Improving Wastewater-Based Tobacco Use Estimates Using Anabasine.

In wastewater-based epidemiology (WBE), nicotine metabolites have been used as biomarkers for monitoring tobacco use. Recently, the minor tobacco alkaloids anabasine and anatabine have been suggested as more specific biomarkers for tobacco use since nicotine use can be from both tobacco and non-tobacco sources. This study aimed to provide an in-depth evaluation of the suitability of anabasine and anatabine as WBE biomarkers of tobacco and subsequently estimate their excretion factors for WBE applications. Pooled urine (n = 64) and wastewater samples (n = 277), collected between 2009 and 2019 in Queensland, Australia, were analyzed for nicotine and its metabolites (cotinine and hydroxycotinine), as well as anabasine and anatabine. Anabasine performed as the better biomarker, showing a similar per capita load in pooled urine (2.2 ± 0.3 µg/day/person) and wastewater samples (2.3 ± 0.3 µg/day/person), while the per capita load of anatabine in wastewater was 50% higher than its load in urine. It is estimated that 0.9 µg of anabasine was excreted per cigarette smoked. Triangulation of tobacco sales data and tobacco use estimated from either anabasine or cotinine showed that anabasine-based estimates were 5% higher than sales data, while cotinine-based estimates were between 2 and 28% higher. Our results provided concrete evidence to confirm the suitability of anabasine as a specific biomarker for monitoring tobacco use by WBE.

Increased Nicotine Consumption in Australia During the First Months of the COVID-19 Pandemic.

INTRODUCTION: Mixed findings have been reported about the impact of the COVID-19 pandemic on smoking behavior in different populations. AIMS AND METHODS: In this study, we aimed to quantify changes in smoking prevalence through the proxy of nicotine consumption in the Australian population from 2017 to 2020 inclusive. Estimates of nicotine consumption between 2017 and 2020 were retrieved from a national wastewater monitoring program that covers up to 50% of the Australian population. National sales data for nicotine replacement therapy (NRT) products from 2017 to 2020 were also acquired. Linear regression and pairwise comparison were conducted to identify data trends and to test differences between time periods. RESULTS: The average consumption of nicotine in Australia decreased between 2017 and 2019 but increased in 2020. Estimated consumption in the first half of 2020 was significantly higher (~30%) than the previous period. Sales of NRT products increased gradually from 2017 to 2020 although sales in the first half of the year were consistently lower than in the second half. CONCLUSION: Total nicotine consumption increased in Australia during the early stage of the pandemic in 2020. Increased nicotine consumption may be due to people managing higher stress levels, such as from loneliness due to control measures, and also greater opportunities to smoke/vape while working from home and during lockdowns in the early stage of the pandemic. IMPLICATIONS: Tobacco and nicotine consumption have been decreasing in Australia but the COVID-19 pandemic may have temporarily disrupted this trend. In 2020, the higher impacts of lockdowns and working from home arrangements may have led to a temporary reversal of the previous downward trend in smoking during the early stage of the pandemic.

In-Sewer Stability Assessment of Anabolic Steroids and Selective Androgen Receptor Modulators.

Wastewater-based epidemiology is a potential complementary technique for monitoring the use of performance- and image-enhancing drugs (PIEDs), such as anabolic steroids and selective androgen receptor modulators (SARMs), within the general population. Assessing in-sewer transformation and degradation is critical for understanding uncertainties associated with wastewater analysis. An electrospray ionization liquid chromatography mass spectrometry method for the quantification of 59 anabolic agents in wastewater influent was developed. Limits of detection and limits of quantification ranged from 0.004 to 1.56 µg/L and 0.01 to 4.75 µg/L, respectively. Method performance was acceptable for linearity (R2 > 0.995, few exceptions), accuracy (68-119%), and precision (1-21%RSD), and applicability was successfully demonstrated. To assess the stability of the selected biomarkers in wastewater, we used laboratory-scale sewer reactors to subject the anabolic agents to simulated realistic sewer environments for 12 h. Anabolic agents, including parent compounds and metabolites, were spiked into freshly collected wastewater that was then fed into three sewer reactor types: control sewer (no biofilm), gravity sewer (aerobic conditions), and rising main sewer (anaerobic conditions). Our results revealed that while most glucuronide conjugates were completely transformed following 12 h in the sewer reactors, 50% of the investigated biomarkers had half-lives longer than 4 h (mean residence time) under gravity sewer conditions. Most anabolic agents were likely subject to biofilm sorption and desorption. These novel results lay the groundwork for any future wastewater-based epidemiology research involving anabolic steroids and SARMs.

Multisite Calibration of a Microporous Polyethylene Tube Passive Sampler for Quantifying Drugs in Wastewater.

Passive sampling approaches to monitor licit and illicit drugs of concern in wastewater shows promise as a supplementary sampling technique to grab sampling when conventional composite autosampling may not be possible. Recent studies have assessed the applicability of passive sampling at a single wastewater treatment plant (WWTP). However, it remains unknown whether a single-site calibration can be applied to other WWTPs. This study evaluated the in situ calibration of microporous polyethylene tube passive samplers (MPTs) against simultaneously collected composite samples for 22 different WWTPs. Samples were analyzed for methylamphetamine, amphetamine, hydroxycotinine, cotinine, benzoylecgonine, 3,4-methylenedioxymethamphetamine, and noroxycodone. Estimated rates of chemical uptake (sampling rates) were calculated using the mass accumulated in the samplers, the concentration measured in composite samples, and the duration of deployment. The estimated sampling rates were consistent between WWTPs (>90% within a factor of two) and ranged from 5 mL day-1 (amphetamine) to 9 mL day-1 (noroxycodone). The samplers were effective at estimating analyte concentrations, with 77% of results having a normalized difference to 24 h composite samples of below 30%. Our study suggests that MPT passive samplers provide a tool for the spatiotemporal monitoring of drug use where automated integrative sampling techniques may not be feasible.

Using Prescription and Wastewater Data to Estimate the Correction Factors of Atenolol, Carbamazepine, and Naproxen for Wastewater-Based Epidemiology Applications.

The correction factor (CF) is a critical parameter in wastewater-based epidemiology (WBE) that significantly influences the accuracy of the final consumption estimates. However, most CFs have been derived from a few old pharmacokinetic studies and should be re-evaluated and refined to improve the accuracy of the WBE approach. This study aimed to review and estimate the CFs for atenolol, carbamazepine, and naproxen for WBE using the daily mass loads of those pharmaceuticals in wastewater and their corresponding dispensed prescription data in Australia. Influent wastewater samples were collected from wastewater treatment plants serving approximately 24% of the Australian population and annual national dispensed prescription data. The estimated CFs for atenolol and carbamazepine are 1.37 (95% CI: 1.17-1.66) and 8.69 (95% CI: 7.66-10.03), respectively. Due to significant over-the-counter sales of naproxen, a reliable CF could not be estimated based on prescription statistics. Using an independent dataset of 186 and 149 wastewater samples collected in an urban catchment in 2011 and 2012, WBE results calculated using the new CFs matched well with the dispensed data for atenolol and carbamazepine in the catchment area.

Systematic Evaluation of the In-Sample Stability of Selected Pharmaceuticals, Illicit Drugs, and Their Metabolites in Wastewater.

The in-sample stability of selected pharmaceuticals, illicit drugs, and their metabolites in wastewater was assessed under six different conditions-untreated, addition of hydrochloric acid or sodium metabisulfite solution, combined with or without sterile filtration, and at four representative temperatures, at 35 °C for up to 28 days, 22 °C for 56 days, and 4 °C and -20 °C for 196 days, or freeze/thaw cycles for 24 weeks. Paracetamol, 6-monoacetylmorphine, morphine, and cocaine were poorly stable in untreated wastewater-e.g., with 50% transformation within 1.2-8.1 days at 22 °C, and acidification reduced their in-sample transformations. Acesulfame, carbamazepine, cotinine, methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), ketamine, norfentanyl, 3,4-methylenedioxy-N-ethylamphetamine (MDEA), and norbuprenorphine were highly or moderately stable over the observed period, even in untreated wastewater. Fitting of pseudo-first-order kinetics and the Arrhenius equation was used to develop a multistage transformation estimation model combined with an interactive tool to evaluate possible transformation scenarios of selected biomarkers for the processes from sampling to preanalysis. However, as the wastewater composition can vary between sites and over time, the variability of in-sample stability requires further exploration.

Urinary Concentrations of Bisphenols in the Australian Population and Their Association with the Per Capita Mass Loads in Wastewater.

Health concerns and related regulation of bisphenol A (BPA) in some countries have led to an increase in the production and use of unregulated and poorly understood BPA analogues, including bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), and bisphenol AF (BPAF). To assess the temporal trends of human exposure to BPA analogues, urine and wastewater samples were collected from South East Queensland, Australia between 2012 and 2017 and analyzed for five bisphenols using validated isotope dilution liquid chromatography tandem mass spectrometry methods. BPA and BPS were the predominant bisphenols detected in both urine and wastewater samples, with median concentrations of 2.5 and 0.64 µg/L in urine and 0.94 and 1.1 µg/L in wastewater, respectively. BPB, BPF, and BPAF had low detection frequencies in both urine and wastewater samples. Concentrations of BPA in both urine and wastewater decreased over the sampling period, whereas concentrations of BPS increased, suggesting that BPS has become a BPA replacement. The contributions of urinary excretion to wastewater were calculated by the ratio of daily per capita urinary excretion to wastewater-based mass loads of bisphenols. Urinary BPA and BPS contributed to less than 1% of the load found in wastewater, indicating that much of the BPA and BPS originates from other sources.

Release of Plastics to Australian Land from Biosolids End-Use.

Plastics are contaminants of emerging concern that can enter the environment from multiple sources, including via land application of treated sewage sludge (biosolids). Biosolids samples collected from 82 wastewater treatment plants (WWTPs) across Australia and covering 34% of the population during census week in 2016 were quantitatively analyzed to estimate the release of seven common plastics. Quantitative analysis was performed by pressurized liquid extraction followed by double-shot microfurnace pyrolysis coupled to gas chromatography mass spectrometry. Ninety nine percent of the samples contained plastics (Σ6plastics) at concentrations of between 0.4 and 23.5 mg/g dry weight (median; 10.4 mg/g dry weight), while polycarbonate was not detected in any sample. Per-capita mass loads of plastics (Σ6plastics) released were between 8 and 877 g/person/year across all investigated WWTPs. Polyethylene was the predominant plastic detected, contributing to 69% of Σ6plastics. Based on the concentrations measured, it was projected that around 4700 metric tons (Mt) of plastics are released into the Australian environment through biosolids end-use each year, equating to approximately 200 g/person/year, which represents 0.13% of total plastics use in Australia. Of this, 3700 Mt of plastics are released to agricultural lands and 140 Mt to landscape topsoil. Our results provide a first quantitative per-capita mass loads and emission estimate of plastic types through biosolids end-use.

Harnessing the Power of the Census: Characterizing Wastewater Treatment Plant Catchment Populations for Wastewater-Based Epidemiology.

Wastewater studies that provide per capita estimates of consumption (influent) or release (effluent) via wastewater systems rely heavily on accurate population data. This study evaluated the accuracy of Wastewater Treatment Plant (WWTP) reported populations, as well as hydrochemical parameters, against accurate populations from a population census. 104 catchment maps were received from WWTPs, geolocated in geospatial software and overlaid with the smallest area unit of the Australian census, equating to 14.9 million Australians or 64% of the national population. We characterized each catchment for population counts, as well as by age profile, income profile, and education level. For a subset of sites, population estimates using hydrochemical parameters BOD, COD, and dissolved ammonia were evaluated for accuracy against census populations. Population estimates provided by WWTP personnel were on average 18% higher than census-based populations. Furthermore, hydrochemical-based population estimates had high RSD (>44%) for BOD, COD, and ammonium between sites, suggesting that their applicability for use in population estimation may not be appropriate for every WWTP. Catchment age distributions were evaluated and 46% of catchments had skewed age distributions: 6% were skewed older, and 40% were skewed younger. Through this process WWTP catchment populations can be characterized in a way that will enhance the interpretations of per capita estimates.

Improving wastewater-based epidemiology for new psychoactive substance surveillance by combining a high-throughput in vitro metabolism assay and LC-HRMS metabolite identification.

One of the primary criteria for a suitable drug biomarker for wastewater-based epidemiology (WBE) is having a unique source representing human metabolism. For WBE studies, this means it is important to identify and monitor metabolites rather than parent drugs, to capture consumption of drugs and not fractions that could be directly disposed. In this study, a high-throughput workflow based on a human liver S9 fraction in vitro metabolism assay was developed to identify human transformation products of new chemicals, using α-pyrrolidino-2-phenylacetophenone (α-D2PV) as a case study. Analysis by liquid chromatography coupled to high resolution mass spectrometry identified four metabolites. Subsequently, a targeted liquid chromatography - tandem mass spectrometry method was developed for their analysis in wastewater samples collected from a music festival in Australia. The successful application of this workflow opens the door for future work to better understand the metabolism of chemicals and their detection and application for wastewater-based epidemiology.

Refining the correction factor for a better monitoring of antidepressant use by wastewater-based epidemiology: A case study of amitriptyline.

Wastewater-based epidemiology (WBE) is proposed as a cost-effective approach to objectively monitor the antidepressant use but it requires more accurate correction factors (CF) than what had been used in previous studies. Amitriptyline is a popular prescription medicine for treating depression and nerve pain, which could be prone to misuse and need monitoring. The CF of amitriptyline employed in previous WBE studies varied from 10 to 100, leading to substantial disparities between WBE estimates and expected mass of antidepressants in wastewater. Hence, this study aimed to take amitriptyline as a case study and refine the CF by correlating mass loads measured in wastewater from 12.2 million inhabitants collected during the 2016 Census with corresponding annual sales data. The triangulation of WBE data and sales data resulted in a newly-derived CF of 7, which is significantly different from the CF values used in previous studies. The newly derived CF was applied to a secondary, multi-year (2017 to 2020) WBE dataset for validation against sales data in the same period, demonstrating the estimated amitriptyline use (380 ± 320 mg/day/1000 inhabitants) is consistent with sales data (450 ± 190 mg/day/1000 inhabitants). When we applied the new CF to previous studies, the wastewater consumption loads matched better to prescription data than previous WBE estimations. The refined CF of amitriptyline can be used in future WBE studies to improve the accuracy of the consumption estimates.

Analysis of wastewater from 2013 to 2021 detected a recent increase in nicotine use in Queensland, Australia.

Previous wastewater-based epidemiology (WBE) studies have reported decreasing trends of nicotine and tobacco use in Australia before 2017, but there is concern that increasing illicit use of nicotine in vaping products and illicit tobacco could reverse this progress. This study aimed to assess temporal trends of nicotine consumption and specifically tobacco consumption via wastewater analysis in a population in Australia between 2013 and 2021. One week of daily wastewater samples were analyzed every two months from February 2013 to December 2021 in a regional city serving ∼100,000 people. A total of 340 daily samples were analyzed for anabasine (tobacco specific biomarker) and nicotine metabolites, cotinine and hydroxycotinine, using direct injection method by liquid chromatography with tandem mass spectrometry. Daily consumption estimates were calculated from daily flow data, population estimates and previously reported excretion factors. Linear spline regression was performed to identify periods when significant change of slopes occurred and to evaluate the temporal trends. Tobacco use monitored using anabasine as a biomarker, showed a decreasing trend over the whole period with a higher rate of decrease during the first two years (2013-2014, 21 % decrease) compared to the later 7 years (2015-2021, 10 % decrease). Nicotine use, monitored using cotinine and hydroxycotinine, showed a downward trend between 2013 and 2018 (2013-2014: 18 % decrease, p < 0.05; 2015-2016: 6 % increase, p = 0.48; Feb-Dec 2017: 15 % decrease, p = 0.39) followed by a significant increase from 2018 to 2021 (40 % increase, p < 0.001). This finding suggests the increasing use of non-tobacco nicotine-based products. Additionally, the tobacco use estimate by wastewater analysis was higher than the tobacco sales data, which suggests the use of illicit tobacco in the catchment.

Monitoring the use of novel psychoactive substances in Australia by wastewater-based epidemiology.

Users of novel psychoactive substances (NPS) are at risk, due to limited information about the toxicity and unpredictable effects of these compounds. Wastewater-based epidemiology (WBE) has been used as a tool to provide insight into NPS use at the population level. To understand the preferences and trends of NPS use in Australia, this study involved liquid chromatography mass spectrometry analysis of wastewater collected from Australian states and territories from February 2022 to February 2023. In total, 59 different NPS were included across two complementary analytical methods and covered up to 57 wastewater catchments over the study. The NPS detected in wastewater were 25-B-NBOMe, buphedrone, 1-benzylpiperazine (BZP), 3-chloromethcathinone, N,N-dimethylpentylone (N,N-DMP), N-ethylheptedrone, N-ethylpentylone, eutylone, 4F-phenibut, 2-fluoro deschloroketamine, hydroxetamine, mephedrone, methoxetamine, methylone, mitragynine, pentylone, phenibut, para-methoxyamphetamine (PMA), alpha-pyrrolidinovalerophenone (α-PVP) and valeryl fentanyl. The detection frequency for these NPS ranged from 3 % to 100 % of the sites analysed. A noticeable decreasing trend in eutylone detection frequency and mass loads was observed whilst simultaneously N,N-DMP and pentylone increased over the study period. The emergence of some NPS in wastewater pre-dates other sources of monitoring and provides further evidence that WBE can be used as an additional early warning system for alerting potential NPS use.

High throughput and sensitive quantitation of tobacco-specific alkaloids and nitrosamines in wastewater.

Tobacco-specific alkaloids and nitrosamines are important biomarkers for the estimation of tobacco use and human exposure to tobacco-specific nitrosamines that can be monitored by wastewater analysis. Thus far their analysis has used solid phase extraction, which is costly and time-consuming. In this study, we developed a direct injection liquid chromatography-tandem mass spectrometry method for the quantification of two tobacco-specific alkaloids and five nitrosamines in wastewater. The method achieved excellent linearity (R2 > 0.99) for all analytes, with calibration ranging from 0.10 to 800 ng/L. Method limits of detection and quantification were 0.17 ng/L (N-nitrosonornicotine, NNN) and 1.0 ng/L (N-nitrosoanatabine (NAT) and NNN), with acceptable accuracy (100 % ± 20 %) and precision (± 15 %). Analyte loss during filtration was < 15 %, and the relative matrix effect was < 10 %. The method was applied to 43 pooled wastewater samples collected from three wastewater treatment plants in Australia between 2017 and 2021. Anabasine and anatabine were detected in all samples at concentrations of 5.0 - 33 ng/L and 12 - 41 ng/L, respectively. Three of the five tobacco-specific nitrosamines (NAT, NNN, and (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL)) were detected, in < 50 % of the wastewater samples, with concentrations nearly ten times lower than the tobacco alkaloids (< 1.0 - 6.2 ng/L). In-sewer stability of the nitrosamines was also assessed in this study, with four (NAT, NNAL, NNN, and N-nitrosoanabasine (NAB)) being stable (i.e. < 20 % transformation over 12 h in both control reactor (CR) and rising main reactor (RM) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) being moderately stable (< 40 % loss over 12 h in RM). This direct injection method provides a high-throughput approach in simultaneous investigation of tobacco use and assessment of public exposure to tobacco-specific nitrosamines.

Wastewater-based evaluation of the efficacy of oxycodone regulations in Australia.

BACKGROUND AND AIMS: Between 2018 and 2020, Australia implemented major policy changes to improve the quality and safety of opioid prescribing, with a specific focus on oxycodone. This study used wastewater-based epidemiology to assess the efficacy of Australia's regulatory reforms by measuring change in consumption of oxycodone via exploratory analysis. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: Wastewater analysis data on oxycodone consumption was from the National Wastewater Drug Monitoring Program. The program captures data from more than 50 wastewater treatment plant catchments across Australia, equivalent to more than 50% of the national population. Geographic trend analyses were conducted for both major cities and regional areas within all states and territories of Australia over a 6-year period between 2017 and 2023. FINDINGS: Oxycodone consumption showed a statistically significant increase nationally from 78 mg/day/1000 people (95% confidence interval [CI] = 71, 84) in 2017 to 120 mg/day/1000 people in August 2019 (95% CI = 110, 120), an increase of 52% (95% CI = 42, 62, P < 0.0001). From August 2019 to December 2020, there was a statistically significant decrease from 120 to 65 mg/day/1000 people (95% CI = 60, 71), a decrease of 45% (95% CI = 40, 51), followed by a modest 2.4% increase to the end of the study period in April 2023 (95% CI [2.0,2.7]). CONCLUSIONS: A 45% reduction in oxycodone consumption in Australia from 2019 to 2020 coincided with national policy changes that aimed to reduce consumption of prescription opioids. The overall declining trend in consumption was suggestive of the effectiveness of national interventions in reducing pharmaceutical opioid use. Wastewater-based epidemiology provides an effective approach for assessing the effectiveness of controlled substances policy changes.

Reporting population size in wastewater-based epidemiology: A scoping review.

Knowledge of the number of people present in a catchment is fundamental for the assessment of spatio-temporal trends in wastewater-based epidemiology (WBE). Accurately estimating the number of people connected to wastewater catchments is challenging however, because populations are dynamic. Methods used to estimate population size can significantly influence the calculation and interpretation of population-normalised wastewater data (PNWD). This paper systematically reviews the reporting of population data in 339 WBE studies. Studies were evaluated based on their reporting of population size, the source of population data, the population calculation methods, and the uncertainties in population estimates. Most papers reported population size (96 %) and the source of population data (60 %). Fewer studies reported the uncertainties in their population data (50 %) and the methods used to calculate these estimates (28 %). This is relevant because different methods have unique strengths and limitations which can affect the accuracy of PNWD. Only 64 studies (19 %) reported all four components of population data. The reporting of population data has remained consistent in the past decade. Based on the findings, we recommend generalised reporting criteria for population data in WBE. As WBE is further mainstreamed and applied, the clear and comprehensive reporting of population data will only become increasingly important.

Exploring drug consumption patterns across varying levels of remoteness in Australia.

Wastewater-based epidemiology (WBE) relies on representative sampling that is typically achieved with autosamplers that collect time, flow, or volume proportional samples. The expense, resources and operational know-how associated with autosampler operation means they are only typically available at major wastewater treatment plants (WWTPs). This results in a lack of data on consumption levels in regional and remote areas, or in countries that lack the financial means. The aim of this study was to estimate and investigate trends in drug consumption across varying levels of remoteness in Australia. Field-calibrated, microporous polyethylene passive samplers were deployed over 2 periods (Aug/Sept 2019 and 2020) at 43 treatment plants covering all five categories of remoteness, as per Australian Bureau of Statistics definitions (Major cities, Inner regional, Outer regional, Remote, and Very remote). The per capita consumption of cocaine, methylamphetamine, nicotine, oxycodone and MDMA were estimated. No spatial trends between remoteness and drug consumption were observed, except for cocaine, where Major cities had a 5-to-10-fold higher consumption compared to the other levels of remoteness in 2019 and 2020, respectively. Outer regional sites had the highest and lowest methylamphetamine consumption. The variance in drug use among sites was much higher in Remote (and Inner/Outer regional) sites when compared with Major cities. A significant and consistent decrease in oxycodone consumption was observed at all sites between 2019 and 2020, possibly related to regulatory changes and the COVID-19 pandemic where elective surgeries were suspended. The majority of sites experienced a decrease in cocaine and methylamphetamine consumption, possibly due to border restrictions or changes in supply and demand dynamics. This was the first extensive passive sampling study to assess drug consumption in urban, regional, and remote locations, demonstrating that passive samplers can facilitate extension of wastewater-based drug monitoring programs to sites where other representative sampling options are very difficult to implement.

Monitoring medication and illicit drug consumption in a prison by wastewater-based epidemiology: Impact of COVID-19 restrictions.

Drug consumption in prisons is a concern for the safety of incarcerated people and staff. Typically, drug use prevalence in prisons is estimated through urinalysis and intelligence operations, which can be intrusive and stressful. An alternative approach, wastewater-based epidemiology (WBE), was used in this study to estimate the consumption of licit and illicit drugs for the entire population of a prison in Australia. Wastewater samples were collected from March to December 2020, covering periods of no restrictions and periods when prison access was restricted to prevent the transmission of COVID-19. Target biomarkers were analysed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The average consumption of common illicit drugs (MDMA, methamphetamine and cocaine) over the sampling period in the prison (0.5 - 4.5 mg/1000 people/day) was two to three orders of magnitude lower than in the community population (254 - 1000 mg/1000 people/day). Comparison of WBE estimates against pharmacy dispensing data suggested potential illicit buprenorphine consumption at the prison. Methamphetamine and buprenorphine use decreased when no visitors were allowed (18% - 72% decrease for methamphetamine; about half decrease for buprenorphine) and increased once these restrictions were eased (22% - 39% increase for methamphetamine; 44% - 67% increase for buprenorphine). The changes in drug use may be attributed in part to a reduction of drug trafficking into the prison from visitors or non-essential staffs and in part to the reduced contribution of urine from staff who used toilets within the prison. This study provided useful information on the scale of illicit drug use and extra-medical use of licit drugs in prison, and its changes under different security conditions.

A wastewater-based evaluation of the effectiveness of codeine control measures in Australia.

BACKGROUND AND AIM: From 1 February 2018, codeine was rescheduled from an over-the-counter (OTC) to a prescription-only medicine in Australia. We used wastewater-based epidemiology to measure changes in population codeine consumption before and after rescheduling. METHODS: We analysed 3703 wastewater samples from 48 wastewater treatment plants, taken between August 2016 and August 2019. Our samples represented 10.6 million people, 45% of the Australian population in state capitals and regional areas in each state or territory. Codeine concentrations were determined by liquid chromatography-tandem mass spectrometry and converted to per-capita consumption estimates using the site daily wastewater volume, catchment populations and codeine excretion kinetics. RESULTS: Average per-capita consumption of codeine decreased by 37% nationally immediately after the rescheduling in February 2018 [95% confidence interval (CI) = 35.3-39.4%] and substantially in all states between 24 and 51% (95% CI = 22.4-27.0% and 41.8-59.4%). The decrease was sustained at the lower level to August 2019. Locations with least pharmacy access decreased by 51% (95% CI = 41.7-61.7%), a greater decrease than 37% observed for those with greater pharmacy access (95% CI = 35.1-39.4%). Regional areas decreased by a smaller margin to cities (32 versus 38%, 95% CI = 30.2-34.1% versus 34.9-40.4%, respectively) from a base per-capita usage approximately 40% higher than cities. CONCLUSION: Wastewater analysis shows that codeine consumption in Australia decreased by approximately 37% following its rescheduling as a prescription-only medicine in 2018. Wastewater-based epidemiology can be used to evaluate changes in population pharmaceutical consumption in responses to changes in drug scheduling.