The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.

The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.

The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.

Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.

Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.

Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.

Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.

Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.

Maternal mental health during pregnancy and postpartum predicts later emotional and behavioural problems in children. Even though most perinatal mental health problems begin before pregnancy, the consequences of preconception maternal mental health for children's early emotional development have not been prospectively studied.

We used data from two prospective Australian intergenerational cohorts, with 756 women assessed repeatedly for mental health problems before pregnancy between age 13 and 29 years, and during pregnancy and at 1 year postpartum for 1231 subsequent pregnancies. Offspring infant emotional reactivity, an early indicator of differential sensitivity denoting increased risk of emotional problems under adversity, was assessed at 1 year postpartum.

Thirty-seven percent of infants born to mothers with persistent preconception mental health problems were categorised as high in emotional reactivity, compared to 23% born to mothers without preconception history (adjusted OR 2.1, 95% CI 1.4–3.1). Ante- and postnatal maternal depressive symptoms were similarly associated with infant emotional reactivity, but these perinatal associations reduced somewhat after adjustment for prior exposure. Causal mediation analysis further showed that 88% of the preconception risk was a direct effect, not mediated by perinatal exposure.

Maternal preconception mental health problems predict infant emotional reactivity, independently of maternal perinatal mental health; while associations between perinatal depressive symptoms and infant reactivity are partially explained by prior exposure. Findings suggest that processes shaping early vulnerability for later mental disorders arise well before conception. There is an emerging case for expanding developmental theories and trialling preventive interventions in the years before pregnancy.

Although cognitive-behavioural therapy (CBT) is an effective treatment for depression, less than half of patients achieve satisfactory symptom reduction during treatment. Targeting known psychopathological processes such as rumination may increase treatment efficacy. The aim of this study was to test whether adding group rumination-focused CBT (RFCBT) that explicitly targets rumination to routine medical management is superior to adding group CBT to routine medical management in treating major depression.

A total of 131 outpatients with major depression were randomly allocated to 12 sessions group RFCBT v. group CBT, each in addition to routine medical management. The primary outcome was observer-rated symptoms of depression at the end of treatment measured on the Hamilton Rating Scale for Depression. Secondary outcomes were rumination at post-treatment and depressive symptoms at 6 months follow-up (Trial registered: NCT02278224).

RFCBT significantly improved observer-rated depressive symptoms (Cohen's d 0.38; 95% CI 0.03–0.73) relative to group CBT at post-treatment on the primary outcome. No post-treatment differences were found in rumination or in depressive symptoms at 6 months follow-up, although these secondary analyses may have been underpowered.

This is the first randomized controlled trial providing evidence of benefits of RFCBT in major depression compared with CBT. Group RFCBT may be a beneficial alternative to group CBT for major depression.

To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.

To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.

Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.

Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.

To characterize the microbiology of hepatobiliary surgical site infections (SSIs) and to explore the relationship between specific antimicrobial prophylaxis regimens and the development of SSIs.

Retrospective matched case-control study comparing patient, procedure, and antimicrobial prophylaxis characteristics among patients undergoing a hepatobiliary surgical procedure with and without an SSI.

A tertiary referral acute-care facility.

Patients undergoing procedures defined as “BILI” (bile duct, liver, or pancreas surgery) using National Healthcare Safety Network (NHSN) definitions, excluding those undergoing concomitant liver transplantation, from January 2013 through June 2016 were included in the study population. The SSIs were identified through routine infection control surveillance using NHSN definitions. All patients who developed an SSI were considered cases. Controls were selected randomly matched 2:1 with cases based on fiscal quarter of the procedure. Logistic regression modeling was performed to explore variables associated with SSI, including antimicrobial prophylaxis received.

Among 975 procedures, 80 (8.2%) resulted in an SSI. Most cases involved an organism nonsusceptible to standard prophylaxis regimens, including cefazolin (68.8%), cefazolin plus metronidazole (61.3%), and ampicillin-sulbactam (52.5%). In a multivariate model, antimicrobial coverage against Enterococcus spp (aOR, 0.58; 95% confidence interval [CI], 0.17–2.04; P=.40) and against Pseudomonas spp (aOR, 2.40; 95% CI, 0.56–10.29; P=.24) were not protective against the development of an SSI. The presence of a documented β-lactam allergy was significantly associated with the development of an SSI (aOR, 3.54; 95% CI, 1.36–9.19; P=.009).

Although SSIs at the study institution were associated with pathogens nonsusceptible to the most commonly used prophylaxis regimens, broader-spectrum coverage was not associated with a reduction in SSIs.

Few studies have examined the challenges faced by emergency medicine (EM) physicians in conducting goals of care discussions. This study is the first to describe the perceived barriers and facilitators to these discussions as reported by Canadian EM physicians and residents.

A team of EM, palliative care, and internal medicine physicians developed a survey comprising multiple choice, Likert-scale and open-ended questions to explore four domains of goals-of-care discussions: training; communication; environment; and patient beliefs.

Surveys were sent to 273 EM staff and residents in six sites, and 130 (48%) responded. Staff physicians conducted goals-of-care discussions several times per month or more, 74.1% (80/108) of the time versus 35% (8/23) of residents. Most agreed that goals-of-care discussions are within their scope of practice (92%), they felt comfortable having these discussions (96%), and they are adequately trained (73%). However, 66% reported difficulty initiating goals-of-care discussions, and 54% believed that admitting services should conduct them. Main barriers were time (46%), lack of a relationship with the patient (25%), patient expectations (23%), no prior discussions (21%), and the inability to reach substitute decision-makers (17%). Fifty-four percent of respondents indicated that the availability of 24-hour palliative care consults would facilitate discussions in the emergency department (ED).

Important barriers to discussing goals of care in the ED were identified by respondents, including acuity and lack of prior relationship, highlighting the need for system and environmental interventions, including improved availability of palliative care services in the ED.

The application of digital monitoring biomarkers in health, wellness and disease management is reviewed. Harnessing the near limitless capacity of these approaches in the managed healthcare continuum will benefit from a systems-based architecture which presents data quality, quantity, and ease of capture within a decision-making dashboard.

A framework was developed which stratifies key components and advances the concept of contextualized biomarkers. The framework codifies how direct, indirect, composite, and contextualized composite data can drive innovation for the application of digital biomarkers in healthcare.

The de novo framework implies consideration of physiological, behavioral, and environmental factors in the context of biomarker capture and analysis. Application in disease and wellness is highlighted, and incorporation in clinical feedback loops and closed-loop systems is illustrated.

The study of contextualized biomarkers has the potential to offer rich and insightful data for clinical decision making. Moreover, advancement of the field will benefit from innovation at the intersection of medicine, engineering, and science. Technological developments in this dynamic field will thus fuel its logical evolution guided by inputs from patients, physicians, healthcare providers, end-payors, actuarists, medical device manufacturers, and drug companies.

Little is known about the joint mental health effects of air pollution and tobacco smoking in low- and middle-income countries.

To investigate the effects of exposure to ambient fine particulate matter pollution (PM2.5) and smoking and their combined (interactive) effects on depression.

Multilevel logistic regression analysis of baseline data of a prospective cohort study (n=41785). The 3-year average concentrations of PM2.5 were estimated using US National Aeronautics and Space Administration satellite data, and depression was diagnosed using a standardised questionnaire. Three-level logistic regression models were applied to examine the associations with depression.

The odds ratio (OR) for depression was 1.09 (95% CI 1.01–1.17) per 10 μg/m3 increase in ambient PM2.5, and the association remained after adjusting for potential confounding factors (adjusted OR = 1.10, 95% CI 1.02–1.19). Tobacco smoking (smoking status, frequency, duration and amount) was also significantly associated with depression. There appeared to be a synergistic interaction between ambient PM2.5 and smoking on depression in the additive model, but the interaction was not statistically significant in the multiplicative model.

Our study suggests that exposure to ambient PM2.5 may increase the risk of depression, and smoking may enhance this effect.

The impact of underlying parental psychological vulnerability on the future mental health of offspring is not fully understood. Using a prospective cohort design, we investigated the association between dysfunctional parental personality traits and risks of offspring self-harm, depression and anxiety.

The association between dysfunctional parental personality traits (monotony avoidance, impulsivity, anger, suspicion, and detachment), measured in both mothers and fathers when offspring were age 9 years, and risk of offspring depression, anxiety and self-harm at age 18 years, was investigated in a population-based cohort (ALSPAC) from over 8000 parents and children.

Higher levels of dysfunctional maternal, but not paternal, personality traits were associated with an increased risk of self-harm, depression, and anxiety in offspring. Maternal associations were best explained by the accumulation of dysfunctional traits. Associations were strongest for offspring depression: Offspring of mothers with three or more dysfunctional personality traits were 2.27 (1.45–3.54, p < 0.001) times as likely to be depressed, compared with offspring of mothers with no dysfunctional personality traits, independently of maternal depression and other variables.

The accumulation of dysfunctional maternal personality traits is associated with the risk of self-harm, depression, anxiety in offspring independently of maternal depression and other confounding variables. The absence of associations for equivalent paternal traits makes a genetic explanation for the findings unlikely. Further research is required to elucidate the underlying mechanism. Mothers with high levels of dysfunctional personality traits may benefit from additional support to reduce the risk of adverse psychological outcomes occurring in their offspring.