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

Paediatric cystic ovarian torsion masquerading appendicitis

A 7-year-old girl presented with a 2-day history of right iliac fossa pain, fever and elevated inflammatory markers. Clinical examination supported a diagnosis of appendicitis. The patient was taken to theatre for an open appendicectomy the following morning. Intraoperatively, a right-sided ovarian haemorrhagic cyst with 360 degrees torsion was discovered. The ovary was torted along with the cyst. Both were detorted and the abdomen was closed. The patient was discharged 48 hours later, with gynaecology outpatient follow-up 6–8 weeks later. Paediatric ovarian torsions caused by a haemorrhagic cyst greater than 2 cm are rare. Here, we discuss an atypical presentation of ovarian torsion and how the clinical presentation can mimic appendicitis.</jats:p

Effects of titanium oxide coating on the antimicrobial properties, surface characteristics, and cytotoxicity of orthodontic brackets - A systematic review and meta analysis of in-vitro studies

Objective: The objective of this review is to systematically analyze the available literature on the effects of titanium oxide (TiO₂) coating on the antimicrobial properties, surface characteristics, and cytotoxicity of orthodontic brackets. Methods: In-vitro studies reporting on the effects of Titanium oxide (TiO₂) coatings on antimicrobial properties, surface roughness, cytotoxic activity and bacterial adhesion of orthodontic brackets were included in the review. Electronic databases such as PubMed, SCOPUS, Web of Science and Google Scholar, were searched till September 2022. Risk of Bias was analyzed by using RoBDEMAT tool. Meta-analysis using Random Effects Model was performed for assessing the antimicrobial activity against S. mutans, C. albicans and L. Acidophilus. Results: A total of 11 studies were included the RoB analysis revealed sufficient reporting across all the domains and inconsistent reporting in only two of the domains. On qualitative analysis, a significant antimicrobial effect of TiO2 coating on orthodontic brackets against Streptococcus mutans, Candida albicans and Lactobacillus acidophilus was reported. The meta analysis revealed a significant overall antimicrobial effect with a high heterogeneity. (SMD: 3.5; p < 0.00001; i2 - 99.2%) Conclusion: An overall significant antimicrobial effect of TiO₂ coated brackets against S. mutans, L. Acidophilus, C. Albicans was noted but with a high heterogeneity. The subgroup analysis revealed a significant antimicrobial effect on C albicans with a low heterogeneity but it was limited by a publication bias. The included studies reported reduced surface roughness, minimal bacterial adhesion and less cytotoxic activity with TiO₂ coated brackets than uncoated brackets

Synthesis and Characterization of Folic Acid Conjugated Gemcitabine Tethered Silver Nanoparticles (FA-GEM-AgNPs) for Targeted Delivery

Background: Silver nanoparticles (AgNPs) have attracted considerable interest in the medical industry due to their physicochemical properties, small size, and surface plasmon behavior. Their smaller particle size and instability in blood circulation leads to toxicity due to its aggregation as Ag+ ions and accumulation at the deepseated organ. In the present study, we aimed at reducing the toxicity of AgNPs by conjugation with an anticancer drug GEM and to improve their internalization through folate receptors-mediated endocytosis by capping the nanoparticles with folic acid (FA). Methods: One-pot facile synthesis of FA capped silver nanoparticles (FA-AgNPs) has been achieved by using FA as a reducing agent. FA-AgNPs were mixed with Gemcitabine (GEM) to obtain tethered FA-GEM-AgNPs. Nanoparticles were characterized by Dynamic Light Scattering (DLS), UV-Visible spectroscopy, Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Analysis (EDAX), Selected Area Electron Diffraction (SAED), and Atomic Absorption Spectroscopy (AAS). The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cytotoxic effect of the prepared nanoformulations. The apoptotic cell death induced by FA-GEM-AgNPs in breast cancer cells were monitored with Acridine orange (AO)/Ethidium Bromide (EtBr) staining. Conclusion: Compared to GEM and AgNPs, FA-GEM-AgNPs showed enhanced cytotoxic effect and internalization in MDA-MB-453 breast cancer cell line. FA-GEM-AgNPs could be an ideal candidate for targeting cancer cells via folate receptor-mediated endocytosis. </jats:sec

Perceptions about psychosis and psychiatric services: a qualitative study from Vellore, India

Each culture influences the perceptions of illness and pathways to health care that its members follow. Non-biomedical beliefs about psychosis and treatment are reported from the developing world. This study explored people's perceptions on psychosis to understand local perceptions of the condition. Focus group discussions were conducted with people who have relatives with psychosis (in five focus groups), with members of the general public (in four focus groups), and with patients who had recovered from psychosis (one group) in Vellore, South India. These discussions were recorded, transcribed and analyzed. Participants recognized psychosis as an illness category, and viewed indigenous healing methods as complementary to allopathic treatments. Multiple and apparently contradictory beliefs on different aspects of psychosis were often simultaneously held by participants. People in the community were more likely to express negative views about mental illness. Relatives of patients with psychosis wanted more support from mental health professionals and community in combating stigma against mental illness. Results of this study reveal the complex nature of illness perspectives among patients with psychosis, their relatives and community. Bio-medical and indigenous beliefs are simultaneously held by a significant number of people who often seek help from both modern and traditional health systems at the same time. The results indicate the need for better understanding of local perceptions of psychosis.</p

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background: Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods: The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results: A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion: Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov).ESCP; NIHR Global Health Research Unit on Global Surgery [NIHR133364]The EAGLE study was funded by the ESCP. Ethicon provided an unrestricted educational grant to the ESCP which was used in supporting the development of the online education materials. The NIHR Global Health Research Unit on Global Surgery (NIHR133364) provided support, notably in accessing and supporting collaborating teams in low-and middle-income countries. The funders had no role in the design, set-up, running or analysis of this study, or writing of this report. The views expressed are those of the authors and not necessarily those of the ESCP, Ethicon, or NIHR