Stroke clinical registries are critical for systems planning, quality improvement, advocacy and informing policy. We describe the methodology and evolution of the Registry of the Canadian Stroke Network/Ontario Stroke Registry in Canada.

At the launch of the registry in 2001, trained coordinators prospectively identified patients with acute stroke or transient ischemic attack (TIA) at comprehensive stroke centers across Canada and obtained consent for registry participation and follow-up interviews. From 2003 onward, patients were identified from administrative databases, and consent was waived for data collection on a sample of eligible patients across all hospitals in Ontario and in one site in Nova Scotia. In the most recent data collection cycle, consecutive eligible patients were included across Ontario, but patients with TIA and those seen in the emergency department without admission were excluded.

Between 2001 and 2013, the registry included 110,088 patients. Only 1,237 patients had follow-up interviews, but administrative data linkages allowed for indefinite follow-up of deaths and other measures of health services utilization. After a hiatus, the registry resumed data collection in 2019, with 13,828 charts abstracted to date with a focus on intracranial vascular imaging, identification of intracranial occlusions and treatment with thrombectomy.

The Registry of the Canadian Stroke Network/Ontario Stroke Registry is a large population-based clinical database that has evolved throughout the last two decades to meet contemporary stroke needs. Registry data have been used to monitor stroke quality of care and conduct outcomes research to inform policy.

Patients with major depressive disorder (MDD) commonly experience comorbid anxiety and somatization, which can complicate treatment. Adjunctive therapy with atypical antipsychotics can be an effective treatment option for patients with MDD who had inadequate responses to antidepressant therapy (ADT) alone. Cariprazine is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist that is approved as an adjunctive treatment for MDD. This post hoc analysis examined the effect of adjunctive cariprazine therapy on anxiety and somatization symptoms in patients with MDD.

A post hoc analysis was conducted using data from a phase 3, double-blind, placebo-controlled, fixed-dose study of patients with MDD who had inadequate responses to ADT alone. Patients were randomized (1:1:1) to receive ADT plus cariprazine 1.5 mg/d, 3 mg/d, or placebo for 6 weeks. The least squares (LS) mean change from baseline to week 6 in Hamilton Rating Scale for Depression (HAM-D) Anxiety/Somatization subscale was measured. The Anxiety/Somatization subscale includes six HAM-D items: anxiety-psychic, anxiety-somatic, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. The modified intent to treat population included 751 patients (placebo=249; cariprazine 1.5 mg/d=250; cariprazine 3 mg/d=252).

The LS mean change from baseline in HAM-D Anxiety/Somatization subscale at week 6 was significantly greater than placebo + ADT for both cariprazine + ADT dose groups (placebo: -3.22; cariprazine 1.5 mg/d: -4.00, P<.001; 3 mg/d: -3.75, P<.05). LS mean change from baseline in the cariprazine 1.5 mg/d + ADT group was also significantly greater than placebo + ADT on the anxiety-psychic (placebo: -0.88; cariprazine 1.5 mg/d: -1.08, P<.01) and anxiety-somatic (placebo: -0.78; cariprazine 1.5 mg/d: -0.96, P<.05) items. In patients treated with cariprazine 3 mg/d + ADT, LS mean changes from baseline on anxiety-psychic and anxiety-somatic items were numerically larger than placebo + ADT but not statistically significant. Both cariprazine + ADT dose groups had significantly larger LS mean changes compared with placebo + ADT on the gastrointestinal somatic symptoms item (placebo: -0.51; cariprazine 1.5 mg/d: -0.66, P<.01; cariprazine 3 mg/d: -0.68, P<.01). General somatic symptoms, hypochondriasis, and insight items showed no significant difference between placebo + ADT and cariprazine + ADT groups.

Patients treated with adjunctive cariprazine demonstrated greater improvements than patients treated with adjunctive placebo on HAM-D Anxiety/Somatization subscale scores, as shown by reduced scores on anxiety-psychic, anxiety-somatic, and gastrointestinal items. These findings suggest adjunctive cariprazine therapy may be effective in reducing anxiety and somatization symptoms in patients with MDD.

AbbVie

Study Registration Number: NCT03738215

Akathisia is a common adverse effect associated with use of dopamine receptor blocking agents.1,2 Symptoms of akathisia, in severe cases, may lead to discontinuation of treatment. Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist approved to treat schizophrenia and acute manic, mixed, and depressive episodes of bipolar 1 disorder. Cariprazine is well tolerated in patients across its indications, but is associated with a higher incidence of akathisia compared with placebo.3,4 This pooled post hoc analysis of data from phase 3 clinical trials of adjunctive cariprazine aimed to characterize the incidence, severity, and management of akathisia and other extrapyramidal symptoms (EPS) in adult patients with MDD.

Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to cariprazine 1.5 mg/d + ADT, cariprazine 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analysis evaluated incidence, severity, and time to resolution of akathisia, restlessness, and other EPS; use of rescue medications; and the rate of discontinuation due to these treatment-emergent adverse events (TEAEs).

A total of 1508 patients (cariprazine + ADT: 1.5 mg/d, n=502, 3 mg/d, n=503; placebo + ADT, n=503) were included in these 2 studies. The incidence of akathisia was greater with cariprazine 3 mg/d + ADT (9.7%) than with cariprazine 1.5 mg/d + ADT (6.4%) and placebo + ADT (2.0%). Most patients treated with cariprazine + ADT (94%) experienced only mild or moderate akathisia. The incidence of restlessness was 3.8% for patients treated with cariprazine 3 mg/d + ADT, 3.6% for cariprazine 1.5 mg/d + ADT, and 1.8% for placebo + ADT. The incidence of EPS excluding akathisia and restlessness was 4.4% for patients treated with cariprazine 3 mg/d + ADT, 4.6% for cariprazine 1.5 mg/d + ADT, and 3.2% for placebo + ADT. For patients treated with cariprazine + ADT and placebo + ADT, respectively, EPS-related study discontinuations were 1.4% and 0.4% due to akathisia, 0.2% and 0.0% due to restlessness, and 0.1% and 0.4% due to EPS excluding akathisia and restlessness. Rescue medications were used to treat EPS-related TEAEs during the double-blind treatment period in 3% of cariprazine-treated patients and 0.4% of placebo-treated patients. The mean time to resolution of akathisia during treatment was slightly shorter in cariprazine-treated patients (15.6 days) versus placebo-treated patients (19.5 days).

Incidence of akathisia was higher for cariprazine than placebo, with a lower incidence observed for patients treated with cariprazine 1.5 + ADT than with cariprazine 3 mg/d + ADT, suggestive of a dose related effect. Most patients experienced mild or moderate akathisia. Rates of study discontinuation and rescue medication use due to akathisia were low, suggesting that akathisia was tolerated by most patients.

This data was previously presented at the CINP World Congress; Montreal, Canada; May 7-10, 2023.

AbbVie

Anhedonia, a multidimensional domain including the reduced ability to experience pleasure, is a core diagnostic symptom of major depressive disorder (MDD) and a common residual symptom. In patients with MDD, anhedonia has been associated with poor treatment outcomes, suicide and reduced functioning and quality of life. This post-hoc analysis of data from a phase 3 trial (NCT03738215) evaluated the efficacy of adjunctive cariprazine (CAR) treatment on anhedonia symptoms in patients with MDD.

Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to CAR 1.5 mg/d + ADT, CAR 3 mg/d + ADT, or placebo + ADT for 6 weeks of double-blind treatment. Post hoc analyses evaluated the change from baseline to Week 6 in Montgomery–Åsberg Depression Rating Scale (MADRS) total score, MADRS anhedonia subscale score (items: 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]), and MADRS anhedonia item 8 in the overall modified intent-to-treat (mITT) population and in subgroups of patients with baseline MADRS anhedonia item 8 score of ≥4 or baseline anhedonia subscale score of ≥18. Least square (LS) mean change from baseline to Week 6 was analyzed using a mixed-effects model for repeated measures.

There were 751 patients in the mITT population (CAR + ADT: 1.5 mg/d=250, 3 mg/d=252; placebo + ADT=249). At baseline, 508 (67.6%) patients had MADRS anhedonia item 8 scores ≥4, and 584 (77.8%) had MADRS anhedonia subscale scores ≥18. In the overall mITT population, LS mean change from baseline to Week 6 in anhedonia subscale score was significantly greater for CAR 1.5 mg/d + ADT (-8.4) and CAR 3 mg/d + ADT (-7.9) than for placebo + ADT (-6.8; both P<.05). The LS mean change from baseline in MADRS individual item 8 was also significantly greater for CAR 1.5 mg/d + ADT (-1.7) vs placebo + ADT (-1.3; P=.0085). In both subgroups of patients with baseline anhedonia, CAR 1.5 mg/d + ADT was associated with significantly greater reduction in MADRS total score, MADRS anhedonia subscale score, and MADRS item 8 score compared with placebo + ADT (all P<.05). In the CAR 3 mg/d + ADT group, significantly greater reductions vs placebo + ADT were observed for MADRS total score and MADRS anhedonia subscale score in the subgroup of patients with baseline anhedonia subscale scores ≥18 (both P<.05).

Adjunctive treatment with CAR was associated with a reduction in symptoms of anhedonia relative to adjunctive placebo in patients with MDD and inadequate response to ADT alone. In subgroups of patients with moderate-to-severe anhedonia at baseline, CAR + ADT demonstrated greater improvements than placebo + ADT in overall depressive symptoms and symptoms of anhedonia. These results suggest that adjunctive CAR treatment may be effective for improving symptoms of anhedonia in patients with MDD who have symptoms of anhedonia.

AbbVie

The depression, obstructive sleep apnea and cognitive impairment (DOC) screen assesses three post-stroke comorbidities, but additional information may be gained from the time to complete the screen. Cognitive screening completion time is rarely used as an outcome measure.

To assess DOC screen completion time as a predictor of cognitive impairment in stroke/transient ischemic attack clinics.

Consecutive English-speaking stroke prevention clinic patients consented to undergo screening and neuropsychological testing (n = 437). DOC screen scores and times were compared to scores on the NINDS-CSC battery using multiple linear regression (controlling for age, sex, education and stroke severity) and receiver operating characteristic (ROC) curve analysis.

Completion time for the DOC screen was 3.8 ± 1.3 minutes. After accounting for covariates, the completion time was a significant predictor of the speed of processing (p = 0.002, 95% CI: −0.016 to −0.004), verbal fluency (p < 0.001, CI: −0.012 to −0.006) and executive function (p = 0.004, CI: −0.006 to −0.001), but not memory. Completion time above 5.5 minutes was associated with a high likelihood of impairment on executive and speed of processing tasks (likelihood ratios 3.9–5.2).

DOC screen completion time is easy to collect in routine care. People needing over 5.5 minutes to be screened likely have deficits in executive functioning and speed of processing – areas commonly impaired, but challenging to screen for, after stroke. DOC screen time provides a simple, feasible approach to assess these under-identified cognitive impairments.

We investigated trends in Staphylococcus aureus (staph) bacteremia incidence stratified by methicillin susceptibility (methicillin-susceptible S. aureus [MSSA] vs. methicillin-resistant S. aureus [MRSA]) and onset designation (community-onset [CO] vs. hospital-onset [HO]).

We evaluated the microbiological data among adult patients who were admitted to 267 acute-care hospitals during October 1, 2015, to February 28, 2020. Using a subset of data from 41 acute-care hospitals, we conducted a retrospective cohort study to assess patient demographics, characteristics, mortality, length of stay, and costs. We also conducted a case-control study between those with and without staph bacteremia.

The incidence of MSSA bacteremia significantly increased from 2.43 per 1,000 admissions to 2.87 per 1,000 admissions (estimate=0.0047, P-value=.0006). The incidence of MRSA significantly increased from 2.11 per 1,000 admissions to 2.42 per 1,000 admissions (estimate=0.0126, P-value <.0001). While the incidence of CO MSSA and CO MRSA demonstrated a significant increase (p=0.0023, and p < 0.0001), the incidence of HO MSSA and HO MRSA did not significantly change (p=0.2795 and p < 0.4464). Compared to those without staph bacteremia, mortality, length of stay, and total cost were significantly higher in those with staph bacteremia, regardless of methicillin susceptibility or onset designation.

The increasing incidence of CO MSSA and MRSA bacteremia might suggest the necessity for dedicated infection control measures and interventions for community members colonized with or at risk of acquiring Staphylococcus aureus.

Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).

Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).

Smoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).

Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada.

We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models’ discriminative values using Uno’s c-statistic, comparing models with versus without PaSSV.

We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable.

PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.