Background Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection. Methods This phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 107 cells and 1.0 × 108 cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period. Results There were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups. Conclusions Our clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19. Trial registration ClinicalTrials.gov, NCT04535856. Registered 2 September 2020, https://clinicaltrials.gov/ct2/show/NCT04535856
The burden of antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs) is largely unknown. Here, we evaluate attributable mortality of AMR infections in Indonesia. We used routine databases of the microbiology laboratory and hospital admission at Dr. Wahidin Sudirohusodo Hospital, a tertiary-care hospital in South Sulawesi from 2015 to 2018. Of 77,752 hospitalized patients, 8,341 (10.7%) had at least one blood culture taken. Among patients with bacteriologically confirmed bloodstream infections (BSI), the proportions of patients with AMR BSI were 78% (81/104) for third-generation cephalosporin-resistant (3GCR) Escherichia coli, 4% (4/104) for 3GCR plus carbapenem-resistant E. coli, 56% (96/171) for 3GCR Klebsiella pneumoniae, 25% (43/171) for 3GCR plus carbapenem-resistant K. pneumoniae, 51% (124/245) for methicillin-resistant Staphylococcus aureus, 48% (82/171) for carbapenem-resistant Acinetobacter spp., and 19% (13/68) for carbapenem-resistant Pseudomonas aeruginosa. Observed in-hospital mortality of patients with AMR BSI was 49.7% (220/443). Compared with patients with antimicrobial-susceptible BSI and adjusted for potential confounders, the excess mortality attributable to AMR BSI was -0.01 (95% CI: -15.4, 15.4) percentage points. Compared with patients without a BSI with a target pathogen and adjusted for potential confounders, the excess mortality attributable to AMR BSI was 29.7 (95%CI: 26.1, 33.2) percentage points. This suggests that if all the AMR BSI were replaced by no infection, 130 (95%CI: 114, 145) deaths among 443 patients with AMR BSI might have been prevented. In conclusion, the burden of AMR infections in Indonesian hospitals is likely high. Similar large-scale evaluations should be performed across LMICs to inform interventions to mitigate AMR-associated mortality.
Latar Belakang: Gabapentin dapat mencegah nyeri nosiseptif, nyeri neuropatik, inflamasi akut dan mengurangi nyeri pasca operasi. Tujuan: penelitian ini membandingkan tiga dosis gabapentin oral pada operasi histerektomi total dengan anestesi spinal untuk efeknya pada sedasi, mual-muntah, dan nyeri pascabedahSubjek dan Metode: Desain yang digunakan pada penelitian ini adalah uji klinis acak tersamar tunggal. Sampel terbagi dalam kelompok G600: gabapentin 600 mg, kelompok G750 gabapentin 750 mg dan kelompok G900: gabapentin 900 mg dengan jumlah sampel masing-masing 14 orang. Data dianalisis menggunakan uji statistik uji Mann Whitney U.Hasil: Perbandingan analgesik tambahan pascabedah kelompok G600 membutuhkan lebih banyak analgesik tambahan dibanding kelompok G750 (p = 0,021) dan begitu juga untuk kelompok G750 dibanding kelompok G900(p = 0,004). Perbandingan kelompok G600 dan G750 untuk skor sedasi dan agitasi Richmond berbeda bermakna pada jam ke-3,6, dan 9 (nilai p 0,004; 0,007; dan 0,03) dan kelompok G600 dan G900 juga berbeda bermakna pada jam ke-3,6, dan 9 (p = 0,007). Untuk post operative nausea and vomiting (PONV) terdapat perbedaan bermakna antara kelompok G600 dan G900 dan juga antara kelompok G750 dan G900 (p = 0,043). Simpulan: Pemberian gabapentin oral 900 mg memberikan total rescue analgetik paling sedikit dibanding dengan pemberian gabapentin 600 mg dan 750 mg. Ketiga kelompok gabapentin mengalami efek samping sedasi ringan. Kejadian PONV paling rendah pada kelompok gabapentin 900 mg. Comparison Between Three Doses of Oral Gabapentin Against Postoperative Pain, Sedation, and Nausea-Vomiting in Total Hysterectomy with Spinal Anesthesia Abstract Background: Gabapentin can prevent nociceptive pain, neuropathic pain, acute inflammation and reduce postoperative painObjective: this study aimed to compare three doses of oral gabapentin in total hysterectomy with spinal anesthesia for its effect on sedation, postoperative nausea and vomiting, and post operative painSubject and Method: This study was a single blind randomized clinical trial. Samples were divided into groups of G600: gabapentin 600 mg, group G750 gabapentin 750 mg and group G900: gabapentin 900 mg with the number of samples was 14 people each. Data were analyzed using statistical analysis using the Mann Whitney U test.Results: Comparison of postoperative adjunctive analgesics in the G600 group required more additional analgesics than the G750 group (p = 0.021) and likewise for the G750 group compared to the G900 group (p = 0.004). Comparison of the G600 and G750 groups for sedation and agitation scores for Richmond was significantly different at the 3.6 and 9 hours (p value 0.004; 0.007; and 0.03) and the G600 and G900 groups were also significantly different at the 3.6 hour, and 9 (p = 0.007). For post operative nausea and vomiting (PONV), there were significant differences between the G600 and G900 groups and also between the G750 and G900 groups (p = 0.043).Conclusion: Gabapentin oral 900 mg with the least total analgesic rescue compared to gabapentin 600 mg and 750 mg. All three gabapentin groups experienced mild side effects of sedation. The lowest incidence of PONV was in the gabapentin 900 mg group
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