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In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Objective: To develop a detailed profile of individuals living with migraine in Canada. Such a profile is important for planning and administration of services. Methods: The 2011–2012 Survey of Living with Neurological Conditions in Canada (SLNCC), a cross-sectional community-based survey, was used to examine a representative sample of migraineurs (N = 949) aged 15 years and older. Several health-related variables were examined (e.g., general health, health utility index (HUI) [a measure of health status and health-related quality of life, where dead = 0.00 and perfect health = 1.00], stigma, depression, and social support). Respondents were further stratified by sex, age, and age of migraine onset. Weighted overall and stratified prevalence estimates and odds ratios, both with 95% CIs, were used to estimate associations. Results: Overall, males had poorer health status compared with females (e.g., mean HUI was 0.67 in males vs. 0.82 in females; men had over two times the odds of their migraine limiting educational and job opportunities compared with females). Poorer health-related variables were seen in the older age groups (35–64 years/≥65 years) compared with the 15–34-year age group. There were no differences between those whose migraine symptoms began before versus after the age of 20 years. Conclusions: In this Canadian sample, migraine was associated with worse health-related variables in men compared with women. However, both men and women were significantly affected by migraine across various health-related variables. Thus, it is important to improve clinical and public health interventions addressing the impact of migraine across individuals of all ages, sexes, and sociodemographic backgrounds.
Use of second-generation antipsychotics (SGA) has increased in recent years; however, their use and effect on metabolic outcomes has been poorly characterised in population-level studies.
This study aimed to determine the associations between SGA use and metabolic indicators in a general population.
We used data from the Canadian Health Measures Survey, a cross-sectional survey of Canadian households. Participants were Canadians aged 3–79 years, living in one of the ten provinces. Several metabolic indicators were examined, including weight, body mass index, waist circumference, hypertension, diabetes and two definitions of metabolic syndrome.
The proportion of Canadians taking an SGA tripled over the study period. SGA use was significantly associated with hypertension (odds ratio 1.94, 95% CI 1.07–3.55) and abdominal obesity in adults, as defined by the National Cholesterol Education Program–Adult Treatment Panel III (odds ratio 2.62, 95% CI 1.45–4.71).
Evidence of metabolic dysfunction with SGAs is seen in the Canadian population, along with a rapid increase in prevalence of use since 2007.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Our primary objective was to understand the barriers and facilitators associated with the implementation of high-quality clinical practice guidelines (CPGs) for depression and anxiety in patients with dementia or Parkinson’s disease (PD). We conducted focus groups or interviews with participants experiencing dementia or PD, their caregivers, and physicians in Calgary, Alberta, and applied the theoretical domains framework and behaviour change wheel to guide data collection and perform a framework analysis. Thirty-three physicians and seven PD patients/caregivers participated. We report barriers and facilitators to the implementation of guideline recommendations for diagnosis, management, and the use of the guidelines. An overarching theme was the lack of evidence for depression or anxiety disorders in dementia or PD, which was prominent for anxiety versus depression. Patients noted difficulties with communicating symptoms and accessing services. Although guidelines are available, physicians have difficulty implementing certain recommendations due primarily to a lack of evidence regarding efficacy.
Background: Health administrative data are a common population-based data source for traumatic brain injury (TBI) surveillance and research; however, before using these data for surveillance, it is important to develop a validated case definition. The objective of this study was to identify the optimal International Classification of Disease , edition 10 (ICD-10), case definition to ascertain children with TBI in emergency room (ER) or hospital administrative data. We tested multiple case definitions. Methods: Children who visited the ER were identified from the Regional Emergency Department Information System at Alberta Children’s Hospital. Secondary data were collected for children with trauma, musculoskeletal, or central nervous system complaints who visited the ER between October 5, 2005, and June 6, 2007. TBI status was determined based on chart review. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each case definition. Results: Of 6639 patients, 1343 had a TBI. The best case definition was, “1 hospital or 1 ER encounter coded with an ICD-10 code for TBI in 1 year” (sensitivity 69.8% [95% confidence interval (CI), 67.3-72.2], specificity 96.7% [95% CI, 96.2-97.2], PPV 84.2% [95% CI 82.0-86.3], NPV 92.7% [95% CI, 92.0-93.3]). The nonspecific code S09.9 identified >80% of TBI cases in our study. Conclusions: The optimal ICD-10–based case definition for pediatric TBI in this study is valid and should be considered for future pediatric TBI surveillance studies. However, external validation is recommended before use in other jurisdictions, particularly because it is plausible that a larger proportion of patients in our cohort had milder injuries.
Family caregivers are an integral and increasingly overburdened part of the health care system. There is a gap between what research evidence shows is beneficial to caregivers and what is actually provided. Using an integrated knowledge translation approach, a stakeholder meeting was held among researchers, family caregivers, caregiver associations, clinicians, health care administrators, and policy makers. The objectives of the meeting were to review current research evidence and conduct multi-stakeholder dialogue on the potential gaps, facilitators, and barriers to the provision of caregiver supports. A two-day meeting was attended by 123 individuals. Three target populations of family caregivers were identified for discussion: caregivers of seniors with dementia, caregivers in end-of-life care, and caregivers of frail seniors with complex health needs. The results of this meeting can and are being used to inform the development of implementation research endeavours and policies targeted at providing evidence-informed caregiver supports.
Background: Understanding the epidemiology of traumatic brain injury (TBI) is essential to shape public health policy, implement prevention strategies, and justify allocation of resources toward research, education, and rehabilitation in TBI. There is not, to our knowledge, a systematic review of population-based studies addressing the epidemiology of TBI that includes all subtypes. We performed a comprehensive systematic review and meta-analysis of the worldwide incidence of TBI. Methods: A search was conducted on May 23, 2014, in Medline and EMBASE according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Abstracts were screened independently and in duplicate to identify original research. Study quality and ascertainment bias were assessed in duplicate using a previously published tool. Demographic data and incidence estimates from each study were recorded, along with stratification by age, gender, year of data collection, and severity. Results: The search strategy yielded 4944 citations. Two hundred and sixteen articles met criteria for full-text review; 144 were excluded. Hand searching resulted in ten additional articles. Eighty-two studies met all eligibility criteria. The pooled annual incidence proportion for all ages was 295 per 100,000 (95% confidence interval: 274-317). The pooled incidence rate for all ages was 349 (95% confidence interval: 96.2-1266) per 100,000 person-years. Incidence proportion and incidence rate were examined to see if associated with age, sex, country, or severity. Conclusions: We conclude that most TBIs are mild and most TBIs occur in males among the adult population. The incidence of TBI varies widely by ages and between countries. Despite being an important medical, economic, and social problem, the global epidemiology of TBI is still not well-characterized in the current literature. Understanding the incidence of TBI, particularly mild TBI, remains challenging because of nonstandardized reporting among neuroepidemiological studies.
Population-based prevalence and incidence studies are essential for understanding the burden of frontotemporal dementia (FTD).
The MEDLINE and EMBASE databases were searched to identify population-based publications from 1985 to 2012, addressing the incidence and/or prevalence of FTD. References of included articles and prior systematic reviews were searched for additional studies. Two reviewers screened all abstracts and full-text reviews, abstracted data and performed quality assessments.
Twenty-six studies were included. Methodological limitations led to wide ranges in the estimates for prevalence (point prevalence 0.01-4.6 per 1000 persons; period prevalence 0.16-31.04 per 1000 persons) and incidence (0.0-0.3 per 1000 person-years). FTD accounted for an average of 2.7% (range 0-9.1%) of all dementia cases among prevalence studies that included subjects 65 and older compared to 10.2% (range 2.8-15.7%) in studies restricted to those aged less than 65. The cumulative numbers of male (373 [52.5%]) and female (338 [47.5%]) cases from studies reporting this information were nearly equal (p=0.18). The behavioural variant FTD (bvFTD) was almost four times as common as the primary progressive aphasias.
Population-based estimates for the epidemiology of FTD varied widely in the included studies. Refinements in the diagnostic process, possibly by the use of validated biomarkers or limiting case ascertainment to specialty services, are needed to obtain more precise estimates of the prevalence and incidence of FTD.
Population-based prevalence and incidence studies are essential for understanding the societal burden of dementia with Lewy bodies (DLB).
The MEDLINE and EMBASE databases were searched to identify publications addressing the incidence and/or prevalence of DLB. References of included articles and prior systematic reviews were searched for additional studies. Two reviewers screened all abstracts and full-text reviews, abstracted data and performed quality assessments.
Twenty-two studies were included. Incidence rates ranged from 0.5 to 1.6 per 1000 person-years. DLB accounted for 3.2-7.1% of all dementia cases in the incidence studies. Point and period prevalence estimates ranged from 0.02 to 63.5 per 1000 persons. Increasing prevalence estimates were reported with increasing age. DLB accounted for from 0.3 to 24.4% of all cases of dementia in the prevalence studies.
DLB becomes more common with increasing age and accounts for about 5% of all dementia cases in older populations.
Updated information on the epidemiology of dementia due to Alzheimer’s disease (AD) is needed to ensure that adequate resources are available to meet current and future healthcare needs. We conducted a systematic review and meta-analysis of the incidence and prevalence of AD.
The MEDLINE and EMBASE databases were searched from 1985 to 2012, as well as the reference lists of selected articles. Included articles had to provide an original population-based estimate for the incidence and/or prevalence of AD. Two individuals independently performed abstract and full-text reviews, data extraction and quality assessments. Random-effects models were employed to generate pooled estimates stratified by age, sex, diagnostic criteria, location (i.e., continent) and time (i.e., when the study was done).
Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 119 studies met the inclusion criteria. In community settings, the overall point prevalence of dementia due to AD among individuals 60+ was 40.2 per 1000 persons (CI95%: 29.1-55.6), and pooled annual period prevalence was 30.4 per 1000 persons (CI95%: 15.6-59.1). In community settings, the overall pooled annual incidence proportion of dementia due to AD among individuals 60+ was 34.1 per 1000 persons (CI95%: 16.4-70.9), and the incidence rate was 15.8 per 1000 person-years (CI95%: 12.9-19.4). Estimates varied significantly with age, diagnostic criteria used and location (i.e., continent).
The burden of AD dementia is substantial. Significant gaps in our understanding of its epidemiology were identified, even in a high-income country such as Canada. Future studies should assess the impact of using such newer clinical diagnostic criteria for AD dementia such as those of the National Institute on Aging–Alzheimer’s Association and/or incorporate validated biomarkers to confirm the presence of Alzheimer pathology to produce more precise estimates of the global burden of AD.
Dementia is a common neurological condition affecting many older individuals that leads to a loss of independence, diminished quality of life, premature mortality, caregiver burden and high levels of healthcare utilization and cost. This is an updated systematic review and meta-analysis of the worldwide prevalence and incidence of dementia.
The MEDLINE and EMBASE databases were searched for relevant studies published between 2000 (1985 for Canadian papers) and July of 2012. Papers selected for full-text review were included in the systematic review if they provided an original population-based estimate for the incidence and/or prevalence of dementia. The reference lists of included articles were also searched for additional studies. Two individuals independently performed abstract and full-text review, data extraction, and quality assessment of the papers. Random-effects models and/or meta-regression were used to generate pooled estimates by age, sex, setting (i.e., community, institution, both), diagnostic criteria utilized, location (i.e., continent) and year of data collection.
Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 160 studies met the inclusion criteria. Among individuals 60 and over residing in the community, the pooled point and annual period prevalence estimates of dementia were 48.62 (CI95%: 41.98-56.32) and 69.07 (CI95%: 52.36-91.11) per 1000 persons, respectively. The respective pooled incidence rate (same age and setting) was 17.18 (CI95%: 13.90-21.23) per 1000 person-years, while the annual incidence proportion was 52.85 (CI95%: 33.08-84.42) per 1,000 persons. Increasing participant age was associated with a higher dementia prevalence and incidence. Annual period prevalence was higher in North America than in South America, Europe and Asia (in order of decreasing period prevalence) and higher in institutional compared to community and combined settings. Sex, diagnostic criteria (except for incidence proportion) and year of data collection were not associated with statistically significant different estimates of prevalence or incidence, though estimates were consistently higher for females than males.
Dementia is a common neurological condition in older individuals. Significant gaps in knowledge about its epidemiology were identified, particularly with regard to the incidence of dementia in low- and middle-income countries. Accurate estimates of prevalence and incidence of dementia are needed to plan for the health and social services that will be required to deal with an aging population.
Background: Many Canadians with multiple sclerosis (MS) have recently travelled internationally to have procedures for a putative condition called chronic cerebrospinal venous insufficiency (CCSVI). Here, we describe where and when they went and describe the baseline characteristics of persons with MS who participated in this non–evidence-based medical tourism for CCSVI procedures. Methods: We conducted a longitudinal observational study that used online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following procedures for CCSVI. A convenience sample of all Albertans with MS was recruited between July 2011 and March 2013. Results: In total, 868 individuals enrolled; 704 were included in this cross-sectional, baseline analysis. Of these, 128 (18.2%) participants retrospectively reported having procedures for CCSVI between April 2010 and September 2012. The proportion of participants reporting CCSVI procedures declined from 80 (62.5%) in 2010, to 40 (31.1%) in 2011, and 8 (6.3%) in 2012. In multivariable logistic regression analysis, CCSVI procedures were independently associated with longer disease duration, secondary progressive clinical course, and greater disability status. Conclusions: Although all types of people with MS pursued procedures for CCSVI, a major driver of participation was greater disability. This highlights that those with the greatest disability are the most vulnerable to unproven experimental procedures. Participation in CCSVI procedures waned over time possibly reflecting unmet expectations of treated patients, decreased media attention, or that individuals who wanted procedures had them soon after the CCSVI hypothesis was widely publicized.
Background: The muscular dystrophies are a heterogeneous group of genetic muscle diseases with variable distribution of weakness and mode of inheritance.Methods: We previously performed a systematic review of worldwide population-based studies on Duchenne and Becker muscular dystrophies; the current study focused on the epidemiology of other muscular dystrophies using Medline and EMBASE databases. Two reviewers independently reviewed all abstracts, full-text articles, and abstracted data from 1985 to 2011. Pooling of prevalence estimates was performed using random-effect models.Results: A total of 1104 abstracts and 167 full-text articles were reviewed. Thirty-one studies met all eligibility criteria and were included in the final analysis. The overall pooled prevalence of combined muscular dystrophies was 16.14 (confidence interval [CI], 11.21-23.23) per 100,000. The prevalence estimates per 100,000 were 8.26 (CI, 4.99-13.68) for myotonic dystrophy, 3.95 (CI, 2.89-5.40) for facioscapulohumeral dystrophy, 1.63 (CI, 0.94-2.81) for limb girdle muscular dystrophy, and 0.99 (CI, 0.62-1.57) for congenital muscular dystrophies.Conclusions: The studies differed widely in their approaches to case ascertainment, and substantial gaps remain in the global estimates of many other types of muscular dystrophies. Additional epidemiological studies using standardized diagnostic criteria as well as multiple sources of case ascertainment will help address the economic impact and health care burden of muscular dystrophies worldwide.
Non-convulsive seizures have been reported to be common in neurocritical care patients. Many jurisdictions do not have sufficient resources to enable routine continuous electroencephalography (cEEG) and instead use primarily intermittent EEG, for which the diagnostic yield remains uncertain. Determining risk factors for epileptiform activity and seizures could help identify patients who might particularly benefit from EEG monitoring.
We performed a cohort study involving neurocritical care patients with admission Glascow Coma Scale (GCS) scores =≤ 12, who underwent ≥ 1 EEG. EEGs were reviewed for presence of interictal discharges, periodic epileptiform discharges (PEDs), and seizures. Multivariate analysis was used to identify predictors of these findings and to describe their prognostic implications.
393 patients met inclusion criteria. 34 underwent cEEG, usually because epileptiform activity was first detected on a routine EEG. The prevalence of PEDs or electrographic seizures was 13%, and was highest with anoxic encephalopathy and central nervous system infections. Other independent predictors for epileptiform activity included a history of convulsive seizure(s), increasing age, deeper coma, and female gender. Although patients with epileptiform activity had higher mortality, this association disappeared after adjustment for confounders.
Approximately 7-8 neurocritical care patients must undergo intermittent EEG monitoring in order to diagnose one with PEDs or seizures. The predictors we identified could potentially help guide use of resources. Repeated intermittent studies, or cEEG, should be considered in patients with multiple risk factors, or when interictal discharges are identified on an initial EEG. It remains unclear whether aggressive prevention and treatment of electrographic seizures improves neurologic outcomes.
Although randomized controlled trials (RCTs) are the gold standard for evaluating therapeutic interventions, surgical RCTs are particularly challenging and few have been done in the field of epilepsy surgery. We assess the level of RCT activity in epilepsy surgery and propose feasible alternatives to develop sustainable research initiatives in this area.
We undertook a systematic review of the world literature to assess the level of RCT activity in epilepsy surgery. Previous personal experience with RCTs in epilepsy surgery and examples of successful Canadian multicentre research networks were reviewed to propose initiatives for sustainable, valid research in epilepsy surgery.
We identified 12 RCTs in epilepsy surgery, including 692 patients, of whom 416 were involved in vagus nerve stimulation, 16 in various brain electrostimulation procedures, 180 in comparisons of different surgical techniques, and 80 in a comparison of medical versus surgical therapy. Most studies were of short duration (median = 3 months, range 3-12 months). In the area of resective surgery, only temporal lobe epilepsy has been subjected to any type of RCT comparison. All RCTs have been done within the last 13 years. There were no multicentre Canadian surgical studies.
The adoption of RCTs in epilepsy surgery has been slow and difficult worldwide. Because of its universal health care system and its well established epilepsy surgery centres, Canada is in a strong position to create a national epilepsy surgery research initiative capable of undertaking high quality, sustainable research in epilepsy surgery.