Toine Pieters

Cultural enthusiasm, resistance and the societal embedding of new technologies: Psychotropic drugs in the 20th century

Abstract The societal embedding of new (medical) technologies involves not only market success, but also regulation and public acceptance. Cultural enthusiasm about their benefits and social concerns about their risks and dangers are in this respect important. Conceptualizing interactions between product championing, cultural enthusiasm and resistance, the article analyses three patterns of societal embedding: (1) hype-cycle, (2) contested embedding, and (3) controversy and stalemate. A fourth pattern of waves of enthusiasm and concern is proposed for technologies with unexpected side effects. This pattern is explored and elaborated with a longitudinal case study of the introduction of a particular form of medical technology: psychotropic drugs such as Veronal and Valium in the period 1900–2000.

A 10-Year Analysis of the Effects of Media Coverage of Regulatory Warnings on Antidepressant Use in The Netherlands and UK

Background In 2003–2004 and 2007–2008, the regulatory banning of SSRI use in pediatrics and young adults due to concerns regarding suicidality risk coincided with negative media coverage. SSRI use trends were analyzed from 2000–2010 in the Netherlands (NL) and the UK, and whether trend changes might be associated with media coverage of regulatory warnings. Methods Monthly SSRIs sales were presented as DDDs/1000 inhabitants/day. SSRI-use trends were studied using time-series segmented regression analyses. Timing of trend changes was compared with two periods of media coverage of warnings. Annual Dutch SSRI prescription data were analyzed by age group. Results Trend changes in SSRI use largely corroborated with the periods of media coverage of warnings. British SSRI use declined from 3.9 to 0.7 DDDs/month (95%CI 3.3;4.5 & 0.5;0.9, respectively) before the first warning period (2003–2004). A small decrease of −0.6 DDDs/month (−1.2; −0.05) was observed in Dutch SSRI use shortly after 2003–2004. From 2007–2008, British SSRI use stabilized, whilst Dutch SSRI use diminished to −0.04 DDDs/month (−0.4;0.3). Stratified analyses showed a rapid decrease of −1.2 DDDs/month (−2.1; −1.7) in UK paroxetine use before 2003–2004, but only a minimal change in Dutch paroxetine use (−0.3 DDDs/month −0.8;0.2). Other SSRI use, especially (es)citalopram, increased during 2003–2004 in both countries. Significant reductions in Dutch paroxetine use were observed in pediatrics, adolescents, and young adults after 2003–2004. Conclusion Changes in SSRI use (NL & UK) were associated with the timing of the combined effect of media coverage and regulatory warnings. Our long-term assessment illustrates that changes in SSRI use were temporal, drug-specific and more pronounced in pediatrics and young adults. The twofold increase in SSRI use over one decade indicates that regulatory warnings and media coverage may come and go, but they do not have a significant impact on the overall upward trend of SSRI use as a class in both countries.

Gene doping: an overview and current implications for athletes

The possibility of gene doping, defined as the transfer of nucleic acid sequences and/or the use of normal or genetically modified cells to enhance sport performance, is a real concern in sports medicine. The abuse of knowledge and techniques gained in the area of gene therapy is a form of doping, and is prohibited for competitive athletes. As yet there is no conclusive evidence that that gene doping has been practiced in sport. However, given that gene therapy techniques improve continuously, the likelihood of abuse will increase. A literature search was conducted to identify the most relevant proteins based on their current gene doping potential using articles from Pubmed, Scopus and Embase published between 2006 and 2011. The final list of selected proteins were erythropoietin, insulin-like growth factor, growth hormone, myostatin, vascular endothelial growth factor, fibroblast growth factor, endorphin and enkephalin, α actinin 3, peroxisome proliferator-activated receptor-delta (PPARδ) and cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C). We discuss these proteins with respect to their potential benefits, existing gene therapy experience in humans, potential risks, and chances of detection in current and future anti-doping controls. We have identified PPARδ and PEPCK-C as having high potential for abuse. But we expect that for efficiency reasons, there will be a preference for inserting gene target combinations rather than single gene doping products. This will also further complicate detection.

Effective pharmaceutical regulation needs alignment with doctors

Concerns emanating from the medical community about the safety and efficacy of biosimilars indicate an increasing distrust of the outcome of the drug regulatory process. To illustrate this, we analysed the creation of the European biosimilar regulatory framework, specifically focussing on the guidelines outlining approval criteria for biosimilar erythropoietins, which have been recently adopted. We observed an absence of the organised medical community in the public process of creating and updating the guidelines. In this article we argue that, to ensure that innovative medicines continue to find their way to the patients who might benefit from them, a closer collaboration between the organised medical community and regulators is needed.

Semantic document selection: historical research on collections that span multiple centuries

The availability of digitized collections of historical data, such as newspapers, increases every day. With that, so does the wish for historians to explore these collections. Methods that are traditionally used to examine a collection do not scale up to todays collection sizes. We propose a method that combines text mining with exploratory search to provide historians with a means of interactively selecting and inspecting relevant documents from very large collections. We assess our proposal with a case study on a prototype system.

Systematic review of the mechanisms and evidence behind the hypocholesterolaemic effects of HPMC, pectin and chitosan in animal trials

Dietary fibres have diverse mechanisms in reducing plasma cholesterol, which could be useful for treating high levels of low-density lipoprotein cholesterol (LDL-C). The objective of this review is to determine the state of the evidence for the cholesterol-lowering effects of three selected fibres and their mechanisms, using the most recent animal trials. Therefore, a systematic review was conducted for hydroxypropyl methylcellulose (HPMC), pectin and chitosan in Pubmed, Embase and the Cochrane Library. All fibres reviewed reduced total cholesterol, very low-density lipoprotein cholesterol (VLDL-C) and LDL-C. Pectin gave a small, and chitosan an impressive rise in high-density lipoprotein cholesterol (HDL-C). A limitation of this study is the variety of animal models, each with distinct cholesterol profiles. Possible publication bias was also detected. In conclusion, chitosan seems to be the most promising of the studied fibres. A dietary fibre could be designed that yields the best cholesterol-lowering effect, using experiences in tailoring physicochemical properties and primarily exploiting the biophysical mechanisms of action.

Neurobiological Correlates in Forensic Assessment : A Systematic Review

Background With the increased knowledge of biological risk factors, interest in including this information in forensic assessments is growing. Currently, forensic assessments are predominantly focused on psychosocial factors. A better understanding of the neurobiology of violent criminal behaviour and biological risk factors could improve forensic assessments. Objective To provide an overview of the current evidence about biological risk factors that predispose people to antisocial and violent behaviour, and determine its usefulness in forensic assessment. Methods A systematic literature search was conducted using articles from PsycINFO, Embase and Pubmed published between 2000 and 2013. Results This review shows that much research on the relationship between genetic predisposition and neurobiological alterations with aggression is performed on psychiatric patients or normal populations. However, the number of studies comparing offenders is limited. There is still a great need to understand how genetic and neurobiological alterations and/or deficits are related to violent behaviour, specifically criminality. Most studies focus on only one of the genetic or neurobiological fields related to antisocial and/or violent behaviour. To reliably correlate the findings of these fields, a standardization of methodology is urgently needed. Conclusion Findings from the current review suggest that violent aggression, like all forms of human behaviour, both develops under specific genetic and environmental conditions, and requires interplay between these conditions. Violence should be considered as the end product of a chain of life events, during which risks accumulate and potentially reinforce each other, displaying or triggering a specific situation. This systematic review did not find evidence of predispositions or neurobiological alterations that solely explain antisocial or violent behaviour. With better designed studies, more correlation between diverse fields, and more standardisation, it might be possible to elucidate underlying mechanisms. Thus, we advocate maintaining the current case-by-case differentiated approach to evidence-based forensic assessment.

A digital humanities approach to the history of science: eugenics revisited in hidden debates by means of semantic text mining

Comparative historical research on the the intensity, diversity and fluidity of public discourses has been severely hampered by the extraordinary task of manually gathering and processing large sets of opinionated data in news media in different countries. At most 50,000 documents have been systematically studied in a single comparative historical project in the subject area of heredity and eugenics. Digital techniques, like the text mining tools WAHSP and BILAND we have developed in two successive demonstrator projects, are able to perform advanced forms of multi-lingual text-mining in much larger data sets of newspapers. We describe the development and use of WAHSP and BILAND to support historical discourse analysis in large digitized news media corpora. Furthermore, we argue how text mining techniques overcome the problem of traditional historical research that only documents explicitly referring to eugenics issues and debates can be incorporated. Our tools are able to provide information on ideas and notions about heredity, genetics and eugenics that circulate in discourses that are not directly related to eugenics (e.g., sport, education and economics).

The introduction of chlorpromazine in Belgium and the Netherlands (1951–1968); tango between old and new treatment features

The introduction of chlorpromazine in Belgium and the Netherlands demonstrates an intriguing tango between old and new treatments. Chlorpromazine, marketed by the French company Rhône Poulenc entered psychiatry as an adjunct to existing therapies. Instead of promoting chlorpromazine as a revolutionary therapy, we see early efforts to market Largactil as a supplement to the armoury of psychiatric treatments. These marketing efforts matched the idiosyncrasies of national and local styles and cultures. Despite continuities with earlier therapeutic developments, we support the notion of a therapeutic revolution. In the early sixties supply and demand provoked a turn towards more standardized therapeutic regimes.

Addressing the challenge of high-priced prescription drugs in the era of precision medicine : a systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks.

Context Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. Method A systematic review of Pubmed, the Financial Times, the New York Times, the Wall Street Journal and the Guardian was performed to identify articles related to the pricing of medicines. Findings Changes in drug life cycles have dramatically affected patent medicine markets, which have long been considered a self-evident and self-sustainable source of income for highly profitable drug companies. Market failure in combination with high merger and acquisition activity in the sector have allowed price increases for even off-patent drugs. With market interventions and the introduction of QALY measures in health care, governments have tried to influence drug prices, but often encounter unintended consequences. Patent reform legislation, reference pricing, outcome-based pricing and incentivizing physicians and pharmacists to prescribe low-cost drugs are among the most promising short-term policy options. Due to the lack of systematic research on the effectiveness of policy measures, an increasing number of ad hoc decisions have been made with counterproductive effects on the availability of essential drugs. Future challenges demand new policies, for which recommendations are offered. Conclusion A fertile ground for high-priced drugs has been created by changes in drug life-cycle dynamics, the unintended effects of patent legislation, government policy measures and orphan drug programs. There is an urgent need for regulatory reform to curtail prices and safeguard equitable access to innovative medicines.