Using novel methodology to estimate the prevalence of mental disorders in British Columbia, Canada.

PURPOSE: A needs-based model of health systems planning uses a systematic estimate of service needs for a given population. Our objective was to derive annual prevalence estimates of specific mental disorders in the adult population of British Columbia, Canada and use a novel triangulation approach encompassing multiple data sources and stratifying these estimates by age, sex, and severity to inform Ministry partners, who commissioned this work. METHODS: We performed systematic literature reviews and subsequent meta-analyses to derive an annual prevalence estimate for each mental disorder. We then generated age- and sex-specific estimates by triangulating published epidemiological studies, routinely collected province-wide health administrative data, and nationally representative health survey data sources. The age- and sex-specific estimates were further stratified by severity using the Global Burden of Disease severity distributions and published literature. RESULTS: Anxiety disorders had the highest annual prevalence estimates (6.93%), followed by depressive disorders (6.42%). All other mental disorders had an annual prevalence of less than 1%. Prevalence estimates were consistently higher in younger age groups. Depressive disorders, anxiety disorders, and eating disorders were higher in women, while estimates for bipolar disorders, schizophrenia, and ADHD were slightly higher in men in younger age groups. CONCLUSION: We generated robust annual prevalence estimates stratified by age, sex, and severity using a triangulation approach. Variation by age, sex, and severity implies that these factors need to be considered when planning for mental health services. Our approach is replicable and can be used as a model for needs-based planning in other jurisdictions.

Evaluating the population-level effects of oxycodone restrictions on prescription opioid utilization in Ontario.

PURPOSE: To investigate the impact of restrictions on access to long acting oxycodone on prescription opioid use and opioid-related harms. METHODS: Administrative health data from Ontario, Canada was used to measure differences in opioids dispensed and emergency department (ED) visits for opioid-related overdose, poisoning, or substance use following provincial restrictions on access to publicly insured OxyContin (February 29, 2012) and OxyNeo (February 28, 2013). This study focused on the cohort of provincial drug insurance eligible people (people 65+ and select low-income populations) who were dispensed oxycodone prior to the restrictions. Difference-in-differences models with a propensity score matched comparison group of people who were dispensed non-oxycodone opioids were used to estimate the main effects. RESULTS: In 6 months following the delisting of OxyContin, milligrams of morphine equivalents (MMEs) per person per week for all opioids fell by an average of 7.5% in people dispensed oxycodone relative to the comparison group, and an average of 13.8% in chronic recipients of oxycodone. In the 6 months following the restrictions on OxyNeo, MMEs per person per week fell by an average of 3.1% in all people dispensed oxycodone, and 25.2% in chronic oxycodone recipients. The decline in oxycodone dispensing among chronic oxycodone recipients corresponded with an increase in dispensing of other opioid formulations, particularly hydromorphone and fentanyl. No important differences were observed for ED visits related to opioid poisoning, overdose, or substance use disorder. CONCLUSIONS: Province-wide restrictions on access to long acting oxycodone had an impact on quantities of all opioids dispensed to chronic recipients of oxycodone, but small impacts on the full population of people dispensed oxycodone; the decline in use was partially offset by increases in use of other publicly-funded opioid formulations. This study suggests that policies limiting access to specific prescription opioids led to overall reductions in publicly funded prescription opioid use, particularly in chronic oxycodone recipients, without immediate evidence of changes in opioid-related ED visits.

The relationship between outpatient service use and emergency department visits among people treated for mental and substance use disorders: analysis of population-based administrative data in British Columbia, Canada.

BACKGROUND: Research findings on the association between outpatient service use and emergency department (ED) visits for mental and substance use disorders (MSUDs) are mixed and may differ by disorder type. METHODS: We used population-based linked administrative data in British Columbia, Canada to examine associations between outpatient primary care and psychiatry service use and ED visits among people ages 15 and older, comparing across people treated for three disorder categories: common mental disorders (MDs) (depressive, anxiety, and/or post-traumatic stress disorders), serious MDs (schizophrenia spectrum and/or bipolar disorders), and substance use disorders (SUDs) in 2016/7. We used hurdle models to examine the association between outpatient service use and odds of any ED visit for MSUDs as well count of ED visits for MSUDs, stratified by cohort in 2017/8. RESULTS: Having had one or more MSUD-related primary care visit was associated with lower odds of any ED visit among people treated for common MDs and SUDs but not people treated for serious MDs. Continuity of primary care was associated with slightly lower ED use in all cohorts. One or more outpatient psychiatrist visits was associated with lower odds of ED visits among people treated for serious MDs and SUDs, but not among people with common MDs. CONCLUSION: Findings highlight the importance of expanded access to outpatient specialist mental health services, particularly for people with serious MDs and SUDs, and collaborative models that can support primary care providers treating people with MSUDs.

Trends in dispensing of individual prescription opioid formulations, Canada 2005-2020.

BACKGROUND: Canada has experienced a distinctly bifurcated pattern of (strong) opioid utilization post-2000, with multifold increases rendering it one of the world's highest opioid consumption rates, followed by subsequent substantive declines since 2011/2012. Several interventions to control especially high-risk opioid use have been implemented post-2010 at different levels, yet with their effects assessed mostly for overall opioid utilization. Little knowledge exists for over-time patterns of individual opioid formulations. METHODS: Raw information on community-based prescription opioid dispensing for years 2005-2020 were obtained from a large national database based on a stratified sample of 6500 retail pharmacies across Canada (IQVIA/Compuscript), These data were converted into Defined-Daily-Doses/1000 population/day (DDD/1000/day) for individual (strong and weak) opioid formulations-specifically: fentanyl, hydromorphone, hydrocodone, morphine, oxycodone, codeine-per standard methods. Descriptive data on individual opioid dispensing were computed, and segmented regression (or 'broken-stick') analysis was applied to the overtime dispensing towards assessing potentially significant 'breakpoints' interrupting linear utilization trends. Akaike information criterion (AIC) values were computed to assess the resulting models' quality-of-fit. RESULTS: Five of the six opioid formulations featured a lower dispensing level in 2020 compared with 2005, but mostly with peak values in years between, contributing to the overall inversion pattern. For five of the six opioid formulations, a three-segmented model emerged as the best fit for the dispensing observed; only hydrocodone presented a linear (downward) dispensing trend. Among the five interrupted trend models for individual formulations, four (fentanyl, morphine, oxycodone, codeine but not hydromorphone) indicated their initial breakpoint during 2011-2014 introducing a downward dispensing trend. Inconsistently, morphine also featured a recent breakpoint (2018) towards a dispensing increase. CONCLUSIONS: While all opioids showed marked declines, we found heterogeneous patterns of dispensing for individual opioid formulations. While we cannot estimate direct causal effects, opioid control interventions appear to have had differential impacts on dispensing of individual formulations. The earliest breakpoint occurred towards substantive decreases for oxycodone dispensing in 2011; subsequently, there were increases in dispensing of hydromorphone and fentanyl likely due to substitution effects, followed by across-the-board declines post-2015/2016. Recent 'safer opioid' distribution programs to reduce illicit/toxic opioid exposure linked with high levels of poisoning fatalities seem to fuel resurgences in select opioid (e.g., morphine) dispensing.

Emergency department use for mental and substance use disorders: descriptive analysis of population-based, linked administrative data in British Columbia, Canada.

OBJECTIVES: Information on emergency department (ED) visits for mental and substance use disorders (MSUDs) is important for planning services but has not been explored in British Columbia (BC), Canada. We describe all MSUD ED visits for people ages 15 and older in the province of BC in 2017/2018 and document trends in MSUD ED visits between 2007/2008 and 2017/2018 by disorder group. DESIGN: Population-based linked administrative data comprised of ED records and physician billings capturing all MSUD ED visits in BC. SETTING: BC is Canada's westernmost province with a population of approximately 5 million. Permanent residents receive first-dollar coverage for all medically necessary services provided by licensed physicians or in hospitals, including ED services. POPULATION: All people age >15 with MSUD ED visits during the study period. MEASURES: All claims with a service location in the ED or corresponding to fee items billed only in the ED were examined alongside ED visits reported through a national reporting system. Patient characteristics (sex/gender, age, location of residence, income, treated disorders and comorbidities) and previous outpatient service use for all ED visits by visit diagnosis are also described. RESULTS: A total of 72 363 people made 134 063 visits to the ED in 2017/2018 for needs related to MSUD. MSUD ED visits have increased since 2010, particularly visits for substance use and anxiety disorders. People with more frequent visits were more likely to be male, on public prescription drug plans for income assistance, prescribed psychiatric medications, and living in lower-income neighbourhoods. They used more community-based primary care and psychiatry services and had lower continuity of primary care. CONCLUSIONS: MSUD ED visits are substantial and growing in BC. Findings underscore a need to strengthen and target community healthcare services and adequately resource and support EDs to manage growing patient populations.

Estimating the Prevalence of Mental and Substance Use Disorders: A Systematic Approach to Triangulating Available Data to Inform Health Systems Planning.

OBJECTIVE: To estimate the prevalence of specific mental and substance use disorders (MSUDs), by age and sex, as a first step toward informing needs-based health systems planning by decision-makers. METHODS: We developed a conceptual framework and a systematic methodology for combining available data sources to yield prevalence estimates for specific MSUDs. Data sources used included published, peer-reviewed literature from Canada and comparable countries, Canadian population survey data, and health administrative data from British Columbia. Several well-established methodologies including systematic review and meta-analyses of published prevalence estimates, modelling of age- and sex-specific distributions, and the Global Burden of Disease severity distribution model were incorporated in a novel mode of triangulation. RESULTS: Using this novel approach, we obtained prevalence estimates for 10 MSUDs for British Columbia, Canada, as well as prevalence distributions across age groups, by sex. CONCLUSION: Obtaining reliable assessments of disorder prevalence and severity is a useful first step toward rationally estimating service need and plan health services. We propose a methodology to leverage existing information to obtain robust estimates in a timely manner and with sufficient granularity to, after adjusting for comorbidity and matching with severity-specific service bundles, inform need-based planning efforts for adult (15 years and older) mental health and substance use services.

Patterns, trends and determinants of medical opioid utilization in Canada 2005-2020: characterizing an era of intensive rise and fall.

BACKGROUND: Into the 21st century, the conflation of high rates of chronic pain, systemic gaps in treatment availability and access, and the arrival of potent new opioid medications (e.g., slow-release oxycodone) facilitated strong increases in medical opioid dispensing in Canada. These persisted until post-2010 alongside rising opioid-related adverse (e.g., morbidity/mortality) outcomes. We examine patterns, trends and determinants of opioid dispensing in Canada, and specifically its 10 provinces, for the years 2005-2020. METHODS: Raw data on prescription opioid dispensing were obtained from a large national community-based pharmacy database (IQVIA/Compuscript), converted into Defined-Daily-Doses/1,000 population/day for 'strong' and 'weak' opioid categories per standard methods. Dispensing by opioid category and formulations by province/year was assessed descriptively; regression analysis was applied to examine possible segmentation of over-time strong opioid dispensing. RESULTS: All provinces reported starkly increasing strong opioid dispensing peaking 2011-2016, and subsequent marked declines. About half reported lower strong opioid dispensing in 2020 compared to 2005, with continuous inter-provincial differences of > 100 %; weak opioids also declined post-2011/12. Segmented regression suggests breakpoints for strong opioids in 2011/12 and 2015/16, coinciding with main interventions (e.g., selective opioid delisting, new prescribing guidelines) towards more restrictive opioid utilization control. CONCLUSIONS: We characterized an era of marked rise and fall, while featuring stark inter-provincial heterogeneity in opioid dispensing in Canada. While little evidence for improvements in pain care outcomes exists, the starkly inverting opioid utilization have been associated with extensive population-level harms (e.g., misuse, morbidity, mortality) over-time. This national case study raises fundamental questions for opioid-related health policy and practice.

Correlations between Changes in Medical Opioid Dispensing and Contributions of Fentanyl to Opioid-Related Overdose Fatalities: Exploratory Analyses from Canada.

Canada is experiencing an epidemic of opioid-related mortality, with increasing yet heterogeneous fatality patterns from illicit/synthetic (e.g., fentanyl) opioids. The present study examined whether differential provincial reductions in medical opioid dispensing following restrictive regulations (post-2010) were associated with differential contributions of fentanyl to opioid mortality. Annual provincial opioid dispensing totals in defined daily doses/1000 population/day, and change rates in opioid dispensing for the 10 provinces for (1) 2011-2018 and (2) "peak-year" to 2018 were derived from a pan-Canadian pharmacy-based dispensing panel. Provincial contribution rates of fentanyl to opioid-related mortality (2016-2019) were averaged. Correlation values (Pearson's R) between provincial changes in opioid dispensing and the relative fentanyl contributions to mortality were computed for the two scenarios. The correlation between province-based changes in opioid dispensing (2011-2018) and the relative contribution of fentanyl to total opioid deaths (2016-2019) was -0.70 (t = 2.75; df = 8; p = 0.03); the corresponding correlation for opioid dispensing changes ("peak-year" to 2018) was -0.59 (t = -2.06; df = 8; p = 0.07). Provincial reductions in medical opioid dispensing indicated (near-)significant correlations with fentanyl contribution rates to opioid-related death totals. Differential reductions in pharmaceutical opioid availability may have created supply voids for nonmedical use, substituted with synthetic/toxic (e.g., fentanyl) opioids and leading to accelerated opioid mortality. Implications of these possible unintended adverse consequences warrant consideration for public health policy.

Comparison of Crude Population-Level Indicators of Opioid Use and Related Harm in New Zealand and Ontario (Canada).

North America and select other Commonwealth jurisdictions have been experiencing unprecedented opioid epidemics characterized by excessive and persistently high levels of opioid misuse, morbidity and mortality, and related disease burden. Recent discussions have considered whether New Zealand might undergo or needs to expect a similar 'opioid crisis'. Towards further informing these considerations, we examine and compare essential, publicly available indicators of opioid utilization and harms (mortality) from New Zealand and the Canadian province of Ontario, due to the fact that both operate public health care systems in similar socio-cultural settings. We find that the two jurisdictions have featured vastly different population levels of opioid exposure, opioid consumption patterns (e.g., high-dose/long-term/high-risk prescribing) known as key predictors of adverse outcomes, and levels of opioid mortality as evidenced by concrete epidemiological indicators and data. Specifically for opioid-related death rates, these were already approximately threefold higher in Ontario compared to New Zealand based on most recent comparison data (e.g., 2012); these differentials have likely further grown more recently given major and distinct changes in population-level opioid exposure and risks, and subsequent opioid-related deaths since then in Ontario. Based on the present data and related evidence, New Zealand does not seem to need to anticipate an opioid mortality epidemic similar to that experienced in North America; however, it would be of interest to establish more comprehensive and timely surveillance of key system-level indicators of opioid use and harms as are standard in North America. As such, this inter-jurisdictional comparison makes for a case study in starkly contrasting scenarios of opioid use and harms, the drivers behind which deserve further systematic examination.

Prescription opioid dispensing in Canada: an update on recent developments to 2018.

Canada has been home to comparatively extreme developments in prescription opioid (PO) availability and related harms (e.g. morbidity, mortality) post-2000. Following persistent pan-Canadian increases in PO use, select control measures were implemented and PO dispensing levels-while only inconsistently by province-inverted, and began to plateau or decrease post-2012. We examined annual PO dispensing levels in Canada up until 2018, based on representative prescription sample data from community-based retail pharmacies. Annual prescription-based dispensing data were converted into defined daily doses/1000 population/day by province, and mainly categorized into 'weak' and 'strong' opioids. All provinces indicated decreasing trends in strong PO levels in most recent years, yet with inter-provincial differences of up to one magnitude in 2018; in about half the provinces, dispensing fell to below-2005 levels. British Columbia had the largest decline in strong PO dispensing from its peak rate (- 48.5%) in 2011. Weak opioid dispensing trends remained more inconsistent and bifurcated across Canada. The distinct effects of individual-including many provincially initiated and governed-PO control measures urgently need to be evaluated. In the meantime, recent reductions in general PO availability across Canada appear to have contributed to shortages in opioid supply for existent, sizable (including non-medical) user populations and may have contributed to recent marked increases in illicit opioid use and harms (including rising deaths).

Examining correlations between opioid dispensing and opioid-related hospitalizations in Canada, 2007-2016.

BACKGROUND: High levels of opioid-related mortality, as well as morbidity, contribute to the excessive opioid-related disease burden in North America, induced by high availability of opioids. While correlations between opioid dispensing levels and mortality outcomes are well-established, fewer evidence exists on correlations with morbidity (e.g., hospitalizations). METHODS: We examined possible overtime correlations between medical opioid dispensing and opioid-related hospitalizations in Canada, by province, 2007-2016. For dispensing, we examined annual volumes of medical opioid dispensing derived from a representative, stratified sample of retail pharmacies across Canada. Raw dispensing information for 'strong opioids' was converted into Defined Daily Doses per 1000 population per day (DDD/1000/day). Opioid-related hospitalization rates referred to opioid poisoning-related admissions by province, for fiscal years 2007-08 to 2016-17, drawn from the national Hospital Morbidity Database. We assessed possible correlations between opioid dispensing and hospitalizations by province using the Pearson product moment correlation; correlation values (r) and confidence intervals were reported. RESULTS: Significant correlations for overtime correlations between population-levels of opioid dispensing and opioid-related hospitalizations were observed for three provinces: Quebec (r = 0.87, CI: 0.49-0.97; p = 0.002); New Brunswick (r = 0.85;CI: 0.43-0.97; p = 0.004) and Nova Scotia (r = 0.78; CI:0.25-0.95; p = 0.012), with an additional province, Saskatchewan, (r = 0.073; CI:-0.07-0.91;p = 0.073) featuring borderline significance. CONCLUSIONS: The correlations observed further add to evidence on opioid dispensing levels as a systemic driver of population-level harms. Notably, correlations were not identified principally in provinces with reported high contribution levels (> 50%) of illicit opioids to mortality, which are not captured by dispensing data and so may have distorted or concealed potential correlation effects due to contamination.

Is supported self-management for depression effective for adults in community-based settings in Vietnam?: a modified stepped-wedge cluster randomized controlled trial.

BACKGROUND: This study tested the effectiveness of a supported self-management (SSM) intervention to reduce symptoms of depression among adults compared with enhanced treatment as usual in community-based and primary care settings in Vietnam. METHODS: The cluster randomized trial included 376 adults in 32 communes in eight provinces. Eligible participants scored > 7 on the SRQ-20 depression scale. Patients with severe symptoms were excluded and referred to tertiary care. Randomization took place at the commune level. The immediate intervention group included 16 communes with 190 participants and the delayed group included 16 communes with 186 participants. Participants in communes randomized to the immediate intervention group received a two-month course of SSM, consisting of a workbook and supportive coaching. Those in communes randomized to the delayed group received enhanced treatment as usual and, for ethical purposes, received the SSM intervention after 4 months. The primary outcome is the effect of SSM on reduction in depression scores as indicated by a reduced proportion of participants with SRQ-20 scores > 7 at 2 months after commencement of SSM intervention. Blinding was not possible during intervention delivery but outcome assessors were blinded. Analysis was intention-to-treat. RESULTS: At 2 months, 26.4% of the intervention group and 42.3% of the delayed group had SRQ-20 scores > 7. The adjusted odds ratio of having depression between the intervention and control was 0.42 (p < 0.0001), 95% CI (0.28, 0.63). Receiving the intervention thus reduces the odds of having depression by 58%, compared with receiving the control after 2 months of treatment. No adverse events were reported. CONCLUSIONS: Results suggest that SSM is effective for decreasing depression symptoms among adults in community-based settings in Vietnam.Trial Registration This trial is registered at ClinicalTrials.gov, number NCT03001063.

Correlations between opioid mortality increases related to illicit/synthetic opioids and reductions of medical opioid dispensing - exploratory analyses from Canada.

BACKGROUND: North America has been experiencing a persistent epidemic of opioid-related overdose mortality, which has increasingly been driven by fatalities from illicit, toxic opioids in most recent years. Patterns of synthetic opioid availability and related mortality are heterogeneous across Canada, and differing explanations exist as to their differentiated proliferation. We examined the perspective that heterogeneous province-based variations in prescription opioid availability, facilitated by various control strategies, post-2010 may have created regionally differential supply gaps for non-medical opioid use substituted by synthetic opioid products with differential impacts on mortality risks and outcomes in Canada. METHODS: We examined annual, prescription opioid dispensing rates and changes in the ten Canadian provinces (for the periods of 1) 2011-2018, 2) 'peak-year'-to-2018) in Defined Daily Doses/1000 population/day, derived from data from a large representative, stratified sample of community pharmacies projected to a Canada total. Annual, provincial opioid-related mortality rates and changes for years 2016-2018 were calculated from federal data. We computed correlation values (Pearson's R) between respective province-based change rates for prescription opioid dispensing and opioid-related mortality for the two over-time scenarios. RESULTS: All but one province featured reductions in prescription opioid dispensing 2011-2018; seven of the ten provinces had increases in opioid mortality 2016-2018. The correlation between changes in opioid dispensing (2011-2018) and in opioid-mortality (2016-2018) was r = 0.63 (df = 8, p-value: 0.05); the correlation was r = 0.57 (df = 8, p-value: 0.09) for changes in opioid dispensing 'peak year'-to-2018, respectively. CONCLUSIONS: Quasi-significant results indicate that recent increases in opioid-related deaths driven by illicit, synthetic opioids tended to be larger in provinces where reductions in prescription opioid availability have been more extensive. It is a plausible explanation that these reductions created supply gaps for non-medical opioid use increasingly filled by illicit, synthetic opioids differentially contributing to opioid-related deaths, generating un-intended adverse effects for previous interventions. General prevention measures to reduce opioid availability, and targeted prevention for at-risk opioid users exposed to toxic drug supply may be include counteractive effects and require coordinated reconciliation.

The opioid mortality epidemic in North America: do we understand the supply side dynamics of this unprecedented crisis?

While there has been extensive attention to the 'demand side' - or use and adverse consequences, including mortality - of the 'opioid crisis' presently unfolding across North America, few considerations have focused on the supply side. This paper examines the supply side dynamics of this unprecedented public health phenomenon. We provide evidence for several interrelated supply-side elements that have contributed to the present public health crisis. We observe that initially, persistently high levels of prescription opioid availability and use exposed large proportions of the North American population to opioids, resulting in correspondingly high levels of medical and non-medical use (e.g., involving diversion). While various intervention measures to control prescription opioid availability and use have been implemented in recent years, leading to eventual reductions in opioid dispensing levels, these occurred late in the crisis's evolution. Moreover, these supply reductions have not been met by corresponding reductions in opioid use or demand levels. These growing discrepancies between opioid demand and prescription-based sources have left major gaps in opioid supplies. In response to such supply gaps, highly potent and toxic illicit opioid products have rapidly proliferated across North America, and become a core driver of the dramatic spikes in opioid overdose fatality levels in recent years. These supply-related interrelations are corroborated by a corresponding increase in illicit opioid-related fatalities, which arose just as medical opioid supplies began to decrease in many jurisdictions. Improved analyses and understanding of the supply-side dynamics of the opioid crisis are urgently needed in order to inform future intervention and policy development. Meanwhile, the high mortality toll related to illicit, highly toxic opioid exposure requires sustained solutions, including supply-oriented measures (e.g., safer opioid distribution for at-risk users) towards improved public health protection.

Near Infrared-Activated Dye-Linked ZnO Nanoparticles Release Reactive Oxygen Species for Potential Use in Photodynamic Therapy.

Novel dye-linked zinc oxide nanoparticles (NPs) hold potential as photosensitizers for biomedical applications due to their excellent thermal- and photo-stability. The particles produced reactive oxygen species (ROS) upon irradiation with 850 nm near infrared (NIR) light in a concentration- and time-dependent manner. Upon irradiation, ROS detected in vitro in human umbilical vein endothelial cells (HUVEC) and human carcinoma MCF7 cells positively correlated with particle concentration and interestingly, ROS detected in MCF7 was higher than in HUVEC. Preferential cytotoxicity was also exhibited by the NPs as cell killing was higher in MCF7 than in HUVEC. In the absence of irradiation, dye-linked ZnO particles minimally affected the viability of cell (HUVEC) at low concentrations (<30 µg/mL), but viability significantly decreased at higher particle concentrations, suggesting a need for particle surface modification with poly (ethylene glycol) (PEG) for improved biocompatibility. The presence of PEG on particles after dialysis was indicated by an increase in size, an increase in zeta potential towards neutral, and spectroscopy results. Cell viability was improved in the absence of irradiation when cells were exposed to PEG-coated, dye-linked ZnO particles compared to non-surface modified particles. The present study shows that there is potential for biological application of dye-linked ZnO particles in photodynamic therapy.

Metal Hydroxide/Polymer Textiles for Decontamination of Toxic Organophosphates: An Extensive Study of Wettability, Catalytic Activity, and the Effects of Aggregation.

Electrospun nanofibers (NFs) incorporated with catalytically active components have gained significant interest in chemical protective clothing. This is because of the desirable properties of the NFs combined with decontamination capability of the active component. Here, a series of metal hydroxide catalysts Ti(OH)x, Zr(OH)4, and Ce(OH)4 were incorporated into three different polymer NF systems. These new polymer/metal hydroxide composite NFs were then evaluated for their catalytic activity against a nerve agent simulant. Two methods were utilized to incorporate the metal hydroxides into the NFs. Method one used direct incorporation of Ti(OH)x, Zr(OH)4, and Ce(OH)4 catalysts, whereas method two employed incorporation of Ti(OH)x via a precursor molecule. Composite NFs prepared via method one resulted in greatly improved reaction rates over the respective pure metal hydroxides due to reduced aggregation of catalysts, with polymer/Ce(OH)4 composite NFs having the fastest reaction rates out of method one materials. Interestingly, composite samples prepared by method two yielded the fastest reaction rates overall. This is because of the homogeneous distribution of the metal hydroxide catalyst throughout the NF. This homogeneous distribution created a hydroxyl-decorated NF surface with a greater number of exposed active sites for catalysis. The hydroxyl-decorated NF surface also resulted in an unexpected highly wettable composite NF, which also was found to contribute to the observed reaction rates. These results are not only promising for applications in chemical protective clothing but also show great potential for application in areas which need highly wettable membrane materials. This includes areas such as separators, antifouling membranes, and certain medical applications.

Tramadol dispensing patterns and trends in Canada, 2007-2016.

PURPOSE: Opioid use and associated mortality and morbidity have substantially increased in Canada, which recent interventions have aimed to reduce. Tramadol is an atypical prescription-only (but unscheduled under Canada's narcotics law) opioid analgesic and not subject to controls for other (eg, strong) opioids. Given experiences in different jurisdictions, tramadol may have been increasingly dispensed as a "substitute" drug during a period with increasingly restrictive controls for other (scheduled) opioids. METHODS: We examined the annual population-level retail dispensing (as a proxy for use) of tramadol and (scheduled) "strong opioids" in Canadian provinces for 2007-2016 based on data from a representative national sample of community pharmacies, covering the majority of episodes of opioid dispensing. Data for both aforementioned formulation categories were converted into defined daily doses (DDD)/1000 population/day and examined descriptively and by segmented regression analyses (to identify significant breakpoints in trends). RESULTS: Tramadol use strongly increased in all provinces until 2009. After 2009, tramadol dispensing levels either decelerated their increase or plateaued; "strong opioid" dispensing levels, in comparison, increased strongly until 2011 and decelerated or decreased for the remaining period. Tramadol was consistently dispensed at lower levels than "strong opioids." CONCLUSIONS: Tramadol and "strong opioids" showed similar (bifurcated) use trends, with initial increases and subsequent inflections, yet reductions in dispensing occurred earlier for tramadol than for "strong opioids" (the latter occurring following with recent interventions). Distinct from experiences with differential opioid control regimes elsewhere, there is no evidence that tramadol figured as a "substitution" drug for increasingly restricted "strong opioids" in Canada.

Chemical Protective Textiles of UiO-66-Integrated PVDF Composite Fibers with Rapid Heterogeneous Decontamination of Toxic Organophosphates.

Metal-organic frameworks (MOFs) are a new and growing area of materials with high porosity and customizability. UiO-66, a zirconium-based MOF, has shown much interest to the military because of the ability of the MOF to catalytically decontaminate chemical warfare agents (CWAs). Unfortunately, the applications for MOFs are limited because of their powder form, which is difficult to incorporate into protective clothing. As a result, a new area of research has developed to functionalize fabrics with MOFs to make a wearable multifunctional fabric that retains the desired properties of the MOF. In this work, UiO-66 was incorporated into poly(vinylidene) fluoride/Ti(OH)4 composite fabric using electrospinning and evaluated for its use in chemical protective clothing. The base triethanolamine (TEA) was added to the composite fabric to create a self-buffering system that would allow for catalytic decontamination of CWAs without the need for a buffer solution. The fabrics were tested against the simulants methyl-paraoxon (dimethyl (4-nitrophenyl) phosphate, DMNP), diisopropyl fluorophosphate (DFP), and the nerve agent soman (GD). The results show that all of the samples have high moisture vapor transport and filtration efficiency, which are desirable for protective clothing. The incorporation of TEA decreased air permeation of the fabric, but increased the catalytic activity of the composite fabric against DMNP and DFP. Samples with and without TEA have rapid half-lives ( t1/2) as short as 35 min against GD agent. These new catalytically active self-buffering multifunctional fabrics have great potential for application in chemical protective clothings.

Correlations between population-levels of prescription opioid dispensing and related deaths in Ontario (Canada), 2005-2016.

Canada is experiencing an ongoing opioid-related public health crisis, including persistently rising opioid (e.g., poisoning) mortality. Previous research has documented marked correlations between population-levels of opioid dispensing and deaths. We examined possible correlations between annual population-level dispensing of specific opioid formulations and related poisoning deaths in Ontario (Canada), for the period 2005-2016. Annual coroner statistics-based numbers of poisoning deaths associated with six main opioid formulations (codeine, fentanyl, hydromorphone, methadone, morphine, and oxycodone) for Ontario were converted into annual death rates (per 100,000 population). Annual dispensing data for the opioid formulations under study were based on commercial retail-sales data from a representative, stratified sample of community pharmacies (IMSQuintiles/IQVIA CompuScript), converted into Defined Daily Doses (DDD/1,000 population/day). Possible relationships between the annual death and dispensing rates were assessed by Pearson's correlation coefficient analyses. Death rates increased for almost all, while dispensing rates increased for half of the opioid categories. A significant positive correlation between death and dispensing rates was found for hydromorphone (r = 0.97, 95% CI: 0.88-0.99) and oxycodone (r = 0.90, 95% CI: 0.68-0.97) formulations; a significant negative correlation was found for codeine (r = -0.78, 95% CI: -0.93 to -0.37). No significant correlations were detected for fentanyl, methadone, and morphine related deaths. Strong correlations between levels of dispensing and deaths for select opioid formulations were found. For select others, extrinsic factors - e.g., increasing involvement of non-medical opioid products (e.g., fentanyl) in overdose deaths - likely confounded underlying correlation effects. Opioid dispensing levels continue to influence population-level mortality levels, and need to be addressed by prevention strategies.