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The Evidence Speaks (June 2018)

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The Evidence Speaks Series is a recurring feature highlighting the latest in CHÉOS research. This series features summaries of select publications as well as in-depth features on the latest work from our investigators.

In the early days of CHÉOS, the Centre had a series known as “The Evidence Speaks,” a monograph series to keep media and the research community up-to-date with CHÉOS’ current research results in the health outcomes field.


Kalyan S, Pick N, Mai A, Murray MCM, Kidson K, Chu J, Albert AYK, Côté HCF, Maan EJ, Goshtasebi A, Money DM, Prior JC. Premature spinal bone loss in women living with HIV is associated with shorter leukocyte telomere length. Int J Environ Res Public Health. 2018 May 18;15(5):1018.

Evidence continues to suggest that individuals living with HIV are at greater risk of low bone mineral density (BMD), osteoporosis, and fracture. Bone loss may result through mechanisms involving the virus, antiretroviral therapies, or risk factors prevalent among people living with HIV. As this population progressively ages as a result of extended survival, bone health is a growing concern. With women making up over 50% of the population living with HIV globally, CHÉOS Scientist Dr. Shirin Kalyan and a team of researchers aimed to identify biological factors linked to low BMD specifically in women living with HIV. In a cross-sectional study including women from the Canadian Mulicentre Osteoporosis Study (CaMos) and participants from the Children and Women: Antiretrovirals and Markers of Aging (CARMA) study, the researchers assessed the relationships among health-related characteristics, leukocyte telomere length (LTL—an indicator of cellular aging), combination antiretroviral therapy (cART), and BMD using linear regression analysis. Seventy-three women living with HIV and 280 controls from CaMos were included in the analysis. Of the women living with HIV, only two were cART naïve, the majority had undetectable HIV plasma viral loads, and 23% had active HCV co-infection. On average, these women also had lower BMD than the CaMos participants. In the univariate analyses LTL and BMI were the strongest predictors of reduced lumbar spine BMD, whereas for total hip and femoral neck BMD, cumulative months on cART, age, and body mass index (BMI) were significant predictors. LTL remained the greatest predictor of lumbar spine BMD in multivariate analyses, while BMI and age were the only variables that remained significantly associated with lower BMD for total hip and femoral neck. Furthermore, lifetime exposure to cART therapy tenofovir disoproxil fumarate was associated with LTL. This study is consistent with previous research linking HIV and its treatment with accelerated bone aging, justifying the need for greater emphasis on bone health throughout HIV care. The association found between LTL and BMD further solidifies the role of cellular aging in loss of bone renewal potential and provides insight to help inform future prevention and treatment strategies.

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Kurz MC, Schmicker RH, Leroux B, Nichol G, Aufderheide TP,…Grunau B, et al. Advanced vs. basic life support in the treatment of out-of-hospital cardiopulmonary arrest in the Resuscitation Outcomes ConsortiumResuscitation. 2018 Apr 30 epub ahead of print.

Advancements have been made to the level of interventions that emergency medical services (EMS) can provide for out-of-hospital cardiac arrest (OHCA). However recent studies have called into question additional survival benefits of advanced methods, such as endotracheal intubation, manual defibrillation, and intravenous drug therapy, relative to basic methods, primarily cardiopulmonary resuscitation (CPR) and automatic defibrillation. Emergency physician and CHÉOS Scientist Dr. Brian Grunau was among researchers from the Resuscitation Outcomes Consortium that examined whether advanced life support (ALS) care impacts OHCA outcomes compared to basic life support (BLS). The ROC is one of the world’s largest series of OHCA care consisting of regional centres across North America, collecting highly detailed information on care rendered and clinical presentation of OHCA cases. The outcomes of interest—return of spontaneous circulation, survival to hospital discharge, and survival with favourable neurological outcomes—were compared between patients receiving BLS only, BLS and ALS within six minutes, ALS after six minutes, and ALS before BLS. Six minutes was chosen as the threshold, representing the time required to complete three BLS CPR cycles. Prospective clinical data on 35,065 cases receiving care between 2011 and 2015 from the ROC were analyzed. Less than 5% of cases received BLS only whereas nearly half of the cases received ALS care first. On average, those who received BLS only were older and less likely to be male than the other groups. Analyses were adjusted for demographic variables such as age and sex, as well as witnessed arrest, bystander CPR, public location, EMS response time, presenting ECG rhythm, metrics of CPR quality, and geographic site. Using multivariate logistic regression, the researchers found that ALS care was associated with improvement in return to spontaneous circulation and survival to hospital discharge, unless provided more than six minutes after BLS care. However, ALS care was not found to improve neurological outcomes. Additional analyses were also conducted to verify the main results of the study, further supporting ALS use in prehospital care of OHCA, but conflicting with findings from studies done elsewhere. Though ALS was found to be beneficial, the study’s authors also discussed additional considerations that must be made before implementing ALS across EMS systems, such as the need for far more extensive training than is needed to provide BLS and a better understanding of the mechanisms resulting in improved outcomes.

Chen W, Fitzgerald JM, Lynd LD, Sin DD, Sadatsafavi M. Long-term trajectories of mild asthma in adulthood and risk factors of progressionJ Allergy Clin Immunol Pract. 2018 May 7 epub ahead of print.

Asthma is one of the most prevalent chronic diseases, most often presenting as mild disease. The long-term prognosis of mild asthma, especially when diagnosed in younger age, has typically been found to be good. Most research on the progression of asthma has focused on changes in lung function and changes from childhood to adulthood, but little attention has been paid to the long-term trajectory of disease according to degree of severity. Recognizing this gap, researchers from UBC, including CHÉOS Scientist Dr. Larry Lynd, sought to examine the long-term trajectories of mild asthma and the early stage risk factors for subsequent disease progression. Using administrative health data from BC from 1997-2012, 70,829 patients aged 14-45 years with newly diagnosed mild asthma were identified using validated algorithms. These patients were followed in the data, on average for a duration of 5.4 years. Patients’ asthma severity was categorized for subsequent 12-month periods as either dormant/mild, moderate, or severe based on medication use and occurrence of exacerbations. Using ordinal logistic regression, the researchers were able to estimate the probability of severity or death in the next year as a function of previous severity and baseline risk factors. Just over 90% of the patients’ asthma remained mild over the 10 years, less than 2% transitioning to severe disease and roughly 7% to moderate. The strongest predictors of disease progression from mild was inappropriate use of rescue medication, older age, and comorbidity score. Inhaled corticosteroids (ICS)/ long-acting beta-agonist combination therapy was associated with reduced risk of progression compared to monotherapy. Allergic rhinitis did not have significant effects, while effects of sex and socioeconomic status were relatively minimal. Overall, these results indicate that mild asthma generally remains stable over time but may be exacerbated through inappropriate use of rescue medication. For clinicians, there may be a precedent for regular use of low-dose ICS in mild asthma patients that require frequent rescue therapy.

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