'Planning for a healthy baby and a healthy pregnancy': A critical analysis of Canadian clinical practice guidelines for the treatment of opioid dependence during pregnancy.

As opioid fatalities rise in North America, the need to improve the supports available to those who are dependent on opioids and pregnant has become more urgent. This paper discusses the social organisation of drug treatment supports for those who are pregnant, using Canadian clinical practice guidelines (CPGs) for methadone maintenance treatment (MMT) as a case study. Pregnant patients are a priority population for MMT, both in Canada and internationally; the regulatory bodies that oversee MMT in Canada are the provincial Colleges of Physician and Surgeons and Health Canada. The paper analyses MMT CPGs published by these agencies, comparing their general recommendations to those specific to pregnant patients. We demonstrate that the guidelines address few treatment considerations for pregnant patients, other than improved birth outcomes and child welfare, despite acknowledging their more complex needs. Drawing on social science studies of gender and drugs, we argue that MMT CPGs therefore perpetuate the intensified surveillance and foetal prioritisation that have long generated barriers to care for opiate-dependent pregnant patients. We also discuss how and why the CPGs ultimately only reinforced these current limitations in the drug treatment sector.

Immortalized striatal precursor neurons from Huntington's disease patient-derived iPS cells as a platform for target identification and screening for experimental therapeutics.

We have previously established induced pluripotent stem cell (iPSC) models of Huntington's disease (HD), demonstrating CAG-repeat-expansion-dependent cell biological changes and toxicity. However, the current differentiation protocols are cumbersome and time consuming, making preparation of large quantities of cells for biochemical or screening assays difficult. Here, we report the generation of immortalized striatal precursor neurons (ISPNs) with normal (33) and expanded (180) CAG repeats from HD iPSCs, differentiated to a phenotype resembling medium spiny neurons (MSN), as a proof of principle for a more tractable patient-derived cell model. For immortalization, we used co-expression of the enzymatic component of telomerase hTERT and conditional expression of c-Myc. ISPNs can be propagated as stable adherent cell lines, and rapidly differentiated into highly homogeneous MSN-like cultures within 2 weeks, as demonstrated by immunocytochemical criteria. Differentiated ISPNs recapitulate major HD-related phenotypes of the parental iPSC model, including brain-derived neurotrophic factor (BDNF)-withdrawal-induced cell death that can be rescued by small molecules previously validated in the parental iPSC model. Proteome and RNA-seq analyses demonstrate separation of HD versus control samples by principal component analysis. We identified several networks, pathways, and upstream regulators, also found altered in HD iPSCs, other HD models, and HD patient samples. HD ISPN lines may be useful for studying HD-related cellular pathogenesis, and for use as a platform for HD target identification and screening experimental therapeutics. The described approach for generation of ISPNs from differentiated patient-derived iPSCs could be applied to a larger allelic series of HD cell lines, and to comparable modeling of other genetic disorders.

Controversy of TMEM230 Associated with Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease with movement disorders including resting tremor, bradykinesia, rigidity, and postural instability. The key pathological features of PD are selective loss of dopaminergic (DA) neurons in substantial nigra and the presence of Lewy bodies (LBs). Mutations in TMEM230 (transmembrane protein 230) have been recently reported to play a pathological role and contribute to PD pathogenesis. TMEM230 gene encodes two isoforms of TMEM230 proteins, isoform I (183 amino acids) and isoform II (120 amino acids). The function of TMEM230 is not clear, but it may be involved in vesicle trafficking and recycling, autophagy, protein aggregation, and cell toxicity. There are four reported PD-linked TMEM230 mutations (p.Y92C, p.R141L, p.*184Wext*5, p.*184PGext*5). TMEM230-linked PD cases exhibit late-onset, good-response to levodopa, and typical clinical features of sporadic PD with DA neuronal loss in substantial nigra and Lewy body pathology. In this mini review, we recap the current literature of TMEM230 in genetic, neurobiological, and pathological studies in order to further understand the potential roles of TMEM230 in PD pathogenesis.

Sociomateriality: a theoretical framework for studying distributed medical education.

Distributed medical education (DME) is a type of distance learning in which students participate in medical education from diverse geographic locations using Web conferencing, videoconferencing, e-learning, and similar tools. DME is becoming increasingly widespread in North America and around the world.Although relatively new to medical education, distance learning has a long history in the broader field of education and a related body of literature that speaks to the importance of engaging in rigorous and theoretically informed studies of distance learning. The existing DME literature is helpful, but it has been largely descriptive and lacks a critical "lens"-that is, a theoretical perspective from which to rigorously conceptualize and interrogate DME's social (relationships, people) and material (technologies, tools) aspects.The authors describe DME and theories about distance learning and show that such theories focus on social, pedagogical, and cognitive considerations without adequately taking into account material factors. They address this gap by proposing sociomateriality as a theoretical framework allowing researchers and educators to study DME and (1) understand and consider previously obscured actors, infrastructure, and other factors that, on the surface, seem unrelated and even unimportant; (2) see clearly how the social and material components of learning are intertwined in fluid, messy, and often uncertain ways; and (3) perhaps think differently, even in ways that disrupt traditional approaches, as they explore DME. The authors conclude that DME brings with it substantial investments of social and material resources, and therefore needs careful study, using approaches that embrace its complexity.

Prescribing practices amid the OxyContin crisis: examining the effect of print media coverage on opioid prescribing among physicians.

UNLABELLED: The pain medication OxyContin (hereafter referred to as oxycodone extended release) has been the subject of sustained, and largely negative, media attention in recent years. We sought to determine whether media coverage of oxycodone extended release in North American newspapers has led to changes in prescribing of the drug in Nova Scotia, Canada. An interrupted time-series design examined the effect of media attention on physicians' monthly prescribing of opioids. The outcome measures were, for each physician, the monthly proportions of all opioids prescribed and the proportion of strong opioids prescribed that were for oxycodone extended release. The exposure of interest was media attention defined as the number of articles published each month in 27 North American newspapers. Variations in media effects by provider characteristics (specialty, prescribing volume, and region) were assessed. Within-provider changes in the prescribing of oxycodone extended release in Nova Scotia were observed, and they followed changes in media coverage. Oxycodone extended release prescribing rose steadily prior to receiving media attention. Following peak media attention in the United States, the prescribing of oxycodone extended release slowed. Likewise, following peak coverage in Canadian newspapers, the prescribing of oxycodone extended release declined. These patterns were observed across prescriber specialties and by prescriber volume, though the magnitude of change in prescribing varied. PERSPECTIVE: This study demonstrates that print media reporting of oxycodone extended release in North American newspapers, and its continued portrayal as a social problem, coincided with reductions in the prescribing of oxycodone extended release by physicians in Nova Scotia.

The OxyContin crisis: problematisation and responsibilisation strategies in addiction, pain, and general medicine journals.

BACKGROUND: OxyContin(®) (Purdue Pharma, L.P., Stamford, CT) is now widely regarded as a drug of abuse fueling a larger opioid health crisis. While coverage in the North American press about OxyContin overwhelmingly focused upon the problems of related crime and addiction/misuse and the perspectives of law enforcement officials and police, coverage in those fields of medicine most intimately concerned with OxyContin-pain medicine and addiction medicine-was more nuanced. METHODS: In this article, we draw upon the constructivist social problems tradition and Hunt's theory of moral regulation in a qualitative analysis of 24 medical journal articles. We compare and contrast pain medicine and addiction medicine representations of the OxyContin problem, the agents responsible for it, and proposed solutions. RESULTS: While there are some significant differences, particularly concerning the nature of the problem and the agents responsible for it, both pain medicine and addiction medicine authors 'take responsibility' in ways that attempt to mitigate the potential appropriation of the issue by law enforcement and regulatory agencies. CONCLUSIONS: The responses of pain medicine and addiction medicine journal articles represent strategic moves to recapture lost credibility, to retain client populations and tools necessary to their jobs, and to claim a seat at the table in responding to the OxyContin crisis.

Representations of OxyContin in North American newspapers and medical journals.

BACKGROUND: There are public concerns regarding OxyContin (Purdue Pharma, Canada) and charges within the pain medicine community that media coverage of the drug has been biased. OBJECTIVE: To analyze and compare representations of OxyContin in medical journals and North American newspapers in an attempt to shed light on how each contributes to the 'social problem' associated with OxyContin. METHODS: Using searches of newspaper and medical literature databases, two samples were drawn: 924 stories published between 1995 and 2005 in 27 North American newspapers, and 197 articles published between 1995 and 2007 in 33 medical journals in the fields of addiction/substance abuse, pain/anesthesiology and general/internal medicine. The foci, themes, perspectives represented and evaluations of OxyContin presented in these texts were analyzed statistically. RESULTS: Newspaper coverage of OxyContin emphasized negative evaluations of the drug, focusing on abuse, addiction, crime and death rather than the use of OxyContin for the legitimate treatment of pain. Newspaper stories most often conveyed the perspectives of law enforcement and courts, and much less often represented the perspectives of physicians. However, analysis of physician perspectives represented in newspaper stories and in medical journals revealed a high degree of inconsistency, especially across the fields of pain medicine and addiction medicine. CONCLUSION: The prevalence of negative representations of OxyContin is often blamed on biased media coverage and an ignorant public. However, the proliferation of inconsistent messages regarding the drug from physicians plays a role in the drug's persistent status as a social problem.

Negotiating science and experience in medical knowledge: gynaecologists on endometriosis.

This paper analyses the gynaecological literature on endometriosis, particularly endometriosis classification, to evaluate the epistemological concepts it uses. A qualitative content analysis was conducted on a sample of gynaecological literature published between 1985 and 2000, a period that witnessed the explosion of both evidence-based and patient-centred models of medicine, with their dwelling emphases on science and experience. It was found that the discourse of science is used strategically in this literature as a formal epistemology to lend weight to authors' claims and to guide medical thinking and research. However, gynaecologists also use the notion of experience to assert their own credibility and to question the credibility of other experts. In fact, accounts of their own experience and the experiential accounts of their patients are foundational to gynaecologists' claims-making activities, including their engagement with scientific research.

'No one agrees except for those of us who have it': endometriosis patients as an epistemological community.

This paper contributes to the literature on patients' claims-making work by analysing the epistemological strategies and standards used by members of an endometriosis patient community. It draws upon focus group research with members of a support group for endometriosis sufferers, and an open-ended survey of an e-mail list for women with the disease. Lynn Hankinson Nelson's (1993) concept of epistemological community is used to examine standards and practices for developing and evaluating knowledge used by women with endometriosis. Particular attention is paid to the use and centrality of the notion of experience within this community.

A resolved outflow of matter from a brown dwarf.

The birth of stars involves not only accretion but also, counter-intuitively, the expulsion of matter in the form of highly supersonic outflows. Although this phenomenon has been seen in young stars, a fundamental question is whether it also occurs among newborn brown dwarfs: these are the so-called 'failed stars', with masses between stars and planets, that never manage to reach temperatures high enough for normal hydrogen fusion to occur. Recently, evidence for accretion in young brown dwarfs has mounted, and their spectra show lines that are suggestive of outflows. Here we report spectro-astrometric data that spatially resolve an outflow from a brown dwarf. The outflow's characteristics appear similar to, but on a smaller scale than, outflows from normal young stars. This result suggests that the outflow mechanism is universal, and perhaps relevant even to the formation of planets.