Assessment of Usefulness of Randomized Control Trials in Child Health Research Published in 2007 and 2017.

OBJECTIVE: To examine how clinical usefulness in pediatric research with randomized controlled trials (RCTs) has changed over a 10-year period via a research usefulness tool composed of unique clinical usefulness criteria. STUDY DESIGN: We leveraged a pre-existing sample of child health RCTs published in 2007, used by our team in a previous study. Using the same methods, a research librarian executed a literature search in the Cochrane Central Register of Controlled Trials for the 2017 cohort. We included the first 300 eligible citations from the randomly ordered list for each year, creating two cohorts of 300 publications each, 1 in 2007 and 1 in 2017. Each publication was analyzed and data regarding primary and secondary outcomes, as well as 11 unique criteria of clinical usefulness, were extracted. Each publication was then graded using a tool created by our research team. After quality review, statistical analysis was then performed. RESULTS: Six hundred pediatric RCT publications were included in this review. The mean score increased from 6.07 in 2007 to 9.20 in 2017 (P < .001). Usefulness factors that saw the largest increase in reporting were context placement, funding statements, and conflict of interest statements, while patient centeredness, value for money, and raw data availability remained infrequently reported. CONCLUSION: Our results demonstrate that clinical usefulness of pediatric research improved over this 10-year period, but there are still areas that need a great deal of improvement in order to maximize clinical usefulness and reduce research waste.

Mind-body internet and mobile-based interventions for depression and anxiety in adults with chronic physical conditions: A systematic review of RCTs.

This review summarizes the effectiveness of scalable mind-body internet and mobile-based interventions (IMIs) on depression and anxiety symptoms in adults living with chronic physical conditions. Six databases (MEDLINE, PsycINFO, SCOPUS, EMBASE, CINAHL, and CENTRAL) were searched for randomized controlled trials published from database inception to March 2023. Mind-body IMIs included cognitive behavioral therapy, breathwork, meditation, mindfulness, yoga or Tai-chi. To focus on interventions with a greater potential for scale, the intervention delivery needed to be online with no or limited facilitation by study personnel. The primary outcome was mean change scores for anxiety and depression (Hedges' g). In subgroup analyses, random-effects models were used to calculate pooled effect size estimates based on personnel support level, intervention techniques, chronic physical condition, and survey type. Meta-regression was conducted on age and intervention length. Fifty-six studies met inclusion criteria (sample size 7691, mean age of participants 43 years, 58% female): 30% (n = 17) neurological conditions, 12% (n = 7) cardiovascular conditions, 11% cancer (n = 6), 43% other chronic physical conditions (n = 24), and 4% (n = 2) multiple chronic conditions. Mind-body IMIs demonstrated statistically significant pooled reductions in depression (SMD = -0.33 [-0.40, -0.26], p<0.001) and anxiety (SMD = -0.26 [-0.36, -0.17], p<0.001). Heterogeneity was moderate. Scalable mind-body IMIs hold promise as interventions for managing anxiety and depression symptoms in adults with chronic physical conditions without differences seen with age or intervention length. While modest, the effect sizes are comparable to those seen with pharmacological therapy. The field would benefit from detailed reporting of participant demographics including those related to technological proficiency, as well as further evaluation of non-CBT interventions. Registration: The study is registered with PROSPERO ID #CRD42022375606.

Associations between SARS-CoV-2 infection and incidence of new chronic condition diagnoses: a systematic review.

Because of the large number of infected individuals, an estimate of the future burdens of the long-term consequences of SARS-CoV-2 infection is needed. This systematic review examined associations between SARS-CoV-2 infection and incidence of categories of and selected chronic conditions, by age and severity of infection (inpatient vs. outpatient/mixed care). MEDLINE and EMBASE were searched (1 January 2020 to 4 October 2022) and reference lists scanned. We included observational studies from high-income OECD countries with a control group adjusting for sex and comorbidities. Identified records underwent a two-stage screening process. Two reviewers screened 50% of titles/abstracts, after which DistillerAI acted as second reviewer. Two reviewers then screened the full texts of stage one selections. One reviewer extracted data and assessed risk of bias; results were verified by another. Random-effects meta-analysis estimated pooled hazard ratios (HR). GRADE assessed certainty of the evidence. Twenty-five studies were included. Among the outpatient/mixed SARS-CoV-2 care group, there is high certainty of a small-to-moderate increase (i.e. HR 1.26-1.99) among adults ≥65 years of any cardiovascular condition, and of little-to-no difference (i.e. HR 0.75-1.25) in anxiety disorders for individuals <18, 18-64, and ≥65 years old. Among 18-64 and ≥65 year-olds receiving outpatient/mixed care there are probably (moderate certainty) large increases (i.e. HR ≥2.0) in encephalopathy, interstitial lung disease, and respiratory failure. After SARS-CoV-2 infection, there is probably an increased risk of diagnoses for some chronic conditions; whether the magnitude of risk will remain stable into the future is uncertain.

Screening for the primary prevention of fragility fractures among adults aged 40 years and older in primary care: systematic reviews of the effects and acceptability of screening and treatment, and the accuracy of risk prediction tools.

BACKGROUND: To inform recommendations by the Canadian Task Force on Preventive Health Care, we reviewed evidence on the benefits, harms, and acceptability of screening and treatment, and on the accuracy of risk prediction tools for the primary prevention of fragility fractures among adults aged 40 years and older in primary care. METHODS: For screening effectiveness, accuracy of risk prediction tools, and treatment benefits, our search methods involved integrating studies published up to 2016 from an existing systematic review. Then, to locate more recent studies and any evidence relating to acceptability and treatment harms, we searched online databases (2016 to April 4, 2022 [screening] or to June 1, 2021 [predictive accuracy]; 1995 to June 1, 2021, for acceptability; 2016 to March 2, 2020, for treatment benefits; 2015 to June 24, 2020, for treatment harms), trial registries and gray literature, and hand-searched reviews, guidelines, and the included studies. Two reviewers selected studies, extracted results, and appraised risk of bias, with disagreements resolved by consensus or a third reviewer. The overview of reviews on treatment harms relied on one reviewer, with verification of data by another reviewer to correct errors and omissions. When appropriate, study results were pooled using random effects meta-analysis; otherwise, findings were described narratively. Evidence certainty was rated according to the GRADE approach. RESULTS: We included 4 randomized controlled trials (RCTs) and 1 controlled clinical trial (CCT) for the benefits and harms of screening, 1 RCT for comparative benefits and harms of different screening strategies, 32 validation cohort studies for the calibration of risk prediction tools (26 of these reporting on the Fracture Risk Assessment Tool without [i.e., clinical FRAX], or with the inclusion of bone mineral density (BMD) results [i.e., FRAX + BMD]), 27 RCTs for the benefits of treatment, 10 systematic reviews for the harms of treatment, and 12 studies for the acceptability of screening or initiating treatment. In females aged 65 years and older who are willing to independently complete a mailed fracture risk questionnaire (referred to as "selected population"), 2-step screening using a risk assessment tool with or without measurement of BMD probably (moderate certainty) reduces the risk of hip fractures (3 RCTs and 1 CCT, n = 43,736, absolute risk reduction [ARD] = 6.2 fewer in 1000, 95% CI 9.0-2.8 fewer, number needed to screen [NNS] = 161) and clinical fragility fractures (3 RCTs, n = 42,009, ARD = 5.9 fewer in 1000, 95% CI 10.9-0.8 fewer, NNS = 169). It probably does not reduce all-cause mortality (2 RCTs and 1 CCT, n = 26,511, ARD = no difference in 1000, 95% CI 7.1 fewer to 5.3 more) and may (low certainty) not affect health-related quality of life. Benefits for fracture outcomes were not replicated in an offer-to-screen population where the rate of response to mailed screening questionnaires was low. For females aged 68-80 years, population screening may not reduce the risk of hip fractures (1 RCT, n = 34,229, ARD = 0.3 fewer in 1000, 95% CI 4.2 fewer to 3.9 more) or clinical fragility fractures (1 RCT, n = 34,229, ARD = 1.0 fewer in 1000, 95% CI 8.0 fewer to 6.0 more) over 5 years of follow-up. The evidence for serious adverse events among all patients and for all outcomes among males and younger females (<65 years) is very uncertain. We defined overdiagnosis as the identification of high risk in individuals who, if not screened, would never have known that they were at risk and would never have experienced a fragility fracture. This was not directly reported in any of the trials. Estimates using data available in the trials suggest that among "selected" females offered screening, 12% of those meeting age-specific treatment thresholds based on clinical FRAX 10-year hip fracture risk, and 19% of those meeting thresholds based on clinical FRAX 10-year major osteoporotic fracture risk, may be overdiagnosed as being at high risk of fracture. Of those identified as being at high clinical FRAX 10-year hip fracture risk and who were referred for BMD assessment, 24% may be overdiagnosed. One RCT (n = 9268) provided evidence comparing 1-step to 2-step screening among postmenopausal females, but the evidence from this trial was very uncertain. For the calibration of risk prediction tools, evidence from three Canadian studies (n = 67,611) without serious risk of bias concerns indicates that clinical FRAX-Canada may be well calibrated for the 10-year prediction of hip fractures (observed-to-expected fracture ratio [O:E] = 1.13, 95% CI 0.74-1.72, I2 = 89.2%), and is probably well calibrated for the 10-year prediction of clinical fragility fractures (O:E = 1.10, 95% CI 1.01-1.20, I2 = 50.4%), both leading to some underestimation of the observed risk. Data from these same studies (n = 61,156) showed that FRAX-Canada with BMD may perform poorly to estimate 10-year hip fracture risk (O:E = 1.31, 95% CI 0.91-2.13, I2 = 92.7%), but is probably well calibrated for the 10-year prediction of clinical fragility fractures, with some underestimation of the observed risk (O:E 1.16, 95% CI 1.12-1.20, I2 = 0%). The Canadian Association of Radiologists and Osteoporosis Canada Risk Assessment (CAROC) tool may be well calibrated to predict a category of risk for 10-year clinical fractures (low, moderate, or high risk; 1 study, n = 34,060). The evidence for most other tools was limited, or in the case of FRAX tools calibrated for countries other than Canada, very uncertain due to serious risk of bias concerns and large inconsistency in findings across studies. Postmenopausal females in a primary prevention population defined as <50% prevalence of prior fragility fracture (median 16.9%, range 0 to 48% when reported in the trials) and at risk of fragility fracture, treatment with bisphosphonates as a class (median 2 years, range 1-6 years) probably reduces the risk of clinical fragility fractures (19 RCTs, n = 22,482, ARD = 11.1 fewer in 1000, 95% CI 15.0-6.6 fewer, [number needed to treat for an additional beneficial outcome] NNT = 90), and may reduce the risk of hip fractures (14 RCTs, n = 21,038, ARD = 2.9 fewer in 1000, 95% CI 4.6-0.9 fewer, NNT = 345) and clinical vertebral fractures (11 RCTs, n = 8921, ARD = 10.0 fewer in 1000, 95% CI 14.0-3.9 fewer, NNT = 100); it may not reduce all-cause mortality. There is low certainty evidence of little-to-no reduction in hip fractures with any individual bisphosphonate, but all provided evidence of decreased risk of clinical fragility fractures (moderate certainty for alendronate [NNT=68] and zoledronic acid [NNT=50], low certainty for risedronate [NNT=128]) among postmenopausal females. Evidence for an impact on risk of clinical vertebral fractures is very uncertain for alendronate and risedronate; zoledronic acid may reduce the risk of this outcome (4 RCTs, n = 2367, ARD = 18.7 fewer in 1000, 95% CI 25.6-6.6 fewer, NNT = 54) for postmenopausal females. Denosumab probably reduces the risk of clinical fragility fractures (6 RCTs, n = 9473, ARD = 9.1 fewer in 1000, 95% CI 12.1-5.6 fewer, NNT = 110) and clinical vertebral fractures (4 RCTs, n = 8639, ARD = 16.0 fewer in 1000, 95% CI 18.6-12.1 fewer, NNT=62), but may make little-to-no difference in the risk of hip fractures among postmenopausal females. Denosumab probably makes little-to-no difference in the risk of all-cause mortality or health-related quality of life among postmenopausal females. Evidence in males is limited to two trials (1 zoledronic acid, 1 denosumab); in this population, zoledronic acid may make little-to-no difference in the risk of hip or clinical fragility fractures, and evidence for all-cause mortality is very uncertain. The evidence for treatment with denosumab in males is very uncertain for all fracture outcomes (hip, clinical fragility, clinical vertebral) and all-cause mortality. There is moderate certainty evidence that treatment causes a small number of patients to experience a non-serious adverse event, notably non-serious gastrointestinal events (e.g., abdominal pain, reflux) with alendronate (50 RCTs, n = 22,549, ARD = 16.3 more in 1000, 95% CI 2.4-31.3 more, [number needed to treat for an additional harmful outcome] NNH = 61) but not with risedronate; influenza-like symptoms with zoledronic acid (5 RCTs, n = 10,695, ARD = 142.5 more in 1000, 95% CI 105.5-188.5 more, NNH = 7); and non-serious gastrointestinal adverse events (3 RCTs, n = 8454, ARD = 64.5 more in 1000, 95% CI 26.4-13.3 more, NNH = 16), dermatologic adverse events (3 RCTs, n = 8454, ARD = 15.6 more in 1000, 95% CI 7.6-27.0 more, NNH = 64), and infections (any severity; 4 RCTs, n = 8691, ARD = 1.8 more in 1000, 95% CI 0.1-4.0 more, NNH = 556) with denosumab. For serious adverse events overall and specific to stroke and myocardial infarction, treatment with bisphosphonates probably makes little-to-no difference; evidence for other specific serious harms was less certain or not available. There was low certainty evidence for an increased risk for the rare occurrence of atypical femoral fractures (0.06 to 0.08 more in 1000) and osteonecrosis of the jaw (0.22 more in 1000) with bisphosphonates (most evidence for alendronate). The evidence for these rare outcomes and for rebound fractures with denosumab was very uncertain. Younger (lower risk) females have high willingness to be screened. A minority of postmenopausal females at increased risk for fracture may accept treatment. Further, there is large heterogeneity in the level of risk at which patients may be accepting of initiating treatment, and treatment effects appear to be overestimated. CONCLUSION: An offer of 2-step screening with risk assessment and BMD measurement to selected postmenopausal females with low prevalence of prior fracture probably results in a small reduction in the risk of clinical fragilityfracture and hip fracture compared to no screening. These findings were most applicable to the use of clinical FRAX for risk assessment and were not replicated in the offer-to-screen population where the rate of response to mailed screening questionnaires was low. Limited direct evidence on harms of screening were available; using study data to provide estimates, there may be a moderate degree of overdiagnosis of high risk for fracture to consider. The evidence for younger females and males is very limited. The benefits of screening and treatment need to be weighed against the potential for harm; patient views on the acceptability of treatment are highly variable. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO): CRD42019123767.

Systematic Review of Antimicrobial Lock Solutions for Prevention of Bacteremia in Pediatric Patients With Intestinal Failure.

OBJECTIVES: The goal of this systematic review was to determine whether antimicrobial lock (AML) solutions prevent catheter-related bloodstream infections (CRBSI) in children with intestinal failure (IF). METHODS: Electronic databases were searched: Ovid MEDLINE (1946-), Ovid Embase (1974-), Wiley Cochrane Library (inception-), and Web of Science Core Collection via Clarivate Analytics (1900-). Randomized and nonrandomized trials, case or cohort studies that studied any AML solution, and used comparator groups were included if they studied children with IF. A meta-analysis compared the rates of CRBSI with AML solutions versus controls, and a Boucher analysis was used to indirectly compare AML solutions. RESULTS: Twenty-eight studies met eligibility criteria (1 open label and 27 observational studies). Quality was good (N = 13), fair (N = 9), and poor (N = 6). All but 4 studied ethanol and taurolidine. Of 15 ethanol studies, 11 reported a decrease and 3 reported a trend toward a decreased incidence of CRBSI compared to controls; 1 reported no difference. Of 9 taurolidine studies, 7 reported a decrease and 2 a trend toward decreased CRBSI rates. There was a decrease in CRBSI with ethanol versus control ( P = 0.008) and with taurolidine-citrate versus control ( P < 0.0005). Using Bucher indirect comparison of the pooled estimates from ethanol versus control to taurolidine versus control, the estimated difference was -0.99 (-4.125, 2.27; P = 0.55). CONCLUSIONS: There were no randomized trials and over half of the 28 included studies were fair or poor quality. All but 1 reported at least a trend toward reduction in CRBSI. AML solutions appear to prevent CRBSI.

Virtual reality-based distraction for intravenous insertion-related distress in children: a study protocol for a randomised controlled trial.

INTRODUCTION: Intravenous (IV) insertions are among the most performed procedures for children seeking medical care; they are often a painful and stressful experience for both children and their caregivers. Paediatric distress and pain that is inadequately treated may lead to a frightened and uncooperative child, repeated IV attempts and overall frustration with care for both the family and clinical team. We hypothesise that distraction via an immersive virtual reality (VR) experience may reduce the associated distress for children undergoing IV insertions. METHODS AND ANALYSIS: This two-armed randomised controlled superiority trial will be conducted in a Canadian paediatric emergency department and will aim to enrol 80 children overall. Children will be randomised to receive either departmental standard of care alone or standard of care plus an immersive VR experience. Children 6-17 years of age who are undergoing IV insertion and have topical anaesthetic application will be considered for inclusion. Our primary objective is to compare the reduction of distress between the two study arms. The primary outcome will be the child's observed distress score as measured by the Observational Signs of Behavioral Distress-Revised tool. Secondary outcomes include the child's pain intensity and fear, parental anxiety, satisfaction with the IV procedure, as well as adverse events. Recruitment launched in September 2020 and is expected to end in March 2022. ETHICS AND DISSEMINATION: This study has been approved by the Health Research Ethics Board (University of Alberta). Informed consent will be obtained from parents or guardians, and assent from children. Study data will be submitted for publication irrespective of results. This study is funded through a Women and Children's Health Research Institute Innovation grant. Purchase of the VR equipment was facilitated through a Stollery Children's Hospital Foundation small equipment grant. TRIAL REGISTRATION NUMBER: NCT04291404Cite Now.

Defining COVID-19-associated pulmonary aspergillosis: systematic review and meta-analysis.

BACKGROUND: Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is poorly understood, in part due to discordant definitions across studies. OBJECTIVES: We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions. DATA SOURCES: PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021. STUDY ELIGIBILITY CRITERIA: ICU cohort studies and CAPA case series including ≥3 patients were included. PARTICIPANTS: Adult patients in ICUs with COVID-19. INTERVENTIONS: Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews. METHODS: We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman's rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis. RESULTS: Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival. CONCLUSIONS: The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions.

Outcomes of Long-Term Noninvasive Ventilation Use in Children with Neuromuscular Disease: Systematic Review and Meta-Analysis.

Objectives: To determine whether children with neuromuscular disorders using long-term noninvasive ventilation (NIV), continuous or bilevel positive airway pressure, have improved health outcomes compared with alternative treatment strategies. Data Sources: This systematic review is an extension of a scoping review. The search strategy used Medical Subject Headings and free-text terms for "child" and "noninvasive ventilation." Studies of humans from 1990 onward were searched in MEDLINE (Ovid), Embase (Ovid), CINAHL (Ebsco), Cochrane Library (Wiley), and PubMed. The results were reviewed for articles reporting on neuromuscular disorders and health outcomes including mortality, hospitalization, quality of life, lung function, sleep study parameters, and healthcare costs. Data Extraction: Extracted data included study design, study duration, sample size, age, type of NIV, follow-up period, primary disease, and primary and secondary outcome measures. Studies were grouped by primary disease into three groups: spinal muscular atrophy, Duchenne muscular dystrophy, and other/multiple neuromuscular diseases. Data Synthesis: A total of 50 articles including 1,412 children across 36 different neuromuscular disorders are included in the review. Mortality is lower for children using long-term NIV compared with supportive care across all neuromuscular disease types. Overall, mortality does not differ when comparing the use of NIV with invasive mechanical ventilation, though heterogeneity suggests that mortality with NIV is higher for spinal muscular atrophy type 1 and lower for other/multiple neuromuscular diseases. The impact of long-term NIV on hospitalization rate differed by neuromuscular disease type with lower rates compared with supportive care but higher rates compared with supportive care use for spinal muscular atrophy type 1, and lower rates compared with before NIV for other/multiple neuromuscular diseases. Overall, lung function was unaltered and sleep study parameters were improved from baseline by long-term NIV use. There are few data to assess the impact of long-term NIV use on quality of life and healthcare costs. Conclusions: Long-term NIV for children provides benefit for mortality, hospitalizations, and sleep study parameters for some sub-groups of children with neuromuscular disorders. High risk of bias and low study quality preclude strong conclusions.

A randomized trial of iPad distraction to reduce children's pain and distress during intravenous cannulation in the paediatric emergency department.

OBJECTIVES: We compared the addition of iPad distraction to standard care, versus standard care alone, to manage the pain and distress of intravenous (IV) cannulation. METHODS: Eighty-five children aged 6 to 11 years requiring IV cannulation (without child life services present) were recruited for a randomized controlled trial from a paediatric emergency department. Primary outcomes were self-reported pain (Faces Pain Scale-Revised [FPS-R]) and distress (Observational Scale of Behavioral Distress-Revised [OSBD-R]), analyzed with two-sample t-tests, Mann-Whitney U-tests, and regression analysis. RESULTS: Forty-two children received iPad distraction and 43 standard care; forty (95%) and 35 (81%) received topical anesthesia, respectively (P=0.09). There was no significant difference in procedural pain using an iPad (median [interquartile range]: 2.0 [0.0, 6.0]) in addition to standard care (2.0 [2.0, 6.0]) (P=0.35). There was no significant change from baseline behavioural distress using an iPad (mean ± SD: 0.53 ± 1.19) in addition to standard care (0.43 ± 1.56) (P=0.44). Less total behavioural distress was associated with having prior emergency department visits (odds ratio [95% confidence interval]: -1.90 [-3.37, -0.43]) or being discharged home (-1.78 [-3.04, -0.52]); prior hospitalization was associated with greater distress (1.29 [0.09, 2.49]). Significantly more parents wished to have the same approach in the future in the iPad arm (41 of 41, 100%) compared to standard care (36 of 42, 86%) (P=0.03). CONCLUSIONS: iPad distraction during IV cannulation in school-aged children was not associated with less pain or distress than standard care alone. The effects of iPad distraction may have been blunted by topical anesthetic cream usage. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT02326623.

Burden of illness in infants and young children hospitalized for respiratory syncytial virus: A rapid review.

Respiratory syncytial virus (RSV) infections are common among young children and represent a significant burden to patients, their families and the Canadian health system. Here we conduct a rapid review of the burden of RSV illness in children 24 months of age or younger. Four databases (Medline, Embase, Cochrane Database of Clinical Trials, ClinicalTrials.gov from 2014 to 2018), grey literature and reference lists were reviewed for studies on the following: children with or without a risk factor, without prophylaxis and with lab-confirmed RSV infection. Of 29 studies identified, 10 provided within-study comparisons and few examined clinical conditions besides prematurity. For infants of 33-36 weeks gestation (wGA) versus term infants, there was low-to-moderate certainty evidence for an increase in RSV-hospitalizations (n=599,535 infants; RR 2.05 [95% CI 1.89-2.22]; 1.3 more per 100 [1.1-1.5 more]) and hospital length of stay (n=7,597 infants; mean difference 1.00 day [95% CI 0.88-1.12]). There was low-to-moderate certainty evidence of little-to-no difference for infants born at 29-32 versus 33-36 wGA for hospitalization (n=12,812 infants; RR 1.20 [95% CI 0.92-1.56]). There was low certainty evidence of increased mechanical ventilation for hospitalized infants born at 29-32 versus 33-35 wGA (n=212 infants; RR 1.58, 95% CI 0.94-2.65). Among infants born at 32-35 wGA, hospitalization for RSV in infancy may be associated with increased wheeze and asthma-medication use across six-year follow-up (RR range 1.3-1.7). Children with versus without Down syndrome may have increased hospital length of stay (n=7,206 children; mean difference 3.00 days, 95% CI 1.95-4.05; low certainty). Evidence for other within-study comparisons was of very low certainty. In summary, prematurity is associated with greater risk for RSV-hospitalization and longer hospital length of stay, and Down syndrome may be associated with longer hospital stay for RSV. Respiratory syncytial virus-hospitalization in infancy may be associated with greater wheeze and asthma-medication use in early childhood. Lack of a comparison group was a major limitation for many studies.

Prevalence of Detection of Clostridioides difficile Among Asymptomatic Children: A Systematic Review and Meta-analysis.

Importance: Detection of Clostridioides difficile has frequently been described in asymptomatic infants and children, but accurate estimates across the age spectrum are unavailable. Objective: To assess the prevalence of C difficile detection among asymptomatic children across the age spectrum. Data Sources: This systematic review and meta-analysis included a search of the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, Scopus, and Web of Science for articles published from January 1, 1990, to December 31, 2020. Search terms included Clostridium difficile, Peptoclostridium difficile, Clostridioides difficile, CDF OR CDI OR c diff OR c difficile, Clostridium infections OR cd positive diarrhea OR cd positive diarrhea OR Clostridium difficile OR Peptoclostridium difficile OR pseudomembranous colitis OR pseudomembranous enterocolitis, enterocolitis, and pseudomembranous. These were combined with the following terms: bacterial colonization and colonization OR colonized OR colonizing OR epidemiology OR prevalence OR seroprevalence. Study Selection: Studies were screened independently by 2 authors. Studies were included if they reported testing for C difficile among asymptomatic children (ie, children without diarrhea) younger than 18 years. Data Extraction and Synthesis: Data were extracted independently and in duplicate by 2 reviewers. Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. Data were pooled using a random-effects model. Main Outcomes and Measures: The primary outcome was prevalence of C difficile detection among asymptomatic children. Secondary outcomes included prevalence of toxigenic vs nontoxigenic strains of C difficile and prevalence of C difficile detection stratified by geographic region, income status, testing method, and year of testing. Results: A total of 95 studies with 19 186 participants were included. Rates of detection of toxigenic or nontoxigenic C difficile were greatest among infants aged 6 to 12 months (41%; 95% CI, 32%-50%) and decreased to 12% (95% CI, 7%-18%) among children aged 5 to 18 years. The prevalence of toxigenic C difficile colonization was lower, peaking at 14% (95% CI, 8%-21%) among infants aged 6 to 12 months and decreasing to 6% (95% CI, 2%-11%) among children older than 5 years. Although prevalence differed by geographic region (ie, North and South America vs Europe: ß, -0.151, P = .001; North and South America vs Western Pacific: ß, 0.136, P = .007), there was no difference by testing method (ie, culture vs polymerase chain reaction: ß, 0.069, P = .052; culture vs enzyme immunoassay: ß, -0.178, P = .051), income class (low-middle income vs high income: ß, -0.144, P = .23; upper-middle vs high income: ß, -0.020, P = .64), or period (before 1990 vs 2010-2020: ß, -0.125, P = .19; 1990-1999 vs 2010-2020: ß, -0.037, P = .42; 2000-2009 vs 2010-2020: ß, -0.006, P = .86). Conclusions and Relevance: In this systematic review and meta-analysis, C difficile colonization rates among children were greatest at 6 to 12 months of age and decreased thereafter. These estimates may provide context for interpreting C difficile test results among young children.

Screening for Gestational Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Gestational diabetes is associated with several poor health outcomes. Objective: To update the 2012 review on screening for gestational diabetes to inform the US Preventive Services Task Force. Data Sources: MEDLINE, EMBASE, and CINAHL (2010 to May 2020), ClinicalTrials.gov, reference lists; surveillance through June 2021. Study Selection: English-language intervention studies for screening and treatment; observational studies on screening; prospective studies on screening test accuracy. Data Extraction and Synthesis: Dual review of titles/abstracts, full-text articles, and study quality. Single-reviewer data abstraction with verification. Random-effects meta-analysis or bivariate analysis (accuracy). Main Outcomes and Measures: Pregnancy, fetal/neonatal, and long-term health outcomes; harms of screening; accuracy. Results: A total of 76 studies were included (18 randomized clinical trials [RCTs] [n = 31 241], 2 nonrandomized intervention studies [n = 190], 56 observational studies [n = 261 678]). Direct evidence on benefits of screening vs no screening was limited to 4 observational studies with inconsistent findings and methodological limitations. Screening was not significantly associated with serious or long-term harm. In 5 RCTs (n = 25 772), 1-step (International Association of Diabetes and Pregnancy Study Group) vs 2-step (Carpenter and Coustan) screening was significantly associated with increased likelihood of gestational diabetes (11.5% vs 4.9%) but no improved health outcomes. At or after 24 weeks of gestation, oral glucose challenge tests with 140- and 135-mg/dL cutoffs had sensitivities of 82% and 93%, respectively, and specificities of 82% and 79%, respectively, against Carpenter and Coustan criteria, and a test with a 140-mg/dL cutoff had sensitivity of 85% and specificity of 81% against the National Diabetes Group Data criteria. Fasting plasma glucose tests with cutoffs of 85 and 90 mg/dL had sensitivities of 88% and 81% and specificities of 73% and 82%, respectively, against Carpenter and Coustan criteria. Based on 8 RCTs and 1 nonrandomized study (n = 3982), treatment was significantly associated with decreased risk of primary cesarean deliveries (relative risk [RR], 0.70 [95% CI, 0.54-0.91]; absolute risk difference [ARD], 5.3%), shoulder dystocia (RR, 0.42 [95% CI, 0.23-0.77]; ARD, 1.3%), macrosomia (RR, 0.53 [95% CI, 0.41-0.68]; ARD, 8.9%), large for gestational age (RR, 0.56 [95% CI, 0.47-0.66]; ARD, 8.4%), birth injuries (odds ratio, 0.33 [95% CI, 0.11-0.99]; ARD, 0.2%), and neonatal intensive care unit admissions (RR, 0.73 [95% CI, 0.53-0.99]; ARD, 2.0%). The association with reduction in preterm deliveries was not significant (RR, 0.75 [95% CI, 0.56-1.01]). Conclusions and Relevance: Direct evidence on screening vs no screening remains limited. One- vs 2-step screening was not significantly associated with improved health outcomes. At or after 24 weeks of gestation, treatment of gestational diabetes was significantly associated with improved health outcomes.

Risk factors for severity of COVID-19: a rapid review to inform vaccine prioritisation in Canada.

OBJECTIVES: Rapid review to determine the magnitude of association between potential risk factors and severity of COVID-19, to inform vaccine prioritisation in Canada. SETTING: Ovid MEDLINE(R) ALL, Epistemonikos COVID-19 in L·OVE Platform, McMaster COVID-19 Evidence Alerts and websites were searched to 15 June 2020. Eligible studies were conducted in high-income countries and used multivariate analyses. PARTICIPANTS: After piloting, screening, data extraction and quality appraisal were performed by a single experienced reviewer. Of 3740 unique records identified, 34 were included that reported on median 596 (range 44-418 794) participants, aged 42-84 years. 19/34 (56%) were good quality. OUTCOMES: Hospitalisation, intensive care unit admission, length of stay in hospital or intensive care unit, mechanical ventilation, severe disease, mortality. RESULTS: Authors synthesised findings narratively and appraised the certainty of the evidence for each risk factor-outcome association. There was low or moderate certainty evidence for a large (≥2-fold) magnitude of association between hospitalisation in people with COVID-19, and: obesity class III, heart failure, diabetes, chronic kidney disease, dementia, age >45 years, male gender, black race/ethnicity (vs non-Hispanic white), homelessness and low income. Age >60 and >70 years may be associated with large increases in mechanical ventilation and severe disease, respectively. For mortality, a large magnitude of association may exist with liver disease, Bangladeshi ethnicity (vs British white), age >45 years, age >80 years (vs 65-69 years) and male gender among 20-64 years (but not older). Associations with hospitalisation and mortality may be very large (≥5-fold) for those aged ≥60 years. CONCLUSIONS: Increasing age (especially >60 years) may be the most important risk factor for severe outcomes. High-quality primary research accounting for multiple confounders is needed to better understand the magnitude of associations for severity of COVID-19 with several other factors. PROSPERO REGISTRATION NUMBER: CRD42020198001.

Evidence-Based Decision-Making 2: Systematic Reviews and Meta-Analysis.

The number of studies published in the biomedical literature has dramatically increased over the last few decades. This massive proliferation of literature makes clinical medicine increasingly complex, and information from multiple studies is often needed to inform a particular clinical decision. However, available studies often vary in their design, methodological quality, and population studied, and may define the research question of interest quite differently. This can make it challenging to synthesize the conclusions of multiple studies. In addition, since even highly cited trials may be challenged over time, clinical decision-making requires ongoing reconciliation of studies which provide different answers to the same question. Because it is often impractical for readers to track down and review all the primary studies, systematic reviews and meta-analyses are an important source of evidence on the diagnosis, prognosis and treatment of any given disease. This chapter summarizes methods for conducting and reading systematic reviews and meta-analyses, as well as describes potential advantages and disadvantages of these publications.

Screening for chlamydia and/or gonorrhea in primary health care: systematic reviews on effectiveness and patient preferences.

BACKGROUND: We conducted systematic reviews on the benefits and harms of screening compared with no screening or alternative screening approaches for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in non-pregnant sexually active individuals, and on the relative importance patients' place on the relevant outcomes. Findings will inform recommendations by the Canadian Task Force on Preventive Health Care. METHODS: We searched five databases (to January 24, 2020), trial registries, conference proceedings, and reference lists for English and French literature published since 1996. Screening, study selection, and risk of bias assessments were independently undertaken by two reviewers, with consensus for final decisions. Data extraction was conducted by one reviewer and checked by another for accuracy and completeness. Meta-analysis was conducted where appropriate. We used the GRADE approach to rate the certainty of the evidence. The Task Force and content experts provided input on determining thresholds for important effect sizes and on interpretation of findings. RESULTS: Of 41 included studies, 17 and 11 reported on benefits and harms of screening, respectively, and 14 reported on patient preferences. Universal screening for CT in general populations 16 to 29 years of age, using population-based or opportunistic approaches achieving low screening rates, may make little-to-no difference for a female's risk of pelvic inflammatory disease (PID) (2 RCTs, n=141,362; 0.3 more in 1000 [7.6 fewer to 11 more]) or ectopic pregnancy (1 RCT, n=15,459; 0.20 more per 1000 [2.2 fewer to 3.9 more]). It may also not make a difference for CT transmission (3 RCTs, n=41,709; 3 fewer per 1000 [11.5 fewer to 6.9 more]). However, benefits may be achieved for reducing PID if screening rates are increased (2 trials, n=30,652; 5.7 fewer per 1000 [10.8 fewer to 1.1 more]), and for reducing CT and NG transmission when intensely screening high-prevalence female populations (2 trials, n=6127; 34.3 fewer per 1000 [4 to 58 fewer]; NNS 29 [17 to 250]). Evidence on infertility in females from CT screening and on transmission of NG in males and both sexes from screening for CT and NG is very uncertain. No evidence was found for cervicitis, chronic pelvic pain, or infertility in males from CT screening, or on any clinical outcomes from NG screening. Undergoing screening, or having a diagnosis of CT, may cause a small-to-moderate number of people to experience some degree of harm, mainly due to feelings of stigmatization and anxiety about future infertility risk. The number of individuals affected in the entire screening-eligible population is likely smaller. Screening may make little-to-no difference for general anxiety, self-esteem, or relationship break-up. Evidence on transmission from studies comparing home versus clinic screening is very uncertain. Four studies on patient preferences found that although utility values for the different consequences of CT and NG infections are probably quite similar, when considering the duration of the health state experiences, infertility and chronic pelvic pain are probably valued much more than PID, ectopic pregnancy, and cervicitis. How patients weigh the potential benefits versus harms of screening is very uncertain (1 survey, 10 qualitative studies); risks to reproductive health and transmission appear to be more important than the (often transient) psychosocial harms. DISCUSSION: Most of the evidence on screening for CT and/or NG offers low or very low certainty about the benefits and harms. Indirectness from use of comparison groups receiving some screening, incomplete outcome ascertainment, and use of outreach settings was a major contributor to uncertainty. Patient preferences indicate that the potential benefits from screening appear to outweigh the possible harms. Direct evidence about which screening strategies and intervals to use, which age to start and stop screening, and whether screening males in addition to females is necessary to prevent clinical outcomes is scarce, and further research in these areas would be informative. Apart from the evidence in this review, information on factors related to equity, acceptability, implementation, cost/resources, and feasibility will support recommendations made by the Task Force. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42018100733 .

Comparative Efficacy of Bronchiolitis Interventions in Acute Care: A Network Meta-analysis.

CONTEXT: Uncertainty exists as to which treatments are most effective for bronchiolitis, with considerable practice variation within and across health care sites. OBJECTIVE: A network meta-analysis to compare the effectiveness of common treatments for bronchiolitis in children aged ≤2 years. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched from inception to September 1, 2019. STUDY SELECTION: A total 150 randomized controlled trials comparing a placebo or active comparator with any bronchodilator, glucocorticoid steroid, hypertonic saline solution, antibiotic, helium-oxygen therapy, or high-flow oxygen therapy were included. DATA EXTRACTION: Data were extracted by 1 reviewer and independently verified. Primary outcomes were admission rate on day 1 and by day 7 and hospital length of stay. Strength of evidence was assessed by using Confidence in Network Meta-Analysis . RESULTS: Nebulized epinephrine (odds ratio: 0.64, 95% confidence interval [CI]: 0.44 to 0.93, low confidence) and nebulized hypertonic saline plus salbutamol (odds ratio: 0.44, 95% CI: 0.23 to 0.84, low confidence) reduced the admission rate on day 1. No treatment significantly reduced the admission rate on day 7. Nebulized hypertonic saline (mean difference: -0.64 days, 95% CI: -1.01 to -0.26, low confidence) and nebulized hypertonic saline plus epinephrine (mean difference: -0.91 days, 95% CI: -1.14 to -0.40, low confidence) reduced hospital length of stay. LIMITATIONS: Because we did not report adverse events in this analysis, we cannot make inferences about the safety of these treatments. CONCLUSIONS: Although hypertonic saline alone, or combined with epinephrine, may reduce an infant's stay in the hospital, poor strength of evidence necessitates additional rigorous trials.

P value and Bayesian analysis in randomized-controlled trials in child health research published over 10 years, 2007 to 2017: a methodological review protocol.

BACKGROUND: There is an unresolved debate about the reliability of the interpretation of P value. Some investigators have suggested that an alternative Bayesian method is preferred in conducting health research. As randomized-controlled trials (RCTs) are important in generating research evidence, we decided to investigate the extent, if any, the inferential statistical framework in published RCTs in child health research have changed over 10 years. We aim to examine the change in P value and Bayesian analysis in RCTs in child health research papers published from 2007 to 2017. METHODS: We will search the Cochrane Central Register of Controlled Trials (Wiley) to identify relevant citations. We will leverage a pre-existing sample of child health RCTs published in 2007 (n=300) used in our previous study of reporting quality of pediatric RCTs. Using the same strategy and study selection methods, we will identify a comparable random sample of child health RCTs published in 2017 (n=300). Eligible studies will include RCTs in health research among individuals aged 21 years and below. One reviewer will select studies for inclusion and extract the data and another reviewer will verify these. Disagreements will be resolved by a discussion between reviewers or by involving another reviewer. We will perform a descriptive analysis of 2007 and 2017 samples and analyze the results using both the frequentist and Bayesian methods. We will present specific characteristics of the clinical trials from 2007 and 2017 in tabular and graphical forms. We will report the difference in the proportion of P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. Clustering around P values of significance, if observed, will be reported. DISCUSSION: This review will present the difference in the proportion of trials that reported on P value and Bayesian analysis between 2007 and 2017 to assess the 10-year change. The implications for future clinical research will be discussed and this research work will be published in a peer-reviewed journal. This review has the potential to help inform the need for a change in the methodological approach from the null hypothesis significance test to Bayesian methods. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework https://osf.io/aj2df.

A randomized trial of robot-based distraction to reduce children's distress and pain during intravenous insertion in the emergency department.

OBJECTIVES: Our objectives were to evaluate the effectiveness of humanoid robot-based distraction on reducing distress and pain in children undergoing intravenous insertion. METHODS: A two-arm, open-label randomized controlled trial was conducted April 2017-May 2018, in a pediatric emergency department (ED). A sample of 86 children aged 6-11 years who required intravenous insertion were recruited. Exclusion criteria included hearing/visual impairments, neurocognitive delay, sensory impairment to pain, previous enrollment, and ED clinical staff discretion. Outcome measures included the Observed Scale of Behavioral Distress-Revised (OSBD-R) (distress) and the Faces Pain Scale-Revised (FPS-R) (pain). RESULTS: Of the 86 children recruited (median age 9 years, IQR 7,10); 55% (47/86) were male, 9% (7/82) were premature, 82% (67/82) had a previous ED visit, 31% (25/82) had a previous hospitalization and 78% (64/82) had previous intravenous insertion. Ninety-six percent (78/81) received topical anesthetic prior to intravenous insertion. Total OSBD-R distress score was 1.49 ± 2.36 (standard care) versus 0.78 ± 1.32 (robot) (p < 0.05). FPS-R pain score was 4 (IQR 2,6) (standard care) versus 2 (IQR 0,4) (robot) (p = 0.13). Parental anxiety immediately after the procedure was 36.7 (11.1) (standard care) versus 31.3 (8.5) (robot) (p = 0.04). Parents were more satisfied with pain management in the robotic distraction group (95% vs 72% very satisfied) (p = 0.002). CONCLUSIONS: Humanoid robot-based distraction therapy is associated with a modest positive impact on child distress for pediatric intravenous insertion, but not pain. It can be considered a potential tool in the ED toolkit for procedural pain-associated distress reduction. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02997631.

RéSUMé: OBJECTIFS: Nos objectifs étaient d'évaluer l'efficacité de la distraction robotique humanoïde pour réduire la détresse et la douleur chez les enfants subissant une insertion intraveineuse. MéTHODES: Un essai contrôlé randomisé ouvert à deux bras a été mené d'avril 2017 à mai 2018, dans un service d'urgence pédiatrique. Un échantillon de 86 enfants âgés de 6 à 11 ans ayant besoin d'une insertion intraveineuse a été recruté. Les critères d'exclusion comprenaient des déficiences auditives / visuelles, un retard neurocognitif, une déficience sensorielle de la douleur, une inscription antérieure et la discrétion du personnel clinique des urgences. Les mesures des résultats comprenaient l'échelle d'hétéro-évaluation comportementale (OSBD-R: Observational Scale of Behavioral Distress ­ Revised) (détresse) et l'échelle de visages (FPS-R: Faces Pain Scale-Revised) (douleur). RéSULTATS: Sur les 86 enfants recrutés (âge médian 9 ans, IQR 7,10) ; 55 % (47/86) étaient de sexe masculin, 9 % (7/82) étaient prématurés, 82 % (67/82) avaient une visite antérieure aux urgences, 31 % (25/82) avaient déjà été hospitalisés et 78 % (64/82) avaient déjà été insérés par voie intraveineuse. Quatre-vingt-seize pour cent (78/81) ont reçu une anesthésie topique avant l'insertion intraveineuse. Le score total de détresse OSBD-R était de 1,49 ± 2,36 (soins standard) contre 0,78 ± 1,32 (robot) (p < 0,05). Le score de douleur FPS-R était de 4 (IQR 2,6) (soins standard) contre 2 (IQR 0, 4) (robot) (p=0,13). L'anxiété parentale immédiatement après l'intervention était de 36,7 (11,1) (soins standard) contre 31,3 (8,5) (robot) (p=0,04). Les parents étaient plus satisfaits de la gestion de la douleur dans le groupe de distraction robotique (95 % vs 72 % très satisfaits) (p = 0,002). CONCLUSIONS: La thérapie de distraction à base de robot humanoïde est associée à un impact positif modeste sur la détresse de l'enfant pour l'insertion intraveineuse pédiatrique, mais pas la douleur. Il peut être considéré comme un outil potentiel dans la boîte à outils des Services d'Urgences pour la réduction de la détresse associée à la douleur procédurale.

Epidemiology, clinical characteristics and treatment of critically ill patients with COVID-19): a protocol for a living systematic review.

INTRODUCTION: In December 2019, the first cases of COVID-19 associated with SARS-CoV-2 viral infection were described in Wuhan, Hubei Province, China. Since then, it has spread rapidly affecting 188 countries and was declared a pandemic by the WHO on 11 March 2020. Preliminary reports suggest up to 30% of patients require intensive care unit (ICU) admission and case fatality rate estimate is 2.3%-7.2%. The primary reason for ICU admission is hypoxaemic respiratory failure, while factors associated with ICU admission include increased age, presence of comorbidities and cytokine storm. Case series and retrospective trials initially assessed proposed treatments with randomised controlled trials now reporting early outcomes. We conduct a systematic review and meta-analysis to identify epidemiological factors, treatments and complications that predict mortality among critically ill patients with COVID-19. METHODS AND ANALYSIS: Our comprehensive search strategy was developed in consultation with a research librarian. We will search electronic databases: Ovid Medline, Ovid Embase, Ovid Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Wiley Cochrane Library. The search strategy combines concepts from COVID-19, validated COVID-19 search filters and geographical locations of large outbreaks. Citation screening, selection, quality assessment and data abstraction will be performed in duplicate. Clinically homogenous epidemiological characteristics, interventions and complications will be pooled in statistical meta-analysis. Within the framework of a living systematic review, the search and data analysis will be updated every 6 months. ETHICS AND DISSEMINATION: Our systematic review will synthesise literature on risk factors and interventions associated with mortality in critically ill patients with COVID-19. Results will be presented at national and international conferences and submitted for peer-reviewed publication. The pooled analysis can provide guidance to inform clinical guidelines for care of critically ill patients with COVID-19. Iterative updates will be made public through open access. Research ethics approval is not required. PROSPERO REGISTRATION NUMBER: CRD42020176672.

Screening for the prevention and early detection of cervical cancer: protocol for systematic reviews to inform Canadian recommendations.

PURPOSE: To inform recommendations by the Canadian Task Force on Preventive Health Care on screening in primary care for the prevention and early detection of cervical cancer by systematically reviewing evidence of (a) effectiveness; (b) test accuracy; (c) individuals' values and preferences; and (d) strategies aimed at improving screening rates. METHODS: De novo reviews will be conducted to evaluate effectiveness and to assess values and preferences. For test accuracy and strategies to improve screening rates, we will integrate studies from existing systematic reviews with search updates to the present. Two Cochrane reviews will provide evidence of adverse pregnancy outcomes from the conservative management of cervical intraepithelial neoplasia. We will search Medline, Embase, and Cochrane Central (except for individuals' values and preferences, where Medline, Scopus, and EconLit will be searched) via peer-reviewed search strategies and the reference lists of included studies and reviews. We will search ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. Two reviewers will screen potentially eligible studies and agree on those to include. Data will be extracted by one reviewer with verification by another. Two reviewers will independently assess risk of bias and reach consensus. Where possible and suitable, we will pool studies via meta-analysis. We will compare accuracy data per outcome and per comparison using the Rutter and Gatsonis hierarchical summary receiver operating characteristic model and report relative sensitivities and specificities. Findings on values and preferences will be synthesized using a narrative synthesis approach and thematic analysis, depending on study designs. Two reviewers will appraise the certainty of evidence for all outcomes using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and come to consensus. DISCUSSION: The publication of guidance on screening in primary care for the prevention and early detection of cervical cancer by the Task Force in 2013 focused on cytology. Since 2013, new studies using human papillomavirus tests for cervical screening have been published that will improve our understanding of screening in primary care settings. This review will inform updated recommendations based on currently available studies and address key evidence gaps noted in our previous review.