Accuracy of ED Bedside Ultrasound for Identification of gallstones: retrospective analysis of 575 studies

Study Objective: To determine the ability of emergency department (ED) physicians to diagnose cholelithiasis with bedside ultrasound. Methods: ED gallbladder ultrasounds recorded over 37 months were compared to radiology ultrasound interpretation. Results: Of 1,690 ED gallbladder ultrasound scans performed during this period, radiology ultrasound was performed in 575/1690 (34%) cases. ED physician bedside interpretation was 88% sensitive [95% CI, 84-91] and 87% specific [95% CI, 82-91], while positive predictive value (PPV) was 91% [88- 94%] and negative predictive value (NPV) was 83% [78-87%], using radiology interpretation as the criterion reference. Conclusion: ED physician ultrasound of the gallbladder for cholelithiasis is both sensitive and specific

Probability of sepsis after infection consultations in primary care in the United Kingdom in 2002-17:population-based cohort study and decision analytic model

BackgroundEfforts to reduce unnecessary antibiotic prescribing have coincided with increasing awareness of sepsis. We aimed to estimate the probability of sepsis following infection consultations in primary care when antibiotics were or were not prescribed.Methods and findingsWe conducted a cohort study including all registered patients at 706 general practices in the United Kingdom Clinical Practice Research Datalink, with 66.2 million person-years of follow-up from 2002 to 2017. There were 35,244 first episodes of sepsis (17,886, 51%, female; median age 71 years, interquartile range 57-82 years). Consultations for respiratory tract infection (RTI), skin or urinary tract infection (UTI), and antibiotic prescriptions were exposures. A Bayesian decision tree was used to estimate the probability (95% uncertainty intervals [UIs]) of sepsis following an infection consultation. Age, gender, and frailty were evaluated as association modifiers. The probability of sepsis was lower if an antibiotic was prescribed, but the number of antibiotic prescriptions required to prevent one episode of sepsis (number needed to treat [NNT]) decreased with age. At 0-4 years old, the NNT was 29,773 (95% UI 18,458-71,091) in boys and 27,014 (16,739-65,709) in girls; over 85 years old, NNT was 262 (236-293) in men and 385 (352-421) in women. Frailty was associated with greater risk of sepsis and lower NNT. For severely frail patients aged 55-64 years, the NNT was 247 (156-459) in men and 343 (234-556) in women. At all ages, the probability of sepsis was greatest for UTI, followed by skin infection, followed by RTI. At 65-74 years, the NNT following RTI was 1,257 (1,112-1,434) in men and 2,278 (1,966-2,686) in women; the NNT following skin infection was 503 (398-646) in men and 784 (602-1,051) in women; following UTI, the NNT was 121 (102-145) in men and 284 (241-342) in women. NNT values were generally smaller for the period from 2014 to 2017, when sepsis was diagnosed more frequently. Lack of random allocation to antibiotic therapy might have biased estimates; patients may sometimes experience sepsis or receive antibiotic prescriptions without these being recorded in primary care; recording of sepsis has increased over the study period.ConclusionsThese stratified estimates of risk help to identify groups in which antibiotic prescribing may be more safely reduced. Risks of sepsis and benefits of antibiotics are more substantial among older adults, persons with more advanced frailty, or following UTIs

Vacuum aspiration for induced abortion could be safely and legally performed by nurses and midwives

Background: Some 40% of abortions carried out in England and Wales are done by vacuum aspiration. It is widely assumed that, in order to be lawful, these procedures must be performed by doctors. Aim and design: This study aimed to provide a detailed reassessment of the relevant law and the clinical evidence that supports this assumption. Conclusions: A close reading of relevant law reveals that this assumption is unfounded. On the contrary, it would be lawful for appropriately trained nurses or midwives, acting as part of a multidisciplinary team, to carry out vacuum aspiration procedures. This interpretation of the law offers the potential for developing more streamlined, cost-effective abortion services, which would be both safe and highly acceptable to patients

Using the spatial population abundance dynamics engine for conservation management

1. An explicit spatial understanding of population dynamics is often critical for effective management of wild populations. Sophisticated approaches are available to simulate these dynamics, but are largely either spatially homogeneous or agentbased, and thus best suited to small spatial or temporal scales. These approaches also often ignore financial decisions crucial to choosing management approaches on the basis of cost-effectiveness. 2. We created a user-friendly and flexible modelling framework for simulating these population issues at large spatial scales – the Spatial Population Abundance Dynamics Engine (SPADE). SPADE is based on the STAR model (McMahon et al. 2010) and uses a reaction-diffusion approach to model population trajectories and a cost-benefit analysis technique to calculate optimal management strategies over long periods and across broad spatial scales. It expands on STAR by incorporating species interactions and multiple concurrent management strategies, and by allowing full user control of functional forms and parameters. 3. We used SPADE to simulate the eradication of feral domestic cats Felis catus on sub-Antarctic Marion Island (Bester et al. 2002) and compared modelled outputs to observed data. The parameters of the best-fitting model reflected the conditions of the management programme, and the model successfully simulated the observed movement of the cat population to the southern and eastern portion of the island under hunting pressure. We further demonstrated that none of the management strategies would likely have been successful within a reasonable timeframe if performed in isolation. 4. SPADE is applicable to a wide range of population management problems, and allows easy generation, modification and analysis of management scenarios. It is a useful tool for the planning, evaluation and optimisation of the management of wild populations, and can be used without specialised training.Appendix S1. SPADE manual.Appendix S2. Details of algorithms used in SPADE.Appendix S3. Details of statistical models.Appendix S4. Source code for SPADE package.Appendix S5. Description of potential issues in using STAR.The development of SPADE was aided extensively by input from the Australian Alps National Parks Cooperative Management Programme’s Feral Horse Working Group, including participants from Parks Victoria, the NSW National Parks and Wildlife Service, the ACT Parks and Conservation Service and Forestry Corporation NSW.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)2041-210Xhb2017Mammal Research Institut

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication