Irrational addicts and responsible pleasure seekers: Constructions of the drug user

Historically, drug use has been understood as a problem of epidemiology, psychiatry, physiology, and criminality requiring legal and medical governance. Consequently drug research tends to be underpinned by an imperative to better govern, and typically proposes policy interventions to prevent or solve drug problems. We argue that categories of ‘addictive’ and ‘recreational’ drug use are discursive forms of governance that are historically, politically and socially contingent. These constructions of the drug problem shape what drug users believe about themselves and how they enact these beliefs in their drug use practices. Based on qualitative interviews with young illicit drug users in Brisbane, Australia, this paper uses Michel Foucault’s concept of governmentality to provide insights into how the governance of illicit drugs intersects with self-governance to create a drug user self. We propose a reconceptualisation of illicit drug use that takes into account the contingencies and subjective factors that shape the drug experience. This allows for an understanding of the relationships between discourses, policies, and practices in constructions of illicit drug users.

Axial spondyloarthritis: A new disease entity, not necessarily early ankylosing spondylitis

New classification criteria for axial spondyloarthritis have been developed with the goal of increasing sensitivity of criteria for early inflammatory spondyloarthritis. However these criteria substantially increase heterogeneity of the resulting disease group, reducing their value in both research and clinical settings. Further research to establish criteria based on better knowledge of the natural history of non-radiographic axial spondyloarthritis, its aetiopathogenesis and response to treatment is required. In the meantime the modified New York criteria for ankylosing spondylitis remain a very useful classification criteria set, defining a relatively homogenous group of cases for clinical use and research studies.

Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: Results of a randomised placebo-controlled trial (ABILITY-1)

Purpose: To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: Patients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index. Results: Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p<0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases. Conclusions: In patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit-risk profile in active nr-axSpA patients with inadequate response to NSAIDs.

Targeting drug-resistant prostate cancer with dual PI3K/mTOR inhibition

The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is one of the most frequently activated signaling pathways in prostate cancer cells, and loss of the tumor suppressor PTEN and amplification of PIK3CA are the two most commonly detected mechanisms for the activation of these pathways. Aberrant activation of PI3K/Akt/mTOR has been implicated not only in the survival and metastasis of prostate cancer cells but also in the development of drug resistance. As such, selective inactivation of this pathway may provide opportunities to attack prostate cancer from all fronts. However, while preclinical studies examining specific inhibitors of PI3K or mTOR have yielded promising results, the evidence from clinical trials is less convincing. Emerging evidence from the analyses of some solid tumors suggests that a class of dual PI3K/mTOR inhibitors, which bind to and inactivate both PI3K and mTOR, may achieve better anti-cancer outcomes. In this review, we will summarize the mechanisms of action of these inhibitors, their effectiveness when used alone or in combination with other chemotherapeutic compounds, and their potential to serve as the next generation therapies for prostate cancer patients, particularly those who are resistant to the frontline chemotherapeutic drugs.

A compliant, banded outflow cannula for decreased afterload sensitivity of rotary right ventricular assist devices

Biventricular support with dual rotary ventricular assist devices (VADs) has been implemented clinically with restriction of the right VAD (RVAD) outflow cannula to artificially increase afterload and, therefore, operate within recommended design speed ranges. However, the low preload and high afterload sensitivity of these devices increase the susceptibility of suction events. Active control systems are prone to sensor drift or inaccurate inferred (sensor-less) data, therefore an alternative solution may be of benefit. This study presents the in vitro evaluation of a compliant outflow cannula designed to passively decrease the afterload sensitivity of rotary RVADs and minimize left-sided suction events. A one-way fluid-structure interaction model was initially used to produce a design with suitable flow dynamics and radial deformation. The resultant geometry was cast with different initial cross-sectional restrictions and concentrations of a softening diluent before evaluation in a mock circulation loop. Pulmonary vascular resistance (PVR) was increased from 50 dyne s/cm5 until left-sided suction events occurred with each compliant cannula and a rigid, 4.5 mm diameter outflow cannula for comparison. Early suction events (PVR ∼ 300 dyne s/cm5) were observed with the rigid outflow cannula. Addition of the compliant section with an initial 3 mm diameter restriction and 10% diluent expanded the outflow restriction as PVR increased, thus increasing RVAD flow rate and preventing left-sided suction events at PVR levels beyond 1000 dyne s/cm5. Therefore, the compliant, restricted outflow cannula provided a passive control system to assist in the prevention of suction events with rotary biventricular support while maintaining pump speeds within normal ranges of operation.

Characteristics of microbial drug resistance and its correlates in chronic diabetic foot ulcer infections

While virulence factors and the biofilm-forming capabilities of microbes are the key regulators of the wound healing process, the host immune response may also contribute in the events following wound closure or exacerbation of non-closure. We examined samples from diabetic and non-diabetic foot ulcers/wounds for microbial association and tested the microbes for their antibiotic susceptibility and ability to produce biofilms. A total of 1074 bacterial strains were obtained with staphylococci, Pseudomonas, Citrobacter and enterococci as major colonizers in diabetic samples. Though non-diabetic samples had a similar assemblage, the frequency of occurrence of different groups of bacteria was different. Gram-negative bacteria were found to be more prevalent in the diabetic wound environment while Gram-positive bacteria were predominant in non-diabetic ulcers. A higher frequency of monomicrobial infection was observed in samples from non-diabetic individuals when compared to samples from diabetic patients. The prevalence of different groups of bacteria varied when the samples were stratified according to age and sex of the individuals. Several multidrug-resistant strains were observed among the samples tested and most of these strains produced moderate to high levels of biofilms. The weakened immune response in diabetic individuals and synergism among pathogenic micro-organisms may be the critical factors that determine the delicate balance of the wound healing process.

We know this: How to apply what you already know to treat alcohol and other drug problems

Background Implementing effective AOD supports and treatments into our daily practice can occur via a range of strategies. While specialist treatments exclusively targeting pathways toward substance reduction are an option, it is often not within the scope of many psychologists working in generalist or tertiary mental health settings. Regardless of the perceived barriers for integrating AOD practice into our work, there are key principles and approaches that can be adopted to improve the outcomes for many clients. Aim Irrespective of the client’s perceived need to address AOD issues, significant substance use will impact on the development, prognosis and treatment of most mental health conditions. Embedding AOD practice across our clinical work requires an openness to consider evidence-based approaches for all levels of substance use. Method This presentation will outline a series of approaches that all practitioners can adopt, based on the principles of harm reduction and empowerment of client’s choice. An emphasis will be made toward outlining approaches that are consistent with best practice, easily accessible and do not require extensive resources to embed. Conclusion Applying effective AOD treatments as a standard treatment component is achievable for all practitioners and is essential for achieving better outcomes for a high proportion of the community accessing treatment from psychologists.

An analysis of ethical issues in using wastewater analysis to monitor illicit drug use

Aims To discuss ethical issues that may arise in using WWA to monitor illicit drug use in the general population and in entertainment precincts, prisons, schools and work-places. Method Review current applications of WWA and identify ethical and social issues that may be raised with current and projected future uses of this method. Results Wastewater analysis (WWA) of drug residues is a promising method of monitoring illicit drug use that may overcome some limitations of other monitoring methods. When used for monitoring purposes in large populations, WWA does not raise major ethical concerns because individuals are not identified and the prospects of harming residents of catchment areas are remote. When WWA is used in smaller catchment areas (entertainment venues, prisons, schools or work-places) their results could, possibly, indirectly affect the occupants adversely. Researchers will need to take care in reporting their results to reduce media misreporting. Fears about possible use of WWA for mass individual surveillance by drug law enforcement officials are unlikely to be realized, but will need to be addressed because they may affect public support adversely for this type of research. Conclusions Using wastewater analysis to monitor illicit drug use in large populations does not raise major ethical concerns, but researchers need to minimize possible adverse consequences in studying smaller populations, such as workers, prisoners and students.

Profiles of illicit drug use during annual key holiday and control periods in Australia: Wastewater analysis in an urban, a semi-rural and a vacation area

AIMS: To examine changes in illicit drug consumption between peak holiday season (23 December-3 January) in Australia and a control period two months later in a coastal urban area, an inland semi-rural area and an island populated predominantly by vacationers during holidays. DESIGN: Analysis of representative daily composite wastewater samples collected from the inlet of the major wastewater treatment plant in each area. SETTING: Three wastewater treatment plants. PARTICIPANTS: Wastewater treatment plants serviced approximately 350, 000 persons in the urban area, 120,000 in the semi-rural area and 1100-2400 on the island. MEASUREMENTS: Drug residues were analysed using liquid chromatography coupled to a tandem mass spectrometer. Per capita drug consumption was estimated. Changes in drug use were quantified using Hedges' g. FINDINGS: During the holidays, cannabis consumption in the semi-rural area declined (g = -2.8) as did methamphetamine (-0.8), whereas cocaine (+1.5) and ecstasy (+1.6) use increased. In the urban area, consumption of all drugs increased during holidays (cannabis +1.6, cocaine +1.2, ecstasy +0.8 and methamphetamine +0.3). In the vacation area, methamphetamine (+0.7), ecstasy (+0.7) and cocaine (+1.1) use increased, but cannabis (-0.5) use decreased during holiday periods. CONCLUSIONS: While the peak holiday season in Australia is perceived as a period of increased drug use, this is not uniform across all drugs and areas. Substantial declines in drug use in the semi-rural area contrasted with substantial increases in urban and vacation areas. Per capita drug consumption in the vacation area was equivalent to that in the urban area, implying that these locations merit particular attention for drug use monitoring and harm minimisation measures.

Monitoring illicit drug use through wastewater analysis in south east Queensland, Australia

Introduction and Aims: Wastewater analysis has become a useful technique for monitoring illicit drug use in communities. Findings have been reported from different countries in Europe and North America. We applied this technique to gauge the illicit drug consumption in an urban catchment from South East Queensland, Australia. Design and Methods: The sampling campaigns were conducted in 2009 (21st November – 2nd December) and 2010 (19th – 25th November). We collected daily composite wastewater samples from the inlet of the sewage treatment plant using continuous flow-proportional sampling. Ten illicit drug residues (parent compounds and key metabolites) in the samples were measured using liquid chromatography coupled to tandem mass spectrometer. Results: Seven compounds were quantified in all the samples. Our data indicated higher drug consumption on weekends. Cannabis was the highest used drug in both sampling periods. Compared to the first sampling campaign which indicated that cocaine and methamphetamine use exceeded ecstasy usage, the second sampling campaign suggested the use of methamphetamine exceeded that of ecstasy which in turn exceeded cocaine use. Discussion and Conclusions: The observed weekly trend of drug use in our study is in agreement with findings in other studies. The variation between two sampling periods in the prevalence of drug use may relate to the availability and prices of the drugs on markets. The cocaine use we estimated in 2009 was much greater than estimations obtained through the national household survey [1], implying under- reporting of cocaine use in surveys. Future work is underway to tackle methodological challenges for more accurate estimation.

Illicit drug use between an annual key holiday and a control period: Wastewater analysis in a semi-rural, an urban and a vacation area

Introduction and Aims: Holiday periods are potentially a time for increased substance use as social events and private parties are more common. Data on community illicit drug consumption during holiday periods are limited. Besides existing methods for determining drug use, such as population surveys, one emerging method is to measure illicit drugs and/or their metabolites in wastewater samples. This study examined the change in consumption of cannabis, methamphetamine, cocaine and 3,4- methylenedioxymethamphetamine in three different types of areas (an inland semi-rural area, a coastal urban area and a vacation island) with respect to holiday times. Design and Methods: Samples were collected at the inlet of the major wastewater treatment plant in each area during a key annual holiday (i.e. the summer holiday including Christmas and New Year) and control period. Illicit drug residues in the daily composited samples were measured by liquid chromatography coupled with tandem mass spectrometry. Results: Drug use varied substantially among the three areas within each monitoring period as well as between the holiday and control period within each area. Use consistently increased and peaked over New Year particularly for cocaine and 3,4-methylenedioxymethamphetamine whereas cannabis and methamphetamine were relatively less subjected to holiday times in all the areas. Discussion and Conclusions: Wastewater sampling and analysis provides higher spatio-temporal resolution than national surveys and supplements drug epidemiology studies originating primary in metropolitan locations. Such data is essential for policy makers to plan potential intervention strategies associated with these illicit substances in regional areas and other settings besides urban areas in the future.

Challenges and opportunities in using wastewater analysis to measure drug use in a small prison facility

Introduction and Aims Wastewater analysis (WWA) is intended to be a direct and objective method of measuring substance use in large urban populations. It has also been used to measure prison substance use in two previous studies. The application of WWA in this context has raised questions as to how best it might be used to measure illicit drug use in prisons, and whether it can also be used to measure prescription misuse. We applied WWA to a small regional prison to measure the use of 12 licit and illicit substances. We attempted to measure the non-medical use of methadone and buprenorphine and to compare our findings with the results of the prison's mandatory drug testing (MDT). Design and Methods Representative daily composite samples were collected for two periods of 12 consecutive days in May to July 2013 and analysed for 18 drug metabolites. Prescription data and MDT results were obtained from the prison and compared with the substance use estimates calculated from WWA data. Results Daily use of methamphetamine, methadone, buprenorphine and codeine was detected, while sporadic detection of ketamine and methylone was also observed. Overall buprenorphine misuse appeared to be greater than methadone misuse. Discussion and Conclusions Compared with MDT, WWA provides a more comprehensive picture of prison substance use. WWA also has the potential to measure the misuse of medically prescribed substances. However, a great deal of care must be exercised in quantifying the usage of any substance in small populations, such as in prisons.

Systematic and Day-to-Day Effects of Chemical-Derived Population Estimates on Wastewater-Based Drug Epidemiology

Population size is crucial when estimating population-normalized drug consumption (PNDC) from wastewater-based drug epidemiology (WBDE). Three conceptually different population estimates can be used: de jure (common census, residence), de facto (all persons within a sewer catchment), and chemical loads (contributors to the sampled wastewater). De facto and chemical loads will be the same where all households contribute to a central sewer system without wastewater loss. This study explored the feasibility of determining a de facto population and its effect on estimating PNDC in an urban community over an extended period. Drugs and other chemicals were analyzed in 311 daily composite wastewater samples. The daily estimated de facto population (using chemical loads) was on average 32% higher than the de jure population. Consequently, using the latter would systemically overestimate PNDC by 22%. However, the relative day-to-day pattern of drug consumption was similar regardless of the type of normalization as daily illicit drug loads appeared to vary substantially more than the population. Using chemical loads population, we objectively quantified the total methodological uncertainty of PNDC and reduced it by a factor of 2. Our study illustrated the potential benefits of using chemical loads population for obtaining more robust PNDC data in WBDE.

Estimating daily and diurnal variations of illicit drug use in Hong Kong: A pilot study of using wastewater analysis in an Asian metropolitan city

The measurement of illicit drug metabolites in raw wastewater is increasingly being adopted as an approach to objectively monitor population-level drug use, and is an effective complement to traditional epidemiological methods. As such, it has been widely applied in western countries. In this study, we utilised this approach to assess drug use patterns over nine days during April 2011 in Hong Kong. Raw wastewater samples were collected from the largest wastewater treatment plant serving a community of approximately 3.5 million people and analysed for excreted drug residues including cocaine, ketamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and key metabolites using liquid chromatography coupled with tandem mass spectrometry. The overall drug use pattern determined by wastewater analysis was consistent with that have seen amongst people coming into contact with services in relation to substance use; among our target drugs, ketamine (estimated consumption: 1400–1600 mg/day/1000 people) was the predominant drug followed by methamphetamine (180–200 mg/day/1000 people), cocaine (160–180 mg/day/1000 people) and MDMA (not detected). The levels of these drugs were relatively steady throughout the monitoring period. Analysing samples at higher temporal resolution provided data on diurnal variations of drug residue loads. Elevated ratios of cocaine to benzoylecgonine were identified unexpectedly in three samples during the evening and night, providing evidence for potential dumping events of cocaine. This study provides the first application of wastewater analysis to quantitatively evaluate daily drug use in an Asian metropolitan community. Our data reinforces the benefit of wastewater monitoring to health and law enforcement authorities for strategic planning and evaluation of drug intervention strategies.

Analysis of parameter uncertainty and sensitivity in PCPF-1 modeling for predicting concentrations of rice herbicides

This paper demonstrates the procedures for probabilistic assessment of a pesticide fate and transport model, PCPF-1, to elucidate the modeling uncertainty using the Monte Carlo technique. Sensitivity analyses are performed to investigate the influence of herbicide characteristics and related soil properties on model outputs using four popular rice herbicides: mefenacet, pretilachlor, bensulfuron-methyl and imazosulfuron. Uncertainty quantification showed that the simulated concentrations in paddy water varied more than those of paddy soil. This tendency decreased as the simulation proceeded to a later period but remained important for herbicides having either high solubility or a high 1st-order dissolution rate. The sensitivity analysis indicated that PCPF-1 parameters requiring careful determination are primarily those involve with herbicide adsorption (the organic carbon content, the bulk density and the volumetric saturated water content), secondary parameters related with herbicide mass distribution between paddy water and soil (1st-order desorption and dissolution rates) and lastly, those involving herbicide degradations. © Pesticide Science Society of Japan.