Application of exome sequencing for prenatal diagnosis: a rapid scoping review.

Genetic diagnosis provides important information for prenatal decision-making and management. Promising results from exome sequencing (ES) for genetic diagnosis in fetuses with structural anomalies are emerging. The objective of this scoping review was to identify what is known about the use of ES for genetic testing in prenatal cases with known or suspected genetic disease. A rapid scoping review was conducted over a six-week timeframe of English-language peer-reviewed studies. Search strategies for major databases (e.g., Medline) and gray literature were developed, and peer reviewed by information specialists. Identified studies were categorized and charted using tables and diagrams. Twenty-four publications were included from seven countries published between 2014 and 2019. Most commonly reported outcomes were diagnostic yields, which varied widely from 5% to 57%, and prenatal phenotype. Few studies reported clinical outcomes related to impact, decision-making, and clinical utility. Qualitative studies (n = 6) provided useful insights into patient and health-care provider experiences with ES. Findings suggest prenatal ES is beneficial, but more research is needed to better understand the clinical utility, circumstances for ideal use, feasibility, and costs of offering rapid ES as a routine option for prenatal genetic testing.

Care plans for women pregnant using assisted reproductive technologies: a systematic review.

BACKGROUND: Between 1 and 5% of children in industrialized countries are conceived through Assisted Reproductive Technologies (ART). As infertility and the use of ART may be associated with adverse perinatal outcomes, care plans specific to these pregnancies are needed. We conducted a systematic review to examine the existing care plans specific to women pregnant following Assisted Reproductive Technologies (ART). METHODS: MEDLINE, Embase and the Cochrane Library were searched by a senior information specialist. The population of interest included women becoming pregnant with ART (e.g., Intra-Uterine Insemination, In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection (ICSI), and surrogacy). All proposed care plans were sought that pertained to any aspect of care during pregnancy and delivery. Only Clinical Practice Guidelines (CPGs) addressing the recommendations and plans for the care of ART pregnant women were included. The search was restricted to the publication dates 2007 to June 12, 2017 when the search was run. The search was not restricted by language, however only English and French language guidelines were considered for inclusion. RESULTS: After screening 2078 citations, a total of ten CPGs were included. The following key clinical messages were prevalent: (1) although there was no supporting evidence, antenatal care for ART pregnancies should be provided by specialist with knowledge in obstetrics; (2) high-order multiple pregnancies are the greatest risk of ART and selective reduction options should be discussed; (3) there is some evidence of increased risk of congenital abnormalities and prenatal genetic and anatomic screening is recommended, especially in IVF-ICSI pregnancies; (4) due to a lack of or conflicting evidence, treatment of venous thromboembolism, antithrombotic therapy, treatment for hypothyroidism, and women with positive thyroid antibodies is recommended to be the same as in spontaneous pregnancies; and lastly (5) since an increased level of distress is a recognized feature in these pregnancies, psychosocial care and counselling should be considered. CONCLUSIONS: There is a lack of CPGs specific to ART pregnancies. While we identified a small number of recommendations for ART pregnancies, specific interventions and models of care aiming at decreasing adverse maternal and perinatal outcomes following ART should be developed, implemented, and evaluated.

Effectiveness of e-cigarettes as a stop smoking intervention in adults: a systematic review.

BACKGROUND: This systematic review aims to identify the benefits and harms of electronic cigarettes (e-cigarettes) as a smoking cessation aid in adults (aged ≥ 18 years) and to inform the development of the Canadian Task Force on Preventive Health Care's (CTFPHC) clinical practice guidelines on e-cigarettes. METHODS: We searched Ovid MEDLINE®, Ovid MEDLINE® Epub Ahead of Print, In-Process & Other Non-Indexed Citations, PsycINFO, Embase Classic + Embase, and the Cochrane Library on Wiley. Searches were conducted from January 2016 to July 2019 and updated on 24 September 2020 and 25 January 2024. Two reviewers independently performed title-abstract and full-text screening according to the pre-determined inclusion criteria. Data extraction, quality assessments, and the application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) were performed by one independent reviewer and verified by another. RESULTS: We identified 18 studies on 17 randomized controlled trials that compared e-cigarettes with nicotine to e-cigarettes without nicotine and e-cigarettes (with or without nicotine) to other interventions (i.e., no intervention, waitlist, standard/usual care, quit advice, or behavioral support). Considering the benefits of e-cigarettes in terms of smoking abstinence and smoking frequency reduction, 14 studies showed small or moderate benefits of e-cigarettes with or without nicotine compared to other interventions; although, with low, very low or moderate evidence certainty. With a focus on e-cigarettes with nicotine specifically, 12 studies showed benefits in terms of smoking abstinence when compared with usual care or non-nicotine e-cigarettes. In terms of harms following nicotine or non-nicotine e-cigarette use, 15 studies reported mild adverse events with little to no difference between groups and low to very low evidence certainty. CONCLUSION: The evidence synthesis on the e-cigarette's effectiveness shows data surrounding benefits having low to moderate evidence certainty for some comparisons and very low certainty for others, indicating that e-cigarettes may or probably increase smoking cessation, whereas, for harms, there is low to very low evidence certainty. Since the duration for outcome measurement varied among different studies, it may not be long-term enough for Adverse Events (AEs) to emerge, and there is a need for more research to understand the long-term benefits and potential harms of e-cigarettes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099692.

Effectiveness of smoking cessation interventions among adults: an overview of systematic reviews.

BACKGROUND: This overview of reviews aims to identify evidence on the benefits (i.e. tobacco use abstinence and reduction in smoking frequency) and harms (i.e. possible adverse events/outcomes) of smoking cessation interventions among adults aged 18 years and older. METHODS: We searched Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the CADTH Health Technology Assessment Database and several other websites for grey literature. Searches were conducted on November 12, 2018, updated on September 24, 2020, with publication years 2008 to 2020. Two reviewers independently performed title-abstract and full-text screening considering pre-determined inclusion criteria. Data extraction and quality assessments were initially completed by two reviewers independently (i.e. 73% of included studies (n = 22)) using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR 2), and the remainder done by one reviewer and verified by another due to resources and feasibility. The application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) was performed by one independent reviewer and verified by another. RESULTS: A total of 22 Cochrane systematic reviews evaluating the impact of smoking cessation interventions on outcomes such as tobacco use abstinence, reduction in smoking frequency, quality of life and possible adverse events were included. Pharmaceutical (i.e. varenicline, cytisine, nicotine replacement therapy (NRT), bupropion) and behavioural interventions (i.e. physician advice, non-tailored print-based self-help materials, stage-based individual counselling, etc.) showed to have increased smoking cessation; whereas, data for mobile phone-based interventions including text messaging, hypnotherapy, acupuncture, continuous auricular stimulation, laser therapy, electrostimulation, acupressure, St John's wort, S-adenosyl-L-methionine (SAMe), interactive voice response systems and other combination treatments were unclear. Considering harms related to smoking cessation interventions, small/mild harms (i.e. increased palpitations, chest pain, nausea, insomnia, headache) were observed following NRT, varenicline and cytisine use. There were no data on harms related to behavioural therapies (i.e. individual or group counselling self-help materials, internet interventions), combination therapies or other therapies (i.e. laser therapy, electrostimulation, acupressure, St John's wort, SAMe). CONCLUSION: Results suggest that pharmacological and behavioural interventions may help the general smoking population quit smoking with observed small/mild harms following NRT or varenicline. Consequently, evidence regarding ideal intervention strategies and the long-term impact of these interventions for preventing smoking was unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018099691.

Realist review of community coalitions and outreach interventions to increase access to primary care for vulnerable populations: a realist review.

BACKGROUND: There are meaningful gaps in equitable access to Primary Health Care (PHC), especially for vulnerable populations after widespread reforms in Western countries. The Innovative Models Promoting Access-to-Care Transformation (IMPACT) research program is a Canadian-Australian collaboration that aims to improve access to PHC for vulnerable populations. Relationships were developed with stakeholders in six regions across Canada and Australia where access-related needs could be identified. The most promising interventions would be implemented and tested to address the needs identified. This realist review was conducted to understand how community coalition and outreach (e.g., mobile or pop-up) services improve access for underserved vulnerable residents. OBJECTIVE: To inform the development and delivery of an innovative intervention to increase access to PHC for vulnerable populations. METHODS: A realist review was conducted in collaboration with the Local Innovative Partnership (LIP) research team and the IMPACT research members who conducted the review. We performed an initial comprehensive systematic search using MEDLINE, EMBASE, PsycINFO, and the Cochrane Library up to October 19, 2015, and updated it on August 8, 2020. Studies were included if they focused on interventions to improve access to PHC using community coalition, outreach services or mobile delivery methods. We included Randomized Controlled Trials (RCTs), and systematic reviews. Studies were screened by two independent reviewers and the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used for data extraction and framework analysis to obtain themes. The LIP research team was also allowed to suggest additional papers not included at screening. RESULTS: We included 43 records, comprising 31 RCTs, 11 systematic reviews, and 1 case control study that was added by the LIP research team. We identified three main themes of PHC interventions to promote access for vulnerable residents, including: 1) tailoring of materials and services decreases barriers to primary health care, 2) services offered where vulnerable populations gather increases the "reach" of the interventions, 3) partnerships and collaborations lead to positive health outcomes. In addition, implementation designs and reporting elements should be considered. CONCLUSION: Realist reviews can help guide the development of locally adapted primary health care interventions.

Screening for depression among the general adult population and in women during pregnancy or the first-year postpartum: two systematic reviews to inform a guideline of the Canadian Task Force on Preventive Health Care.

BACKGROUND: Depression affects an individual's physical health and mental well-being and, in pregnant and postpartum women, has specific adverse short- and long-term effects on maternal, child, and family health. The aim of these two systematic reviews is to identify evidence on the benefits and harms of screening for depression compared to no screening in the general adult and pregnant and postpartum populations in primary care or non-mental health clinic settings. These reviews will inform recommendations by the Canadian Task Force on Preventive Health Care. METHODS: We searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library using a randomized controlled trial filter, where applicable, October 4, 2018, and updated to May 11, 2020. We also searched for gray literature (e.g., websites of organizations of health professionals and patients). Study selection for depression screening trials was performed first on title and abstract, followed by full-text screening. Data extraction, assessment of the risk of bias using the Cochrane risk of bias tool, and application of Grading of Recommendations Assessment, Development and Evaluation were performed by one reviewer and validated by a second reviewer. RESULTS: A total of three trials were included. All three trials were included in the general adult review, while one of the three trials was included in the pregnant and postpartum review. We did not pool results due to substantial differences between studies and high risk of bias. In the general adult review, the first trial (n = 1001) evaluated whether screening for depression in adults with acute coronary syndrome compared to usual care improves health-related quality of life, depression symptoms, or harms of screening at 6, 12, and 18 months. There were little to no differences between the groups at 18 months for the outcomes. The second trial included adults (n = 1412) undergoing initial consultation for osteoarthritis, evaluated for depression and general health (mental and physical) after initial consultation and at 3, 6, and 12 months. The physical component score was statistically significantly lower (worse health) in the screened group at 6 months; however, this difference was not significant at 3 or at 12 months. There were no clinically important or statistically significant differences for other outcomes between groups at any time. The third trial (included in both reviews) reported on 462 postpartum women. At 6 months postpartum, fewer women in the screening group were identified as possibly depressed compared to the control group (RR 0.59, 95% confidence interval (CI) 0.39 to 0.89) and mean EPDS scores were also statistically significantly lower in the screened group (standardized mean difference 0.34 lower (95% CI 0.15 to 0.52 lower)). All other outcomes did not differ between groups at follow-up. There were serious concerns about the cut-offs used for the questionnaire used to screen, diagnostic confirmation, selective outcome reporting, and the reported magnitude of effects. DISCUSSION: There are limitations of the evidence included in the reviews. There was moderate certainty in the evidence from one trial that screening for depression in the general adult population in primary care or non-mental health clinic settings likely results in little to no difference on reported outcomes; however, the evidence was uncertain from the other two included trials. The evidence is very uncertain about the effect of screening for depression in pregnant or postpartum women in primary care or non-mental health clinic settings. Well-conducted and better-reported trials are needed that meet the screening trial criteria used in this review. SYSTEMATIC REVIEW REGISTRATION: Both protocols have been registered in the International Prospective Registry of Systematic Reviews (PROSPERO) [adult: CRD42018099690 ; pregnancy and postpartum: CRD42018099689 ] and published ( https://systematicreviewsjournal.biomedcentral.com/track/pdf/10.1186/s13643-018-0930-3 ).

Defining Rapid Reviews: a systematic scoping review and thematic analysis of definitions and defining characteristics of rapid reviews.

BACKGROUND AND OBJECTIVE: Rapid reviews were first mentioned in the literature in 1997, when Best et al. described the rapid health technology assessment program in the south and west regions of England but did not provide a formal definition. More recently, the only consensus around a rapid review definition is that a formal definition does not exist. The primary aim of this work is to create a repository of existing definitions and to identify key themes, which may help the knowledge synthesis community in defining rapid review products. METHODS: A systematic scoping review was performed to identify definitions used in journal-published rapid reviews written in English between 2017 and January 2019. We searched Medline, Embase Classic + Embase, PsycINFO, ERIC, Cochrane Library, CINAHL, and Web of Science on December 21, 2018. Two reviewers performed study selection and data extraction using a priori-defined methods published in a protocol. Definitions from rapid review methods articles (published from 1997 onward) identified in another scoping review were added to the results, and all definitions were thematically analyzed using NVivo. A quantitative analysis was also performed around studies cited. RESULTS: Definitions from 216 rapid reviews and 90 rapid review methods articles were included in the thematic analysis. Eight key themes were identified: accelerated/rapid process or approach, variation in methods shortcuts, focus/depth/breadth of scope, compare and contrast to a full traditional systematic review, stakeholder rationale, resource efficiency rationale, systematic approach, bias/limitations. Secondary referencing was a common occurrence. CONCLUSION: Thematic analysis performed in this systematic scoping review has allowed for the creation of a suggested definition for rapid reviews that can be used to inform the systematic review community.

Antenatal and postpartum prevention of Rh alloimmunization: A systematic review and GRADE analysis.

BACKGROUND: Existing systematic reviews of Rh immunoprophylaxis include only data from randomized controlled trials, have dated searches, and some do not report on all domains of risk of bias or evaluate the certainty of the evidence. Our objective was to perform an updated review, by including new trials, any comparative observational studies, and assessing the certainty of the evidence using the GRADE framework. METHODS: We searched MEDLINE, Embase and the Cochrane Library from 2000 to November 26, 2019. Relevant websites and bibliographies of systematic reviews and guidelines were searched for studies published before 2000. Outcomes of interest were sensitization and adverse events. Risk of bias was evaluated with the Cochrane tool and ROBINS-I. The certainty of the evidence was performed using the GRADE framework. RESULTS: Thirteen randomized trials and eight comparative cohort studies were identified, evaluating 12 comparisons. Although there is some evidence of beneficial treatment effects (e.g., at 6-months postpartum, fewer women who received RhIg at delivery compared to no RhIg became sensitized [70 fewer sensitized women per 1,000 (95%CI: 67 to 71 fewer); I2 = 73%]), due to very low certainty of the evidence, the magnitude of the treatment effect may be overestimated. The certainty of the evidence was very low for most outcomes often due to high risk of bias (e.g., randomization method, allocation concealment, selective reporting) and imprecision (i.e., few events and small sample sizes). There is limited evidence on prophylaxis for invasive fetal procedures (e.g. amniocentesis) in the comparative literature, and few studies reported adverse events. CONCLUSION: Serious risk of bias and low to very low certainty of the evidence is found in existing RCTs and comparative observational studies addressing optimal effectiveness of Rh immunoprophylaxis. Guideline development committees should exercise caution when assessing the strength of the recommendations that inform and influence clinical practice in this area.

Few evaluative studies exist examining rapid review methodology across stages of conduct: a systematic scoping review.

OBJECTIVES: The objective is to identify studies that have assessed methodological shortcuts for undertaking rapid reviews (RRs) and mapping these to review conduct stages and Methodological Expectations of Cochrane Intervention Reviews (MECIR) guidance. STUDY DESIGN AND SETTING: We conducted a systematic scoping review. We searched multiple databases (e.g., MEDLINE, Embase), which were supplemented by grey literature searching. Methods were defined a priori in a published protocol. RESULTS: Out of 1,873 records, 90 publications were divided into four RR categories: formal evaluation (n = 14), development, which included four subcategories (n = 65), comparison (n = 2), and applying reporting guidelines/critical appraisal tools (n = 3), and a systematic review surrogate category (n = 6). Four formal evaluation studies were composite evaluations, including more than one shortcut simultaneously. The remaining 10 studies evaluated viable (e.g., including English-only publications) and unviable (e.g., single-reviewer screening) shortcuts, covering five key dimensions and five 'other' (e.g., involving stakeholders) considerations while conducting a review. Because of complexities around shortcuts evaluated, only a cursory mapping to MECIR criteria was possible. CONCLUSION: Some methods shortcuts may be valid in the context of RRs, but limitations in the studies may limit their applicability. The results will serve to inform discussions within Cochrane regarding possible future implementation of RRs.

Screening for esophageal adenocarcinoma and precancerous conditions (dysplasia and Barrett's esophagus) in patients with chronic gastroesophageal reflux disease with or without other risk factors: two systematic reviews and one overview of reviews to inform a guideline of the Canadian Task Force on Preventive Health Care (CTFPHC).

BACKGROUND: Two reviews and an overview were produced for the Canadian Task Force on Preventive Health Care guideline on screening for esophageal adenocarcinoma in patients with chronic gastroesophageal reflux disease (GERD) without alarm symptoms. The goal was to systematically review three key questions (KQs): (1) The effectiveness of screening for these conditions; (2) How adults with chronic GERD weigh the benefits and harms of screening, and what factors contribute to their preferences and decision to undergo screening; and (3) Treatment options for Barrett's esophagus (BE), dysplasia or stage 1 EAC (overview of reviews). METHODS: Bibliographic databases (e.g. Ovid MEDLINE®) were searched for each review in October 2018. We also searched for unpublished literature (e.g. relevant websites). The liberal accelerated approach was used for title and abstract screening. Two reviewers independently screened full-text articles. Data extraction and risk of bias assessments were completed by one reviewer and verified by another reviewer (KQ1 and 2). Quality assessments were completed by two reviewers independently in duplicate (KQ3). Disagreements were resolved through discussion. We used various risk of bias tools suitable for study design. The GRADE framework was used for rating the certainty of the evidence. RESULTS: Ten studies evaluated the effectiveness of screening. One retrospective study reported no difference in long-term survival (approximately 6 to 12 years) between those who had a prior esophagogastroduodenoscopy and those who had not (adjusted HR 0.93, 95% confidence interval (CI) 0.58-1.50). Though there may be higher odds of a stage 1 diagnosis than a more advanced diagnosis (stage 2-4) if an EGD had been performed in the previous 5 years (OR 2.27, 95% CI 1.00-7.67). Seven studies compared different screening modalities, and showed little difference between modalities. Three studies reported on patients' unwillingness to be screened (e.g. due to anxiety, fear of gagging). Eleven systematic reviews evaluated treatment modalities, providing some evidence of early treatment effect for some outcomes. CONCLUSIONS: Little evidence exists on the effectiveness of screening and values and preferences to screening. Many treatment modalities have been evaluated, but studies are small. Overall, there is uncertainty in understanding the effectiveness of screening and early treatments. SYSTEMATIC REVIEW REGISTRATIONS: PROSPERO (CRD42017049993 [KQ1], CRD42017050014 [KQ2], CRD42018084825 [KQ3]).

Benefits and harms of medical cannabis: a scoping review of systematic reviews.

BACKGROUND: There has been increased interest in the role of cannabis for treating medical conditions. The availability of different cannabis-based products can make the side effects of exposure unpredictable. We sought to conduct a scoping review of systematic reviews assessing benefits and harms of cannabis-based medicines for any condition. METHODS: A protocol was followed throughout the conduct of this scoping review. A protocol-guided scoping review conduct. Searches of bibliographic databases (e.g., MEDLINE®, Embase, PsycINFO, the Cochrane Library) and gray literature were performed. Two people selected and charted data from systematic reviews. Categorizations emerged during data synthesis. The reporting of results from systematic reviews was performed at a high level appropriate for a scoping review. RESULTS: After screening 1975 citations, 72 systematic reviews were included. The reviews covered many conditions, the most common being pain management. Several reviews focused on management of pain as a symptom of conditions such as multiple sclerosis (MS), injury, and cancer. After pain, the most common symptoms treated were spasticity in MS, movement disturbances, nausea/vomiting, and mental health symptoms. An assessment of review findings lends to the understanding that, although in a small number of reviews results showed a benefit for reducing pain, the analysis approach and reporting in other reviews was sub-optimal, making it difficult to know how consistent findings are when considering pain in general. Adverse effects were reported in most reviews comparing cannabis with placebo (49/59, 83%) and in 20/24 (83%) of the reviews comparing cannabis to active drugs. Minor adverse effects (e.g., drowsiness, dizziness) were common and reported in over half of the reviews. Serious harms were not as common, but were reported in 21/59 (36%) reviews that reported on adverse effects. Overall, safety data was generally reported study-by-study, with few reviews synthesizing data. Only one review was rated as high quality, while the remaining were rated of moderate (n = 36) or low/critically low (n = 35) quality. CONCLUSIONS: Results from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis-based medicines may outweigh benefits. SYSTEMATIC REVIEW REGISTRATION: The protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).