Current Evidence for Infection Prevention and Control Interventions in Emergency Medical Services: A Scoping Review.

OBJECTIVES: The aim of this review was to summarize current evidence from the United States on the effectiveness of practices and interventions for preventing, recognizing, and controlling occupationally acquired infectious diseases in Emergency Medical Service (EMS) clinicians. REPORT AND METHODS: PubMed, Embase, CINAHL, and SCOPUS were searched from January 1, 2006 through March 15, 2022 for studies in the United States that involved EMS clinicians and firefighters, reported on one or more workplace practices or interventions that prevented or controlled infectious diseases, and included outcome measures. Eleven (11) observational studies reported on infection prevention and control (IPC) practices providing evidence that hand hygiene, standard precautions, mandatory vaccine policies, and on-site vaccine clinics are effective. Less frequent handwashing (survey-weight adjusted odds ratio [OR] 4.20; 95% confidence interval [CI], 1.02 to 17.27) and less frequent hand hygiene after glove use (survey-weight adjusted OR 10.51; 95% CI, 2.54 to 43.45) were positively correlated with nasal colonization of Methicillin-resistant Staphylococcus aureus (MRSA). Lack of personal protective equipment (PPE) or PPE breach were correlated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity (unadjusted risk ratio [RR] 4.2; 95% CI, 1.03 to 17.22). Workers were more likely to be vaccinated against influenza if their employer offered the vaccine (unadjusted OR 3.3; 95% CI, 1.3 to 8.3). Active, targeted education modules for H1N1 influenza were effective at increasing vaccination rates and the success of on-site vaccine clinics. CONCLUSIONS: Evidence from the United States exists on the effectiveness of IPC practices in EMS clinicians, including hand hygiene, standard precautions, mandatory vaccine policies, and vaccine clinics. More research is needed on the effectiveness of PPE and vaccine acceptance.

Active cycle of breathing technique for cystic fibrosis.

BACKGROUND: People with cystic fibrosis (CF) experience chronic airway infections as a result of mucus buildup within the lungs. Repeated infections often cause lung damage and disease. Airway clearance therapies aim to improve mucus clearance, increase sputum production, and improve airway function. The active cycle of breathing technique (ACBT) is an airway clearance method that uses a cycle of techniques to loosen airway secretions including breathing control, thoracic expansion exercises, and the forced expiration technique. This is an update of a previously published review. OBJECTIVES: To compare the clinical effectiveness of ACBT with other airway clearance therapies in CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched clinical trials registries and the reference lists of relevant articles and reviews. Date of last search: 29 March 2021. SELECTION CRITERIA: We included randomised or quasi-randomised controlled clinical studies, including cross-over studies, comparing ACBT with other airway clearance therapies in CF. DATA COLLECTION AND ANALYSIS: Two review authors independently screened each article, abstracted data and assessed the risk of bias of each study. We used GRADE to assess our confidence in the evidence assessing quality of life, participant preference, adverse events, forced expiratory volume in one second (FEV1) % predicted, forced vital capacity (FVC) % predicted, sputum weight, and number of pulmonary exacerbations. MAIN RESULTS: Our search identified 99 studies, of which 22 (559 participants) met the inclusion criteria. Eight randomised controlled studies (259 participants) were included in the analysis; five were of cross-over design. The 14 remaining studies were cross-over studies with inadequate reports for complete assessment. The study size ranged from seven to 65 participants. The age of the participants ranged from six to 63 years (mean age 18.7 years). In 13 studies follow up lasted a single day. However, there were two long-term randomised controlled studies with follow up of one to three years. Most of the studies did not report on key quality items, and therefore, have an unclear risk of bias in terms of random sequence generation, allocation concealment, and outcome assessor blinding. Due to the nature of the intervention, none of the studies blinded participants or the personnel applying the interventions. However, most of the studies reported on all planned outcomes, had adequate follow up, assessed compliance, and used an intention-to-treat analysis. Included studies compared ACBT with autogenic drainage, airway oscillating devices (AOD), high-frequency chest compression devices, conventional chest physiotherapy (CCPT), positive expiratory pressure (PEP), and exercise. We found no difference in quality of life between ACBT and PEP mask therapy, AOD, other breathing techniques, or exercise (very low-certainty evidence). There was no difference in individual preference between ACBT and other breathing techniques (very low-certainty evidence). One study comparing ACBT with ACBT plus postural exercise reported no deaths and no adverse events (very low-certainty evidence). We found no differences in lung function (forced expiratory volume in one second (FEV1) % predicted and forced vital capacity (FVC) % predicted), oxygen saturation or expectorated sputum between ACBT and any other technique (very low-certainty evidence). There were no differences in the number of pulmonary exacerbations between people using ACBT and people using CCPT (low-certainty evidence) or ACBT with exercise (very low-certainty evidence), the only comparisons to report this outcome. AUTHORS' CONCLUSIONS: There is little evidence to support or reject the use of the ACBT over any other airway clearance therapy and ACBT is comparable with other therapies in outcomes such as participant preference, quality of life, exercise tolerance, lung function, sputum weight, oxygen saturation, and number of pulmonary exacerbations. Longer-term studies are needed to more adequately assess the effects of ACBT on outcomes important for people with cystic fibrosis such as quality of life and preference.

A review of infectious disease epidemiology in emergency medical service clinicians.

BACKGROUND: The emergency medical service (EMS) workforce is at high risk of occupationally-acquired infections. This review synthesized existing literature on the prevalence, incidence, and severity of infections in the EMS workforce. METHODS: We searched PubMed, Embase, CINAHL, and SCOPUS from January 1, 2006 to March 15, 2022 for studies in the US that involved EMS clinician or firefighter populations and reported 1 or more health outcomes related to occupationally-acquired infections. RESULTS: Of the 25 studies that met the inclusion criteria, most focused on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with prevalence rates ranging from 1.1% to 36.2% (median 6.7%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in 4 studies ranged from 1.9% to 6.4%, and the prevalence of Hepatitis C in 1 study was 1.3%. Few studies reported incidence rates. The prevalence or incidence of these infections generally did not differ by age or gender, but 4 studies reported differences by race or ethnicity. In the 4 studies that compared infection rates between EMS clinicians and firefighters, EMS clinicians had a higher chance of hospitalization or death from SAR-CoV-2 (odds ratio 4.23), a higher prevalence of Hepatitis C in another study (odds ratio 1.74), and no significant difference in MRSA colonization in a separate study. CONCLUSIONS: More research is needed to better characterize the incidence and severity of occupationally-acquired infections in the EMS workforce.

Diet-Related and Gut-Derived Metabolites and Health Outcomes: A Scoping Review.

We conducted a scoping review to map available evidence about the health impact of gut microbiota-derived metabolites. We searched PubMed and Embase for studies that assessed the health impact of ten metabolites on any health condition: deoxycholate or deoxycholic acid (DCA), lithocholate or lithocholic acid (LCA), glycolithocholate or glycolithocholic acid, glycodeoxycholate or glycodeoxycholic acid, tryptamine, putrescine, d-alanine, urolithins, N-acetylmannosamine, and phenylacetylglutamine. We identified 352 eligible studies with 168,072 participants. Most (326, 92.6%) were case-control studies, followed by cohort studies (14, 4.0%), clinical trials (8, 2.3%), and cross-sectional studies (6, 1.7%). Most studies assessed the following associations: DCA on hepatobiliary disorders (64 studies, 7976 participants), colorectal cancer (19 studies, 7461 participants), and other digestive disorders (27 studies, 2463 participants); LCA on hepatobiliary disorders (34 studies, 4297 participants), colorectal cancers (14 studies, 4955 participants), and other digestive disorders (26 studies, 2117 participants); putrescine on colorectal cancers (16 studies, 94,399 participants) and cancers excluding colorectal and hepatobiliary cancers (42 studies, 4250 participants). There is a need to conduct more prospective studies, including clinical trials. Moreover, we identified metabolites and conditions for which systemic reviews are warranted to characterize the direction and magnitude of metabolite-disease associations.

Feasibility of the A-STEP for the assessment of exercise capacity in people with cystic fibrosis.

OBJECTIVES: To evaluate feasibility of the Alfred Step Test Exercise Protocol (A-STEP) for the assessment of exercise capacity in adults and children with cystic fibrosis (CF); in adults to test whether demographics and/or lung function correlated with exercise capacity. METHODS: Adults and children with stable CF from two centres completed the A-STEP (a recently developed incremental maximal-effort step test). Feasibility was evaluated by: usefulness for exercise capacity assessment (measures of exercise capacity were: level reached, exercise-induced desaturation, and achievement of at least one maximal effort criteria); safety; operational factors; time to complete; floor and/or ceiling effects. We used multiple linear regression to test whether demographics and/or lung function correlated with exercise capacity. RESULTS: A total of 49 participants: 38 adults (18 male), percent predicted (pp) forced expiration in one second (FEV1 ) 29-109, aged 22-48 years and 11 children (6 male), ppFEV1 68-107, aged 10-15 years were included. Levels reached (mean (SD) [range]) were 10.2 (2.4) [6-15] (adults), 10.1 (2.5) [7-14] (children); desaturation (change between baseline and peak-exercise SpO2 ): was 8.4 (3.8 [0-15]% (adults), 2.0 (2.0) [0-7]% (children). A total of 8 (21%) adults and no children desaturated <90% SpO2 . At least one criterion for maximal effort was reached by 33 (84%) adults and 10 (91%) children. There were no adverse events. The A-STEP was straightforward to use and carried out by one operator. A total of 26 (68.4%) adults and 7 (63.6%) children completed the test within the recommended 8-12 min. All participants completed a minimum of 6 levels, and completed the test before the final 16th level. In adults, ppFEV1 and ppFVC correlated with the level reached (r = 0.55; p = <0.001 and r = 0.66, p = <0.0001) and desaturation (r = 0.55, p = <0.001 and r = 0.45, p = <0.005). CONCLUSION: In adults and children with stable CF, the A-STEP was feasible, safe, and operationally easy to use for the assessment of exercise capacity, without floor or ceiling effects. In adults, lung function correlated with exercise capacity.

Development of the A-STEP: A new incremental maximal exercise capacity step test in cystic fibrosis.

BACKGROUND: Exercise testing is important in people with cystic fibrosis (pwCF). The aim was to develop an incremental maximal step test to assess exercise capacity across the range of pwCF, without floor or ceiling effects, within restrictions of space, and infection prevention. METHODS: The step test was developed in adults with stable CF. Subjects assisted in selecting: step height, start rate, increments, stage and test duration parameters. Equipment to externally pace and time the test and measure exercise parameters were selected. Reasons for stopping, criteria for achieving a maximal test, and key outcome measures were determined. Documentation to record and standardize the test and instructions to set up the metronome and timer App were developed. Infection control practices were considered. RESULTS: Eight subjects were recruited to develop the Alfred Step Test Exercise Protocol (A-STEP) on a 20 cm portable step. The A-STEP package included a pretest information sheet, clinical assessment and instructions, recording worksheet, and the metronome/timer instructions. The test started at 18 steps/min. Each level increased by two steps/min to a maximum of 48 steps (Level 16). Results were presented as mean (SD) [range] for: age 30.63 (5.89) [21-39] years; FEV1 58.13 (18.33) [32-89]%; levels: 10.31 (3.29) [6-15.5]. The A-STEP required space of 2 m2 and complied with current infection control guidelines. CONCLUSIONS: The A-STEP is a new incremental maximal step test to assess exercise capacity in pwCF, without floor or ceiling effects. It addresses the issues of space restrictions and the need for strict infection prevention in the clinical setting.

The AWESCORE, a patient-reported outcome measure: development, feasibility, reliability, validity and responsiveness for adults with cystic fibrosis.

BACKGROUND: Quality of life has improved dramatically over the past two decades in people with cystic fibrosis (CF). Quantification has been enabled by patient-reported outcome measures (PROMs); however, many are lengthy and can be challenging to use in routine clinical practice. We propose a short-form PROM that correlates well with established quality-of-life measures. METHODS: We evaluated the utility of a 10-item score (AWESCORE) by measuring reliability, validity and responsiveness in adults with CF. The questions were developed by thematic analysis of survey questions to patients in a single adult CF centre. Each question was scored using a numerical rating scale 0 to 10. Total scores ranged from 0 to 100. Test-retest reliability was assessed over 24 h. To determine validity, comparisons were sought between stable subjects and those in pulmonary exacerbation, and between AWESCORE and Cystic Fibrosis Questionnaire - Revised (CFQ-R). Responsiveness to pulmonary exacerbation in individual subjects was evaluated. RESULTS: Five domains, each with two questions, were identified for respiratory, physical, nutritional, psychological and general health. A total of 246 consecutive adults attending the outpatient clinic completed the AWESCORE. Scores were higher during clinical stability compared to pulmonary exacerbation (mean± sd): 73±11 versus 48±11 (p<0.001). Each domain scored worse during an acute exacerbation (p<0.001). No differences in reliability were observed in scores on retesting using Bland-Altman comparison. The CFQ-R scores (mean±sd: 813±125) and AWESCORE (81±13) were moderately correlated (Pearson's r=0.649; p=0.002). CONCLUSIONS: The AWESCORE is valid, reliable and responsive to altered health status in CF.

The Effect of Lutein/Zeaxanthin Intake on Human Macular Pigment Optical Density: A Systematic Review and Meta-Analysis.

Lutein, zeaxanthin, and meso-zeaxanthin are the only carotenoids found in the human macula and may have a role in visual function. These carotenoids are reported to protect the retina, and thus vision, as antioxidants and by acting as a blue light filter. Our objective was to determine a minimum concentration of lutein/zeaxanthin intake that is associated with a statistically significant and/or clinically important change in macular pigment optical density (MPOD) among adults with healthy eyes. We searched Ovid MEDLINE, CENTRAL, and the Commonwealth of Agriculture Bureau for English-language studies through to July 2020. Two reviewers screened results to identify studies that evaluated supplements or dietary sources of lutein/zeaxanthin on MPOD among adults with healthy eyes. One reviewer extracted data and assessed strength of evidence, which was confirmed by a second reviewer. Two independent reviewers assessed the risk of bias. Meta-analyses were stratified by total lutein/zeaxanthin dose. We included 46 studies (N = 3189 participants; mean age = 43 y; 42% male). There was no statistically significant change in MPOD among studies evaluating <5 mg/d of total lutein/zeaxanthin intake which primarily assessed dietary interventions for 3-6 mo (pooled mean difference, 0.02; 95% CI: -0.01 to 0.05). The pooled mean increase in MPOD was 0.04 units (95% CI: 0.02 to 0.07) among studies evaluating 5 to <20 mg/d of lutein/zeaxanthin and was 0.11 units (95% CI: 0.06 to 0.16) among studies evaluating ≥20 mg/d of lutein/zeaxanthin for 3-12 mo. MPOD increased with lutein/zeaxanthin intake, particularly at higher doses, among adults with healthy eyes. The effects of lutein/zeaxanthin intake at doses <5 mg/d or from dietary sources is less clear. Increased lutein/zeaxanthin intake can help with maintaining ocular health. Future research is needed to determine the minimum dose and duration of lutein/zeaxanthin intake that is associated with a clinically important change in MPOD or visual function.

Hormone Therapy, Mental Health, and Quality of Life Among Transgender People: A Systematic Review.

We sought to systematically review the effect of gender-affirming hormone therapy on psychological outcomes among transgender people. We searched PubMed, Embase, and PsycINFO through June 10, 2020 for studies evaluating quality of life (QOL), depression, anxiety, and death by suicide in the context of gender-affirming hormone therapy among transgender people of any age. We excluded case studies and studies reporting on less than 3 months of follow-up. We included 20 studies reported in 22 publications. Fifteen were trials or prospective cohorts, one was a retrospective cohort, and 4 were cross-sectional. Seven assessed QOL, 12 assessed depression, 8 assessed anxiety, and 1 assessed death by suicide. Three studies included trans-feminine people only; 7 included trans-masculine people only, and 10 included both. Three studies focused on adolescents. Hormone therapy was associated with increased QOL, decreased depression, and decreased anxiety. Associations were similar across gender identity and age. Certainty in this conclusion is limited by high risk of bias in study designs, small sample sizes, and confounding with other interventions. We could not draw any conclusions about death by suicide. Future studies should investigate the psychological benefits of hormone therapy among larger and more diverse groups of transgender people using study designs that more effectively isolate the effects of hormone treatment.

Effects of antiandrogens on prolactin levels among transgender women on estrogen therapy: A systematic review.

BACKGROUND: Gender-affirming hormone therapy for transgender women includes estrogen and antiandrogens (cyproterone acetate, spironolactone, or gonadotropin-releasing hormone agonists). Both estrogen and antiandrogens are reported to increase prolactin levels. The objective is to systematically review the evidence of the effects of antiandrogens on prolactin levels, hyperprolactinemia, and prolactinomas among transgender women on estrogen therapy. METHODS: We searched PubMed, Embase, and PsycInfo up to May 2020. We included studies with at least 3 months follow-up that evaluated the effects of antiandrogens among transgender women and reported on prolactin levels, hyperprolactinemia, or image-confirmed prolactinomas. Two reviewers independently screened studies for eligibility, serially abstracted data, and independently assessed risk of bias and graded strength of evidence. FINDINGS: We included 17 studies (16 publications): 8 prospective cohorts, 8 retrospective cohorts, and 1 cross-sectional study, each with a moderate to serious risk of bias. Among transgender women on estrogen, prolactin levels increased by over 100% with cyproterone acetate and by up to 45% with spironolactone. However, we were unable to isolate the effects of antiandrogens from estrogen therapy. We were unable to draw conclusions about effects of antiandrogens on hyperprolactinemia and prolactinomas. INTERPRETATION: Prolactin levels may be increased in transgender women who are taking both estrogens and an antiandrogen. Future research is needed to determine the effects of different antiandrogens on prolactin levels separately from estrogen therapy. Ideally, future studies would be prospective, provide either a comparison of two different antiandrogens or compare combination of estrogen and antiandrogen therapy to estrogen alone, and control for possible confounders.

Antipsychotics for Treating Delirium in Hospitalized Adults: A Systematic Review.

Background: Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear. Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults. Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions. Study Selection: Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms. Data Extraction: One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers. Data Synthesis: Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, with insufficient or no evidence for antipsychotics versus placebo. For direct comparisons of different second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for multiple other outcomes. There was little evidence demonstrating neurologic harms associated with short-term use of antipsychotics for treating delirium in adult inpatients, but potentially harmful cardiac effects tended to occur more frequently. Limitations: Heterogeneity was present in terms of dose and administration route of antipsychotics, outcomes, and measurement instruments. There was insufficient or no evidence regarding multiple clinically important outcomes. Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Antipsychotics for Preventing Delirium in Hospitalized Adults: A Systematic Review.

Background: Delirium is an acute disorder marked by impairments in attention and cognition, caused by an underlying medical problem. Antipsychotics are used to prevent delirium, but their benefits and harms are unclear. Purpose: To conduct a systematic review evaluating the benefits and harms of antipsychotics for prevention of delirium in adults. Data Sources: PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception through July 2019, without restrictions based on study setting, language of publication, or length of follow-up. Study Selection: Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group. Data Extraction: One reviewer extracted data and graded the strength of the evidence, and a second reviewer confirmed the data. Two reviewers independently assessed the risk of bias. Data Synthesis: A total of 14 RCTs were included. There were no differences in delirium incidence or duration, hospital length of stay (high strength of evidence [SOE]), and mortality between haloperidol and placebo used for delirium prevention. Little to no evidence was found to determine the effect of haloperidol on cognitive function, delirium severity (insufficient SOE), inappropriate continuation, and sedation (insufficient SOE). There is limited evidence that second-generation antipsychotics may lower delirium incidence in the postoperative setting. There is little evidence that short-term use of antipsychotics was associated with neurologic harms. In some of the trials, potentially harmful cardiac effects occurred more frequently with antipsychotic use. Limitations: There was significant heterogeneity in antipsychotic dosing, route of antipsychotic administration, assessment of outcomes, and adverse events. There were insufficient or no data available to draw conclusions for many of the outcomes. Conclusion: Current evidence does not support routine use of haloperidol or second-generation antipsychotics for prevention of delirium. There is limited evidence that second-generation antipsychotics may lower the incidence of delirium in postoperative patients, but more research is needed. Future trials should use standardized outcome measures. Primary Funding Source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).

Airway clearance techniques for cystic fibrosis: an overview of Cochrane systematic reviews.

BACKGROUND: Cystic fibrosis is a life-limiting genetic condition in which thick mucus builds up in the lungs, leading to infections, inflammation, and eventually, deterioration in lung function. To clear their lungs of mucus, people with cystic fibrosis perform airway clearance techniques daily. There are various airway clearance techniques, which differ in terms of the need for assistance or equipment, and cost. OBJECTIVES: To summarise the evidence from Cochrane Reviews on the effectiveness and safety of various airway clearance techniques in people with cystic fibrosis. METHODS: For this overview, we included Cochrane Reviews of randomised or quasi-randomised controlled trials (including cross-over trials) that evaluated an airway clearance technique (conventional chest physiotherapy, positive expiratory pressure (PEP) therapy, high-pressure PEP therapy, active cycle of breathing techniques, autogenic drainage, airway oscillating devices, external high frequency chest compression devices and exercise) in people with cystic fibrosis.We searched the Cochrane Database of Systematic Reviews on 29 November 2018.Two review authors independently evaluated reviews for eligibility. One review author extracted data from included reviews and a second author checked the data for accuracy. Two review authors independently graded the quality of reviews using the ROBIS tool. We used the GRADE approach for assessing the overall strength of the evidence for each primary outcome (forced expiratory volume in one second (FEV1), individual preference and quality of life). MAIN RESULTS: We included six Cochrane Reviews, one of which compared any type of chest physiotherapy with no chest physiotherapy or coughing alone and the remaining five reviews included head-to-head comparisons of different airway clearance techniques. All the reviews were considered to have a low risk of bias. However, the individual trials included in the reviews often did not report sufficient information to adequately assess risk of bias. Many trials did not sufficiently report on outcome measures and had a high risk of reporting bias.We are unable to draw definitive conclusions for comparisons of airway clearance techniques in terms of FEV1, except for reporting no difference between PEP therapy and oscillating devices after six months of treatment, mean difference -1.43% predicted (95% confidence interval -5.72 to 2.87); the quality of the body of evidence was graded as moderate. The quality of the body of evidence comparing different airway clearance techniques for other outcomes was either low or very low. AUTHORS' CONCLUSIONS: There is little evidence to support the use of one airway clearance technique over another. People with cystic fibrosis should choose the airway clearance technique that best meets their needs, after considering comfort, convenience, flexibility, practicality, cost, or some other factor. More long-term, high-quality randomised controlled trials comparing airway clearance techniques among people with cystic fibrosis are needed.

The Pediatric Critical Care Transfusion and Anemia Expertise Initiative Consensus Conference Methodology.

OBJECTIVES: This article describes the methodology used for Pediatric Critical Care Transfusion and Anemia Expertise Initiative Consensus Conference. DESIGN: Consensus conference of international experts in pediatric critical care and transfusion medicine, following standards set by the Institute of Medicine, using the Research and Development/UCLA Appropriateness Method, modeled after the Pediatric Acute Lung Injury Consensus Conference. Topics related to RBC transfusion in children with or at risk for critical illness were divided into nine subgroups with a systematic review of the literature. METHODS: The panel of 38 content and four methodology experts met three times over the course of 2 years and collaborated to develop evidence-based and, when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children or those at risk for critical illness. Electronic searches were conducted using PubMed, Embase, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. We used a standardized data extraction form to construct evidence tables and graded the evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. MAIN RESULTS: The consensus conference resulted in 102 recommendation statements, of which 57 were clinical (20 evidence based and 37 based on expert consensus) and 45 detailed recommendations for future research. Dissemination was done via decision tree, a primary publication listing all statements, and separate publications for each subtopic that include supporting arguments for each recommendation. CONCLUSIONS: A consensus conference of experts from around the world developed recommendations for RBC transfusions in critically ill children or children at risk for critical illness, the identification of current research gaps, and future research priorities.

Does information from ClinicalTrials.gov increase transparency and reduce bias? Results from a five-report case series.

BACKGROUND: We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. METHOD: We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review's last literature search, screened the records using the review's eligibility criteria, extracted information, and assessed risk of bias and applicability. Each team then evaluated the impact of the evidence found in ClinicalTrials.gov on the conclusions in the review. RESULTS: Across the five reviews, the number of studies that had both a registry record and a publication varied widely, from none in one review to 43% of all studies identified in another. Among the studies with both a record and publication, there was also wide variability in the match between published outcomes and those listed in ClinicalTrials.gov. Of the 173 total ClinicalTrials.gov records identified across the five projects, between 11 and 43% did not have an associated publication. In the 14% of records that contained results, the new data provided in the ClinicalTrials.gov records did not change the results or conclusions of the reviews. Finally, a large number of published studies were not registered in ClinicalTrials.gov, but many of these were published before ClinicalTrials.gov's inception date of 2000. CONCLUSION: Improved prospective registration of trials and consistent reporting of results in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in finding unpublished information and identifying potential biases. In addition, consistent indexing in databases, such as MEDLINE, would allow for better matching of records and publications, leading to increased utility of these searches for systematic review projects.

Searching ClinicalTrials.gov did not change the conclusions of a systematic review.

OBJECTIVES: We assessed the effect of searching ClinicalTrials.gov on the conclusions of a systematic review. STUDY DESIGN AND SETTING: We conducted this case study concurrently with a systematic review. We searched ClinicalTrials.gov on March 9, 2016, to identify trial records eligible for inclusion in the review. Two independent reviewers screened ClinicalTrials.gov records. We compared conclusions and strength of evidence grade with and without ClinicalTrials.gov records for 31 comparisons and 2 outcomes. RESULTS: We identified 106 trials (53 in the peer-reviewed literature only, 23 in ClinicalTrials.gov only, and 30 in both sources). For one comparison, the addition of results identified through ClinicalTrials.gov reduced the pooled effect size. We found evidence of selective outcome reporting for two comparisons and suspected publication bias for another two comparisons. For all other comparisons, searching ClinicalTrials.gov did not change conclusions or the strength of evidence grading for the two outcomes. CONCLUSION: Our search of ClinicalTrials.gov bolstered suspicions of reporting biases but did not change either the conclusions or the strength of evidence grading. Further research is needed to determine the effect of searching ClinicalTrials.gov on the conclusions of systematic reviews in different topic areas and as the new rules for registration of trial results take effect.