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

Crohn's Disease treated with azathioprine and basal cell carcinoma : three cases and literature review

Three cases of basal cell carcinoma in Crohn's disease patients treated with azathioprine are described. A review of the literature is conducted concerning this association between the occurrence of basal cell carcinoma and the use of azathioprine. Recently, practical advice on screening and follow-up of these situations have been proposed but there are no validated dermatological recommendations

Assessment of the one-year Efficacy and Safety of Tofacitinib in biologic-refractory patients with Ulcerative Colitis: a real-world Belgian cohort study

peer reviewedIntroduction: Tofacitinib, an oral Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. Efficacy and safety data from long-term real-world studies are scarce. Aim: The aim of the study was to evaluate the real-world long-term efficacy and safety of tofacitinib in a Belgian cohort of patients with refractory UC who were exposed to both anti-TNF and vedolizumab. Methods: We performed an observational, national, retrospective multicenter study including all patients whith active UC who started on tofacitinib between November 2018 and August 2019 in 26 Belgian centers (Ethics Committee approval number P2019/429, date: 10/12/2019; amendment for study extension received on 16/07/2020). Data were prospectively collected and retrospectively analyzed according to intention-to-treat. Clinical response (decrease from baseline in partial adapted Mayo score (stool frequency and rectal bleeding) by ≥ 1 and ≥ 30%), clinical remission (Partial Adapted Mayo score ≤ 1), steroid-free clinical remission, endoscopic response (decrease from baseline in Mayo endoscopic subscore of ≥ 1), endoscopic remission (endoscopic Mayo subscore of 0), drug survival, need for colectomy and adverse events (AEs) were assessed at week 8, 16 and 52. Results: A total of 75 patients were included with a median follow-up of 45 weeks (IQR: 19-51). Patients were predominately men (59%), and median age at baseline was 44 years (IQR: 31-59). Median disease duration was 8 years (IQR: 4-17). Fifty-five percent had left-sided UC and 45% had pancolitis. Overall, 72 (96%), 51 (68%) and 6 (8%) patients were exposed to at least 1, 2 or 3 antiTNFs respectively, and 73 (97%) to vedolizumab. At baseline, 42 (56%) patients were under steroids. Median Partial Adapted Mayo score at baseline was 4 (IQR: 3-5), and median endoscopic Mayo subscore was 2 (IQR: 2-3). Thirty-nine (52%) patients required prolonged induction at 10mg twice daily for 8 additional weeks. Dose optimization was needed in 12 (16%) patients due to disease relapse after induction response, 9 (12%) of which could regain response. After 1 year, 52% and 43% of patients had experienced clinical response and clinical remission respectively, and 39% achieved steroid-free clinical remission. Endoscopic response and remission were observed in 37% and 9% of patients. Faecal calprotectin < 250 µg/g at week 16 (OR: 0.03(95%CI: 0.003-0.4)) was a positive predictor of clinical remission at week 52. Overall, 34 (45%) patients discontinued tofacitinib (22 due to primary non response, 11 due to secondary loss of response and 1 due to AE) during follow-up with a median exposure duration of 17 weeks (IQR: 11-42). Among these patients, 6 underwent colectomy for disease worsening after a median treatment duration of 15 weeks (IQR: 11-19) and a median follow-up of 20 weeks (IQR: 12-25) , while the others switched to another medical therapy. Forty AEs were reported in 25 (33%) patients, with only one (pneumonia) leading to treatment discontinuation. The most common AEs were arthralgia and lower respiratory tract infections followed by herpes zoster, urinary tract and upper respiratory tract infections. Two cases of prostate cancer have been reported. No opportunistic infection, venous thromboembolism, pulmonary embolism or cardiovascular event were reported. A statistically significant increase of 43% in the low-density lipoprotein (LDL) level was observed between baseline and week 52 among patients in clinical remission at week 52 , with no significant changes in total cholesterol and high-density lipoprotein (HDL). Conclusions: Tofacitinib effectively induced long-term clinical and endoscopic response and remission in a refractory cohort of patients with UC in a real-world clinical setting. During this one-year follow-up, tofacitinib was relatively well tolerated with respect to adverse events

Archeologisch booronderzoek Reitdiepwijken 3 te Groningen, gemeente Groningen (GR)

Voor het bureauonderzoek wordt verwezen naar MUG Publicatie 2009-23 (De Roller 2009) dat betrekking heeft op de aangrenzende noordelijke percelen. In de afgelopen twee jaar is de situatie niet zodanig gewijzigd dat er aanvullingen op het bureauonderzoek uit 2009 noodzakelijk zijn. Langs de Friesestraatweg loopt mogelijke een geul met bijbehorende oeverwallen. De oeverwallen zijn aantrekkelijke vestigingsplaatsen voor de mens omdat ze over het algemeen wat droger zijn en hoger liggen dan de omgeving. Uit het booronderzoek blijkt dat binnen het onderzoeksgebied een geul aanwezig is, die vermoedelijk rond de jaartelling zover verland is dat ze geen watervoerende functie meer had. Deels op de geulvulling en op de oeverwallen is een vegetatiehorizont aanwezig dat vermoedelijk uit de 3e eeuw stamt. In twee boringen zijn sporen van fosfaat aangetroffen. Het vegetatiehorizont en de fosfaatsporen zijn aanwijzingen voor menselijke activiteit in het onderzoeksgebied. Mogelijk horen de fosfaatsporen bij de nederzetting net ten oosten van het onderzoeksgebied. Deze nederzetting dateert uit het begin van de jaartelling (Hielkema & De Wit 2007). De terreinomstandigheden (oeverwal en de aanwezigheid van een vegetatiehorizont) binnen het onderzoeksgebied zijn zodanig dat er een goede kans is op menselijke sporen uit de periode ijzertijd-nieuwe tijd. Er wordt daarom aanbevolen vervolgonderzoek uit te voeren in de vorm van een proefsleuvenonderzoek waarbij duidelijk moet worden of er daadwerkelijk bewoningsresten aanwezig zij

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population