A risk-based approach to community illicit drug toxicosurveillance: operationalisation of the Emerging Drugs Network of Australia - Victoria (EDNAV) project.

INTRODUCTION: The Emerging Drugs Network of Australia - Victoria (EDNAV) project is a newly established toxicosurveillance network that collates clinical and toxicological data from patients presenting to emergency departments with illicit drug related toxicity in a centralised clinical registry. Data are obtained from a network of sixteen public hospital emergency departments across Victoria, Australia (13 metropolitan and three regional). Comprehensive toxicological analysis of a purposive sample of 22 patients is conducted each week, with reporting of results to key alcohol and other drug stakeholders. This paper describes the overarching framework and risk-based approach developed within Victoria to assess drug intelligence from EDNAV toxicosurveillance. METHODS: Risk management principles from other spheres of public health surveillance and healthcare clinical governance have been adapted to the EDNAV framework with the aim of facilitating a consistent and evidence-based approach to assessing weekly drug intelligence. The EDNAV Risk Register was reviewed over the first two years of EDNAV project operation (September 2020 - August 2022), with examples of eight risk assessments detailed to demonstrate the process from signal detection to public health intervention. RESULTS: A total of 1112 patient presentations were documented in the EDNAV Clinical Registry, with 95 signals of concern entered into the EDNAV Risk Register over the two-year study period. The eight examples examined in further detail included suspected drug adulteration (novel opioid adulterated heroin, para-methoxymethamphetamine adulterated 3,4-methylenedioxymethamphetamine (MDMA)), drug substitution (25B-NBOH sold as lysergic acid diethylamide, five benzodiazepine-type new psychoactive substances in a single tablet, protonitazene sold as ketamine), new drug detection (N,N-dimethylpentylone), contamination (unreported acetylfentanyl) and a fatality subsequent to MDMA use. A total of four public Drug Alerts were issued over this period. CONCLUSIONS: Continued toxicosurveillance efforts are paramount to characterising the changing landscape of illicit drug use. This work demonstrates a functional model for risk assessment of illicit drug toxicosurveillance, underpinned by analytical confirmation and evidence-based decision-making.

Real or fake? Sourcing and marketing of non-prescribed benzodiazepines amongst two samples of people who regularly use illicit drugs in Australia.

INTRODUCTION: There is concern around non-prescribed benzodiazepine use, particularly with increasing detections of counterfeit products containing high-risk novel compounds. The aims of this study were to investigate how and which non-prescribed benzodiazepines are being sourced; forms, appearance and packaging; and awareness of risks associated with non-prescribed benzodiazepines. METHODS: Data were collected from a sample of Australians who inject drugs or use ecstasy and/or other illicit stimulants on a monthly or more frequent basis, and who reported past 6-month use of non-prescribed benzodiazepines (n = 235 and n = 250, respectively). Data were collected on source, diversion from a known/trusted prescription, product name and aesthetic characteristics for the last non-prescribed benzodiazepine obtained. RESULTS: Amongst participants who injected drugs, 71% reported that their last non-prescribed benzodiazepines were diverted from a known/trusted prescription, compared to 59% of participants who used ecstasy/other stimulants. Sourcing via cryptomarkets was rare. Across both samples, the majority reported last obtaining substances sold/marketed as diazepam or alprazolam. Participants sourcing via non-diverted means were twice as likely to obtain alprazolam. Known sourcing of novel compounds was rare. Amongst participants who used ecstasy/other stimulants, 36% reported confidence in the content/dose of non-prescribed benzodiazepines even when the source is unknown. DISCUSSION AND CONCLUSIONS: Most participants obtained substances sold as classic/registered benzodiazepines, mostly via diverted prescriptions, with a substantial minority potentially unaware of counterfeits circulating. While diverted use undeniably presents risks, tightening of prescriptions in Australia could inadvertently lead to greater supply of novel benzodiazepines as seen internationally, reinforcing prioritisation of demand and harm reduction strategies.

Co-designing drug alerts for health and community workers for an emerging early warning system in Victoria, Australia.

BACKGROUND: Alerts about changes in unregulated drug markets may be useful for supporting health and community workers to anticipate, prevent, and respond to unexpected adverse drug events. This study aimed to establish factors influencing the successful design and implementation of drug alerts for use in clinical and community service settings in Victoria, Australia. METHODS: An iterative mixed methods design was used to co-produce drug alert prototypes with practitioners and managers working across various alcohol and other drug services and emergency medicine settings. A quantitative needs-analysis survey (n = 184) informed five qualitative co-design workshops (n = 31). Alert prototypes were drafted based on findings and tested for utility and acceptability. Applicable constructs from the Consolidated Framework for Implementation Research helped to conceptualise factors that impact successful alert system design. RESULTS: Timely and reliable alerts about unexpected drug market changes were important to nearly all workers (98%) yet many reported insufficient access to this kind of information (64%). Workers considered themselves 'conduits' for information-sharing and valued alerts for increasing exposure to drug market intelligence; facilitating communication about potential threats and trends; and improving capacity for effective responding to drug-related harm. Alerts should be 'shareable' across a range of clinical and community settings and audiences. To maximise engagement and impact, alerts must command attention, be easily recognisable, be available on multiple platforms (electronic and printable formats) in varying levels of detail, and be disseminated via appropriate notification mechanisms to meet the needs of diverse stakeholder groups. Three drug alert prototypes (SMS prompt, summary flyer, and a detailed poster) were endorsed by workers as useful for supporting their work responding to unexpected drug-related harms. DISCUSSION: Alerts informed by coordinated early warning networks that offer close to real-time detection of unexpected substances can provide rapid, evidence-based drug market intelligence to inform preventive and responsive action to drug-related harm. The success of alert systems requires adequate planning and resourcing to support design, implementation, and evaluation, which includes consultation with all relevant audiences to understand how to maximise engagement with information, recommendations, and advice. Our findings about factors impacting successful alert design have utility to inform the development of local early warning systems.

'We don't live in a harm reduction world, we live in a prohibition world': tensions arising in the design of drug alerts.

BACKGROUND: Drug alerts designed for health and community workforces have potential to avert acute harms associated with unpredictable illicit drug markets, by preparing workers to respond to unusual drug-related events, and distribute information to service users. However, the design of such alerts is complicated by diverse needs of individuals, and broader socio-political contexts. Here, we discuss the tensions that arose in the process of co-designing drug alert templates with health and community workers. METHODS: We conducted five in-depth digital co-design workshops with 31 workers employed in alcohol and other drug and urgent care settings. Our approach to analysis was informed by Iterative Categorisation and reflexive thematic analysis methods. RESULTS: We identified five key tensions. First, there is a need to provide comprehensive information to meet the information needs of a diverse group of workers with varying knowledge levels, while also designing alerts to be clear, concise, and relevant to the work of individuals. Second, it is important that alerts do not create 'information overload'; however, it is also important that information should be available to those who want it. Third, alert design and dissemination must be perceived to be credible, to avoid 'alert scepticism'; however, credibility is challenging to develop in a broader context of criminalisation, stigmatisation, and sensationalism. Fourth, alerts must be carefully designed to achieve 'intended effects' and avoid unintended effects, while acknowledging that it is impossible to control all potential effects. Finally, while alerts may be intended for an audience of health and community workers, people who use drugs are the end-users and must be kept front of mind in the design process. CONCLUSIONS: The co-design process revealed complexities in designing drug alerts, particularly in the context of stigmatised illicit drug use, workforce diversity, and dissemination strategies. This study has highlighted the value of developing these important risk communication tools with their target audiences to ensure that they are relevant, useful, and impactful. The findings have informed the development of our drug alert prototypes and provide local context to complement existing best-practice risk-communications literature.

Climate and landscape drivers of tree decline in a Mediterranean ecoregion.

Climate change and anthropogenic land use are increasingly affecting the resilience of natural ecosystems. In Mediterranean ecoregions, forests and woodlands have shown progressive declines in health. This study focuses on the decline of an endemic woodland tree species, Eucalyptus wandoo (wandoo), occurring in the biodiversity hotspot of southwest Western Australia. We determined the change in health of wandoo stands between 2002 and 2008 across its geographic and climatic range, and associated this change in health with non-biotic variables focusing on: (1) fragment metrics; (2) topography; (3) soil characteristics; and (4) climate. Only fragment metrics and climate variables were found to be significantly related to the observed change in health. Stands that were small with high perimeter/area ratios were found to be most sensitive to health declines. Recent increases in autumn temperatures and decreases in annual rainfall were negatively affecting health of wandoo most prominently in the low rainfall zone of its climatic range. Together, these results suggest the onset of range contraction for this ecologically important species, which is likely to be exacerbated by projected future changes in climate. Our results emphasize the importance of establishing monitoring programs to identify changes in health and decline trends early to inform management strategies, particularly in the sensitive Mediterranean ecoregions.

Internet use and sexual health of young men who have sex with men: a mixed-methods study.

Young gay, bisexual, and other men who have sex with men (MSM) experience sexual health disparities due to a lack of support in settings that traditionally promote positive youth development. The Internet may help to fill this void, but little is known about how it is used for sexual health purposes among young MSM. This mixed-methods study reports quantitative results of a large survey of 18- to 24-year-old MSM in an HIV testing clinic (N = 329) as well as qualitative results from interviews. Level of Internet use was high in this sample and the majority of participants reported using the Internet to find HIV/AIDS information. Black and Latino youth used the Internet less frequently than White youth, and after controlling for age, education, and frequency of Internet use, Black youth were 70% less likely to use the Internet to find HIV/AIDS information. Qualitative analyses identified themes related to the role of the Internet in finding sexual health information, sexual minority identity development, and sexual risk taking behaviors. Participants reported that the Internet filled an important and unmet need for sexual health education. It allowed for connections to the gay community and support during the coming out process, but also exposure to homophobic messages. There was no evidence of increased risk behaviors with partners met online, but at the same time the potential for the use of the Internet to facilitate safer sex communication was largely untapped. Our findings generally present an optimistic picture about the role of the Internet in the development of sexual health among young MSM.

Merging claims databases with a tumor registry to evaluate variations in cancer mortality: results from a pilot study of 698 colorectal cancer patients treated at one hospital in the 1990s.

BACKGROUND: Prognostic models are essential for evaluating variations in cancer mortality statistics. While cancer stage is the most widely accepted and commonly used predictor of survival for cancer, electronic claims databases contain large amounts of information on cancer patients. Previous studies have used Medicare databases and tumor registry information from the Surveillance Epidemiology and End Results data sets to evaluate variations in outcomes for older cancer patients. We evaluated if similar analytic efforts could be carried out with readily available data sets for colorectal cancer patients of all ages who received care at a single hospital during the 1990s. METHODS: Hospital tumor registry and discharge claims data for patients at one mid-western hospital with surgically treated stage I-III colorectal cancer from 1990-1998 were used to model survival. Kaplan-Meier logrank tests and Cox proportional hazards models tested the statistical significance of demographic, operative, and clinicopathological factors as predictors of survival. Survival probabilities also were compared to U.S. population life table data to determine if survival deficits were larger for younger cancer patients. RESULTS: Of the 698 colorectal cancer patients, overall five-year survival probability was 65%, with a median follow-up of 44.7 months. Factors associated with higher relative risks of death included sociodemographic characteristics [female gender (1.5, 95% CI: 1.1-1.9), ages 70-79 years (1.7, 95% CI: 1.2-2.3), and > or = 80 years (3.3, 95% CI: 2.4-4.7) as compared to younger patients], clinical characteristics [moderate (1.5, 95% CI: 1.1-2.1) or severe (2.1, 95%: 1.4-3.2) comorbid illness, as compared to mild or no comorbid illnesses and emergency admission (2.1, 95% CI: 1.5-2.9)], pathological characteristics [positive surgical margins (3.5, 95% CI: 2.3-5.3): and higher cancer stage (stage II RR = 1.5, 95% CI = 1.1-2.2; stage III RR = 2.2, 95% CI = 1.5-3.2), as compared to stage I]. A comparison to the age- and gender-matched survival probabilities of the general population demonstrated similar deficits in survival for older patients (> or = 70 years) and younger patients (< 70 years). CONCLUSIONS: While cancer stage is a reliable predictor of survival, other sociodemographic and clinical data elements can improve the evaluation of expected survival rates for patients with surgically resectable colorectal cancers. To facilitate comparative interpretations of mortality data, consideration should be given to merging hospital discharge claims data sets with tumor registry information in a manner analogous to that which has been done for older cancer patients who are covered by the Medicare program.

Over-expression of ascorbate oxidase in the apoplast of transgenic tobacco results in altered ascorbate and glutathione redox states and increased sensitivity to ozone.

Transgenic tobacco ( Nicotiana tabacum L. cv. Xanthi) plants expressing cucumber ascorbate oxidase (EC.1.10.3.3) were used to examine the role of extracellular ascorbic acid in mediating tolerance to the ubiquitous air pollutant, ozone (O(3)). Three homozygous transgenic lines, chosen on the basis of a preliminary screen of AO activity in the leaves of 29 lines, revealed up to a 380-fold increase in AO activity, with expression predominantly associated with leaf cell walls. Over-expression of AO resulted in no change in the total ascorbate content recovered in apoplast washing fluid, but the redox state of ascorbate was reduced from 30% in wild-type leaves to below the threshold for detection in transgenic plants. Levels of ascorbic acid and glutathione in the symplast were not affected by AO over-expression, but the redox state of ascorbate was reduced, while that of glutathione was increased. AO over-expressing plants exposed to 100 nmol mol(-1) ozone for 7 h day(-1) exhibited a substantial increase in foliar injury, and a greater pollutant-induced reduction in both the light-saturated rate of CO(2) assimilation and the maximum in vivo rate of ribulose-1,5-bisphosphate carboxylase/oxygenase carboxylation, compared with wild-type plants. Transgenic plants also exhibited a greater decline in CO(2) assimilation rate when exposed to a brief ozone episode (300 nmol mol(-1) for 8 h). Stomatal conductance, hence O(3) uptake, was unaffected by AO over-expression. Our findings illustrate the important role played by ascorbate redox state and sub-cellular compartmentation in mediating the tolerance of plants to ozone-induced oxidative stress.

The association of health literacy with cervical cancer prevention knowledge and health behaviors in a multiethnic cohort of women.

OBJECTIVE: Our purpose was to describe the relationship between health literacy, ethnicity, and cervical cancer screening practices and to evaluate physician recognition of low literacy. STUDY DESIGN: We studied a prospective cohort of English-speaking patients > or =18 years (n = 529) in ambulatory women's clinics. Univariate and multivariate analyses were used to evaluate demographics, health practices and beliefs, and knowledge regarding cervical cancer screening and prevention. Physicians' assessments of patient reading skills were obtained. RESULTS: Low health literacy (<9th grade) was found among 40% of participants. Minority women were half as likely to know the purpose of the Papanicolaou test (9% vs 21%; P <.03) and were significantly more likely to have low literacy levels compared with white women (46% vs 15%; P <.05). Literacy was the only factor independently associated with knowledge related to cervical cancer screening (adjusted odds ratio, 2.25; 95% CI, 1.05-4.80). Physicians detected only 20% of the lowest readers. CONCLUSION: Poor health literacy was a better predictor of cervical cancer screening knowledge than ethnicity or education, yet physicians infrequently recognized low literacy. Improved physician awareness and development of low literacy interventions may improve cervical cancer screening, particularly for the most vulnerable women.

Hydroponically cultivated radish fed L-galactono-1,4-lactone exhibit increased tolerance to ozone.

Leaf L-ascorbate content of an ozone (O3)-sensitive radish genotype (Raphanus sativus L. cv. Cherry Belle) was increased 2-fold by feeding hydroponically cultivated plants L-galactono- 1,4-lactone (GalL). Plants were grown in controlled-environment chambers ventilated with charcoal/Purafil-filtered air, and administered one of two O3 fumigation regimes: chronic exposure (75 nmol O3 mol(-1) for 7 h day(-1) for 21 days) and acute exposure (180 nmol O3 mol(-1) for 9 h). Chronic O3 exposure decreased root growth by 11% in plants maintained in pure nutrient solution (-GalL), but resulted in no change in root growth in GalL-fed plants (+GalL). Similarly, GalL-feeding counteracted the negative effects of O3 on CO2 assimilation rate observed in control plants (-GalL). Under acute O3 exposure, GalL-fed plants showed none of the visible symptoms of injury, which were extensive in plants not fed GalL. Leaf CO2 assimilation rate was decreased by acute 03 exposure in both GalL treatments, but the extent of the decline was less marked in GalL-fed plants. No significant changes in stomatal conductance resulted from GalL treatment, so O3 Uptake into leaves was equivalent in + GalL and -GalL plants. Feeding GalL, on the other hand, enhanced the level of ascorbate, and resulted in the maintenance of the redox state of ascorbate under acute O3 fumigation, in both the leaf apoplast and symplast. The effect of GalL treatment on ascorbate pools was consistent with the reduction in O3 damage observed in GalL-fed plants. Attempts to model O3 interception by the ascorbate pool in the leaf apoplast suggested a greater capacity for O3 detoxification in GalL-fed plants, which corresponded with the increase in O3 tolerance observed. However, modelled data for GalL-fed plants suggested that additional constituents of the leaf apoplast may play an important role in the attenuation of environmentally-relevant O3 fluxes.

Impacts of ozone on Plantago major: apoplastic and symplastic antioxidant status.

The aim of this work was to examine the correspondence between apoplastic/symplastic antioxidant status and previously reported plant age-related shifts in the ozone (O3 ) resistance of Plantago major L. Seed-grown plants were fumigated in duplicate controlled environment chambers with charcoal/Purafil?-filtered air (CFA) or CFA plus 70 nmol mol-1 O3 for 7 h d-1 over a 42 d period. Measurements of stomatal conductance and antioxidants were made after 14, 28 and 42 d fumigation, on leaves at an equivalent stage of development (youngest fully expanded leaf, measured c. 9 d after emergence). Ozone exposure resulted in a similar decline in stomatal conductance across plant ages, indicating that increases in O3 resistance with plant age were mediated through changes in the tolerance of leaf tissue rather than enhanced pollutant exclusion. Leaf apoplastic washing fluid was found to contain 'unspecific' peroxidase, ascorbate peroxidase, superoxide dismutase and ascorbate, but not glutathione and the enzymes required to facilitate the regeneration of ascorbate from its oxidized forms. A weak induction in the activity of certain symplastic antioxidants was found after 14 d O3 fumigation, despite a lack of visible symptoms of injury, but shifts in symplastic antioxidant enzyme activity were not consistent with previously observed increases in resistance to O3 with plant age. By contrast, changes in 'unspecific' peroxidase activity and in the small pool of ascorbate in the leaf apoplast were found to accompany age-related shifts in O3 resistance. It is concluded that constituents of the leaf apoplast may constitute a potentially important front line defence against O3 .

Relationships between ozone resistance and climate in European populations of Plantago major.

The relative ozone resistance of 20 European and two American populations of Plant ago major was examined, and relationships with climatic factors at the source of the plant material were explored using data provided by participants in the ICP-Crops initiative (International Co-operative Programme to Investigate the Effects of Air Pollutants and Other Stresses on Agricultural and Semi-Natural Vegetation). Plants grown from seed were exposed to either charcoal/Purafil® filtered air (CF < 5 nmol mol-1 O3 ) or CF + ozone (70 nmol mol-1 O3 7 h d-1 ) over a 2-wk period in controlled environment chambers, and effects on mean plant relative growth rate (R) and allometric root/shoot growth (K) determined. Ozone resistance (R%) was calculated from (R03 /RCF ) × 100. Populations exhibited contrasting sensitivities to ozone, without the development of typical visible symptoms of injury. A positive relationship was found between relative ozone resistance and descriptors of the ozone-climate at the site of seed collection for the year of, and the 2 yr before, seed collection. The best predictors of inherent ozone resistance were shown to be cumulative ozone exposure indices calculated according to current United Nations Economic Commission for Europe (UN-ECE) critical level guidelines for the pollutant (i.e. the accumulated hourly average ozone exposure over a threshold level of 40 nmol mol-1 (AOT40) or 30 nmol mol-1 (AOT30) calculated during daylight hours for the consecutive 3-month period of the year experiencing the highest ozone concentrations). No relationships were found between ozone resistance and climatic factors (temperature, precipitation, sunshine hours, humidity) or the concentrations of other air pollutants (SO2 , NO2 , NO). These findings support the view that current ambient levels of ozone in many regions of Europe are high enough to promote evolution of resistance to the pollutant in native plant populations. The significance of these findings to the debate over the establishment of separate critical levels for the protection of natural and semi-natural vegetation is discussed.