Background Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19. Methods In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause. Results A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, −6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. Conclusions The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767 .)

BackgroundDermatomyositis (DM) is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood.Methodology and FindingsWe analyzed genome-wide expression data in DM skin and compared them to those from healthy controls. We observed a robust upregulation of interferon (IFN)-inducible genes in DM skin, as well as several other gene modules pertaining to inflammation, complement activation, and epidermal activation and differentiation. The interferon (IFN)-inducible genes within the DM signature were present not only in DM and lupus, but also cutaneous herpes simplex-2 infection and to a lesser degree, psoriasis. This IFN signature was absent or weakly present in atopic dermatitis, allergic contact dermatitis, acne vulgaris, systemic sclerosis, and localized scleroderma/morphea. We observed that the IFN signature in DM skin appears to be more closely related to type I than type II IFN based on in vitro IFN stimulation expression signatures. However, quantitation of IFN mRNAs in DM skin shows that the majority of known type I IFNs, as well as IFN g, are overexpressed in DM skin. In addition, both IFN-beta and IFN-gamma (but not other type I IFN) transcript levels were highly correlated with the degree of the in vivo IFN transcriptional response in DM skin.Conclusions and SignificanceAs in the blood and muscle, DM skin is characterized by an overwhelming presence of an IFN signature, although it is difficult to conclusively define this response as type I or type II. Understanding the significance of the IFN signature in this wide array of inflammatory diseases will be furthered by identification of the nature of the cells that both produce and respond to IFN, as well as which IFN subtype is biologically active in each diseased tissue.

Objective Prescription opioid overdoses are a leading cause of death in the United States. Emergency departments (EDs) are potentially high risk environments for doctor shopping and diversion. We hypothesized that opioid prescribing rates from the ED have increased over time. Methods We analyzed data on ED discharges from the 2006–2010 NHAMCS, a probability sample of all United States EDs. The outcome was documentation of an opioid prescription on discharge. The primary independent predictor was time. Covariates included severity of pain, a pain-related discharge diagnosis, age, gender, race, payer, hospital ownership, and geographic location of hospital. Up to three discharge diagnoses were available in NHAMCS to identify ‘pain-related’ (e.g. back pain, fracture, dental/jaw pain, nephrolithiasis) ED visits. We performed multivariate logistic regression to assess the independent associations between opioid prescribing and predictors. All analyses incorporated NHAMCS survey weights, and all results are presented as national estimates. Results Opioids were prescribed for 18.7% (95% CI: 17.7–19.7%) of all ED discharges, representing 18.8 million prescriptions per year. There were no significant temporal trends in opioid prescribing overall (adjusted p=0.93). Painful discharge diagnoses that received the top 3 highest proportion of opioids prescriptions included: nephrolithiasis (62.1%), neck pain (51.6%), and dental/jaw pain (49.7%). A pain-related discharge diagnosis, non-Hispanic white race, older age, male gender, uninsured status and Western region were associated with opioid prescribing (p<0.05). Conclusions We found with no temporal trend towards increased prescribing from 2006–2012. Our results suggest that problems with opioid over-prescribing are multifactorial and not solely rooted in the ED.

Consensus development sprang from a desire to synthesize clinician and expert opinions on clinical practice and research agendas in the 1950s. And since the American Institute of Medicine formally defined “guidelines” in 1990, there has been a proliferation of clinical practice guidelines (CPG) both formally and informally. This modern decision making tool used by both physicians and patients, requires extensive planning to meet the challenges of consensus development while reaping its rewards. Consensus allows for a group approach with multiple experts sharing ideas to form consensus on topics ranging from appropriateness of procedures to research agenda development. Disagreements can shed light on areas of controversy and launch further discussions. It has five main components: three inputs (defining the task, participant identification and recruitment, and information synthesis), the approach (consensus development by explicit or implicit means), and the output (dissemination of results). Each aspect requires extensive planning a priori as they influence the entire process, from how information will be interpreted, the interaction of participants, the resulting judgment, to whether there will be uptake of results. Implicit approaches utilize qualitative methods and/or a simple voting structure of majority wins, and are used in informal consensus development methods and consensus development conferences. Explicit approaches aggregate results or judgments using explicit rules set a priori with definitions of “agreement” or consensus. Because the implicit process can be more opaque, unforeseen challenges can emerge such as the undue influence of a minority. And yet, the logistics of explicit approaches may be more time consuming and not appropriate when speed is a priority. In determining which method to use, it is important to understand the pros and cons of the different approaches and how it will affect the overall input, approach, and outcome.

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