Don't Blame the ‘Bio’ — Blame the ‘Ethics’: Varieties of (bio) ethics and the challenge of pluralism

We tend to think that the difficulties in bioethics spring from the novel and alarming issues that arise due to discoveries in the new biosciences and biotechnologies. But many of the crucial difficulties in bioethics arise from the assumption we make about ethics. This paper offers a brief overview of bioethics, and relates ethical 'principlism' to 'ethical fundamentalism.' It then reviews some alternative approaches that have emerged during the second phase of bioethics and argues for a neo-Aristotelian approach. Misconceptions about ethical principles and ethical reasoning not only distort our views of the business of bioethics, but they also prevent us from facing up to the formidable problems posed by ethical pluralism in so-called liberal societies.     

Will the Evolution of Overactive Bladder Delivery Systems Increase Patient Compliance?

The negative impact of overactive bladder (OAB) on daily quality of life drives the large market of pharmacotherapy targeted at symptoms of urinary frequency and urgency, with or without urinary urge incontinence. Currently, the primary pharmacologic treatment modality is aimed at modulation of the efferent muscarinic receptors (M2 and M3) predominant in detrusor smooth muscle and responsible for involuntary or unwanted bladder contractions. However, due to drug effects in the muscarinic receptors of the salivary glands and intestinal smooth muscle, as well as extensive first-pass metabolism in the liver and intestinal tract yielding parent drug metabolites, adverse side effects are common and can be quite bothersome. These issues, encountered with many of the oral antimuscarinic formulations, limit their tolerability and affect long-term patient compliance and satisfaction. Thus, the benefit of pharmacotherapy for OAB must be a balance between efficacy and tolerability, also known as therapeutic index. This article reviews the current pharmacologic delivery systems available for the treatment of OAB, patient compliance, and reasons for discontinuation of medication.Key words: Overactive bladder, Pharmacotherapy, Compliance, Antimuscarinic agent, Transdermal delivery systemOveractive bladder syndrome (OAB) is a condition affecting millions of adults in the aging US population, with prevalence rates estimated at 17% in both men and women.¹ Quality of life and symptom bother have become important parameters in the treatment of many disease states, with efficacy of treatment measured by perceived improvements in these variables. OAB is largely characterized by its negative impact on daily quality of life. Specifically, the subjective impact of urinary frequency and urgency (with or without urge incontinence) on psychosocial and physical factors has become an important aspect of caring for this group of patients. The severity and degree of bother associated with OAB symptoms can directly influence a person’s mobility, degree of social isolation, and impairment in work-related productivity, and may also cause clinical depression, disruptions in sleep, and impairment in domestic and sexual life.² In addition, the patient may develop extreme coping strategies including severe, self-imposed fluid restrictions, avoidance of social events and travel, and dependence on costly protective undergarments. Although all of these factors drive patients to seek evaluation and treatment, persistence and compliance with medical OAB therapy remain astoundingly low both in the clinical setting and in large-scale clinical trials. High rates of discontinuation are multifactorial: adverse side effects, lack of perceived efficacy, polypharmacy, medication cost, poor counseling regarding compliance and successful treatment, and dosing frequency. Because adverse side effects are experienced by a significant portion of patients treated with oral antimuscarinic therapy, thereby limiting their long-term utilization, the development of new drug delivery systems for OAB pharmacotherapy has been critical. The focus has been on less frequent dosing intervals with longer acting formulations, reduction in side-effect profile by altering pharmacokinetics of both parent compound and active metabolites, and alternative methods of drug delivery that avoid first-pass liver metabolism.     

Exploration of Perceptions of Dog Bites among YouTube™ Viewers and Attributions of Blame

Dog bites are a human public health and dog welfare problem. This qualitative study is the first to use YouTube^? to examine how viewers perceive risk of, and attribute blame for, dog bites. Comments underneath 10 videos, chosen to represent a diversity of dog-bite scenarios, were analyzed inductively using thematic analysis. Six themes emerged: 1) Commentators thought that dogs are inherently good-natured but wild animals and emphasized how dogs try to avoid biting people; 2) all recognized breeds of dogs were stereotyped and breed stereotypes were used to shift the blame away from the dog and onto a bite victim, unless the dog identified in a video was a pit bull type. The dog was often blamed in such case; 3) It was argued that a breed limits the extent to which a dog can be trained and controlled; 4) Owners/handlers were often blamed for bites due to their inability to control the dog, and commentators identified the need for appropriate training and socialization in order to control dogs and reduce bite risk; 5) Bite victims were also blamed for the bites when their behavior was perceived as provoking a dog. Although children's behavior was identified as causing a risk, parents of children bitten in the videos were blamed for bites instead due to their approach to child supervision; 6) Bites in a range of contexts, such as play or when viewers thought that the victim's behavior provoked a dog, were seen as well-de-served and normal. It was concluded that although comments on publicly available videos need to be interpreted with caution due to a self-selection bias, their analysis can help to identify attitudes and perceptions towards risk around dogs that could aid bite prevention interventions and policies.     

Do Breast Cancer Cell Lines Provide a Relevant Model of the Patient Tumor Methylome?

It is well documented that tumor cells undergo dramatic genetic and epigenetic changes during initial establishment as cell lines and in subsequent serial passaging, and that the resultant cell lines may have evolved significantly from the primary tumors from which they were derived. This has potential implications due to their widespread use in drug response experiments and studies of genomic function. One approach to optimizing the design of such cell line studies is to identify and use the cell lines that faithfully recapitulate critical features of primary tumors. To evaluate the epigenetic fidelity of breast cancer cell lines in the context of primary tumors, we performed methylation profiling of 55 well-characterized breast cancer cell lines on the Illumina HumanMethylation27 BeadChip platform, and compared them to publicly available methylation profiles of primary breast tumors. We found that the DNA methylation profiles of breast cancer cell lines largely retain the features that characterize primary tumors, although there are crucial differences as well. We describe these similarities and differences between primary tumors and breast cancer cell lines in detail, and develop a quantitative measure of similarity that is used to score each cell line with respect to how faithfully its methylation profile mirrors that of primary tumors.     

Patient Parents: Do Offspring Decide on the Timing of Fledging in Zebra Finches?

Parent–offspring conflict over parental care is predicted to become most pronounced during offspring transition to independence when offspring are predicted to attempt to extend care for longer than parents are selected to provide it. However, on the proximate level, it is difficult to determine who plays the most important role in this process, parents or offspring. For several vertebrate taxa, it has been documented that parents end brood care by abandoning offspring after a fixed period or else show high flexibility in the duration of care, but teasing apart the role of offspring and parents underlying this flexibility has been difficult. Here, we studied the decision to fledge in captive zebra finches (Taeniopygia guttata), an altricial songbird. We experimentally delayed the time of fledging to determine who decides about the end of feeding inside the nest, parents or offspring. The experiment indicates that parents do not primarily rely on phenotypic offspring traits in their decision to feed offspring in the nest, but appear to adjust the duration of parental care as long as offspring are in the nest which parents may take as an indicator of offspring need and locomotor abilities. Delayed‐fledging offspring appeared not to suffer a disadvantage in terms of age at the onset of independent feeding. Our study suggests that, in zebra finches, offspring play a major role in determining the time of fledging and leave the nest on their own, possibly to reduce the risk of nest predation, or to evade sibling competition in the nest.     

Ebola and Localized Blame on Social Media: Analysis of Twitter and Facebook Conversations During the 2014–2015 Ebola Epidemic

Culture, Medicine, and Psychiatry - This study aimed to analyze main groups accused on social media of causing or spreading the 2014–2016 Ebola epidemic in West Africa. In this analysis,...     

How Should the Impact of Different Presentations of Treatment Effects on Patient Choice Be Evaluated? A Pilot Randomized Trial

Background

Different presentations of treatment effects can affect decisions. However, previous studies have not evaluated which presentations best help people make decisions that are consistent with their own values. We undertook a pilot study to compare different methods for doing this.

Methods and Findings

We conducted an Internet-based randomized trial comparing summary statistics for communicating the effects of statins on the risk of coronary heart disease (CHD). Participants rated the relative importance of treatment consequences using visual analogue scales (VAS) and category rating scales (CRS) with five response options. We randomized participants to either VAS or CRS first and to one of six summary statistics: relative risk reduction (RRR) and five absolute measures of effect: absolute risk reduction, number needed to treat, event rates, tablets needed to take, and natural frequencies (whole numbers). We used logistic regression to determine the association between participants'' elicited values and treatment choices. 770 participants age 18 or over and literate in English completed the study. In all, 13% in the VAS-first group failed to complete their VAS rating, while 9% of the CRS-first group failed to complete their scoring (p = 0.03). Different ways of weighting the elicited values had little impact on the analyses comparing the different presentations. Most (51%) preferred the RRR compared to the other five summary statistics (1% to 25%, p = 0.074). However, decisions in the group presented the RRR deviated substantially from those made in the other five groups. The odds of participants in the RRR group deciding to take statins were 3.1 to 5.8 times that of those in the other groups across a wide range of values (p = 0.0007). Participants with a scientific background, who were more numerate or had more years of education were more likely to decide not to take statins.

Conclusions

Internet-based trials comparing different presentations of treatment effects are feasible, but recruiting participants is a major challenge. Despite a slightly higher response rate for CRS, VAS is preferable to avoid approximation of a continuous variable. Although most participants preferred the RRR, participants shown the RRR were more likely to decide to take statins regardless of their values compared with participants who were shown any of the five other summary statistics.

Trial Registration

Controlled-Trials.com ISRCTN85194921     

How Did the TB Patients Reach DOTS Services in Delhi? A Study of Patient Treatment Seeking Behavior

Setting

Revised National Tuberculosis Control Programme (RNTCP), Delhi, India.

Objective

To ascertain the number and sequence of providers visited by TB patients before availing treatment services from DOTS; to describe the duration between onset of symptoms to treatment.

Study design

A cross sectional, qualitative study. Information was gathered through in-depth interviews of TB patients registered during the month of Oct, 2012 for availing TB treatment under the Revised National TB Control Programme from four tuberculosis diagnosis and treatment centers in Delhi.

Results

Out of the 114 patients who registered, 108 participated in the study. The study showed that informal providers and retail chemists were the first point of contact and source of clinical advice for two-third of the patients, while the rest sought medical care from qualified providers directly. Most patients sought medical care from more than two providers, before being diagnosed as TB. Female TB patients and patients with extra-pulmonary TB had long mean duration between onset of symptoms to initiation of treatment (6.3 months and 8.4 months respectively).

Conclusion

The pathways followed by TB patients, illustrated in this study, provide valuable lessons on the importance of different types of providers (both formal and informal) in the health system in a society like India and the delays in the diagnosis and treatment of tuberculosis.     

No Negative Impact of Palliative Sedation on Relatives’ Experience of the Dying Phase and Their Wellbeing after the Patient’s Death: An Observational Study

Background

Palliative sedation is the widely-used intervention of administering sedating agents to induce a state of unconsciousness to take away a dying patient’s perception of otherwise irrelievable symptoms. However, it remains questionable whether this ethically complex intervention is beneficial for patients and whether the associated lack of communication in the last phase of life has a negative impact on relatives’ wellbeing.

Methods

An observational questionnaire study was conducted among relatives of a consecutive sample of patients who died a non-sudden death in the Erasmus MC Cancer Institute or in the hospice ‘Laurens Cadenza’ (both in Rotterdam) between 2010 and 2013.

Results

Relatives filled in questionnaires regarding 151 patients who had been sedated and 90 patients who had not been sedated. The median time since all patients had passed away was 21 (IQR 14–32) months. No significant differences were found in relatives´ assessments of the quality of end-of-life care, patients´ quality of life in the last week before death and their quality of dying, between patients who did and did not receive sedation, or in relatives’ satisfaction with their own life, their general health and their mental wellbeing after the patient’s death.

Conclusions

The use of sedation in these patients appears to have no negative effect on bereaved relatives’ evaluation of the patient’s dying phase, or on their own wellbeing after the patient’s death.     

Molecular Characterization of a Deletion in the HPRT1 Gene in a Patient with Lesch–Nyhan Syndrome

Lesch–Nyhan syndrome is caused by a deficiency of hypoxanthine phosphoribosyltransferase (HPRT) encoded by HPRT1. About 20% of patients have a deletion of HPRT1 and large deletions of HPRT1 are not always fully characterized at the molecular level. Here, we report on a case of Lesch–Nyhan syndrome with a 33-kb deletion involving exon 1 of HPRT1. This novel mutation is caused by a nonhomologous recombination between different classes of interspersed repetitive DNA.     

“When Treatment Is More Challenging than the Disease”: A Qualitative Study of MDR-TB Patient Retention

Background

One-fifth of the patients on multidrug-resistant tuberculosis treatment at the Drug-Resistant-TB (DR-TB) Site in Gujarat are lost-to-follow-up(LFU).

Objective

To understand patients’ and providers'' perspectives on reasons for LFU and their suggestions to improve retention-in-care.

Design

Qualitative study conducted between December 2013-March 2014, including in-depth interviews with LFU patients and DOT-providers, and a focus group discussion with DR-TB site supervisors. A thematic-network analysis approach was utilised.

Results

Three sub-themes emerged: (i) Struggle with prolonged treatment; (ii) Strive against stigma and toward support; (iii) Divergent perceptions and practices. Daily injections, pill burden, DOT, migratory work, social problems, prior TB treatment, and adverse drugs effects were reported as major barriers to treatment adherence and retention-in-care by patients and providers. Some providers felt that despite their best efforts, LFU patients remain. Patient movements between private practitioners and traditional healers further influenced LFU.

Conclusion

The study points to a need for repeated patient counselling and education, improved co-ordination between various tiers of providers engaged in DR-TB care, collaboration between the public, private and traditional practitioners, and promotion of social and economic support to help patients adhere to MDR-TB treatment and avoid LFU.     

Are Natural Killer Cells Protecting the Metabolically Healthy Obese Patient?

With the emerging obesity pandemic, identifying those who appear to be protected from adverse consequences such as type 2 diabetes and certain malignancies will become important. We propose that the circulating immune system plays a role in the development of these comorbidities. Clinical data and blood samples were collected from 52 patients with severe obesity attending a hospital weight‐management clinic and 11 lean healthy controls. Patients were classified into metabolically “healthy obese” (n = 26; mean age 42.6 years, mean BMI 46.8 kg/m²) or “unhealthy obese” (n = 26; mean age 45 years, mean BMI 47.5 kg/m²) groups, based upon standard cutoff points for blood pressure, lipid profile, and fasting glucose. Circulating lymphoid populations and phenotypes were assessed by flow cytometry. Obese patients had significantly less circulating natural killer (NK) and cytotoxic T lymphocytes (CTL) compared to lean controls. There were significantly higher levels of NK cells and CTLs in the healthy obese group compared to the unhealthy obese group (NK: 11.7% vs. 6.5%, P < 0.0001, CD8 13.4% vs. 9.3%, P = 0.04), independent of age and BMI and these NK cells were also less activated in the healthy compared to the unhealthy group (CD69, 4.1% vs. 11.8%, P = 0.03). This is the first time that quantitative differences in the circulating immune system of obese patients with similar BMI but different metabolic profiles have been described. The significantly higher levels of CTLs and NK cells, which express fewer inhibitory molecules, could protect against malignancy, infection, and metabolic disease seen in obesity.     

Determining the Variability of Lesion Size Measurements from CT Patient Data Sets Acquired under “No Change” Conditions

PURPOSE: To determine the variability of lesion size measurements in computed tomography data sets of patients imaged under a “no change” (“coffee break”) condition and to determine the impact of two reading paradigms on measurement variability. METHOD AND MATERIALS: Using data sets from 32 non-small cell lung cancer patients scanned twice within 15 minutes (“no change”), measurements were performed by five radiologists in two phases: (1) independent reading of each computed tomography dataset (timepoint): (2) a locked, sequential reading of datasets. Readers performed measurements using several sizing methods, including one-dimensional (1D) longest in-slice dimension and 3D semi-automated segmented volume. Change in size was estimated by comparing measurements performed on both timepoints for the same lesion, for each reader and each measurement method. For each reading paradigm, results were pooled across lesions, across readers, and across both readers and lesions, for each measurement method. RESULTS: The mean percent difference (± SD) when pooled across both readers and lesions for 1D and 3D measurements extracted from contours was 2.8 ± 22.2% and 23.4 ± 105.0%, respectively, for the independent reads. For the locked, sequential reads, the mean percent differences (± SD) reduced to 2.52 ± 14.2% and 7.4 ± 44.2% for the 1D and 3D measurements, respectively. CONCLUSION: Even under a “no change” condition between scans, there is variation in lesion size measurements due to repeat scans and variations in reader, lesion, and measurement method. This variation is reduced when using a locked, sequential reading paradigm compared to an independent reading paradigm.     

Effect of cortisone on the developmental pattern of the neutral and the acid β-galactosidases of the small intestine of the rat

1. The developmental pattern and effect of cortisone on acid beta-galactosidase and neutral beta-galactosidase were studied in postnatal rats by a recently proposed method for their independent determination. 2. After birth the acid beta-galactosidase activity increases in the ileum, whereas it decreases slightly in the jejunum. On day 16 after birth the activity in the ileum decreases and in 20-day-old rats activity in both parts of the intestine decreases to adult values. In suckling animals the activity in the ileum exceeds the jejunal activity severalfold and in adult animals the activity in the jejunum is slightly higher than that in the ileum. 3. Neutral beta-galactosidase activity is high after birth and decreases in both jejunum and ileum after day 20 after birth. In 12-20-day-old rats activity in both parts is essentially the same, but in adult animals jejunal activity exceeds ileal activity four-to five-fold. 4. Cortisone (0.5, 2.0 or 5.0mg/100g body wt. daily for 4 days) does not influence the activity of either enzyme in 60-day-old rats. Acid beta-galactosidase activity is decreased after cortisone treatment in 8-, 12-, 16-and 18-day-old rats, with sensitivity to cortisone increasing with the approach of weaning. No effect of cortisone on acid beta-galactosidase is seen in 8-day-old rats. Neutral beta-galactosidase activity is increased in the ileum of 8-, 12-, 16- and 18-day old rats, but only in the jejunum of 8-and 12-day-old rats.     

Forget Evil: Autonomy,the Physician–Patient Relationship,and the Duty to Refer

Aulisio and Arora argue that the moral significance of value imposition explains the moral distinction between traditional conscientious objection and non-traditional conscientious objection. The former objects to directly performing actions, whereas the latter objects to indirectly assisting actions on the grounds that indirectly assisting makes the actor morally complicit. Examples of non-traditional conscientious objection include objections to the duty to refer. Typically, we expect physicians who object to a practice to refer, but the non-traditional conscientious objector physician refuses to refer. Aulisio and Arora argue that physicians have a duty to refer because refusing to do so violates the patient’s values. While we agree with Aulisio and Arora’s conclusions, we argue value imposition cannot adequately explain the moral difference between traditional conscientious objection and non-traditional conscientious objection. Treating autonomy as the freedom to live in accordance with one’s values, as Aulisio and Arora do, is a departure from traditional liberal conceptions of autonomy and consequently fails to explain the moral difference between the two kinds of objection. We outline how a traditional liberal understanding of autonomy would help in this regard, and we make two additional arguments—one that maintains that non-traditional conscientious objection undermines society’s autonomy, and another that maintains that it undermines the physician-patient relationship—to establish why physicians have a duty to refer.     

The Patient’s View: Issues of Theory and Practice

Almost all the knowledge now produced about psychiatry includes what is called “the patient’s or client’s perspective.” This paper analyzes how this notion has been framed in the discourses on mental health over the last two decades, particularly in mental health research and in anthropology. The very concept of the “patient’s perspective” is a social and historical construct. Despite its remarkable prevalence, the notion remains vague. Mental health research pictures it as a stable attribute of the individual. Anthropologists integrate the contextual nature of the patient view; but they still largely envision the psychiatric patient as a rational actor producing narratives based on common sense. However, in psychiatric practice, the client’s perspective is not something the patient individually produces; it is rather shaped by and in a context. To explore this process, my research investigated interactions between staff and patients in a French community mental health center, and showed that the client’s perspective is the result of a collective process. Further analysis demonstrates that eliciting or producing the patient’s view is sometimes considered a therapeutic goal in itself, since being granted the status of a rational and narrative actor gives access to the most valued model of care, one that is based on partnership. Being an outcome that is negotiated between patients and care providers, the “patient’s view” then becomes a new resource in mental health settings.

Utility of the NavX® Electroanatomic Mapping System for Permanent Pacemaker Implantation in a Pregnant Patient with Chagas Disease

Chagas disease is a highly prevalent zoonosis in Mexico, Central, and South America. Early cardiac involvement is one of the most serious complications of this disease, and conduction disturbances may occur at an early age. We describe a young pregnant woman with Chagas disease and a high degree atrioventricular block, who required implantation of a permanent dual chamber pacemaker. Using an electroanatomic navigation EnSite NavX® system the pacemaker was successfully implanted with minimal fluoroscopic exposure. This case demonstrates the safety and feasibility of using an electroanatomic navigation system to guide permanent pacemaker implantation minimizing x-ray exposure in pregnant patients.