ObjectiveTo describe the contributions of prescribed and non-prescribed opioids to opioid related deaths.DesignPopulation based cohort study.SettingOntario, Canada, from 1 January 2013 to 31 December 2016.ParticipantsAll Ontarians who died of an opioid related cause.ExposureActive opioid prescriptions, defined as those with a duration overlapping the date of death, and recent opioid prescriptions, defined as those dispensed in the 30 and 180 days preceding death. Postmortem toxicology results from the Drug and Drug/Alcohol Related Death database were used to characterise deaths on the basis of presence of prescribed and non-prescribed (that is, diverted or illicit) opioids, overall and stratified by year and age.Results2833 opioid related deaths occurred. An active opioid prescription on the date of death was relatively common but declined slightly throughout the study period (38.2% (241/631) in 2013 and 32.5% (278/855) in 2016; P for trend=0.03). Older people and women were relatively more likely to have an active opioid prescription at time of death. In 2016, 46% (169/364) of people aged 45-64 had an active opioid prescription compared with only 12% (8/69) among those aged 24 or younger (P for trend<0.001). Similarly, 46% (124/272) of women had an active opioid prescription at time of death compared with 26.4% (154/583) of men (P<0.001). Among people with active opioid prescriptions at time of death, 37.8% (375/993) also had evidence of a non-prescribed opioid on postmortem toxicology. By 2016, the non-prescribed opioid most commonly identified after death was fentanyl (41%; 47 of 115 cases). Among people without an active opioid prescription at time of death, fentanyl was detected in 20% (78/390) of deaths in 2013, increasing to 47.5% (274/577) by 2016 (P<0.001).ConclusionsPrescribed, diverted, and illicit opioids all play an important role in opioid related deaths. Although more than half of all opioid related deaths still involved prescription drugs (either dispensed or diverted) in 2016, the increased rate of deaths involving fentanyl between 2015 and 2016 is concerning and suggests the need for a multifactorial approach to this problem that considers both the prescribed and illicit opioid environments.

Recollection of previously experienced events is a key element of human memory that entails recovery of spatial, perceptual, and mental state details. While deficits in this capacity in association with brain disease have serious functional consequences, little is known about individual differences in autobiographical memory (AM) in healthy individuals. Recently, healthy adults with highly superior autobiographical capacities have been identified (e.g., LePort, A.K., Mattfeld, A.T., Dickinson-Anson, H., Fallon, J.H., Stark, C.E., Kruggel, F., McGaugh, J.L., 2012. Behavioral and neuroanatomical investigation of Highly Superior Autobiographical Memory (HSAM). Neurobiol. Learn. Mem. 98(1), 78-92. doi: 10.1016/j.nlm.2012.05.002). Here we report data from three healthy, high functioning adults with the reverse pattern: lifelong severely deficient autobiographical memory (SDAM) with otherwise preserved cognitive function. Their self-reported selective inability to vividly recollect personally experienced events from a first-person perspective was corroborated by absence of functional magnetic resonance imaging (fMRI) and event-related potential (ERP) biomarkers associated with naturalistic and laboratory episodic recollection, as well as by behavioral evidence of impaired episodic retrieval, particularly for visual information. Yet learning and memory were otherwise intact, as long as these tasks could be accomplished by non-episodic processes. Thus these individuals function normally in day-to-day life, even though their past is experienced in the absence of recollection.

BackgroundThe majority of people with hypertension require more than one medication to achieve blood pressure control. Many patients are prescribed multipill antihypertensive regimens rather than single-pill fixed-dose combination (FDC) treatment. Although FDC use may improve medication adherence, the impact on patient outcomes is unclear. We compared clinical outcomes and medication adherence with FDC therapy versus multipill combination therapy in a real-world setting using linked clinical and administrative databases.Methods and findingsWe conducted a population-based retrospective cohort study of 13,350 individuals 66 years and older in Ontario, Canada with up to 5 years of follow-up. We included individuals who were newly initiated on one angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II-receptor blocker (ARB) plus one thiazide diuretic. High-dimensional propensity score matching was used to compare individuals receiving FDC versus multipill therapy. The primary outcome was a composite of death or hospitalization for acute myocardial infarction (AMI), heart failure, or stroke. We conducted 2 analyses to examine the association between adherence and patient outcomes. First, we performed an on-treatment analysis to determine whether outcomes differed between groups while patients were on treatment, censoring patients when they first discontinued treatment, defined as not receiving medications within 150% of the previous days’ supply. Second, we conducted an intention-to-treat analysis that followed individuals allowing for breaks in treatment to quantify the difference in drug adherence between groups and assess its impact on clinical outcomes. As expected, there was no significant difference in the primary outcome between groups in the on-treatment analysis (HR 1.06, 95% CI 0.86–1.31, P = 0.60). In the intention-to-treat analysis, the proportion of total follow-up days covered with medications was significantly greater in the FDC group (70%; IQR 19–98) than in the multipill group (42%, IQR 11–91, P < 0.01), and the primary outcome was less frequent in FDC recipients (3.4 versus 3.9 events per 100 person-years; HR 0.89, 95% CI 0.81–0.97, P < 0.01). The main limitations of this study were the lack of data regarding cause of death and blood pressure measurements and the possibility of residual confounding.ConclusionsAmong older adults initiating combination antihypertensive treatment, FDC therapy was associated with a significantly lower risk of composite clinical outcomes, which may be related to better medication adherence.

Background: Spinal muscular atrophy (SMA) is a rare neurodegenerative disease characterized by progressive muscular weakness, which occurs in one in 6,000 to 10,000 live births. The burden of SMA on Canadian patients and caregivers is not known. Objective: To characterize the burden of SMA in Canada as reported by patients and caregivers, including disease and treatment impacts, indirect costs, and caregiver burden. Methods: Surveys were distributed by Cure SMA Canada and Muscular Dystrophy Canada to individuals with SMA and their caregivers. The online surveys were anonymous and completed between January 28 and February 21, 2020. Results: 965 patient and 962 caregiver responses met the eligibility criteria. Patients reported SMA subtypes as: type I (25.0%), type II (41.3%), type III (29.3%). Using the EQ-5D, patients were shown to have impaired quality of life with an average health utility index of 0.49 (SD: 0.26). The median expenditure was $4,500 CAD (IQR: $1,587 – $11,000) for assistive devices; $6,800 CAD ($3,900–$13,000) on health professional services; and $1,200 CAD (IQR: $600 –$3,100) on SMA-related travel and accommodation in the past 12 months. Caregivers reported needing respite care (45.7%), physiotherapy for an injury from a lift/transfer (45.7%), or other health impacts (63.3%). Caregivers reported changes to personal plans, sleep disturbances, and work adjustments, with a mean Caregiver Strain Index score of 7.5 [SD: 3.3]. Conclusion: SMA in Canada is associated with a significant burden for patients and their caregivers.