they experienced WAHN for a newborn. The study included 25 cases from 5 different clinical neonatology departments. We interviewed both the parents and some of the HCP who cared for the baby, at least 6 months after this latter deceased. We proceeded through in-depth individual qualitative interviews. Content was analyzed for themes and patterns that emerged from the data. Some parents expressed that WANH offered an opportunity to the family to spend a few demedicalized days with the baby before she dies, without any tubes and machines, and to be well supported by the HCP during this palliative stage. But others evaluated the practice in retrospect as a terrible ordeal. All said that, at least, the time of waiting for death to ensue should not last too long. After a few days, it becomes unbearable because of the transformation of the baby's appearance and because they, as parents, began to wonder if she was not dying from starvation rather than from her initial disease. An important proportion of HCP also expressed some kind of ethical unease. This was due to the psychological violence involved in the decision for a human being to stop feeding a little one, and also to the difficulty to deal with the fundamental intention behind the decision of WANH: indeed, could it be claim that it does not presuppose the intention of provoking the infant's death? The discussion focuses on the point to know if WANH can be considered as a source of progress from an ethical point of view, particularly in comparison with earlier practices-that in France could involve active euthanasia by lethal injection. We argue that when HCP are merely focused on avoiding that WAHN could be construed as a way of intending to hasten the baby's death, the practice is at risk to be implemented in a way that becomes ethically counterproductive. Focusing on this intention easily distract the clinical teams from what should be their ultimate concern, namely the baby's comfort during the dying process, as well as the support owned to her parents. To conclude, we suggest that the ethical priorities, when WANH is decided, should be the support due to the patient and her family on the one hand, and, on the other hand to implement it in such a way that at least the baby seems to have died of her initial disease and never of starvation. This means that HCP have a duty to control the timing of death, even though this might be incompatible with the worry to avoid the intention of hastening the baby's death.

The near-failure of advance directives: why they should not be abandoned altogether, but their role radically reconsidered.

Advance directives (ADs) have been hailed for two decades as the best way to safeguard patients' autonomy when they are totally or partially incompetent. In many national contexts they are written into law and they are mostly associated with end-of-life decisions. Although advocates and critics of ADs exchange relevant empirical and theoretical arguments, the debate is inconclusive. We argue that this is so for good reasons: the ADs' project is fraught with tensions, and this is the reason why they are both important and deeply problematic. We outline six such tensions, and conclude with some positive suggestions about how to better promote patients' autonomy in end-of-life decision. We argue that ADs should continue to be an option but they cannot be the panacea that they are expected to be.

The "Commitment Model" for Clinical Ethics Consultations: Society's Involvement in the Solution of Individual Cases.

Several approaches to clinical ethics consultation (CEC) exist in medical practice and are widely discussed in the clinical ethics literature; different models of CECs are classified according to their methods, goals, and consultant's attitude. Although the "facilitation" model has been endorsed by the American Society for Bioethics and Humanities (ASBH) and is described in an influential manual, alternative approaches, such as advocacy, moral expertise, mediation, and engagement are practiced and defended in the clinical ethics field. Our Clinical Ethics Center in Paris was founded in 2002 in the wake of the Patients' Rights Act, and to date it is the largest center that provides consultation services in France. In this article we shall describe and defend our own approach to clinical ethics consultation, which we call the "Commitment Model," in comparison with other existing models. Indeed commitment implies, among other meanings, continuity through time, a series of coherent actions, and the realization of important social goals. By drawing on a recent consultation case, we shall describe the main steps of our consultation procedure: interviews with major stakeholders, including patients and proxies; case conferences; and follow up. We shall show why we have chosen the term "commitment" to represent our approach at three different but interrelated levels: commitment towards patients, within the case conference group, and towards society as a whole.

Anogenital distribution of mucosal HPV in males and females before and after renal transplantation.

INTRODUCTION: Immunosuppressive drugs taken by transplant recipients may favor HPV infection at anogenital sites. HPV-type prevalence was studied in males and females before and after renal transplantation. PATIENTS AND METHODS: Anal, cervical and penile samples were taken from 62 patients before transplantation and from 41 patients after transplantation. HPV DNA was investigated using the INNO-LiPA HPV genotyping extra test and HPV-type distribution determined. RESULTS: Before transplantation, up to 30% of analyzed samples harbored HPV DNA, with the highest prevalence found in cervical specimens (60%). After transplantation, a trend toward HPV clearance was observed in females. By contrast, a trend toward incident infections by a wide variety of HPV genotypes at the penis and anal level was documented in men. CONCLUSION: High prevalence of HPV at anogenital sites was documented before and after renal transplantation. Immunosuppressive drugs taken after transplantation may impact HPV acquisition or reactivation, especially in males. Special attention should be paid in view of preventing HPV-associated diseases in this vulnerable population.

The French bioethics debate: norms, values and practices.

In 1994, France passed bioethics laws regulating assisted reproductive technologies, organ donations and prenatal diagnosis. These laws were based upon a few principles considered as fundamental: the anonymity and gratuity of all donations concerning the elements of the human body, free and informed consent, and the interdiction of all commercial transactions on the human body. These laws have been the object of heated debates which continue to this day. On the basis on a few clinical ethics studies conducted by the Center for clinical ethics at the Cochin Hospital in Paris, the articles presented in this special issues explore several aspects of the bioethics debate, and relate it to the more general question of the complex relationship between norms, practices and values.

The ethics of living donation for liver transplant: beyond donor autonomy.

This paper will present and discuss our conclusions about the ethics of living donation for liver transplant (LDLT) after 8 year of collaboration between our clinical ethics consultation service and liver transplant teams, in the course of which we met with all donor-candidates. We will focus on the results of a follow-up study that was conducted in order to evaluate the long-term consequences for potential donors and to interview them on the ethical aspects of the screening process. This study was conducted from April 2007 to November 2009 and consisted of interviews with donor-candidates, regardless of whether they underwent harvest surgery, at least 1 year after the recipient's transplant. We explored their views about their own and the recipients' physical and psychological condition, changes in family and career dynamics, their experience as potential or real donors, and their views about LDLT process in general. Results shed new light on the ethical grounds of LDLT and allow us to envisage new ways of improving the ethical soundness of current procedures and practices. In particular, we argue that the purpose of an ethics committee should be to provide follow-up support for the donors rather than merely to check the freedom of donors' consent. We also suggest that the recipient's consent deserves more attention than it currently receives.

Access to assisted reproductive technologies in France: the emergence of the patients' voice.

Is there any ethical justification for limiting the reproductive autonomy and not make assisted reproductive technologies available to certain prospective parents? We present and discuss the results of an interdisciplinary clinical ethics study concerning access to assisted reproductive technologies (ART) in situations which are considered as ethically problematic in France (overage or sick parents, surrogate motherhood). The study focused on the arguments that people in these situations put forward when requesting access to ART. It shows that requester's arguments are based on sound ethical values, and that their legitimacy is at least as strong as that of those used by doctors to question access to ART. Results reveal that the three implicit normative arguments that founded the law in 1994, which are still in force after the bioethics law revision in July 2011-the welfare of the child, the illegitimacy of a "right to a child," and the defense of the so called "social order"-are challenged on several grounds by requesters as reasons for limiting their reproductive autonomy. Although these results are limited to exceptional situations, they are of special interest insofar as they give voice to the requesters' own ethical concerns in the ongoing political debate over access to ART.

Continuous Deep Sedation Until Death: First National Survey in France after the 2016 Law Promulgating It.

CONTEXT: The French parliament passed a groundbreaking law in 2016, opening a right for patients to access continuous and deep sedation until death (CDS) at the end of life, under conditions. Parliamentarians' goal was to consolidate patients' rights whilst avoiding legislating on medical aid in dying. OBJECTIVES: To conduct a first national retrospective survey on CDS to evaluate the number of CDS requested, proposed and performed in 2017 and to elicit qualitative data from physicians on the practice and on the terms used by patients to refer to CDS. METHODS: Early 2018, an online survey was sent to all French hospitals, nursing homes, hospital at homes services and general practitioners (GPs). Descriptive statistics and qualitative inductive content analysis were used to analyze the data and comments of respondents. RESULTS: The qualitative data show that respondents generally approve the law on CDS as it sets a legal framework; nonetheless, there is a persistent controversy about CDS vs. euthanasia for some physicians in all settings. GPs reported limited access to midazolam and the difficulty in organizing multidisciplinary procedures as major constraints. In hospital settings in particular, differentiating CDS from other sedation practices is uneasy. All physicians reported patients use multiple elements of language to request CDS. CONCLUSION: After the law was passed in France, CDS were requested, proposed and performed in all medical settings, in nursing homes, at home. The qualitative data presented here show the relevance of exploring physicians' reflexive stances on this practice in different settings and within the context of a patient-physician relationship marked by a new patient's right. The study highlights the wide range of elements of language used by patients at the end of life, as understood by respondent physicians to mean a request for CDS and underscores the polymorphous meaning of CDS.

Characteristics of Adult Patients with Idiopathic Retroperitoneal Fibrosis and Assessment of Risk of Relapse at Diagnosis.

OBJECTIVES: To compare adult patients' characteristics suffering from idiopathic retroperitoneal fibrosis between "relapse-free" and relapsing patients at the diagnosis and identify factors associated with relapse at initial presentation. METHODS: We conducted a retrospective multicentric study in four hospitals in Eastern France, from 1993 to 2020, of adult patients suffering from idiopathic retroperitoneal fibrosis. We analyzed clinical, biological, and radiological features at diagnosis and during a forty-month follow-up. RESULTS: Of 47 patients suffering from retroperitoneal fibrosis, 21 patients had idiopathic retroperitoneal fibrosis. Among them, 13 experienced one or more relapses during follow-up. At diagnosis, clinical characteristics, relevant comorbidities, biological and radiological features were similar between groups. Smoking cessation seems associated with decreased relapse risk (p: 0.0624). A total of 8 patients developed chronic renal failure during follow-up. Ureteral infiltration at diagnosis was associated with evolution to chronic renal failure (p: 0.0091). CONCLUSION: No clinical, biological, or radiological features could predict relapse at retroperitoneal fibrosis diagnosis, but smoking cessation may prevent relapse.

Isolation and structural analysis of the cyclic fatty acid monomers formed from eicosapentaenoic and docosahexaenoic acids during fish oil deodorization.

Long-chain polyunsaturated fatty acids (LC-PUFAs) present in fish oils are thermolabile molecules. Among the degradation reactions encountered, thermal cyclization occurs during refining or other heat treatments. Numerous studies have been carried out in the past to quantify and determine the structures of cyclic fatty acid monomers (CFAMs) formed from oleic, linoleic and linolenic acids in heated vegetable oils. Recently, much attention have been given to LC-PUFAs due to their potential health benefits. However, data on quantification of CFAMs formed from these fatty acids, such as eicosapentaenoic acid (EPA, cis-5, cis-8, cis-11, cis-14, cis-17 20:5) and docosahexaenoic acid (DHA, cis-4, cis-7, cis-10, cis-13, cis-16, cis-19 22:6), the two main LC-PUFAs in fish oils, are scarce. In the present study, structural analyses of CFAMs formed from EPA and DHA during the deodorization of fish oil are presented. Fish oil sample was deodorized at 250 degrees C for 3 h under a pressure of 1.5 mbar in a laboratory deodorizer. The CFAMs formed during heat treatment of fish oil were isolated by a combination of saponification, esterification, urea fractionations and column chromatography. Structural analyses of C20- and C22-CFAMs were achieved by gas-chromatography electronic-ionization mass-spectrometry (GC-EI-MS) of their 4,4-dimethyloxazoline (DMOX) derivatives. We identified seven out of 13 possible structures of hydrogenated CFAMs formed from EPA, and nine out of 16 possible structures of CFAM formed from DHA. Major CFAMs from both EPA and DHA were cyclohexyl isomers. All possible cyclohexyl isomers were found but only nine out of 18 of the cyclopentyl isomers were present in concentration sufficient for identification. Chemical mechanisms involved in the formation of polyunsaturated LC-PUFAs have been investigated. The results have shown that general principle involved in the cyclization of LC-PUFAs is same as that for the thermal cyclization of oleic, linoleic and alpha-linolenic acids.

Quantification of eicosapentaenoic and docosahexaenoic acid geometrical isomers formed during fish oil deodorization by gas-liquid chromatography.

Long-chain polyunsaturated fatty acids (LC-PUFAs) of the n-3 series and especially eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively) have important biological properties. The main dietary sources of LC-PUFAs are fish and fish oil. Geometrical isomerization is one of the main reactions happening during the thermal treatment of polyunsaturated fatty acids. Refined fish oils are used to supplement food products in LC-PUFAs and the quality of these nutritional ingredients have to be controlled. In the present study, a suitable method for the quantification of EPA and DHA geometrical isomers in fish oils by gas-liquid chromatography (GC) is presented. A highly polar capillary column (CP-Sil 88, 100 m) operating under optimal conditions was used. Method selectivity was studied by GC-mass spectrometry. The performance characteristics of the quantification method were studied using samples of fish oil deodorized at 220 degrees C for 3 h. The linearity of the method was assessed by analyzing composite samples obtained by mixing fish oil deodorized at 220 degrees C with semi-refined fish oil (control). Precision was evaluated by analyzing the same samples in triplicate. Results showed that the validated method is suitable to quantify low amounts of geometrical (trans) isomers of EPA and DHA in refined fish oils. The limits of quantification of the EPA and DHA geometrical isomers are 0.16 and 0.56 g/100 g of fish oil, for EPA and DHA, respectively. Commercially available LC-PUFA oil samples were evaluated by using the validated method. The results show that the oils analyzed contain low amounts (<1% of total fatty acids) of geometrical isomers of EPA and DHA.

Analysis of eicosapentaenoic and docosahexaenoic acid geometrical isomers formed during fish oil deodorization.

Addition of long-chain polyunsaturated fatty acids (LC-PUFAs) from marine oil into food products implies preliminary refining procedures of the oil which thermal process affects the integrity of LC-PUFAs. Deodorization, the major step involving high temperatures, is a common process used for the refining of edible fats and oils. The present study evaluates the effect of deodorization temperature on the formation of LC-PUFA geometrical isomers. Chemically isomerized eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were used as reference samples. Fish oil samples have been deodorized at 180, 220 and 250 degrees C for 3 h and pure EPA and DHA fatty acid methyl esters (FAMEs) were chemically isomerized using p-toluenesulfinic acid as catalyst. FAMEs prepared from fish oil were fractionated by reversed-phase high-performance liquid chromatography (RP-HPLC). Geometrical isomers produced by both processes were fractionated by silver-ion thin-layer chromatography (Ag-TLC) and silver-ion high-performance liquid chromatography (Ag-HPLC). The FAME fractions were subsequently analyzed by gas chromatography (GC) on a 100 m highly polar cyanopropylpolysiloxane coated capillary column, CP-Sil 88. Our results show that thermally induced geometrical isomerization appears to be a directed reaction and some ethylenic double bond positions on the hydrocarbon chain are more prone to stereomutation. Only minor changes were observed in the EPA and DHA trans isomers content and distribution after deodorization at 180 degrees C. The analyses of EPA and DHA isomer fractions revealed that it is possible to quantify EPA geometrical isomers by GC using the described conditions. However, we notice that a mono-trans isomer of DHA, formed during both chemical and thermal treatments, co-elute with all-cis DHA. This feature should be taken into consideration for the quantification of DHA geometrical isomers.

[Cochin Hospital Clinical Ethics Center: the first two years]. / Bilan d'activité du Centre d'éthique clinique de l'hôpital Cochin après deux ans de fonctionnement.

INTRODUCTION: In September 2002, Cochin Hospital (Paris, France) opened a Clinical Ethics Center for patients, health proxies and members of the healthcare staff to consult when they face medical decisions raising ethical issues, that is, presenting possible conflicts in values. Three years after the opening of this experimental center that remains unique in France, we evaluated its activities. OBJECTIVES: To describe and compare consultations in 2003 and 2004 and to compare our activity with that of similar units abroad. METHODS: The descriptive analysis is based on data routinely collected for all consultations. RESULTS: The Center received 47 calls in 2003 and 83 in 2004. The most frequent reasons for consultation were: end of life issues (28%), patients' rights (25%), and questions about assisted reproduction technologies (16%). Two factors explain the increase in activity between 2003 and 2004. First, patients and their proxies called much more often: 24 calls in 2004, compared with only 10 in 2003. Second, research protocols designed to focus on specific ethical questions faced by medical teams in their daily practice required them to call systematically in the relevant situations (39 calls in 2004, compared with 15 in 2003). Calls from healthcare workers about one-time or ad hoc ethics questions remained stable (22 in 2003 and 21 in 2004). DISCUSSION/CONCLUSION: Healthcare staff appear to need clinical ethics consultations less for help on ad hoc issues than for long-term collaboration on specific and frequent ethical issues that remain difficult, despite their familiarity. These findings refute earlier fears that healthcare personnel would use these consultations to avoid their own ethical responsibilities. The increasing direct demand from patients and proxies should continue during the next few years, for it corresponds to a profound social trend, to defend one's autonomy in the face of illness and to make decisions and take responsibility for oneself.

[Are advance directives useful for doctors and what for?]. / Quelle utilité des directives anticipées pour les médecins ?

OBJECTIVES: In France, the law has introduced the possibility to write advance directives since 2005. In this paper, we will present the results of a study designed for checking how much people over 75 years are interested by this new tool. METHODS: The inquiry consisted in deep qualitative interviews (around 45') to further understand what people included in the study have to say about advance directives, but also about the conditions of ageing and dying. The study sample was composed of 8 over 75 years subgroups, chosen for being illustrative of different health status and/or disabling status. Finally, a last subgroup was also included, called "referent", because composed of people, all members of the "Association pour le droit à mourir dans la dignité" (ADMD), and as such supposed to be pro-advance directives. Interviews content was analysed through qualitative analysis referent methods ("Analyse qualitative en sciences humaines et sociales", Paillé et Muschielli, "Grounded Theory", Glaser). POPULATION OF THE STUDY: One hundred and eighty-six patients were included (106 female, 80 male, mean age 82.7 ans), 167 in the general group and 19 in the "ADMD" group. RESULTS: Ninety percent in the general group said that they never heard about advance directives before the inquiry. After having been informed by us about what advance directives were for, 83% remained not interested they said, some because they felt they were not personally concerned, others expressed that the tool appears to them inefficient - "things never happen the way you planned it", not useful - "doctors will act as they will decide whatever will be written", or even more potentially dangerous - "writing advance directives might lead doctors not to be as much therapeutically aggressive as for other people". Only 28 persons in the general group (17%), together with the 19 of the ADMD group, said they were interested by advance directives. They all were quite similar according to their personal character: they were quite strong and voluntary people, claiming firmly about their autonomy, independently of any sociodemographic profile. Furthermore, the interest for advance directives appears to be completely independent from the health or disabling status. Another important result of the study is that patients generally express themselves as being very confident and trustful in their doctors. They do not fear to be over-treated and having to support any futile treatment. CONCLUSION: Around 20% of people are very much concerned by advance directives and do really expect that their wishes will be respected. The authors suggest that advance directives should be for them really respected, even if the French law let doctors free at this point to decide what the best interest of the patient actually is and if they should or not respect in this case what the patient wrote as advance directives. Around 30% of other people appear interested to speak with someone of the time they will still live. Their concern is more to express what is important for them in terms of still living and quality of life, than to express very clear advance directives about the way they would like to dye. The last learning of the study is that there is still a lot to do if we want more people precisely express something on the conditions of their dying. Doctors might have a fundamental pedagogic role in that respect: they should better inform patients about the limits of medicine and tell them more about the new complexity of medical decision-making at the end of life due to recent improvements in techniques.

Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12.

BACKGROUND: In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose, i.v. folinic acid combined with high-dose i.v. pyridoxine was highly effective in correcting plasma total homocysteine (tHcy) concentrations in haemodialysis patients. To confirm these findings, we conducted a randomized, controlled trial aimed at evaluating whether i.v. or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid. METHODS: In a 6-month prospective, randomized, controlled trial, 60 chronic haemodialysis patients, matched for age, gender, dialysis duration, and average screening pre-treatment-fasting tHcy levels, were given either 50 mg/week of i.v. calcium folinate (group 1), 50 mg/week of oral calcium folinate (group 2), or 45 mg/week oral folic acid (group 3). All 60 patients also received 750 mg/week of i.v. vitamin B6 and 3 mg/week of oral vitamin B12. RESULTS: Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months (16.6+/-3.5, 18.3+/-4, and 19.1+/-3.1, in groups 1, 2, and 3, respectively, P=NS). Mean percentage reduction at 6 months was also similar in the three treatment groups (46, 43, and 42% in groups 1, 2, and 3, respectively, P=NS). CONCLUSIONS: These findings show that the tHcy-lowering effects of high-dose i.v. folinic acid, oral folinic acid, or oral folic acid were comparable, suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism. Furthermore, they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients.