Stephanie Sanger

Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4–25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00–12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m ^2.7 [95% CI, 2.51–5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50–3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14–0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.

Background: The Health Sciences Library and the Bachelor of Health Sciences (Honours) Program (BHSc) at McMaster University worked together to build a multi-year information literacy (IL) curriculum embedded within the program under a suite of courses called Praxis Pathways. Description: Praxis Pathways consists of four Threads. Thread 4: Information Literacy is the focus of this case report. The authors will describe the multi-year embedded IL curriculum, which is scaffolded to build both IL skills, such as database searching, and introduce students to key conceptual conversations in IL, production and dissemination. Outcomes: BHSc program graduates in 2023 will be the first to have completed all four years of the Praxis Pathways courses, including the IL program developed and delivered by the library. The authors will describe how the impact of the program will be evaluated qualitatively and quantitatively going forward. Conclusion: Embedded librarianship for multi-year, scaffolded IL education in undergraduate programs continues to be a rarity, despite the acknowledgement that one-shot instruction has several limitations. The authors present this case report to share how they embedded a for-cred IL curriculum in an undergraduate program that looks beyond the one-shot, skill-based tutorial and focuses on developing adaptive, information-literate lifelong learners.

Background: Target organ damage (TOD) such as left ventricular hypertrophy (LVH), abnormal pulse wave velocity, and elevated carotid intima-media thickness are common among adults with hypertension and are associated with overt cardiovascular events. The risk of TOD among children and adolescents with hypertension confirmed by ambulatory blood pressure monitoring is poorly understood. In this systematic review, we compare the risks of TOD among children and adolescents with ambulatory hypertension to normotensive individuals. Methods: A literature search was conducted to include all relevant English-language publications from January 1974 to March 2021. Studies were included if patients underwent 24-hour ambulatory blood pressure monitoring and ≥1 TOD was reported. Ambulatory hypertension was defined by society guidelines. Primary outcome was the risk of TOD, including LVH, left ventricular mass index, pulse wave velocity, and carotid intima-media thickness among children with ambulatory hypertension compared with those with ambulatory normotension. Meta-regression calculated the effect of body mass index on TOD. Results: Of 12 252 studies, 38 (n=3609 individuals) were included for analysis. Children with ambulatory hypertension had an increased risk of LVH (odds ratio, 4.69 [95% CI, 2.69–8.19]), elevated left ventricular mass index (pooled difference, 5.13 g/m ^2.7 ; [95% CI, 3.78–6.49]), elevated pulse wave velocity (pooled difference, 0.39 m/s [95% CI, 0.20–0.58]), and elevated carotid intima-media thickness (pooled difference, 0.04 mm [95% CI, 0.02–0.05]), compared with normotensive children. Meta-regression showed a significant positive effect of body mass index on left ventricular mass index and carotid intima-media thickness. Conclusions: Children with ambulatory hypertension have adverse TOD profiles, which may increase their risk for future cardiovascular disease. This review highlights the importance of optimizing blood pressure control and screening for TOD in children with ambulatory hypertension. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42020189359

Background: Patients with opioid use disorder (OUD) display an interindividual variability in their response to medications for opioid use disorder (MOUD). A genetic basis may explain the variability in this response. However, no consensus has been reached regarding which genetic variants significantly contribute to MOUD outcomes. Objectives: This systematic review aims to summarize genome-wide significant findings on MOUD outcomes and critically appraise the quality of the studies involved. Methods: Databases searched from inception until August 21st, 2020 include: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog and GWAS Central. The included studies had to be GWASs that assessed MOUD in an OUD population. All studies were screened in duplicate. The quality of the included studies was scored and assessed using the Q-Genie tool. Quantitative analysis, as planned in the protocol, was not feasible, so the studies were analyzed qualitatively. Results: Our search identified 7292 studies. Five studies meeting the eligibility criteria were included. However, only three studies reported results that met our significance threshold of p ≤ 1.0 × 10^–7. In total, 43 genetic variants were identified. Variants corresponding to CNIH3 were reported to be associated with daily heroin injection in Europeans, OPRM1, TRIB2, and ZNF146 with methadone dose in African Americans, EYS with methadone dose in Europeans, and SPON1 and intergenic regions in chromosomes 9 and 3 with plasma concentrations of S-methadone, R-methadone, and R-EDDP, respectively, in Han Chinese. Limitations: The limitations of this study include not being able to synthesize the data in a quantitative way and a conservative eligibility and data collection model. Conclusion: The results from this systematic review will aid in highlighting significant genetic variants that can be replicated in future OUD pharmacogenetics research to ascertain their role in patient-specific MOUD outcomes. Systematic review registration number CRD42020169121.

Background: With the increase in cannabis use rates, cannabis use disorder is being reported as one of the most common drug use disorders globally. Cannabis use has several known physical, psychological, and social adverse events, such as altered judgement, poor educational outcomes, and respiratory symptoms. The propensity for taking cannabis and the development of a cannabis use disorder may be genetically influenced for some individuals. Heritability estimates suggest a genetic basis for cannabis use, and several genome-wide association studies (GWASs) have identified possible regions of association, albeit with inconsistent findings. This systematic review aims to summarize the findings from GWASs investigating cannabis use and cannabis use disorder. Methods: This systematic review incorporates articles that have performed a GWAS investigating cannabis use or cannabis use disorder. MEDLINE, Web of Science, EMBASE, CINAHL, GWAS Catalog, GWAS Central, and NIH Database of Genotype and Phenotype were searched using a comprehensive search strategy. All studies were screened in duplicate, and the quality of evidence was assessed using the quality of genetic association studies (Q-Genie) tool. All studies underwent qualitative synthesis; however, quantitative analysis was not feasible. Results: Our search identified 5984 articles. Six studies met our eligibility criteria and were included in this review. All six studies reported results that met our significance threshold of p ≤ 1.0 × 10^–7. In total 96 genetic variants were identified. While meta-analysis was not possible, this review identified the following genes, ANKFN1, INTS7, PI4K2B, CSMD1, CST7, ACSS1, and SCN9A, to be associated with cannabis use. These regions were previously reported in different mental health conditions, however not in relation to cannabis use. Conclusion: This systematic review summarized GWAS findings within the field of cannabis research. While a meta-analysis was not possible, the summary of findings serves to inform future candidate gene studies and replication efforts. Systematic Review Registration PROSPERO CRD42020176016.

Background: Lung cancer is one of the most commonly diagnosed cancers and is the leading cause of cancer-related deaths. Metastatic bone disease occurs in 20% to 40% of patients with lung cancer, and these patients often present with pain or skeletal-related events (SREs) that are associated with decreased survival. Bone-modifying agents such as denosumab or bisphosphonates are routinely used; however, to our knowledge, there has been no quantitative synthesis of randomized controlled trial data to determine the most effective pharmacologic treatment of metastatic bone disease because of lung cancer. Questions/purposes: We aimed to perform a network meta-analysis of randomized trials to identify the bone-modifying agent that is associated with the (1) highest overall survival, (2) longest time to SRE, (3) lowest SRE incidence, and (4) greatest likelihood of pain resolution. Methods: We conducted our study according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and pre-registered the analysis on PROSPERO (ID: CRD42019124364). We performed a librarian-assisted search of MEDLINE, PubMed, EMBASE, Cochrane Library, and Chinese databases including China National Knowledge Infrastructure and Wanfang Data. We included randomized controlled trials reporting outcomes specifically for patients with lung cancer treated with a bisphosphonate or denosumab. SREs included pathologic fractures, spinal cord compression, hypercalcemia of malignancy, or pain resulting in surgical intervention or radiation therapy. We excluded trials exclusively reporting surrogate outcomes such as changes in bone turnover markers. Screening, data extraction, risk of bias evaluation, and Grading of Recommendations Assessment, Development, and Evaluation evaluations were performed in duplicate. We included 131 randomized controlled trials that evaluated 11,105 patients with skeletal metastases from lung cancer. The network meta-analysis was performed using a frequentist model and the R statistical software. Results are reported as relative risks or mean differences, and the I² value is reported for heterogeneity. The P-score, a measure of ranking certainty that accounts for standard error, is reported for each outcome. Heterogeneity in the network was considered moderate for overall survival and time to SRE, mild for the incidence of SRE, and low for pain resolution. Results: For overall survival, denosumab was ranked above zoledronic acid and estimated to confer a mean of 3.3 months (95% CI 0.3-6.3) of increased overall survival compared with untreated patients (P-score = 89%). For the time to SRE, denosumab was ranked first with a mean of 9.1 additional SRE-free months (95% CI 6.7-11.5) compared with untreated patients (P-score = 99%), while zoledronic acid conferred an additional 4.8 SRE-free months (95% CI 3.6-6.1). Reduction in the incidence of SREs was not different between patients treated with denosumab (relative risk 0.54; 95% CI 0.33-0.87) and those treated with zoledronic acid (relative risk 0.56; 95% CI 0.46-0.67). Patients treated with the combination of ibandronate and systemic therapy were more likely to experience successful pain resolution than untreated patients (relative risk 2.4; 95% CI 1.8-3.2). Conclusion: In this comprehensive synthesis of all available randomized controlled trial evidence guiding the pharmacologic treatment of bone metastases from lung cancer, denosumab was ranked above zoledronic acid for overall survival and time to SRE and was not different for reducing the incidence of SRE. Both were superior to no treatment for each of these outcomes. Given this, we encourage physicians to consider the use of denosumab or zoledronic acid in treating this patient population. The combination of ibandronate and systemic therapy was the most effective at reducing pain because of metastases. No cost-effectiveness analysis has yet been performed for denosumab and zoledronic acid on patients with metastatic lung cancer, and this represents an avenue for future research. Level of Evidence: Level I, therapeutic study.

Background: The burden of opioid use disorder (OUD) has been increasing in North America. Administration of medication-assisted treatments (MATs) for OUD on an individual-dose basis has been shown to affect patient responses to treatment, proving to be, on occasion, dangerous. A genetic basis has been identified for some MAT responses in a candidate gene context, but consensus has not been reached for any genome-wide significant associations. This systematic review aims to identify and assess any genetic variants associated with MAT patient outcomes at genome-wide significance. Methods: The databases searched by the authors will be: MEDLINE, Web of Science, EMBASE, CINAHL and Pre-CINAHL, GWAS Catalog, GWAS Central, and NIH Database of Genotypes and Phenotypes. A title and abstract screening, full-text screening, data extraction, and quality assessment will be completed in duplicate for each study via Covidence. Treatment outcomes of interest include continued opioid use or abstinence during treatment or at follow-up, time to relapse, treatment retention rates, opioid overdose, other substance use, comorbid psychiatric disorders, risk taking behaviors, MAT plasma concentrations, and mortality rates. Analysis methods applied, if appropriate, will include random effects meta-analysis with pooled odds ratios for all outcomes. Subgroup analyses will also be implemented, when possible. Discussion: This systematic review can hopefully inform the direction of future research, aiding in the development of a safer and more patient-centered treatment. It will be able to highlight genome-wide significant variants that are replicable and associated with MAT patient outcomes. Systematic review registration: This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration ID CRD42020169121).

Background: With the legalization of cannabis in Canada, there is an increase trend in use. Cannabis has been known to have several health implications, one of which is the development of cannabis use disorder (CUD). CUD is more common in males than females, as well as in certain ethnic groups such as Native Americans. Additionally, both environmental and genetic risk factors have been found for cannabis use. The objective of this systematic review will be to summarize the genetic variants associated with cannabis use which have reached borderline genome-wide significance. Methods: This systematic review will incorporate articles that have performed a genome-wide association study (GWAS) investigating cannabis use. MEDLINE, Web of Science, EMBASE, GWAS Catalog, GWAS Central, and NIH Database of Genotype and Phenotype will be searched using a comprehensive search strategy. The quality of genetic association studies (Q-Genie) tool will be utilized to assess the quality of the included studies. All screening and data extraction will occur independently by two authors. If feasible, a random-effects meta-analysis will be conducted on pooled odds ratios of single nucleotide polymorphisms reaching borderline genome-wide significance. Discussion: This systematic review will synthesize available GWAS on cannabis use. Results from this review will inform and direct further investigation of genetic variants associated with cannabis use. Systematic review registration: PROSPERO CRD42020176016

Introduction Glucocorticoid (GC) administration is an effective therapy commonly used in the treatment of autoimmune and inflammatory diseases. However, the use of GC can give rise to serious complications. The main detrimental side effect of GC therapy is significant bone loss, resulting in glucocorticoid-induced osteoporosis (GIOP). There are a variety of treatments available for preventing and managing GIOP; however, without clearly defined guidelines, it can be very difficult for physicians to choose the optimal therapy for their patients. Previous network meta-analyses (NMAs) and meta-analyses did not include all available RCT trials, or only performed pairwise comparisons. We present a protocol for a NMA that incorporates all available RCT patient data to provide the most comprehensive ranking of all available GIOP treatments in terms of their ability to increase bone mineral density (BMD) and decrease fracture incidences among adult patients undergoing GC treatments. Methods and Analysis We will search MEDLINE, EMBASE, PubMed, Web of Science, CINAHL, CENTRAL and Chinese literature sources (CNKI, CQVIP, Wanfang Data, Wanfang Med Online) for randomized controlled trials (RCTs) which fit our criteria. RCTs that evaluate different antiresorptive regimens taken by adult patients undergoing GC therapy during the study or had taken GC for at least 3 months in the year prior to study commencement with lumbar spine BMD, femoral neck BMD, total hip BMD, vertebral fracture incidences and/or non-vertebral fracture incidences as outcomes will be selected. We will perform title/abstract and full-text screening as well as data extraction in duplicate. Risk of bias (ROB) will be evaluated in duplicate for each study, and the quality of evidence will be examined using CINeMA in accordance to the GRADE framework. We will use R and gemtc to perform the NMA. We will report BMD results as weighted mean differences (WMDs) and standardized mean differences (SMDs), and we will report fracture incidences as odds ratios. We will use the surface under the cumulative ranking curve (SUCRA) scores to provide numerical estimations of the rankings of interventions. Ethics and Dissemination The study will not require ethical approval. The findings of the NMA will be disseminated in a peer-reviewed journal and presented at conferences. We aim to produce the most comprehensive quantitative analysis regarding the management of GIOP. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with GIOP. Systematic Review Registration International Prospective Register for Systematic Reviews (PROSPERO): CRD42019127073