Anticonvulsants in the Treatment of Behavioral and Psychological Symptoms in Dementia: A Systematic Review.

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are common and impart a significant burden to patients, caregivers, and the health system. However, there are few pharmacological options for treating BPSD. We conducted a systematic review of clinical trials examining the efficacy of anticonvulsants in BPSD. METHODS: We searched five electronic databases through January 2023, for randomized controlled trials and systematic reviews evaluating the efficacy of non-benzodiazepine anticonvulsants for the treatment of BPSD. We used the Cochrane risk of bias tool to ascertain the risk of bias in included trials. Because statistical pooling of results using meta-analysis was not feasible, we synthesized findings using the Cochrane Synthesis Without Meta-analysis reporting guidelines. RESULTS: We identified 12 studies, including randomized controlled trials (RCTs) and 1 systematic review. Five RCTs evaluating valproic acid were synthesized by a recent Cochrane review which concluded that this drug is likely ineffective for BPSD. We extracted data from 6 trials involving 248 individuals comparing non-benzodiazepine anticonvulsants to either placebo or risperidone. Four trials (n = 97 participants) evaluated carbamazepine, only one of which demonstrated an improvement in the Brief Psychiatric Rating Scale measuring agitation, hostility, psychosis, and withdrawal/depression (effect size: 1.13; 95% confidence interval [CI]: 0.54-1.73) relative to placebo. Adverse effects were more common in patients receiving carbamazepine (20/27; 74%) relative to placebo (5/24; 21%). There is low quality evidence that oxcarbazepine is likely ineffective and that topiramate may be comparable to risperidone. CONCLUSION: Anticonvulsants are unlikely to be effective in BPSD, although the quality of existing evidence is low.

Primary outcome reporting in clinical trials for older adults with depression.

BACKGROUND: Findings from randomised controlled trials (RCTs) are synthesised through meta-analyses, which inform evidence-based decision-making. When key details regarding trial outcomes are not fully reported, knowledge synthesis and uptake of findings into clinical practice are impeded. AIMS: Our study assessed reporting of primary outcomes in RCTs for older adults with major depressive disorder (MDD). METHOD: Trials published between 2011 and 2021, which assessed any intervention for adults aged ≥65 years with a MDD diagnosis, and that specified a single primary outcome were considered for inclusion in our study. Outcome reporting assessment was conducted independently and in duplicate with a 58-item checklist, used in developing the CONSORT-Outcomes statement, and information in each RCT was scored as 'fully reported', 'partially reported' or 'not reported', as applicable. RESULTS: Thirty-one of 49 RCTs reported one primary outcome and were included in our study. Most trials (71%) did not fully report over half of the 58 checklist items. Items pertaining to outcome analyses and interpretation were fully reported by 65% or more of trials. Items reported less frequently included: outcome measurement instrument properties (varied from 3 to 30%) and justification of the criteria used to define clinically meaningful change (23%). CONCLUSIONS: There is variability in how geriatric depression RCTs report primary outcomes, with omission of details regarding measurement, selection, justification and definition of clinically meaningful change. Outcome reporting deficiencies may hinder replicability and synthesis efforts that inform clinical guidelines and decision-making. The CONSORT-Outcomes guideline should be used when reporting geriatric depression RCTs.

Comparison of national and international sedentary behaviour and physical activity guidelines for older adults: A systematic review and quality appraisal with AGREE II.

Most older adults 65 years and older accumulate over 8.5 hours/day of sedentary time, which is associated with increased risk of metabolic syndromes and falls. The impact of increased sedentary time in older adults has prompted development of sedentary behaviour guidelines. The purpose of our review was to compare national and international sedentary behaviour and physical activity guidelines for older adults and appraise the quality of guidelines using AGREE II. We conducted our search in Medline, Embase, Global Health, Web of Science, CINAHL, and relevant grey literature. We included the most recent guidelines for older adults written in English. We identified 18 national and international guidelines; ten of the 18 guidelines included sedentary behaviour recommendations while all 18 included physical activity recommendations for older adults. The ten sedentary behaviour guidelines were developed using cohort studies, knowledge users' opinions, systematic reviews, or other guidelines while the physical activity guidelines were developed using randomized controlled trials, systematic reviews, meta-analysis, and overview of reviews. The definition of sedentary behaviour and the recommendations were inconsistent between the guidelines and were based on very low to low quality and certainty of evidence. All guidelines provided consistent recommendations for aerobic and resistance training; the recommendations were developed using moderate to high quality and certainty of evidence. Only eight physical activity guidelines provided recommendations for balance training and six on flexibility training; the balance training recommendations were consistent between guidelines and based on moderate quality evidence. Further work is needed to develop evidenced-based sedentary behaviour recommendations and flexibility training recommendations for older adults.

Prevalence of Pediatric Masked Hypertension and Risk of Subclinical Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

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/m2.7 [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.

Scaffolded, embedded required: information literacy education in undergraduate health sciences.

Background: The Health Sciences Library and Bachelor of Health Sciences (BHSc) program 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 acknowledgement that one-shot instruction has several limitations. The authors present this case report to share how they embedded a for-credit IL curriculum in an undergraduate program that looks beyond the one-shot, skill-based tutorial and focuses on developing adaptive, information literate lifelong learners.

Heterogeneity across outcomes reported in clinical trials for older adults with depression: a systematic survey.

OBJECTIVES: The objective of our study was to identify outcomes reported in trials for older adults with depression and describe outcome heterogeneity. STUDY DESIGN AND SETTING: We searched four databases to identify trials assessing any intervention for major depressive disorder among older adults published between 2011 and 2021. We grouped reported outcomes thematically and mapped them onto core outcome areas (physiological/clinical, life impact, resource use, adverse events, and death) and used descriptive analysis to summarize outcome heterogeneity. RESULTS: There were 434 total outcomes reported by 49 included trials, which were measured using 135 different outcome measurement instruments and grouped into 100 unique outcome terms. Most outcome terms mapped to the physiological/clinical core area (47%), followed by life impact (42%). More than half of all terms (53%) were reported by only a single study. Most trials (n = 31/49) reported a single, discernible primary outcome. The most commonly reported outcome "depressive symptom severity" was assessed by 36 studies using 19 different outcome measurement instruments. CONCLUSION: There is substantial heterogeneity in the outcomes and outcome measurement instruments used in geriatric depression trials. A standard set of outcomes and accompanying measurement tools is necessary to facilitate comparison and synthesis of trial findings.

Risk of Target Organ Damage in Children With Primary Ambulatory Hypertension: A Systematic Review and Meta-Analysis.

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/m2.7; [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.

Engaging medical students and residents in nephrology education: an updated scoping review.

BACKGROUND: There is global recognition that interest in nephrology among pediatric and adult trainees is waning, while the burden of kidney disease continues to wax. There is a growing need to engage trainees in nephrology education. The objective of this study was to systematically review the literature on nephrology education for medical students and residents published in the last six years, collate the findings, and extract major themes in order to better define the gaps in this field. METHODS: A systematic literature search was conducted on four major academic search engines including MEDLINE (OvidSP), ERIC, EMBASE and Web of Science until October 22, 2020, retrieving a total of 2,694 studies. Forty studies published after September 2014 met the inclusion and exclusion criteria. These studies were analyzed based on study focus, type of study design, and outcomes. RESULTS: The studies fell into three main areas of focus: (a) factors that influence interest in nephrology careers (b) current gaps in nephrology knowledge and (c) innovative educational strategies. Barriers to engaging learners in nephrology include a lack of exposure, lack of mentorship, and perceived complexity of nephrology. Baseline awareness is deficient in the management of chronic kidney disease and acute kidney injury. Applying active learning strategies may reduce the perceived barriers to understanding nephrology. CONCLUSION: The importance of engaging the future nephrology workforce is well-recognized. Nephrologist educators should focus their efforts in studying curriculum interventions and their impact not only on learner satisfaction, but also future behavior, career choices, and patient outcomes.

Delirium and other neuropsychiatric manifestations of COVID-19 infection in people with preexisting psychiatric disorders: a systematic review.

BACKGROUND: Psychiatric disorders increase risk of neuropsychiatric disease and poor outcomes, yet little is known about the neuropsychiatric manifestations of COVID-19 in the psychiatric population. The primary objective is to synthesize neuropsychiatric outcomes of COVID-19 in people with preexisting psychiatric disorders. METHODS: Data were collected during an ongoing review of the impact of pandemics on people with existing psychiatric disorders. All study designs and gray literature were included. Medline, PsychInfo, CINAHL, EMBASE, and MedRx were searched from inception to September 1 2020. Risk of bias was assessed using a published tool that can accommodate all study types. Two independent authors screened the studies and extracted data. Data were narratively synthesized, as there were insufficient data to meta-analyze. Evidence was appraised according to GRADE. RESULTS: Four case reports were included, comprising 13 participants from three countries. Many large-sample, relevant papers were omitted for not reporting psychiatric history, despite reporting other comorbidities. Included participants (n = 13) were hospitalized with COVID-19 and appeared to meet criteria for delirium. Myoclonus, rigidity, and alogia were also reported. The most commonly reported preexisting psychiatric diagnoses were mood disorders, schizophrenia, and alcohol use disorder. CONCLUSIONS: People with preexisting psychiatric disorders may experience delirium, rigidity, myoclonus, and alogia during COVID-19 infection; although higher quality and longitudinal data are needed to better understand these phenomena. Relevant COVID-19 literature does not always report psychiatric history, despite heightened neuropsychiatric vulnerability within this population. TRIAL REGISTRATION:  PROSPERO (CRD42020179611).

Outcomes reported in randomised controlled trials of major depressive disorder in older adults: protocol for a methodological review.

INTRODUCTION: Major depressive disorder (MDD or depression) is prevalent among adults aged 65 years and older. The effectiveness and safety of interventions used to treat depression is often assessed through randomised controlled trials (RCTs). However, heterogeneity in the selection, measurement and reporting of outcomes in RCTs renders comparisons between trial results, interpretability and generalisability of findings challenging. There is presently no core outcome set (COS) for use in RCTs that assess interventions for older adults with MDD. We will conduct a methodological review of the literature for outcomes reported in trials for adults 65 years and older with depression to assess the heterogeneity of outcome measures. METHODS AND ANALYSIS: RCTs evaluating pharmacotherapy, psychotherapy, or any other treatment intervention for older adults with MDD published in the last 10 years will be located using electronic database searches (MEDLINE, Embase, PsycINFO and the Cochrane Central Register of Controlled Trials). Reviewers will conduct title and abstract screening, full-text screening and data extraction of trials eligible for inclusion independently and in duplicate. Outcomes will be synthesised and mapped to core outcome-domain frameworks. We will summarise characteristics associated with trials and outcomes. ETHICS AND DISSEMINATION: We hope that findings from our methodological review will reduce variability in outcome selection, measurement and reporting and facilitate the development of a COS for older adults with MDD. Our review will also inform evidence synthesis efforts in identifying the best treatment practices for this clinical population. Ethics approval is not required, as this study is a literature review. PROSPERO REGISTRATION NUMBER: CRD42021244753.

A systematic review of GWAS identified SNPs associated with outcomes of medications for opioid use disorder.

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.

ALK inhibitor-induced bradycardia: A systematic-review and meta-analysis.

INTRODUCTION: Anaplastic Lymphoma Kinase (ALK) inhibitors have revolutionized the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC), improving progression-free survival. Bradycardia is a potential adverse effect of these agents. We aimed to determine the risk of bradycardia associated with ALK inhibitors in patients with advanced NSCLC. MATERIALS AND METHODS: We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, National clinical trial registry, and Web of Science Core Collection. We included all randomized controlled trials in which an ALK-inhibitor was compared with another ALK-inhibitor or standard chemotherapy. Meta-analyses were conducted to evaluate the pooled incidence rates of bradycardia and dizziness using fixed effect models. RESULTS: The pooled incidence of bradycardia among 1737 individuals prescribed ALK inhibitors was 8% during a mean follow-up of 1.26 years. Crizotinib led to more bradycardia than standard chemotherapy (relative risk, RR 24.68, 95% CI 7.11-85.), while no difference was seen between crizotinib and alectinib (RR 1.12, 95% CI 0.79-1.59). The next-generation ALK inhibitors alectinib, brigatinib and lorlatinib combined resulted in a similar rate of bradycardia when compared to crizotinib (RR 0.77, 95% CI 0.57-1.04). All ALK inhibitors (as an aggregate) caused more dizziness (as a potential symptom of bradycardia) than standard chemotherapy (RR 1.88, 95% CI 1.44-2.44). CONCLUSION: Crizotinib for the treatment of NSCLC is associated with a higher risk for bradycardia compared to standard chemotherapy. There is no evidence of a difference in bradycardia risk between crizotinib and newer ALK inhibitors.

Genetic basis of cannabis use: a systematic review.

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.

Which Bone-Modifying Agent is Associated with Better Outcomes in Patients with Skeletal Metastases from Lung Cancer? A Systematic Review and Network Meta-analysis.

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.

Association between vaping and health outcomes in patients with opioid use disorder: a systematic review protocol.

INTRODUCTION: Vaping behaviour has increased in popularity and is particularly important to examine how it effects health outcomes in vulnerable populations, including those with opioid use disorder (OUD). With polysubstance use including cigarette and cannabis use being highly prevalent in the OUD population and cannabis/nicotine increasingly being consumed by vaping, vaping may have an important contribution to health outcomes in these individuals. The primary objective of this review is to systematically assess the literature related to patients with OUD and the effects vaping has shown on their physical and mental health. METHOD AND ANALYSIS: A systematic search of databases including MEDLINE, Embase, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry and the WHO International Clinical Trials Registry Platform from inception to 31 December 2020 will be conducted. Identified citations will be screened by two reviewers to determine eligibility at the title and abstract level, and then at the full text and data extraction phases. Any disagreements in inclusion will be resolved through unblinded discussion by these reviewers, with any remaining disagreements being resolved by a third reviewer. Data collection from eligible studies will be conducted according to the data extraction form tested prior to abstraction. Included studies will be examined for quality and bias and will be meta-analysed where applicable. This protocol is reported in keeping with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. ETHICS AND DISSEMINATION: The results for this review will be disseminated through publications in peer-reviewed journals, posters and presentations at scientific conferences. Additionally, we are collaborating with the Canadian Addiction Treatment Centre clinics to help disseminate the findings for this review. As this is a systematic review, no ethics approval is needed. REVIEW REGISTRATION NUMBER: CRD42020178441.

Pharmacological prevention of fractures in patients undergoing glucocorticoid therapies: a systematic review and network meta-analysis.

OBJECTIVE: To perform a network meta-analysis (NMA) on the efficacy of antiosteoporotic interventions in the prevention of vertebral and non-vertebral fractures in adult patients taking glucocorticoids (GCs). METHODS: We performed NMAs based on a prospectively developed protocol. A librarian-assisted database search of MEDLINE, EMBASE, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), the Cochrane Central Register of Controlled Trials (CENTRAL) and Chinese databases was conducted for randomized controlled trials (RCTs) comparing antiosteoporotic interventions in adult patients taking GCs. Outcomes were vertebral and non-vertebral fracture incidences. RESULTS: We included 56 RCTs containing 6479 eligible patients in our analysis. We found that alendronate and teriparatide were associated with decreased odds of both vertebral and non-vertebral fractures. Denosumab and risedronate were associated with decreased odds of vertebral fractures, while etidronate, ibandronate and alfacalcidol were associated with decreased odds of non-vertebral fractures. We observed low network heterogeneity as indicated by the I2 statistic, and we did not detect evidence of publication bias. All outcomes were based on a moderate quality of evidence according to GRADE. CONCLUSION: Bisphosphonates, teriparatide and denosumab are associated with decreased odds of fracture in patients undergoing GC therapy. Vitamin D metabolites and analogues (e.g. alfacalcidol) may have greater anti-fracture efficacy compared with plain vitamin D. SYSTEMATIC REVIEW REGISTRATION: The International Prospective Register of Systematic Reviews (PROSPERO)-CRD42019127073.

Evolution and change in paradigm of hemodialysis in children: a systematic review.

BACKGROUND: There are similarities in hemodialysis (HD) between adults and children and also unique pediatric aspects. In this systematic review, we evaluated the existing HD literature, including vascular access, indications, parameters, and outcomes as a reflection on real-life HD practices. METHODS: Medline, Embase, CINAHL, Web of Science, and Cochrane Library were systematically searched for literature on HD in children (1-20 years). Two reviewers independently assessed the literature and data on indications; vascular access, outcomes, and specific parameters for HD were extracted. RESULTS: Fifty-four studies (8751 patients) were included in this review. Studies were stratified into age groups 1-5, 6-12, and 13-20 years based on median/mean age reported in the study, as well as era of publication (1990-2000, 2001-2010, and 2011-2019). Across all age groups, both arteriovenous fistulas and central venous catheters were utilized for vascular access. Congenital abnormalities and glomerulopathy were the most common HD indications. HD parameters including HD session duration, dialysate and blood flow rates, urea reduction ratio, and ultrafiltration were characterized for each age group, as well as common complications including catheter dysfunction and intradialytic hypotension. Median mortality rates were 23.3% (3.3), 7.6% (14.5), and 2.0% (3.0) in ages 1-5, 6-12, and 13-20 years, respectively. Median transplantation rates were 41.6% (38.3), 52.0% (32.0), and 21% (25.6) in ages 1-5, 6-12, and 13-20, respectively. CONCLUSION: This comprehensive systematic review summarizes available literature on HD in children and young adults, including best vascular access, indications, technical aspects, and outcomes, and reflects on HD practices over the last three decades.

Treatment Outcomes in Patients With Opioid Use Disorder Who Were First Introduced to Opioids by Prescription: A Systematic Review and Meta-Analysis.

OBJECTIVE: Prescription opioid misuse has led to a new cohort of opioid use disorder (OUD) patients who were introduced to opioids through a legitimate prescription. This change has caused a shift in the demographic profile of OUD patients from predominantly young men to middle age and older people. The management of OUD includes medication-assisted treatment (MAT), which produces varying rates of treatment response. In this study, we will examine whether the source of first opioid use has an effect on treatment outcomes in OUD. Using a systematic review of the literature, we will investigate the association between source of first opioid introduction and treatment outcomes defined as continuing illicit opioid use and poly-substance use while in MAT. METHODS: Medline, EMBASE, CINHAL, and PsycInfo were searched from inception to December 31st, 2019 inclusive using a comprehensive search strategy. Five pairs of reviewers conducted screening and data extraction independently in duplicate. The review is conducted and reported according to the PRISMA guidelines. A random-effects model was used for meta analyses assuming heterogeneity among the included studies. RESULTS: The initial search results in 27,345 articles that were screened, and five observational studies were included in the qualitative and quantitative analyses. Our results found that those who were introduced to opioids through a legitimate prescription were significantly less likely to have illicit opioid use (0.70, 95% CI 0.50, 0.99) while on MAT. They were also less likely to use cannabis (0.54, 95% CI 0.32, 0.89), alcohol (0.75, 95% CI 0.59, 0.95), cocaine (0.50, 95% CI 0.29, 0.85), and injection drug use (0.25, 95% CI 0.14, 0.43) than those introduced to opioids through recreational means. CONCLUSION: This study shows that the first exposure to opioids, whether through a prescription or recreationally, influences prognosis and treatment outcomes of opioid use disorder. Although the increased pattern of prescribing opioids may have led to increased OUD in a new cohort of patients, these patients are less likely to continue to use illicit drugs and have a different prognostic and clinical profile that requires a tailored approach to treatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017058143.

GWAS-identified genetic variants associated with medication-assisted treatment outcomes in patients with opioid use disorder: a systematic review and meta-analysis protocol.

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).

Impact of COVID-19 and other pandemics and epidemics on people with pre-existing mental disorders: a systematic review protocol and suggestions for clinical care.

INTRODUCTION: The current COVID-19 pandemic has resulted in high rates of infection and death, as well as widespread social disruption and a reduction in access to healthcare services and support. There is growing concern over how the pandemic, as well as measures put in place to curb the pandemic, will impact people with mental disorders. We aim to study the effect of pandemics and epidemics on mental health outcomes for people with premorbid mental disorders. METHODS AND ANALYSIS: With our predefined search strategy, we will search five databases for studies reporting on mental health outcomes in people with pre-existing mental disorders during pandemic and epidemic settings. Search dates are planned as follows: 5 May 2020 and 23 July 2020. The following databases will be searched: MEDLINE/PubMed, CINAHL, PsycINFO, MedRxiv and EMBASE. Data will be screened and extracted in duplicate by two independent reviewers. Studies involving non-clinical populations or patients diagnosed with a mental disorder during a pandemic/epidemic will be excluded. We will include data collected from all pandemics and epidemics throughout history, including the present COVID-19 pandemic. If possible, study findings will be combined in meta-analyses, and subgroup analyses will be performed. We hope that this review will shed light on the impact of pandemics and epidemics on those with pre-existing mental disorders. Knowledge generated may inform future intervention studies as well as healthcare policies. Given the potential implications of the current pandemic measures (ie, disruption of healthcare services) on mental health, we will also compile a list of existing mental health resources. ETHICS AND DISSEMINATION: No ethical approval is required for this protocol and proposed systematic review as we will only use data from previously published papers that have themselves received ethics clearance and used proper informed consent procedures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020179611.