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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. New and prevalent opioid prescription dispensations were quantified, and patterns related to duration of use were identified. Generalized linear models were used to test the association between IBD, psychiatric comorbidity, and opioid use adjusting for sociodemographic characteristics, physical comorbidities, and healthcare use., Results: Opioids were dispensed to 27% of persons with IBD and to 12.9% of the unaffected reference cohort. The unadjusted crude incidence per 1000 person-years of opioid use was nearly twice as high for the IBD cohort (88.63; 95% CI, 82.73-91.99) vs the reference cohort (45.02; 95% CI, 43.49-45.82; relative risk 1.97; 95% CI, 1.86-2.08). The incidence rate per 1000 person-years was highest in those 18-44 years at diagnosis (98.01; 95% CI, 91.45-104.57). The relative increase in opioid use by persons with IBD compared to reference cohort was lower among persons with psychiatric comorbidity relative to the increased opioid use among persons with IBD and reference cohort without psychiatric comorbidity., Discussion: The use of opioids is more common in people with IBD than in people without IBD. This does not appear to be driven by psychiatric comorbidity., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Fatigue is highly prevalent in people with inflammatory bowel disease (IBD). Fatigue scales are important for studies testing fatigue interventions, but information about psychometric properties of many scales is insufficient in IBD. We compared the psychometric properties of multiple generic fatigue scales in participants with IBD., Methods: Individuals with IBD (N = 216) completed the Daily Fatigue Impact Scale (DFIS), the vitality subscale of the RAND-36, and the Patient Health Questionnaire-9 (PHQ-9) fatigue item twice. A subgroup (n = 84) also completed the Fatigue Impact Scale (FIS) once, from which we also scored the 21 items from the Modified Fatigue Impact Scale (MFIS-IBD). We assessed floor/ceiling effects, construct validity, and internal consistency reliability. Using relative efficiency (RE), we compared discriminating ability and comparative responsiveness of the measures regarding disease activity and employment status and changes., Results: The FIS, MFIS, and RAND-36-vitality scales did not exhibit floor or ceiling effects. The DFIS showed mild floor effects (19.4%), and the PHQ-9 fatigue item showed floor (18.1%) and ceiling (20.8%) effects. Internal consistency reliability exceeded 0.93 for FIS, MFIS-IBD, and DFIS and was 0.81 for the RAND-36-vitality scale. In the subgroup analysis, the FIS, MFIS-IBD, and DFIS were strongly correlated with each other (r ≥ 0.90). The ability to discriminate between disease activity groups was highest for the FIS and MFIS-IBD, followed by the DFIS. The FIS, MFIS-IBD, and DFIS were responsive to changes in work impairment., Conclusions: The FIS, MFIS-IBDs and DFIS had adequate validity and reliability for assessing fatigue in IBD., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

The SPIN-CHAT Program was designed to support mental health among individuals with systemic sclerosis (SSc; commonly known as scleroderma) and at least mild anxiety symptoms at the onset of COVID-19. The program was formally evaluated in the SPIN-CHAT Trial. Little is known about program and trial acceptability, and factors impacting implementation from the perspectives of research team members and trial participants. Thus, the propose of this follow-up study was to explore research team members' and trial participants' experiences with the program and trial to identify factors impacting acceptability and successful implementation. Data were collected cross-sectionally through one-on-one, videoconference-based, semi-structured interviews with 22 research team members and 30 purposefully recruited trial participants (Mage = 54.9, SD = 13.0 years). A social constructivist paradigm was adopted, and data were analyzed thematically. Data were organized into seven themes: (i) getting started: the importance of prolonged engagement and exceeding expectations; (ii) designing the program and trial: including multiple features; (iii) training: research team members are critical to positive program and trial experiences; (iv) offering the program and trial: it needs to be flexible and patient-oriented; (v) maximizing engagement: navigating and managing group dynamics; (vi) delivering a videoconference-based supportive care intervention: necessary, appreciated, and associated with some barriers; and (vii) refining the program and trial: considering modification when offered beyond the period of COVID-19 restrictions. Trial participants were satisfied with and found the SPIN-CHAT Program and Trial to be acceptable. Results offer implementation data that can guide the design, development, and refinement of other supportive care programs seeking to promote psychological health during and beyond COVID-19., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

Background: Adolescent and young adult (AYA) cancer survivors face physical and psychological sequelae related to having cancer decades after treatment completion. It is unclear if AYA cancer survivors are at increased risk for late psychiatric disorders., Methods: We used the Alberta AYA Cancer Survivor Study that includes 5-year survivors of cancer diagnosed at age 15-39 years during 1991 to 2013. The primary outcome was incidence of psychiatric disorder (composite outcome) including anxiety, depressive, trauma- and stressor-related, psychotic, and substance use disorders that were identified using coding algorithms for administrative health databases. A validated coding algorithm identified people who experienced a suicide attempt or event of self-harm. Secondary outcomes were incidences of diagnoses by type of psychiatric disorder., Results: Among 12 116 AYA 5-year cancer survivors (n = 4634 [38%] males; n = 7482 [62%] females), 7426 (61%; n = 2406 [32%] males; n = 5020 [68%] females) were diagnosed with at least 1 of 5 psychiatric disorders occurring at least 3 years after cancer diagnosis. Survivors of all cancer types were most often diagnosed with anxiety (males: 39.0%, 95% confidence interval [CI] = 37.6% to 40.4%; females: 54.5%, 95% CI = 53.3% to 55.6%), depressive (males: 32.7%, 95% CI = 31.3% to 34.0%; females: 47.0%, 95% CI = 45.8% to 48.1%), and trauma- and stressor-related disorders (males: 13.5%, 95% CI =12.5% to 14.5%; females: 22.5%, 95% CI = 21.6% to 23.5%)., Conclusions: Anxiety, depressive, and trauma- and stressor-related disorders are common among 5-year survivors of AYA cancer. Primary, secondary, or tertiary preventive strategies for AYAs diagnosed with cancer, particularly at an early age, are needed to mitigate risk of potentially severe outcomes because of psychiatric disorders., (© The Author(s) 2022. Published by Oxford University Press.)

Background: Inflammatory bowel disease (IBD) is associated with an increase in psychiatric comorbidity (PC) compared with the general population. We aimed to determine the impact of PC on health care utilization in persons with IBD., Methods: We applied a validated administrative definition of IBD to identify all Manitobans with IBD from April 1, 2006, to March 31, 2016, and a matched cohort without IBD. A validated definition for PC in IBD population was applied to both cohorts; active PC status meant ≥2 visits for psychiatric diagnoses within a given year. We examined the association of active PC with physician visits, inpatient hospital days, proportion with inpatient hospitalization, and use of prescription IBD medications in the following year. We tested for the presence of a 2-way interaction between cohort and PC status., Results: Our study matched 8459 persons with IBD to 40,375 controls. On crude analysis, IBD subjects had ≥3.7 additional physician visits, had >1.5 extra hospital days, and used 2.1 more drug types annually than controls. Subjects with active PC had >10 more physician visits, had 3.1 more hospital days, and used >6.3 more drugs. There was a synergistic effect of IBD (vs no IBD) and PC (vs no PC) across psychiatric disorders of around 4%. This synergistic effect was greatest for anxiety (6% [2%, 9%]). After excluding psychiatry-related visits and psychiatry-related hospital stays, there remained an excess health care utilization in persons with IBD and PC., Conclusion: Inflammatory bowel disease with PC increases health care utilization compared with matched controls and compared with persons with IBD without PC. Active PC further increases health care utilization., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Brackground: We aimed to examine associations between elevated symptoms of depression and anxiety and disease activity in inflammatory bowel disease (IBD). Previous findings have been inconsistent and have not accounted for variability in the courses of these conditions over time., Methods: We followed 247 participants with IBD (153 Crohn's disease [CD], 94 ulcerative colitis [UC]) for 3 years. Annually, participants underwent an abdominal examination, reported therapies used for IBD, and completed the Hospital Anxiety and Depression Scale (HADS) questionnaire. We evaluated associations of elevated symptoms (scores ≥11) of anxiety (HADS-A) and depression (HADS-D) with the presence of active IBD as measured using the Powell Tuck Index for UC and the Harvey-Bradshaw Disease Activity Index for CD. We employed logistic regression with generalized estimating equations, simultaneously estimating between-person and within-person effects., Results: Of 247 participants, 15 (6.1%) had elevated symptoms of depression (HADS-D ≥11) at enrollment, 41 (16.6%) had elevated symptoms of anxiety (HADS-A ≥11), and 101 (40.9%) had active IBD. On average, individuals with elevated symptoms of depression (odds ratio [OR], 6.27; 95% CI, 1.39-28.2) and anxiety (OR, 2.17; 95% CI, 1.01-4.66) had increased odds of active IBD. Within individuals, elevations in symptoms of depression over time were associated with increased odds of active IBD (OR, 2.70; 95% CI, 1.15-6.34), but elevated symptoms of anxiety were not. After adjustment for covariates (including disease activity), elevated symptoms of depression were also associated with increased odds of biologic therapy use (OR, 2.02; 95% CI, 1.02-4.00)., Conclusion: Symptoms of depression and anxiety are associated with disease activity in IBD over time. Reducing these symptoms should be incorporated into the management of IBD., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Substance use disorders (SUDs) impose a substantial individual and societal burden; however, the prevalence and associated factors in persons with inflammatory bowel disease (IBD) are largely unknown. We evaluated the prevalence and risk factors of SUD in an IBD cohort., Methods: Inflammatory bowel disease participants (n = 247) were recruited via hospital- and community-based gastroenterology clinics, a population-based IBD research registry, and primary care providers as part of a larger cohort study of psychiatric comorbidity in immune-mediated inflammatory diseases. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV was administered to participants to identify lifetime SUD, anxiety disorder, and major depressive disorder. Additional questionnaires regarding participants' sociodemographic and clinical characteristics were also completed. We examined demographic and clinical factors associated with lifetime SUD using unadjusted and adjusted logistic regression modeling., Results: Forty-one (16.6%) IBD participants met the criteria for a lifetime diagnosis of an SUD. Factors associated with elevated odds of SUD were ever smoking (adjusted odds ratio [aOR], 2.96; 95% confidence interval [CI], 1.17-7.50), male sex (aOR, 2.44; 95% CI, 1.11-5.36), lifetime anxiety disorder (aOR, 2.41; 95% CI, 1.08-5.37), and higher pain impact (aOR, 1.08; 95% CI, 1.01-1.16)., Conclusions: One in six persons with IBD experienced an SUD, suggesting that clinicians should maintain high index of suspicion regarding possible SUD, and inquiries about substance use should be a part of care for IBD patients, particularly for men, smokers, and patients with anxiety disorders and pain., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

We conducted a systematic review and a fixed-effects meta-analysis to determine whether incident adverse psychiatric events (APE) including depression, anxiety, psychosis, or suicide were associated with biologic therapy in IBD. Six randomized controlled trials and a cohort study met criteria, reporting an incidence of APE in 4,882 patients. The risk difference per 100 person-months of any APE with a biologic medication was 0.01 (95% confidence interval = 0.00-0.02). There was insufficient evidence available in randomized controlled trials to conclude that biologic therapy in IBD is associated with an increased incidence of APE., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Inflammatory bowel disease (IBD) is associated with a high prevalence of comorbid depressive and anxiety disorders. A significant proportion of IBD patients with comorbid psychiatric disorders remain undiagnosed and untreated, but factors associated with diagnosis are unknown. We evaluated the prevalence of undiagnosed depression and anxiety in an IBD cohort, along with the associated demographic and clinical characteristics., Methods: We obtained data from the enrollment visit of a cohort study of psychiatric comorbidity in immune-mediated diseases including IBD. Each participant underwent a Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) to identify participants who met lifetime criteria for a diagnosis of depression or anxiety. Those with a SCID-based diagnosis were classified as diagnosed or undiagnosed based on participant report of a physician diagnosis., Results: Of 242 eligible participants, 97 (40.1%) met SCID criteria for depression, and 74 (30.6%) met criteria for anxiety. One-third of participants with depression and two-thirds with anxiety were undiagnosed. Males were more likely to have an undiagnosed depressive disorder (odds ratio [OR], 3.36; 95% confidence interval [CI], 1.28-8.85). Nonwhite participants were less likely to have an undiagnosed anxiety disorder (OR, 0.17; 95% CI, 0.042-0.72)., Conclusion: Our findings highlight the importance of screening for depression and anxiety in patients with IBD, with particular attention to those of male sex and with a lower education level., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Psychiatric comorbidity in inflammatory bowel disease (IBD) is well known; however, data from a truly representative sample are sparse. We aimed to estimate the incidence and prevalence of psychiatric disorders in an IBD cohort compared with a matched cohort without IBD., Methods: Using population-based administrative health data from Manitoba, Canada, we identified all persons with incident IBD from 1989 to 2012 and a general population matched cohort (5:1). We applied validated algorithms for IBD, depression, anxiety disorders, bipolar disorder, and schizophrenia to determine the annual incidence of these conditions post-IBD diagnosis and their lifetime and current prevalence., Results: There were 6119 incident cases of IBD and 30,573 matched individuals. After adjustment for age, sex, socioeconomic status, region of residence, and year, there was a higher incidence in the IBD cohort compared with controls for depression (incidence rate ratio [IRR], 1.58; 95% confidence interval [CI], 1.41-1.76), anxiety disorder (IRR, 1.39; 95% CI, 1.26-1.53), bipolar disorder (IRR, 1.82; 95% CI, 1.44-2.30), and schizophrenia (IRR, 1.64; 95% CI, 0.95-2.84). Incidence rate ratios were similar for Crohn's disease and ulcerative colitis between males and females and were stable over time. However, within the IBD cohort, the incidence rates of depression, anxiety, and bipolar disorders were higher among females, those aged 18-24 years vs those older than 44 years, urbanites, and those of lower socioeconomic status. The lifetime and current prevalence rates of psychiatric disorders were also higher in the IBD than the matched cohort., Conclusions: The incidence and prevalence of psychiatric disorders are elevated in the IBD population.

Background: We evaluated the validity and reliability of multiple symptom scales for depression and anxiety for persons with inflammatory bowel disease (IBD)., Methods: IBD participants in a cohort study completed a Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), Kessler-6 Distress Scale, PROMIS Emotional Distress Depression Short-Form 8a (PROMIS Depression) and Anxiety Short-Form 8a (PROMIS Anxiety), Generalized Anxiety Disorder 7-item Scale, and Overall Anxiety and Severity Impairment Scale. We computed sensitivity, specificity, and positive and negative predictive values for the screening measures with the SCID diagnoses as the reference standard, conducted receiver operating curve (ROC) analysis, and assessed internal consistency and test-retest reliability., Results: Of 242 participants, the SCID classified 8.7% as having major depression and 17.8% as having anxiety disorders. Among the depression scales, the PHQ-9 had the highest sensitivity (95%). Specificity was generally higher than sensitivity and was highest for the HADS-D (cut-point of 11; 97%). The area under the ROC curve (AUC) did not differ significantly among depression scales. Among the anxiety scales, sensitivity was highest for the PROMIS (79%). Specificity ranged from 82% to 88% for all tools except the HADS-A (cut-point of 8; 65%). The AUC did not differ between depression and anxiety tools., Conclusions: Overall, the symptom scales for depression and anxiety were similar in their psychometric properties. The anxiety scales did not perform as well as the depression scales. Alternate cut-points may be more relevant when these scales are used in an IBD sample., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Early childhood experiences of poverty are associated with adverse developmental outcomes that have impli cations for individual and population health. Low educational attainment and early childbearing are two such important outcomes that can perpetuate childhood poverty into adulthood. Child hunger, or severe food insecurity, is an extreme manifestation of household food insecurity that is associated with the stressful experience of deep family poverty. Life-course theories suggest that childhood experiences of hunger could have adverse effects in the developmental pathway. The objective of this study was to examine the independent contribution of the child hunger experience to subsequent educational attainment and early childbearing in young adult men and women, in consideration of other latent, cumulative or shock effects associated with child poverty., Methods: We analyzed National Longitudinal Survey of Children and Youth data using logistic regression based on 15,468 Canadian children followed over 16 years., Results: The prevalence of the experience of child hunger was 5.0%. Child hunger was independently predictive of youth leaving high school, yet was not a factor in the achievement of higher educational attainment if youth were able to graduate from high school. Having always lived in rental accommodation and repeated reports of child hunger over time were predictive of early childbearing., Conclusions: Interventions directed at children and youth who are at risk of poor developmental outcomes because of severe food insecurity should focus on steering families toward their income entitlements, and providing support for youth to complete high school and to avoid early fertility.

Background: Suicide is a leading cause of death worldwide. Transition from suicidal ideation (SI) to suicide attempt is high within a year of SI onset. The risk of suicide and SI is elevated in persons with inflammatory bowel disease (IBD) versus the general population. We aimed to validate the Patient Heath Questionnaire (PHQ)-9 as a screening tool for SI in IBD and to determine factors associated with SI in IBD., Methods: IBD participants (n = 247) recruited from the community and clinics completed the PHQ-9 and participated in the Structured Clinical Interview for DSM-IV (SCID). We determined the sensitivity, specificity, and positive and negative predictive value (PPV and NPV) of the PHQ-9 in identifying SI as compared to the SCID. Using logistic regression we examined the association of SI with demographic and clinical factors., Results: SI was endorsed by 24 (9.7%) participants on the PHQ-9 and 5 (2.0%) based on the SCID. The PHQ-9 had good sensitivity (100%), specificity (92.2%), and NPV (100%) but low PPV (20.8%) for SI. On univariate analysis, factors strongly associated with SI were depression (OR 13.1; 95%CI: 4.46, 40.5), anxiety (OR 11.3; 95%CI: 4.46, 28.6), and active disease (OR 3.87; 95%CI: 1.54, 9.71). On multivariable analysis, depression (OR 5.54; 95%CI: 1.67, 18.4) and pain (OR 1.14; 95%CI: 1.03, 1.25) were associated with SI., Conclusions: Overall the PHQ-9 is a valid screening tool for SI in IBD patients, and routine implementation of this tool would support screening for depression and SI effectively and efficiently in clinical practice.

Despite many years of clinical use of isotretinoin, a comprehensive review of evidence for isotretinoin therapy in patients with acne is lacking. We searched MEDLINE, Embase, Cochrane Central, relevant web pages and bibliographies for randomized controlled trials in acne evaluating isotretinoin vs. control (placebo or other therapy). Data were extracted and summarized descriptively. Eleven trials were identified (total 760 patients randomized), containing mostly men. Mean treatment ages ranged from 18 to 47·9 years and participants generally had moderate-to-severe acne. Across all trials, isotretinoin therapy reduced acne lesion counts by a clinically relevant amount, and always by a greater amount than control, which was either placebo (two studies), oral antibiotics (seven studies) or other control (two studies). Across trials with an overall low risk of bias, two of three demonstrated statistically significant differences between isotretinoin and control. The frequency of adverse events was twice as high with isotretinoin (751 events) than with control (388 events). More than half of all adverse events were dermatological and related to dryness. Adverse events from isotretinoin causing participant withdrawal from trials (12 patients) included Stevens-Johnson syndrome, cheilitis, xerosis, acne flare, photophobia, elevated liver enzymes, decreased appetite, headaches and depressed mood. This review suggests that isotretinoin is effective in reducing acne lesion counts, but adverse events are common. This study was registered with PROSPERO number CRD42015025080., (© 2017 British Association of Dermatologists.)

In studies of diagnostic test accuracy, authors sometimes report results only for a range of cutoff points around data-driven "optimal" cutoffs. We assessed selective cutoff reporting in studies of the diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) depression screening tool. We compared conventional meta-analysis of published results only with individual-patient-data meta-analysis of results derived from all cutoff points, using data from 13 of 16 studies published during 2004-2009 that were included in a published conventional meta-analysis. For the "standard" PHQ-9 cutoff of 10, accuracy results had been published by 11 of the studies. For all other relevant cutoffs, 3-6 studies published accuracy results. For all cutoffs examined, specificity estimates in conventional and individual-patient-data meta-analyses were within 1% of each other. Sensitivity estimates were similar for the cutoff of 10 but differed by 5%-15% for other cutoffs. In samples where the PHQ-9 was poorly sensitive at the standard cutoff, authors tended to report results for lower cutoffs that yielded optimal results. When the PHQ-9 was highly sensitive, authors more often reported results for higher cutoffs. Consequently, in the conventional meta-analysis, sensitivity increased as cutoff severity increased across part of the cutoff range-an impossibility if all data are analyzed. In sum, selective reporting by primary study authors of only results from cutoffs that perform well in their study can bias accuracy estimates in meta-analyses of published results., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To investigate the relation between work environmental factors and the risk of major depressive disorder (MDD) over 1 year, the authors conducted a population-based longitudinal study of randomly selected employees in Alberta, Canada (January 2008 to November 2011). Participants without a current or lifetime diagnosis of MDD at baseline (n = 2,752) were followed for 1 year. MDD was assessed using the World Health Organization's Composite International Diagnostic Interview-Auto 2.1. The overall 1-year incidence of MDD was 3.6% (95% confidence interval: 2.8, 4.6); it was 2.9% (95% confidence interval: 1.9, 4.2) in men and 4.5% (95% confidence interval: 3.3, 6.2) in women. The relations between work environmental factors and MDD differed by sex. In men, high job strain increased the risk of MDD in those who worked 35-40 hours per week; job insecurity and family-to-work conflict were predictive of MDD. Women who worked 35-40 hours per week and reported job insecurity, a high effort-reward imbalance, and work-to-family conflict were at a higher risk of developing MDD. Job strain, effort-reward imbalance, job insecurity, and work-to-family conflicts are important risk factors for the onset of MDD and should be targets of primary prevention. However, these work environmental factors appear to operate differently in men and in women.

Introduction: We assessed whether major depression (MD) predicts progression of nicotine dependence (ND) as measured by reduction in the time to first cigarette (TTFC) after waking and the roles of the number of cigarettes smoked per day (CPD) and stress as explanatory variables of this association., Methods: Ten years of follow-up data from the National Population Health Survey (NPHS) were used. The analyses were based on this nationally representative sample of the Canadian population who were over the age of 12 years in 1996 (n = 13,298). The NPHS included measures of MD and TTFC. Shorter TTFC was defined as TTFC within 5 min of waking. Heavy smoking (HS) was defined by smoking 20 or more CPD. Using proportional hazard models, unadjusted and adjusted hazard ratios (HRs) for shorter TTFC were estimated for those with and without MD., Results: The unadjusted HR for shorter TTFC among those with MD versus those without MD was 3.7 (95% CI: 2.6-5.3, p < .001). MD predicted onset of shorter TTFC even after adjustment for HS and tendency to smoke more under stress (HR: 1.7; 95% CI: 1.1-2.5, p = .02). When TTFC was defined using longer cutoffs (30 and 60 min), HS completely accounted for the effect of MD on TTFC onset., Conclusions: MD appears to be a risk factor for transition to shorter TTFC independent of effects of HS and the tendency to smoke more under stress. As MD is often modifiable, the above association points toward a preventive opportunity in relation to worsening of ND.

The objectives of this prospective study were to calculate incidence rates for fall-related hospitalization, to compare the effect of risk factors among benzodiazepine (BZD) users and unexposed controls, and to examine variations in risks according to length of time following a BZD prescription. Data were derived from Saskatchewan Health linked data bases, leading to information on 468 hospitalizations for injury due to falls among a study population of 321422. Incidence rates per 10000 within 28 days of the prescription fill date were 26.2, 12.1 and 9.0 for BZD sedative users, BZD tranquillizer users and for unexposed controls, respectively. Incidence rates increased with age, and were higher for women than for men. Results from multivariate logistic regression models also showed a greater risk of falling for BZD users but the odds ratio was higher for men than for women. A history of treatment for alcohol abuse was a very strong risk factor for falls among both men (odds ratio, 10.7) and women (odds ratio, 4.3). The highest risk of serious injury due to falls was within 15 days of filling the prescription, with an odds ratio of 3.6 for BZD sedatives and 2.6 for BZD tranquillizers. Risk decreased with further increase of time after the BZD fill date. For the individual BZD, flurazepam and triazolam showed the highest increase in risk with odds ratios of 3.4 and 2.7, respectively, while oxazepam, lorazepam and diazepam showed odds ratios of 2.2, 2.0 and 1.8 (all odds ratios mentioned are statistically significant at p < 0.05).