Physician Attitudes towards Pharmacological Cognitive Enhancement: Safety Concerns Are Paramount

The ethical dimensions of pharmacological cognitive enhancement have been widely discussed in academic circles and the popular media, but missing from the conversation have been the perspectives of physicians - key decision makers in the adoption of new technologies into medical practice. We queried primary care physicians in major urban centers in Canada and the United States with the aim of understanding their attitudes towards cognitive enhancement. Our primary hypothesis was that physicians would be more comfortable prescribing cognitive enhancers to older patients than to young adults. Physicians were presented with a hypothetical pharmaceutical cognitive enhancer that had been approved by the regulatory authorities for use in healthy adults, and was characterized as being safe, effective, and without significant adverse side effects. Respondents overwhelmingly reported increasing comfort with prescribing cognitive enhancers as the patient age increased from 25 to 65. When asked about their comfort with prescribing extant drugs that might be considered enhancements (sildenafil, modafinil, and methylphenidate) or our hypothetical cognitive enhancer to a normal, healthy 40 year old, physicians were more comfortable prescribing sildenafil than any of the other three agents. When queried as to the reasons they answered as they did, the most prominent concerns physicians expressed were issues of safety that were not offset by the benefit afforded the individual, even in the face of explicit safety claims. Moreover, many physicians indicated that they viewed safety claims with considerable skepticism. It has become routine for safety to be raised and summarily dismissed as an issue in the debate over pharmacological cognitive enhancement; the observation that physicians were so skeptical in the face of explicit safety claims suggests that such a conclusion may be premature. Thus, physician attitudes suggest that greater weight be placed upon the balance between safety and benefit in consideration of pharmacological cognitive enhancement

The Future of Psychopharmacological Enhancements: Expectations and Policies

The hopes and fears expressed in the debate on human enhancement are not always based on a realistic assessment of the expected possibilities. Discussions about extreme scenarios may at times obscure the ethical and policy issues that are relevant today. This paper aims to contribute to an adequate and ethically sound societal response to actual current developments. After a brief outline of the ethical debate concerning neuro-enhancement, it describes the current state of the art in psychopharmacological science and current uses of psychopharmacological enhancement, as well as the prospects for the near future. It then identifies ethical issues regarding psychopharmacological enhancements that require attention from policymakers, both on the professional and on the governmental level. These concern enhancement research, the gradual expansion of medical categories, off-label prescription and responsibility of doctors, and accessibility of enhancers on the Internet. It is concluded that further discussion on the advantages and drawbacks of enhancers on a collective social level is still needed

Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

OBJECTIVE: To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. METHODS: In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. RESULTS: Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker. CONCLUSIONS: The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome

A proteinuria cut-off level of 0.7 g /day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: Data from the MAINTAIN Nephritis Trial

Background: Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). Methods: Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). Results: After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells 645/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. Conclusions: In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts

Defining ourselves:Personal bioinformation as a tool of narrative self-conception

Where ethical or regulatory questions arise about an individual’s interests in accessing bioinformation about herself (such as findings from screening or health research), the value of this information has traditionally been construed in terms of its clinical utility. It is increasingly argued, however, that the “personal utility” of findings should also be taken into account. This article characterizes one particular aspect of personal utility: that derived from the role of personal bioinformation in identity construction. The suggestion that some kinds of information are relevant to identity is not in itself new. However, the account outlined here seeks to advance the debate by proposing a conception of the relationship between bioinformation and identity that does not depend on essentialist assumptions and applies beyond the narrow genetic contexts in which identity is customarily invoked. The proposal is that the identity-value of personal bioinformation may be understood in terms of its instrumental role in the construction of our narrative identities, specifically that its value lies in helping us to develop self-narratives that support us in navigating our embodied existences. I argue that this narrative conception provides useful insights that are pertinent to the ethical governance of personal bioinformation. It illuminates a wider range of ethical considerations in relation to information access; it accounts for variations in the utility of different kinds of information; and it highlights that the context in which information is conveyed can be as important as whether it is disclosed at all. These arguments are illustrated using an example drawn from psychiatric neuroimaging research

Sleep better than medicine? Ethical issues related to "wake enhancement".

This paper deals with new pharmacological and technological developments in the manipulation and curtailment of our sleep needs. While humans have used various methods throughout history to lengthen diurnal wakefulness, recent advances have been achieved in manipulating the architecture of the brain states involved in sleep. The progress suggests that we will gradually become able to drastically manipulate our natural sleep-wake cycle. Our goal here is to promote discussion on the desirability and acceptability of enhancing our control over biological sleep, by illustrating various potential attendant ethical problems. We draw attention to the risks involved, possible conflicts of interests underlying the development of wake enhancement, and the potential impact on accountability for fatigue related errors

Sleep better than medicine? Ethical issues related to "wake enhancement".

This paper deals with new pharmacological and technological developments in the manipulation and curtailment of our sleep needs. While humans have used various methods throughout history to lengthen diurnal wakefulness, recent advances have been achieved in manipulating the architecture of the brain states involved in sleep. The progress suggests that we will gradually become able to drastically manipulate our natural sleep-wake cycle. Our goal here is to promote discussion on the desirability and acceptability of enhancing our control over biological sleep, by illustrating various potential attendant ethical problems. We draw attention to the risks involved, possible conflicts of interests underlying the development of wake enhancement, and the potential impact on accountability for fatigue related errors