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Purpose: Our objectives were to identify characteristics of response shift studies using patient-reported outcomes (PROMs) that explain variability in (1) the detection and (2) the magnitude of response shift effects., Methods: We conducted a systematic review of quantitative studies published before June 2023. First, two-level multivariable logistic regression models (effect- and sample-levels) were used to explain variability in the probability of finding a response shift effect. Second, variability in effect sizes (standardized mean differences) was investigated with 3-level meta-regression models (participant-, effect- and sample-levels). Explanatory variables identified via the purposeful selection methodology included response shift method and type, and population-, study design-, PROM- and study-quality characteristics., Results: First, logistic regression analysis of 5597 effects from 206 samples in 171 studies identified variables explaining 41.5% of the effect-level variance, while no variables explained sample-level variance. The average probability of response shift detection is 0.20 (95% CI: 0.17-0.28). Variation in detection was predominantly explained by response shift methods and type (recalibration vs. reprioritization/reconceptualization). Second, effect sizes were analyzed for 769 effects from 114 samples and 96 studies based on the then-test and structural equation modeling methods. Meta-regression analysis identified variables explaining 11.6% of the effect-level variance and 26.4% of the sample-level variance, with an average effect size of 0.30 (95% CI: 0.26-0.34)., Conclusion: Response shift detection is influenced by study design and methods. Insights into the variables explaining response shift effects can be used to interpret results of other comparable studies using PROMs and inform the design of future response shift studies., Competing Interests: Declarations. Ethics approval: Not applicable. Consent to participate: Not applicable. Research involving human participants and/or animals: Not applicable. Informed consent: Not applicable. Conflict of interest: The authors declare that they have no conflict of interest that are relevant to the content of this article. JRB is Co-Editor in Chief of Quality of Life Research and is not part of the decision-making process for this manuscript., (© 2024. The Author(s).)

Background: Patterns of health services utilization among children with inflammatory bowel disease (IBD) are important to understand as the number of children with IBD continues to increase. We compared health services utilization and surgery among children diagnosed <10 years of age (Paris classification: A1a) and between 10 and <16 years of age (A1b)., Methods: Incident cases of IBD diagnosed <16 years of age were identified using validated algorithms from deterministically linked health administrative data in 5 Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec) to conduct a retrospective cohort study. We compared the frequency of IBD-specific outpatient visits, emergency department visits, and hospitalizations across age groups (A1a vs A1b [reference]) using negative binomial regression. The risk of surgery was compared across age groups using Cox proportional hazards models. Models were adjusted for sex, rural/urban residence location, and mean neighborhood income quintile. Province-specific estimates were pooled using random-effects meta-analysis., Results: Among the 1165 (65.7% Crohn's) children with IBD included in our study, there were no age differences in the frequency of hospitalizations (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.06) or outpatient visits (RR, 0.95; 95% CI, 0.78-1.16). A1a children had fewer emergency department visits (RR, 0.70; 95% CI, 0.50-0.97) and were less likely to require a Crohn's-related surgery (hazard ratio, 0.49; 95% CI, 0.26-0.92). The risk of colectomy was similar among children with ulcerative colitis in both age groups (hazard ratio, 0.71; 95% CI, 0.49-1.01)., Conclusions: Patterns of health services utilization are generally similar when comparing children diagnosed across age groups., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Importance: Fragility fractures are often defined as those that occur after a certain age (eg, 40-50 years). Whether fractures occurring in early adulthood are equally associated with future fractures is unclear., Objective: To examine whether the age at which a prior fracture occurred is associated with future fracture risk., Design, Setting, and Participants: This observational, population-based cohort study included individuals from the Manitoba Bone Mineral Density Registry with a first bone mineral density (BMD) measurement between January 1, 1996, and March 31, 2018, with and without prior fracture in adulthood. Data analysis was completed between April 1, and May 31, 2023., Exposure: Individuals with fractures before their first dual-energy x-ray absorptiometry were stratified by the age at first fracture (10-year intervals from 20-29 to ≥80 years of age)., Main Outcomes and Measures: Incident fractures occurring after dual-energy x-ray absorptiometry (index date) and before March 31, 2021, were identified using linked provincial administrative health data., Results: The cohort included 88 696 individuals (80 066 [90.3%] female; mean [SD] age, 64.6 [11.0] years) with a mean (SD) femoral neck T score of -1.4 (1.0). A total of 21 105 individuals (23.8%) had sustained a prior fracture at a mean (SD) age of 57.7 (13.6) years (range, 20.0-102.4 years) at the time of first prior fracture. During a mean (SD) of 9.0 (5.5) years of follow-up, incident fractures occurred in 13 239 individuals (14.6%), including 12 425 osteoporotic fractures (14.0%), 9440 major osteoporotic fractures (MOFs) (10.6%), and 3068 hip fractures (3.5%). The sex- and age-adjusted hazard ratios for all incident fractures, osteoporotic fractures, and MOFs, according to age at first fracture, were all significantly elevated, with point estimates ranging from 1.55 (95% CI, 1.28-1.88) to 4.07 (95% CI, 2.99-5.52). After adjusting for the additional covariates, the effect estimates were similar and remained significantly elevated, with point estimates ranging from fully adjusted hazard ratios of 1.51 (95% CI, 1.42-1.60) to 2.12 (95% CI, 1.67-2.71) across age categories. Sensitivity analyses examining age at last prior fracture and in those with multiple prior fractures showed similar results., Conclusions and Relevance: In this cohort study, fractures in adulthood were associated with future fractures regardless of the age at which they occurred. Thus, fractures in early adulthood should not be excluded when assessing an individual's ongoing fracture risk.

Introduction: Multiple sclerosis (MS) has a high comorbidity burden. Despite known associations with adverse outcomes, a comprehensive evaluation of the specific associations between individual comorbidities and disability, treatment initiation, and mortality remains underexplored. This study aimed to review and summarize existing evidence on the association between comorbidities and these three MS outcomes., Methods: A rapid review spanning the period from January 2002 to October 2023 was conducted following the Cochrane Rapid Review Methods Group recommendations. MEDLINE, Embase, and the grey literature were searched to identify studies examining the effects of comorbidities on disability, treatment initiation, and mortality among individuals with MS. Data extraction and risk of bias assessments were systematically performed, with the Newcastle-Ottawa scale and A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) criteria for observational studies and systematic reviews respectively., Results: The review included 100 primary studies, encompassing 88 different comorbidities. Most study populations were between 60-80% female, with an average age of 30-45 years at study start. The majority of included studies were conducted in Europe, North America, and Asia (specifically the Middle East). Over half (66%) of specific comorbidity-outcome relationships were examined within a single study only, and just two studies examined treatment initiation as an outcome. Methods used to assess comorbidities and outcomes varied widely and included self-report measures, medical records and diagnostic codes, and standardized clinical assessments. Depression was consistently associated with greater disability (adjusted hazard ratio (aHR): 1.50-3.59) and mortality (aHR: 1.62-3.55). Epilepsy was similarly associated with increased disability (aOR: 1.13-1.77) and increased mortality (aHR: 2.23-3.85). Diabetes was generally associated with increased mortality (aHR: 1.39-1.47), but results for disability were inconsistent. Most other conditions were examined in one or two studies only or findings varied across studies, unable to collectively indicate a clear association. Although the anxiety-disability relationship was assessed by 24 studies, the findings varied in terms of the presence, direction, and strength of a possible association, requiring nuanced interpretation., Conclusions: This study identifies relationships between various comorbidities and three outcomes in MS, providing a foundation for future research and clinical guidelines. People with psychiatric, metabolic, and neurological conditions may be at a higher risk of MS disease progression and may therefore benefit from the targeted treatment of their comorbidities. Overall, comorbidities have varying associations with MS outcomes and individual associations require further exploration. However, there is evidence that some comorbidities indicate worse disability and higher mortality risk, and present barriers to initiating MS treatment, making the prevention and management of comorbidities an integral piece of MS patient care., Protocol: The protocol for this rapid review was registered on PROSPERO (ID: CRD42023475565) and published on Protocol Exchange (https://doi.org/10.21203/rs.3.pex-2438/v1)., Competing Interests: Declaration of competing interest The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HT has, in the last five years, received research support from the Canada Research Chair Program, the National Multiple Sclerosis Society, the Canadian Institutes of Health Research, MS Canada, the Multiple Sclerosis Scientific Research Foundation and the EDMUS Foundation (‘Fondation EDMUS contre la sclérose en plaques’). In addition, in the last five years, HT has had travel expenses or registration fees prepaid or reimbursed to present at CME conferences or attend meetings (as a member of the International Advisory Committee on Clinical Trials in Multiple Sclerosis) from the Consortium of MS Centres (2023), the Canadian Neurological Sciences Federation (2023), National MS Society (2022, 2023, 2024), ECTRIMS/ ACTRIMS (2017–2024), American Academy of Neurology (2019). Speaker honoraria are either declined or donated to an MS charity or to an unrestricted grant for use by HT's research group. RAM receives research funding from: CIHR, MS Canada, Crohn's and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society, Pfizer Foundation and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. She holds the Waugh Family Chair in Multiple Sclerosis. LML receives research funding from CIHR, the Arthritis Society, and the Canadian Agency for Drugs and Technology in Health. She holds a Canada Research Chair. KAM receives research funding from StratNeuro and has received speaker honoraria from Biogen Inc and Sanofi. MEK is supported by the Michael Smith Foundation for Health Research Scholar award. Over the past 3 years, MEK has received consulting fees from Biogen Inc. for consulting unrelated to this current work. HAF, MC, YF, and FZ have no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely, Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health), was established to develop guidance for the standardization of reporting of RWE for regulatory and HTA decision-making in Canada., Study Design and Setting: A collaborative initiative to create structured guidance for RWE reporting in the context of regulatory and HTA decision-making., Results: The developed guidance aims to standardize and ensure transparent reporting of RWE to improve its reliability and usefulness in regulatory and HTA processes., Conclusion: This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making., Competing Interests: Declaration of competing interest M. T. received financial support from the Canadian Agency for Drugs and Technologies in Health. M. T., T. A., and K. N. H. report a relationship with Canadian Agency for Drugs and Technologies in Health that includes consulting or advisory. N. M., L. L., and F. H. are employed with the Canadian Agency for Drugs and Technologies in Health. There are no competing interests for any other author., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Patient-reported outcome measures (PROMs) such as the Neurological Disorders Depression Inventory in Epilepsy (NDDI-E), a 6-item epilepsy-specific PROM, is used to screen for major depressive disorder symptoms for patients with epilepsy (PWE). The validity and interpretation of PROMs can be affected by differential item functioning (DIF), which occurs when subgroups of patients with the same underlying health status respond to and interpret questions about their health status differently. This study aims to determine whether NDDI-E items exhibit DIF and to identify subgroups of PWE that exhibit DIF in NDDI-E items., Methods: Data were from the Calgary Comprehensive Epilepsy Program database, a clinical registry of adult PWE in Calgary, Canada. A tree-based partial credit model based on recursive partitioning (PCTree) was used to identify subgroups that exhibit DIF on NDDI-E items using patients' characteristics as covariates. Differences in the identified subgroups were characterized using multinomial logistic regression., Results: Of the 1,576 patients in this cohort, 806 (51.1%) were female, and the median age was 38.0 years. PCTree identified four patient subgroups defined by employment status, age, and sex. Subgroup 1 were unemployed patients ≤ 26 years old, subgroup 2 were unemployed patients > 26 years, subgroup 3 were employed females, while subgroup 4 were employed male patients. The subgroups exhibited significant differences on education level, comorbidity index scores, marital status, type of epilepsy, and driving status., Conclusion: PWE differed in their interpretation and responses to questions about their depression symptoms, and these differences were a function of sociodemographic and clinical characteristics., Competing Interests: Declarations. Ethical approval: Ethics approval for the study was obtained through the University of Calgary’s Conjoint Health Research Ethics Board (REB22-0135). Consent to participate: Not applicable. Consent to publish: Not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: This study aimed to investigate the impact of pregnancy and pre-existing comorbidities on COVID-19 infections and associated complications of hospitalisation and mortality in women of reproductive age (WRA). The study also compared the risk of severe COVID-19 complications between pregnant women (PW) and non-pregnant women (NPW) with and without pre-existing comorbidities. Special focus was placed on some understudied comorbidities of immunosuppression, chronic renal disease and chronic obstructive pulmonary disease (COPD)., Methods: The study utilized anonymized patient-related information for a population of 7,342,869 WRA from the Mexican Ministry of Health data repository on COVID-19. Descriptive variables were characterized using frequencies, percentages, means, and standard deviations. Adjusted odds ratios (aORs) were used to assess the associations between risk factors and outcomes of hospitalisation and mortality. The study covered the entire COVID-19 pandemic period from January 30, 2020, to May 5, 2023., Results: The findings revealed that PW were not more likely to get COVID-19 infections than NPW. PW with COVID-19 infections were more likely to require hospital admission, intubation treatments, and ICU admission compared to NPW with COVID-19. PW with immunosuppression had an increased odds ratio (aOR) of getting COVID-19 infections compared to NPW (PW: aOR = 1.0396; NPW: aOR = 0.8373). NPW with immunosuppression had higher risk of mortality (all-cause death: aOR = 1.7084; COVID-19-associated death: aOR = 1.4079) and hospitalisation (all-cause hospitalisation: aOR = 4.1328; COVID-19-associated hospitalisation: aOR = 3.0451) than NPW without immunosuppression. Renal disease was identified as a concerning pre-existing condition that increased the risks of COVID-19 associated mortality/hospitalizations and all-cause mortality/hospitalizations for both PW and NPW. NPW with renal disease had much higher odds ratio (aOR) of either COVID-19-associated-hospitalisations (NPW: aOR = 8.639; PW: aOR = 1.7603) or all-cause hospitalisations (NPW: aOR = 8.8594; PW: aOR = 1.786) than PW with renal disease., Conclusions: This study provides valuable insights into the impact of pregnancy and pre-existing comorbidities on COVID-19 outcomes in WRA. The findings underscore the importance of considering demographic factors and pre-existing comorbidities in the management of PW with COVID-19. The study also highlights the need for further research to understand the unique impacts of different comorbidities, particularly immunosuppression and renal disease, on COVID-19 outcomes in WRA., Competing Interests: Declarations Ethical approval This data was obtained in accordance with the Decree published in the Official Gazette of Mexico Government on Open Data, the General Directorate of Epidemiology [22]. Only anonymised patient-related information was available. No patient identifiable data were used. No ethical approval was necessary for this study because the data were publicly available. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Importance: The Fracture Risk Assessment Tool (FRAX) is a fracture risk prediction tool for 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Whether FRAX is useful in individuals with cancer is uncertain., Objective: To determine the performance of FRAX for predicting incident fractures in individuals with cancer., Design, Setting, and Participants: This retrospective population-based cohort study included residents of Manitoba, Canada, with and without cancer diagnoses from 1987 to 2014. Diagnoses were identified through the Manitoba Cancer Registry. Incident fractures to March 31, 2021, were identified in population-based health care data. Data analysis occurred between January and March 2023., Main Outcomes and Measures: FRAX scores were computed for those with bone mineral density (BMD) results that were recorded in the Manitoba BMD Registry., Results: This study included 9877 individuals with cancer (mean [SD] age, 67.1 [11.2] years; 8693 [88.0%] female) and 45 877 individuals in the noncancer cohort (mean [SD] age, 66.2 [10.2] years; 41 656 [90.8%] female). Compared to individuals without cancer, those with cancer had higher rates of incident MOF (14.5 vs 12.9 per 1000 person-years; P < .001) and hip fracture (4.2 vs 3.5 per 1000 person-years; P = .002). In the cancer cohort, FRAX with BMD results were associated with incident MOF (HR per SD increase, 1.84 [95% CI, 1.74-1.95]) and hip fracture (HR per SD increase, 3.61 [95% CI, 3.13-4.15]). In the cancer cohort, calibration slopes for FRAX with BMD were 1.03 for MOFs and 0.97 for hip fractures., Conclusions and Relevance: In this retrospective cohort study, FRAX with BMD showed good stratification and calibration for predicting incident fractures in patients with cancer. These results suggest that FRAX with BMD can be a reliable tool for predicting incident fractures in individuals with cancer.

Introduction and Objectives: The burden of chronic liver disease and cirrhosis continues to increase in North America. We sought to estimate the incidence and prevalence of cirrhosis in Manitoba, Canada over time and assess changes in trends between 2010-2019., Material and Methods: We performed a population-based study using Manitoba administrative health care data, and two validated case-finding algorithms. Annual incidence and prevalence rates were estimated using a generalized linear model with generalized estimating equations, adjusting for age and sex. Changes in estimates were tested using linear trend regression models., Results: Two algorithms estimated the number of prevalent cirrhosis to be 16,140 and 29,943 respectively. The age- and sex-adjusted incidence rates increased over the study (from 149 to 264 cases per 100,000 population in 2010, to 177 to 388 cases per 100,000 population in 2019). Cirrhosis incidence increased annually by 2-6 %, with the largest increase (6-8 % 95 % CI 7-9 %, p <0.0001) in those aged 18-44 years. Irrespective of the algorithm used, females consistently exhibited higher cirrhosis incidence and prevalence compared to males over time (P <0.0001). Prevalence demonstrated an upward trend among all age groups over time for both algorithms (P < 0.0001)., Conclusions: This population-based study highlights concerning temporal trends in cirrhosis, characterized by rising annual incidence and prevalence estimates, particularly among young adults and females. These findings underscore the urgent need for comprehensive strategies that encompass prevention, early detection, and the delivery of high-quality healthcare and public health initiatives to effectively tackle this escalating health burden., Competing Interests: Declaration of interests Financial Disclosures: Dr. Singh has been on advisory boards or consulted for Abbvie Canada, Amgen Canada, Roche Canada, Sandoz Canada, Organon Canada, Eli Lilly Canada, Takeda Canada, Pendopharm Inc, and Guardant Health, Inc. and has received research funding for an investigator-initiated study from Pfizer. Declarations of interest from all other authors: none, (Crown Copyright © 2024. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: The Canadian Institute of Health Information's (CIHI) Discharge Abstract Database (DAD) contains standardised administrative data on all hospitalisations in Canada, excluding Quebec., Objectives: We aimed to validate preterm birth related perinatal and neonatal data in DAD by assessing its accuracy against the reference standard of the Canadian Neonatal Network (CNN) database., Methods: We linked birth hospitalization data between the DAD and CNN databases for all neonates born <33 weeks gestational age (GA) admitted to the Neonatal Intensive Care Units in Winnipeg, Canada, between 2010 and 2022. A comprehensive list of maternal and neonatal variables relevant to preterm birth was chosen a priori for validation. For categorical variables, we measured correlation using Cohen's weighted kappa (k) and for continuous variables, we measured agreement using Lin's concordance correlation coefficient (LCCC)., Results: 2084 neonates were included (mean GA 29.4 ± 2.4 weeks; birth weight 1430 ± 461g). Baseline continuous maternal and neonatal variables showed excellent accuracy in DAD [Maternal age: LCCC = 0.99 (0.99, 0.99); GA: LCCC = 0.95 (0.95, 0.96); birth weight: LCCC = 0.97 (0.96, 0.97); sex: k = 0.99 (0.98-0.99)]. In contrast, the accuracy of the maternal baseline categorical variables and neonatal outcomes and interventions ranged from very good to poor [e.g., Caesarean section: k = 0.91 (0.89-0.93), pre-gestational diabetes: k = 0.04 (0.03-0.05), neonatal sepsis: k = 0.37 (0.31-0.42), bronchopulmonary dysplasia: k = 0.26 (0.19-0.33), neonatal laparotomy: k = 0.55 (0.43-067)]., Conclusion: Neonatal variables such as gestational age and birth weight had high accuracy in DAD, while the accuracy of maternal and neonatal morbidities and interventions were variable, with some being poor. Reasons for the inaccuracy of these variables should be identified and measures taken to improve them., Competing Interests: Conflicts of interest: The authors have no conflicts of interest to disclose.

Objectives: Adolescents and young adults (AYAs, 18-39 years) with cancer identifying as racially/ethnically minoritized or 2SLGBTQIA+ (Two-Spirit, lesbian, gay, bisexual, transgender, queer, intersex, asexual and "+" referring to other queer identities) have been underrepresented in cancer research. This study explores the aspects of identity that hold significance for these minoritized AYAs and how these facets impact their healthcare experiences., Methods: Eligible participants comprised English-speaking AYAs who self-identified as racially/ethnically minoritized and/or 2SLGBTQIA+, were diagnosed with cancer between the ages of 15-39, currently aged > 18, and had received or were receiving cancer care within Canadian healthcare system. Additionally, four patient partners meeting the same criteria were recruited as research collaborators. Semi-structured one-on-one virtual interviews guided by an interview script were conducted, and qualitative analysis employed a framework approach., Results: We recruited 23 participants from 4 Canadian provinces (mean age: 28, Range: 20-44); 17 identified as racially/ethnically minoritized, one as sexual/gender minoritized, and five as racially/ethnically and sexually/gender minoritized. Participants emphasized that their culture/ethnicity, religion/spirituality, sexuality, gender, family, career, and being an immigrant are important aspects of their identity, with only one participant recognizing their identity as a "person with cancer". A cancer diagnosis altered the aspects of identity deemed most significant by participants. Both visible and invisible aspects of identity shaped participants' experiences and influenced their level of trust in the healthcare system., Conclusion: Racially, ethnically, gender, or sexually minoritized AYAs with cancer place considerable importance on aspects of their identity that are shaped by their respective communities. Recognizing and respecting these identities are paramount for healthcare professionals to deliver safe and inclusive care., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

We found that a standardized order set after hip fracture increased initiation of anti-osteoporosis medication and increased persistence at 1 year, but did not reduce secondary fractures., Background: A treatment gap exists after osteoporosis-related fractures. Introducing standardized care can improve treatment. We evaluated the impact of a hip fracture order set (OS) on anti-osteoporosis medication (AOM) initiation, persistence, and secondary fracture prevention., Methods: In 2015, one hospital in Manitoba, Canada, introduced a hip fracture OS including recommendations for the initiation of AOM (OS group). A control group was identified from the other hospitals in the same region. A retrospective cohort study was conducted using linked administrative health data. All individuals 50 + years with surgical treatment for low-energy hip fracture between 2010 and 2019 were included and followed for AOM initiation, medication persistence at 1 year, and secondary fractures. Between-group differences for each year were assessed using chi-square tests. Logistic regression models tested the impact of socio-demographic and clinical factors on initiation, persistence of AOM. Cox regression tested the risk of secondary fracture., Results: No baseline differences between OS group (813 patients) and control group (2150 patients) were observed in demographics, socioeconomic factors, or comorbidities. An increase in post-fracture AOM initiation was seen with OS introduction (OS group year before 16.7% versus year after 48.6%, p < 0.001). No change was seen in the control group. Persistence on AOM also increased (OS group year before 17.7% versus year after 28.4%, p < 0.001). No difference in secondary fractures was observed (OS group 19.8% versus control group 18.8%, p = 0.38)., Conclusion: Introduction of a hip fracture OS significantly increased AOM initiation and persistence at 1-year post-fracture. There was no significant difference in secondary fractures., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Osteoporosis Canada 2023 clinical practice guidelines increase the number of individuals recommended or suggested for anti-osteoporosis pharmacotherapy by refining treatment guidance for those who fell within the 2010 guidelines' moderate-risk category., Purpose: In 2023, Osteoporosis Canada updated its 2010 clinical practice guidelines based upon consideration of fracture history, 10-year major osteoporotic fracture (MOF) risk, and BMD T-score in conjunction with age. The 2023 guidelines eliminated risk categories, including the moderate-risk group that did not provide clear treatment guidance. The current study was performed to appreciate the implications of the shift from 2010 risk categories to 2023 treatment guidance., Methods: The study population consisted of 79,654 individuals age ≥ 50 years undergoing baseline DXA testing from January 1996 to March 2018. Each individual was assigned to mutually exclusive categories based on 2010 and 2023 guideline recommendations. Treatment qualification, 10-year predicted and 10-year observed MOF risk were compared., Results: Treatment reclassification under the 2023 guidelines only affected 33.8% of individuals in the 2010 moderate-risk group, with 13.0% assigned to no treatment, 14.4% to suggest treatment, and 6.4% to recommend treatment. During the mean follow-up of 7.2 years, 6364 (8.0%) individuals experienced one or more incidents of MOF. The observed 10-year cumulative incidence of MOF in the study population was 10.5% versus the predicted 10.7% (observed to predicted mean calibration ratio 0.98, 95% CI 0.96-1.00). Individuals reclassified from 2010 moderate risk to 2023 recommend treatment were at greater MOF risk than those in the 2010 moderate-risk group assigned to 2023 suggest treatment or no treatment, but at lower risk than those in the 2010 high-risk group., Conclusions: Osteoporosis Canada 2023 clinical practice guidelines affect individuals within the 2010 moderate-risk category, increasing the number for whom anti-osteoporosis pharmacotherapy is recommended or suggested. Increased treatment could reduce the population burden of osteoporotic fractures, though moderate-risk individuals now qualifying for treatment have a lower predicted and observed fracture risk than high-risk individuals recommended for treatment under the 2010 guidelines., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: We estimated the short-term effects of an educational workshop and 10-week outdoor walk group (OWG) compared to the workshop and 10 weekly reminders (WR) on increasing outdoor walking (primary outcome) and walking capacity, health-promoting behavior, and successful aging defined by engagement in meaningful activities and well-being (secondary outcomes) in older adults with difficulty walking outdoors., Methods: In a 4-site, parallel-group randomized controlled trial, two cohorts of community-living older adults (≥ 65 years) reporting difficulty walking outdoors participated. Following a 1-day workshop, participants were stratified and randomized to a 10-week OWG in parks or 10 telephone WR reinforcing workshop content. Masked evaluations occurred at 0, 3, and 5.5 months. We modeled minutes walked outdoors (derived from accelerometry and global positioning system data) using zero-inflated negative binomial regression with log link function, imputing for missing observations. We modeled non-imputed composite measures of walking capacity, health-promoting behavior, and successful aging using generalized linear models with general estimating equations based on a normal distribution and an unstructured correlation matrix. Analyses were adjusted for site, participation on own or with a partner, and cohort., Results: We randomized 190 people to the OWG (n = 98) and WR interventions (n = 92). At 0, 3, and 5.5 months, median outdoor walking minutes was 22.56, 13.04, and 0 in the OWG, and 24.00, 26.07, and 0 in the WR group, respectively. There was no difference between groups in change from baseline in minutes walked outdoors based on incidence rate ratio (IRR) and 95% confidence interval (CI) at 3 months (IRR = 0.74, 95% CI 0.47, 1.14) and 5.5 months (IRR = 0.77, 95% CI 0.44, 1.34). Greater 0 to 3-month change in walking capacity was observed in the OWG compared to the WR group (βz-scored difference = 0.14, 95% CI 0.02, 0.26) driven by significant improvement in walking self-efficacy; other comparisons were not significant., Conclusions: A group, park-based OWG was not superior to WR in increasing outdoor walking activity, health-promoting behavior or successful aging in older adults with difficulty walking outdoors; however, the OWG was superior to telephone WR in improving walking capacity through an increase in walking self-efficacy. Community implementation of the OWG is discussed., Trial Registration: ClinicalTrials.gov NCT03292510 Date of registration: September 25, 2017., (© 2024. The Author(s).)

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.)

Objectives: To understand the burden associated with pediatric chronic pain (CP) on the health care system compared with other costly chronic diseases prior to subspecialty care., Study Design: In this retrospective cohort study, we assessed all-cause health care utilization and direct health care costs associated with pediatric CP (n = 91) compared with juvenile arthritis (n = 135), inflammatory bowel disease (n = 90), type 1 diabetes (n = 475) or type 2 diabetes (n = 289), anxiety (n = 7193), and controls (n = 273) 2 and 5 years prior to patients entering subspecialty care in Manitoba, Canada. Linked data from physician encounters, emergency department visits, hospitalizations, and prescriptions were extracted from administrative databases. Differences in health care utilization and direct health care costs associated with CP vs the other conditions were tested using negative binomial and zero-inflated negative binomial regression models, respectively., Results: After adjustment for age at diagnosis, sex, location of residence, and socioeconomic status, CP continued to be associated with the highest number of consulted physicians and subspecialists and the highest number of physician billings compared with all other conditions (P < .01, respectively). CP was significantly associated with higher physician costs than juvenile arthritis, inflammatory bowel disease, type 1 diabetes, type 2 diabetes, or controls (P < .01, respectively); anxiety was associated with the highest physician and prescription costs among all cohorts (P < .01, respectively)., Conclusion: Compared with chronic inflammatory and endocrinologic conditions, pediatric CP and anxiety were associated with substantial burden on the health care system prior to subspecialty care, suggesting a need to assess gaps and resources in the management of CP and mental health conditions in the primary care setting., Competing Interests: Declaration of Competing Interest This research was funded by the Children Hospital Research Institute of Manitoba and the Children's Hospital Foundation of Manitoba. The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The aetiology of mental disorders involves genetic and environmental factors, both reflected in family health history. We examined the intergenerational transmission of multiple mental disorders from parents and grandparents using population-based, objectively measured family histories., Methods: This population-based retrospective cohort study used administrative healthcare databases in Manitoba, Canada and included adults living in Manitoba from 1977 to 2020 with linkages to at least one parent and one grandparent. Index date was when individuals turned 18 or 1 April 1977, whichever occurred later. Mental disorder diagnoses (mood and anxiety, substance use and psychotic disorders) were identified in individuals, parents and grandparents from hospitalization and outpatient records. Cox proportional hazards regression models included sociodemographic characteristics, individual's comorbidity and mental disorder history in a grandparent, mother and father., Results: Of 109,359 individuals with no mental disorder prior to index date, 47.1% were female, 36.3% had a mental disorder during follow-up, and 90.9% had a parent or grandparent with a history of a mental disorder prior to the index date. Both paternal and maternal history of a mental disorder increased the risk of the disorder in individuals. Psychotic disorders had the strongest association with parental history and were mostly influenced by paternal (hazards ratio [HR] 3.73, 95% confidence interval [CI] 2.99 to 4.64) compared to maternal history (HR 2.23, 95% CI, 1.89 to 2.64). Grandparent history was independently associated with the risk of all mental disorders but had the strongest influence on substance use disorders (HR 1.42, 95% CI, 1.34 to 1.50)., Conclusions: Parental history of mental disorders was associated with an increased risk of all mental disorders. Grandparent history of mental disorders was associated with a small risk increase of the disorders above and beyond parental history influence. This three-generation study further highlights the need for family-based interventional programs in families affected by mental disorders., Plain Language Summary Title: The Intergenerational Transfer of Mental Illnesses., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Although care of Parkinsonism (PKM) is assumed to be optimally provided by movement disorder neurologists within an interdisciplinary clinic model, there is a paucity of published data to support this., Objectives: To investigate the impact of movement disorder neurologist care of individuals with Parkinsonism (PKM)., Methods: A retrospective exposure design was adopted using administrative data. Incident PKM individuals were identified in billing claims. A nine-year exposure period to movement disorder neurologist, general neurologist and non-neurologist care was calculated based on the billing codes. Regression models were used to test the association of provider exposure on time to death and long-term care (LTC) admission. Linear models were used to test varying provider exposure and hospital admissions, hospital days and emergency department visits., Results: 1914 incident individuals were identified. There was no difference in PKM mortality, emergency visits, hospital admissions, or hospital days between providers, however exposure to general neurology and non-neurology care was associated with a significantly higher risk of admission to LTC compared to movement disorder neurologist care (HR 1.43; 95% CI 1.09-1.87 for general neurology (p-value = 0.0089); HR 1.61; 95% CI 1.25-2.05 for non-neurology (p-value = 0.0002), respectively., Conclusion: Movement disorder neurologist care is associated with a lower risk of admission to LTC over general neurologist care in individuals with PKM., Competing Interests: Declaration of competing interest The author group has no competing interest in regard to this manuscript. No AI was used during the creation of this submission. Financial disclosures are individually listed in each author's declaration. There is no conflict of interest relating to those mentioned that pertain to the content within this submission., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Importance: Data on the middle school outcomes of preterm children are limited and have methodologic issues., Objective: To study the association between preterm birth and grade 7 school performance., Methods: A retrospective population-based cohort study of children born in Manitoba, Canada between 1994 and 2006 using their grade 7 school performance data. A secondary sibling cohort was created comprising children born preterm and their full-term siblings. Primary exposure was preterm birth categorized as <28, 28-33 and 34-36 weeks gestation. The two co-primary grade 7 outcome measures were: not meeting the mathematics competencies, and not meeting the student engagement competencies. Multivariable logistic regression models tested the association between preterm birth and both co-primary outcomes; adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated., Results: 7653 preterm (gestational age median [IQR]: 35 weeks [34,36]) and 110,313 term (40 [39,40]) were included. 43% of < 28 weeks, 18% of 28-33 weeks and 17% of 34-36 weeks had the mathematics co-primary outcome compared to 13% of term children. The corresponding % for the student engagement outcome were 42%, 24%, 24% and 24% respectively. Preterm birth was associated with the mathematics (<28 weeks: 5.48, 3.89-7.70; 28-33 weeks: 1.47, 1.27-1.70; 34-36 weeks: 1.26, 1.16-1.35) and student engagement outcomes (<28 weeks: 2.49, 1.76-3.51; 28-33 weeks: 1.21, 1.06-1.39; 34-36 weeks: 1.09, 1.01-1.16). However, there was no difference in outcomes among the sibling cohort., Conclusions and Relevance: Children born preterm had lower grade 7 performance compared to children born term in this population-based cohort. Screening and supports for them in their middle school years are warranted., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP&#95;320, 360/420 nm for FlOP&#95;360, and 400/475 nm for FlOP&#95;400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats., Methods: In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure., Results: In humans, higher levels of FlOP&#95;320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01-2.20) and FlOP&#95;360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07-2.37) were associated with increased odds of osteoporosis. FlOP&#95;400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP&#95;320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm 3 ; P = 0.001) than the control group., Conclusion: In conclusion, higher FlOP&#95;320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The Royal Canadian Mounted Police (RCMP) Study includes longitudinal multimodal assessments of RCMP cadets from pre-training (i.e., starting the Cadet Training Program [CTP]) to post-deployment and for five years thereafter. The data allow for investigating the multidimensionality of volitional participation in digital health data collection frameworks within serial data collection platforms and the impact of participation inequalities by classifying cadets using the 90-9-1 rule. By classifying cadets as Lurkers, Contributors, and Superusers formally described by the 90-9-1 rule, where 90% of actors do not participate, 9% seldom contribute, and 1% contribute substantially allows for the assessing of relationships between participation inequalities in self-monitoring behaviors as well as whether mental health disorder symptoms at pre-training (i.e., starting the CTP) were associated with subsequent participation., Methods: Participants were asked to complete a Full Assessment prior to their training at CTP, as well as short daily surveys throughout their training. Participation frequency was described using a process where participants were rank ordered by the number of daily surveys completed and classified into one of three categories. Full assessment surveys completed prior to their training at CTP included screening tools for generalized anxiety disorder (GAD), major depressive disorder (MDD), posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), and panic disorder (PD). The Kruskal-Wallis H test was used to assess differences in participation rates between mental health disorder symptom screening groups for each measure at pre-training, and Spearman's Rho was used to test for associations amongst self-reported Full Assessment screening tool responses and the number of daily surveys completed during CTP., Results: There were 18557 daily survey records collected from 772 participants. The rank-ordering of cadets by the number of daily surveys completed produced three categories in line with the 90-9-1 rule: Superusers who were the top 1% of cadets ( n =8) and produced 6.4% of all recordings; Contributors who were the next 9% of cadets ( n =68) and produced 49.2% of the recordings; and Lurkers who were the next 90% of cadets ( n =695) and produced 44.4% of daily survey recordings. Lurkers had the largest proportion of positive screens for self-reported mental health disorders at pre-training., Conclusion: The creation of highly individualized, population-based mental health injury programs has been limited by an incomplete understanding of the causal relationships between protective factors and mental health. Disproportionate rates of disengagement from persons who screen positive for mental health disorders further compounds the difficulty in understanding the relationships between training programs and mental health. The current results suggest persons with mental health challenges may be less likely to engage in some forms of proactive mental health training. The current results also provide useful information about participation, adherence, and engagement that can be used to inform evidence-based paradigm shifts in health-related data collection in occupational populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Teckchandani, Shields, Andrews, Maguire, Jamshidi, Nisbet, Afifi, Lix, Stewart, Sauer-Zavala, Krakauer, Neary, Krätzig and Carleton.)

Purpose: To measure the impact of beliefs, expectations, side effects, and their combined effects on the risk for medication nonpersistence., Patients and Methods: Using a cross-sectional design, individuals from Saskatchewan, Canada who started a new antihypertensive, cholesterol-lowering, or antihyperglycemic medication were surveyed about risk factors for nonpersistence including: (a) beliefs measured by a composite score of three questions asking about the threat of the condition, importance of the drug, and harm of the drug; (b) incident side effects attributed to treatment; and (c) expectations for side effects before starting treatment. Descriptive statistics and logistic regression models were used to quantify the influence of these risk factors on the outcome of nonpersistence. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated., Results: Among 3,029 respondents, 5.8% (n=177) reported nonpersistence within four months after starting the new drug. After adjustment for numerous covariates representing sociodemographics, health-care providers, medication experiences and beliefs, both negative beliefs (OR: 7.26, 95%CI: 4.98-10.59) and incident side effects (OR: 8.00, 95%CI: 5.49-11.68) were associated with the highest odds of nonpersistence with no evidence of interaction. In contrast, expectations for side effects before starting treatment exhibited an important interaction with incident side effects following treatment initiation. Among respondents with incident side effects (n=741, 24.5%), the risk for early nonpersistence was 11.5% if they indicated an expectation for side effects before starting the medication compared to 23.6% if they did not (adjusted OR: 0.38, 95%CI: 0.25-0.60)., Conclusion: Expectations for side effects may be a previously unrecognized but important marker of the probability to persist with treatment. A high percentage of new medication users appeared unprepared for the possibility of side effects from their new medication making them less resilient if side effects occur., Competing Interests: Dr Niteesh Choudhry reports grants from National Institutes of Health, personal fees from RxAnte, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Blackburn et al.)

Purpose: To compare the cumulative incidence of mental disorders among adolescents and young adults (AYAs) diagnosed with cancer with the general population and their unaffected siblings., Methods: A retrospective, population-based, matched cohort design was used to investigate the impact of cancer diagnosis on mental disorders among individuals age 15-39 diagnosed between 1989 and 2019. Two cancer-free cohorts were identified: matched population-based and sibling cohorts. Outcomes included incidence of mood and anxiety disorders, substance use disorders, suicide outcomes, psychotic disorders, and any of the preceding four categories within 5 years of cancer diagnosis. Competing risk regression was used to estimate adjusted subhazard ratios (aSHR) and 95% CIs., Results: Among 3,818 AYAs with cancer matched to the population-based cancer-free cohort, individuals with cancer were more likely to be diagnosed with incident mental disorders than those without cancer; the risk was highest immediately after a cancer diagnosis and decreased over time with aSHR [95% CI] for mood and anxiety disorders at 0-6 months (11.27 [95% CI, 6.69 to 18.97]), 6-12 months (2.35 [95% CI, 1.54 to 3.58]), and 12-24 months (2.06 [95% CI, 1.55 to 2.75]); for substance use disorders at 0-6 months (2.73 [95% CI, 1.90 to 3.92]); for psychotic disorders at 0-6 months (4.69 [95% CI, 2.07 to 10.65]); and for any mental disorder at 0-6 months (4.46 [95% CI, 3.41 to 5.85]), 6-12 months (1.56 [95% CI, 1.14 to 2.14]), and 12-24 months (1.7 [95% CI, 1.36 to 2.13]) postcancer diagnosis. In sibling comparison, cancer diagnosis was associated with a higher incidence of mood and anxiety and any mental disorder during first 6 months of cancer diagnosis., Conclusion: AYAs with cancer experience a greater incidence of mental disorders after cancer diagnosis relative to population-based and sibling cohorts without cancer, primarily within first 2 years, underscoring the need to address mental health concerns during this period.

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. Participants reported fatigue impact (Daily Fatigue Impact Scale [DFIS]), depression and anxiety symptoms (Hospital Anxiety and Depression Scale [HADS]), and pain (Pain Effects Scale [PES]). Physician-diagnosed comorbidities, IBD characteristics, and physical and cognitive functioning were also assessed. We tested factors associated with fatigue using multivariable generalized linear models that estimated within-person and between-person effects., Results: Most participants were women (63.2%), White (85.4%), and had Crohn's disease (62%). At baseline, 27.9% reported moderate-severe fatigue impact, 16.7% had clinically elevated anxiety (HADS-A ≥11), and 6.5% had clinically elevated depression (HADS-D ≥11). Overall fatigue burden was stable over time, although approximately half the participants showed improved or worsening fatigue impact between annual visits during the study. On multivariable analysis, participants with a one-point higher HADS-D score had, on average, a 0.63-point higher DFIS score, whereas participants with a one-point higher PES score had a 0.78-point higher DFIS score. Within individuals, a one-point increase in HADS-D scores was associated with 0.61-point higher DFIS scores, in HADS-A scores with 0.23-point higher DFIS scores, and in PES scores with 0.38-point higher DFIS scores. No other variables predicted fatigue., Discussion: Anxiety, depression, and pain predicted fatigue impact over time in IBD, suggesting that targeting psychological factors and pain for intervention may lessen fatigue burden., (Copyright © 2024 by The American College of Gastroenterology.)

Peak bone mineral density (BMD) is one of the most important factors influencing the development of osteoporosis. It was predicted that a 10% increase in peak BMD will delay the onset of osteoporosis by 13 years. However, changes in peak BMD over time are unknown. This study aimed to investigate secular trends in peak BMD among young adults in the United States. Based on the National Health and Nutrition Examination Survey from 1999-2018, 3,975 males aged 19-28 years and 2370 females aged 31-40 years were our target population for estimating peak lumbar spine BMD. BMD was measured by dual-energy X-ray absorptiometry. Generalized linear models adjusted for multiple covariates were used to examine the secular trends in peak BMD in males and females, respectively. Secular trends for peak lumbar spine BMD from 1999-2000 to 2017-2018 were not statistically significant in males or females (all P linear and P quadratic  > 0.05). Similar results were observed in race/ethnicity subgroups (all P linear and P quadratic  > 0.05). However, in stratified analyses by obesity category, peak lumbar spine BMD in obese males and females increased from 1999-2000 to 2009-2010 and then decreased until 2017-2018, while peak lumbar spine BMD in non-obese females decreased from 1999-2000 to 2005-2006 and then increased until 2017-2018 (all P quadratic  < 0.05). Peak lumbar spine BMD was greater in obese males and females than in non-obese males and females up to 2009-2010, but not from 2011-2012 onwards. Overall, there were no significant secular trends in peak lumbar spine BMD. However, secular trends differed between obese and non-obese groups., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The validity of chronic disease case definitions for administrative health data may change over time due to changes in data quality. Trend control charts to identify out-of-control (OOC; i.e., unexpected) observations in a time series may indicate where disease estimates are influenced by changes in data quality., Objective: Apply and compare trend control charts methods for multiple sclerosis (MS) incidence and prevalence estimates using previously-validated case definitions for Manitoba, Canada., Methods: Eight case definitions were identified from published literature and applied to Manitoba administrative health data from January 1, 1972 to December 31, 2018. Incidence and prevalence trends were modeled using negative binomial and generalized estimating equation models, respectively. Trend control charts were used to plot predicted case counts against observed case counts. Control limits to identify OOC observations were calculated using two methods: predicted case count ±0.8*standard deviation (0.8*SD) and predicted case count ±2*standard deviation (2*SD). Differences in proportion of OOC observations across case definitions was assessed using McNemar's test., Results: The proportion of OOC observations ranged from 0.71 to 0.90 for incidence and 0.72 to 0.98 for prevalence when using the 0.8*SD control limits. A lower proportion of OOC observations (0.46 to 0.74 for incidence; 0.30 to 0.74 for prevalence) was observed for the 2*SD control limits. Neither method resulted in significant differences in OOC observations across case definitions., Conclusions: The proportion of OOC observations in trend control charts varied with the control limit method adopted, but statistical significance did not. Trend control charts are a potentially useful tool for developing surveillance methods, but may benefit from disease-specific calibrated control limits., Competing Interests: Conflicts of interest: RAM receives research funding from: Canadian Institutes of Health Research (CIHR), Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. LML is supported by funding from the Canada Research Chairs program and CIHR. The other authors have no conflicts of interest to declare.

Context: Osteoporotic fracture is a major public health issue globally. Human research on the association between amino acids (AAs) and fracture is still lacking., Objective: To examine the association between AAs and recent osteoporotic fractures., Methods: This age and sex matched incident case-control study identified 44 recent x-ray confirmed fracture cases in the Second Hospital of Jilin University and 88 community-based healthy controls aged 50+ years. Plasma AAs were measured by high performance liquid chromatography coupled with mass spectrometry. After adjusting for covariates (i.e., body mass index, milk intake >1 time/week, falls and physical activity), we conducted conditional logistical regression models to test the association between AAs and fracture., Results: Among cases there were 23 (52.3%) hip fractures and 21 (47.7%) non-hip fractures. Total, essential, and non-essential AAs were significantly lower in cases than in controls. In the multivariable conditional logistic regression models, after adjusting for covariates, each standard deviation increase in the total (odds ratio [OR]: 0.304; 95% confidence interval [CI]: 0.117-0.794), essential (OR: 0.408; 95% CI: 0.181-0.923) and non-essential AAs (OR: 0.290; 95%CI: 0.107-0.782) was negatively associated with recent fracture. These inverse associations were mainly found for hip fracture, rather than non-hip fractures. Among these AAs, lysine, alanine, arginine, glutamine, histidine and piperamide showed the significantly negative associations with fracture., Conclusion: There was a negative relationship between AAs and recent osteoporotic fracture; such relationship appeared to be more obvious for hip fracture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Shi, Wang, Ma, Leslie, Lix, Shi, Kan and Yang.)

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data. The study population comprised 59 696 women (mean age 65.7 ± 9.4 yr). Over mean 8.7 yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF <10%), moderate (10%-19.9%) and high (≥20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend <.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96-2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events. Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Sex differences in acute myocardial infarction treatment and outcomes are well documented, but it is unclear whether differences are consistent across countries. The objective of this study was to investigate the epidemiology, use of interventional procedures, and outcomes for older females and males hospitalized with ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) in 6 diverse countries., Methods: We conducted a serial cross-sectional cohort study of 1 508 205 adults aged ≥66 years hospitalized with STEMI and NSTEMI between 2011 and 2018 in the United States, Canada, England, the Netherlands, Taiwan, and Israel using administrative data. We compared females and males within each country with respect to age-standardized hospitalization rates, rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery within 90 days of hospitalization, and 30-day age- and comorbidity-adjusted mortality., Results: Hospitalization rates for STEMI and NSTEMI decreased between 2011 and 2018 in all countries, although the hospitalization rate ratio (rate in males/rate in females) increased in virtually all countries (eg, US STEMI ratio, 1.58:1 in 2011 and 1.73:1 in 2018; Israel NSTEMI ratio, 1.71:1 in 2011 and 2.11:1 in 2018). Rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery were lower for females than males for STEMI in all countries and years (eg, US cardiac catheterization in 2018, 88.6% for females versus 91.5% for males; Israel percutaneous coronary intervention in 2018, 76.7% for females versus 84.8% for males) with similar findings for NSTEMI. Adjusted mortality for STEMI in 2018 was higher for females than males in 5 countries (the United States, Canada, the Netherlands, Israel, and Taiwan) but lower for females than males in 5 countries for NSTEMI., Conclusions: We observed a larger decline in acute myocardial infarction hospitalizations for females than males between 2011 and 2018. Females were less likely to receive cardiac interventions and had higher mortality after STEMI. Sex disparities seem to transcend borders, raising questions about the underlying causes and remedies., Competing Interests: Disclosures None.

Purpose: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models., Methods: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics., Results: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease., Conclusion: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF., (© 2023. The Author(s).)

Objectives: Case ascertainment algorithms were developed and validated to identify people living with cirrhosis in administrative health data in Manitoba, Canada using primary care electronic medical records (EMR) to define the reference standards., Methods: We linked provincial administrative health data to primary care EMR data. The validation cohort included 116,675 Manitobans aged >18 years with at least one primary care visit between April 1998 and March 2015. Hospital records, physician billing claims, vital statistics, and prescription drug data were used to develop and test 93 case-finding algorithms. A validated case definition for primary care EMR data was the reference standard. We estimated sensitivity, specificity, positive and negative predictive values (PPV, NPV), Youden's index, area under the receiver operative curve, and their 95% confidence intervals (CIs)., Results: A total of 116,675 people were in the validation cohort. The prevalence of cirrhosis was 1.4% ( n = 1593). Algorithm sensitivity estimates ranged from 32.5% (95% CI 32.2-32.8) to 68.3% (95% CI 68.0-68.9) and PPV from 17.4% (95% CI 17.1-17.6) to 23.4% (95% CI 23.1-23.6). Specificity (95.5-98.2) and NPV (approximately 99%) were high for all algorithms. The algorithms had slightly higher sensitivity estimates among men compared with women, and individuals aged ≥45 years compared to those aged 18-44 years., Conclusion: Cirrhosis algorithms applied to administrative health data had moderate validity when a validated case definition for primary care EMRs was the reference standard. This study provides algorithms for identifying diagnosed cirrhosis cases for population-based research and surveillance studies., Competing Interests: The authors have no conflicts of interest to declare., (© Canadian Association for the Study of the Liver, 2024.)

Purpose: The incidence of childhood-onset inflammatory bowel disease (IBD) is rising. We described variation in health services utilization and need for surgery among children with IBD between six and 60 months following IBD diagnosis across Canadian pediatric centers and evaluated the associations between care provided at diagnosis at each center and the variation in these outcomes., Patients and Methods: Using population-based deterministically-linked health administrative data from four Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario) we identified children diagnosed with IBD <16 years of age using validated algorithms. Children were assigned to a pediatric center of care using a hierarchical approach based on where they received their initial care. Outcomes included IBD-related hospitalizations, emergency department (ED) visits, and IBD-related abdominal surgery occurring between 6 and sixty months after diagnosis. Mixed-effects meta-analysis was used to pool results and examine the association between center-level care provision and outcomes., Results: We identified 3784 incident cases of pediatric IBD, of whom 2937 (77.6%) were treated at pediatric centers. Almost a third (31.4%) of children had ≥1 IBD-related hospitalization and there were 0.66 hospitalizations per person during follow-up. More than half (55.8%) of children had ≥1 ED visit and there were 1.64 ED visits per person. Between-center heterogeneity was high for both outcomes; centers where more children visited the ED at diagnosis had more IBD-related hospitalizations and more ED visits during follow-up. Between-center heterogeneity was high for intestinal resection in Crohn's disease but not colectomy in ulcerative colitis., Conclusion: There is variation in health services utilization among children with IBD and risk of undergoing intestinal resection in those with Crohn's disease, but not colectomy among children with ulcerative colitis, across Canadian pediatric tertiary-care centers. Improvements in clinical care pathways are needed to ensure all children have equitable and timely access to high quality care., Competing Interests: Matthew Carroll has received speaker fees from AbbVie. Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Amgen, Janssen, Pfizer, Sandoz, and Pendopharm. Dr. Kaplan received grants for research from Ferring and for educational activities from AbbVie, Bristol Myers Squibb, Ferring, Fresenius-Kabi, Janssen, Pfizer, Takeda. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. September 7, 2018. Anthony Otley has been on advisory boards of AbbVie Canada, Janssen Canada and Amgen. He has received unrestricted educational grants from AbbVie Canada. His site is involved with clinical trials for AbbVie, Pfizer, Takeda, Eli Lily and BMS. He is co-owner of the copyright for PUCAI and the IMPACT questionnaire. Harminder Singh has been on advisory boards or consulted for Pendopharm, Abbvie Canada, Amgen Canada, Organon Canada, Eli Lilly Canada, Roche Canada, Sandoz Canada, Takeda Canada, Bristol Myers Squibb, and Guardant Health Inc. and has received research funding for an investigator-initiated study from Pfizer. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb. He is on the speaker’s panel for Janssen, Takeda, Abbvie and has participated in educational activities supported by Viatris, Fresenius Kabi, and Amgen. Anne Griffiths is past holder of the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. She has received research support from Abbvie Canada. She is co-owner of copyright for the Pediatric Ulcerative Colitis Activity Index (PUCAI) and for the TUMMY-UC. She has been an advisory board member or consultant for Abbvie, Amgen, BristolMyersSquibb, Janssen, Lilly, Merck, Pfizer, Takeda, and has received speaker fees from Abbvie, Janssen, Takeda. David Mack is co-owner of Biotagenics Inc. Kevan Jacobson has been on Advisory boards of Abbvie Canada, Janssen Canada, Amgen, Merck Canada, Mylan Pharmaceuticals, Viatris, and Mckesson Canada. He has been on the speaker’s bureau of Abbvie Canada and Janssen Canada. He has received investigator-initiated research support from Abbvie Canada and Janssen Canada. He has stock options for Engene. Geoffrey Nguyen has served on advisory boards for Abbvie Canada and Takeda Canada. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada, and Amgen Canada. Charles Bernstein is supported by the Bingham Chair in Gastroenterology. He has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, Eli Lilly Canada, Ferring Canada, JAMP Pharmaceuticals, Pendopharm Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada. He has educational grants from Abbvie Canada, Amgen Canada, Bristol Myers Squibb Canada, Eli Lilly Canada, Organon Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. He is on the speaker’s panel for Abbvie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. He has received research funding from Abbvie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada, and Takeda Canada. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire, and Takeda. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He has also acted as a consultant for the Canadian Agency for Drugs and Technology in Health. The authors report no other conflicts of interest in this work., (© 2024 Kuenzig et al.)

Background: Smoking is a risk factor for many chronic diseases. Multiple smoking status ascertainment algorithms have been developed for population-based electronic health databases such as administrative databases and electronic medical records (EMRs). Evidence syntheses of algorithm validation studies have often focused on chronic diseases rather than risk factors. We conducted a systematic review and meta-analysis of smoking status ascertainment algorithms to describe the characteristics and validity of these algorithms., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. We searched articles published from 1990 to 2022 in EMBASE, MEDLINE, Scopus, and Web of Science with key terms such as validity, administrative data, electronic health records, smoking, and tobacco use. The extracted information, including article characteristics, algorithm characteristics, and validity measures, was descriptively analyzed. Sources of heterogeneity in validity measures were estimated using a meta-regression model. Risk of bias (ROB) in the reviewed articles was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool., Results: The initial search yielded 2086 articles; 57 were selected for review and 116 algorithms were identified. Almost three-quarters (71.6%) of algorithms were based on EMR data. The algorithms were primarily constructed using diagnosis codes for smoking-related conditions, although prescription medication codes for smoking treatments were also adopted. About half of the algorithms were developed using machine-learning models. The pooled estimates of positive predictive value, sensitivity, and specificity were 0.843, 0.672, and 0.918 respectively. Algorithm sensitivity and specificity were highly variable and ranged from 3 to 100% and 36 to 100%, respectively. Model-based algorithms had significantly greater sensitivity (p = 0.006) than rule-based algorithms. Algorithms for EMR data had higher sensitivity than algorithms for administrative data (p = 0.001). The ROB was low in most of the articles (76.3%) that underwent the assessment., Conclusions: Multiple algorithms using different data sources and methods have been proposed to ascertain smoking status in electronic health data. Many algorithms had low sensitivity and positive predictive value, but the data source influenced their validity. Algorithms based on machine-learning models for multiple linked data sources have improved validity., (© 2024. The Author(s).)

Purpose: The objective of this systematic review was to describe the prevalence and magnitude of response shift effects, for different response shift methods, populations, study designs, and patient-reported outcome measures (PROM)s., Methods: A literature search was performed in MEDLINE, PSYCINFO, CINAHL, EMBASE, Social Science Citation Index, and Dissertations & Theses Global to identify longitudinal quantitative studies that examined response shift using PROMs, published before 2021. The magnitude of each response shift effect (effect sizes, R-squared or percentage of respondents with response shift) was ascertained based on reported statistical information or as stated in the manuscript. Prevalence and magnitudes of response shift effects were summarized at two levels of analysis (study and effect levels), for recalibration and reprioritization/reconceptualization separately, and for different response shift methods, and population, study design, and PROM characteristics. Analyses were conducted twice: (a) including all studies and samples, and (b) including only unrelated studies and independent samples., Results: Of the 150 included studies, 130 (86.7%) detected response shift effects. Of the 4868 effects investigated, 793 (16.3%) revealed response shift. Effect sizes could be determined for 105 (70.0%) of the studies for a total of 1130 effects, of which 537 (47.5%) resulted in detection of response shift. Whereas effect sizes varied widely, most median recalibration effect sizes (Cohen's d) were between 0.20 and 0.30 and median reprioritization/reconceptualization effect sizes rarely exceeded 0.15, across the characteristics. Similar results were obtained from unrelated studies., Conclusion: The results draw attention to the need to focus on understanding variability in response shift results: Who experience response shifts, to what extent, and under which circumstances?, (© 2023. The Author(s).)

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.)

Aim: To identify the risk factors for optic nerve hypoplasia (ONH) and septo-optic dysplasia (SOD)., Method: A retrospective, population-based study with case-control design was undertaken using the Population Research Data Repository at the Manitoba Center for Health Policy in Manitoba, Canada. Cases were 111 patients (63 males, 48 females; age range 1-35 years [mean 11 years 6 months, SD 7 years 2 months]) with ONH and SOD diagnosed from 1990 to 2019, matched to 555 unrelated population-based controls (315 males, 240 females; age range 1-35 years [mean 11 years 6 months, SD 7 years 2 months]) on year of birth, sex, and area of residence. Additionally, 75 cases (46 males, 29 females; age range 2-35 years [mean 12 years 6 months, SD 7 years 2 months]) with ONH and SOD were matched one-on-one with sibling controls (40 males, 35 females; age range 0-33 years [mean 11 years 7 months, SD 7 years 10 months], the rest did not have siblings). Several antenatal maternal risk factors associated with ONH and SOD were tested for their association with case and control group membership using adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from a multivariate conditional logistic regression model. The outcome was the risk of developing ONH and SOD., Results: Maternal age at conception (OR = 0.91, 95% CI = 0.86-0.96), primigravida (OR = 3.39, 95% CI = 1.92-6.01), and smoking (OR = 2.86, 95% CI = 1.61-5.05) were independently associated with ONH and SOD in the cohort matched to unrelated controls (p < 0.001). In the sibling cohort, smoking was an important risk factor (OR = 3.65, 95% CI = 1.2-11.1, p = 0.02)., Interpretation: Unmodifiable and modifiable antenatal maternal risk factors are associated with ONH and SOD. Our investigation suggests that several risk factors reported in previous studies may have been due to confounding bias and that maternal smoking during pregnancy is the main modifiable risk factor associated with ONH and SOD., What This Paper Adds: Historically, many antenatal risk factors have been associated with optic nerve hypoplasia (ONH) and septo-optic dysplasia (SOD). Population-based data with matched controls for potential confounding bias are lacking. Young maternal age at conception, primigravida, and smoking during pregnancy are the main risk factors for ONH and SOD using a population-based, case-control design., (© 2023 Mac Keith Press.)

Objectives: FRAX® uses clinical risk factors, with or without bone mineral density (BMD), to calculate 10-year fracture risk. Rheumatoid arthritis (RA) is a risk factor for osteoporotic fracture and a FRAX input variable. FRAX predates the current era of RA treatment. We examined how well FRAX predicts fracture in contemporary RA patients., Methods: Administrative data from patients receiving BMD testing were linked to the Manitoba Population Health Research Data Repository. Observed cumulative 10-year Major Osteoporotic Fracture (MOF) probability was compared with FRAX-predicted 10-year MOF probability with BMD for assessing calibration. MOF risk stratification was assessed using Cox regression., Results: RA patients (N = 2,099, 208 with incident MOF) and non-RA patients (N = 2,099, with 165 incident MOF) were identified. For RA patients, FRAX predicted 10-year risk was 13.2% and observed 10-year MOF risk was 13.2% (95% CI 11.6% to 15.1%). The slope of the calibration plot was 0.67 (95% CI 0.53-0. 81) in those with RA vs 0.98 (95% CI 0.61-1.34) in non-RA patients. Risk was overestimated in RA patients with high FRAX scores (>20%), but FRAX was well-calibrated in other groups. FRAX stratified risk in those with and without RA (hazard ratios 1.52, 95% 1.25-1.72 vs 2.00, 95% 1.73-2.31), with slightly better performance in the latter (p-interaction = 0.004)., Conclusions: FRAX predicts fracture risk in contemporary RA patients but may slightly overestimate risk in those already at high predicted risk. Thus, the current FRAX tool continues to be appropriate for fracture risk assessment in RA patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Hip fractures are costly and common in older adults, but there is limited understanding of how treatment patterns and outcomes might differ between countries., Methods: We performed a retrospective serial cross-sectional cohort study of adults aged ≥66 years hospitalized with hip fracture between 2011 and 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. We examined mortality, hip fracture treatment approaches (total hip arthroplasty [THA], hemiarthroplasty [HA], internal fixation [IF], and nonoperative), and health system performance measures, including hospital length of stay (LOS), 30-day readmission rates, and time-to-surgery., Results: The total number of hip fracture admissions between 2011 and 2018 ranged from 23,941 in Israel to 1,219,696 in the US. In 2018, 30-day mortality varied from 3% (16% at 1 year) in Taiwan to 10% (27%) in the Netherlands. With regards to processes of care, the proportion of hip fractures treated with HA (range 23%-45%) and THA (0.2%-10%) differed widely across countries. For example, in 2018, THA was used to treat approximately 9% of patients in England and Israel but less than 1% in Taiwan. Overall, IF was the most common surgery performed in all countries (40%-60% of patients). IF was used in approximately 60% of patients in the US and Israel, but only 40% in England. In 2018, rates of nonoperative management ranged from 5% of patients in Taiwan to nearly 10% in England. Mean hospital LOS in 2018 ranged from 6.4 days (US) to 18.7 days (England). The 30-day readmission rate in 2018 ranged from 8% (in Canada and the Netherlands) to nearly 18% in England. The mean days to surgery in 2018 ranged from 0.5 days (Israel) to 1.6 days (Canada)., Conclusions: We observed substantial between-country variation in mortality, surgical approaches, and health system performance measures. These findings underscore the need for further research to inform evidence-based surgical approaches., (© 2023 The American Geriatrics Society.)

Introduction: Administrative health records (AHRs) are used to conduct population-based post-market drug safety and comparative effectiveness studies to inform healthcare decision making. However, the cost of data extraction, and the challenges associated with privacy and securing approvals can make it challenging for researchers to conduct methodological research in a timely manner using real data. Generating synthetic AHRs that reasonably represent the real-world data are beneficial for developing analytic methods and training analysts to rapidly implement study protocols. We generated synthetic AHRs using two methods and compared these synthetic AHRs to real-world AHRs. We described the challenges associated with using synthetic AHRs for real-world study., Methods: The real-world AHRs comprised prescription drug records for individuals with healthcare insurance coverage in the Population Research Data Repository (PRDR) from Manitoba, Canada for the 10-year period from 2008 to 2017. Synthetic data were generated using the Observational Medical Dataset Simulator II (OSIM2) and a modification (ModOSIM). Synthetic and real-world data were described using frequencies and percentages. Agreement of prescription drug use measures in PRDR, OSIM2 and ModOSIM was estimated with the concordance coefficient., Results: The PRDR cohort included 169,586,633 drug records and 1,395 drug types for 1,604,734 individuals. Synthetic data for 1,000,000 individuals were generated using OSIM2 and ModOSIM. Sex and age group distributions were similar in the real-world and synthetic AHRs. However, there were significant differences in the number of drug records and number of unique drugs per person for OSIM2 and ModOSIM when compared with PRDR. For the average number of days of drug use, concordance with the PRDR was 16% (95% confidence interval [CI]: 12%-19%) for OSIM2 and 88% (95% CI: 87%-90%) for ModOSIM., Conclusions: ModOSIM data were more similar to PRDR than OSIM2 data on many measures. Synthetic AHRs consistent with those found in real-world settings can be generated using ModOSIM. Synthetic data will benefit rapid implementation of methodological studies and data analyst training., Competing Interests: Competing interests: The authors declare that they have no competing interests.

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. Models were fit to participant average scores and change scores on distress symptom measures. Covariates included sociodemographic factors, comorbidity, physical disability and cognitive function., Results: In the primary univariate analyses of overall work impairment at the 50th percentile, greater severity of distress symptoms was associated with greater work impairment: pain (average β = 0.27, p < 0.001; change β = 0.08, p < 0.001), fatigue (average β = 0.21, p < 0.001; change β = 0.09, p < 0.001) depression (average, β = 0.35, p < 0.001; change, β = 0.16, p < 0.001), anxiety (average, β = 0.24, p < 0.001; change, β = 0.08, p < 0 0.01). Findings were similar in multivariable analyses., Conclusion: Pain, fatigue, depression, and anxiety symptoms are important determinants of work impairment in persons with immune-mediated diseases and persons with psychiatric disorders. Successful clinical management of these symptoms has potential to improve work-related outcomes across IMIDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Identifying children at high risk of developing asthma can facilitate prevention and early management strategies. We developed a prediction model of children's asthma risk using objectively collected population-based children and parental histories of comorbidities., Methods: We conducted a retrospective population-based cohort study using administrative data from Manitoba, Canada, and included children born from 1974 to 2000 with linkages to ≥1 parent. We identified asthma and prior comorbid condition diagnoses from hospital and outpatient records. We used two machine-learning models: least absolute shrinkage and selection operator (LASSO) logistic regression (LR) and random forest (RF) to identify important predictors. The predictors in the base model included children's demographics, allergic conditions, respiratory infections, and parental asthma. Subsequent models included additional multiple comorbidities for children and parents., Results: The cohort included 195,666 children: 51.3% were males and 17.7% had asthma diagnosis. The base LR model achieved a low predictive performance with sensitivity of 0.47, 95% confidence interval (0.45-0.48), and specificity of 0.67 (0.66-0.67) using a predicted probability threshold of 0.20. Sensitivity significantly improved when children's comorbidities were included using LASSO LR: 0.71 (0.69-0.72). Predictive performance further improved by including parental comorbidities (sensitivity = 0.72 [0.70-0.73], specificity = 0.69 [0.69-0.70]). We observed similar results for the RF models. Children's menstrual disorders and mood and anxiety disorders, parental lipid metabolism disorders and asthma were among the most important variables that predicted asthma risk., Conclusion: Including children and parental comorbidities to children's asthma prediction models improves their accuracy., (© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Optimal duration of bisphosphonate therapy was unknown until the FLEX study was published in 2006 showing a 5-year course to be adequate for most women. In 2008, a link between long-term bisphosphonate and atypical femoral fractures was reported and confirmed in later studies. We hypothesized these landmark observations should have led to a decrease in use of bisphosphonates for >5 or 10 years, from 2010 onward. The Manitoba Bone Mineral Density (BMD) Registry with linkage to provincial pharmacy data was used to determine the percentage of long- and very long-term bisphosphonate users from therapy start. The cohort comprised women aged >50 years with BMD between 1995 and 2018 with oral bisphosphonate first prescribed for >90 days with adherence >75% in the first year. For each calendar year of continued therapy, the percentage of patients and medication possession rate was tabulated. The percentage of users beyond 5 years was compared among patients who started therapy in 1998-2004 (those taking 5 years of therapy still finish before 2010) versus 2005-2012 (all new therapy starts overlap 2010 in those taking ≥5 years of treatment). The cohort included 2991 women with mean follow-up 8.8 (1.3) years, 64.9% of whom took continuous oral bisphosphonate for >5 years and 41.9% for >10 years. In the earlier versus later era, there were 74.4% versus 70.2% who completed 5 years. With respect to longer treatment, there were 68.0% and 60.5% of patients treated for 6 or more years (p < 0.0001) and 46.6% versus 33.5% treated for >10 years (p = 0.08). Medication possession rate was >79% in every year of therapy. Landmark studies leading to more limited bisphosphonate courses may have slightly reduced longer-term treatment, but up to one-third of adherent patients in the modern era still receive continuous bisphosphonate therapy for >10 years. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

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., Methods: Adults with MS underwent physical and cognitive assessments and reported symptoms of fatigue (Daily Fatigue Impact Scale), depression and anxiety (Hospital Anxiety and Depression Scale (HADS)), and HRQoL (RAND-36) annually ( n = 4 visits). We evaluated associations of elevated symptoms of anxiety (HADS-A) and depression (HADS-D), fatigue, physical function (timed-walk and nine-hole peg test), cognitive function and comorbidity count with physical (PCS-36) and mental (MCS-36) HRQoL using multivariable linear models-estimating between-person and within-person effects., Results: Of 255 participants with MS enrolled, 81.6% were women. After adjustment, within-person increases in depression and fatigue were associated with decreases in physical HRQoL. Increases in depression, anxiety, and comorbidity count were associated with decreases in mental HRQoL., Conclusions: Within-person increases in symptoms of depression, anxiety and fatigue, and comorbidity count are associated with HRQoL decreases among adults with MS, highlighting the potential magnitude of individual benefit of intervention for these symptoms., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ruth Ann Marrie receives research funding from CIHR, Research Manitoba, MS Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense, and is a co-investigator on studies receiving funding from Biogen Idec and Roche Canada. She holds the Waugh Family Chair in Multiple Sclerosis. Dr Bernstein is supported by the Bingham Chair in Gastroenterology. Dr Bernstein has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, JAMP Pharmaceuticals, Lilly Canada, Roche Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada; Consultant for Mylan Pharmaceuticals and Takeda; Educational grants from Abbvie Canada, Bristol Myers Squibb Canada, Ferring Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. Speaker’s panel for Abbvie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from Abbvie Canada, Amgen Canada, Sandoz Canada, Takeda Canada and Pfizer Canada. Ms Dolovich has no conflicts to declare. Dr Graff has consulted to Roche Canada. She receives research funding from CIHR, MS Canada and Crohn’s and Colitis Canada. Dr Bolton receives research funding from CIHR, Brain and Behavior Research Foundation, Crohn’s and Colitis Canada and the MS Canada. Dr Fisk receives research grant support from the Canadian Institutes of Health Research, the National Multiple Sclerosis Society, MS Canada, Crohn’s and Colitis Canada, Research Nova Scotia; consultation and distribution royalties from MAPI Research Trust. Dr Hitchon receives research funding from CIHR, unrelated grant funding from Pfizer; Advisory board for Astra-Zeneca Canada for unrelated product, unrelated research funds from Research Manitoba, Health Sciences Center foundation, International League of Associations for Rheumatology, unrelated educational funds from the Royal College of Physicians and Surgeons of Canada. Dr Lix receives funding from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. Dr Patten receives research funding from CIHR, the MS Society of Canada, Roche, Biogen, and the Government of Alberta. He holds the Cuthbertson & Fisher Chair in Pediatric Mental Health at the University of Calgary. Dr Marriott has conducted trials for Biogen Idec, Sanofi and Roche, and receives research funding from MS Canada.

Objective: The current study examined variations in cardioautonomic lability during the Royal Canadian Mounted Police (RCMP) Cadet Training Program (CTP) between cadets starting their training who did or did not screen positive for one or more mental health disorders (i.e., posttraumatic stress disorder [PTSD], major depressive disorder [MDD], social anxiety disorder [SAD], generalized anxiety disorder [GAD], panic disorder [PD], alcohol use disorder [AUD])., Methods: Electrocardiogram (ECG) signals integrated into Hexoskin garments were used to record ECG and heart rate Over the 26-week CTP. There were 31 heart rate variability (HRV) parameters calculated using Kubios Premium HRV analysis software. Mann-Whitney U -tests were used to perform groupwise comparisons of participant raw values and HRV during the CTP., Results: A total of 157 cadets (79% male) were screened for any mental disorder using self-report surveys and then grouped by positive and negative screening. Analyses indicated a statistically significant ( p  < 0.05) decrease in low frequency (LF): High Frequency (HF) variability during CTP, but only for cadets who endorsed clinically significant anxiety symptoms on the GAD-7 at the start of their training. There were no other statistically significant groupwise differences., Conclusion: The results indicate the participants have excellent cardiac health overall and suggest potentially important differences between groups, such that cadets who endorsed clinically significant anxiety symptoms on the GAD-7 showed less variability in the LF:HF ratio over the course of the CTP. The relatively lower variability suggests decreased parasympathetic tone in those without clinically significant anxiety symptoms. The results also have important implications for future investigations of cardioautonomic dysfunction and chronic hypothalamic pituitary adrenal (HPA) axis deviations in policing populations with anxiety disorders; specifically, cardioautonomic inflexibility related to cardiovascular morbidity and mortality. In any case, the current results provide an important baseline for future cardiac research with cadets and serving officers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Teckchandani, Neary, Andrews, Maguire, Jamshidi, Nisbet, Shields, Afifi, Sauer-Zavala, Lix, Krakauer, Asmundson, Krätzig and Carleton.)

Background: Accurate coding of diagnoses of SARS-CoV-2 infection in administrative data benefits population-based studies about the epidemiology, treatment and outcomes of COVID-19. We describe the validity of diagnoses of SARS-CoV-2 infection recorded in hospital discharge abstracts, emergency department records and outpatient physician service claims from 3 Canadian provinces., Methods: In this cohort study, population-based inpatient, emergency department and outpatient records were linked to SARS-CoV-2 polymerase chain reaction (PCR; reference standard) test results from British Columbia, Manitoba and Ontario for Apr. 1, 2020, to Mar. 31, 2021. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of diagnoses of SARS-CoV-2 infection were estimated for each quarter in the study period, overall and by province, age group and sex., Results: Our study encompassed more than 13 million SARS-CoV-2 PCR test results. Specificity and NPV of diagnoses of SARS-CoV-2 infection were consistently high (i.e., most estimates were > 95%). Overall sensitivity estimates were 86.2%, 60.4% and 20.3% in the first quarter for inpatient, emergency department and outpatient cohorts, and 66.2%, 47.5% and 25.0% in the last quarter, respectively. For inpatients, overall PPV estimates ranged from 50.0% to 66.4%. For emergency department patients, overall PPV estimates were 76.9% and 68.3% in the first and last quarters, respectively. For outpatients, PPV estimates were 6.8% and 29.1% in the first and last quarters, respectively., Interpretation: We found variations in the validity of diagnoses for SARS-CoV-2 infection recorded in different health care settings, geographic areas and over time. Our multiprovince validation study provides evidence about the potential use of inpatient and emergency department records as an alternative to population-based laboratory data for identification of patients with SARS-CoV-2 infection, but does not support the use of outpatient claims for this purpose., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

Objective: To test the association of early disease severity with grade 12 standards test performance in individuals with childhood-onset chronic rheumatic diseases (ChildCRDs), including juvenile arthritis and systemic autoimmune rheumatic diseases., Methods: We used linked provincial administrative data to identify patients with ChildCRDs born between 1979 and 1998 in Manitoba, Canada. Primary outcomes were Language and Arts Achievement Index (LAI) scores and Math Achievement Index (MAI) scores from grade 12 standards test results as well as enrollment data. The secondary outcome was enrollment in grade 12 by 17 years of age. Latent class trajectory analysis identified disease severity groups using physician visits following diagnosis. Multivariable linear regression tested the association of disease severity groups with LAI and MAI scores, and logistic regression tested the association of disease severity with age-appropriate enrollment, after adjusting for sociodemographic factors and psychiatric morbidities., Results: The study cohort included 541 patients, 70.1% of whom were female. A 3-class trajectory model provided the best fit; it classified 9.7% of patients as having severe disease, 54.5% as having moderate disease, and 35.8% as having mild disease. After covariate adjustment, severe disease was associated with poorer LAI and MAI scores but not with age-appropriate enrollment., Conclusion: Among patients with ChildCRDs, those with severe disease performed more poorly on grade 12 standards tests, independent of sociodemographic and psychiatric risk factors. Clinicians should work with educators and policy makers to advocate for supports to improve educational outcomes of patients with ChildCRDs., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: Serving Royal Canadian Mounted Police (RCMP) have screened positive for one or more mental disorders based on self-reported symptoms with substantial prevalence (i.e., 50.2%). Mental health challenges for military and paramilitary populations have historically been attributed to insufficient recruit screening; however, cadet mental health when starting the Cadet Training Program (CTP) was unknown. Our objective was to estimate RCMP Cadet mental health when starting the CTP and test for sociodemographic differences., Method: Cadets starting the CTP completed a survey assessing self-reported mental health symptoms ( n  = 772, 72.0% male) and a clinical interview ( n  = 736, 74.4% male) with a clinician or supervised trainee using the Mini-International Neuropsychiatric Interview to assess current and past mental health., Results: The percentage of participants screening positive for one or more current mental disorders based on self-reported symptoms (15.0%) was higher than the diagnostic prevalence for the general population (10.1%); however, based on clinical interviews, participants were less likely to screen positive for any current mental disorder (6.3%) than the general population. Participants were also less likely to screen positive for any past mental disorder based on self-report (3.9%) and clinical interviews (12.5%) than the general population (33.1%). Females were more likely to score higher than males (all p s<.01; Cohen's d s .23 to .32) on several self-report mental disorder symptom measures., Conclusions: The current results are the first to describe RCMP cadet mental health when starting the CTP. The data evidenced a lower prevalence of anxiety, depressive, and trauma-related mental disorders than the general population based on clinical interviews, contrasting notions that more rigorous mental health screening would reduce the high prevalence of mental disorders among serving RCMP. Instead, protecting RCMP mental health may require ongoing efforts to mitigate operational and organizational stressors.

Introduction: Royal Canadian Mounted Police (RCMP) officers self-report high levels of mental health disorder symptoms, such as alcohol use disorder, generalized anxiety disorder, major depressive disorder, panic disorder, and posttraumatic stress disorder. Participation in regular mental health monitoring has been associated with improved mental health disorder symptom reporting and may provide an accessible tool to support RCMP mental health. The current study assessed relationships between self-reported mental health disorder symptoms and the completion of daily surveys (i.e., daily mental health disorder symptom monitoring) by RCMP cadets during the Cadet Training Program (CTP)., Methods: Participants were RCMP cadets ( n  = 394; 76.1% men) in the Standard Training Program who completed the 26-week CTP and daily self-monitoring surveys, as well as full mental health assessments at pre-training (i.e., starting the CTP) and pre-deployment (i.e., ~2 weeks prior to deployment to the field). Symptoms of alcohol use disorder, generalized anxiety disorder, major depressive disorder, panic disorder, and posttraumatic stress disorder were assessed. Changes in mental health disorder symptom reporting from pre-training to pre-deployment were calculated. Spearman's rank correlations were estimated for number of daily surveys completed and change in mental health disorder symptom scores between pre-training and pre-deployment., Results: There were statistically significant inverse relationships between number of daily surveys completed and number of mental health disorder symptoms reported; specifically, cadets who completed more daily surveys during CTP reported fewer symptoms of alcohol use disorder, generalized anxiety disorder, major depressive disorder, panic disorder, and posttraumatic stress disorder., Conclusion: An inverse correlation between number of daily surveys completed and mental health disorder symptom scores indicated that participation in daily mental health monitoring was associated with improvements in self-reported mental health disorder symptoms between pre-training and pre-deployment. Regular self-monitoring of mental health disorder symptoms may help to mitigate mental health challenges among RCMP cadets and officers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shields, Teckchandani, Asmundson, Nisbet, Krakauer, Andrews, Maguire, Jamshidi, Afifi, Lix, Brunet, Sauer-Zavala, Krätzig, Neary, Sareen and Carleton.)

Purpose: Our aim is to advance response shift research by explicating the implications of published syntheses by the Response Shift - in Sync Working Group in an integrative way and suggesting ways for improving the quality of future response shift studies., Methods: Members of the Working Group further discussed the syntheses of the literature on definitions, theoretical underpinnings, operationalizations, and response shift methods. They outlined areas in need of further explication and refinement, and delineated additional implications for future research., Results: First, the proposed response shift definition was further specified and its implications for the interpretation of results explicated in relation to former, published definitions. Second, the proposed theoretical model was further explained in relation to previous theoretical models and its implications for formulating research objectives highlighted. Third, ways to explore alternative explanations per response shift method and their implications for response shift detection and explanation were delineated. The implications of the diversity of the response shift methods for response shift research were presented. Fourth, the implications of the need to enhance the quality and reporting of the response shift studies for future research were sketched., Conclusion: With our work, we intend to contribute to a common language regarding response shift definitions, theory, and methods. By elucidating some of the major implications of earlier work, we hope to advance response shift research., (© 2023. The Author(s).)

Importance: FRAX is the most widely used and validated fracture risk prediction tool worldwide. Vertebral fractures, which are an indicator of subsequent osteoporotic fractures, can be identified using dual-energy x-ray absorptiometry (DXA) vertebral fracture assessment (VFA)., Objective: To assess the calibration of FRAX and develop a simple method for improving FRAX-predicted fracture probability in the presence of VFA-identified fracture., Design, Setting, and Participants: This prognostic study analyzed the DXA and VFA results of all individuals who underwent a VFA between March 31, 2010, and March 31, 2018, who were included in the Manitoba Bone Mineral Density Registry. These individuals were randomly assigned to either the development cohort or validation cohort. A modified algorithm-based qualitative approach was used by expert readers to code VFAs as positive (≥1 vertebral fractures detected) or negative (0 vertebral fracture detected). Statistical analysis was conducted from August 7, 2022, to May 22, 2023., Exposures: FRAX scores for major osteoporotic fracture (MOF) and hip fracture were calculated with or without VFA results., Main Outcomes and Measures: Incident fractures and death were ascertained using linked population-based health care provincial data. Cumulative incidence curves for MOF and hip fracture were constructed, including competing mortality, to predict the 10-year observed risk of fracture. The observed probability was compared with FRAX-predicted fracture probability with and without VFA results and recalibrated FRAX from derived multipliers., Results: The full cohort of 11 766 individuals was randomly allocated to the development cohort (n = 7854; 7349 females [93.6%]; mean [SD] age, 75.7 [6.8] years) or the validation cohort (n = 3912; 3713 females [94.9%]; mean [SD] age, 75.5 [6.9] years). Over a mean (SD) observation time of 3.8 (2.3) years, with the longest observation at 7.5 years, FRAX was well calibrated in subgroups with negative VFA results. For individuals without a prior clinical fracture but with a positive VFA result, the 10-year FRAX-predicted MOF probability was 16.3% (95% CI, 15.7%-16.8%) without VFA information and 23.4% (95% CI, 22.7%-24.1%) with VFA information. The observed 10-year probabilities were 26.9% (95% CI, 26.0%-27.8%) and 11.2% (95% CI, 10.3%-12.1%), respectively, resulting in recalibration multipliers of 1.15 (95% CI, 0.87-1.43) for MOF and 1.31 (95% CI, 0.75-1.87) for hip fracture. For individuals with a prior clinical fracture and a positive VFA result, the 10-year FRAX-predicted probabilities were 25.0% (95% CI, 24.2%-25.7%) for MOF and 9.3% (95% CI, 8.7%-10.0%) for hip fracture. The observed 10-year probabilities were 38.1% (95% CI, 37.0%-39.1%) for MOF and 16.4% (95% CI, 15.4%-17.4%) for hip fracture, resulting in a recalibration multiplier of 1.53 (95% CI, 1.10-1.96) for MOF and 1.76 (95% CI, 1.17-2.35) for hip fracture. Good calibration (>0.90) was confirmed using the derived multipliers in the validation cohort., Conclusions and Relevance: Results of this prognostic study suggest that FRAX underestimated fracture risk in patients with VFA-identified fractures. Simple multipliers could recover FRAX calibration in individuals with VFA-identified fractures.