The relationship of illicit drug use to HIV-infection among commercial sex workers in the city of Santos, São Paulo, Brazil

Objective: To assess the role of illicit drug use as a risk factor of HIV infection among female commercial sex workers (CSWs) in the city of Santos, Brazil. Design: Cross-sectional survey of 697 chain-referred CSWs. Methodology: The study included information on social-demographic characteristics, sexual practices and use of illicit drugs. Blood samples were tested for HIV. Associations between the response variable and drug-related variables, controlling for potential confounders, were assessed through multiple logistic regression procedures. Results: The univariate analyses for all drug-related variables evidenced that ‘use of injecting drugs’ (odds-ratios (OR)=10.9) and ‘use of crack in the previous month’ (OR=9.0), were the two variables most highly associated to the outcome. The multivariate analysis emphasized the role of crack use, the first variable included in the stepwise procedure (adjusted OR=5.3, P=0.0001). Other relevant predictors were ‘educational level’ (P=0.0003), ‘practice of anal intercourse with customers’ (P=0.0031), ‘use of injecting drugs’ (adjusted OR=3.1, P=0.0647), ‘age at first intercourse’ (P=0.0188) and ‘age’ (P=0.0175). Additional multivariate results showed that crack-users tend to use other drugs simultaneously, to agree more frequently to have unprotected sex and to earn a significantly smaller payment per sexual encounter than crack non-users. Conclusions: The analysis showed the vulnerability of CSWs in relation to drug use, lack of education and unprotected sex. These findings highlight the need for preventive programs focused on the general use of drugs in this population as well as efforts to help CSWs to acquire educational and professional skills.     

Casting light on harm reduction: Introducing two instruments for analysing contradictions between harm reduction and ‘non-harm reduction’

Background: Harm reduction is commonly regarded as complementary to other drug problem responses—as the fourth tier. Yet even core examples of harm reduction such as the provision of injection equipment and methadone treatment have over and over encountered considerable opposition, and harm reduction in its more comprehensive forms continuously stirs up controversy. In spite of this the notion of complementarity is commonly upheld leaving opposition to harm reduction inexplicable and non-researchable. Methods: Teaching experience in multiple settings in which opposing views have surfaced and a review of relevant literature on contradictions involved in drug policy debates have been utilized to analyse and summarize policy contradictions involved implicitly or explicitly in disagreements on harm reduction. Results: Analysing contradictions is a difficult endeavour, but many opposing views appear if you approach the task systematically. For this purpose two instruments have been constructed: ‘The Harm Reduction Inventory’ (25 items) and ‘The Drug Policy Propensity Index’ (11 items). These tentative instruments are presented in full and their potentials are discussed. Conclusion: Harm reduction may in fact represent goals, methods, priorities and understandings which are to a considerable extent at odds with the opposite of harm reduction – here termed ‘non-harm reduction’. This insight may be overlooked if assuming complementarity. To describe and analyse harm reduction by way of juxtaposing opposites seems a feasible and illuminative approach. The instruments provided could perhaps facilitate better understanding of conflicts of vision and contribute towards illuminating policy barriers.     

Understanding post 9/11 drug control policy and politics in Central Asia

This paper exposes contemporary drug policy challenges in Central Asia by focusing on a single point in the history of drug control, in a single region of the global war against drugs and terrorism, and on one agency whose mission is to help make the world safer from crime, drugs and terrorism. By looking closely at the post 9/11 security-oriented donor priorities, I conclude that, in Central Asia, the rhetoric of the taking a more ‘balanced approach’ to drug policy is bankrupt. When enacted by the national law enforcement agencies in the Central Asian republics, the ‘Drug Free’ aspirational goal is driving the HIV epidemic among IDUs. The face-saving ‘containment’ thesis does not reflect the drug situation in this region but rather the failure to adopt an evidence-based approach. The harm reduction agenda continues to face many challenges including resistance to substitution treatment, the harm from drug treatment, from poorly designed drug prevention programmes and from repressive counter-narcotics policies and practices.     

Revisioning women and drug use: gender sensitivity, embodiment and reducing harm

The purpose of this paper is ‘to revision’ our approach to women's use of drugs – which means to let go of how we have seen in order to construct new perceptions. Women use a variety of substances for a range of reasons, including pleasure. Yet, women who experience problems are left feeling stigmatised, marginalised and demoralised. The paper includes three inter-related discussions. First, two co-existing approaches to drug use, the classical and the postmodern, are explained. Second, after demonstrating how the postmodern approach is more valuable for the development of a gender-sensitive perspective, I will, with special reference to drug use, explain the complexities of two contemporary concepts, gender and embodiment. Here, I attempt to generate a deeper appreciation of these concepts in the postmodern approach. Third, I ask, ‘How can we develop a gender-sensitive, harm reduction approach’? The contention is that while harm reduction philosophies are admirable, these need to be gender-sensitive in order to be effective. A multi-levelled, ‘gender-sensitive’ view of harm reduction is put forward, as harm reduction is examined at the subjective, treatment, relationship, occupational and leisure levels.     

Insights in the application of research-grade diagnostic kits for biomarker assessments in support of clinical drug development: bioanalysis of circulating concentrations of soluble receptor activator of nuclear factor kappaB ligand

Application of research-grade diagnostic kits in clinical drug development has grown commensurate with the increased interest in utilization of biomarkers as drug development tools. Since novel biomarkers are frequently macromolecular, immunoassay methodology comprises the ‘technology-of-choice’ for biomarker quantification. In particular, commercial research-grade immunoassay kits are appealing for use in biomarker quantification during clinical phase drug development because of their ready availability, ease of operation and perceived convenience. However, bioanalytical validation issues arise often during the application of commercial kits, as GLP regulatory-compliant application places greater demands on kit design and performance. In this review, we have used the receptor activator of nuclear factor κB ligand (RANKL) as a model system to offer some insights into the challenges that can be encountered in the application of ‘research-grade’ diagnostic kits in support of clinical drug development.Currently only a few assays are available commercially for the determination of circulating concentrations of sRANKL. Of these, two immunoassay designs have been most often. The first design employs human osteoprotegerin to capture unbound sRANKL from serum and, thereby, provides a measure of circulating free concentrations. In contrast, the other common assay design first involves preincubation of serum samples with human osteoprotegerin to convert the free fraction of sRANKL to the osteoprotegerin-bound complex. The bound fraction is subsequently captured by an anti-osteoprotegerin antibody. In both immunoassay designs, detection is accomplished with an anti-sRANKL enzyme conjugation system. In this report we review these sRANKL immunoassay designs critically from the perspective of their potential suitability as drug development biomarker tools. In addition, analytical challenges relevant to the application of these ‘research-grade’ diagnostic kits for regulatory-compliant determination of sRANKL concentrations are discussed.     

Drug use as a ‘practice of the self’: is there any place for an ‘ethics of moderation’ in contemporary drug policy?

This paper offers a series of critical interrogations of the principles and practice of harm minimisation. This critique draws from Michel Foucault's account of ethics, pleasure and moderation in pointing to some significant gaps and conceptual problems within Australia's National Drug Strategy. I argue that this strategy has had only indirect impacts upon the ways in which illicit drugs are consumed in Australia, and on the behaviour of individual users. Part of this problem lies in the ways in which the cultures and the contexts of illicit drug use have been conceptualised within contemporary drug policy. Following Foucault, I argue that drug use ought to be conceptualised as a distinctive ‘practice of the self’. I argue further that Foucault's work on pleasure and ethics offers important new ways of understanding the changing nature of drug use for young people, as well as providing new conceptual bases for the design and delivery of harm minimisation strategies within those settings and contexts in which drug use takes place.     

The interface between pharmacoepidemiology and pharmacogenetics

One of the most challenging areas of research in pharmacoepidemiology is to understand why individuals respond differently to drug therapy, both in terms of beneficial and adverse effects. Pharmacogenetics focuses on the question to what extent variability in genetic make-up is responsible for these observed differences. Pharmacoepidemiologic research can contribute to pharmacogenetics by explaining the observed variability in drug response in ‘real life’ patient populations with known polymorphisms in their genetic profile. Genetic pharmacoepidemiologists also are interested in the distribution of polymorphisms and correlated frequencies of responders and non-responders in the general population, and in searching for unknown genetic links to variability in drug response. In the future, we will probably have fewer drugs that suit all individuals. Genetic pharmacoepidemiology is going to play a major role in the development and evaluation of the concept of ‘tailor-made’ pharmacotherapy.     

Pharmaco-epidemiological perspectives

Parallel with increasing concerns about drug safety, the importance of drug surveillance and the application of epidemiologic techniques have grown rapidly during the past decades. The increasing use of computerized health care data facilitates the establishment of populations large enough (millions) to allow epidemiological studies. Such extensive studies are now being done routinely in North America. By the use of computerized pharmacy or billing records, drug exposure is linked to files which include diagnoses. These record-linkage systems provide objective drug histories for pharmaco-epidemiological cohort and case-control studies and these large data bases offer powerful tools for drug evaluation. A number of new drug-disease associations, many of potential importance for European populations, will be discovered through the increased use of large data bases in North America. The European community needs to develop a strategy to respond to these overseas findings to protect the society from either overreaction or underreaction to drug safety issues.This article is based on a paper presented in the session Drug utilization and ADR surveillance — new technology and methods, at the WHO Drug Utilization Research Group meeting in Oslo, Norway, 28–30 September 1987.     

Anxiety and containment in the risk society: theorising young people and drug prevention policy

This paper sets out to make sense of government responses to young people and drug use through an application of some central concepts arising from the work of Ulrich Beck and risk society theory. It is primarily concerned with recent universal and targeted drug prevention initiatives in the UK. With regard to universal educational and health promotion, it is argued that initiatives have struggled to define their communicative rationality in the context of young people's changing social encounter with drugs. Policy-based initiatives have also become increasingly expansive in nature as they seek to contain a complex and contested social risk environment. Yet, in so doing they encounter operational difficulties associated with ‘manufactured risks’. Meanwhile, targeted drug prevention has become increasingly driven by the science of risk and vulnerability. However, rather than managing hazards, both ‘risk science’ associated policy-based interventions encounter definitional problems and system-generated risks associated with their praxis. Government agencies have, in turn, responded through introducing formalized systems for co-ordination and the responsibilisation of an increasing range of actors. Notwithstanding some difficulties, it is suggested therefore that risk society theory elucidates some of the conflicts and instabilities that underlie contemporary young people and drug prevention policy.     

The inhibition of human immunodeficiency virus proteases by ‘interface peptides’

The active human immuondeficiency virus type 1 (HIV-1) protease has a homodimeric structure, the subunits are connected by an ‘interface’ β-sheet formed by the NH₂- and COOH-terminal amino acid segments. Short peptides derived from these segments are able to inhibit the protease activity in the range of micromolar IC₅₀ values. We have further improved the inhibitory power of such peptides by computer modelling. The best inhibitor, the palmitoyl-blocked peptide Pam-Thr-Val-Ser-Tyr-Glu-Leu, has an IC₅₀ value of less than 1 μM. Some of the peptides also showed very good inhibition of the HIV-2 protease. The C-terminal segment of the HIV-1 matrix protein, Acetyl-Gln-Val-Ser-Gln-Asn-Tyr, also inhibits HIV-1 protease. Kinetic studies confirmed the ‘dissociative’ mechanism of inhibition by the peptides. Depending on the peptide structure and ionic strength, both dimerization inhibition and competitive inhibition were observed, as well as synergistic effects between competitive inhibitors and interface peptides.     

Differences in attitudes towards drug taking among drug addicts: Implications for treatment

Addicts attending a London drug dependence clinic (N = 147) completed questionnaires exploring their attitudes towards their own drug taking. Three factors were extracted from the data and these were called ‘Hooked’, ‘Sick’ and ‘Therapeutic Optimism’. In-patients, regular out-patients and new out-patients, differed in attitudes towards drug taking. New out-patients regarded themselves as more Hooked and Sick than did in-patients. Regular out-patients had lower therapeutic optimism than did the other two groups. Whether these differences arise through self-selection, that is, those who regard themselves as more sick and hooked tend to drop out early, or whether increasing contact with the clinic leads to shifts in these attitudes is discussed.     

Drugalities: the generative capabilities of criminalized ‘drugs’

Drawing on cultural studies and actor-network theoretical traditions, this article explores the generative capacities of the ‘drugalities’ or personalities of different drugs. This article explores technologies of generalisation as well as specification in order to show that the ways in which a substance behaves pharmacologically, as well as the ways in which it is constituted culturally and officially, work to shape attempts to control its use.     

Monosodium L-glutamate: A double-blind study and review

71 healthy subjects were treated with placebos and monosodium L-glutamate (MSG) doses of 1.5, 3.0 and 3.15 g/person, which represented a body mass-adjusted dose range of 0.015–0.07 g/kg body weight before a standardized breakfast over 5 days. The study used a rigorous randomized double-blind crossover design that controlled for subjects who had MSG after-tastes. Capsules and specially formulated drinks were used as vehicles for placebo and MSG treatments. Subjects mostly had no responses to placebo (86%) and MSG (85%) treatments. Sensations, previously attributed to MSG, did not occur at a significantly higher rate than did those elicited by placebo treatment. A significant (P < 0.05) negative correlation between MSG dose and after-effects was found. The profound effect of food in negating the effects of large MSG doses was demonstrated. The common practice of extrapolating food-free experimental results to ‘in use’ situations was called into question. An exhaustive review of previous methodologies identified the strong taste of MSG as the factor invalidating most ‘blind’ and ‘double-blind’ claims by previous researchers. The present study led to the conclusion that ‘Chinese Restaurant Syndrome’ is an anecdote applied to a variety of postprandial illnesses; rigorous and realistic scientific evidence linking the syndrome to MSG could not be found.     

Stimulation of insulin secretion by the imidazoline α2-adrenoceptor antagonist efaroxan is mediated by a novel, stereoselective, binding site

We have studied the stereospecificity of three responses mediated by the α₂-antagonist efaroxan in rat islets of Langerhans. α₂-Adrenergic inhibition of insulin secretion was relieved most effectively by the (+) enantiomer. In contrast, direct stimulation of insulin secretion and antagonism of the inhibitory effects of diazoxide were both preferentially mediated by the (−) enantiomer. Culture of islets in the presence of efaroxan resulted in loss of responsiveness to subsequent re-addition of the drug. On the basis of these results we propose the existence, in islets, of a novel ‘non-adrenergic’ binding site at which efaroxan acts as an agonist.     

Infovigilance: Reporting Errors in Official Drug Information Sources

Introduction: The French drug database Thériaque (http://www.theriaque.org) developed by the (Centre National Hospitalier d’Information sur le Médicament) (CNHIM), is responsible for the dissemination of independent information about all drugs available in France. Each month the CNHIM pharmacists report problems due to inaccuracies in these sources to the French drug agency. In daily practice we devised the term “infovigilance”: “Activity of error or inaccuracy notification in information sources which could be responsible for medication errors”. The aim of this study was to evaluate the impact of CNHIM infovigilance on the contents of the Summary of Product Characteristics (SPCs).Method: The study was a prospective study from 09/11/2001 to 31/12/2002. The problems related to the quality of information were classified into four types (inaccuracy/confusion, error/lack of information, discordance between SPC sections and discordance between generic SPCs).Main outcome measures:(1) Number of notifications and number of SPCs integrated into the database during the study period.(2) Percentage of notifications for each type: with or without potential patient impact, with or without later correction of the SPC, per section.Results: 2.7% (85/3151) of SPCs integrated into the database were concerned by a notification of a problem. Notifications according to type of problem were inaccuracy/confusion (32%), error/lack of information (13%), discordance between SPC sections (27%) and discordance between generic SPCs (28%). 55% of problems were evaluated as ‘likely to have an impact on the patient’ and 45% as ‘unlikely to have an impact on the patient’. 22 of problems which have been reported to the French drug agency were corrected and new updated SPCs were published with the corrections.Conclusions: Our efforts to improve the quality of drug information sources through a continuous “infovigilance” process need to be continued and extended to other information sources.     

Novel trends in high-throughput screening

Lead discovery by high-throughput screening (HTS) has evolved into a mature scientific discipline in modern drug discovery since its beginning about 10–15 years ago. Owing to the strong efforts in automation and miniaturization, even relatively large compound collections of over one million compounds or more can be screened against a large number of biological targets in relatively short time and at relatively low cost compared to the efforts of just 5 or 10 years ago. This was only possible with the concomitant development of high-quality readout technologies for highly miniaturized screening. Whereas most of the conventional drug targets can be approached via current HTS-readout technologies, the challenge goes toward the hitherto non-tractable families of drug targets. Future trends will focus strongly toward these novel target classes such as ion channels, transporters, protein–protein interactions, among many others. It will be essential to make proper readout technologies and adequate chemical libraries available for these target classes. Chemical libraries derived from natural products, but also derived from combinatorial chemistry and automated synthesis will be a key prerequisite for success in the field, as long as enough diversity and drug-like properties are included in these chemical libraries [25]. The proper readout technologies for screening of large chemical libraries have seen strong advances in recent years [^{[2], [7] and [22••]}], nevertheless none of these technologies is void of artifacts, in particular artifacts derived from the inherent physical nature of chemical compounds in aqueous buffer [11^••]. We therefore propose that future lead discovery should pay more attention toward unambiguous identification of these compound related artifacts and toward efficient removal of these false-positive compounds from the HTS hit-lists. We strongly recommend the use of biophysical and enzymological studies in the HTS hit-list follow-up phase (‘hit validation’) in order to deliver information of the highest possible quality for subsequent hit-to-lead studies. Finally, the science and art of HTS has evolved in various phases from its beginning in the early 1990s toward today's state-of-the-art operation in lead discovery. During these 15 years, one can distinguish three phases (‘generations’) of HTS operations: during the first phase, HTS has been just the same as laboratory screening, albeit at much larger capacity; in the second phase (‘second generation HTS’), HTS has evolved toward more sophisticated assay development/adaptation, more toward dedicated tool production, but also more toward counter-screening and hit-list follow-up; in the current phase (‘third generation HTS’) we see much more flexibility with regards to the applied processes for lead discovery, a stronger focus on quality and validation of the obtained results and a better awareness for choosing a proper lead finding strategy in a target-by-target specific manner.Taken together, we can conclude that better flexibility and creativity, more quality and the use of project-related, tailor-made lead finding strategies in the discovery process will become the key drivers for the successful application of high-throughput screening in the Pharmaceutical, Biotech, and Academic drug discovery programs of the future.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest

•• of outstanding interest

中国罕见病药物研发政策及研发现状简析

罕见病发病率低、病情复杂、诊断难度大，导致其治疗药物研发面临诸多困难。为满足临床迫切需求，鼓励罕见病药物研发，近年来国家出台一系列政策及技术指导原则。梳理了2015年至今的罕见病治疗药物研发激励政策，通过查阅文献及公开资料，整理2018—2023年批准上市的用于治疗第一批罕见病目录中罕见病治疗的药物信息，分析中国罕见病药物研发现状。建议定期更新罕见病目录，加强罕见病药物研发者权益保护，鼓励优质罕见病药物仿制，以推动罕见病药物研发产业创新发展、满足罕见病患者的用药需求。     

Studying illicit drug markets: Disciplinary contributions

This paper provides a reflective account of the different disciplinary approaches to studying illicit drug markets. The term ‘drug market’ is used widely in illicit drug research, and means different things to different researchers. An economist may have a very specific view of what is meant by a drug market, and that will differ from one held by an ethnographer. The paper endeavours to describe and explain five different disciplinary approaches to studying drug markets—ethnographic and qualitative approaches; economic approaches; behavioural and psychological research; population-based and survey research; criminology and law enforcement evaluation. Each discipline has strengths and limitations. I do not argue for the supremacy of one approach, but that we need to appreciate the different approaches and develop better multi-disciplinary models.     

Methods for assessing HIV and HIV risk among IDUs and for evaluating interventions

A wide range of methods is now available for assessing the nature and characteristics of drug injecting populations, and for evaluating the effectiveness of interventions developed to reduce injecting related harms. The public health surveillance tasks in relation to injecting drug use populations and associated health problems are the same, in principle, as for the surveillance of other health problems. These are: to describe the patterns of the condition, the nature of the problem and the environment (context) in which it occurs; to determine the scale of interventions needed and estimated coverage required, to forecast future health care needs; to mobilise resources and target prevention; and to evaluate interventions. Countries vary in their existing levels of information as well as resources for surveillance systems, research and evaluation. We propose three levels of assessment: basic assessment, which is suitable in situations of low awareness and information, routine surveillance, and enhanced surveillance, which requires more complex research and/or analyses of data collected from routine surveillance.