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    Clozapine, Relapse, and Adverse Events: A 10-Year Electronic Cohort Study in Canada: Commentary, Author Response
    (2024) Halayka, Shawn; Balbuena, Lloyd
    We agree with Kikuchi that the diversity of diagnoses may have obscured clozapine’s risk-benefit balance in our paper (1). Hence, our findings may have reflected the lower range of the overall benefit of clozapine. Table 1 shows the expected count of rehospitalization events stratified by index diagnosis in adult patients. These were calculated using flexible survival models implemented in the STPM3 Stata package (2). The above figures show that clozapine had fewer relapse events compared to other drugs in patients with schizophrenia and schizoaffective disorders. In patients with bipolar disorder, the relapse events were the same, but clozapine had higher adverse events. The reverse was true in schizoaffective disorder patients: lower relapse events for clozapine but the same adverse event counts as other drugs. The child and youth cohort could not be stratified by diagnosis because of low numbers. We agree with Kikuchi that the adverse events analysis was tilted in favor of other antipsychotics. Suicide attempts and deaths were not available in the data, so clozapine’s benefit is probably underestimated (3) while adverse events more specific to other drugs are probably underestimated. The decision to exclude unmedicated periods was deliberate, since our objective was a head-to-head comparison of medications. In a previous paper (4) we found that over a five-year period, schizophrenia patients, on average, spent 11 months without medication and only 17 days in clozapine. Within-person analysis was considered, but this technique discards the records of people who did not switch from other drugs to clozapine or vice-versa. In our data, these patients made up the majority. In summary, our register-based study shows that clozapine is an effective medication, with benefits and risks that require balancing.
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    SASKATOON HIV PROGRAM EVALUATION FINAL REPORT 2024
    (2024) Spence, Cara; Zettl, Mary; Morin, Emmannuelle
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    General unemployment and serious workplace injury rates: workers compensation claims analysis from the Canadian province of Saskatchewan, 2007-2018
    (Springer, 10/15/2024) Essien, Samuel Kwaku; Feng, Cindy; Trask, Catherine
    Abstract Objectives There is conflicting published evidence that unemployment impacts workplace safety. Some studies suggest that the workplace injury rate decreases during economic contractions, while others propose an increased rate of injuries during periods of economic contractions. This study investigated the association between unemployment rates and traumatic work-related non-fatal injury (WRNFI) in Saskatchewan, 2007–2018, in order to provide new insight into injury prevention. Methods Saskatchewan’s retrospective linked workplace claims data from 2007 to 2018 were grouped by year, season, and worker characteristics (e.g., age and sex). Total employment, total labour force, and the number of unemployed workers from the Statistics Canada Labour Force Survey were grouped by year, season, sex, and age. These data were linked to the worker’s compensation board injury claim data to determine the number of people at risk, serving as the denominator (offset term) for WRNFI rates, calculated as WRNFI cases per total employed workers. A negative binomial generalized additive model was used to examine the association between unemployment rates and WRNFI, adjusted for age, sex, industry types, and seasons. Results The WRNFI rate has declined since 2007. On average, workers aged 20–29 years had the highest WRNFI rate (541.6 ± 84.8/100,000). Men had 3.2 times higher WRNFI risk than women (RR = 3.2, 95% CI 3.12–3.22), with the highest WRNFI risk observed in the manufacturing (RR = 1.68, 95% CI 1.63–1.73) and construction (RR = 1.67, 95% CI 1.63–1.72) industries. WRNFI risk decreased non-linearly with an increasing unemployment rate, indicating a pro-cyclic pattern. Conclusion This analysis showed that WRNFI rates tracked unemployment rates. This suggests a need to increase prevention strategies and reduce disincentives for under-reporting during an economic downturn.
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    Head circumference values among Inuit children in Nunavut, Canada: A retrospective cohort study
    (Canadian Medical Association Journal, 2024-10) Joyal, Kristina; Collins, Sorcha; Miners, Amber; Barrowman, Nick; Sucha, Ewa; Allen, Jean; Edmunds, Sharon; Caughey, Amy; Doucette, Michelle; Khatun, Selina; Akearok, Gwen Healey; Arbour, Laura; Venkateswaran, Sunita
    Background: Inuit children from Nunavut have been observed to have high rates of macrocephaly, which sometimes leads to burdensome travel for medical evaluation, often with no pathology identified upon assessment. Given reports that World Health Organization (WHO) growth charts may not reflect all populations, we sought to compare head circumference measurements in a cohort of Inuit children with the WHO charts. Methods: We extracted head circumference data from a previous retrospective cohort study where, with Inuit partnership, we reviewed medical records of Inuit children (from birth to age 5 yr) born between Jan. 1, 2010, and Dec. 31, 2013, and residing in Nunavut. To create a cohort of Inuit children similar to the cohorts used in the development of the WHO growth charts, we excluded children with preterm birth, documented neurologic or genetic disease, and most congenital anomalies. We compared head circumference values with the 2007 WHO charts using centiles estimated with a generalized additive model. Results: We analyzed records of 1960 Inuit children (8866 data points), of whom 993 (50.8%) were female. Most data were from ages 0 to 36 months. At all age points, we found that the study cohort had statistically significantly larger head circumferences than WHO medians, with most z scores for head circumference measurements among Inuit children falling 0.5–1 standard deviations above the WHO reference (p < 0.001). At age 12 months, median head circumferences were 1.3 cm and 1.5 cm larger for male and female Inuit children, respectively. Using WHO growth curves, macrocephaly was significantly overdiagnosed and microcephaly was underdiagnosed (p < 0.001). Interpretation: Our results support the observation that Inuit children from Nunavut have larger head circumferences than other populations, and use of the WHO charts may thus lead to overdiagnosis of macrocephaly and underdiagnosis of microcephaly. Population-specific growth curves for Inuit children should be considered to provide timely and appropriate diagnoses of microcephaly and avoid overinvestigation of macrocephaly.
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    Enabling Implementation of Competency Based Medical Education through an Outcomes-Focused Accreditation System
    (Ubiquity Press, 2/6/2024) Dalseg, Timothy; Thoma, Brent; Wycliffe-Jones, Keith; Frank, Jason; Taber, Sarah
    Competency based medical education is being adopted around the world. Accreditation plays a vital role as an enabler in the adoption and implementation of competency based medical education, but little has been published about how the design of an accreditation system facilitates this transformation. The Canadian postgraduate medical education environment has recently transitioned to an outcomes-based accreditation system in parallel with the adoption of competency based medical education. Using the Canadian example, we characterize four features of an accreditation system that can facilitate the implementation of competency based medical education: theoretical underpinning, quality focus, accreditation standards, and accreditation processes. Alignment of the underlying educational theories within the accreditation system and educational paradigm drives change in a consistent and desired direction. An accreditation system that prioritizes quality improvement over quality assurance promotes educational system development and progressive change. Accreditation standards that achieve the difficult balance of being sufficiently detailed yet flexible foster a high fidelity of implementation without stifling innovation. Finally, accreditation processes that recognize the change process, encourage program development, and are not overly punitive all enable the implementation of competency based medical education. We also discuss the ways in which accreditation can simultaneously hinder the implementation of this approach. As education bodies adopt competency based medical education, particular attention should be paid to the role that accreditation plays in successful implementation.
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    Sharing Is Caring: Helping Institutions and Health Organizations Leverage Data for Educational Improvement
    (Ubiquity Press, 10/7/2024) Sebok-Syer, Stefanie S.; Smirnova, Alina; Duwell, Ethan; George, Brian; Triola, Marc; Feddock, Christopher; Chahine, Saad; Rubright, Jonathan D.; Thoma, Brent
    Competency-based medical education (CBME) has produced large collections of data, which can provide valuable information about trainees and medical education systems. Many organizations continue to struggle with accessing, collecting, governing, analyzing, and visualizing their clinical and/or educational data. This hinders data sharing efforts within and across organizations, which are foundational in supporting system-wide improvements. Challenges to data sharing within medical education include variability in legislation, existing data policies, heterogeneity of data, inadequate data infrastructure, and various intended purposes or uses. In this eye opener, the authors describe four case studies to illustrate some of the aforementioned challenges and characterize the complexity of data sharing within medical education along two dimensions: organizational (single vs. multiple) and data type (clinical and/or educational). With the goal of better supporting data sharing initiatives, the authors introduce an action-oriented blueprint that includes a three-stage process (i.e., preparation, execution, and iteration) to highlight crucial aspects of data sharing. This evidence-informed model incorporates current best practices and aims to support data sharing initiatives within their own organizations and across multiple organizations. Finally, organizations can use this model to conceptually guide and track their progression throughout the data sharing process.
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    Translating the Interplay of Cognition and Physical Performance in COPD and Interstitial Lung Disease
    (CHEST Journal, 2024-10) Rozenberg, Dmitry; Reid, W Darlene; Camp, Pat; Campos, Jennifer L.; Dechman, Gail; Davenport, Paul W; Egan, Helga; Fisher, Jolene H.; Guenette, Jordan A.; Gold, David; Goldstein, Roger S.; Goodridge, Donna; Janaudis-Ferreira, Tania; Kaplan, Alan G.; Langer, Daniel; Pepin, Veronique; Marciniuk, Darcy D.; Moore, Barbara; Orchanian-Cheff, Ani; Otoo-Appiah, Jessica; Rassam, Peter; Rotenberg, Shlomit; Ryerson, Chris; Spruit, Martijn A.; Stanbrook, Matthew B.; Stickland, Michael K.; Tom, Jeannie; Wentlandt, Kirsten
    Topic Importance Cognitive and physical limitations are common in individuals with chronic lung diseases, but their interactions with physical function and activities of daily living are not well characterized. Understanding these interactions and potential contributors may provide insights on disability and enable more tailored rehabilitation strategies. Review Findings This review summarizes a 2-day meeting of patient partners, clinicians, researchers, and lung associations to discuss the interplay between cognitive and physical function in people with chronic lung diseases. This report covers four areas: (1) cognitive-physical limitations in patients with chronic lung diseases; (2) cognitive assessments; (3) strategies to optimize cognition and motor control; and (4) future research directions. Cognitive and physical impairments have multiple effects on quality of life and daily function. Meeting participants acknowledged the need for a standardized cognitive assessment to complement physical assessments in patients with chronic lung diseases. Dyspnea, fatigue, and age were recognized as important contributors to cognition that can affect motor control and daily physical function. Pulmonary rehabilitation was highlighted as a multidisciplinary strategy that may improve respiratory and limb motor control through neuroplasticity and has the potential to improve physical function and quality of life. Summary There was consensus that cognitive function and the cognitive interference of dyspnea in people with chronic lung diseases contribute to motor control impairments that can negatively affect daily function, which may be improved with pulmonary rehabilitation. The meeting generated several key research questions related to cognitive-physical interactions in individuals with chronic lung diseases.
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    The Relative Risk of COVID-19 in Solid Organ Transplant Recipients Over Waves of the Pandemic
    (Frontiers Media S.A., 9/5/2024) Vinson, Amanda J.; Anzalone, Alfred J.; Schissel, Makayla; Dai, Ran; Agarwal, Dr Gaurav; Lee, Stephen B.; Olex, Amy; Mannon, Roslyn B.
    Solid organ transplant recipients (SOTR) are at increased risk from COVID-19. Over time, the absolute risk of adverse outcomes after COVID-19 has decreased in both the non-immunosuppressed/immunocompromised (non-ISC) general population, and amongst SOTR. Using the N3C, we examined the absolute risk of mortality, major adverse renal or cardiac events, and hospitalization after COVID-19 diagnosis amongst non-ISC and SOTR populations over five waves of the pandemic (Wave 1: Ancestral COVID; Wave 2: Alpha; Wave 3: Delta; Wave 4: Omicron; Wave 5: Omicron). Within each wave, we determined the relative risk of each outcome for SOTR versus the non-ISC population based on crude event rates, and then used multivariable cox proportional hazards models and logistic regression to determine the adjusted risk of each outcome based on SOT status. Throughout the pandemic, including during the Omicron wave (Wave 5), SOTR were at greater absolute risk for each outcome than non-ISC patients (p-values all <0.001). The adjusted risk of SOT status for each outcome was relatively stable over time (aHR 1.28–1.61 for mortality; aHR 1.31–1.47 for MACE; aHR 1.72–1.90 for MARCE; aHR 1.75–2.07 for AKI; and aOR 1.53–1.81 for hospitalization). Despite a reduction in the absolute risk of COVID-19 complications, the relative risk for SOTR versus the non-ISC population has not improved.
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    Educator's blueprint: Key considerations for using social media in survey-based medical education research
    (Wiley, 9/4/2024) Ogle, Kathleen Y.; Hill, Jeffery; Santen, Sally A.; Gottlieb, Michael; Artino Jr., Anthony R.; Thoma, Brent
    In this paper, we present a set of recommendations for using social media as a tool for participant recruitment in survey-based medical education research. Drawing from a limited but growing body of literature, we discuss the opportunities and challenges inherent to social media recruitment. This article builds on the authors’ previous educator's blueprints about survey design and administration. We highlight the advantages of social media, including its wide reach, cost-effectiveness, and capability to access diverse and geographically dispersed populations, which can significantly enhance the representativeness of research samples. However, we also caution against potential pitfalls, such as ethical concerns, sampling bias, and the fluid nature of social media platforms. Our recommendations are informed by both empirical evidence and best practices, aiming to provide researchers with practical advice for effectively leveraging social media in survey-based medical education research. We emphasize the importance of selecting suitable platforms and engaging with targeted demographics thoughtfully. By sharing our insights, we hope to assist fellow medical education researchers in navigating the complexities of social media recruitment, thereby enriching the quality and impact of survey-based research in this field.
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    Clozapine, relapse, and adverse events: a 10-year electronic cohort study in Canada
    (The British Journal of Psychiatry, 2024-09) Balbuena, Lloyd; Halayka, Shawn; Lee, Andrew; AHMED, AG; Hinz, Tamara; Kolla, Nathan; Pylypow, Jenna
    Background Clozapine is the most effective medication for treatment-resistant psychoses, but the balance of benefits and risks is understudied in real-world settings. Aims To examine the relative re-hospitalisation rates for mental health relapse and adverse events associated with clozapine and other antipsychotics in adult and child/youth cohorts. Method Data were obtained from the Canadian Institute of Health Information for adults (n = 45 616) and children/youth (n = 1476) initially hospitalised for mental health conditions in British Columbia, Manitoba and Saskatchewan from 2008 to 2018. Patient demographics and hospitalisations were linked with antipsychotic prescriptions dispensed following the initial visit. Recurrent events survival analysis for relapse and adverse events were created and compared between clozapine and other antipsychotics. Results In adults, clozapine was associated with a 14% lower relapse rate versus other drugs (adjusted hazard ratio: 0.86, 95% CI: 0.83–0.90) over the 10-year follow-up. In the first 21 months, the relapse rate was higher for clozapine but then reversed. Over 1000 person-months, clozapine-treated adults could be expected to have 38 relapse hospitalisations compared with 45 for other drugs. In children/youth, clozapine had a 38% lower relapse rate compared with other antipsychotic medications (adjusted hazard ratio: 0.62, 95% CI: 0.49–0.78) over the follow-up period. This equates to 29 hospitalisations for clozapine and 48 for other drugs over 1000 person-months. In adults, clozapine had a higher risk for adverse events (hazard ratio: 1.34, 95% CI: 1.18–1.54) over the entire follow-up compared with other antipsychotics. This equates to 1.77 and 1.30 hospitalisations over 1000 person-months for clozapine and other drugs, respectively. Conclusions Clozapine was associated with lower relapse overall, but this was accompanied by higher adverse events for adults. For children/youth, clozapine was associated with lower relapse all throughout and had no difference in adverse events compared with other antipsychotics.
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    To stop or not to stop an asthma biologic, that is the question
    (Elsevier, 2024-09) Philipenko, Brianne S.; Davis, Beth; Cockcroft, Donald W.
    During a time when anti-asthma biologics are readily accessible, the article by Brightling et al1 in the current issue provides additional much needed evidence to discuss with patients with severe asthma when the inevitable question arises of “How long do I need to continue on my asthma biologic therapy?” With now 6 biologics available, including most recently tezepelumab that can be prescribed without biomarker restrictions, it has become increasingly easy to prescribe these medications. After achieving good asthma control, physicians are left to contemplate the question of “now what?” Are these medications lifelong therapies?
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    Fast oxygen dynamics as a potential biomarker for epilepsy
    (Nature Research, 12/18/2018) Farrell, Jordan S.; Greba, Quentin; Snutch, Terrance P.; Howland, John G.; Teskey, G. Campbell
    Changes in brain activity can entrain cerebrovascular dynamics, though this has not been extensively investigated in pathophysiology. We assessed whether pathological network activation (i.e. seizures) in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) could alter dynamic fluctuations in local oxygenation. Spontaneous absence seizures in an epileptic rat model robustly resulted in brief dips in cortical oxygenation and increased spectral oxygen power at frequencies greater than 0.08 Hz. Filtering oxygen data for these fast dynamics was sufficient to distinguish epileptic vs. non-epileptic rats. Furthermore, this approach distinguished brain regions with seizures from seizure-free brain regions in the epileptic rat strain. We suggest that fast oxygen dynamics may be a useful biomarker for seizure network identification and could be translated to commonly used clinical tools that measure cerebral hemodynamics.