No abstract

Study objective To review the effects of prone position and supine position on oxygenation parameters in patients with Coronavirus Disease 2019 (COVID-19). Design Systematic review and meta-analysis of non-randomised trials. Patients Databases of EMBASE, MEDLINE and CENTRAL were systematically searched from its inception until March 2021. Interventions COVID-19 patients being positioned in the prone position either whilst awake or under general anaesthesia. Measurements Primary outcomes were oxygenation parameters (PaO₂/FiO₂ ratio, PaCO2, SpO2). Secondary outcomes included the rate of intubation and mortality rate. Results Thirty-five studies ( n = 1712 patients) were included in this review. In comparison to the supine group, prone position significantly improved the PaO₂/FiO₂ ratio (study = 13, patients = 1002, Mean difference, MD 52.15, 95% CI 37.08 to 67.22; p < 0.00001) and SpO₂ (study = 11, patients = 998, MD 4.17, 95% CI 2.53 to 5.81; p ≤0.00001). Patients received prone position were associated with lower incidence of mortality (study = 5, patients = 688, Odd ratio, OR 0.44, 95% CI 0.24 to 0.80; p = 0.007). No significant difference was noted in the incidence of intubation rate (study = 5, patients = 626, OR 1.20, 95% CI 0.77 to 1.86; p = 0.42) between the supine and prone groups. Conclusion Our meta-analysis demonstrated that prone position improved PaO2/FiO2 ratio with better SpO2 than supine position in COVID-19 patients. Given the limited number of studies with small sample size and substantial heterogeneity of measured outcomes, further studies are warranted to standardize the regime of prone position to improve the certainty of evidence. PROSPERO Registration: CRD42021234050

Background Intravenous (IV) infliximab is a well-established therapy for inflammatory bowel diseases (IBD) patients. A subcutaneous (SC) formulation of infliximab (CT-P13) has recently been shown to be as effective as IV infliximab after 2 doses of IV induction in a randomised trial but there are no data to support elective switching of patients on maintenance IV infliximab therapy. We aimed to assess the effectiveness of an elective switching program to SC CT-P13 in patients treated with IV infliximab. Methods Patients on established maintenance IV infliximab who switched to SC CT-P13 were included in this retrospective multi-centre cohort study. Disease activity was monitored serially with Harvey-Bradshaw Index (HBI) for Crohn’s disease (CD) and simple clinical colitis activity index (SCCAI) for up to 12 months at months 3, 6 and 12. Faecal calprotectin (FC) and C-reactive protein (CRP) was recorded at baseline and follow-up, if available. Infliximab trough levels were measured prior to switch and at months 3, 6 and 12 following switch. The primary outcome measure was treatment persistence at last follow-up. Secondary outcome measures included infliximab pharmacokinetics (PK), safety, need for corticosteroid rescue therapy and need for surgery. Results We included 181 patients of who 115 (63.5%) had CD. The majority (72.4%) were on 8-weekly dosing of intravenous infliximab prior to switching and more than half (59.1%) were on concomitant immunomodulatory therapy. The majority of patients (CD: N=106, 92.2%, UC: N=46, 76.7% and IBD-U: N=5, 83.3%) were in clinical remission. Treatment persistence rate was high (N=167, 92.3%) and only 14 patients (7.7%) stopped treatment during the follow-up period. There was no significant difference between baseline and repeat measurements at 3, 6 or 12 months for HBI, SCCAI, CRP or FC. Of the total cohort, 25 patients (21.7%) had perianal CD. Of these, only two patients (8%) had worsening of perianal CD and required antibiotic therapy and further examination under anaesthesia (EUA). Both these patients also switched back to intravenous infliximab. Median infliximab level increased from a baseline of 8.9 µg/dl (range 0.4-16) to 16.0 µg/dl (range 2.3-16, P&lt;0.001) at 3 months. Serum levels stayed stable at 6 months (median 16 µg/dl, range 0.3-17.2) and 12 months (median 16 µg/dl, range 0.3-19.1, both P&lt;0.001 compared to baseline). Among the variables examined, only antibodies to infliximab (ATI) was associated with infliximab levels (OR -13.369, 95% CI -15.405, -11.333, P&lt;0.001). A total of 14 patients (7.7%) developed ATI of which 9 (64.3%) were on concomitant immunomodulatory therapy. Immunomodulatory therapy was not significantly associated with development of ATI (P=0.15). In a subset of patients receiving escalated IV infliximab dosing frequency prior to switch, no difference in treatment persistence was observed in patients receiving weekly versus alternate weekly SC CT-P13. Patient acceptance and satisfaction rates with SC CT-P13 were very high. Conclusions Among patients on IV infliximab maintenance therapy switched to SC CT-P13, we observed high treatment persistence rates and low rates of immunogenicity with no change in clinical disease activity indices or biomarkers. Infliximab levels increased after switch to SC CT-P13 and only ATI was associated with serum infliximab levels. Patient acceptance and satisfaction rates were high with SC CT-P13.

BACKGROUND Several studies suggest that systemic magnesium reduces postoperative opioid consumption and the intensity of pain, but others report conflicting results. The efficacy and safety profile of intravenous magnesium in noncardiac surgery remain uncertain. OBJECTIVES The aim of this review was to investigate the effect of intravenous magnesium on the consumption of postoperative morphine in the first 24 h in adults undergoing noncardiac surgery. DESIGN Systematic review and meta-analysis with trial sequential analysis. DATA SOURCES MEDLINE, EMBASE, CENTRAL from their inception until January 2019. ELIGIBILITY CRITERIA All randomised clinical trials comparing intravenous magnesium versus placebo in noncardiac surgery were systematically searched in the databases. Observational studies, case reports, case series and nonsystematic reviews were excluded. RESULTS Fifty-one trials (n=3311) were included for quantitative meta-analysis. In comparison with placebo, postoperative morphine consumption at 24-h was significantly reduced in the magnesium group, with a mean difference [95% confidence interval (CI)] of −5.6 mg (−7.54 to −3.66, P < 0.001, I 2 = 92%, level of evidence low). The trial sequential analysis for the effect of magnesium on postoperative morphine consumption was conclusive. Patients who received magnesium had a longer time to the first analgesia request [143 (103 to 183) min, P < 0.001, I 2 = 99%, level of evidence low] and a lower incidence of shivering [0.26 (0.15 to 0.44), P < 0.001, I 2 = 35%, level of evidence very low]. However, no significance differences were demonstrated in postoperative pain scores in the first 24 h (mean difference, 95% CI) −0.30 (−0.69 to 0.09, P = 0.13, I 2 = 91%, level of evidence low), bradycardia (odds ratio, 95% CI) 1.13 (0.43 to 2.98, P = 0.80, I 2 = 35%, level of evidence very low) and postoperative nausea and vomiting (odds ratio, 95% CI) 0.90 (0.67 to 1.22, P = 0.49, I 2 = 25%, level of evidence moderate). CONCLUSION The current meta-analysis demonstrates that the use of intravenous magnesium as part of multimodal analgesia may reduce morphine consumption in the first 24 h after surgery and delay the time to the first request for analgesia in patients undergoing noncardiac surgery. However, the included studies were of low-quality with substantial heterogeneity. TRIAL REGISTRATION CRD42018086846.