Lesley Graff - Academia.edu (original) (raw)

Papers by Lesley Graff

Frontiers in Neurology, May 24, 2022

Objective: Vascular comorbidities are associated with reduced cognitive performance and with chan... more Objective: Vascular comorbidities are associated with reduced cognitive performance and with changes in brain structure in people with multiple sclerosis (MS). Understanding causal pathways is necessary to support the design of interventions to mitigate the impacts of comorbidities, and to monitor their effectiveness. We assessed the interrelationships among vascular comorbidity, cognition and brain structure in people with MS. Methods: Adults with neurologist-confirmed MS reported comorbidities, and underwent assessment of their blood pressure, HbA1c, and cognitive functioning (i.e., Symbol Digit Modalities Test, California Verbal Learning Test, Brief Visuospatial Memory Test-Revised, and verbal fluency). Test scores were converted to age-, sex-, and education-adjusted z-scores. Whole brain magnetic resonance imaging (MRI) was completed, from which measures of thalamic and hippocampal volumes, and mean diffusivity of gray matter and normal-appearing white matter were converted to age and sex-adjusted z-scores. Canonical correlation analysis was used to identify linear combinations of cognitive measures (cognitive variate) and MRI measures (MRI variate) that accounted for the most correlation between the cognitive and MRI measures. Regression analyses were used to test whether MRI measures mediated the relationships between the number of vascular comorbidities and cognition measures. Results: Of 105 participants, most were women (84.8%) with a mean (SD) age of 51.8 (12.8) years and age of symptom onset of 29.4 (10.5) years. Vascular comorbidity Marrie et al. Comorbidity Cognition and MRI was common, with 35.2% of participants reporting one, 15.2% reporting two, and 8.6% reporting three or more. Canonical correlation analysis of the cognitive and MRI variables identified one pair of variates (Pillai's trace = 0.45, p = 0.0035). The biggest contributors to the cognitive variate were the SDMT and CVLT-II, and to the MRI variate were gray matter MD and thalamic volume. The correlation between cognitive and MRI variates was 0.50; these variates were used in regression analyses. On regression analysis, vascular comorbidity was associated with the MRI variate, and with the cognitive variate. After adjusting for the MRI variate, vascular comorbidity was not associated with the cognitive variate. Conclusion: Vascular comorbidity is associated with lower cognitive function in people with MS and this association is partially mediated via changes in brain macrostructure and microstructure.

Alimentary Pharmacology & Therapeutics, Sep 27, 2020

AC is the CEO and shareholder of Biomedal S.L. He is also partner of Glutenostics LLC. Biomedal w... more AC is the CEO and shareholder of Biomedal S.L. He is also partner of Glutenostics LLC. Biomedal was the licensor of G12/A1 monoclonal antibodies for detection in food, urine and stool at the time of the study. DRD has received research funding from Biomedal S.L. and has served as a consultant for Takeda Pharmaceuticals and Shire Canada and is Chair of the Professional Advisory Council of the Canadian Celiac Association. RD was an employee of Biomedal S.L. at the time of the study. CPK has acted as a scientific advisor to Cour Pharma, Glutenostics, Innovate, ImmunogenX, Innovate and Takeda. He also acts as Principal Investigator on a research grant on coeliac disease supported by Aptalis. DAL is a Medical Director for Takeda Pharmaceuticals. FL was an employee of Celimmune at the time of the study, and is currently an employee of Provention Bio. He also serves as a partner in Biomedal and Glutenostics. JAS has served on an advisory board of Takeda Pharmaceuticals and received research support from Cour Pharma, Glutenostics and the Celiac Disease Foundation. IC, KHG, LAG, LNR, CS, VS and DW have no disclosures.

International journal of MS care, Nov 1, 2016

; for the CIHR Team "Defining the Burden and Managing the Effects of Psychiatric Comorbidity in C... more ; for the CIHR Team "Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease" Background: Anxiety is prevalent in people with multiple sclerosis (MS). Screening measures are used to identify symptoms of anxiety, but the optimal measure to screen for anxiety disorders in MS has not been established. Methods: We searched the MEDLINE, Embase, PsycINFO, PsycARTICLES Full Text, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Scopus databases from database inception until August 7, 2015. Two independent reviewers screened abstracts and full-text reports for study inclusion, extracted data, and assessed risk of bias. We included studies that evaluated the criterion validity of anxiety screening tools when measuring anxiety in individuals with well-documented MS, as measured by sensitivity, specificity, and positive and negative predictive values. Results: Of the 3181 abstracts screened, 18 articles were reviewed in full text, of which 4 met the inclusion criteria. The criterion validity of three screening tools was assessed: the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), Beck Anxiety Inventory (BAI), and 7-item Generalized Anxiety Disorder Scale (GAD-7). The HADS-A was validated against the Structured Clinical Interview for DSM-IV, the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) interview, and the BAI. The BAI was validated against the SCAN, and the GAD-7 was validated against the HADS-A. The HADS-A had higher measures of sensitivity and specificity than did the BAI and the GAD-7. Conclusions: Based on this small sample, the HADS-A shows promise as an applicable measure for people with MS. Screening scales used to identify anxiety in MS must be validated against appropriate reference standards.

Jcr-journal of Clinical Rheumatology, Dec 1, 2017

and for the CIHR Team "Defining the Burden and Managing the Effects of Psychiatric Comorbidity in... more and for the CIHR Team "Defining the Burden and Managing the Effects of Psychiatric Comorbidity in Chronic Immunoinflammatory Disease" Background: Psychiatric comorbidities, such as depression and anxiety, are very common in persons with rheumatoid arthritis (RA) and can lead to adverse outcomes. By appropriately treating these comorbidities, diseasespecific outcomes and quality of life may be improved. Objective: The aim of this study was to systematically review the literature from controlled trials of treatments for depression and anxiety in persons with RA. Methods: We searched multiple online databases from inception until March 25, 2015, without restrictions on language, date, or location of publication. We included controlled trials conducted in persons with RA and depression or anxiety. Two independent reviewers extracted information including trial and participant characteristics. The standardized mean differences (SMDs) of depression or anxiety scores at postassessment were pooled between treatment and comparison groups, stratified by active versus inactive comparators. Results: From 1291 unique abstracts, we included 8 RA trials of depression interventions (6 pharmacological, 1 psychological, 1 both). Pharmacological interventions for depression with inactive comparators (n = 3 trials, 143 participants) did not reduce depressive symptoms (SMD, −0.21; 95% confidence interval [CI], −1.27 to 0.85), although interventions with active comparators (n = 3 trials, 190 participants) did improve depressive symptoms (SMD, −0.79; 95% CI, −1.34 to −0.25). The single psychological trial of depression treatment in RA did not improve depressive symptoms (SMD, −0.44; 95% CI, −0.96 to 0.08). Seven of the trials had an unclear risk of bias. Conclusions: Few trials examining interventions for depression or anxiety in adults with RA exist, and the level of evidence is low to moderate because of the risk of bias and small number of trials.

Journal of the Canadian Association of Gastroenterology

Background The Inflammatory Bowel Disease Symptom Inventory (IBDSI) is a validated patient self-r... more Background The Inflammatory Bowel Disease Symptom Inventory (IBDSI) is a validated patient self-reported measure used to assess IBD disease activity. Purpose We aimed to assess the prevalence of symptoms, and examine which symptoms are most associated with disease activity as measured by a symptom index and objective measure of inflammation. Method The Manitoba Living with IBD Study is a prospective study of 156 participants with confirmed IBD who completed bi-weekly Inflammatory Bowel Disease Symptom Inventory (IBDSI) surveys. Relative risks (RR) (with 95% confidence interval (CI)), positive and negative predictive values (PPV, NPV), and area under receiver operator curve (AUC) were reported for each symptom to predict active disease defined as: (1) active IBDSI, (2) self-reported flare, and (3) elevated fecal calprotectin (FCAL) (>250µg/g). Analyses were undertaken following stratification based on sex, and disease type (Crohn’s disease (CD) and ulcerative colitis (UC)). Result...

Multiple Sclerosis and Related Disorders, 2018

a,h, ⁎ , for the CIHR team "Defining the burden and managing the effects of psychiatric comorbidi... more a,h, ⁎ , for the CIHR team "Defining the burden and managing the effects of psychiatric comorbidity in chronic inflammatory disease"

The American Journal of Gastroenterology, May 19, 2009

Background: A single-item indicator of disease activity over an extended time, the Manitoba IBD I... more Background: A single-item indicator of disease activity over an extended time, the Manitoba IBD Index (MIBDI) is proposed, and compared against several standard measures for assessing activity in patients with Crohn's disease (CD) and ulcerative colitis (UC). Methods: Participants enrolled in the Manitoba IBD Cohort Study, a population based longitudinal cohort (n=353) were assessed semi-annually by survey, clinical interview, and blood sample across a two-year period. The MIBDI is based on patient self-report of symptom persistence for the previous 6 months, using a 6-level response format. Results: The MIBDI had good sensitivity compared to the Harvey-Bradshaw (HB; 0.88), Powell-Tuck (PT; 0.84) and Inflammatory Bowel Disease Questionnaire (IBDQ; 0.89), which was maintained at two subsequent annual measurements. Test-retest reliability was also strong (Spearman r = 0.81). Discriminant function analyses identified common discriminating variables of active disease for CD and UC that included HB, PT, IBDQ subscales of bowel and systemic symptoms, prolonged symptom severity (e.g., abdominal and joint pain, tiredness, diarrhea), and recent persistent pain related to IBD. Unique discriminators included weight problems (CD) and blood in stool (UC). Conclusions: A singleitem patient-defined disease activity measure, the MIBDI, showed a high degree of sensitivity for classifying individuals with regard to disease status over time compared to existing disease activity measures, and strong convergent validity with expected proxy measures of disease. These relationships remained consistent over time. Thus, the MIBDI shows promise as a valid brief tool for measuring disease activity over an extended period.

Calcified Tissue International, Sep 16, 2012

Background: Persons with inflammatory bowel disease (IBD) are reported to have a high prevalence ... more Background: Persons with inflammatory bowel disease (IBD) are reported to have a high prevalence of osteoporosis and reduced bone mineral density (BMD), and are at higher risk of fracture. The course of BMD loss over time is poorly characterized in persons with IBD Methods: 86 persons, stratified by age, were enrolled from a population based longitudinal IBD cohort study to undergo BMD testing at baseline, with final BMD testing mean 4.3 years later. The proportion of subjects with significant change in BMD at the lumbar spine, total hip, and femoral neck was assessed, as were clinical, biochemical, and anthropomorphic changes. Vertebral radiographs were also obtained at baseline and at end of follow-up in those age 50 years and older to detect vertebral fractures. Results: The change in BMD seen in this cohort of IBD patients was similar to the expected rate of BMD loss in the general population. Age >50 years, decreasing BMI and corticosteroid use were most notably correlated with BMD loss. Subjects age <50 years did not have statistically significant declines in BMD. IBD symptom activity scores correlated poorly with BMD loss. Vertebral fractures were uncommon, with only two subjects out of 41 over age 50 years developing a definite radiographic fracture over the course of follow-up. No major nonvertebral fractures were observed. Conclusion: Patients with IBD do not appear to have significantly accelerated BMD loss. Older age, decreasing BMI and corticosteroid use may identify IBD patients at greater risk for BMD loss.

Gut, Aug 11, 2011

Background: We aimed to determine the prevalence of complementary and alternative medicine (CAM) ... more Background: We aimed to determine the prevalence of complementary and alternative medicine (CAM) use over time in a population-based cohort of IBD patients. Methods: The Manitoba IBD Cohort Study is a longitudinal, population-based study of multiple determinants of health outcomes in persons with IBD. Participants completed semi-annual surveys, and annual in-person interviews. Inquiries about use of 12 types of CAM service providers and 13 CAM products, based on items from a national survey, were included at month 0, 12, 30 and 54. Results: Overall, 74% of respondents used a CAM service or product in the 4.5 year period, with approximately 40% using some type of CAM at each time point, and 14% using CAM consistently at every time point. There was a trend for females to use CAM more than males; there was no difference in CAM use between Crohn's disease and UC groups. The most often used CAM services (on average) were massage therapy (29.8%) and chiropractic (13.6%), physiotherapy (3.7%), acupuncture (3.5%) and Naturopath /Homeopath (3.5%). There was a wide range of CAM products used, with Lactobacillus/acidophilus (7.6%), fish and other oils (5.5%), glucosamine (3.7%) and chamomile (3.5%) as the most common. On average only 18% of consumers used CAM for their IBD, so the majority chose it for other issues. There were no differences between CAM users and non-users on psychological variables. Conclusions: Those with IBD commonly try CAM, although very few use these approaches regularly over years. CAM is not usually used by IBD patients for disease management, but clinicians should be aware that many will trial the services and products.

Alimentary Pharmacology & Therapeutics, Jun 3, 2013

Background: Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating... more Background: Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating behaviour, and surgery have largely been derived from referral center populations. We investigate whether serological markers, susceptibility genes, or psychological characteristics are associated with complicated CD or surgery in a population-based cohort. Methods: 182 members of the Manitoba IBD Cohort with CD phenotyped using the Montreal classification underwent genetic and serologic analysis at enrolment and after 5 years. 127 had paired sera at baseline and 5 years later and their data were used to predict outcomes at a median of 9.3 years.. Serologic analysis consisted of a seven antibody panel, and DNA was tested for CD-associated NOD2 variants (rs2066845,rs2076756,rs2066847), ATG16L1 (rs3828309, rs2241880) and IL23R (rs11465804). Psychological characteristics were assessed using semistructured interviews and validated survey measures. Results: 65% had complicated CD and 42% underwent surgery. Multivariate analysis indicated that only ASCA IgG positive serology was predictive of stricturing/penetrating behavior (OR=3.01; 95%CI:1.28-7.09; p=0.01) and ileal CD (OR=2.2; 95%CI:1.07-4.54, p=0.03). Complicated CD behavior was strongly associated with surgery (OR=5.6; 95%CI:2.43-12.91; p<0.0001) while in multivariate analysis, only ASCA IgG was associated (OR=2.66; 95% CI, 1.40-5.06, p=0.003). ASCA titre results were similar at baseline and follow-up. Psychological characteristics were not significantly associated with disease behavior, serologic profile, or genotype. Ryan et al 3 Conclusions: ASCA IgG at baseline was significantly associated with stricturing/penetrating disease at 9 to 10 years from diagnosis. Stricturing/penetrating disease was significantly associated with surgery. In a model including serology, the genotypes assessed did not significantly associate with complicated disease or surgery.

The Canadian journal of gastroenterology, 2012

O ptimal management of chronic disease involves a partnership between the patient and physician. ... more O ptimal management of chronic disease involves a partnership between the patient and physician. This relationship aims to facilitate the involvement of the patient in their own care. Good collaboration is associated with better treatment adherence and improved general health (1,2). An important aspect of this partnership is the exchange of information concerning the disease and its management (3). Studies of the information preferences and needs of patients have generally found that patients receive less information than they prefer

Inflammatory Bowel Diseases, Aug 1, 2017

Background: People with inflammatory bowel disease (IBD) require disease and lifestyle informatio... more Background: People with inflammatory bowel disease (IBD) require disease and lifestyle information to make health-related decisions in their daily lives. Derived from a larger qualitative study of the lived experiences of people with IBD, we report on findings that explored how people with IBD engage with health-related information in their daily lives. Methods: Participants were recruited primarily from the Manitoba IBD Cohort Study. We used purposive sampling to select people with a breadth of characteristics and experiences. Individual interviews were audio-recorded and transcribed verbatim. Data were analyzed using inductive qualitative methods consistent with a phenomenological approach. Results: Forty-five people with IBD participated; 51% were female. Findings highlighted the temporal and contextual influences on engagement with health-related information. Temporal influences were described as the changing need for health-related information over time. Participants identified six contextual factors influencing engagement with information to make health decisions: (1) emotional and attitudinal responses, (2) perceived benefits and risks, (3) trust in the source of the information, (4) knowledge and skills to access and use information, (5) availability of evidence to support decisions, and (6) social and economic environments. Conclusions: Findings illustrate the changing needs for health-related information over the course of IBD, and with evolving health and life circumstances. Practitioners can be responsive to information needs of people with IBD by having high quality information available at the right time in a variety of formats and by supporting the incorporation of information in daily life.

Journal of Psychosomatic Research, Oct 1, 2016

Objectives: Comorbid depression and anxiety are common in inflammatory bowel disease (IBD), but f... more Objectives: Comorbid depression and anxiety are common in inflammatory bowel disease (IBD), but few population-based estimates of the burden of depression and anxiety exist. Methods to support population-based studies are needed. We aimed to test the performance of administrative case definitions for depression and anxiety in IBD and to understand what the prevalence estimated using such definitions reflects. Methods: We linked administrative (health claims) data from the province of Manitoba, Canada with clinical data for 266 persons in the Manitoba IBD Cohort Study. We compared the performance of administrative case definitions for depression and anxiety with (a) diagnoses of depression and anxiety as identified based on the Composite International Diagnostic Interview (CIDI), which identifies disorders meeting formal diagnostic criteria, and (b) participant report of physician-diagnosed depression or anxiety. Results: Administrative definitions for depression showed moderate agreement with the CIDI (κ = 0.39-0.42). Agreement was higher with participant report of physician-diagnosed depression (κ = 0.54). The lifetime prevalence of depression was 29.3% based on the CIDI, 17.7% based on participant report of physician-diagnosed depression, and 21.8-22.5% based on administrative data. Compared to the CIDI, administrative definitions for anxiety showed fair agreement (κ = 0.21-0.25). The lifetime prevalence of anxiety was 31.2% based on the CIDI, 9.7% based on participant report of physiciandiagnosed anxiety, and 24.4-31.9% based on administrative data. Conclusions: Administrative data may be used for population-level surveillance of depression and anxiety in IBD, although they will not capture undiagnosed or untreated cases.

Gastroenterology, May 1, 2013

co-morbidity. The majority of IBD patients with pain did not demonstrate biochemical evidence of ... more co-morbidity. The majority of IBD patients with pain did not demonstrate biochemical evidence of inflammation suggesting additional mechanisms underlie these symptoms.

Neurogastroenterology and Motility, Jun 18, 2021

Background: The mental health response to the coronavirus (COVID-19) pandemicrelated product shor... more Background: The mental health response to the coronavirus (COVID-19) pandemicrelated product shortages in those living with chronic gastrointestinal (GI) disorders has received little attention. We aimed to explore the association between the pandemic-related product shortages and psychological distress in people with GI disorders. Methods: This online cross-sectional survey was nested within an ongoing, international, prospective study of well-being in people with GI disorders. The study was advertised in multiple countries in May-September 2020 via patient organizations and social media. The primary outcome measure was distress, evaluated by the Depression Anxiety Stress Scale. We utilized linear regressions, adjusting for covariates and testing individual moderation effects.

American Journal of Gastroenterology

INTRODUCTION: We estimated the incidence and prevalence of benzodiazepine and Z-drug (separately ... more INTRODUCTION: We estimated the incidence and prevalence of benzodiazepine and Z-drug (separately and jointly as BZD) use in the inflammatory bowel disease (IBD) population compared with matched controls without IBD and examined the association of mood/anxiety disorders (M/ADs) with the use of BZD from 1997 to 2017. METHODS: Using administrative data from Manitoba, Canada, we identified 5,741 persons with incident IBD who were matched in a 1:5 ratio to controls on sex, birth year, and region. Validated case definitions were used to identify M/AD. Dispensations of BZD were identified. Multivariable generalized linear models were used to assess the association between IBD, M/AD, and BZD use. RESULTS: In 2016, the incident age/sex-standardized benzodiazepine use rates per 1,000 were 28.06 (95% confidence interval [CI] 26.41–29.81) in the IBD cohort and 16.83 (95% CI 16.28–17.39) in controls (adjusted rate ratio = 1.69 [95% CI 1.56–1.79]). Benzodiazepine incidence rates were higher for w...

Journal of Psychosomatic Research

Journal of Psychosomatic Research, 2022

OBJECTIVE Positive and negative psychological attributes have been shown to influence disease out... more OBJECTIVE Positive and negative psychological attributes have been shown to influence disease outcomes in many chronic health conditions. We aimed to evaluate the association between self-efficacy, optimism, health anxiety and intolerance of uncertainty and disease activity in inflammatory bowel disease (IBD). METHODS Adults with confirmed and recently active IBD enrolled in a prospective cohort study. Demographics, disease information, validated measures of psychological functioning related to general self-efficacy, optimism, health anxiety and intolerance of uncertainty were collected at baseline, week 26 and week 52. Clinical disease activity was assessed using the Inflammatory Bowel Disease Symptom Inventory (IBDSI), self-reported flares, and intestinal inflammation using fecal calprotectin (FCAL), collected at baseline, weeks 26 and 52. Generalized estimating equations were used to test the association between psychological functioning and disease activity. RESULTS Participants' (n = 154) mean age was 43.4 years (SD 12.5), 69.5% were women and 64.1% had Crohn's disease. Adjusting for demographic variables, higher self-efficacy was associated with lower likelihood of flare by self-report (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.71, 0.91) and IBDSI (OR 0.89, 95% CI 0.80, 0.99), while higher health anxiety was associated with greater likelihood of flare by self-report (OR 1.07, 95% CI 1.01, 1.18) and higher symptomatic disease activity (IBDSI; OR 1.14, 95% CI 1.05, 1.24). The psychological attributes were not significantly associated with active disease as measured by inflammation (FCAL). CONCLUSION General self-efficacy and health anxiety are relevant in understanding patient experience with disease activity, and may be appropriate targets for psychological intervention in the care of individuals with IBD.

Inflammatory Bowel Diseases, 2021

BackgroundFlare is a poorly defined term used by patients and clinicians to indicate inflammatory... more BackgroundFlare is a poorly defined term used by patients and clinicians to indicate inflammatory bowel disease (IBD) status. This study aimed to evaluate the validity of a single-item 7-point flare indicator relative to other measures of disease flare.MethodsThe longitudinal Manitoba Living with IBD Study followed persons with IBD for 1 year; they completed biweekly online surveys and provided 3 stool samples. Disease flare on a single-item flare indicator with 7 possible responses developed for the study was defined by report of symptoms as “moderately” or “much” worse. The flare indicator was evaluated against 5 measures of disease activity: fecal calprotectin score (FCAL), a 2-point disease status indicator, a 4-point flare certainty indicator, the IBD Symptom Index short form (SIBDSI), and the short form IBD Questionnaire (SIBDQ). Participants in a flare, based on the 7-point measure, were matched to a nonflaring participant, and a stool sample was collected.ResultsOf the 155 I...