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.

The first application of wastewater-based drug epidemiology in five South Korean cities

Illicit drug consumption in five cities in South Korea was estimated by analyzing 17 drug residues in untreated wastewater samples collected during the Christmas and New Year period of 2012-13. Only methamphetamine, amphetamine, and codeine were detected at concentrations of tens of nanograms per liter or even lower concentrations in more than 90% of the samples. Other illicit drug residues (including cocaine, methadone, and benzoylecgonine) that have been detected frequently in wastewater from other countries were not found in this study. Methamphetamine was found to be the most widely used illicit drug in South Korea, and the estimated average consumption rate was 22 mg d−1 (1000 people)−1. This rate is, for example, 2-5 times lower than the estimated average consumption rates in Hong Kong and other parts of China and 4-80 times lower than the estimated average consumption rates in cities in Western countries. It should be noted that the wastewater samples analyzed in this study were collected during a holiday season, when daily consumption of illicit drugs is often higher than on an average day. The methamphetamine usage rates were calculated for different cities in South Korea, and the usage rates in smaller cities was higher (2-4 times) than the average.

Measuring drug use patterns in Queensland through wastewater analysis

Estimating the use of illicit drugs in the general community is an important task with ramifications for law enforcement agencies, as well as health portfolios. Australia has four ongoing drug monitoring systems, including the AIC’s DUMA program, the National Drug Strategy Household Survey, the Illicit Drug Reporting System and the Ecstasy and Related Drug Reporting System. The systems vary in methods, but broadly they are reliant upon self-report data and may be subject to selection biases. The present study employed a completely different method. By chemically analysing sewerage water, the study produced daily estimates of consumption of methamphetamine, MDMA and cocaine. Samples were collected in November 2009 and November 2010 from a municipality in Queensland, with an population of over 150,000 people. Estimates were made of the average daily dose and average daily street value per 1,000 people. On the basis of estimated dose and price, the methamphetamine market appeared considerably stronger than either MDMA or cocaine. This paper explains the strengths and weaknesses of wastewater analysis. It considers the potential value of wastewater analysis in measuring net consumption of illicit drugs and the effectiveness of law enforcement agency strategies.

Effects of sewer conditions on the degradation of selected illicit drug residues in wastewater

The stability of five illicit drug markers in wastewater was tested under different sewer conditions using laboratory-scale sewer reactors. Wastewater was spiked with deuterium labelled isotopes of cocaine, benzoyl ecgonine, methamphetamine, MDMA and 6-acetyl morphine to avoid interference from the native isotopes already present in the wastewater matrix. The sewer reactors were operated at 20 °C and pH 7.5, and wastewater was sampled at 0, 0.25, 0.5, 1, 2, 3, 6, 9 and 12 h to measure the transformation/degradation of these marker compounds. The results showed that while methamphetamine, MDMA and benzoyl ecgonine were stable in the sewer reactors, cocaine and 6-acetyl morphine degraded quickly. Their degradation rates are significantly higher than the values reportedly measured in wastewater alone (without biofilms). All the degradation processes followed first order kinetics. Benzoyl ecgonine and morphine were also formed from the degradation of cocaine and 6-acetyl morphine, respectively, with stable formation rates throughout the test. These findings suggest that, in sewage epidemiology, it is essential to have relevant information of the sewer system (i.e. type of sewer, hydraulic retention time) in order to accurately back-estimate the consumption of illicit drugs. More research is required to look into detailed sewer conditions (e.g. temperature, pH and ratio of biofilm area to wastewater volume among others) to identify their effects on the fate of illicit drug markers in sewer systems.

Imaging tumour distribution of a polymeric drug delivery platformin vivoby PET-MRI

Background Over the past decade, molecular imaging has played a key role in the progression of drug delivery platforms from concept to commercialisation. Of the molecular imaging techniques commonly utilised, positron emission tomography (PET) can yield a breadth of information not easily accessible by other methodologies and when combined with other complementary imaging modalities, is a powerful tool for pre- and clinical development of therapeutics. However, very little research has focussed on the information available from complimentary imaging modalities. This paper reports on the data-rich methodologies of contrast enhanced PET/CT and PET/MRI for probing efficacy of polymer drug delivery platforms. Results The information available from an ExiTron nano 6000 contrast enhanced PET/CT and a gadolinium (Gd) enhanced PET/MRI image of a 64Cu labeled HBP in the same mouse was qualitatively compared. Conclusions Gd contrast enhanced PET/MRI offers a powerful methodology for investigating the distribution of polymer drug delivery platforms in vivo and throughout a tumour volume. Furthermore, information about depth of penetration away from primary blood vessels can be gleaned, potentially leading to development of more efficacious delivery vehicles for clinical use.

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2, 3, 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci6 and pathway analyses7, 8, 9—as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes—to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

The emerging role of extracellular vesicle-mediated drug resistance in cancers: Implications in advanced prostate cancer

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

Label-free isolation of a prostate cancer cell among blood cells and the single-cell measurement of drug accumulation using an integrated microfluidic chip

Circulating tumor cells (CTCs) are found in the blood of patients with cancer. Although these cells are rare, they can provide useful information for chemotherapy. However, isolation of these rare cells from blood is technically challenging because they are small in numbers. An integrated microfluidic chip, dubbed as CTC chip, was designed and fabricated for conducting tumor cell isolation. As CTCs usually show multidrug resistance (MDR), the effect of MDR inhibitors on chemotherapeutic drug accumulation in the isolated single tumor cell is measured. As a model of CTC isolation, human prostate tumor cells were mixed with mouse blood cells and the labelfree isolation of the tumor cells was conducted based on cell size difference. The major advantages of the CTC chip are the ability for fast cell isolation, followed by multiple rounds of single-cell measurements, suggesting a potential assay for detecting the drug responses based on the liquid biopsy of cancer patients.

Drink driving among Indigenous people in Far North Queensland and northern New South Wales: A summary of the qualitative findings

Purpose In response to the threat that drink drivers pose to themselves and others, drink driving programs form an important part of a suite of countermeasures used in Australia and internationally. Unlike New Zealand/Aotearoa, United States and Canada that have programs catering for their First Peoples, all Australian programs are designed for the general driver population. The aim of this study was to identify the factors that contribute to Indigenous drink driving in order to inform appropriate recommendations related to developing a community-based program for Indigenous communities. Broader drivers licensing policy recommendations are also discussed. Methods A sample of 73 Indigenous people from Queensland and in New South Wales with one or more drink driving convictions completed a semi-structured interview in respect of the to their drink driving behaviour. Participants were asked to disclose information regarding their drink driving history, and alcohol and drug use. If participants self-reported no longer drink driving, they were probed about what factors had assisted them to avoid further offending. Results Key themes which emerged to maintain drink driving include motivations to drink and drive, and belief in the ability to manage the associated risks. Factors that appeared to support others from avoiding further offending include re-connecting with culture and family support. Conclusions and Implications A range of recommendations regarding delivery and content of a program for regional and remote communities as well as other policy implications are discussed.

Evolution of the concept of compulsory licensing: A critical analysis of key developments before and after TRIPS

Patents provide monopoly rights to patent holders. There are safeguards in patent regime to ensure that exclusive right of the patent holder is not misused. Compulsory licensing is one of the safeguards provided under TRIPS using which patent granting state may allow a third party to exploit the invention without patent holder’s consent upon terms and conditions decided by the government. This concept existed since 1623 and was not introduced by TRIPS for the first time. But this mechanism has undergone significant changes especially in post-TRIPS era. History of evolution of compulsory licensing is one of the least explored areas of intellectual property law. This paper undertakes an analysis of different phases in the evolution of the compulsory licensing mechanism and sheds light on reasons behind developments especially after TRIPS.