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Pulmonary arterial hypertension is characterized by progressive pulmonary vascular remodeling and the eventual development of right heart failure. Multiple mechanisms are responsible, including vasoconstriction, metabolic flux, and inflammation. Since the early descriptions of pulmonary hypertension, female sex has been associated with increased prevalence of the disease, with research showing both detrimental and beneficial effects of estrogen and its metabolites. This article aims to describe how the female paradox arises from sex differences in pulmonary hypertension and how this has an impact on pathophysiology and future treatment.

Entamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon. IL-33, the IL-1 family cytokine, is released after cell injury to alert the immune system of tissue damage. Treatment with recombinant IL-33 protected mice from amebic infection and intestinal tissue damage; moreover, blocking IL-33 signaling made mice more susceptible to amebiasis. IL-33 limited the recruitment of inflammatory immune cells and decreased the pro-inflammatory cytokine IL-6 in the cecum. Type 2 immune responses were upregulated by IL-33 treatment during amebic infection. Interestingly, administration of IL-33 protected RAG2-/- mice but not RAG2-/-γc-/- mice, demonstrating that IL-33-mediated protection required the presence of innate lymphoid cells (ILCs). IL-33 induced recruitment of ILC2 but not ILC1 and ILC3 in RAG2-/- mice. At baseline and after amebic infection, there was a significantly higher IL13+ILC2s in C57BL/J mice, which are naturally resistant to amebiasis, than CBA/J mice. Adoptive transfer of ILC2s to RAG2-/-γc-/- mice restored IL-33-mediated protection. These data reveal that the IL-33-ILC2 pathway is an important host defense mechanism against amebic colitis.

Right ventricular (RV) functional adaptation to afterload determines outcome in pulmonary hypertension (PH). RV afterload is determined by the dynamic interaction between pulmonary vascular resistance (PVR), characteristic impedance (Z(c)), and wave reflection. Pulmonary vascular impedance (PVZ) represents the most comprehensive measure of RV afterload; however, there is an unmet need for an easier bedside measurement of this complex variable. Although a recent study showed that Z(c) and wave reflection can be estimated from RV pressure waveform analysis and cardiac output, this has not been validated. Estimations of Z(c) and wave reflection coefficient (λ) were validated relative to conventional spectral analysis in an animal model. Z(c), λ, and the single-beat ratio of end-systolic to arterial elastance (E(es)/E(a)) to estimate RV-pulmonary arterial (PA) coupling were determined from right heart catheterization (RHC) data. The study included 30 pulmonary artery hypertension (PAH) and 40 heart failure with preserved ejection fraction (HFpEF) patients [20 combined pre- and postcapillary PH (Cpc-PH) and 20 isolated postcapillary PH, (Ipc-PH)]. Also included were 10 age- and sex-matched controls. There was good agreement with minimal bias between estimated and spectral analysis-derived Z(c) and λ. Z(c) in PAH and Cpc-PH groups exceeded that in the Ipc-PH group and controls. λ was increased in Ipc-PH (0.84 ± 0.02), Cpc-PH (0.87 ± 0.05), and PAH groups (0.85 ± 0.04) compared with controls (0.79 ± 0.03); all P values were

ObjectivesExisting scores are not accurate at predicting mortality in upper (UGIB) and lower (LGIB) gastrointestinal bleeding. We aimed to develop and validate a new pre-endoscopy score for predicting mortality in both UGIB and LGIB.Design and settingInternational cohort study. Patients presenting to hospital with UGIB at six international centres were used to develop a risk score for predicting mortality using regression analyses. The score’s performance in UGIB and LGIB was externally validated and compared with existing scores using four international datasets. We calculated areas under receiver operating characteristics curves (AUROCs), sensitivities, specificities and outcome among patients classified as low risk and high risk.Participants and resultsWe included 3012 UGIB patients in the development cohort, and 4019 UGIB and 2336 LGIB patients in the validation cohorts. Age, Blood tests and Comorbidities (ABC) score was closer associated with mortality in UGIB and LGIB (AUROCs: 0.81–84) than existing scores (AUROCs: 0.65–0.75; p≤0.02). In UGIB, patients with low ABC score (≤3), medium ABC score (4–7) and high ABC score (≥8) had 30-day mortality rates of 1.0%, 7.0% and 25%, respectively. Patients classified low risk using ABC score had lower mortality than those classified low risk with AIMS65 (threshold ≤1) (1.0 vs 4.5%; pConclusionsIn contrast to previous scores, ABC score has good performance for predicting mortality in both UGIB and LGIB, allowing early identification and targeted management of patients at high or low risk of death.

Background Acute lower gastrointestinal bleeding (LGIB) is a common reason for emergency hospitalization. In most patients, bleeding resolves spontaneously but some cases can be fatal. Risk prediction scores can be useful in risk stratifying patients with LGIB at the time of presentation although the most discriminative LGIB risk score is unknown. Aims To perform a systematic review and meta-analysis comparing LGIB risk prediction scores. Methods Following the PRISMA statement, a systematic search for relevant publications after 1990 was conducted in Ovid Medline, EMBASE, Web of Science and CENTRAL electronic databases. We also searched published conference abstracts over the past 5 years. Studies with a primary aim of deriving or validating a LGIB risk score were included. Title and abstracts were reviewed by two independent reviewers followed by full text review and data extraction by both reviewers. Diagnostic classification data for combinations of risk score and clinical outcome were meta-analyzed using a hierarchical summary receiver operator characteristic curve (ROC) model, allowing for random-effects by study, and fixed-effect of the risk score thresholds to influence both sensitivity and specificity. Area under the summary ROC were estimated from model parameters for the pre-specified LGIB risk score thresholds-of-interest. Results Our search identified 2,331 citations for review, of which 100 remained after the title and abstract screen, and 18 ultimately met criteria for inclusion in the meta-analysis after full text review. From these, we identified 21 risk prediction scores for LGIB, although only four had sufficient number of papers to meta-analyze (Oakland, Strate, NOBLADS, and BLEED score). For the outcome safe discharge from hospital, the Oakland score had an area under the receiver operating characteristics curve (AUROC) of 85.5% (95% CI: 82.1%, 88.3%). For the outcome major bleeding, the Oakland score had an AUROC of 78.9% (95% CI: 75.1%, 82.2%); the Strate score had an AUROC of 74.4% (95% CI: 70.4%, 78.0%); the NOBLADS score had an AUROC of 60.3% (95% CI: 55.9%, 64.5%); and the BLEED score had an AUROC of 65.6% (95% CI: 61.4%, 69.7%). For the outcome, need for hemostasis, the Oakland had an AUROC of 99.0% (95% CI: 97.7%, 99.6%); the Strate score had an AUROC of 82.1% (95% CI: 78.5%, 85.2%); the NOBLADS score had an AUROC of 23.9% (95% CI: 20.3%, 27.8%). For the outcome, need for transfusion, the Oakland score had an AUROC of 99.0% (95% CI: 97.7%, 99.6%); the NOBLADS score had an AUROC of 87.7% (95% CI: 84.5%, 90.3%). Conclusions The Oakland score was the most discriminative risk prediction model for safe discharge from hospital, major bleeding, need for hemostasis, and need for transfusion. Funding Agencies None

Recovery trajectories from restoration projects are poorly understood, making it difficult to set restoration targets as part of project planning. As part of the Delaware River Watershed Initiative (DRWI), we collected baseline environmental and biological data at 84 sites in watersheds where agricultural Best Management Practices (BMPs) are being implemented and forested land is being preserved. The objective of this study was to understand which diatom and macroinvertebrate community measures best characterize biological integrity along a gradient of land cover, habitat measures, and water chemistry in order to later set targets for recovery. To this end, we ran separate Redundancy Analysis (RDA) ordinations in which environmental variables constrained (1) community metrics and (2) relative abundance (taxonomic composition) for macroinvertebrates and diatoms. To understand where along the environmental gradient the sites were represented differently by the respective biotic community measures (community metrics and taxonomic composition), the two constrained ordinations were then compared using Procrustes distance. For macroinvertebrate communities, we saw the most agreement in site characterization between the ordinations at intermediate % agricultural land, but disagreement at both high and low % agricultural land. For diatom communities, we saw the most agreement between the site characterizations at high to intermediate % agricultural land, with increasing disagreement associated with increasing % forested land cover. Use of baseline data to set targets for ecosystem recovery requires consideration of which data are most relevant for the site conditions and what amount of change is feasible based on project implementation and effectiveness. A key aspect of choosing endpoints is when the loss of information inherent to metrics makes them less useful for accurately evaluating ecological integrity, especially when looking to capture incremental changes. Based on our findings, we suggest the use of some community metrics and some key taxa to set targets of recovery in biotic communities in agricultural streams, and that these targets be adjusted to best fit the ecological conditions at a given site within a larger data set. Accordingly, monitoring must take place in the context of regional conditions and must be designed to inform target‐setting.

Functional adaptation of the right ventricle (RV) to its afterload plays an important prognostic role in pulmonary hypertension (PH) [1]. The preferred “multibeat” (MB) method for assessing RV–pulmonary vascular interaction involves the measurement of end-systolic elastance (Ees), the slope of the end-systolic pressure (ESP) to end-systolic volume over sequential heart beats with varying preload. The Ees value is then matched to simultaneous pulmonary arterial (PA) elastance at end systole (Ea), calculated as ESP pressure divided by stroke volume (SV). The ratio of Ees to Ea (Ees/Ea) is termed RV–PA coupling, preservation of which indicates maintenance RV functioning in the face of increasing afterload [1]. However, while the MB method is generally regarded as the reference standard, it requires continuous, accurate measurement of RV volume and is therefore not readily applicable in most clinical settings., Surrogates of right ventricle (RV) end-systolic pressure (ESP) used to determine RV–pulmonary artery coupling vary across studies. ESP using point of maximal time varying elastance provides most accurate estimate of actual ESP. https://bit.ly/3xuqX3B

BackgroundClostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of IL-25, and that FMT protected in part by restoring gut commensal bacteria-mediated IL-25 signaling. Here we conducted a prospective clinical trial to test the impact of FMT on immunity, specifically testing in humans if FMT induced IL-25 expression in the colon.MethodsSubjects received colonic biopsies and blood sampling at the time of FMT and 60-days later. Colon biopsies were assayed for IL-25 by immunoassay, for mRNA by RNAseq, and for bacterial content by 16 S rDNA sequencing. High dimensional flow cytometry was also conducted on peripheral blood mononuclear cells pre- and post-FMT.ResultsAll 10 subjects who received FMT had no CDI recurrences over a 2 year follow-up post FMT. FMT increased alpha diversity of the colonic microbiota and was associated with several immunologic changes. The cytokine IL-25 was increased in colonic tissue. In addition, increased expression of homeostatic genes and repression of inflammatory genes was observed in colonic mRNA transcripts. Finally, circulating Th17 cells were decreased post-FMT.ConclusionThe increase in the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity.

Main Recommendations 1 ESGE recommends that the initial assessment of patients presenting with acute lower gastrointestinal bleeding should include: a history of co-morbidities and medications that promote bleeding; hemodynamic parameters; physical examination (including digital rectal examination); and laboratory markers. A risk score can be used to aid, but should not replace, clinician judgment.Strong recommendation, low quality evidence. 2 ESGE recommends that, in patients presenting with a self-limited bleed and no adverse clinical features, an Oakland score of ≤ 8 points can be used to guide the clinician decision to discharge the patient for outpatient investigation.Strong recommendation, moderate quality evidence. 3 ESGE recommends, in hemodynamically stable patients with acute lower gastrointestinal bleeding and no history of cardiovascular disease, a restrictive red blood cell transfusion strategy, with a hemoglobin threshold of ≤ 7 g/dL prompting red blood cell transfusion. A post-transfusion target hemoglobin concentration of 7–9 g/dL is desirable.Strong recommendation, low quality evidence. 4 ESGE recommends, in hemodynamically stable patients with acute lower gastrointestinal bleeding and a history of acute or chronic cardiovascular disease, a more liberal red blood cell transfusion strategy, with a hemoglobin threshold of ≤ 8 g/dL prompting red blood cell transfusion. A post-transfusion target hemoglobin concentration of ≥ 10 g/dL is desirable.Strong recommendation, low quality evidence. 5 ESGE recommends that, in patients with major acute lower gastrointestinal bleeding, colonoscopy should be performed sometime during their hospital stay because there is no high quality evidence that early colonoscopy influences patient outcomes.Strong recommendation, low quality of evidence. 6 ESGE recommends that patients with hemodynamic instability and suspected ongoing bleeding undergo computed tomography angiography before endoscopic or radiologic treatment to locate the site of bleeding.Strong recommendation, low quality evidence. 7 ESGE recommends withholding vitamin K antagonists in patients with major lower gastrointestinal bleeding and correcting their coagulopathy according to the severity of bleeding and their thrombotic risk. In patients with hemodynamic instability, we recommend administering intravenous vitamin K and four-factor prothrombin complex concentrate (PCC), or fresh frozen plasma if PCC is not available.Strong recommendation, low quality evidence. 8 ESGE recommends temporarily withholding direct oral anticoagulants at presentation in patients with major lower gastrointestinal bleeding.Strong recommendation, low quality evidence. 9 ESGE does not recommend withholding aspirin in patients taking low dose aspirin for secondary cardiovascular prevention. If withheld, low dose aspirin should be resumed, preferably within 5 days or even earlier if hemostasis is achieved or there is no further evidence of bleeding.Strong recommendation, moderate quality evidence. 10 ESGE does not recommend routinely discontinuing dual antiplatelet therapy (low dose aspirin and a P2Y12 receptor antagonist) before cardiology consultation. Continuation of the aspirin is recommended, whereas the P2Y12 receptor antagonist can be continued or temporarily interrupted according to the severity of bleeding and the ischemic risk. If interrupted, the P2Y12 receptor antagonist should be restarted within 5 days, if still indicated.Strong recommendation, low quality evidence.

BACKGROUND Restrictive red blood cell (RBC) transfusion reduces mortality and rebleeding after upper gastrointestinal bleeding (UGIB). However, there is no evidence to guide transfusion strategies in lower gastrointestinal bleeding (LGIB). AIM To assess the association between RBC transfusion strategies and outcomes in patients with LGIB METHODS: This was a post hoc analysis of the UK National Comparative Audit of LGIB and the Use of Blood. The relationships between liberal RBC transfusion and clinical outcomes of rebleeding, mortality and a composite outcome for safe discharge were examined. Transfusion strategy was dichotomised and defined as "liberal" when transfusion was administered for haemoglobin (Hb) ≥80 g/L (or ≥90 g/L in patients with acute coronary syndrome) or major haemorrhage, and "restrictive" otherwise. Multivariable logistic regression models were used to assess the independent association between liberal RBC transfusion and outcomes. RESULTS Of 2528 consecutive patients enrolled from 143 hospitals in the original study, 666 (26.3%) received RBC transfusion (mean age 73.3 ± 16 years, 49% female, initial mean haemoglobin 90 ± 24 g/L, 2.3% had haemodynamic instability). The rebleeding rate in transfused patients was 42.3%. After adjusting for potential confounders, there was no difference between liberal and restrictive RBC transfusion strategies for the odds of rebleeding (OR 0.89, 95% CI 0.6-1.22), in-hospital mortality (OR 0.54, 95% CI 0.3-1.1) or of achieving the composite outcome (OR 0.72, 95% CI 0.5-1.1). CONCLUSION Although these results could be due to residual confounding, they provide an important foundation for the design of randomised trials to evaluate transfusion strategies for LGIB.

This is the first UK national guideline to concentrate on acute lower gastrointestinal bleeding (LGIB) and has been commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). The Guidelines Development Group consisted of representatives from the BSG Endoscopy Committee, the Association of Coloproctology of Great Britain and Ireland, the British Society of Interventional Radiology, the Royal College of Radiologists, NHS Blood and Transplant and a patient representative. A systematic search of the literature was undertaken and the quality of evidence and grading of recommendations appraised according to the GRADE(Grading of Recommendations Assessment, Development and Evaluation) methodology. These guidelines focus on the diagnosis and management of acute LGIB in adults, including methods of risk assessment and interventions to diagnose and treat bleeding (colonoscopy, computed tomography, mesenteric angiography, endoscopic therapy, embolisation and surgery). Recommendations are included on the management of patients who develop LGIB while receiving anticoagulants (including direct oral anticoagulants) or antiplatelet drugs. The appropriate use of blood transfusion is also discussed, including haemoglobin triggers and targets.

Background Free Open-Access Medical education (FOAM) use among residents continues to rise. However, it often lacks quality assurance processes and residents receive little guidance on quality assessment. The Academic Life in Emergency Medicine Approved Instructional Resources tool (AAT) was created for FOAM appraisal by and for expert educators and has demonstrated validity in this context. It has yet to be evaluated in other populations. Objectives We assessed the AAT's usability in a diverse population of practicing emergency medicine (EM) physicians, residents, and medical students; solicited feedback; and developed a revised tool. Methods As part of the Medical Education Translational Resources: Impact and Quality (METRIQ) study, we recruited medical students, EM residents, and EM attendings to evaluate five FOAM posts with the AAT and provide quantitative and qualitative feedback via an online survey. Two independent analysts performed a qualitative thematic analysis with discrepancies resolved through discussion and negotiated consensus. This analysis informed development of an initial revised AAT, which was then further refined after pilot testing among the author group. The final tool was reassessed for reliability. Results Of 330 recruited international participants, 309 completed all ratings. The Best Evidence in Emergency Medicine (BEEM) score was the component most frequently reported as difficult to use. Several themes emerged from the qualitative analysis: for ease of use-understandable, logically structured, concise, and aligned with educational value. Limitations include deviation from questionnaire best practices, validity concerns, and challenges assessing evidence-based medicine. Themes supporting its use include evaluative utility and usability. The author group pilot tested the initial revised AAT, revealing a total score average measure intraclass correlation coefficient (ICC) of moderate reliability (ICC = 0.68, 95% confidence interval [CI] = 0 to 0.962). The final AAT's average measure ICC was 0.88 (95% CI = 0.77 to 0.95). Conclusions We developed the final revised AAT from usability feedback. The new score has significantly increased usability, but will need to be reassessed for reliability in a broad population.

Background Assessing the risk of post-surgical mortality is a key component of pre-surgical planning. The Surgical Outcome Risk Tool (SORT) uses pre-operative variables to predict 30-day mortality. The aim of this study was to externally validate SORT in patients undergoing major abdominal surgery. Methods Data were collected from patients treated in five independent hospitals in the UK. Individualised SORT scores were calculated, and area under the receiver operating characteristic (AUROC) and precision-recall curves (PRC) plus 95% confidence intervals (CI) were drawn to test the ability of SORT to identify in-hospital death. Outcomes of patients with a SORT predicted risk of mortality of ≥ 5% (high risk) were compared to those with a predicted risk of < 5% (standard risk). Results The study population comprised 3305 patients, mean age 51 years, 2783 (84.2%) underwent elective surgery most frequently involving the colon (24.6%), or liver, pancreas or gallbladder (18.2%). Overall, 1551 (46.9%) patients were admitted to ICU and 29 (0.88%) died. The AUROC of SORT for discriminating patients at risk of death in hospital was 0.899 (95% CI 0.849 to 0.949) and the PRC 0.247. In total, 72 (2.18%) patients were stratified as high risk. There were more unplanned ICU admissions and deaths in this group compared to the standard risk group (25.0% and 3.3%, versus 3.1% and 0.5%, respectively). Conclusion We externally validated SORT in a large population of abdominal surgery patients. SORT performed well in patients with lower risk profiles, but underpredicted adverse outcomes in the higher risk group.

Key Points Question Is the Oakland Score a valid tool for assessing the risk of adverse outcomes among a large population of adult patients with acute lower gastrointestinal bleeding in the United States? Findings In this prognostic study of 38 067 adult patients who were hospitalized with acute lower gastrointestinal bleeding, the Oakland Score consistently identified patients who were at low risk of experiencing adverse outcomes. Extension of the Oakland Score threshold from 8 points or lower to 10 points or lower for assessing whether a patient can safely be discharged from the hospital could detect more patients who have a low risk of experiencing adverse outcomes and potentially avoid hospitalization in 17.8% of patients whose conditions could safely be managed on an outpatient basis. Meaning The findings of this study suggest that adoption of the Oakland Score into the triage process for patients presenting to hospitals in the US could reduce the rate of hospitalization among patients with acute lower gastrointestinal bleeding., Importance Lower gastrointestinal bleeding (LGIB), which manifests as blood in the colon or anorectum, is a common reason for hospitalization. In most patients, LGIB stops spontaneously with no in-hospital intervention. A risk score that could identify patients at low risk of experiencing adverse outcomes could help improve the triage process and allow greater numbers of patients to receive outpatient management of LGIB. Objective To externally validate the Oakland Score, which was previously developed using a score threshold of 8 points to identify patients with LGIB who are at low risk of adverse outcomes. Design, Setting, and Participants This multicenter prognostic study was conducted in 140 US hospitals in the Hospital Corporation of America network. A total of 46 179 adult patients (aged ≥16 years) admitted to the hospital with a primary diagnosis of LGIB between June 1, 2016, and October 15, 2018, were initially identified using diagnostic codes. Of those, 51 patients were excluded because they were more likely to have upper gastrointestinal bleeding, leaving a study population of 46 128 patients with LGIB. For the statistical analysis of the Oakland Score, an additional 8061 patients were excluded because they were missing data on Oakland Score components or clinical outcomes, resulting in 38 067 patients included in the analysis. The study used area under the receiver operating characteristic curves with 95% CIs for external validation of the model. Sensitivity and specificity were calculated for each score threshold (≤8 points, ≤9 points, and ≤10 points). Data were analyzed from October 16, 2018, to September 4, 2019. Main Outcomes and Measures Identification of patients who met the criteria for safe discharge from the hospital and comparison of the performance of 2 score thresholds (≤8 points vs ≤10 points). Safe discharge was defined as the absence of blood transfusion, rebleeding, hemostatic intervention, hospital readmission, and death. Results Among 46 128 adult patients with LGIB, the mean (SD) age was 70.1 (16.5) years; 23 091 patients (50.1%) were female. Of those, 22 074 patients (47.9%) met the criteria for safe discharge from the hospital. In this group, the mean (SD) age was 67.9 (18.1) years, and 11 056 patients (50.1%) were female. In the statistical analysis of the Oakland Score, which included only the 38 067 patients with complete data, the area under the receiver operating characteristic curve for safe discharge was 0.87 (95% CI, 0.87-0.87). An Oakland Score threshold of 8 points or lower identified 3305 patients (8.7%), with a sensitivity and specificity for safe discharge of 98.4% and 16.0%, respectively. Extension of the Oakland Score threshold to 10 points or lower identified 6770 patients (17.8%), with a sensitivity and specificity for safe discharge of 96.0% and 31.9%, respectively. Conclusions and Relevance In this study, the Oakland Score consistently identified patients with acute LGIB who were at low risk of experiencing adverse outcomes and whose conditions could safely be managed without hospitalization. The score threshold to identify low-risk patients could be extended from 8 points or lower to 10 points or lower to allow identification of a greater proportion of low-risk patients., This prognostic study evaluates the external validity of the Oakland Score for use in assessing the risk of adverse outcomes and the likelihood of safe hospital discharge among a large population of adult patients with acute lower gastrointestinal bleeding in the United States.

The objective was to evaluate a multidisciplinary guideline-driven disease management program focused on achievement of asthma control among sustained patients with confirmed asthma in Louisiana and to assess factors affecting achievement of asthma control. Data were extracted from the electronic health records of 1596 adults with confirmed asthma, sustained care for1 year in the outpatient setting, and ≥2 recorded Asthma Control Test (ACT) scores. Multivariable logistic regression modeling was used to assess the association of demographic variables, comorbidities, and process measures with the best achieved asthma control as represented by the highest ACT score. Most subjects were female (81.1%) and African American (63.9%). Approximately half of them (48.9%) were able to achieve asthma control (ACT ≥20). The most prevalent comorbidities were hypertension (79.8%), rhinitis (55.3%), and obesity (50.5%). Most patients received pulmonary function testing (PFT) (88.6%), controller medication therapy (85.5%), or written asthma action plans (92.7%). Asthma control was positively associated with presence of PFT (OR = 1.63, 95% CI: 1.13, 2.37) and being a "never" smoker (OR = 1.49, 95% CI: 1.08, 2.04). Asthma control was less likely to be achieved by patients who were African American (OR = 0.68, 95% CI: 0.52, 0.87), had more comorbidities (OR = 0.89, 95% CI: 0.83, 0.96), or were on more medications (OR = 0.79, 95% CI: 0.72, 0.88). Asthma control was achieved in 48.9% of an adult, primarily African American population with the implementation of comprehensive guideline-driven care. Furthermore, this is the first study to observe that the presence of PFT may be associated with asthma control.

A subset of patients with SARS-CoV-2 infection develoa cytokine release syndrome (CRS) Strategies to mitigate SARS-CoV-2-induced CRS are urgently needed Man

Summary Background Acute lower gastrointestinal bleeding is a common reason for emergency hospital admission, and identification of patients at low risk of harm, who are therefore suitable for outpatient investigation, is a clinical and research priority. We aimed to develop and externally validate a simple risk score to identify patients with lower gastrointestinal bleeding who could safely avoid hospital admission. Methods We undertook model development with data from the National Comparative Audit of Lower Gastrointestinal Bleeding from 143 hospitals in the UK in 2015. Multivariable logistic regression modelling was used to identify predictors of safe discharge, defined as the absence of rebleeding, blood transfusion, therapeutic intervention, 28 day readmission, or death. The model was converted into a simplified risk scoring system and was externally validated in 288 patients admitted with lower gastrointestinal bleeding (184 safely discharged) from two UK hospitals (Charing Cross Hospital, London, and Hammersmith Hospital, London) that had not contributed data to the development cohort. We calculated C statistics for the new model and did a comparative assessment with six previously developed risk scores. Findings Of 2336 prospectively identified admissions in the development cohort, 1599 (68%) were safely discharged. Age, sex, previous admission for lower gastrointestinal bleeding, rectal examination findings, heart rate, systolic blood pressure, and haemoglobin concentration strongly discriminated safe discharge in the development cohort (C statistic 0·84, 95% CI 0·82–0·86) and in the validation cohort (0·79, 0·73–0·84). Calibration plots showed the new risk score to have good calibration in the validation cohort. The score was better than the Rockall, Blatchford, Strate, BLEED, AIMS65, and NOBLADS scores in predicting safe discharge. A score of 8 or less predicts a 95% probability of safe discharge. Interpretation We developed and validated a novel clinical prediction model with good discriminative performance to identify patients with lower gastrointestinal bleeding who are suitable for safe outpatient management, which has important economic and resource implications. Funding Bowel Disease Research Foundation and National Health Service Blood and Transplant.

Gastrointestinal bleeding is a common medical and surgical emergency and is the second most common indication for red blood cell (RBC) transfusion in the UK. Most transfusion guidelines recommend the use of restrictive blood transfusion in stable gastrointestinal bleeding. This review explores the evidence supporting this practice, including whether it is safe in lower as well as upper gastrointestinal bleeding, and the risks of restrictive transfusion in patients with cardiovascular disease. There is a lack of evidence supporting the use of platelet and fresh frozen plasma transfusion in gastrointestinal bleeding. The aim of this review is to serve as a practical guide to transfusion in stable gastrointestinal bleeding.

We thank Dr Leeds et al for their interest and comments1 on the British Society of Gastroenterology guideline on the diagnosis and management of acute lower gastrointestinal bleeding (LGIB).2 They are quite correct to highlight the difference in evidence supporting therapeutic endoscopy in LGIB as opposed to upper. There is only one randomised trial that directly compared timing of colonoscopy in patients hospitalised with LGIB, which as the authors’ state demonstrated no difference in clinical outcomes, however, the trial was terminated before the required sample size had been reached.3 Pooled analysis in a systematic review of non-randomised studies demonstrated that early colonoscopy was associated with higher diagnostic and therapeutic yields and most importantly a shorter length of …

Giardia lamblia is a common intestinal parasitic infection that although often acutely asymptomatic, is associated with debilitating chronic intestinal and extra-intestinal sequelae. In previously healthy adults, a primary sporadic Giardia infection can lead to gut dysfunction and fatigue. These symptoms correlate with markers of inflammation that persist well after the infection is cleared. In contrast, in endemic settings, first exposure occurs in children who are frequently malnourished and also co-infected with other enteropathogens. In these children, Giardia rarely causes symptoms and associates with several decreased markers of inflammation. Mechanisms underlying these disparate and potentially enduring outcomes following Giardia infection are not presently well understood. A body of work suggests that the outcome of experimental Giardia infection is influenced by the nutritional status of the host. Here, we explore the consequences of experimental Giardia infection under conditions of protein sufficiency or deficiency on cytokine responses of ex vivo bone marrow derived dendritic cells (BMDCs) to endotoxin stimulation. We show that BMDCs from Giardia- challenged mice on a protein sufficient diet produce more IL-23 when compared to uninfected controls whereas BMDCs from Giardia challenged mice fed a protein deficient diet do not. Further, in vivo co-infection with Giardia attenuates robust IL-23 responses in endotoxin-stimulated BMDCs from protein deficient mice harboring enteroaggregative Escherichia coli. These results suggest that intestinal Giardia infection may have extra-intestinal effects on BMDC inflammatory cytokine production in a diet dependent manner, and that Giardia may influence the severity of the innate immune response to other enteropathogens. This work supports recent findings that intestinal microbial exposure may have lasting influences on systemic inflammatory responses, and may provide better understanding of potential mechanisms of post-infectious sequelae and clinical variation during Giardia and enteropathogen co-infection., Author summary Giardia is a leading cause of gut infection worldwide, with wide variation in acute symptoms. Giardia infection in non-endemic regions has also been associated with debilitating chronic intestinal and extra-intestinal sequelae, such as irritable bowel syndrome, often occurring weeks or months after exposure and after the parasite has cleared. Mechanisms underlying how Giardia results in an increased risk of chronic intestinal and extra-intestinal sequelae are not currently well understood. However, an emerging body of research suggests that intestinal microbial exposures may have long term influences on inflammatory cytokine production from innate immune cells, and that this process may help explain persistent inflammatory responses following pathogen infection. We therefore hypothesized that Giardia infection could alter innate immune system cells to be more pro-inflammatory. In this work we demonstrate that Giardia exposure in a murine model changes the inflammatory profile of bone marrow derived innate immune cells in in a diet dependent manner and in response to bacterial stimuli. These data suggest that Giardia infection might alter the responsiveness of innate immune cells to other infectious agents or natural products of the host microbiota such as endotoxin. This work may therefore provide better understanding of potential immune mechanisms underlying gut dysfunction following traveler’s diarrhea, as well as variation in disease severity in endemic regions.

Shortness of breath is a common chief complaint in the emergency department (ED), and biomarkers have become standard tools in the evaluation for the etiology and prognosis. Troponin and B-type natriuretic peptide (BNP) are useful for evaluating cardiac etiologies. A D-dimer is a useful rule-out test for pulmonary embolism (PE). Procalcitonin, an acute-phase reactant, has been shown to be useful in detecting bacterial infections. Further research into novel biomarkers and the use of multimarker panels will need further elucidation.

Upper gastrointestinal bleeding (UGIB) develops in the oesophagus, stomach or duodenum and has an incidence of 47/100,000. Lower GIB (LGIB) develops in the small bowel, colon or anorectum and has an incidence of 33/100,000. Where the incidence of UGIB has fallen, driven by helicobacter pylori eradication and the use of proton pump inhibitors, the incidence of LGIB may be increasing. Interventions such as early endoscopy, risk assessment and national guidelines have improved clinical outcomes but have had limited impact on the economic burden of GIB. Previously LGIB was thought to be less severe than UGIB, but contemporary data suggest that patients with LGIB tend to have a longer length of hospital stay and may be at higher risk of death or re-bleeding.

Essentials The optimal management of patients with platelet dysfunction undergoing surgery is unclear. This meta-analysis compared perioperative administration of desmopressin to placebo. Desmopressin reduced red cell transfusions, blood loss and risk of re-operation due to bleeding. There were too few events to determine if there was a change in the risk of thrombotic events. SummaryBackground Platelet dysfunction, including that caused by antiplatelet agents, increases the risk of perioperative bleeding. The optimal management of patients with platelet dysfunction undergoing surgery is unclear. Objectives To assess whether desmopressin reduces perioperative allogeneic red cell transfusion and bleeding in patients with platelet dysfunction. Patients/Methods We searched for randomized controlled trials in The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Transfusion Evidence Library and the ISI Web of Science to 7th July 2016. Data were pooled using mean difference (MD), relative risks or Peto odds ratios (pOR) using a random-effects model. Results Ten trials with 596 participants were identified, all in the setting of cardiac surgery. Platelet dysfunction was due to antiplatelet agents in six trials and cardiopulmonary bypass in four trials. Patients treated with desmopressin were transfused with fewer red cells (MD, −0.65 units; 95% Confidence Interval [CI], −1.16 to −0.13 units), lost less blood (MD, −253.93 mL; 95% CI, −408.01 to −99.85 mL) and had a lower risk of re-operation due to bleeding (pOR, 0.39; 95% CI, 0.18–0.84). The GRADE quality of evidence was very low to moderate, suggesting considerable uncertainty over the results Conclusions Desmopressin may be a useful agent to reduce bleeding and transfusion requirements for people with platelet dysfunction or with a history of recent antiplatelet drug administration undergoing cardiac surgery.

Mucopolysaccharidosis (MPS) VI is an autosomal recessive lysosomal storage disorder arising from deficient activity of N-acetylgalactosamine-4-sulfatase (arylsulfatase B) and subsequent intracellular accumulation of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin-4-sulfate. Manifestations are multi-systemic and include skeletal abnormalities such as dysostosis multiplex and short stature. Reference height-for-age growth charts for treatment-naive MPS VI patients have been published for both the slowly and rapidly progressing populations. Categorization of disease progression for these charts was based on urinary GAG (uGAG) level; high (>200μg/mg creatinine) levels identified subjects as rapidly progressing. Height data for 141 patients who began galsulfase treatment by the age of 18years were collected and stratified by baseline uGAG level and age at ERT initiation in 3-year increments. The reference MPS VI growth charts were used to calculate change in Z-score from pre-treatment baseline to last follow-up. Among patients with high baseline uGAG levels, galsulfase ERT was associated with an increase in Z-score for those beginning treatment at 0-3, >3-6, >6-9, >9-12, and >12-15years of age (p

This article provides guidelines for an entry-level course that prepares psychology students and practitioners to acquire entry-level skills, abilities, knowledge, and attitudes important to the individual assessment of intellectual abilities of children and youth. The article reviews prominent international, regional, and national policies, guidelines, and standards for test development and use, basic training issues, acquisition of competence in core professional behaviors, the identification of clinical assessment skills; scholarship that supports this entry-level course, and national and institutional issues related to psychological assessment. The guidelines are consistent with the International School Psychology Association and the International Testing Commission's recommendations and provide experiences based on U.S. context. The need to adjust course content and instructional methods in light of local conditions is recognized.

Test development and use constitute psychology’s most important contribution to applied psychology. This article summarizes the status of test development and use internationally. Country and regional differences in test development and use exist and are explained in reference to qualities needed to support test development and use. The relevanceof tests, like other technologies, should change in light of changing needs of those who rely on test data. Several somewhat prominent changes to which tests should respond are reviewed.

Assessing progression of disease or response to treatment remains a major challenge in the clinical management of nontuberculous mycobacterial (NTM) infections of the lungs. Serial assessments of validated measures of treatment response address whether the current therapeutic approach is on track toward clinical cure, which remains a fundamental question for clinicians and patients during the course of NTM disease treatment. The 2015 NTM Research Consortium Workshop, which included a patient advisory panel, identified treatment response biomarkers as a priority area for investigation. Limited progress in addressing this challenge also hampers drug development efforts. The Biomarker Qualification Program at the FDA supports the use of a validated treatment response biomarker across multiple drug development programs. Current approaches in clinical practice include microbiologic and radiographic monitoring, along with symptomatic and quality-of-life assessments. Blood-based monitoring, including assessments of humoral and cell-mediated NTM-driven immune responses, remain under investigation. Alignment of data collection schemes in prospective multicenter studies, including the support of biosample repositories, will support identification of treatment response biomarkers under standard-of-care and investigational therapeutic strategies. In this review, we outline the role of treatment monitoring biomarkers in both clinical practice and drug development frameworks.

Background: Few studies have investigated the association between radon and thyroid cancer despite the sensitivity of the thyroid gland to radiation. Our goal is to investigate the association between county-level radon and incidence of female thyroid cancer in the US States of Iowa, New Jersey, and Wisconsin. Methods: Thyroid cancer incidence data were provided by individual state cancer registries and span 1990–2013. Radon data come from a publicly available third-party database, AirChek, accessed in 2017. We tabulated the percent of radon above four picocuries per liter and the female thyroid cancer incidence rate in each county. Quantile maps were constructed, and an ordinary least-squares regression model was run using Geoda 1.10.0.8 (Chicago, IL, USA). Results: No association was observed between county-level radon and incidence of female thyroid cancer in any of the States: New Jersey (β = 0.06, p = 0.23); Iowa (β = −0.07, p = 0.07); or Wisconsin (β = −0.01, p = 0.78). A spatial regression model was considered, but the Moran’s I of the residuals from each of the models was not significant, so no spatial term was required. Discussion: In this county-level ecological study across three different States in the US, we did not find an association between elevated radon and thyroid cancer incidence in women. While this ecologic study reports null findings, due to the ecologic fallacy, individual-level studies of this association may still be warranted.

Study objective Online educational resources such as blogs are increasingly used for education by emergency medicine clinicians. The Social Media Index was developed to quantify their relative impact. The Medical Education Translational Resources: Indicators of Quality (METRIQ) study was conducted in part to determine the association between the Social Media Index score and quality as measured by gestalt and previously derived quality instruments. Methods Ten blogs were randomly selected from a list of emergency medicine and critical care Web sites. The 2 most recent clinically oriented blog posts published on these blogs were evaluated with gestalt, the Academic Life in Emergency Medicine Approved Instructional Resources (ALiEM AIR) score, and the METRIQ-8 score. Volunteer raters (including medical students, emergency medicine residents, and emergency medicine attending physicians) were identified with a multimodal recruitment methodology. The Social Media Index was calculated in February 2016, November 2016, April 2017, and December 2017. Pearson's correlations were calculated between the Social Media Index and the average rater gestalt, ALiEM AIR score, and METRIQ-8 score. Results A total of 309 of 330 raters completed all ratings (93.6%). The Social Media Index correlated moderately to strongly with the mean rater gestalt ratings (range 0.69 to 0.76) and moderately with the mean rater ALiEM AIR score (range 0.55 to 0.61) and METRIQ-8 score (range 0.53 to 0.57) during the month of the blog post's selection and for 2 years after. Conclusion The Social Media Index's correlation with multiple quality evaluation instruments over time supports the hypothesis that it is associated with overall Web site quality. It can play a role in guiding individuals to high-quality resources that can be reviewed with critical appraisal techniques.

10% of patients who undergo a cholecystectomy go on to develop post-cholecystectomy syndrome (PCS). The majority of these patients may suffer from extra-biliary or unrelated organic disorders that may have been present before cholecystectomy. The numerous aetiological causes of PCS result in a wide spectrum of management options, each with varying success in abating symptoms. This systematic review aims to provide a summary of the causative aetiologies of post cholecystectomy syndrome, their incidences and efficacy of available management options.The Medline, Embase and Cochrane databases were searched for studies patients who developed PCS symptoms following laparoscopic cholecystectomy, published between 1990 and 2016. The aetiology, incidence and management options were extracted, with separate collation of randomised control trials and non-randomised studies that reported intervention. Outcomes included recurrent symptoms following intervention, unscheduled primary and secondary care attendances and complications.Twenty-one studies were included (15 case series, 2 cohort studies, 1 case control, 3 RCTs). Five studies described medical treatment (nifedipine, cisapride, opiates); seven studies described endoscopic or surgical intervention. Early presentation of PCS (3 years post-cholecystectomy) was more likely to be gastric in origin, and later presentations were found to be more likely due to retained stones. Sphincter of Oddi dysfunction (SOD) accounted for a third of cases in an unselected population with PCS.Causes of post cholecystectomy syndrome are varied and many can be attributed to extra-biliary causes, which may be present prior to surgery. Early symptoms may warrant early upper gastrointestinal endoscopy. Delayed presentations are more likely to be associated with retained biliary stones. A large proportion of patients will have no cause identified. Treatment options for this latter group are limited.

Background & Aims Patients who develop lower gastrointestinal bleeding (LGIB) while receiving anti-coagulants or anti-platelets have increased severity of bleeding and risk of re-bleeding. We compared outcomes of patients receiving anti-platelets, anti-coagulants, or direct oral anti-coagulants (DOACs) who develop LGIB, as well as the effects of withholding these drugs on their course of bleeding. Methods We performed a retrospective study of 2528 consecutive adult patients with LGIB at 143 hospitals in the United Kingdom, from September through December 2015; 917 were taking anti-coagulant or anti-platelet drugs and 1218 were taking neither (unexposed). We collected data on demographic features of patients, interventions or medications, outcomes, laboratory test results, and patient readmission until patient death, discharge, or 28 days after admission (whichever came first). Re-bleeding was defined as additional transfusion requirements and/or a decrease in hematocrit ≥20% after 24 hrs of clinical stability. Multivariate regression was used to examine the relationship between drug class on presentation with LGIB and re-bleeding, mortality, and cardiovascular events. Rates of re-bleeding and cardiovascular complications in patients who had these drugs withheld were also analyzed. Results Patients receiving anti-platelets, but not those receiving warfarin (n = 232) or DOACs (n = 102), had a higher risk of in-hospital re-bleeding (monotherapy hazard ratio [HR], 3.57; 95% CI, 1.13–11.28; n = 504 and dual anti-platelet therapy hazard ratio, 5.3; 95% CI, 1.56–18.54; n = 79) compared with the unexposed group. This risk was not lower in patients who received anti-platelets and had the drug withheld for fewer than 5 days, compared to those who continued the drug throughout admission (HR, 0.98; 95% CI, 0.45–2.17) No differences were observed in risk-adjusted mortality or re-admission with further bleeding for patients receiving anti-platelets, DOACs, or warfarin. Cardiovascular events were too few to allow meaningful comparison. Conclusions In patients with LGIB, antiplatelet drugs, but not warfarin or DOACs, are associated with an increased risk of re-bleeding. Withholding anti-platelets during admission does not lead to reduction in re-bleeding.

This article provides a 24-year update on the 10 standardized tests used most frequently with children and youth by school psychologists. Data were acquired from 64 countries through an international survey, with one respondent from each country. The informants were solicited due to their expertise in the area of assessment. The data from the current 2013 survey are described and discussed as well as contrasted with the 1989 survey data. The 2013 survey data led to the following rank order of tests based on data from the 64 countries: the Wechsler Intelligence Scales for Children, Ravens Progressive Matrices, Wechsler Preschool and Primary Scales of Intelligence, Child Behavior Checklist, Bender–Gestalt Test, Child and Adult Apperception Tests, Kaufman Assessment Battery for Children, Draw-a-Person Test, Stanford–Binet Intelligence Scales, and the Wechsler Adult Intelligence Scales. Survey data from advanced, developing, and emerging counties also are compared and discussed. Results are discussed in the broader context of international test development and use.

Background: Online education programs are becoming a popular means to disseminate knowledge about evidence-based practice (EBP) among healthcare practitioners. This mode of delivery also offers a viable and potentially sustainable solution for teaching consistent EBP content to learners over time and across multiple geographical locations. We conducted a study with 3 main aims: 1) develop an online distance-learning program about the principles of evidence-based practice (EBP) for chiropractic providers; 2) test the effectiveness of the online program on the attitudes, skills, and use of EBP in a sample of chiropractors; and 3) determine the feasibility of expanding the program for broader-scale implementation. This study was conducted from January 2013 to September 2014. Methods: This was an exploratory randomized trial in which 293 chiropractors were allocated to either an online EBP education intervention or a waitlist control. The online EBP program consisted of 3 courses and 4 booster lessons, and was developed using educational resources created in previous EBP educational programs at 4 chiropractic institutions. Participants were surveyed using a validated EBP instrument (EBASE) with 3 rescaled (0 to 100) subscores: Attitudes, Skills, and Use of EBP. Multiple regression was used to compare groups, adjusting for personal and practice characteristics. Satisfaction and compliance with the program was evaluated to assess feasibility. Results: The Training Group showed modest improvement compared to the Waitlist Group in attitudes (∆ =6.2, p < .001) and skills (∆ =10.0, p < .001) subscores, but not the use subscore (∆ = -2.3, p = .470). The majority of participants agreed that the educational program was 'relevant to their profession' (84 %) and 'was worthwhile' (82 %). Overall, engagement in the online program was less than optimal, with 48 % of the Training Group, and 42 % of the Waitlist Group completing all 3 of the program courses. Conclusions: Online EBP training leads to modest improvements in chiropractors' EBP attitudes and skill, but not their use of EBP. This online program can be delivered to a wide national audience, but requires modification to enable greater individualization and peer-to-peer interaction. Our results indicate that it is feasible to deliver an online EBP education on a broad scale, but that this mode of education alone is not sufficient for making large changes in chiropractors' use of EBP. Refereed/Peer-reviewed

Background and study aims Investigations for lower gastrointestinal bleeding (LGIB) include flexible sigmoidoscopy, colonoscopy, computed tomographic angiography (CTA), and angiography. All may be used to direct endoscopic, radiological or surgical treatment, although their optimal use is unknown. The aims of this study were to determine the diagnostic and therapeutic yields of endoscopy, CTA, and angiography for managing LGIB, and their influence on rebleeding, transfusion, and hospital stay. Patients and methods A systematic search of MEDLINE, PubMed, EMBASE, and CENTRAL was undertaken to identify randomized controlled trials (RCTs) and nonrandomized studies of intervention (NRSIs) published between 2000 and 12 November 2015 in patients hospitalized with LGIB. Separate meta-analyses were conducted, presented as pooled odds (ORs) or risk ratios (RR) with 95 % confidence intervals (CIs). Results Two RCTs and 13 NRSIs were included, none of which examined flexible sigmoidoscopy, or compared endotherapy with embolization, or investigated the timing of CTA or angiography. Two NRSIs (57 – 223 participants) comparing colonoscopy and CTA were of insufficient quality for synthesis but showed no difference in diagnostic yields between the two interventions. One RCT and 4 NRSIs (779 participants) compared early colonoscopy ( Conclusions In LGIB there is a paucity of high-quality evidence, although the limited studies on the timing of colonoscopy suggest increased rates of diagnosis and therapy with early colonoscopy.

Background Blood transfusion is administered during many types of surgery, but its efficacy and safety are increasingly questioned. Evaluation of the efficacy of agents, such as desmopressin (DDAVP; 1-deamino-8-D-arginine-vasopressin), that may reduce perioperative blood loss is needed. Objectives To examine the evidence for the efficacy of DDAVP in reducing perioperative blood loss and the need for red cell transfusion in people who do not have inherited bleeding disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2017, issue 3) in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (from 1937), the Transfusion Evidence Library (from 1980), and ongoing trial databases (all searches to 3 April 2017). Selection criteria We included randomised controlled trials comparing DDAVP to placebo or an active comparator (e.g. tranexamic acid, aprotinin) before, during, or immediately after surgery or after invasive procedures in adults or children. Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results We identified 65 completed trials (3874 participants) and four ongoing trials. Of the 65 completed trials, 39 focused on adult cardiac surgery, three on paediatric cardiac surgery, 12 on orthopaedic surgery, two on plastic surgery, and two on vascular surgery; seven studies were conducted in surgery for other conditions. These trials were conducted between 1986 and 2016, and 11 were funded by pharmaceutical companies or by a party with a commercial interest in the outcome of the trial. The GRADE quality of evidence was very low to moderate across all outcomes. No trial reported quality of life. DDAVP versus placebo or no treatment Trial results showed considerable heterogeneity between surgical settings for total volume of red cells transfused (low-quality evidence) and for total blood loss (very low-quality evidence) due to large differences in baseline blood loss. Consequently, these outcomes were not pooled and were reported in subgroups. Compared with placebo, DDAVP may slightly decrease the total volume of red cells transfused in adult cardiac surgery (mean difference (MD) -0.52 units, 95% confidence interval (CI) -0.96 to -0.08 units; 14 trials, 957 participants), but may lead to little or no difference in orthopaedic surgery (MD -0.02, 95% CI -0.67 to 0.64 units; 6 trials, 303 participants), vascular surgery (MD 0.06, 95% CI -0.60 to 0.73 units; 2 trials, 135 participants), or hepatic surgery (MD -0.47, 95% CI -1.27 to 0.33 units; 1 trial, 59 participants). DDAVP probably leads to little or no difference in the total number of participants transfused with blood (risk ratio (RR) 0.96, 95% CI 0.86 to 1.06; 25 trials; 1806 participants) (moderate-quality evidence). Whether DDAVP decreases total blood loss in adult cardiac surgery (MD -135.24 mL, 95% CI -210.80 mL to -59.68 mL; 22 trials, 1358 participants), orthopaedic surgery (MD -285.76 mL, 95% CI -514.99 mL to -56.53 mL; 5 trials, 241 participants), or vascular surgery (MD -582.00 mL, 95% CI -1264.07 mL to 100.07 mL; 1 trial, 44 participants) is uncertain because the quality of evidence is very low. DDAVP probably leads to little or no difference in all-cause mortality (Peto odds ratio (pOR) 1.09, 95% CI 0.51 to 2.34; 22 trials, 1631 participants) or in thrombotic events (pOR 1.36, 95% CI, 0.85 to 2.16; 29 trials, 1984 participants) (both low-quality evidence). DDAVP versus placebo or no treatment for people with platelet dysfunction Compared with placebo, DDAVP may lead to a reduction in the total volume of red cells transfused (MD -0.65 units, 95% CI -1.16 to -0.13 units; 6 trials, 388 participants) (low-quality evidence) and in total blood loss (MD -253.93 mL, 95% CI -408.01 mL to -99.85 mL; 7 trials, 422 participants) (low-quality evidence). DDAVP probably leads to little or no difference in the total number of participants receiving a red cell transfusion (RR 0.83, 95% CI 0.66 to 1.04; 5 trials, 258 participants) (moderate-quality evidence). Whether DDAVP leads to a difference in all-cause mortality (pOR 0.72, 95% CI 0.12 to 4.22; 7 trials; 422 participants) or in thrombotic events (pOR 1.58, 95% CI 0.60 to 4.17; 7 trials, 422 participants) is uncertain because the quality of evidence is very low. DDAVP versus tranexamic acid Compared with tranexamic acid, DDAVP may increase the volume of blood transfused (MD 0.6 units, 95% CI 0.09 to 1.11 units; 1 trial, 40 participants) and total blood loss (MD 142.81 mL, 95% CI 79.78 mL to 205.84 mL; 2 trials, 115 participants) (both low-quality evidence). Whether DDAVP increases or decreases the total number of participants transfused with blood is uncertain because the quality of evidence is very low (RR 2.42, 95% CI 1.04 to 5.64; 3 trials, 135 participants). No trial reported all-cause mortality. Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 2.92, 95% CI 0.32 to 26.83; 2 trials, 115 participants). DDAVP versus aprotinin Compared with aprotinin, DDAVP probably increases the total number of participants transfused with blood (RR 2.41, 95% CI 1.45 to 4.02; 1 trial, 99 participants) (moderate-quality evidence). No trials reported volume of blood transfused or total blood loss and the single trial that included mortality as an outcome reported no deaths. Whether DDAVP leads to a difference in thrombotic events is uncertain because the quality of evidence is very low (pOR 0.98, 95% CI 0.06 to 15.89; 2 trials, 152 participants). Authors' conclusions Most of the evidence derived by comparing DDAVP versus placebo was obtained in cardiac surgery, where DDAVP was administered after cardiopulmonary bypass. In adults undergoing cardiac surgery, the reduction in volume of red cells transfused and total blood loss was small and was unlikely to be clinically important. It is less clear whether DDAVP may be of benefit for children and for those undergoing non-cardiac surgery. A key area for researchers is examining the effects of DDAVP for people with platelet dysfunction. Few trials have compared DDAVP versus tranexamic acid or aprotinin; consequently, we are uncertain of the relative efficacy of these interventions.