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

Expression of ICAM-1 und VCAM-1 in tumor tissue and plasma of patients with advanced stage ovarian carcinoma

Hintergrund: Das Ovarialkarzinom ist das gynäkologische Malignom mit der schlechtesten Prognose mit einer 5-Jahresmortalität von 30-40 %. Es fehlen Tumormarker für die Früherkennung, Zielmoleküle im Sinne einer „targeted therapy“ und Marker zur Prognose- und Therapieabschätzung für eine individualisierte Therapie. Die Adhäsionsmoleküle ICAM-1 und VCAM-1 sind Zellmembranproteine, die bei der Kommunikation zwischen Zellen und Matrixgewebe und bei der Zellmigration jenseits des Epithels, welches die Grundlage für eine Metastasierung darstellt, eine entscheidende Rolle spielen. Aufgrund dieser Funktionen sind sie daher ein erfolgversprechendes Zielmolekül. Für zahlreiche andere Malignome konnte eine abnorme ICAM-1 und VCAM-1 Expression gezeigt werden. Ziel dieser Untersuchung war die Evaluation der Bedeutung von ICAM-1 und VCAM-1 für das epitheliale Ovarialkarzinom (EOC). Material, Methoden und Ergebnisse: 231 Gewebe- und Plasmaproben von Patientinnen aus dem OVCAD-Register mit fortgeschrittenem EOC wurden auf die Proteinexpression von ICAM-1 und VCAM-1 mittels ELISA untersucht. Es erfolgte eine Korrelation im Plasma und Gewebe und mit etablierten Prognosefaktoren für das EOC. Abschließend wurde die prognostische Bedeutung der Proteinexpression für das Gesamtüberleben (OS) und das progressionsfreie Überleben (PFS) evaluiert. In jeder untersuchten Probe konnten ICAM-1 und VCAM-1 nachgewiesen werden. Die mediane Konzentration im Gewebe lag für ICAM-1 bei 766 ng/ml (Range: 16,7-2061 ng/ml) und für VCAM-1 bei 279 ng/ml (Range: 1,59-1141 ng/ml). Im Plasma lagen die Werte für ICAM-1 bei 353 ng/ml (Range: 135-966 ng/ml) und für VCAM-1 bei 1451 ng/ml (Range: 539-3894 ng/ml). Die VCAM-1 Expression korrelierte mit der von ICAM-1 im Plasma (ρ = 0,275, p < 0,0001) und im Gewebe (ρ = 0,62, p < 0,001). Bei der Korrelation mit den klassischen Prognosefaktoren zeigte sich für ICAM-1 im Gewebe eine negative Assoziation mit dem Alter (p = 0,036) und eine positive mit CA-125 (p = 0,026), FIGO-Stadium (p = 0,032), Vorhandensein von Aszites (p = 0,018) und Metastasen (p = 0,036). Nach Adjustierung für die klassischen Prognosefaktoren in der multivariaten Analyse konnten ICAM-1 im Gewebe (p = 0,042) und VCAM-1 im Gewebe (p = 0,001) als unabhängige Prognosefaktoren für das PFS identifiziert werden. Eine prognostische Bedeutung für das OS konnte nicht gezeigt werden. Schlussfolgerung: Die Proteinexpression im Plasma korrelierte nicht mit der im Gewebe und hatte keine prognostische Bedeutung für das OS oder PFS. Die ICAM-1 und VCAM-1-Expression im Gewebe konnte als unabhängiger Prognosefaktor für das PFS identifiziert werden und kann spezifisch für das Ovarialkarzinom sein. ICAM-1 im Gewebe korrelierte mit fünf etablierten Prognosefaktoren. Die hier erhobenen Ergebnisse müssen nun in einer prospektiven Studie mit einer größeren Patientenzahl bestätigt und weiter differenziert untersucht werden.Background: Ovarian cancer is the gynecological malignancy with the worst prognosis with a 5-year mortality of 30-40 %. There are no tumor markers for early detection, target molecules in the sense of “targeted therapy” and markers for prognosis and therapy assessment to ensure an individualized therapy. The adhesion molecules ICAM-1 and VCAM-1 are cell membrane proteins that play a crucial role in the communication between cells and matrix tissue and in cell migration beyond the epithelium, which is the basis for metastaization. Because of these functions, they are therefore a promising target molecule. Abnormal ICAM-1 and VCAM-1 expression have been shown for numerous other malignancies. The aim of this study was to evaluate the role of ICAM-1 and VCAM-1 for epithelial ovarian cancer (EOC). Material, methods and results: 231 tissue and plasma samples from patients from the OVCAD study with advanced EOC were examined in regards of the protein expression of ICAM-1 and VCAM-1 by ELISA. We did a correlation in plasma and tissue and with established prognostic factors for the EOC. Finally, the prognostic importance of protein expression for overall survival (OS) and progression-free survival (PFS) was evaluated. ICAM-1 and VCAM-1 were detected in each sample examined. The median tissue concentration was 766 ng/ml (range: 16,7-2061 ng/ml) for ICAM-1 and 279 ng/ml (range: 1,59-1141 ng/ml) for VCAM-1. The plasma values for ICAM-1 were 353 ng/ml (range: 135-966 ng/ml) and for VCAM-1 1451 ng/ml (range: 539-3894 ng/ml). VCAM-1 expression correlated with that of ICAM-1 in plasma (ρ = 0,275, p < 0,0001) and in tissue (ρ = 0,62, p < 0,001). When correlated with the classic prognostic factors, ICAM-1 showed a negative association with age (p = 0,036) and a positive association with CA-125 (p = 0,026), FIGO stage (p = 0,032), presence of ascites (p = 0,018) and metastases (p = 0,036). After adjustment for the classic prognostic factors the multivariate analysis showed a significant correlation for ICAM-1 in tissue (p = 0,042) and VCAM-1 in tissue (p = 0,001) for the PFS. A prognostic meaning for the OS could not be shown. Conclusion: There was no correlation between protein expression between plasma and tissue. Protein expression in plasma had no prognostic meaning for OS or PFS. Tissue ICAM-1 and VCAM-1 expression has been identified as an independent prognostic factor for PFS and may be specific for ovarian cancer. Tissue ICAM-1 correlated with five established prognostic factors. The results obtained here must now be confirmed in a prospective study with a larger number of patients and examined further

Comparison of Effectiveness of Dexmedetomidine and Tramadol in the Treatment of Post-Neuraxial Anaesthesia Shivering

Background: Shivering is a common problem encountered after neuraxial anaesthesia and is most likely due to altered afferent thermal input from the blocked region. Tramadol a centrally acting analgesic drug, is effective in the treatment of post-anaesthetic shivering after general and neuraxial anaesthesia, by inhibiting the neuronal reuptake of noradrenaline and 5-hydroxytryptamine (5-HT), facilitates 5-HT release and activates the μ-opioid receptors. Dexmedetomidine, a potent alpha 2-adrenergic receptor agonist, acts by decreasing the vasoconstriction and is known to reduce the shivering threshold. Materials &amp; Methods: This was a prospective, randomised, double-blinded study included 100 patients of either genders, aged 20–65 years with ASA status I-II scheduled to undergo elective surgery under spinal anaesthesia. They were then randomly allocated to receive either intravenous dexmedetomidine 0.5 μg/kg or tramadol 0.5 mg/kg. The response rate to treatment, the degree of sedation and the side-effects were recorded. Results: The response rate to treatment and bradycardia was more in the dexmedetomidine group, whereas, nausea and vomiting were observed more in tramadol group and diferrence was significant when compared between groups. Sedation score was comparable between two groups. Conclusion: Dexmedetomidine is superior to tramadol for shivering treatment, due to higher effective rate of shivering control, earlier onset of action and lesser recurrence of shivering and lower incidences of nausea and vomiting. However, dexmedetomidine is also associated with higher incidences of hypotension and bradycardia than tramadol

Comparative Study between Dexamethasone and Tramadol As an Adjuvant to Ropivacaine Vs Ropivacaine Alone In USG Guided Supraclavicular Block in Upper Limb Surgeries

Background: Brachial plexus block provides superior quality of intraoperative and postoperative analgesia and stable hemodynamics over general anesthesia. Various adjuvants have been used to prolong effects of local anesthetics like epinephrine, midazolam, magnesium sulfate, alpha-2 agonists i.e. Clonidine and dexmedetomidine, dexamethasone and tramadol. Aims &amp; Objective: To compare the efficacy of tramadol and dexamethasone on the characteristics of the block and its effect on postoperative analgesia when added as an adjuvant to ropivacaine in USGguided supraclavicular brachial plexus block. Materials &amp; Methods: Eighty patients belonging to American Society of Anaesthesiologists (ASA) Grade I, II and III, aged between 20 to 55 years, scheduled for undergo elective upper limb surgeries under supraclavicular brachial plexus block were enrolled in this study. Patients were equally divided into two groups : group S received 0.5% ropivacaine 30ml with Dexamethasone 2ml (8mg) and tramadol 2ml (100 mg) And group C received 0.5% ropivacaine 30ml with + normal saline 4ml. Onset and duration of sensory and motor block , duration of postoperative analgesia and any complications were observed. Results: In our study both groups were comparable with respect to their demographic profile of patients, duration of surgery and ASA status. Onset of sensory block was earlier in group S than group C (3.15 ± 0.69 minutes and 7.55± 0.89 minutes respectively, p =0.004). Onset and duration of motor block and postoperat ive analgesia were longer in group S as compared to group C (5.01± 1.33 &amp; 12.32± 0.75 minutes respectively, P= 0.001 and 14.44± 0.635 and 8.24± 0.873hours respectively, p =0.001 for motor block and 16.53± 0.635 and 10.45 ± 0.681 minutes respectively, p= 0.001for postoperative analgesia). No ignificant side effects were noted. Conclusion: Dexamethasone and tramadol when added to ropivacaine in supraclavicular brachial plexus lock prolongs onset and duration of sensory and motor block and postoperative analgesia significantly with minimal side effects

Comparative Study between Intranasal Midazolam and Ketamine as a Premedication in Pediatric Surgical Patients

Background: The preoperative period is a stressful event, especially in the pediatric patients. The goals of preanesthetic medication for children include allaying patient anxiety and facilitating the smooth induction of anaesthesia. For providing premedication to pediatric surgical patients, various drugs and many routes have been studied. Midazolam, a GABA receptor inhibitor, is the most commonly used sedative drug for premedication in children. It provides effective sedation, anxiolysis, and varying degrees of anterograde amnesia. Ketamine is a phencyclidine derivative that antagonizes the N-methyl D-aspartate (NMDA) receptor which produces sedation with a trance-like state, analgesia, and preserves upper airway muscle tone and respiratory drive. Intranasal route is one of the preferred route because of the ease of administration.Aims &amp; objectives: In this study, we compared the effects of intranasal midazolam and ketamine on preoperative sedation, parenteral separation, response to intravenous cannulation and mask acceptance in paediatric patients. Materials &amp; Methods: Sixty children classified as ASA physical status I &amp; II, aged between 2- 10 years, who were scheduled to undergo an elective surgeries, were enrolled for a prospective, randomized, and double-blind controlled trial. All of the children received intranasal premedication approximately 30 min before the induction of anaesthesia. Group M (n = 30) received 0.2 mg/kg of intranasal midazolam, and Group K (n = 30) received intranasal ketamine 5mg/kg. All of the patients were anesthetized with nitrous oxide, oxygen, and sevoflurane, administered via a face mask. Results: No significant differences were observed in demographic, hemodynamic, and respiratory parameters, however significant tachycardia was observed in the ketamine group. Intranasal ketamine results in more successful parental separation and yields a higher sedation score (3.87± 0.66) compared to midazolam group (2.62± 0.69) at 30 minutes, with negligible side effects. Venous cannulation and face mask acceptance was also better in the ketamine group with a significantly higher percentage of patients with satisfactory venous cannulation and face mask acceptance (p&lt;0.05). Conclusion: Intranasal ketamine is superior in decreasing anxiety upon separation from parents and providing satisfactory conditions during mask induction and venous cannulation. No adverse effects of the premedication drugs were observed in any of the groups