George & Fay Yee Centre for Healthcare Innovation

BACKGROUND: No effective oral therapy exists for early coronavirus disease 2019 (COVID-19). OBJECTIVE: To investigate whether hydroxychloroquine could reduce COVID-19 severity in adult outpatients. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from 22 March through 20 May 2020. (ClinicalTrials.gov: NCT04308668). SETTING: Internet-based trial across the United States and Canada (40 states and 3 provinces). PARTICIPANTS: Symptomatic, nonhospitalized adults with laboratory-confirmed COVID-19 or probable COVID-19 and high-risk exposure within 4 days of symptom onset. INTERVENTION: Oral hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 more days) or masked placebo. MEASUREMENTS: Symptoms and severity at baseline and then at days 3, 5, 10, and 14 using a 10-point visual analogue scale. The primary end point was change in overall symptom severity over 14 days. RESULTS: = 0.29). LIMITATION: Only 58% of participants received SARS-CoV-2 testing because of severe U.S. testing shortages. CONCLUSION: Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19. PRIMARY FUNDING SOURCE: Private donors.

BACKGROUND: Conducting research in partnership with stakeholders (e.g. policy-makers, practitioners, organisations, patients) is a promising and popular approach to improving the implementation of research findings in policy and practice. This study aimed to identify the principles, strategies, outcomes and impacts reported in different types of reviews of research partnerships in order to obtain a better understanding of the scope of the research partnership literature. METHODS: This review of reviews is part of a Coordinated Multicenter Team approach to synthesise the research partnership literature with five conceptually linked literature reviews. The main research question was 'What principles, strategies, outcomes and impacts are reported in different types of research partnership approaches?'. We included articles describing a literature review of research partnerships using a systematic search strategy. We used an adapted version of the Revised Assessment of Multiple Systematic Reviews tool to assess quality. Nine electronic databases were searched from inception to April 2018. Principles, strategies, outcomes and impacts were extracted from the included reviews and analysed using direct content analysis. RESULTS: We included 86 reviews using terms describing several research partnership approaches (e.g. community-based participatory research, participatory research, integrated knowledge translation). After the analyses, we synthesised 17 overarching principles and 11 overarching strategies and grouped them into one of the following subcategories: relationship between partners; co-production of knowledge; meaningful stakeholder engagement; capacity-building, support and resources; communication process; and ethical issues related to the collaborative research activities. Similarly, we synthesised 20 overarching outcomes and impacts on researchers, stakeholders, the community or society, and the research process. CONCLUSIONS: This review of reviews is the first that presents overarching principles, strategies, outcomes and impacts of research partnerships. This review is unique in scope as we synthesised literature across multiple research areas, involving different stakeholder groups. Our findings can be used as a first step to guide the initiation and maintenance of research partnerships and to create a classification system of the key domains of research partnerships, which may improve reporting consistency in the research partnership literature. TRIAL REGISTRATION: This study is registered via Open Science Framework: https://doi.org/10.17605/OSF.IO/GVR7Y.

<h3>BACKGROUND</h3> Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects. <h3>METHODS</h3> We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points. <h3>RESULTS</h3> From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference −0.37 kg/m²; 95% confidence interval [CI] −1.10 to 0.36; <i>I</i>² 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; <i>I</i>² 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome. <h3>INTERPRETATION</h3> Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. <b>Protocol registration:</b> PROSPERO-CRD42015019749

BACKGROUND: Women with endometriosis who are treated with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have a lower pregnancy rate compared to women with tubal factor infertility. It has been suggested that the administration of gonadotrophin releasing hormone (GnRH) agonists for a few months prior to IVF or ICSI increases the pregnancy rate. OBJECTIVES: To determine the effectiveness of administering GnRH agonists for three to six months prior to IVF or ICSI in women with endometriosis. SEARCH STRATEGY: We used computer searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the National Research Register (NRR) and the MDSG Specialised Register of controlled trials. We handsearched proceedings of annual meetings of the American Society for Reproductive Medicine (ASRM) and the European Society for Human Reproduction and Embryology (ESHRE). We reviewed lists of references in original research and review articles. We contacted experts in various countries to identify unpublished trials. SELECTION CRITERIA: We included randomised controlled trials using any GnRH agonist prior to IVF or ICSI to treat women with any degree of endometriosis diagnosed by laparoscopy or laparotomy DATA COLLECTION AND ANALYSIS: Two independent review authors abstracted data (HNS and JGV). We sent e-mails to investigators to seek additional information. We assessed the validity of each study using the methods suggested in the Cochrane Handbook. The data were checked by the third review author (SD) and any disagreement was resolved by arbitration with the fourth review author (AA). We generated 2 x 2 tables for principal outcome measures. The Peto-modified Mantel-Haenszel technique was used to calculate odds ratios (OR) and assess statistical heterogeneity between studies. MAIN RESULTS: Three randomised controlled trials (with 165 women) were included. The live birth rate per woman was significantly higher in women receiving the GnRH agonist compared to the control group (OR 9.19, 95% CI 1.08 to 78.22). However, this was based on one trial reporting "viable pregnancy" only. The clinical pregnancy rate per woman was also significantly higher (three studies: OR 4.28, 95% CI 2.00 to 9.15). The information on miscarriage rates came from two trials with high heterogeneity and, therefore, results of the meta-analysis were doubtful. The included studies provided insufficient data to investigate the effects of administration of GnRH agonists on multiple or ectopic pregnancies, fetal abnormalities or other complications. AUTHORS' CONCLUSIONS: The administration of GnRH agonists for a period of three to six months prior to IVF or ICSI in women with endometriosis increases the odds of clinical pregnancy by fourfold. Data regarding adverse effects of this therapy on the mother or fetus are not available at present.

BACKGROUND AND AIMS: The province of British Columbia (BC) Canada has experienced a rapid increase in illicit drug overdoses and deaths during the last 4 years, with a provincial emergency declared in April 2016. These deaths have been driven primarily by the introduction of synthetic opioids into the illicit opioid supply. This study aimed to measure the combined impact of large-scale opioid overdose interventions implemented in BC between April 2016 and December 2017 on the number of deaths averted. DESIGN: We expanded on the mathematical modelling methodology of our previous study to construct a Bayesian hierarchical latent Markov process model to estimate monthly overdose and overdose-death risk, along with the impact of interventions. SETTING AND CASES: Overdose events and overdose-related deaths in BC from January 2012 to December 2017. INTERVENTIONS: The interventions considered were take-home naloxone kits, overdose prevention/supervised consumption sites and opioid agonist therapy MEASUREMENTS: Counterfactual simulations were performed with the fitted model to estimate the number of death events averted for each intervention and in combination. FINDINGS: Between April 2016 and December 2017, BC observed 2177 overdose deaths (77% fentanyl-detected). During the same period, an estimated 3030 (2900-3240) death events were averted by all interventions combined. In isolation, 1580 (1480-1740) were averted by take-home naloxone, 230 (160-350) by overdose prevention services and 590 (510-720) were averted by opioid agonist therapy. CONCLUSIONS: A combined intervention approach has been effective in averting overdose deaths during British Columbia's opioid overdose crisis in the period since declaration of a public health emergency (April 2016-December 2017). However, the absolute numbers of overdose deaths have not changed.

BACKGROUND: There is a plethora of interventions and policies aimed at changing practice habits of primary healthcare professionals, but it is unclear which are the most appropriate, sustainable, and effective. We aimed to evaluate the evidence on behavior change interventions and policies directed at healthcare professionals working in primary healthcare centers. METHODS: Study design: overview of reviews. DATA SOURCE: MEDLINE (Ovid), Embase (Ovid), The Cochrane Library (Wiley), CINAHL (EbscoHost), and grey literature (January 2005 to July 2015). STUDY SELECTION: two reviewers independently, and in duplicate, identified systematic reviews, overviews of reviews, scoping reviews, rapid reviews, and relevant health technology reports published in full-text in the English language. DATA EXTRACTION AND SYNTHESIS: two reviewers extracted data pertaining to the types of reviews, study designs, number of studies, demographics of the professionals enrolled, interventions, outcomes, and authors' conclusions for the included studies. We evaluated the methodological quality of the included studies using the AMSTAR scale. For the comparative evaluation, we classified interventions according to the behavior change wheel (Michie et al.). RESULTS: Of 2771 citations retrieved, we included 138 reviews representing 3502 individual studies. The majority of systematic reviews (91%) investigated behavior and practice changes among family physicians. Interactive and multifaceted continuous medical education programs, training with audit and feedback, and clinical decision support systems were found to be beneficial in improving knowledge, optimizing screening rate and prescriptions, enhancing patient outcomes, and reducing adverse events. Collaborative team-based policies involving primarily family physicians, nurses, and pharmacists were found to be most effective. Available evidence on environmental restructuring and modeling was found to be effective in improving collaboration and adherence to treatment guidelines. Limited evidence on nurse-led care approaches were found to be as effective as general practitioners in patient satisfaction in settings like asthma, cardiovascular, and diabetes clinics, although this needs further evaluation. Evidence does not support the use of financial incentives to family physicians, especially for long-term behavior change. CONCLUSIONS: Behavior change interventions including education, training, and enablement in the context of collaborative team-based approaches are effective to change practice of primary healthcare professionals. Environmental restructuring approaches including nurse-led care and modeling need further evaluation. Financial incentives to family physicians do not influence long-term practice change.

OBJECTIVE: To evaluate the association of probiotic supplementation during pregnancy or infancy with childhood asthma and wheeze. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and Central (Cochrane Library) databases from inception to August 2013, plus the World Health Organization's international clinical trials registry platform and relevant conference proceedings for the preceding five years. Included trials and relevant reviews were forward searched in Web of Science. REVIEW METHODS: Two reviewers independently identified randomised controlled trials evaluating probiotics administered to mothers during pregnancy or to infants during the first year of life. The primary outcome was doctor diagnosed asthma; secondary outcomes included wheeze and lower respiratory tract infection. RESULTS: We identified 20 eligible trials including 4866 children. Trials were heterogeneous in the type and duration of probiotic supplementation, and duration of follow-up. Only five trials conducted follow-up beyond participants' age of 6 years (median 24 months), and none were powered to detect asthma as the primary outcome. The overall rate of doctor diagnosed asthma was 10.7%; overall rates of incident wheeze and lower respiratory tract infection were 33.3% and 13.9%, respectively. Among 3257 infants enrolled in nine trials contributing asthma data, the risk ratio of doctor diagnosed asthma in participants randomised to receive probiotics was 0.99 (95% confidence interval 0.81 to 1.21, I(2)=0%). The risk ratio of incident wheeze was 0.97 (0.87 to 1.09, I(2)=0%, 9 trials, 1949 infants). Among 1364 infants enrolled in six trials, the risk ratio of lower respiratory tract infection after probiotic supplementation was 1.26 (0.99 to 1.61, I(2)=0%). We adjudicated most trials to be of high (ten trials) or unclear (nine trials) risk of bias, mainly due to attrition. CONCLUSIONS: We found no evidence to support a protective association between perinatal use of probiotics and doctor diagnosed asthma or childhood wheeze. Randomised controlled trials to date have not yielded sufficient evidence to recommend probiotics for the primary prevention of these disorders. Extended follow-up of existing trials, along with further clinical and basic research, are needed to accurately define the role of probiotics in the prevention of childhood asthma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42013004385).

BACKGROUND: The concept of patient engagement in health research has received growing international recognition over recent years. Yet despite some critical advancements, we argue that the concept remains problematic as it negates the very real complexities and context of people's lives. Though patient engagement conceptually begins to disrupt the identity of "researcher," and complicate our assumptions and understandings around expertise and knowledge, it continues to essentialize the identity of "patient" as a homogenous group, denying the reality that individuals' economic, political, cultural, subjective and experiential lives intersect in intricate and multifarious ways. DISCUSSION: Patient engagement approaches that do not consider the simultaneous interactions between different social categories (e.g. race, ethnicity, Indigeneity, gender, class, sexuality, geography, age, ability, immigration status, religion) that make up social identity, as well as the impact of systems and processes of oppression and domination (e.g. racism, colonialism, classism, sexism, ableism, homophobia) exclude the involvement of individuals who often carry the greatest burden of illness - the very voices traditionally less heard in health research. We contend that in order to be a more inclusive and meaningful approach that does not simply reiterate existing health inequities, it is important to reconceptualize patient engagement through a health equity and social justice lens by incorporating a trauma-informed intersectional analysis. This article provides key concepts to the incorporation of a trauma-informed intersectional analysis and important questions to consider when developing a patient engagement strategy in health research training, practice and evaluation. In redefining the identity of both "patient" and "researcher," spaces and opportunities to resist and renegotiate power within the intersubjective relations can be recognized and addressed, in turn helping to build trust, transparency and resiliency - integral to the advancement of the science of patient engagement in health research.

BACKGROUND: Male factors leading to subfertility account for at least half of all cases of subfertility worldwide. Although some causes of male subfertility are treatable, treatment of idiopathic male factor subfertility remains empirical. Researchers have used gonadotrophins to improve sperm parameters in idiopathic male factor subfertility with the ultimate goal of increasing birth and pregnancy rates, but results have been conflicting. OBJECTIVES: To determine the effect of systemic follicle-stimulating hormone (FSH) on live birth and pregnancy rates when administered to men with idiopathic male factor subfertility . SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register (14 January 2013), the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12 of 12, 2012), Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE (1946 to 14 January 2013), Ovid EMBASE (1980 to week 2 of 2013), Ovid PsycINFO (1806 to week 2 of 2013), trial registers for ongoing and registered trials at ClinicalTrials.gov (19 January 2013), the World Health Organisation International Trials Registry Platform (19 January 2013), The Cochrane Library Database of Abstracts of Reviews of Effects (19 January 2013) and OpenGrey for grey literature from Europe (19 January 2013). Searches were not limited by language. Bibliographies of included and excluded trials and abstracts of major meetings were searched for additional trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which gonadotrophins were compared with placebo or no treatment for participants with idiopathic male factor subfertility. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, assessed risk of bias and extracted data on live birth, pregnancy and adverse effects. We included data on pregnancies that occurred during or after gonadotrophin therapy. Study authors and pharmaceutical companies were asked to provide missing and unpublished data and/or additional information. MAIN RESULTS: Six RCTs with 456 participants and variable treatment and follow-up periods were included. From the limited data, the live birth rate per couple randomly assigned (27% vs 0%; Peto odds ratio (OR) 9.31, 95% confidence interval (CI) 1.17 to 73.75, one study, 30 participants, very low-quality evidence) and the spontaneous pregnancy rate per couple randomly assigned (16% vs 7%; Peto OR 4.94, 95% CI 2.13 to 11.44, five studies, 412 participants, I(2) = 0%, moderate-quality evidence) were significantly higher in men receiving gonadotrophin treatment than in men receiving placebo or no treatment. No significant difference between groups was noted when intracytoplasmic sperm injection (ICSI) or intrauterine insemination (IUI) was performed. None of the included studies reported miscarriage rates, and adverse events data were sparse. AUTHORS' CONCLUSIONS: Encouraging preliminary data suggest a beneficial effect on live birth and pregnancy of gonadotrophin treatment for men with idiopathic male factor subfertility, but because the numbers of trials and participants are small, evidence is insufficient to allow final conclusions. Large multi-centre trials with adequate numbers of participants are needed.

INTRODUCTION: Sepsis and septic shock are leading causes of intensive care unit (ICU) mortality. They are characterized by excessive inflammation, upregulation of procoagulant proteins and depletion of natural anticoagulants. Plasma exchange has the potential to improve survival in sepsis by removing inflammatory cytokines and restoring deficient plasma proteins. The objective of this study is to evaluate the efficacy and safety of plasma exchange in patients with sepsis. METHODS: We searched MEDLINE, EMBASE, CENTRAL, Scopus, reference lists of relevant articles, and grey literature for relevant citations. We included randomized controlled trials comparing plasma exchange or plasma filtration with usual care in critically ill patients with sepsis or septic shock. Two reviewers independently identified trials, extracted trial-level data and performed risk of bias assessments using the Cochrane Risk of Bias tool. The primary outcome was all-cause mortality reported at longest follow-up. Meta-analysis was performed using a random-effects model. RESULTS: Of 1,957 records identified, we included four unique trials enrolling a total of 194 patients (one enrolling adults only, two enrolling children only, one enrolling adults and children). The mean age of adult patients ranged from 38 to 53 years (n = 128) and the mean age of children ranged from 0.9 to 18 years (n = 66). All trials were at unclear to high risk of bias. The use of plasma exchange was not associated with a significant reduction in all-cause mortality (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.45 to 1.52, I(2) 60%). In adults, plasma exchange was associated with reduced mortality (RR 0.63, 95% CI 0.42 to 0.96; I(2) 0%), but was not in children (RR 0.96, 95% CI 0.28 to 3.38; I(2) 60%). None of the trials reported ICU or hospital lengths of stay. Only one trial reported adverse events associated with plasma exchange including six episodes of hypotension and one allergic reaction to fresh frozen plasma. CONCLUSIONS: Insufficient evidence exists to recommend plasma exchange as an adjunctive therapy for patients with sepsis or septic shock. Rigorous randomized controlled trials evaluating clinically relevant patient-centered outcomes are required to evaluate the impact of plasma exchange in this condition.

IMPORTANCE: The consumption of artificial sweeteners has increased substantially in recent decades, including among pregnant women. Animal studies suggest that exposure to artificial sweeteners in utero may predispose offspring to develop obesity; however, to our knowledge, this has never been studied in humans. OBJECTIVE: To determine whether maternal consumption of artificially sweetened beverages during pregnancy is associated with infant body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]). DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 3033 mother-infant dyads from the Canadian Healthy Infant Longitudinal Development (CHILD) Study, a population-based birth cohort that recruited healthy pregnant women from 2009 to 2012. Women completed dietary assessments during pregnancy, and their infants' BMI was measured at 1 year of age (n = 2686; 89% follow-up). Statistical analysis for this study used data collected after the first year of follow-up, which was completed in October 2013. The data analysis was conducted in August 2015. EXPOSURES: Maternal consumption of artificially sweetened beverages and sugar-sweetened beverages during pregnancy, determined by a food frequency questionnaire. MAIN OUTCOMES AND MEASURES: Infant BMI z score and risk of overweight at 1 year of age, determined from objective anthropometric measurements and defined according to World Health Organization reference standards. RESULTS: The mean (SD) age of the 3033 pregnant women was 32.4 (4.7) years, and their mean (SD) BMI was 24.8 (5.4). The mean (SD) infant BMI z score at 1 year of age was 0.19 (1.05), and 5.1% of infants were overweight. More than a quarter of women (29.5%) consumed artificially sweetened beverages during pregnancy, including 5.1% who reported daily consumption. Compared with no consumption, daily consumption of artificially sweetened beverages was associated with a 0.20-unit increase in infant BMI z score (adjusted 95% CI, 0.02-0.38) and a 2-fold higher risk of infant overweight at 1 year of age (adjusted odds ratio, 2.19; 95% CI, 1.23-3.88). These effects were not explained by maternal BMI, diet quality, total energy intake, or other obesity risk factors. There were no comparable associations for sugar-sweetened beverages. CONCLUSIONS AND RELEVANCE: To our knowledge, we provide the first human evidence that maternal consumption of artificial sweeteners during pregnancy may influence infant BMI. Given the current epidemic of childhood obesity and widespread use of artificial sweeteners, further research is warranted to confirm our findings and investigate the underlying biological mechanisms, with the ultimate goal of informing evidence-based dietary recommendations for pregnant women.

CONTEXT: Failure to acknowledge personhood is often the cause of patient and family dissatisfaction. We developed the Patient Dignity Question (PDQ) as a simple means of inquiring about personhood: "What do I need to know about you as a person to give you the best care possible?" OBJECTIVES: This study aimed to evaluate the impact of the PDQ on patients and families, evaluate its influence on health care providers (HCPs), and determine if HCP characteristics mediate receptivity to PDQ-elicited information. METHODS: Palliative care patients or their family members were asked to respond to the PDQ. Responses were summarized, read to participants to ensure accuracy, and with permission, placed in their charts. Patient, family, and HCP responses to the PDQ were then elicited. RESULTS: A total of 126 participants (66 patients and 60 family members) responded to the PDQ; 99% indicated that the summaries were accurate, 97% permitted the summary to be placed in the chart, 93% felt that the information was important for HCPs to know, and 99% would recommend the PDQ for others. A total of 137 HCPs completed 293 evaluations of individual PDQs; 90% indicated that they learned something new from it, 64% that they were emotionally affected by it, 59% that it influenced their sense of empathy, and 44% that it influenced their care. HCP empathy, job satisfaction, having a meaningful life, and social support mediated responsiveness to PDQ-elicited information. CONCLUSION: The PDQ offers an effective way of eliciting personhood, enhancing patient, family, and HCP experience alike.

Intersectionality is a widely adopted theoretical orientation in the field of women and gender studies. Intersectionality comes from the work of black feminist scholars and activists. Intersectionality argues identities such as gender, race, sexuality, and other markers of difference intersect and reflect large social structures of oppression and privilege, such as sexism, racism, and heteronormativity. The reach of intersectionality now extends to the fields of public health and knowledge translation. Knowledge translation (KT) is a field of study and practice that aims to synthesize and evaluate research into an evidence base and move that evidence into health care practice. There have been increasing calls to bring gender and other social issues into the field of KT. Yet, as scholars outline, there are few guidelines for incorporating the principles of intersectionality into empirical research. An interdisciplinary, team-based, national health research project in Canada aimed to bring an intersectional lens to the field of knowledge translation. This paper reports on key moments and resulting tensions we experienced through the project, which reflect debates in intersectionality: discomfort with social justice, disciplinary divides, and tokenism. We consider how our project advances intersectionality practice and suggests recommendations for using intersectionality in health research contexts. We argue that while we encountered many challenges, our process and the resulting co-created tools can serve as a valuable starting point and example of how intersectionality can transform fields and practices.

BACKGROUND: Many women undergoing an assisted reproductive technology (ART) cycle will not achieve a live birth. Failure at the embryo transfer stage may be due to lack of good-quality embryo/s, lack of uterine receptivity, or the transfer technique itself. Numerous methods, including the use of ultrasound guidance for proper catheter placement in the endometrial cavity, have been suggested as more effective techniques of embryo transfer. This review evaluates the efficacy of ultrasound-guided embryo transfer (UGET) compared with 'clinical touch' (CTET), which is the traditional method of embryo transfer and relies on the clinician's tactile senses to judge when the transfer catheter is in the correct position. OBJECTIVES: To determine whether ultrasound guidance compared with clinical touch improves pregnancy outcomes in women undergoing embryo transfer during ART cycles. SEARCH METHODS: For the 2016 update of this review, we ran updated searches in the Cochrane Gynaecology and Fertility Group trials register (May 2015), the Cochrane Central Register of Controlled Trials (the Cochrane Library, May 2015), MEDLINE (2009 to May 2015), and EMBASE (2009 to May 2015). We also handsearched relevant conference proceedings: American Society for Reproductive Medicine (ASRM), European Society for Human Reproduction and Embryology (ESHRE), and International Federation of Gynecology and Obstetrics (FIGO). There were no language restrictions. SELECTION CRITERIA: We included only randomised controlled trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of trials and extracted data from those selected. We calculated odds ratio (OR) and 95% confidence interval (CI) for dichotomous outcomes. No outcomes were reported using continuous data. We assessed the overall quality of the evidence for the main findings using the GRADE working group methods. MAIN RESULTS: This systematic review now has 21 included studies (four of which we added in the 2016 update), two studies awaiting assessment, and 47 excluded studies. In total, data for meta-analyses were available in 21 trials (n = 6218 women), of which only four reported live births.UGET was associated with an increased chance of a live birth/ongoing pregnancy compared with CTET (OR 1.47, 95% CI 1.30 to 1.65; 13 trials; n = 5859 women; I(2) = 74%; low-quality evidence). Sensitivity analysis by including only trials with low risk of selection bias or by using a random-effects model did not alter the effect. We estimate that for women with a chance of a live birth/ongoing pregnancy of 23% using CTET, this would increase to between 28% and 33% using UGET. We considered the quality of the evidence using GRADE methodology to be low.UGET was associated with an increase in the chance of a clinical pregnancy (OR 1.31, 95% CI 1.17 to 1.45; 20 trials; n = 6711 women; I(2) = 42%; moderate-quality evidence). We identified no differences between groups for the incidence of adverse events including multiple pregnancy, ectopic pregnancy, or miscarriage. These events were relatively rare, and sample sizes limited the ability to detect such differences. AUTHORS' CONCLUSIONS: The evidence suggests ultrasound guidance improves the chance of live birth/ongoing and clinical pregnancies compared with clinical touch, without increasing the chance of multiple pregnancy, ectopic pregnancy, or miscarriage. Methodological limitations included: only four studies reporting details of both computerised randomisation techniques and adequate allocation concealment, only four studies reported on the outcome of live birth, and none of the nine studies that reported on ongoing pregnancy reported on live birth, suggesting possible reporting bias. Adequate reporting of randomisation and allocation concealment will improve the quality of future studies. The primary outcome measure of future studies should be the reporting of live births per woman randomised.

OBJECTIVES: Addressing procedure-related anxiety should improve adherence to colorectal cancer screening programs and diagnostic colonoscopy. We performed a systematic review to assess anxiety among individuals undergoing colonoscopy or flexible sigmoidoscopy (FS). METHODS: We searched multiple electronic databases for studies evaluating anxiety associated with colonoscopy or FS published from 2005 to 2017. Two reviewers independently identified studies, extracted data, and assessed study quality. The main outcomes were the magnitude of pre-procedure anxiety, types of concerns, predictors of anxiety, and effectiveness of anxiety-lowering interventions in individuals undergoing lower endoscopy. The protocol was prospectively registered in PROSPERO. RESULTS: Fifty-eight studies (24,490 patients) met the inclusion criteria. Patients undergoing colonoscopy had a higher mean level of anxiety than that previously reported in the general population, with some studies reporting more than 50% of patients having moderate-to-severe anxiety. Areas of anxiety-related concern included bowel preparation, difficulties with the procedure (embarrassment, pain, possible complications, and sedation), and concerns about diagnosis; including fear of being diagnosed with cancer. Female gender, higher baseline anxiety, functional abdominal pain, lower education, and lower income were associated with greater anxiety prior to colonoscopy. Providing higher-quality information before colonoscopy, particularly with a video, shows promise as a way of reducing pre-procedure anxiety but the studies to date are of low quality. CONCLUSIONS: A large proportion of patients undergoing colonoscopy report anxiety before the procedure. Improvement in pre-procedure information delivery and evaluation of approaches to reduce anxiety is required, especially for those with predictors of pre-procedure anxiety.

Over 95% of hip fractures in older adults are caused by falls, yet only 1% to 2% of falls result in hip fracture. Our current understanding of the types of falls that lead to hip fracture is based on reports by the faller or witness. We analyzed videos of real-life falls in long-term care to provide objective evidence on the factors that separate falls that result in hip fracture from falls that do not. Between 2007 and 2018, we video-captured 2377 falls by 646 residents in two long-term care facilities. Hip fracture was documented in 30 falls. We analyzed each video with a structured questionnaire, and used generalized estimating equations (GEEs) to determine relative risk ratios (RRs) for hip fracture associated with various fall characteristics. All hip fractures involved falls from standing height, and pelvis impact with the ground. After excluding falls from lower than standing height, risk for hip fracture was higher for sideways landing configurations (RR = 5.50; 95% CI, 2.36-12.78) than forward or backward, and for falls causing hip impact (3.38; 95% CI, 1.49-7.67). However, hip fracture risk was just as high in falls initially directed sideways as forward (1.14; 95% CI, 0.49-2.67), due to the tendency for rotation during descent. Falling while using a mobility aid was associated with lower fracture risk (0.30; 95% CI, 0.09-1.00). Seventy percent of hip fractures involved impact to the posterolateral aspect of the pelvis. Hip protectors were worn in 73% of falls, and hip fracture risk was lower in falls where hip protectors were worn (0.45; 95% CI, 0.21-0.99). Age and sex were not associated with fracture risk. There was no evidence of spontaneous fractures. In this first study of video-captured falls causing hip fracture, we show that the biomechanics of falls involving hip fracture were different than nonfracture falls for fall height, fall direction, impact locations, and use of hip protectors. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Objective Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults. Design Systematic review and meta-analysis of randomised controlled trials (RCTs). Setting Primary care. Participants Adults (≥18 years) who were iron deficient but non-anaemic. Interventions Oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included. Comparators Placebo or active therapy. Results We identified RCTs in Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health, SportDiscus and CAB Abstracts from inception to 31 October 2016. We searched the WHO’s International Clinical Trials Registry Platform for relevant ongoing trials and performed forward searches of included trials and relevant reviews in Web of Science. We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment, Development and Evaluation methodology. From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients. Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) −0.38; 95% CI −0.52 to −0.23; I 2 0%; 4 trials; 714 participants) but was not associated with differences in objective measures of physical capacity, including maximal oxygen consumption (SMD 0.11; 95% CI −0.15 to 0.37; I 2 0%; 9 trials; 235 participants) and timed methods of exercise testing. Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I 2 48%; 12 trials; 298 participants) and serum ferritin (MD 9.23 µmol/L; 95% CI 6.48 to 11.97; I 2 58%; 14 trials; 616 participants). Conclusion In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia. PROSPERO registration number CRD42014007085 .

What is new?Key findings•Guidance is available on the conduct of rapid reviews. However, the COVID-19 pandemic has created several unique challenges.•Challenges to the conduct of rapid reviews include the urgency of the request from decision-maker organizations, identification of and access to sources of evidence for inclusion in the rapid reviews, extrapolation of results from indirect evidence, and dissemination of results widely.What this adds to what is known?•There is a need for coordination of efforts internationally to reduce the risk of duplication, and to effectively use global collective evidence synthesis resources.•We outline several methodological challenges to the conduct of rapid reviews that have become apparent during the COVID-19 pandemic using an 8-step framework that follows the knowledge synthesis process.What is the implication and what should change now?•We offer several suggestions to help address the methodological challenges encountered during the conduct of rapid reviews on COVID-19, as well as future research. Key findings•Guidance is available on the conduct of rapid reviews. However, the COVID-19 pandemic has created several unique challenges.•Challenges to the conduct of rapid reviews include the urgency of the request from decision-maker organizations, identification of and access to sources of evidence for inclusion in the rapid reviews, extrapolation of results from indirect evidence, and dissemination of results widely.What this adds to what is known?•There is a need for coordination of efforts internationally to reduce the risk of duplication, and to effectively use global collective evidence synthesis resources.•We outline several methodological challenges to the conduct of rapid reviews that have become apparent during the COVID-19 pandemic using an 8-step framework that follows the knowledge synthesis process.What is the implication and what should change now?•We offer several suggestions to help address the methodological challenges encountered during the conduct of rapid reviews on COVID-19, as well as future research.

BACKGROUND: A key component of the implementation process is identifying potential barriers and facilitators that need to be addressed. The Theoretical Domains Framework (TDF) is one of the most commonly used frameworks for this purpose. When applying the TDF, it is critical to understand the context in which behaviours occur. Intersectionality, which accounts for the interface between social identity factors (e.g. age, gender) and structures of power (e.g. ageism, sexism), offers a novel approach to understanding how context shapes individual decision-making and behaviour. We aimed to develop a tool to be used alongside applications of the TDF to incorporate an intersectionality lens when identifying implementation barriers and enablers. METHODS: An interdisciplinary Framework Committee (n = 17) prioritized the TDF as one of three models, theories, and frameworks (MTFs) to enhance with an intersectional lens through a modified Delphi approach. In collaboration with the wider Framework Committee, a subgroup considered all 14 TDF domains and iteratively developed recommendations for incorporating intersectionality considerations within the TDF and its domains. An iterative approach aimed at building consensus was used to finalize recommendations. RESULTS: Consensus on how to apply an intersectionality lens to the TDF was achieved after 12 rounds of revision. Two overarching considerations for using the intersectionality alongside the TDF were developed by the group as well as two to four prompts for each TDF domain to guide interview topic guides. Considerations and prompts were designed to assist users to reflect on how individual identities and structures of power may play a role in barriers and facilitators to behaviour change and subsequent intervention implementation. CONCLUSIONS: Through an expert-consensus approach, we developed a tool for applying an intersectionality lens alongside the TDF. Considering the role of intersecting social factors when identifying barriers and facilitators to implementing research evidence may result in more targeted and effective interventions that better reflect the realities of those involved.

BACKGROUND: Over the last two decades, researchers have placed increasing attention on understanding how food allergy affects the health-related quality of life (HRQL) and psychosocial well-being of children and teens. In response, a number of reviews have been published that aim at synthesizing the literature. However, many of these papers focus narrowly on HRQL or suffer from methodological limitations. METHOD: The current review aims to fill this gap by providing a comprehensive overview of the burden of pediatric food allergy by synthesizing the quantitative and qualitative literature. RESULTS: Findings from the present review provide evidence of reduced HRQL among children and teens with food allergy, particularly older children and those with more severe manifestations of the condition. In comparison to HRQL, the link between food allergy and psychosocial functioning is less clear; however, some evidence can be cited linking food allergy to greater levels of psychological distress. Qualitative evidence suggests that the burden of pediatric food allergy largely stems from worries surrounding exposures outside of the home and the social consequences of the condition. The current review also highlights several gaps in the literature, including a paucity of longitudinal research, research focused on predictors of psychological distress among children and teens with food allergy as well as a dearth of studies comparing rates of bullying in food-allergic and non-food-allergic samples. CONCLUSION: More emphasis should be placed on not only alleviating the social and psychological consequences of food allergy, but also on identifying and assisting those most acutely burdened by the condition.