Adherence at 2 years with distribution of essential medicines at no charge: The CLEAN Meds randomized clinical trial.

BACKGROUND: Adherence to medicines is low for a variety of reasons, including the cost borne by patients. Some jurisdictions publicly fund medicines for the general population, but many jurisdictions do not, and such policies are contentious. To our knowledge, no trials studying free access to a wide range of medicines have been conducted. METHODS AND FINDINGS: We randomly assigned 786 primary care patients who reported not taking medicines due to cost between June 1, 2016 and April 28, 2017 to either free distribution of essential medicines (n = 395) or to usual medicine access (n = 391). The trial was conducted in Ontario, Canada, where hospital care and physician services are publicly funded for the general population but medicines are not. The trial population was mostly female (56%), younger than 65 years (83%), white (66%), and had a low income from wages as the primary source (56%). The primary outcome was medicine adherence after 2 years. Secondary outcomes included control of diabetes, blood pressure, and low-density lipoprotein (LDL) cholesterol in patients taking relevant treatments and healthcare costs over 2 years. Adherence to all appropriate prescribed medicines was 38.7% in the free distribution group and 28.6% in the usual access group after 2 years (absolute difference 10.1%; 95% confidence interval (CI) 3.3 to 16.9, p = 0.004). There were no statistically significant differences in control of diabetes (hemoglobin A1c 0.27; 95% CI -0.25 to 0.79, p = 0.302), systolic blood pressure (-3.9; 95% CI -9.9 to 2.2, p = 0.210), or LDL cholesterol (0.26; 95% CI -0.08 to 0.60, p = 0.130) based on available data. Total healthcare costs over 2 years were lower with free distribution (difference in median CAN$1,117; 95% CI CAN$445 to CAN$1,778, p = 0.006). In the free distribution group, 51 participants experienced a serious adverse event, while 68 participants in the usual access group experienced a serious adverse event (p = 0.091). Participants were not blinded, and some outcomes depended on participant reports. CONCLUSIONS: In this study, we observed that free distribution of essential medicines to patients with cost-related nonadherence substantially increased adherence, did not affect surrogate health outcomes, and reduced total healthcare costs over 2 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT02744963.

Quantifying the statistical power of monitoring programs for marine protected areas.

Marine Protected Areas (MPAs) are increasingly established globally as a spatial management tool to aid in conservation and fisheries management objectives. Assessing whether MPAs are having the desired effects on populations requires effective monitoring programs. A cornerstone of an effective monitoring program is an assessment of the statistical power of sampling designs to detect changes when they occur. We present a novel approach to power assessment that combines spatial point process models, integral projection models (IPMs) and sampling simulations to assess the power of different sample designs across a network of MPAs. We focus on the use of remotely operated vehicle (ROV) video cameras as the sampling method, though the results could be extended to other sampling methods. We use empirical data from baseline surveys of an example indicator fish species across three MPAs in California, USA as a case study. Spatial models simulated time series of spatial distributions across sites that accounted for the effects of environmental covariates, while IPMs simulated expected trends over time in abundances and sizes of fish. We tested the power of different levels of sampling effort (i.e., the number of 500-m ROV transects) and temporal replication (every 1-3 yr) to detect expected post-MPA changes in fish abundance and biomass. We found that changes in biomass are detectable earlier than changes in abundance. We also found that detectability of MPA effects was higher in sites with higher initial densities. Increasing the sampling effort had a greater effect than increasing sampling frequency on the time taken to achieve high power. High power was best achieved by combining data from multiple sites. Our approach provides a powerful tool to explore the interaction between sampling effort, spatial distributions, population dynamics, and metrics for detecting change in previously fished populations.

Costs and compensation in zooplankton pigmentation under countervailing threats of ultraviolet radiation and predation.

Evolutionary responses to opposing directions of natural selection include trade-offs, where the phenotype balances selective forces, and compensation, where other traits reduce the impact of one selective force. Zooplankton pigmentation protects from ultraviolet radiation (UVR) but attracts visual predators. This trade-off is understudied in the ocean where planktonic larvae in surface waters face ubiquitous UVR and visual predation threats. We tested whether crab larvae can behaviorally reduce UVR risk through downward swimming or expansion of photoprotective chromatophores. Then we examined whether more pigmented larvae are more heavily predated by silverside fish under natural sunlight in the tropics in three UVR treatments (visible light, visible + UVA, visible + UVA + UVB). Lastly, we tested the behavioral chromatophore response of larvae to predation threats in two light treatments. Armases ricordi avoided surface waters after exposure to sunlight with UVR. Armases ricordi, Armases americanum, and Eurypanopeus sp. consistently expanded chromatophores in UVR or visible light, while Mithraculus sculptus and Mithraculus coryphe showed no response. Fish preferred pigmented larvae on sunnier days in visible light lacking UVR. Lastly, both M. coryphe and M. sculptus unexpectedly expanded chromatophores in fish cues, but responses were inconsistent over trials and across light treatments. The more consistent larval responses to UVR than to predator cues and the lack of predator preferences in natural light conditions suggest that UVR may have a stronger influence on pigmentation than predation. This study improves our understanding of planktonic adaptation to countervailing selection caused by visual predation and exposure to UVR.

Shifts in intertidal zonation and refuge use by prey after mass mortalities of two predators.

Recent mass mortalities of two predatory sea star species provided an unprecedented opportunity to test the effect of predators on rocky intertidal prey. Mass mortalities provide insight that manipulative experiments cannot because they alter ecosystems on a larger scale, for longer time periods, and remove both organisms and their cues from the environment. We examined shifts in population size structure, vertical zonation, and use of emersed refuge habitats outside tidepools by the abundant herbivorous black turban snail Tegula funebralis, both before and after the successive mortalities of two predatory sea stars. The small cryptic predator Leptasterias spp. suffered a localized but extreme mortality event in November 2010, followed by two mass mortalities of the keystone predator Pisaster ochraceus in August 2011 and autumn 2013. After the local extinction of Leptasterias, the population size of Tegula more than doubled. Also, since Leptasterias primarily inhabited only mid to low intertidal tidepools at this site, small and medium sized snails (which are preferred by Leptasterias) shifted lower in the intertidal and into tidepools after the mortality of Leptasterias. After the mortality of Pisaster in August 2011, large snails did not shift lower in the intertidal zone despite being preferred by Pisaster. Small and medium sized snails became denser in the higher zone and outside tidepools, which was not likely due to Pisaster mortality. Previous studies concluded that Pisaster maintained vertical size gradients of snails, but our data implicate the overlooked predator Leptasterias as the primary cause. This natural experiment indicated that (1) predators exert top-down control over prey population sizes and lower limits, (2) vertical zonation of prey are dynamic and controlled in part by prey behavior, and (3) predators exert the strongest effects on more vulnerable individuals, which typically inhabit stressful habitats higher on the shore or outside tidepools to avoid predation. Because the mass mortalities of two predators drastically reduced both the predation pressure and the chemical cues of predators in the environment, we were able to investigate both the effects of predators on prey populations and the effects on mobile prey behavior.

Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study.

BACKGROUND: Erectile dysfunction (ED) can be a sentinel marker for future cardiovascular disease and has been described as providing a "window of curability" for men to receive targeted cardiovascular risk assessment. AIM: To determine whether the prescription of phosphodiesterase type 5 inhibitors (PDE5is) for ED leads to the detection and treatment of previously undiagnosed cardiometabolic risk factors. METHODS: We performed a retrospective population-based cohort study of residents of British Columbia, Canada using linked health care databases from 2004 to 2011. An individual-level time series analysis with switching replications was used to determine changes in drug use for hypertension, hypercholesterolemia, and diabetes in men 40 to 59 years old. The observation window for each patient was 720 days before and 360 days after the index date. OUTCOMES: The primary outcome was changes in prescriptions for antihypertensive, statin, and oral antidiabetic drugs, with secondary outcomes being laboratory tests for plasma cholesterol and glucose. RESULTS: 5,858 men 40 to 59 years old newly prescribed a PDE5i were included in the analysis. We found a sudden increase in prescriptions for antihypertensive drugs (40 per 1,000; P < .001), statins (10 per 1,000; P = .001), and antidiabetic drugs (17 per 1,000; P = .002) in the 90 days after a new prescription for a PDE5i. For hypercholesterolemia and diabetes, most of this change was observed in men with relevant screening tests performed in the 30 days after their PDE5i prescription. Only 15% and 17% of men who did not have a screening test for cholesterol and glucose, respectively, in the year before their PDE5i prescription went on to have one in the subsequent 30 days. CLINICAL IMPLICATIONS: The paucity of screening tests observed in our study after PDE5i prescriptions suggests that physicians should be educated on the recommended screening guidelines for men newly diagnosed with ED. STRENGTHS AND LIMITATIONS: The number of men who were ordered a laboratory test or written a prescription but chose not to complete or fill it, respectively, is unknown. CONCLUSION: Treatment for ED with PDE5is can be a trigger or "gateway drug" for the early detection and treatment of cardiometabolic risk factors provided physicians perform the requisite screening investigations. Skeldon SC, Cheng L, Morgan SG, et al. Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study. J Sex Med 2017;14:1597-1605.

Estimated effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada.

BACKGROUND: Canada's universal health care system does not include universal coverage of prescription drugs. We sought to estimate the effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada. METHODS: We used administrative and market research data to estimate the 2015 shares of the volume and cost of prescriptions filled in the community setting that were for 117 drugs on a model list of essential medicines for Canada. We compared prices of these essential medicines in Canada with prices in the United States, Sweden and New Zealand. We estimated the cost of adding universal public drug coverage of these essential medicines based on anticipated effects on medication use and pricing. RESULTS: The 117 essential medicines on the model list accounted for 44% of all prescriptions and 30% of total prescription drug expenditures in 2015. Average prices of generic essential medicines were 47% lower in the US, 60% lower in Sweden and 84% lower in New Zealand; brand-name drugs were priced 43% lower in the US. Estimated savings from universal public coverage of these essential medicines was $4.27 billion per year (range $2.72 billion to $5.83 billion; 28% reduction) for patients and private drug plan sponsors, at an incremental government cost of $1.23 billion per year (range $373 million to $1.98 billion; 11% reduction). INTERPRETATION: Our analysis showed that adding universal public coverage of essential medicines to the existing public drug plans in Canada could address most of Canadians' pharmaceutical needs and save billions of dollars annually. Doing so may be a pragmatic step forward while more comprehensive pharmacare reforms are planned.

Drivers of expenditure on primary care prescription drugs in 10 high-income countries with universal health coverage.

BACKGROUND: Managing expenditures on pharmaceuticals is important for health systems to sustain universal access to necessary medicines. We sought to estimate the size and sources of differences in expenditures on primary care medications among high-income countries with universal health care systems. METHODS: We compared data on the 2015 volume and cost per day of primary care prescription drug therapies purchased in 10 high-income countries with various systems of universal health care coverage (7 from Europe, in addition to Australia, Canada and New Zealand). We measured total per capita expenditure on 6 categories of primary care prescription drugs: hypertension treatments, pain medications, lipid-lowering medicines, noninsulin diabetes treatments, gastrointestinal preparations and antidepressants. We quantified the contributions of 5 drivers of the observed differences in per capita expenditures. RESULTS: Across countries, the average annual per capita expenditure on the primary care medicines studied varied by more than 600%: from $23 in New Zealand to $171 in Switzerland. The volume of therapies purchased varied by 41%: from 198 days per capita in Norway to 279 days per capita in Germany. Most of the differences in average expenditures per capita were driven by a combination of differences in the average mix of drugs selected within therapeutic categories and differences in the prices paid for medicines prescribed. INTERPRETATION: Significant international differences in average expenditures on primary care medications are driven primarily by factors that contribute to the average daily cost of therapy, rather than differences in the volume of therapy used. Average expenditures were lower among single-payer financing systems that appeared to promote lower prices and the selection of lower-cost treatment options.

Patterns, predictors and persistence of chronic sedative use: a population-based observational study of older adults in British Columbia, Canada.

BACKGROUND: Benzodiazepines and benzodiazepine-like sedatives (zopiclone, zolpidem and zaleplon) are commonly prescribed to treat anxiety and insomnia but are contraindicated for chronic use. We sought to study the persistence, over multiple years, of chronic use of benzodiazepines and benzodiazepine-like sedatives among community-dwelling adults in British Columbia, Canada. METHODS: This is a retrospective analysis of linked health data for adults aged 50 to 69 in 2004 who resided in British Columbia, Canada, between 2004 and 2013. We assigned subjects to one of four groups according to the total number of days of benzodiazepines and benzodiazepine-like sedatives that they were dispensed from retail pharmacies in each observation year. We estimated logistic regression models to measure associations between the odds of chronic sedative use and explanatory variables. We computed transition probability matrices that depict likelihood of changes in sedative utilization levels across years. RESULTS: Nearly one in ten (9.4%) community-dwelling older adults in British Columbia filled prescriptions with more than 90 days' worth of benzodiazepines or benzodiazepine-like sedatives in 2013. The odds of such chronic sedative use were higher for people who were older, had lower income, were sicker, or lived in rural communities; odds were lower for people with Chinese or South Asian surnames and for men who were married. Controlling for other factors, chronic users of sedatives in 2008 were 15 times more likely than non-users of sedatives in 2008 to be chronic sedative users in 2013 (OR = 14.73; 95% CI = [14.24, 15.24]). Approximately two out of every five older British Columbians who were chronic sedative users in 2013 had been chronic users of sedatives 10 years prior. Two out of every three chronic sedative users in 2004 were either chronic users (57%) or dead (16%) by 2013. INTERPRETATION: Chronic use of sedatives is prevalent and persistent among older adults in British Columbia. The persistence of chronic sedative use between when patients were 50 to 59 years old and when they were 60 to 69 years old suggests that earlier interventions to curb chronic sedative use may be warranted even if patients do not experience significant risks until later ages.

Postmarket policy considerations for biosimilar oncology drugs.

Oncology biological products are some of the most expensive drugs on the market and are a growing financial burden on patients and health-care systems. By 2020, numerous major biological cancer drugs will lose their patent protection allowing follow-on competitors, known as biosimilars, to enter the market. Clinical and regulatory considerations for biosimilars have begun to harmonise in Europe and the USA to help to define and streamline the pathway for biosimilar market authorisation. Yet, substantial international variation still exists in the pricing and market uptake of approved biosimilar oncology drugs. Differences in national postmarket policies for biosimilars might explain these disparities in pricing and uptake. In this Policy Review, policy approaches to competition between biosimilars and originators used by seven European countries--Belgium, France, Germany, Italy, the Netherlands, Norway, and the UK--and the USA are discussed, chosen because these countries represent a variety of postmarket policies and build on conclusions from previous work. We discuss these policies within the context of interchangeability, physician prescribing, substitutability, pharmacist dispensing, hospital financing and tendering, and pricing.

Inverse approach to estimating larval dispersal reveals limited population connectivity along 700 km of wave-swept open coast.

Demographic connectivity is fundamental to the persistence and resilience of metapopulations, but our understanding of the link between reproduction and recruitment is notoriously poor in open-coast marine populations. We provide the first evidence of high local retention and limited connectivity among populations spanning 700 km along an open coast in an upwelling system. Using extensive field measurements of fecundity, population size and settlement in concert with a Bayesian inverse modelling approach, we estimated that, on average, Petrolisthes cinctipes larvae disperse only 6.9 km (±25.0 km s.d.) from natal populations, despite spending approximately six weeks in an open-coast system that was once assumed to be broadly dispersive. This estimate differed substantially from our prior dispersal estimate (153.9 km) based on currents and larval duration and behaviour, revealing the importance of employing demographic data in larval dispersal estimates. Based on this estimate, we predict that demographic connectivity occurs predominantly among neighbouring populations less than 30 km apart. Comprehensive studies of larval production, settlement and connectivity are needed to advance an understanding of the ecology and evolution of life in the sea as well as to conserve ecosystems. Our novel approach provides a tractable framework for addressing these questions for species occurring in discrete coastal populations.

Surfzone hydrodynamics as a key determinant of spatial variation in rocky intertidal communities.

Larvae of intertidal species develop at sea and must return to adult habitats to replenish populations. Similarly, nutrients, detritus and plankton provide important subsidies spurring growth and reproduction of macroalgae and filter-feeding invertebrates that form the foundation of intertidal communities. Together, these factors determine the density and intensity of interactions among community members. We hypothesized that spatial variation in surfzone hydrodynamics affects the delivery of plankton subsidies. We compared entire zooplankton communities inside and outside the surf zone daily while monitoring physical conditions for one month each at two shores with different surfzone characteristics. Opposite cross-shore distributions of larvae and other zooplankters occurred at the two sites: zooplankton was much more abundant inside the mildly sloping dissipative surf zone (DSZ) with rip currents and was more abundant outside the steep reflective surf zone (RSZ). Biophysical numerical simulations demonstrated that zooplankters were concentrated in rip channels of the DSZ and were mostly unable to enter the RSZ, indicating the hydrodynamic processes behind the observed spatial variation of zooplankters in the surf zone. Differences in the concentration of larvae and other zooplankters between the inner shelf and surf zone may be an underappreciated, key determinant of spatial variation in inshore communities.

Sensitivity and specificity of administrative mortality data for identifying prescription opioid-related deaths.

BACKGROUND: Comprehensive systems for surveilling prescription opioid-related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid-related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid-related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. METHODS: We identified all prescription opioid-related deaths from Ontario coroners' data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid-related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid-related deaths. RESULTS: Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. INTERPRETATION: In the absence of specific systems for monitoring prescription opioid-related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid-related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies.

Determinants of trends in prescription opioid use in British Columbia, Canada, 2005-2013.

PURPOSE: To explore the determinants of total opioid consumption in a Canadian province, and to examine patterns of opioid dispensations by sex, age, and income quintile. METHODS: We used population-based administrative data on prescription drug dispensations in British Columbia (BC; population ~4 million). We apply an index-based approach to examine how changes in population exposure, type of opioids used, and intensity of use contributed to changes in total morphine equivalents dispensed per 1000 population. RESULTS: Between 2005 and 2013 in BC, opioid consumption increased by 31%, driven by longer duration of opioid therapy and by an increase in the use of stronger opioids. Consumption increased for oxycodone, hydromorphone, fentanyl, and tramadol; and declined for morphine, codeine, and other opioids. While we did not find large sex and age differences, the total level of opioid consumption was three times as high among individuals in the lowest income quintile compared to those in the highest income quintile. CONCLUSIONS: Our findings on changes in the type of opioids used and changes in intensity of use suggest that modifications to clinical management of patients on opioid therapy may be warranted. Similar drug utilization statistics, derived from drug information systems, can be reproduced in other jurisdictions to enable a better understanding of the opioid crisis. Copyright © 2016 John Wiley & Sons, Ltd.

The association between domperidone and ventricular arrhythmia in the postpartum period.

PURPOSE: The aim of this study is to examine the relationship between domperidone (commonly used off-label for lactation stimulation), ventricular arrhythmia and all-cause mortality during the postpartum period. METHODS: This is a retrospective, population-based cohort study of all women with a live birth between 1 January 2002 and 31 December 2011 in British Columbia, Canada. Cox proportional hazards models, yielding hazard ratios (HRs), were used to estimate the risk of hospitalization for ventricular arrhythmia associated with domperidone exposure within six months postpartum. RESULTS: The study population consisted of 225 532 women with 320 351 live births. There was only one death during the six-month postpartum period among the study population, and thus we did not perform any analyses of all-cause mortality. We identified 21 hospitalizations for ventricular arrhythmia. Adjusting for age, smoking and prior history of ventricular arrhythmia and cardiovascular disease, the risk of ventricular arrhythmia hospitalization was approximately double among those exposed to domperidone, but the results were not statistically significant (HR = 2.25, 95%CI 0.84-6.01). Adjustment for body mass index in the 74% of women for whom it was known further reduced the association (HR = 1.69, 95%CI 0.48-5.96). CONCLUSIONS: We found a possible association between exposure to domperidone and hospitalization for ventricular arrhythmia among a cohort of women who have recently given birth. Future studies are needed to confirm this association. Copyright © 2016 John Wiley & Sons, Ltd.

Sex differences in the risk of receiving potentially inappropriate prescriptions among older adults.

OBJECTIVES: to measure sex differences in the risk of receiving potentially inappropriate prescription drugs and to examine what are the factors that contribute to these differences. DESIGN: a retrospective cohort study. SETTING: community setting of British Columbia, Canada. PARTICIPANTS: residents of British Columbia aged 65 and older (n = 660,679). MEASUREMENTS: we measured 2013 period prevalence of prescription dispensations satisfying the American Geriatrics Society's 2012 version of the Beers Criteria for potentially inappropriate medication use in older adults. We used logistic regressions to test for associations between this outcome and a number of clinical and socioeconomic factors. RESULTS: a larger share of women (31%) than of men (26%) filled one or more potentially inappropriate prescription in the community. The odds of receiving potentially inappropriate prescriptions are associated with several clinical and socioeconomic factors. After controlling for those factors, community-dwelling women were at 16% higher odds of receiving a potentially inappropriate prescription than men (adjusted odds ratio = 1.16, 95% confidence interval = 1.12-1.21). Much of this sex difference stemmed from women's increased odds of receiving potentially inappropriate prescriptions for benzodiazepines and other hypnotics, for tertiary tricyclic antidepressants and for non-selective NSAIDs. CONCLUSION: there are significant sex differences in older adults' risk of receiving a potentially inappropriate prescription as a result of complex intersections between gender and other social constructs. Appropriate responses will therefore require changes in the information, norms and expectations of both prescribers and patients.

Trends and sex differences in prescription opioid deaths in British Columbia, Canada.

Increasing rates of prescription opioid-related death are well documented in Ontario (ON) but little is known about prescription opioid-related harms in other Canadian provinces. Using administrative mortality data from 2004 to 2013, we found that rates of prescription opioid-related death in British Columbia (BC) were higher but more stable than published rates for ON over the same period. Methadone was involved in approximately 25% of the prescription opioid-related deaths in BC. The majority of prescription opioid-related deaths among men and women were unintentional. Men had higher overall rates of prescription opioid-related deaths in BC; women had lower rates of prescription opioid-related deaths but a larger proportion of them were suicides. Efforts to reduce prescription opioid-related deaths must consider sex differences in patterns of prescription opioid use and associated harms.

Universal prescription drug coverage in Canada: Long-promised yet undelivered.

Canada's universal public healthcare system is unique among developed countries insofar as it does not include universal coverage of prescription drugs. Universal, public coverage of prescription drugs has been recommended by major national commissions in Canada dating back to the 1960s. It has not, however, been implemented. In this article, we extend research on the failure of early proposals for universal drug coverage in Canada to explain failures of calls for reform over the past 20 years. We describe the confluence of barriers to reform stemming from Canadian policy institutions, ideas held by federal policy-makers, and electoral incentives for necessary reforms. Though universal "pharmacare" is once again on the policy agenda in Canada, arguably at higher levels of policy discourse than ever before, the frequently recommended option of universal, public coverage of prescription drugs remains unlikely to be implemented without political leadership necessary to overcome these policy barriers.

Geographic Variations in Prescription Opioid Dispensations and Deaths Among Women and Men in British Columbia, Canada.

OBJECTIVES: We quantify patterns in prescription opioid dispensations to individuals who suffered a prescription opioid-related death. In addition, we examine the relationship between opioid dispensations and prescription opioid-related deaths in geographic regions of British Columbia (BC). METHODS: We used population-based administrative data on prescription drug dispensations to identify patterns in prescription opioid dispensations to individuals who suffered a prescription opioid-related death. We also computed the quantity of prescription opioids dispensed (morphine equivalents) in small geographic regions in BC from 2004 to 2013. We identified prescription opioid-related deaths in these small geographic areas using mortality data from BC Vital Statistics and investigated the relationship between rates of prescription opioid dispensing and rates of prescription opioid death in small geographic areas in BC by sex. We examined differences in our results when limiting opioid dispensations to strong opioids and weak opioids. RESULTS: Many individuals who suffered a prescription opioid-related death did not have an active opioid prescription in the 60 days before death (46% of women and 71% of men). Rates of prescription opioid dispensing and opioid-related deaths vary substantially across geographic regions in BC. The area-level relationship between rate of prescription opioid dispensing and rate of unintentional prescription opioid-related death is positive and statistically significant for both men and women (P<0.001). This relationship holds when opioid prescribing is limited to strong opioids. CONCLUSION: Targeted efforts to reduce high levels of opioid prescribing in BC, particularly dispensations of strong opioids and codeine, may substantially reduce opioid-related harms.

Estimated cost of universal public coverage of prescription drugs in Canada.

BACKGROUND: With the exception of Canada, all countries with universal health insurance systems provide universal coverage of prescription drugs. Progress toward universal public drug coverage in Canada has been slow, in part because of concerns about the potential costs. We sought to estimate the cost of implementing universal public coverage of prescription drugs in Canada. METHODS: We used published data on prescribing patterns and costs by drug type, as well as source of funding (i.e., private drug plans, public drug plans and out-of-pocket expenses), in each province to estimate the cost of universal public coverage of prescription drugs from the perspectives of government, private payers and society as a whole. We estimated the cost of universal public drug coverage based on its anticipated effects on the volume of prescriptions filled, products selected and prices paid. We selected these parameters based on current policies and practices seen either in a Canadian province or in an international comparator. RESULTS: Universal public drug coverage would reduce total spending on prescription drugs in Canada by $7.3 billion (worst-case scenario $4.2 billion, best-case scenario $9.4 billion). The private sector would save $8.2 billion (worst-case scenario $6.6 billion, best-case scenario $9.6 billion), whereas costs to government would increase by about $1.0 billion (worst-case scenario $5.4 billion net increase, best-case scenario $2.9 billion net savings). Most of the projected increase in government costs would arise from a small number of drug classes. INTERPRETATION: The long-term barrier to the implementation of universal pharmacare owing to its perceived costs appears to be unjustified. Universal public drug coverage would likely yield substantial savings to the private sector with comparatively little increase in costs to government.

Unexpectedly high mortality in Pacific herring embryos exposed to the 2007 Cosco Busan oil spill in San Francisco Bay.

In November 2007, the container ship Cosco Busan released 54,000 gallons of bunker fuel oil into San Francisco Bay. The accident oiled shoreline near spawning habitats for the largest population of Pacific herring on the west coast of the continental United States. We assessed the health and viability of herring embryos from oiled and unoiled locations that were either deposited by natural spawning or incubated in subtidal cages. Three months after the spill, caged embryos at oiled sites showed sublethal cardiac toxicity, as expected from exposure to oil-derived polycyclic aromatic compounds (PACs). By contrast, embryos from the adjacent and shallower intertidal zone showed unexpectedly high rates of tissue necrosis and lethality unrelated to cardiotoxicity. No toxicity was observed in embryos from unoiled sites. Patterns of PACs at oiled sites were consistent with oil exposure against a background of urban sources, although tissue concentrations were lower than expected to cause lethality. Embryos sampled 2 y later from oiled sites showed modest sublethal cardiotoxicity but no elevated necrosis or mortality. Bunker oil contains the chemically uncharacterized remains of crude oil refinement, and one or more of these unidentified chemicals likely interacted with natural sunlight in the intertidal zone to kill herring embryos. This reveals an important discrepancy between the resolving power of current forensic analytical chemistry and biological responses of keystone ecological species in oiled habitats. Nevertheless, we successfully delineated the biological impacts of an oil spill in an urbanized coastal estuary with an overlapping backdrop of atmospheric, vessel, and land-based sources of PAC pollution.