Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them.

Anticonvulsant and gabapentinoids pharmacotherapy in the multiple sclerosis prodrome: A population-based matched cohort study.

Background: Before disease onset, multiple sclerosis (MS) persons fill more prescriptions than controls, including for pain. However, knowledge regarding neuropathic pain-related medications is lacking OBJECTIVE: Compare odds of anticonvulsant/gabapentinoid prescriptions for 4,862 MS-cases versus 22,669 controls, pre-MS onset (defined as first demyelinating disease-related event).

Methods: Matched-cohort study using administrative data (1996-2013), comparing the odds of anticonvulsant/gabapentinoid prescriptions pre-MS onset using multivariable logistic regression.

Psychiatric Comorbidity Does Not Enhance Prescription Opioid Use in Inflammatory Bowel Disease as It Does in the General Population.

Introduction: Little is known about patterns of opioid prescribing in inflammatory bowel disease (IBD), but pain is common in persons with IBD. We estimated the incidence and prevalence of opioid use in adults with IBD and an unaffected reference cohort and assessed factors that modified opioid use.

Methods: Using population-based health administrative data from Manitoba, Canada, we identified 5233 persons with incident IBD and 26 150 persons without IBD matched 5:1 on sex, birth year, and region from 1997 to 2016.

Precise in vivo RNA base editing with a wobble-enhanced circular CLUSTER guide RNA.

Recruiting the endogenous editing enzyme adenosine deaminase acting on RNA (ADAR) with tailored guide RNAs for adenosine-to-inosine (A-to-I) RNA base editing is promising for safely manipulating genetic information at the RNA level. However, the precision and efficiency of editing are often compromised by bystander off-target editing. Here, we find that in 5'-UAN triplets, which dominate bystander editing, G•U wobble base pairs effectively mitigate off-target events while maintaining high on-target efficiency.

Codon decoding by orthogonal tRNAs interrogates the preferences of unmodified adenosine in the wobble position.

The codon decoding preferences of tRNAs with an authentic adenosine residue at position 34 of the anticodon, the wobble position, are largely unexplored because very few unmodified A34 tRNA genes exist across the three domains of life. The expanded wobble rules suggest that unmodified adenosine pairs most strongly with uracil, modestly with cytosine, and weakly with guanosine and adenosine. Inosine, a modified adenosine, on the other hand, pairs strongly with both uracil and cytosine and to a lesser extent adenosine.

Parent implementation of a treatment for late talkers based on cross-situational statistical learning principles: Treatment fidelity and acceptability.

Purpose: Early intervention based on principles of cross-situational statistical learning (CSSL) for late-talking children has shown promise. This study explored whether parents could be trained to deliver this intervention protocol with fidelity and if they found the intervention to be acceptable.

Method: Mothers of four English-speaking children aged 18-30 months who scored <10th centile for expressive vocabulary were recruited to an 8-week group training program.

Disease-modifying drugs, multiple sclerosis and infection-related healthcare use in British Columbia, Canada: a population-based study.

Background: Much remains unknown surrounding the disease-modifying drugs (DMDs) used to treat multiple sclerosis and infection-related healthcare use in the 'real-world' setting. We examined if DMD exposure was associated with altered infection-related healthcare use.

Methods: We assessed if DMD (versus no) exposure was associated with altered infection-related hospitalizations, physician claims, and prescriptions filled in British Columbia, Canada (1996-2017).

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis: A Multiregional Population-Based Study.

Background And Objectives: It is not possible to fully establish the safety of a disease-modifying drug (DMD) for multiple sclerosis (MS) from randomized controlled trials as only very common adverse events occurring over the short-term can be captured, and the quality of reporting has been variable. We examined the relationship between the DMDs for MS and potential adverse events in a multiregion population-based study.

Methods: We identified people with MS using linked administrative health data from 4 Canadian provinces.

Gastrointestinal conditions in the multiple sclerosis prodrome.

Objective: To investigate gastrointestinal (GI)-related physician visits and drug dispensations in the 5 years preceding a first recorded demyelinating event or multiple sclerosis (MS) onset.

Methods: Using linked administrative and clinical data from British Columbia (1996-2013), Canada, we identified an administrative cohort via a validated algorithm (n = 6863), a clinical cohort diagnosed at a MS clinic (n = 966), and matched controls (administrative cohort: n = 31,865; clinical cohort: n = 4534). In each cohort, the 5 years before a first demyelinating event or MS symptom onset (i.

Understanding Predictors of Fatigue Over Time in Persons With Inflammatory Bowel Disease: The Importance of Depressive and Anxiety Symptoms.

Introduction: Fatigue is a complex and frequent symptom in persons with inflammatory bowel disease (IBD), with detrimental impact. We aimed to determine predictors of fatigue over time.

Methods: Two hundred forty-seven adults with IBD participated in a prospective study conducted in Manitoba, Canada, providing data at baseline and annually for 3 years.

Sex differences evident in elevated anxiety symptoms in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis.

Introduction: Immune-mediated inflammatory diseases (IMID), such as multiple sclerosis (MS), inflammatory bowel disease (IBD) or rheumatoid arthritis (RA) have high rates of elevated anxiety symptoms. This can may worsen functioning and increase IMID disease burden. The rate of and factors associated with elevated anxiety symptoms may differ between males and females, which, in turn can affect diagnosis and disease management.

Differences in resting state functional connectivity relative to multiple sclerosis and impaired information processing speed.

Background: Fifty-one percent of individuals with multiple sclerosis (MS) develop cognitive impairment (CI) in information processing speed (IPS). Although IPS scores are associated with health and well-being, neural changes that underlie IPS impairments in MS are not understood. Resting state fMRI can provide insight into brain function changes underlying impairment in persons with MS.

Altered voxel-based and surface-based morphometry in inflammatory bowel disease.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by inflammation of the gastrointestinal tract and is a disorder of the brain-gut axis. Neuroimaging studies of brain function and structure have helped better understand the relationships between the brain, gut, and comorbidity in IBD. Studies of brain structure have primarily employed voxel-based morphometry to measure grey matter volume and surface-based morphometry to measure cortical thickness.

Psychiatric Comorbidity During the Prodromal Period in Patients With Multiple Sclerosis.

Background And Objectives: Psychiatric morbidity is common after a multiple sclerosis (MS) diagnosis. However, little is known about psychiatric comorbidity during the prodromal phase (before MS onset). To compare the prevalence and relative burden of psychiatric morbidity in individuals with MS with matched controls before MS onset.

Vascular Disease Is Associated With Differences in Brain Structure and Lower Cognitive Functioning in Inflammatory Bowel Disease: A Cross-Sectional Study.

Background: Vascular disease and cognitive impairment have been increasingly documented in inflammatory bowel disease (IBD), and both have been individually correlated with changes in brain structure. This study aimed to determine if both macro- and microstructural brain changes are prevalent in IBD and whether alterations in brain structure mediate the relationship between vascular disease and cognitive functioning.

Methods: Eighty-four IBD participants underwent multimodal magnetic resonance imaging.

Perceived Need for Mental Health Care in a Cohort of Persons With Inflammatory Bowel Disease.

Background: Psychiatric comorbidity is common in inflammatory bowel disease (IBD) and can negatively affect disease outcomes. We explored the perceived need for mental health care among persons with IBD.

Study: Persons with IBD completed self-report questionnaires, including the Hospital Anxiety and Depression Scale (HADS), and reported whether they wanted help with their mood.

A longitudinal study of distress symptoms and work impairment in immune-mediated inflammatory diseases.

Objective: We investigated the association between distress symptoms (pain, fatigue, depression, anxiety) and work impairment in four patient populations: multiple sclerosis (N = 107), rheumatoid arthritis (N = 40), inflammatory bowel disease (N = 136) and psychiatric disorders (N = 167).

Methods: Four waves of data collection were completed over three years. The relationship between distress symptoms and overall work impairment was evaluated with univariate and multivariable quantile logistic regression at the 25th, 50th and 75th percentiles.

The comorbidity and cognition in multiple sclerosis (CCOMS) neuroimaging protocol: Study rationale, MRI acquisition, and minimal image processing pipelines.

The Comorbidity and Cognition in Multiple Sclerosis (CCOMS) study represents a coordinated effort by a team of clinicians, neuropsychologists, and neuroimaging experts to investigate the neural basis of cognitive changes and their association with comorbidities among persons with multiple sclerosis (MS). The objectives are to determine the relationships among psychiatric (e.g.

Within-person fluctuations over three years in depression, anxiety, fatigue, and health-related quality of life in multiple sclerosis.

Background: Longitudinal studies of health-related quality of life (HRQoL) in multiple sclerosis (MS) are limited. Most have examined average changes within the population, rather than dynamic changes within individuals.

Objective: To assess the between- and within-individual association between depression, anxiety, fatigue, cognition, physical functioning, and physical comorbidities and HRQoL.

Pain and participation in social activities in people with relapsing remitting and progressive multiple sclerosis.

Background: Differences in pain between subtypes of multiple sclerosis are understudied.

Objective: To compare the prevalence of pain, and the association between pain and: (a) pain interference and (b) social participation in people with relapsing-remitting multiple sclerosis and progressive multiple sclerosis.

Methods: Participants completed the McGill Pain Questionnaire Short-Form-2, Pain Effects Scale and Ability to Participate in Social Roles and Activities-V2.

Assessment of differential item functioning of the PHQ-9, HADS-D and PROMIS-depression scales in persons with and without multiple sclerosis.

Objective: We tested for the presence of differential item functioning (DIF) in commonly used measures of depressive symptoms, in people with multiple sclerosis (MS) versus people with a psychiatric disorder without MS.

Methods: Participants included individuals with MS, or with a lifetime history of a depressive or anxiety disorder (Dep/Anx) but no immune-mediated inflammatory disease. Participants completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), and the Patient Reported Outcome Measurement Information System (PROMIS)-Depression.

Etiology, effects and management of comorbidities in multiple sclerosis: recent advances.

Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that people with MS have an increased incidence of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and psychiatric disorders as compared to people without MS. People with MS from underrepresented minority and immigrant groups have higher comorbidity burdens.

Well-being and flourishing mental health in adults with inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis in Manitoba, Canada: a cross-sectional study.

Objectives: Among people with immune-mediated inflammatory disease (IMID), including multiple sclerosis (MS), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) most research has focused on mental illness rather than on mental health. We assessed dimensions of mental health among persons with IMID and compared them across IMID. We also evaluated demographic and clinical characteristics associated with flourishing mental health.