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ObjectivesWe sought to determine whether underlying thrombophilia helps account for excess Covid-19 mortality rates in males relative to females. Specifically, we asked: What is the contribution of thrombophilia to the excess Covid-19 mortality risk among malesãDesignCross-sectional observational study.SettingData were sourced from electronic medical records (EMRs) drawn from over 200 US hospital systems.Participants16,576 patients hospitalized with Covid-19, aged 40 and above.Main outcome measuresThe primary study outcome was Covid-19 mortality. We measured: 1) the mortality rate of male patients relative to female patients, 2) the rate of thrombotic diagnoses occurring during hospitalization for Covid-19 in male and female patients, and 3) the mortality rate when evidence of thrombosis was present. We used hospital EMR data to determine the rates of a thrombotic diagnosis by sex, and D-dimer levels to help identify undiagnosed thrombosis.ResultsThe Covid-19 mortality rate of males was higher than that of females by 16.1%. Males with Covid-19 also had a 25.4% higher rate of receiving a thrombotic diagnosis compared to females with Covid-19. The mortality rate of all patients with a thrombotic diagnosis was 42.4%—a rate over twice that of Covid-19 patients without a thrombotic diagnosis (adjusted OR 2.4 (2.17 to 2.65), p-value < .001). When defining thrombosis as either a documented thrombotic diagnosis or markedly elevated D-dimer levels, over half of the excess mortality in male patients could be explained by thrombophilia.ConclusionsOur findings suggest the higher Covid-19 mortality rate in males may be significantly accounted for by the increased propensity for thrombophilia among males. This thrombotic tendency is additive to the thrombotic risk associated with Covid-19. Understanding the mechanisms that underlie male thrombophilia may allow for the advancement of effective anticoagulation strategies that reduce Covid-19 mortality.Strengths and limitations of this studyTo our knowledge, this population study is the first to provide evidence of a sex-based clinical association that may help explain the excess Covid-19 mortality in males compared to females.This was an observational study using diagnosis codes and natural language processing (NLP) extractions of detailed electronic health record (EHR) data for 16,576 hospitalized patients with Covid-19.We evaluated underlying thrombosis based on both an inpatient thrombotic diagnosis as well as a markedly elevated D-dimer level relative to CRP level.A limitation of this study was that a portion of the estimated excess male mortality was based on the analysis of a subset of 3,442 patients that had serial D-dimer and CRP levels measured in the hospital, and that a potential undercount of these patients was possible due to the use of NLP.

OBJECTIVE To develop a questionnaire for measuring health-related quality of life (HRQL) in patients with Irritable Bowel Syndrome (IBS). METHODS We surveyed the existing literature, and interviewed patients and clinicians, to develop a list of 182 potential problems for IBS patients. One hundred patients with IBS completed a questionnaire in which they told us whether each of the 182 items was a problem for them, and if so the magnitude of their importance in their lives. RESULTS Patients identified four major problem areas: bowel symptoms, fatigue, activity limitations, and emotional dysfunction. On the basis of these findings, we constructed a 26-item questionnaire which, in pre-testing, 16 patients found clear and easy to complete. CONCLUSION We have developed a questionnaire that measures HRQL in IBS patients and is suitable for use as an outcome measure in clinical trials in IBS.

Introduction: Systematic reviewer authors intending to include all randomized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data. Objective: The objective of this paper is to provide systematic reviewer authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of randomized trials. Methods: This guide is based on a review of the Cochrane handbook and published methodological research. The guide deals with participants excluded from the analysis who were considered 'non-adherent to the protocol' but for whom data are available, and participants with missing data. Results: Systematic reviewer authors should include data from 'non-adherent' participants excluded from the primary study authors' analysis but for whom data are available. For missing, unavailable participant data, authors may conduct a complete case analysis (excluding those with missing data) as the primary analysis. Alternatively, they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data. When the primary analysis suggests important benefit, sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis. The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta-analysis. The proposed guide does not take into account the uncertainty associated with assumed events. Conclusions: This guide proposes methods for handling participants excluded from analyses of randomized trials. These methods can help in establishing the extent to which risk of bias impacts meta-analysis results.

ContextEarly administration of thrombolysis for acute myocardial infarction (AMI) may improve survival if safely and appropriately delivered. No systematic reviews that have comprehensively examined this topic exist in the literature.ObjectiveTo perform a meta-analysis of randomized controlled trials of prehospital vs in-hospital thrombolysis for AMI measuring in-hospital mortality.Data SourcesThe Cochrane search strategy was used to search MEDLINE, EMBASE, and the Science Citation Index (1982-1999); Dissertation Abstracts (1987-1999); and Current Contents (1994-1999) for the terms thrombolysis, thrombolysis therapy, prehospital, and acute myocardial infarction. In addition, text and journal article bibliographies were hand searched, the National Institutes of Health Web site was reviewed, and primary authors and thrombolytic drug manufacturers were contacted for unpublished studies.Study SelectionRandomized controlled trials of prehospital vs in-hospital thrombolysis for AMI measuring all-cause hospital mortality were included. Two authors independently reviewed 175 citations by title, abstract, or complete article. After exclusion of 30 duplicate citations, 145 studies remained, of which 6 studies and 3 follow-up studies met the inclusion criteria.Data ExtractionIndependent data abstraction by 2 reviewers blinded to the journal, title, and author was confirmed by consensus. Trial quality was independently assessed by 2 other coauthors, blinded to the author, title, journal, introduction, and discussion.Data SynthesisThe results of the 6 randomized trials (n=6434) were pooled and indicated significantly decreased all-cause hospital mortality among patients treated with prehospital thrombolysis compared with in-hospital thrombolysis (odds ratio, 0.83; 95% confidence interval, 0.70-0.98). Results were similar regardless of trial quality or training and experience of the provider. Estimated (SE) time to thrombolysis was 104 (7) minutes for the prehospital group and 162 (16) minutes for the in-hospital thrombolysis group (P=.007).ConclusionsOur meta-analysis suggests that prehospital thrombolysis for AMI significantly decreases the time to thrombolysis and all-cause hospital mortality.

We examined the cerebral response to changing hematocrit during hypothermic cardiopulmonary bypass (CPB) in 18 adults. Cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and cerebral oxy gen delivery (CDO2) were determined using the nitrous oxide saturation technique. Measurements were obtained before CPB at 36 degrees C, and twice during 27 degrees C CPB: first with a hemoglobin (Hgb) of 6.2 +/- 1.2 g/dL and then with a Hgb of 85 +/- 1.2 g/dL. During hypothermia, appropriate reductions in CMRO2 were demonstrated, but hemodilution-associated increases in CBF offset the reduction in CBF seen with hypothermia. At 27 degrees C CPB, as the Hgb concentration was increased from 6.2 to 8.5 g/dL, CBF decreased. CDO2 and CMRO2 were no different whether the Hgb was 6.2 or 8.5 g/dL. In eight patients in whom the Hgb was less than 6 g/dL, CDO2 remained more than twice CMRO2. Implications: This study suggests that cerebral oxygen balance during cardiopulmonary bypass is well maintained at more pronounced levels of hemodilution than are typically practiced, because changes in cerebral blood flow compensate for changes in hemoglobin concentration.

To examine the effect of stress ulcer prophylaxis on gastrointestinal bleeding, pneumonia, and mortality.Computerized search of published and unpublished research, bibliographies, pharmaceutical and personal files and abstract reports. Independent review of 257 articles identified 71 relevant randomized trials for inclusion. We made independent, duplicate assessment of the methodologic quality, population, intervention and outcomes of each trial.This overview demonstrates that prophylaxis with histamine-2-receptor antagonists decreases the incidence of overt gastrointestinal bleeding (odds ratio 0.29 [95% CI 0.17-0.45]) and clinically important bleeding (odds ratio 0.35 [95% CI 0.15-0.76]). There is a trend to decreased overt bleeding when antacids are compared with no therapy (odds ratio 0.35 [95% CI 0.08-1.33]). Although sucralfate, antacids, and histamine-2-receptor antagonists are equivalent in reducing clinically important bleeding, sucralfate decreases the incidence of nosocomial pneumonia compared with antacids and/or histamine-2-receptor antagonists (odds ratio 0.50 [95% CI 0.21-0.79]). Sucralfate is associated with lower mortality relative to antacids (odds ratio 0.70 [95% CI 0.52-0.94]), and relative to histamine-2-receptor antagonists (odds ratio 0.71 [95% CI 0.49-1.04]).All stress ulcer prophylactic agents appear to be effective in decreasing bleeding. Prophylaxis with sucralfate is associated with a lower rate of nosocomial pneumonia and mortality, providing strong evidence for use of this agent in clinical practice.