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Background: Medical cannabis use is growing among older adults. In this retrospective study, we aimed to assess the characteristics of older medical cannabis users including the indications, type and amount of cannabis used, perceived changes in symptoms after cannabis use, change in dose of concurrent medications, and adverse effects. Methods: Data were collected between October 2014 and October 2020 from patients who were consulting the Canada-wide network of clinics of a medical cannabis provider and who were willing to answer questionnaires based on their medical status. The current study included older adults (≥ 65 years) who completed questionnaires at intake and first follow-up visits. Data were summarized with descriptive statistics, which were compared between men and women with t tests or chi-squared tests. Tests of proportions assessed categorical responses for perceived effects after cannabis use. Logistic regression was used to assess trends in cannabis usage. Results: Data included that from 9766 older adult users at intake (mean ± SD age = 73.2 ± 6.8 years, females = 60.0%), among whom 4673 (females = 61.4%) returned for follow-up after 90.6 ± 58 days. The most common primary indication for which medical cannabis was sought was pain (67.7%), which was more common in women, whereas oncological and neurological conditions were more common in men. At follow-up, cannabis oil was used by 81.0% of older adults, among whom compositions containing only or mostly cannabidiol (CBD) had been used by 83.6%. Adverse effects reported by older adults at the follow-up visit included dry mouth (12.8%), drowsiness (8.6%), and dizziness (4.0%). The majority of older adults reported improvements in pain (72.7%, z = 1482.6, p < 0.0001, compared to worsening or no change), sleep (64.5%, z = 549.4, p < 0.0001), and mood (52.8%, z = 16.4, p < 0.0001), with 35.6% reporting use of a reduced dose of opioids and 19.9% a reduced dose of benzodiazepines. Interpretation: Among older adults, medical cannabis is used more often by women, with CBD-containing cannabis oils being the most commonly used. Users reported improved pain, sleep, and mood symptoms at follow-up after cannabis use. This study describes the patterns of use of medical cannabis by older adults and highlights the need for research to determine appropriate indications, precise doses of active ingredients, and short- and long-term outcomes among older adults. [ABSTRACT FROM AUTHOR]

Background Infants with congenital diaphragmatic hernia (CDH) are at an increased risk of respiratory morbidity from recurrent respiratory tract infections including those from respiratory syncytial virus (RSV). Prospective studies on RSV prophylaxis in CDH infants are limited. We determined the risk of respiratory illness– and RSV-related hospitalizations (RIH and RSVH, respectively) among infants prophylaxed for CDH, standard indications (SIs) and those without increased risk (NR). Methods The prospective Canadian Respiratory Syncytial Virus Evaluation Study of Palivizumab (CARESS) registry was searched for infants who received palivizumab during 12 RSV seasons (2005–2017) in Canada. Cox proportional hazards analyses were conducted to compare RIH and RSVH risks across the groups adjusted for potential confounders. Results In total, 21 107 infants (201 CDH, 389 NR, and 20 517 SI) were included. RIH incidences were 10.0% (CDH), 2.1% (NR), and 6.2% (SI). CDH patients had a significantly higher RIH hazard compared with NR (hazard ratio [HR], 3.6 [95% confidence interval {CI}, 1.5–8.8]; P =.005) but not SI (HR, 1.2 [95% CI,.8–2.0]; P =.379). RSVH incidences were 0.6%, 0.3%, and 1.5% for CDH, NR, and SI, respectively. RSVH risk was similar across groups (SI: HR, 0.0, P =.922; NR: HR, 0.0, P =.934). Conclusions CDH infants had a 3-fold increased risk of RIH compared to NR but not SI infants. RSVH risk was similar with low RSVH incidences across all groups, implying that CDH infants may benefit from palivizumab during the RSV season, similar to other high-risk groups. Clinical Trials Registration NCT00420966. [ABSTRACT FROM AUTHOR]

Children aged <2 years with chronic lung disease (CLD) have a 10-fold higher risk for respiratory syncytial virus-positive hospitalization (RSVH) compared to healthy term infants. Based on the updated position statements, we compared respiratory-related illness hospitalization (RIH) and RSVH risks in CLD children who received palivizumab during the first year (FY) versus second year (SY) of life in the Canadian Registry of Palivizumab (CARESS). Demographic data were collected at enrolment and RIH events recorded monthly from 2005 to 2015. Eight hundred forty-seven FY and 450 SY children with CLD were identified. SY children had a lower gestational age (27 versus 29 weeks) and required more days of respiratory support (64 versus 43), oxygen therapy (108 versus 55), and length of stay (118 versus 73) during the neonatal course compared to FY children; all p < 0.0005. RIH rates were 12.2 (FY) and 18.2 (SY), and RSVH rates were 2.3 (FY) and 3.9 (SY). Cox regression showed similar hazards for both RIH (hazard ratio 0.9, 95% CI 0.6-1.6, p = 0.812) and RSVH (hazard ratio 1.1, 95% CI 0.4-2.9, p = 0.920).Conclusions: SY and FY children had similar risks for RIH and RSVH. The findings imply that SY children with CLD are correctly selected for palivizumab based on neonatal illness severity and merit prophylaxis. What is Known: • Children with chronic lung disease have a 10-fold higher risk for RSV-positive hospitalization in comparison to healthy term infants and commonly receive palivizumab prophylaxis as a preventative measure against serious RSV-related lower respiratory tract infections. • The American Academy of Pediatrics [ 2 ] and the Canadian Paediatric Society [ 30 ] have recently modified their recommendations for RSV prophylaxis in children with chronic lung disease, limiting palivizumab to either those <32 weeks gestation or those in the first year of life who are oxygen dependent or require medical therapy for the treatment of their condition. What is New: • Children with chronic lung disease receiving an additional course of palivizumab in their second year of life were determined to be at similar risk for both respiratory illness-related hospitalization and RSV-positive hospitalization as palivizumab-naïve children enrolled in the first year of life in the Canadian Registry for palivizumab (CARESS). • CARESS physicians are correctly identifying high-risk children with chronic lung disease in their second year of life, whom they believe will benefit from an additional year of palivizumab prophylaxis, based on neonatal illness severity. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the safety and tolerability of palivizumab for RSV prophylaxis in high-risk children in everyday practice. Methods: High-risk children prophylaxed against RSV infection were recruited into a prospective, observational, Canadian RSV Evaluation Study of Palivizumab (CARESS) registry with active, serious adverse event (SAE) monitoring from 2008 to 2013. SAE reports were systematically collected and assessed for severity and relationship to palivizumab. Data were analyzed by Chi-square or Fisher Exact Tests to examine group differences in proportions. Results: 13025 infants received 57392 injections. Hospitalizations for respiratory-related illness (RIH) were reported in 915 patients, and SAEs other than RIH were reported in 52 patients. Of these, 6 (0.05%) patients had a total of 14 hypersensitivity reactions that were deemed possibly or probably related to palivizumab (incidence: 2.8 per 10,000 patient-months). The SAEs of 42 patients were assessed as not related to palivizumab. SAEs in the remaining 4 patients were not classifiable as their records were incomplete. There were no significant demographic predictors of SAE occurrence. Conclusions: Under active surveillance, a small proportion of infants in the CARESS registry experienced SAEs that had a potential relationship with palivizumab and these appeared to be unpredictable in terms of onset. Palivizumab appears to be a safe and well-tolerated antibody for RSV prophylaxis in high-risk children in routine practice. [ABSTRACT FROM AUTHOR]

Objective: To determine risk factors for clinically significant progression during 12 months in patients with mild-to-moderate Alzheimer disease.Method: Community-dwelling patients with mild-to-moderate Alzheimer disease were enrolled in a 3-year prospective study, the Canadian Outcomes Study in Dementia (commonly referred to as COSID), at 32 Canadian sites. Assessments included the Global Deterioration Scale (GDS) for disease severity, the Mini-Mental State Examination (MMSE) for cognition, the Functional Autonomy Measurement System (SMAF) for daily functioning, and the NeuroPsychiatric Inventory (NPI) for behaviour, measured at baseline and at 12 months. Logistic regression identified factors associated with GDS decline, and subsequent stepwise regression identified key independent predictors. Area under the curve (AUC) was then calculated for the model.Results: Among 488 patients (mean age 76.5 years [SD 6.4], MMSE 22.1 [SD4.6], 44.1% male), 225 (46%) showed GDS decline. After adjusting for age, baseline risk factors for deterioration included the following: poorer cognition (lower MMSE score, OR 0.55; 95% CI 0.4 to 0.72 per 5 points, P ≤ 0.001), greater dependence (lower SMAF, OR 0.72; 95% CI 0.63 to 0.83 per 5 points, P ≤ 0.001), and more neuropsychiatric symptoms (higher NPI, OR 1.11; 95% CI 1.02 to 1.2 per 5 points, P = 0.02), with a protective effect of male sex (OR 0.59; 95% CI 0.39 to 0.9, P = 0.02), and higher (worse) GDS score (very mild, compared with mild OR 0.25; 95% CI 0.09 to 0.70, P ≤ 0.01; compared with moderate, OR 0.08; 95% CI 0.03 to 0.23, P < 0.001; compared with moderately severe, OR 0.03; 95% CI 0.01 to 0.11, P < 0.001). The AUC was 73% (P < 0.001) (sensitivity 90% and specificity 33%).Conclusion: The progression of Alzheimer disease in Canada can be predicted using readily available clinical information. [ABSTRACT FROM AUTHOR]

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Background: Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants, including those in the 32-35 weeks' gestational age (GA) subgroup. The cost-effectiveness of this therapy in Canada is unknown.Objectives: To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants born at 32-35 weeks' GA.Design: A decision analytic model was designed to compare both direct and indirect medical costs and benefits of prophylaxis in this subgroup of premature infants. Sensitivity analyses were performed to ascertain the robustness of the model for five point estimates: mortality rate, discounting rates, health-utility values, degree of vial-sharing and administration costs. A probabilistic sensitivity analysis (PSA) was also conducted.Setting: Canadian publicly funded health-care system (Ministry of Health payer perspective) for base-case analysis. Societal perspective, accounting for future lost productivity, was adopted for a secondary analysis.Participants: Canadian infants born at 32-35 weeks' GA without chronic lung disease.Interventions: Palivizumab prophylaxis versus no prophylaxis.Main Outcome Measures: Expected costs and incremental cost-effectiveness ratio expressed as cost per life-year gained (LYG) and quality-adjusted life-year (QALY) using 2007 Canadian dollars.Results: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratio (ICER) for the base-case scenario was $20 924 per QALY after discounting, which is considered cost-effective in Canada. When the uncertainty of the input parameter assumptions was tested through sensitivity analyses assessing several data sources for five key parameters, no substantial differences were found from the base-case results. The PSA indicated a 0.99 probability that the ICER for palivizumab was less than $50 000/QALY. Sub-analyses that varied the number of risk factors found that for infants with two or more risk factors, or at least moderate risk, palivizumab had incremental costs per QALY that indicated moderate-to-strong evidence for adoption (range: $808-81 331, per QALY).Conclusions: Palivizumab was cost-effective and the authors' model supports prophylaxis for infants born at 32-35 weeks' GA, particularly those with more than two risk factors or at least a moderate level of risk according to a risk scoring tool. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) has been associated with an increased risk of suicide, further increased among individuals with a comorbid psychiatric illness. A paucity of studies have examined details of suicide among individuals with cardiovascular disease (CVD) and comorbid depression. We aimed to compare demographic, clinical and suicide-specific characteristics between suicide victims with CVD with depression (CVD+D) and without comorbid depression (CVD-D).Methods: Coroner data on suicide decedents with CVD (n=413) occurring in Toronto, Canada from 1998 to 2012 were collected. Characteristics were compared between the CVD+D and CVD-D groups. Regression analysis examined for gender differences in these groups.Results: CVD+D subjects compared to CVD-D were more likely to have had a past suicide attempt (p=0.008), and to have experienced a bereavement (p=0.008) or financial stressor (p=0.005) in the past year. Each of these variables remained significantly associated with the presence of depression after the regression analysis. Within the CVD+D group, females were more likely to die from suicide by self-poisoning (p<0.0001) and males by shooting (p=0.001).Limitations: Psychological autopsies were not available. The definition of CVD was broad and the accuracy of its diagnosis could not be confirmed.Conclusion: Individuals with CVD+D who died from suicide had significant differences in clinical characteristics and specific stressors compared to those without depression. These data may help to better characterize suicide risk and prevention in this vulnerable population. [ABSTRACT FROM AUTHOR]

The 2019 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Mood, Cognition and Fatigue following Stroke is a comprehensive set of evidence-based guidelines addressing three important issues that can negatively impact the lives of people who have had a stroke. These include post-stroke depression and anxiety, vascular cognitive impairment, and post-stroke fatigue. Following stroke, approximately 20% to 50% of all persons may be affected by at least one of these conditions. There may also be overlap between conditions, particularly fatigue and depression. If not recognized and treated in a timely matter, these conditions can lead to worse long-term outcomes. The theme of this edition of the CSBPR is Partnerships and Collaborations, which stresses the importance of integration and coordination across the healthcare system to ensure timely and seamless care to optimize recovery and outcomes. Accordingly, these recommendations place strong emphasis on the importance of timely screening and assessments, and timely and adequate initiation of treatment across care settings. Ideally, when screening is suggestive of a mood or cognition issue, patients and families should be referred for in-depth assessment by healthcare providers with expertise in these areas. As the complexity of patients treated for stroke increases, continuity of care and strong communication among healthcare professionals, and between members of the healthcare team and the patient and their family is an even bigger imperative, as stressed throughout the recommendations, as they are critical elements to ensure smooth transitions from acute care to active rehabilitation and reintegration into their community.

Background: Immunocompromised children are at increased risk for respiratory syncytial virus (RSV) infection with associated morbidity and mortality. Prophylaxis is usually provided to these children on a case-by-case basis., Methods: Immunocompromised children who received ≥1 injection of palivizumab were prospectively enrolled across 32 Canadian sites, between 2005 and 2017, during the RSV season. We assessed respiratory illness hospitalization (RIH) and RSV-related hospitalization (RSVH) hazard ratios (HRs) in immunocompromised children versus infants' prophylaxed for standard indications (SI: prematurity ≤35 weeks' gestation, bronchopulmonary dysplasia, and congenital heart disease) and complex medical disorders (CMD). Data were analyzed using t-tests, χ and Cox proportional hazards adjusted for confounders., Results: A total of 25,003 infants were recruited; 214 immunocompromised, 4283 CMD, 20,506 SI. On average, children received 4.4 ± 1.3 injections. A total of 16,231 children were perfectly adherent (58.4% immunodeficiency, 68.9% CMD, 64.2% SI; P < 0.0005). A higher proportion of immunocompromised children were aboriginal and exposed to smoking compared with CMD and SI. Immunocompromised children also had a higher median; gestational and enrollment age and birth weight compared with CMD and SI. Immunodeficient children had a higher RIH risk compared with SI (HR = 2.4, 95% confidence interval, 1.3-4.7, P = 0.009) but were similar to CMD (HR = 1.7, 95% confidence interval, 0.9-3.4, P = 0.118). RSVH in prophylaxed, immunocompromised children was similar to CMD (HR < 0.005, P = 0.955) and SI (HR < 0.005, P = 0.953)., Conclusions: Immunocompromised children who received palivizumab had an increased RIH hazard compared with the SI group. Similar RSVH hazard between the 3 groups suggests that immunocompromised children may benefit from palivizumab during the RSV season.

Background: This study aimed to examine the risk of respiratory-related hospitalization in children with neurologic and muscular disorders (NMDs) who received respiratory syncytial virus (RSV) prophylaxis in the Canadian RSV Evaluation Study of Palivizumab., Methods: Canadian RSV Evaluation Study of Palivizumab is a prospective registry of children who received ≥1 palivizumab injection among 32 Canadian sites. Demographic data were collected at enrollment, and respiratory events were documented monthly. Cox proportional hazard analyses were conducted to compare respiratory illness-related hospitalization (RIH) and RSV-related hospitalization (RSVH) among children with NMD and those prophylaxed for standard indications (SI) and complex medical disorders., Results: Group differences were found in enrollment age and weight, birth weight, household crowding, neonatal stay and supplemental oxygen requirement (all P < 0.05). RIH and RSVH incidences were 19.2%, 3.3% (NMD, n = 605); 6.0%, 1.5% (SI, n = 20,335), 9.4%, 1.6% (complex medical disorders, n = 4063), respectively. Children with NMD had a higher risk of RIH (hazard ratio [HR]: 1.90; 95% confidence interval (CI): 1.41-2.56; P < 0.0005) than those with SI. RSVH risk was greater in children with NMD compared with both the SI (HR: 2.26; 95% CI: 1.38-3.72; P = 0.001) and complex medical disorders groups (HR: 2.74; 95% CI: 1.55-4.84; P = 0.001). Children with more severe infantile onset NMD had a higher risk of RIH than those with general hypotonic disorders (HR: 1.69; 95% CI: 1.06-2.68; P = 0.027) but not RSVH., Conclusions: Children with NMD who received palivizumab had a higher risk of both RIH and RSVH. Our results imply that all children with NMD, regardless of disease severity, are at risk for respiratory-related illness and RSV infection.

Data on respiratory-related illness and respiratory syncytial virus (RSV) infection in children with a tracheostomy are sparse. We determined respiratory illness hospitalization (RIH) and RSV-related hospitalization (RSVH) hazard ratios in children with a tracheostomy following prophylaxis compared with infants' prophylaxed for standard indications (prematurity ≤ 35 weeks' gestational age, bronchopulmonary dysplasia, and significant congenital heart disease) and children with complex medical disorders. Children who received ≥ 1 injection of palivizumab were prospectively enrolled across 32 Canadian sites during the RSV season. Respiratory illness event data were collected monthly. Data were analyzed using t tests, chi-square tests, and Cox proportional hazards adjusted for confounders. A total of 23,597 infants were enrolled; 220 tracheostomy, 19,402 standard indications, 3975 complex medical disorders. Of the 220 tracheostomy infants, 30 had bronchopulmonary dysplasia, 18 were premature, 12 had congenital heart disease, and 160 had other medical complexities. RIH and RSVH incidences (tracheostomy, standard indications, complex medical disorders) were 24.5%, 6.2%, and 9.8% and 2.0%, 1.5%, and 1.8% respectively. RIH hazard was significantly higher in tracheostomy infants compared with standard indications (HR = 1.8, 95% CI 1.1-3.0, p = 0.02) but was similar between the tracheostomy and complex medical disorders groups (HR = 1.3, 95% CI 0.7-2.2, p = 0.37). RSVH hazard was also similar in tracheostomy infants relative to standard indications and complex medical disorders (both p > 0.75). Children with tracheostomies who received palivizumab had an increased RIH hazard compared with the standard indications group. Similar RSVH hazard between tracheostomy, standard indications, and complex medical disorders groups suggests that children with tracheostomies may benefit from palivizumab by reducing RSVH during the RSV season.

Background: Currently, there is no composite screening tool that can efficiently and effectively assess prevalent yet under-recognized cognitive and neuropsychiatric comorbidities in patients with cardiovascular disease. We aimed to determine the validity and feasibility of a novel screen assessing cognitive impairment, anxiety, apathy and depression (CAAD screen) in those attending cardiac rehabilitation (CR)., Methods: All patients diagnosed with cardiovascular disease or cardiovascular risk factors entering CR were screened as part of clinical care. A subset of those patients agreed to complete validation assessments (n = 127). Screen results were compared to widely accepted standards for cognition, anxiety, apathy, and depression using a modified receiver operating characteristic (ROC) and area under the curve analysis., Results: The screen was completed by 97% of participants in 10 min or less with an average completion time of approximately 5 min. Screening scores adjusted for age, sex and years of education had acceptable or excellent validity compared to widely accepted standard diagnoses: CAAD-Cog (AUC = 0.80); CAAD-Anx (AUC = 0.81); CAAD-Apathy (AUC = 0.79) and CAAD-Dep (AUC = 0.85)., Conclusions: The CAAD screen may be a valid and feasible tool for detecting cognitive impairment, anxiety, apathy and depression in CR settings.

Objective: Coronary artery disease (CAD) is frequently accompanied by white matter hyperintensities and executive dysfunction. Because acetylcholine is important in executive function, these symptoms may be exacerbated by subcortical hyperintensities (SH) located in cholinergic (CH) tracts. This study investigated the effects of SH on cognitive changes in CAD patients undergoing a 48-week cardiac rehabilitation program., Methods: Fifty patients (age 66.5 ± 7.1 years, 84% male) underwent the National Institute of Neurological Disorders and Stroke - Canadian Stroke Network neurocognitive battery at baseline and 48 weeks. Patients underwent a 48-week cardiac program and completed neuroimaging at baseline. Subcortical hyperintensities in CH tracts were measured using Lesion Explorer. Repeated measures general linear models were used to examine interactions between SH and longitudinal cognitive outcomes, controlling for age, education, and max VO 2 change as a measure of fitness., Results: In patients with SH in CH tracts, there was a significant interaction with the Trail Making Test (TMT) part A and part B over time. Patients without SH improved on average 16.6 and 15.0% on the TMT-A and TMT-B, respectively. Patients with SH on average showed no improvements in either TMT-A or TMT-B over time. There were no significant differences in other cognitive measures., Conclusion: These results suggest that CAD patients with SH in CH tracts improve less than those without SH in CH tracts, over 48 weeks of cardiac rehabilitation. Thus, SH in CH tracts may contribute to longitudinal cognitive decline following a cardiac event and may represent a vascular risk factor of cognitive decline. © 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd., (© 2017 The Authors. International Journal of Geriatric Psychiatry Published by John Wiley & Sons Ltd.)

Background: Aboriginal infants are at risk for serious respiratory infection., Objective: To determine the hazard rate (HR) for respiratory-related illness (RIH) and respiratory syncytial virus (RSV) specific infection hospitalization (RSVH) in Aboriginal versus non-Aboriginal children receiving palivizumab and the effect of adherence on hospitalization., Methods: Palivizumab recipients in the Canadian registry from 2005 to 2014 were included. Adherence was determined by the number of palivizumab doses received during the RSV season and interdose time interval. Adherence proportions between groups were compared by χ test. Cox proportional hazard analysis determined the effect of Aboriginal status and adherence on the risk of RIH and RSVH., Results: Aboriginal infants comprised 3.6% (701/19,235) of the registry. HR was 1.6 [95% confidence interval (CI): 1.3-2.0, P < 0.001] and 1.2 (95% CI: 0.7-2.2, P = 0.383) for RIH and RSVH. Aboriginal infants were 62.8% and 63.3% adherent with all recommended injections and within stipulated time intervals, respectively, whereas 81.9% (χ = 162.45, df = 1, P < 0.001) and 72.4% (χ = 27.35, df = 1, P = 0.002) of non-Aboriginal infants were correspondingly adherent. Only 39.9% of Aboriginals were perfectly adherent (adherent to total number and injection intervals), compared with 61.7% of non-Aboriginals (χ = 133.89, df = 1, P < 0.001). Even after adjustment for known risk factors, being Aboriginal and nonadherent was associated with higher RIH hazard (HR = 1.4, 95% CI: 1.1-1.8; HR = 1.3, 95% CI: 1.1-1.4, P = 0.004), respectively. Aboriginals nonadherent with interdose intervals had a 2.2-fold increased HR for RSVH (HR = 2.2, 95% CI: 1.2-4.2, P = 0.015)., Conclusions: Prophylaxed Aboriginal infants have a significantly increased RIH and RSVH hazard than non-Aboriginal infants. Improving adherence especially interdose frequency may further reduce hospitalizations in this vulnerable population.

Background and Purpose: The Montreal Cognitive Assessment (MoCA) is used commonly to identify cognitive impairment (CI), but there are multiple published cut points for normal and abnormal. We seek to validate a pragmatic approach to screening for moderate-severe CI, by classifying patients into high-, intermediate-, and low-risk categories., Methods: A total of 390 participants attending an academic Stroke Prevention Clinic completed the MoCA and more detailed neuropsychological testing. Between April 23, 2012 and April 30, 2014, all consecutive new referrals to the regional Stroke Prevention Clinic who were English-speaking, not severely aphasic, and could see and write well enough to complete neuropsychological testing were assessed for inclusion, and consenting patients were enrolled. CI was defined as ≥2 SDs below normal for age and education on at least 2 cognitive subtests. A single cut point for CI was compared with 2 cut points (high sensitivity and high specificity) generated using receiver operator characteristic and area under the curve analyses. The intermediate-risk group contained those scoring between the 2 cut points., Results: Thirty-four percent of participants had a symptomatic or silent stroke, 34% were seen for possible or probable transient ischemic attack, and 32% were diagnosed with other vascular or nonvascular conditions. Using a single cut point, sensitivity and specificity were optimal with MoCA ≤22, (sensitivity=60.4%, specificity=89.9%, area under the curve=0.801, positive predictive value=48.5%, negative predictive value=93.5%, positive likelihood ratio=6, and negative likelihood ratio=0.4). Using 2 cut points, sensitivity was optimal with MoCA ≥28 (sensitivity=96.2%, negative predictive value =97.6%, and negative likelihood ratio=1.27), and specificity was optimal with MoCA ≤22 (specificity=89.9%, positive predictive value=48.5%, and positive likelihood ratio=6)., Conclusions: Stratifying participants into 3 categories facilitates the identification of a homogenous group at low risk for CI, as well as 2 other groups with intermediate and higher risk. This approach could facilitate clinical care pathways and patient selection for research., (© 2016 American Heart Association, Inc.)

Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals, and the evidence suggests one-third or more will experience vascular-cognitive impairment, and/or intractable fatigue, either alone or in combination. The 2015 update of the Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Module guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. The three consequences of stroke that are the focus of the this guideline (poststroke depression, vascular cognitive impairment, and fatigue) have high incidence rates and significant impact on the lives of people who have had a stroke, impede recovery, and result in worse long-term outcomes. Significant practice variations and gaps in the research evidence have been reported for initial screening and in-depth assessment of stroke patients for these conditions. Also of concern, an increased number of family members and informal caregivers may also experience depressive symptoms in the poststroke recovery phase which further impact patient recovery. These factors emphasize the need for a system of care that ensures screening occurs as a standard and consistent component of clinical practice across settings as stroke patients transition from acute care to active rehabilitation and reintegration into their community. Additionally, building system capacity to ensure access to appropriate specialists for treatment and ongoing management of stroke survivors with these conditions is another great challenge., (© 2015 World Stroke Organization.)

Objective: Coronary artery disease (CAD) is associated with an increased risk of cognitive decline. Although cerebral white matter (WM) damage predicts cognitive function in CAD, conventional neuroimaging measures only partially explain the effect of CAD on cognition. The purpose of this study was to determine if WM microstructural integrity and CAD using diffusion tensor imaging (DTI) correlates with cognitive function in older adults with CAD., Methods: Forty-nine CAD patients (66 ± 7 years old, 86% male) underwent neurocognitive assessments using the cognitive battery recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network for the study of vascular cognitive impairment. Composite scores for each cognitive domain were calculated. Microstructural integrity in normal-appearing WM was quantified as fractional anisotropy (FA) using DTI in nine bilateral and two interhemispheric WM tracts from the Johns Hopkins University WM Tractography Atlas. Linear regression models examined associations between FA and cognitive performance, controlling for age, sex, and education, with correction for multiple comparisons using a false discovery rate of 5%., Results: Executive function was most significantly associated with FA in the left parahippocampal cingulum (β = 0.471, t = 3.381, df = 44, p = 0.002) and left inferior fronto-occipital fasciculus (β = 0.430, t = 2.984, df = 44, p = 0.005). FA was not associated with memory in any of the WM tracts examined., Conclusion: These results suggest that WM microstructural integrity may be an important neural correlate of executive function even in cognitively intact CAD patients. This study suggests WM damage may be relevant to subtle cognitive decline in a population that may have early neural risk for dementia., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

We studied caregivers' willingness-to-pay for Alzheimer's disease drug therapy. We recruited 216 caregivers of persons with mild or moderate Alzheimer's disease and presented them with four scenarios describing a hypothetical Alzheimer's disease medication. The scenarios described the medication as capable of either treating the symptoms of disease or modifying the course of disease. The scenarios also presented two different probabilities of adverse effects occurrence, i.e., 0% or 30%. Most caregivers said they would pay out-of-pocket for the medication, with support for such payment ranging from 68% to 93%, depending on the specific scenario. The highest level of support was for the 'disease modifying and no adverse effects' scenario, while the lowest level was for the 'symptom treatment and 30% chance of adverse effects' scenario. On average, caregivers' monthly willingness-to-pay out-of-pocket for the medication ranged from $214 to $277 (Canadian dollars). Dollar amounts were highest for the 'disease modifying and no adverse effects' scenario and lowest for the 'symptom treatment and 30% chance of adverse effects' scenario. Support for out-of-pocket payment and specific dollar amounts were highest when the medication did not involve adverse effects. Caregivers placed more value on the absence of adverse effects than on drug efficacy., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background and Objectives: Children with Down syndrome (DS) are at significant risk for respiratory syncytial virus (RSV) infection and related hospitalization. We compared hospitalization rates due to respiratory tract infection in children with DS aged <2 years who prospectively received palivizumab during the RSV season with a previously published, similar untreated DS birth cohort., Methods: A total of 532 children with DS who prospectively received palivizumab were assembled from the prospective Canadian RSV Evaluation Study of Palivizumab registry between 2005 and 2012. The untreated group included 233 children with DS derived from a nationwide Dutch birth cohort from 2003 to 2005. Events during the RSV seasons were counted. Poisson regression analysis was performed to compare incidence rate ratios (95% confidence intervals [CIs]) between groups while controlling for observation length and known risk factors for severe RSV infection., Results: In total, 31 (23 untreated, 8 treated) RSV-related hospitalizations were documented. The adjusted risk of RSV-related hospitalizations was higher in untreated subjects than in palivizumab recipients (incidence rate ratio 3.63; 95% CI, 1.52-8.67). The adjusted risk of hospitalization for all respiratory tract infection (147 events; 73 untreated, 74 treated) was similar (incidence rate ratio untreated versus palivizumab 1.11; 95% CI, 0.80-1.55)., Conclusions: These results suggest that palivizumab is associated with a 3.6-fold reduction in the incidence rate ratio for RSV-related hospitalization in children with DS during the first 2 years of life. A randomized trial is needed to determine the efficacy of RSV immunoprophylaxis in this specific high-risk patient population., (Copyright © 2014 by the American Academy of Pediatrics.)

Background: Down syndrome (DS) is a risk factor for respiratory syncytial virus (RSV) hospitalization, but little is known about prophylaxis in these children., Methods: CARESS is a prospective registry of children who received ≥1 dose of palivizumab during the 2006-2012 RSV seasons across 32 sites in Canada. The objective was to compare respiratory illness hospitalization and RSV hospitalization (RSVH) hazard ratios in DS children aged <2 years who received palivizumab versus children who received prophylaxis for standard indications (SI) and for other medical illnesses (MI)., Results: 13,310 children were enrolled; DS (600; 4.5%), SI (11,081; 83.3%) and MI (1629, 12.2%), with DS children increasing over the duration from 0.1% (2006) to 4.5% (2012). Participants were significantly different in mean birth weight, gestational and enrollment age and risk factors. Children in each group received an average of 4.3 ± 1.4 (DS), 4.1 ± 1.6 (SI) and 4.5 ± 1.4 (MI) palivizumab injections per RSV season, with DS, differing significantly from SI [F(2, 13,307) = 43.6, P = 0.01] but not MI [F(2, 13 307) = 43.6, P = 0.07]. Compliance rates were similar across the groups. While a significantly greater proportion of SI children had RIHs compared with DS, [hazard ratio: 0.64 (0.48-0.84); P = 0.001] hazard ratios were similar for DS and MI. RSVH incidence rates were: 1.53%, 1.45% and 2.27% for DS, SI and MI, respectively. Neither group nor compliance affected time to RSVH., Conclusions: The proportion of DS children who received palivizumab in CARESS has increased almost 45-fold. RSVH rates were low in DS following prophylaxis and hazards were similar to those found in SI and MI.

Respiratory syncytial virus (RSV) infection occurs commonly in infants aged ≤2 years, and severe infection results in hospitalization with accompanying morbidity and mortality. Palivizumab has been available for prophylaxis for the past 15 years. Prospective data on patients who received palivizumab from 2005 to 2012 has been assembled in the Canadian registry (CARESS) to document utilization, compliance, and health outcomes in both hospital and community settings. Long-term data is necessary to evaluate the impact of palivizumab on the incidence of RSV infections, minimize healthcare resources, and identify which infant subpopulations are receiving prophylaxis. A database search was also conducted for similar information from published registries, and hospitalization rates were compared to results from randomized clinical trials (RCTs).Overall hospitalization rates (percent; range) for respiratory-related illnesses and RSV-specific infection in infants who meet standard indications for prophylaxis were 6.6 (3.3-7.7) and 1.55 (0.3-2.06), respectively, in CARESS, which closely aligns with registry data from 4 other countries, despite the former comprising the largest cohort of complex patients internationally. Overall RSV-related hospitalization rates were lower across registries compared to equivalent patients in RCTs. Registry data provides valuable information regarding real-world experience with palivizumab, while facilitating the genesis of new research themes.

Background: Palivizumab is indicated for respiratory syncytial virus (RSV) prophylaxis in high-risk children. However, relatively little is known about the current use, compliance, and outcomes associated with this medication., Methods: A prospective, observational, registry based on 27 sites, with monthly follow-up of infants at high risk for RSV who received at least 1 dose of palivizumab during the 2005-2009 RSV seasons., Results: A total of 5286 children were enrolled (56.6% male; 71.7% white; average gestational age, 32.1 ± 5.5 weeks). Of them, 3741 patients (70.8%) were prophylaxed for prematurity only, 449 (8.5%) for bronchopulmonary dysplasia/chronic lung disease, 508 (9.6%) for congenital heart disease, and 588 (11.1%) for other reasons. Overall, 19,485 doses were given. On average, infants received 86.0% ± 28.4% of their expected number of injections; 71.2% of infants received their injections in the recommended time periods. Of the 5286 participants enrolled, 308 patients were hospitalized for respiratory tract illness (hospitalization rate, 5.8%). The RSV-hospitalization rate was calculated as 1.38%. Having siblings increased likelihood of hospitalization (66.9% vs. 55.7%, P < 0.005), and was significantly correlated with time to hospitalization in this cohort (P = 0.050)., Conclusions: The overall RSV-hospitalization rate in our study was within the range found in previous reports (1.3%-5.3%), although it did not mimic the declining rates of the US Palivizumab Outcomes Registry. This could be due to increased testing for RSV when hospitalized and increasing rates of prophylaxis of infants with underlying medical disorders.

Background: Cholinesterase inhibitors (ChEIs) are being used for increasingly long periods of time, even in patients with severe Alzheimer's disease. Because there is little data to help clinicians to decide on when it is safe and appropriate to discontinue ChEIs after long-term use, practices may vary widely., Methods: An internet-based survey was undertaken of Canadian dementia experts (geriatric psychiatrists, neurologists, geriatricians) involved in clinical trial research. Recommendations for ChEI discontinuation were determined based on responses to questions dealing with patient/caregiver preference, administrative considerations, effectiveness, and adverse events., Results: There was reasonable consensus that ChEIs should be discontinued based on patient and caregiver preference, and in the presence of severe bothersome adverse events. There was much less consensus on issues related to effectiveness - in particular, what constitutes greater than expected decline. There was a general reluctance to rely on any single measure of cognition, function and/or behavior, and in particular, the MMSE was seen as unhelpful for making decisions about discontinuation., Conclusion: Recommendations for discontinuing ChEIs after long-term use from a survey of dementia experts are presented. Ideally, clinical practice guidelines based on controlled discontinuation trials are needed.

Objective: Acquisition costs of palivizumab have increased in Canada since 2007. This analysis aims to re-evaluate the cost effectiveness of palivizumab in Canada for premature infants born between 32 and 35 weeks' gestational age using updated 2010 healthcare costs compared to those used in a 2007 decision analytic model., Methods: New costs (CAN$) were acquired from the same Health Canada and Ontario Ministry of Health sources that were utilized in the previously published 2007 model. Palivizumab prices were acquired from Abbott Laboratories Ltd., current as of August 2010., Results: Incremental cost-effectiveness ratios (ICERs) rose by $742, going from $30,618/QALY to $31,360/QALY. ICER changes increased from a range of $801,297 to $820,701 for infants with zero risk factors to a decrease from $808 to $192 for infants with four or more risk factors., Conclusions: Palivizumab ICERs remained fairly stable from 2007 to 2010. The original recommendation stating that palivizumab is cost effective in infants born between 32 and 35 weeks' GA with two or more risk factors, or who are at moderate-to-high risk based on a risk assessment model, does not change. Analyses founded on evolving country-specific variables are needed in order to accurately reassess the cost effectiveness of interventions as costs change worldwide., Limitations: There are a limited number of publications reporting mortality in premature Canadian infants with RSV as a primary outcome. In addition, conclusions drawn from this analysis are country-specific and limited to premature infants dwelling in Canada.

Objectives: To examine risk factors for lower respiratory tract infections (LRTI) hospital admission in the Canadian Arctic., Methods: This was a case-control study during a 14-month period among children less than 2 years of age. Cases were admitted to the Baffin Regional Hospital in Iqaluit, Nunavut with LRTI. Controls were age matched and came from Iqaluit and 2 communities. Odds ratios (ORs) of hospital admission for LRTI were estimated through multivariate conditional logistic regression modeling for following risk factors: smoking in pregnancy, Inuit race, prematurity, adoption status, breast-feeding, overcrowding, and residing outside of Iqaluit. Viruses in nasophayngeal aspirates were sought at the time of each hospital admission., Results: There were 101 age-matched cases and controls. The following risk factors were significantly associated with an increased risk of admission for LRTI (adjusted OR): smoking in pregnancy (OR = 4.0; 95% CI: 1.1-14.6), residence outside of Iqaluit (OR = 2.7; 95% CI: 1.0 -7.2), full Inuit race (OR = 3.8; 95% CI: 1.1-12.8), and overcrowding (OR = 2.5, 95% CI: 1.1- 6.1). Non-breast-fed children had a 3.6-fold risk of being admitted for LRTI (95% CI: 1.2-11.5) and non-breast-fed adopted children had a 4.4-fold increased risk (95% CI: 1.1-17.6) when compared with breast-fed, nonadopted children. Prematurity was not associated with an increased risk of admission. Viruses were identified in 88 (72.7%) of admissions, with respiratory syncytial virus being identified in the majority of admissions, 62 (51.2%). Multiple viruses were isolated in 19 (15.7%) admissions., Conclusions: Smoking during pregnancy, place of residence, Inuit race, lack of breast-feeding, and overcrowding were all independently associated with increased risk of hospital admission for LRTI among Inuit children less than 2 years of age. Future research on the role of adoption and genetics on the health of Inuit children are required.

Background: The objectives were to compare actual respiratory syncytial virus (RSV) hospitalization rates and costs in a cohort of Inuit infants to hypothetical palivizumab prophylaxis strategies for infants of all gestational ages in the Eastern Canadian Arctic., Methods: Incidence and costs of RSV hospitalization were collected for infants admitted to the Baffin Regional Hospital in 2002, before the initiation of palivizumab. There was a comparison of the actual costs to the costs associated with 8 palivizumab strategies stratified by age (<6 months, <1 year) and location (overall, town [Iqaluit], rural communities). It was assumed that each category would receive universal palivizumab prophylaxis resulting in a 78% decrease in RSV admissions. The net costs incurred, number needed to treat (NNT), and incremental costs per hospitalization avoided were calculated for each comparison., Results: There was a great variation in the rates and costs associated with RSV admissions between Iqaluit and the communities. For infants <1 year of age residing in Iqaluit, the mean admission cost was $3915, and palivizumab prophylaxis had an NNT of 20.4 and cost of $162,551 per admission avoided. For rural infants <6 months, the mean cost of admission was $23,030, and palivizumab prophylaxis resulted in an NNT of 3.9 to 2.5 and cost savings of up to $8118 per admission avoided., Conclusions: Due to the high rates and costs associated with RSV admissions, administration of palivizumab in rural communities in the Canadian Arctic to infants less than 6 months of age could result in net cost savings.

Introduction: Canadian, Inuit, full term infants have the highest rate of respiratory syncytial virus (RSV) infection globally, which results in substantial costs associated hospitalisation., Methods: Decision-analytical techniques were used to estimate the incremental cost-effectiveness ratio (ICER) for palivizumab compared to no prophylaxis for Inuit infants of all gestational age. The time horizon was that of life-time follow-up, and costs and effectiveness were discounted at 5% per year. Costs (2007 CAD$) for palivizumab, hospitalisation (including medical evacuation, intensive care unit [ICU]), physician visits, and transportation were calculated based on the Canadian payer's perspective. Benefits on decreasing RSV hospitalisation were expressed as quality-adjusted life-years (QALYs). One-way and probabilistic sensitivity analysis (PSA) were conducted, varying: mortality rates, utilities, length of stay in hospital and ICU., Results: For all of Baffin Island infants (<1 year), the ICER was $39,435/QALY. However, when infants were grouped by age and area of residence, those residing in Iqaluit (<1 year) had an ICER of $152,145/QALY, while those residing in rural areas (outside of Iqaluit) had an ICER of $24,750/QALY. Prophylaxis was a dominant strategy (cost saving) for rural infants under 6 months of age, with the PSA demonstrating that it was dominant 98% of the time., Conclusions: The ICERs suggested that palivizumab is a cost-effective option for the prevention of RSV for Inuit infants on Baffin Island compared to no prophylaxis. Palivizumab is highly cost effective in Arctic infants <1 year of age specifically residing outside of Iqaluit and is a dominant strategy for those under 6 months of age in rural areas. However, palivizumab is not cost effective compared to no treatment for infants of all ages residing in Iqaluit.

Background: Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants, including those in the 32-35 weeks' gestational age (GA) subgroup. The cost-effectiveness of this therapy in Canada is unknown., Objectives: To evaluate the cost-effectiveness of palivizumab as respiratory syncytial virus prophylaxis in premature infants born at 32-35 weeks' GA., Design: A decision analytic model was designed to compare both direct and indirect medical costs and benefits of prophylaxis in this subgroup of premature infants. Sensitivity analyses were performed to ascertain the robustness of the model for five point estimates: mortality rate, discounting rates, health-utility values, degree of vial-sharing and administration costs. A probabilistic sensitivity analysis (PSA) was also conducted., Setting: Canadian publicly funded health-care system (Ministry of Health payer perspective) for base-case analysis. Societal perspective, accounting for future lost productivity, was adopted for a secondary analysis., Participants: Canadian infants born at 32-35 weeks' GA without chronic lung disease., Interventions: Palivizumab prophylaxis versus no prophylaxis., Main Outcome Measures: Expected costs and incremental cost-effectiveness ratio expressed as cost per life-year gained (LYG) and quality-adjusted life-year (QALY) using 2007 Canadian dollars., Results: The expected costs were higher for palivizumab prophylaxis as compared with no prophylaxis. The incremental cost-effectiveness ratio (ICER) for the base-case scenario was $20 924 per QALY after discounting, which is considered cost-effective in Canada. When the uncertainty of the input parameter assumptions was tested through sensitivity analyses assessing several data sources for five key parameters, no substantial differences were found from the base-case results. The PSA indicated a 0.99 probability that the ICER for palivizumab was less than $50 000/QALY. Sub-analyses that varied the number of risk factors found that for infants with two or more risk factors, or at least moderate risk, palivizumab had incremental costs per QALY that indicated moderate-to-strong evidence for adoption (range: $808-81 331, per QALY)., Conclusions: Palivizumab was cost-effective and the authors' model supports prophylaxis for infants born at 32-35 weeks' GA, particularly those with more than two risk factors or at least a moderate level of risk according to a risk scoring tool.

Objective: To estimate the contribution of behavioral and psychological symptoms of dementia (BPSD) to the costs of care., Method: A one-year prospective study of resource utilization recorded monthly by 500 caregivers of community dwelling patients with dementia. The effect of behavior on total, direct and indirect costs of care was examined., Results: The total cost of care was $1,298 per month and there was a significant independent relationship between costs and BPSD. The incremental cost of a one point increase in Neuropsychiatric Inventory score was $30 per month (95% CI: $19-$41)., Conclusion: BPSD contribute significantly to the overall costs of dementia care. Interventions targeted at BPSD may help to reduce the staggering societal costs of this illness., (Copyright (c) 2006 John Wiley & Sons, Ltd.)

Objective: To provide information on the use and outcomes of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus (RSV) infection., Design: Observational, prospective, longitudinal, multicenter study., Setting: Eighteen hospitals and pediatric clinics located in six provinces across Canada., Patients: Infants enrolled in the palivizumab Special Access Programme of Canada's Therapeutic Products Programme throughout the 1999 to 2000 RSV season. Most were premature infants born at < or = 32 weeks of gestation and/or had bronchopulmonary dysplasia., Methods and Main Outcome Measures: Neonatal and demographic data were recorded for each subject. The parent/caregiver was contacted on a monthly basis until the end of the RSV season to obtain information on palivizumab utilization and compliance as well as incidence and severity of respiratory infections., Results: There were 444 evaluable subjects who each received 1 to 7 injections of palivizumab for a total of 1702 doses from September 1999 to April 2000. Most subjects received 5 injections with high compliance. Prophylaxis was discontinued in 2% of children. There were 116 clinical events or hospitalizations involving respiratory tract infections reported in 91 children. Eighty-six of these were managed in an outpatient setting, and 30 required hospitalization. The estimated incidence of hospitalization for RSV-positive lower respiratory tract infections (LRTIs) was 2.4%. Hospitalization for RSV LRTI occurred more often in children with bronchopulmonary dysplasia (6.0%) than in those with prematurity only (1.6%)., Conclusions: This study demonstrates that prophylaxis with palivizumab during the RSV season was associated with a low rate of hospitalization for RSV-positive LRTIs. Palivizumab was well-tolerated, and compliance was high. The findings confirm the results of the major randomized clinical trial of palivizumab and demonstrate the safety and effectiveness of RSV prophylaxis.