We found that physicians often individualize their CRC screening recommendations for older women by electing to engage patients in discussions and seeking their input before making a CRC recommendation. Physicians were more likely to elect to engage the patients represented by the good and fair health vignette, where the potential benefits likely outweigh the potential harms, than the patient in poor health, where the potential harms likely outweigh the potential benefits.
Summary Recent epidemiologic data suggest that sickle cell trait (HbAS; AS) is a risk factor for venous thromboembolism. We conducted an exploratory study of healthy subjects with AS under baseline conditions to determine whether a chronic basal hyperactivation of coagulation exists, and if so, what mechanism(s) contribute to this state. Eighteen healthy AS individuals were compared to 22 African-American controls with a normal haemoglobin profile (HbAA; AA) and 17 patients with sickle cell disease (HbSS; SS). Plasma thrombin-antithrombin complexes and D-dimer levels were elevated in AS relative to AA patients (P = 0.0385 and P = 0.017, respectively), and as expected, were much higher in SS versus AA (P < 0.0001 for both). Thrombin generation in platelet poor plasma was indistinguishable between AA and AS subjects, whereas a paradoxical decrease in endogenous thrombin potential was observed in SS (P ≤ 0.0001). Whole blood tissue factor was elevated in SS compared to AA (P = 0.005), but did not differ between AA and AS. Plasma microparticle tissue factor activity was non-significantly elevated in AS (P = 0.051), but was clearly elevated in SS patients (P = 0.004) when compared to AA controls. Further studies in larger cohorts of subjects with sickle cell trait are needed to confirm the results of this preliminary investigation.
Importance: Early treatment of mild SARS-CoV-2 infection might lower the risk of clinical deterioration in COVID-19. Objective: To determine whether oral camostat mesylate would reduce upper respiratory SARS-CoV-2 viral load in newly diagnosed outpatients with mild COVID-19, and would lead to improvement in COVID-19 symptoms. Design: From June, 2020 to April, 2021, we conducted a randomized, double-blind, placebo-controlled phase 2 trial. Setting: Single site, academic medical center, outpatient setting in Connecticut, USA. Participants: Of 568 COVID-19 positive potential adult participants diagnosed within 3 days of study entry and assessed for eligibility, 70 were randomized and 498 were excluded (198 did not meet eligibility criteria, 37 were not interested, 265 were excluded for unknown or other reasons). The primary inclusion criteria were a positive SARS-CoV-2 nucleic acid amplification result in adults within 3 days of screening regardless of COVID-19 symptoms. Intervention: Treatment was 7 days of oral camostat mesylate, 200 mg po four times a day, or placebo. Main Outcomes and Measures: The primary outcome was reduction of 4-day log10 nasopharyngeal swab viral load by 0.5 log10 compared to placebo. The main prespecified secondary outcome was reduction in symptom scores as measured by a quantitative Likert scale instrument, Flu-PRO-Plus modified to measure changes in smell/taste measured using FLU-PRO-Plus. Results: Participants receiving camostat had statistically significant lower quantitative symptom scores (FLU-Pro-Plus) at day 6, accelerated overall symptom resolution and notably improved taste/smell, and fatigue beginning at onset of intervention in the camostat mesylate group compared to placebo. Intention-to-treat analysis demonstrated that camostat mesylate was not associated with a reduction in 4-day log10 NP viral load compared to placebo. Conclusions and relevance: The camostat group had more rapid resolution of COVID-19 symptoms and amelioration of the loss of taste and smell. Camostat compared to placebo was not associated with reduction in nasopharyngeal SARS-COV-2 viral load. Additional clinical trials are warranted to validate the role of camostat mesylate on SARS-CoV-2 infection in the treatment of mild COVID-19. Trial registration: Clinicaltrials.gov, NCT04353284 (04/20/20) (https://clinicaltrials.gov/ct2/show/NCT04353284?term=camostat+%2C+yale&draw=2&rank=1)
BACKGROUND Blood donors represent a healthy population, whose red blood cell (RBC) alloantibody persistence or evanescence kinetics may differ from those of immunocompromised patients. A better understanding of the biologic factors impacting antibody persistence is warranted, as the presence of alloantibodies may impact donor health and the fate of the donated blood product. METHODS Donor/donation data collected from four US blood centers from 2012 to 2016 as part of the Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III) were analyzed. Clinically significant antibodies from blood donors with more than one donation who underwent at least one follow‐up antibody screen after the initial antibody identification were included. Of 632,378 blood donors, 481 (128 males and 353 females) fit inclusion criteria. RESULTS Antibody screens detected 562 alloantibodies, with 368 of 562 (65%) of antibodies being persistently detected and with 194 of 562 (35%) becoming evanescent. Factors associated with antibody persistence included antibody specificity, detection at the first donation, reported history of transfusion, and detection of multiple antibodies concurrently. Anti‐D, C, and Fya were most likely to persist, while anti‐M, Jka, and S were most frequently evanescent. CONCLUSIONS These data provide insight into variables impacting the duration of antibody detection, and they may also influence blood donor center policies regarding donor recruitment/acceptance.
Objective The goal of this study was to examine associations between physicians’ clinical assessments, their certainty in these assessments, and the likelihood of a patient-centered recommendation about colorectal cancer (CRC) screening in the elderly. Methods Two hundred seventy six primary care physicians in the United States read three vignettes about an 80 year old female patient and answered questions about her life expectancy, their confidence in their life expectancy estimate, the balance of benefits/downsides of CRC screening, their certainty in their benefit/downside assessment, and the best course of action regarding CRC screening. We used logistic regression to determine the relationship between these variables and patient-centered recommendations about CRC screening. Results In bivariate analyses, physicians had higher odds of making a patient-centered recommendation about CRC screening when their clinical assessments did not lead to a clear screening recommendation or when they experienced uncertainty in their clinical assessments. However, in a multivariate regression model, only benefit/downside assessment and best course of action remained statistically significant predictors of a patient-centered recommendation. Conclusions Our findings demonstrate that when the results of clinical assessments do not lead to obvious screening decisions or when the physician feels uncertain about their clinical assessments, they are more likely to make patient-centered recommendations. Existing uncertainty frameworks do not adequately describe the uncertainty associated with patient-centered recommendations found in this study. Adapting or modifying these frameworks to better reflect the constructs associated with uncertainty and the interactions between uncertainty and the complexity inherent in clinical decisions will facilitate a more complete understanding of how and when physicians choose to include patients in clinical decisions.
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