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To investigate the clinical efficacy and safety of topical difamilast in mild-to-moderate atopic dermatitis (AD). Only randomized controlled trials (RCTs) that compared topical difamilast with vehicle treatment for patients with AD were included. PubMed, Web of Science, Ovid Medline, Cochrane Library, ClinicalTrials.gov and JapicCTI were searched to 10 April 2022. Five studies enrolling a total of 1009 patients with mild-to-moderate AD were identified. Compared with the topical vehicle, topical difamilast was associated with a significantly higher success rate according to the Investigator’s Global Assessment score at week 4 (relative risk, 2.82; 95% confidence interval [CI]: 2.11–3.77). Compared with the vehicle, difamilast was associated with a significant decrease in day 28 eczema area and severity index scores (mean difference [MD], −4.10; 95% CI: −5.32 to −2.87), verbal rating scale scores (MD, −0.51; 95% CI: −0.71 to −0.32), visual analog scale scores (MD, −12.15; 95% CI: −19.70 to −4.61), patient-oriented eczema measure values (MD, −3.99; 95% CI: −4.91 to −3.07), and total affected body surface area (MD, −6.48; 95% CI: −8.09 to −4.87). No difference in treatment-related adverse events was identified. This meta-analysis suggests that topical difamilast is an effective and safe treatment for mild-to-moderate AD.

This meta-analysis of randomized controlled trials (RCTs) investigated the clinical efficacy and safety of favipiravir for patients with mild-to-critical COVID-19.PubMed, Web of Science, Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials were searched for RCTs published before 30 October 2021. Only RCTs that compared the clinical efficacy and safety of favipiravir -based antiviral regimens (study group) with other alternative treatments or placebos (control group) in patients with COVID-19 were included.Overall, the clinical improvement rate was significantly higher in the study group than in the control group at the assessment conducted after 14 days (OR, 1.83; 95% CI, 1.12-2.98). The rate of virological eradication was significantly higher in the study group than in the control group at the assessment conducted after 28 days (OR, 2.09; 95% CI, 1.15-3.78). No significant difference was observed in the rates of invasive mechanical ventilation requirement or ICU admission, mortality, or risk of an adverse event between the study and control groups.Except the clinical improvement rate within 14 days and the virological eradication rate within 28 days, favipiravir-based treatment did not provide significantly additional benefit for patients with COVID-19. Therefore, more evidence is necessary.

Background Anti-interleukin-5 (IL-5) therapy has been proposed as a novel treatment option for patients with chronic obstructive pulmonary disease (COPD). However, its efficacy for preventing COPD exacerbation remains unclear. Methods A literature review was conducted to August 26th 2019. Only randomized controlled trials (RCTs) that investigated the clinical efficacy and adverse effects of anti-IL-5 therapy were included in the meta-analysis. The primary outcome was the risk of COPD exacerbation. Results A total of 3 articles containing 5 RCTs were included in the study. Overall, 2837 and 1442 patients received anti-IL-5 therapy (mepolizumab, n = 865; benralizumab, n = 1972) and placebo, respectively. In the pooled analysis, anti-IL-5 therapy was associated with a lower risk of COPD exacerbation compared with the placebo (rate ratio, 0.92; 95% CI, 0.86–0.97, I2 = 0%). In addition, no significant differences in the changes in SGRQ scores and FEV1 from baseline were found between the anti-IL-5 therapy and placebo (SGRQ, mean difference, −0.86, 95% CI, −1.92 – 0.19, I2 = 0%; FEV1, mean difference, 0.01, 95% CI, −0.01 – 0.03, I2 = 0%). Anti-IL-5 therapy had a similar risk of any adverse event (risk ratio, 1.02; 95% CI, 0.99–1.05), an event leading to treatment discontinuation (risk ratio, 1.04; 95% CI, 0.72–1.48) and any serious adverse events (risk ratio, 0.93; 95% CI, 0.85–1.01) when compared with the placebo. Conclusion Anti-IL-5 therapy was associated with a lower rate of COPD exacerbation compared with placebo. In addition, anti-IL-5 therapy was well tolerated for COPD patients.

Background This meta-analysis of randomized controlled trials (RCTs) investigated the usefulness of Janus kinase (JAK) inhibitors among hospitalized patients with COVID-19. Methods PubMed, Web of Science, the Cochrane Library, and Ovid MEDLINE were searched for RCTs published before 7 September 2021. Only RCTs that compared the clinical efficacy and safety of JAK inhibitors with other alternative treatments or placebos in the treatment of hospitalized patients with COVID-19 were included. Results Overall, patients receiving JAK inhibitors exhibited a lower 28-day mortality rate than the control group (risk ratio [RR], 0.60; 95% CI, 0.47–0.77; I2 = 0%). Compared with the control group, the study group also had a lower 14-day mortality rate (RR, 0.60; 95% CI, 0.42–0.85; I2 = 0%), a higher rate of clinical improvement (RR, 1.05; 95% CI, 1.02–1.09; I2 = 0%), and less need of mechanical ventilation or extracorporeal membrane oxygenation (RR, 0.64; 95% CI, 0.50–0.84; I2 = 0%). Finally, JAK inhibitor use was associated with a similar risk of adverse events and infections as that observed in the control group. Conclusions JAK inhibitors can help reduce mortality and improve clinical outcomes among hospitalized patients with COVID-19. Additionally, JAK inhibitors can be used safely in this clinical entity.

Background: In this systematic review and meta-analysis, we aimed to assess the clinical efficacy and safety of cefoperazone–sulbactam against alternative antibiotics in the treatment of intra-abdo...

Objectives: To investigate the clinical efficacy and safety of ceftobiprole for acute bacterial skin and skin structure infections (ABSSSIs).Methods: PubMed, Web of Science, EBSO, Ovid Medline, ClinicalTrial.gov and Cochrane Library were searched until December 25, 2020. Only randomized controlled trials that compared the treatment efficacy of ceftobiprole with that of other antibiotics for adult patients with ABSSSIs were included in this meta-analysis.Results: The 3 RCTs involving 2291 adult patients with ABSSSIs were included. No significant difference in clinical success, as measured by the TOC, was observed between ceftobiprole and comparators among the intention-to-treat population (OR, 1.06; 95% CI, 0.85-1.33; I2 = 0%) and clinical evaluable population (OR, 1.17; 95% CI, 0.76-1.79; I2 = 17%). Ceftobiprole was associated with a similar risk of adverse events (AEs) to that of comparators (treatment-emergent AE [TEAE]: OR, 1.09; 95% CI, 0.92-1.29; I2 = 0%; serious AEs: OR, 0.84; 95% CI, 0.58-1.21; I2 = 0%; treatment discontinuation for TEAE: OR, 0.95; 95% CI, 0.61-1.49; I2 = 0%; death: OR, 0.30; 95% CI, 0.05-1.97; I2 = 0%).Conclusions: Ceftobiprole can achieve similar clinical and microbiological responses as alternative antibiotics in patients with ABSSSIs. In addition, ceftobiprole shares a similar safety profile to comparators.

This study investigated the preventive effects of pro-, pre- and synbiotics on ventilator-associated pneumonia (VAP) among critically ill patients.The PubMed, Web of Science, Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before 19 February 2022. Only randomized controlled trials (RCTs) comparing the clinical efficacy of pro-, pre- and synbiotics with placebos or standard treatments for the prevention of incidental VAP were included.A total of 15 RCTs were included. Patients receiving pro-, pre- and synbiotics had a lower risk than the control group of contracting VAP (risk ratio [RR], 0.70; 95% CI, 0.57-0.85;Pro-, pre- and synbiotics can prevent VAP and the use of probiotics for patients who are critically ill should be supported.

This study investigated the effect of melatonin on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). We searched PubMed, the Web of Science, the Cochrane Library, Ovid MEDLINE, and Clinicaltrials.gov for randomized controlled trials (RCTs) published before September 11, 2021. Only RCTs that compared the clinical efficacy of melatonin with a placebo in the treatment of patients with COVID-19 were included. The primary outcome measure was the clinical recovery rate. We included three RCTs in this meta-analysis. Melatonin 3 mg three times daily was administered in one RCT, and 3 or 6 mg daily before bedtime in the other two trials. Treatment duration was 14 days in two RCTs and 7 days in one trial. The clinical recovery rates were 94.2% (81/86) and 82.4% (70/85) in the melatonin and control groups, respectively. Overall, patients receiving melatonin had a higher clinical recovery rate than did the controls (odds ratio [OR]: 3.67; 95% CI: 1.21-11.12; I

Objectives: This meta-analysis aims to assess the clinical efficacy and safety of ceftaroline in treating acute bacterial infections - community-acquired pneumonia (CAP) and skin and skin structure infection (SSSI) in pediatric patients. Methods: The Pubmed, Embase, ClinicalTrials.gov. and the Cochrane databases were searched up to December 31, 2018. Only randomized controlled trials (RCTs) evaluating ceftaroline and other comparators in the treatment of acute bacterial infection in pediatric patients were included. The primary outcome was the clinical cure rate and the secondary outcome was the risk of adverse event. Results: Three RCTs were included. Overall, ceftaroline had a clinical cure rate at end of therapy (EOT) and test of cure (TOC) similar to comparators in the treatment of acute bacterial infection (at EOT, OR, 1.93; 95% CI, 0.88-4.25, I2 =0%, and at TOC, OR, 1.36; 95% CI, 0.64-2.91, I2 =14%). In addition, ceftaroline had a clinical failure rate at EOT and TOC similar to comparators in the treatment of acute bacterial infection (at EOT, OR, 0.62; 95% CI, 0.22-1.76, I2 =0%, and at TOC, OR, 0.68; 95% CI, 0.24-1.91, I2 =0%). No significant differences were found for the risk of treatment-emergent adverse events (TEAE) in all and different degrees between ceftaroline and comparators (OR, 0.81; 95% CI, 0.37-1.78, I2 =56%). The risks of TEAE and severe adverse events related to study drug were similar between ceftaroline and comparators (TEAE related to study drug, OR, 0.98; 95% CI, 0.52-1.82, I2 =0%, severe adverse event related to study drug, OR, 1.09; 95% CI, 0.22-5.44, I2 =22%). Conclusions: The clinical efficacy of ceftaroline is as good as comparator therapy in the treatment of acute bacterial infections - CAP and SSSI, and this antibiotic is well tolerated as the comparators.

Shen-Peng Chang,1 Hong-Zin Lee,2 Chih-Cheng Lai,3 Hung-Jen Tang4 1Department of Pharmacy, Chi Mei Medical Center, Liouying, Taiwan; 2School of Pharmacy, China Medical University, Taichung, Taiwan; 3Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan; 4Department of Medicine, Chi Mei Medical Center, Tainan, Taiwan Objectives: This meta-analysis aims to assess the clinical efficacy and safety of nemonoxacin in comparison with levofloxacin in treating community-acquired pneumonia (CAP).Materials and methods: The Pubmed, Embase, ClinicalTrials.gov., and the Cochrane databases were searched up to September 2018. Only randomized controlled trials (RCTs) evaluating nemonoxacin and levofloxacin in the treatment of CAP were included. The primary outcome was the clinical cure rate, and the secondary outcomes included the microbiologic response rate and the risk of adverse events.Results: Three RCTs were included. Overall, nemonoxacin and levofloxacin had similar clinical cure rates in the treatment of CAP (OR =1.05, 95% CI =0.67–1.64, I2=0%). Nemonoxacin also had a microbiologic response rate similar to levofloxacin (OR =0.89, 95% CI =0.44–1.81, I2=0%). No significant differences were found in treatment-emergent adverse events between the two drugs (OR =1.08, 95% CI =0.81–1.43, I2=0%). In subgroup analysis, the similarities in the clinical cure rate, microbiologic response rate, and risk of adverse events of these two drugs remained unchanged with the dose of nemonoxacin (500 or 750 mg) and individual pathogens.Conclusion: The clinical and microbiologic efficacy of nemonoxacin is comparable to that of levofloxacin in the treatment of CAP, and this agent is as well tolerated as levofloxacin. Keywords: nemonoxacin, levofloxacin, community-acquired pneumonia &nbsp

This meta-analysis assessed the association between vitamin D supplementation and the outcomes of critically ill adult patients. A literature search was conducted using the PubMed, Web of Science, EBSCO, Cochrane Library, Ovid MEDLINE, and Embase databases until March 21, 2020. We only included randomized controlled trials (RCTs) comparing the efficacy of vitamin D supplementation with placebo in critically ill adult patients. The primary outcome was their 28-day mortality. Overall, 9 RCTs with 1867 patients were included. In the pooled analysis of the 9 RCTs, no significant difference was observed in 28-day mortality between the vitamin D supplementation and placebo groups (20.4% vs 21.7%, OR, 0.73; 95% CI, 0.46–1.15; I2 = 51%). This result did not change as per the method of vitamin D supplementation (enteral route only: 19.9% vs 18.2%, OR, 1.19; 95% CI, 0.88–1.57; I2 = 10%; intramuscular or intravenous injection route: 25.6% vs 40.8%, OR, 0.48; 95% CI, 0.21–1.06; I2 = 19%) or daily dose (high dose: 20.9% vs 19.8%, OR, 0.83; 95% CI, 0.51–1.36; I2 = 53%; low dose: 15.6% vs 21.3%, OR, 0.74; 95% CI, 0.32–1.68; I2 = 0%). No significant difference was observed between the vitamin D supplementation and placebo groups regarding the length of ICU stay (standard mean difference [SMD], − 0.30; 95% CI, − 0.61 to 0.01; I2 = 60%), length of hospital stay (SMD, − 0.17; 95% CI, − 041 to 0.08; I2 = 65%), and duration of mechanical ventilation (SMD, − 0.41; 95% CI, − 081 to 0.00; I2 = 72%). In conclusion, this meta-analysis suggested that the administration of vitamin D did not provide additional advantages over placebo for critically ill patients. However, additional studies are needed to confirm our findings.

Highlights • Systemic review and meta-analysis assessing the efficacy of tocilizumab for treatment of severe COVID-19. • All-cause mortality was similar between tocilizumab and control groups (16.3% vs. 24.1%; RR = 0.62). • Risk of ICU admission was similar between tocilizumab and control groups (35.0% vs. 15.8%; RR = 1.51). • Requirement for mechanical ventilation was similar between tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82). • There is no conclusive evidence that tocilizumab provides any additional benefit to patients with severe COVID-19., This systemic review and meta-analysis aimed to assess the efficacy of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19). Candidate studies up to 24 May 2020 were identified from PubMed, Cochrane Library, Embase, medRxiv and bioRxiv. Treatment outcomes included mortality, risk of intensive care unit (ICU) admission and the requirement for mechanical ventilation (MV). Seven retrospective studies involving 592 adult patients with severe COVID-19, including 240 in the tocilizumab group and 352 in the control group, were enrolled. All-cause mortality of severe COVID-19 patients among the tocilizumab group was 16.3% (39/240), which was lower than that in the control group (24.1%; 85/352). However, the difference did not reach statistical significance [risk ratio (RR) = 0.62, 95% confidence interval (CI) 0.31–1.22; I2 = 68%]. Additionally, risk of ICU admission was similar between the tocilizumab and control groups (35.1% vs. 15.8%; RR = 1.51, 95% CI 0.33–6.78; I2 = 86%). The requirement for MV was similar between the tocilizumab and control groups (32.4% vs. 28.6%; RR = 0.82, 95% CI 0.14–4.94; I2 = 91%). However, these non-significant differences between the tocilizumab and control groups may have been the result of baseline characteristics of the tocilizumab group, which were more severe than those of the control group. Based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19. Therefore, further recommendation of tocilizumab for COVID-19 cases should be halted until high-quality evidence from randomised controlled trials is available.

Objectives This systematic review and meta-analysis of randomized controlled trials (RCTs) investigated whether the clinical efficacy of a 5-day antibiotic course is comparable to that of a longer (≥7 d) course for treating adults with community-acquired bacterial pneumonia (CABP). Methods The PubMed, Web of Science, Cochrane Library, Ovid MEDLINE, and Embase. were searched before January 18, 2020. RCTs comparing the efficacy of a 5-day antibiotic course with a longer course (≥7 d) for CABP treatment were included. Primary outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). Results In this meta-analysis, 7 RCTs were included, and the 5-day antibiotic courses group, and a longer course group comprised 1499 and 1522 patients, respectively. The difference in the overall clinical response rates between the 5-day and longer courses (88.3% vs 88.8%, odds ratio [OR], 0.95, 95% confidence interval [CI], 0.70–1.28, I2 = 19%) was nonsignificant. Additionally, the microbiological eradication rates did not differ significantly between the groups, at 94.8% and 95.8% in the 5-day and longer courses groups, respectively (OR, 0.84, 95% CI, 0.38–1.87, I2 = 0%). Finally, all-cause mortality did not differ between the 2 groups (OR, 0.91, 95% CI, 0.31–2.66, I2 = 0%). Conclusions Five-day treatment and longer antibiotic courses for CABP yield similar clinical and microbiological responses and exhibit similar safety profiles.

Supplemental Digital Content is available in the text, Objectives: This meta-analysis assessed the efficacy and safety of novel β-lactam/β-lactamase inhibitor combinations in the treatment of complicated urinary tract infection (cUTI)/acute pyelonephritis (APN). Methods: PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid MEDLINE, and Embase databases were accessed until November 21, 2019. In this meta-analysis, only randomized controlled trials comparing the treatment efficacy of novel β-lactam/β-lactamase inhibitor combinations with other antibiotics for cUTI/APN in adult patients were included. The outcomes included the clinical and microbiological responses, and risk of adverse events (AEs). Results: Overall, the experimental group treated with a novel β-lactam/β-lactamase inhibitor combination and the control group comprised 1346 and 1376 patients, respectively. No significant difference in the clinical response rate at test-of-cure was observed between the novel β-lactam/β-lactamase inhibitor combination and comparators among the microbiological modified intent-to-treat population (89.1% vs 88.3%, OR, 1.04; 95% confidence interval [CI], 0.76–1.42; I2 = 28%) and the microbiologically evaluable population (95.2% vs 94.7%, OR, 1.12; 95% CI, 0.68–1.84; I2 = 0%). Additionally, the novel β-lactam/β-lactamase inhibitor combination was associated with a better microbiological response at test-of-cure than the comparators among the microbiological modified intent-to-treat population (74.4% vs 68.5%, OR, 1.34; 95% CI, 1.04–1.72; I2 = 45%) and microbiologically evaluable population (80.1% vs 72.5%, OR, 1.49; 95% CI, 1.06–2.10; I2 = 58%). Finally, the risk of AEs associated with the novel β-lactam/β-lactamase inhibitor combination was similar to that associated with the comparators (treatment-emergent adverse events [TEAE], OR, 1.04; 95% CI, 0.87–1.23; I2 = 19%; serious AEs, OR, 1.21; 95% CI, 0.82–1.76; I2 = 0%; treatment discontinuation for drug-related TEAE, OR, 077; 95% CI, 0.38–1.56, I2 = 5%). The all-cause mortality did not differ between the novel β-lactam/β-lactamase inhibitor combination and comparators (OR, 1.19; 95% CI, 0.37–3.81; I2 = 0%). Conclusions: The clinical and microbiological responses of novel β-lactam/β-lactamase inhibitor combinations in the treatment of cUTI/APN are similar to those of other available antibiotics. These combinations also share a safety profile similar to that of other antibiotics.

Background: This study aims to assess the clinical efficacy and safety of omadacycline for the treatment of acute bacterial infections in adult patients through meta-analysis. Methods: PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched up to May 2019. Only randomized controlled trials (RCTs) that evaluated omadacycline and other comparators for treating acute bacterial infections in adult patients were included. The primary outcome was the clinical response rate at the posttreatment evaluation, whereas the secondary outcomes were risk of an adverse event (AE) and mortality. Results: Four RCTs were included. Overall, omadacycline had a clinical response rate noninferior to comparators in the treatment of acute bacterial infection in the modified intent-to-treat population (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04–1.65; I2 = 0%) and in the clinically evaluable population (OR, 1.53; 95% CI, 1.11–2.11; I2 = 0%). Furthermore, no significant differences were found between omadacycline and comparators for the risk of treatment-emergent AEs (OR, 1.13; 95% CI, 0.60–2.14; I2 = 93%), treatment-related AEs (OR, 0.70; 95% CI, 0.46–1.04; I2 = 56%), serious AEs (OR, 1.01; 95% CI, 0.64–1.58; I2 = 0%), and discontinuation of study drug due to an AE (OR, 0.78; 95% CI, 0.47–1.29; I2 = 0%). However, in the clinical trial, NCT02877927, in which omadacycline was used in only oral form, the reported incidence of nausea and vomiting were 30.2% (111/368) and 16.9% (62/368), respectively. Finally, the mortality rate was similar between omadacycline and comparator in the treatment of acute bacterial infection (OR, 1.32; 95% CI, 0.47–3.67; I2 = 0%). Conclusion: The clinical efficacy of omadacycline is not inferior to that of comparators in the treatment of acute bacterial infections in adult patients, and this antibiotic is also well tolerated.

The appropriate timing for initiating renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI) remains unknown. This meta-analysis aims to assess the efficacy of early initiation of RRT in critically ill patients with AKI. The Pubmed, Embase and Cochrane databases were searched up to August 13, 2019. Only randomized controlled trials (RCTs) comparing the effects of early and late RRT on AKI patients were included. The primary outcome was 28-day mortality. Eleven RCTs including 1131 and 1111 AKI patients assigned to early and late RRT strategies, respectively, were enrolled in this meta-analysis. The pooled 28-day mortality was 38.1% (431/1131) and 40.7% (453/1111) in the patients assigned to early and late RRT, respectively, with no significant difference between groups (risk ratio (RR), 0.95; 95% CI, 0.78–1.15, I2 = 63%). No significant difference was found between groups in terms of RRT dependence in survivors on day 28 (RR, 0.90; 95% CI, 0.67–1.25, I2 = 0%), and recovery of renal function (RR, 1.03; 95% CI, 0.89–1.19, I2 = 56%). The early RRT group had higher risks of catheter-related infection (RR, 1.7, 95% CI, 1.01–2.97, I2 = 0%) and hypophosphatemia (RR, 2.5, 95% CI, 1.25–4.99, I2 = 77%) than the late RRT group. In conclusion, an early RRT strategy does not improve survival, RRT dependence, or renal function recovery in critically ill patients with AKI in comparison with a late RRT strategy. However, clinicians should be vigilant because early RRT can carry higher risks of catheter-related infection and hypophosphatemia during dialysis than late RRT.

This meta-analysis assessed the efficacy and safety of novel tetracyclines for treating acute bacterial infections. Data from PubMed, Web of Science, EBSCO, Cochrane databases, Ovid Medline, and Embase databases were accessed until 11 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of novel tetracyclines with that of other antibiotics for treating acute bacterial infections were included. Primary outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of eight RCTs were included, involving 2283 and 2197 patients who received novel tetracyclines and comparators, respectively. Overall, no significant difference was observed in the clinical response rate at test of cure between the experimental and control groups (for modified intent-to-treat [MITT] population, risk ratio [RR]: 1.02, 95% confidence interval [CI]: 0.99&ndash, 1.05, for clinically evaluable [CE] population, RR: 1.02, 95% CI: 1.00&ndash, 1.04, and for microbiological evaluable [ME] population, RR: 1.01, 95% CI: 0.99&ndash, 1.04). No significant difference in the microbiological response at the end of treatment was observed between the experimental and control groups (for ME population, RR: 1.01, 95% CI: 0.99&ndash, 1.03, for microbiological MITT population, RR: 1.01, 95% CI: 0.96&ndash, 1.07). No difference was observed concerning the risk of treatment-emergent adverse events (TEAEs), serious adverse events, and discontinuation of treatment due to TEAEs and all-cause mortality between the two groups. In conclusion, clinical efficacy and safety profile for novel tetracyclines in the treatment of acute bacterial infections were found to be similar to those for other available antibiotics.

Background and objectives: High-flow nasal cannula (HFNC) can be used as a respiratory support strategy for patients with acute respiratory failure (ARF). However, no clear evidence exists to support or oppose HFNC use in immunocompromised patients. Thus, this meta-analysis aims to assess the effects of HFNC, compared to conventional oxygen therapy (COT) and noninvasive ventilation (NIV), on the outcomes in immunocompromised patients with ARF. The Pubmed, Embase and Cochrane databases were searched up to November 2018. Materials and Methods: Only clinical studies comparing the effect of HFNC with COT or NIV for immunocompromised patients with ARF were included. The outcome included the rate of intubation, mortality and length of stay (LOS). Results: A total of eight studies involving 1433 immunocompromised patients with ARF were enrolled. The pooled analysis showed that HFNC was significantly associated with a reduced intubation rate (risk ratio (RR), 0.83, 95% confidence interval (CI), 0.74&ndash, 0.94, I2 = 0%). Among subgroup analysis, HFNC was associated with a lower intubation rate than COT (RR, 0.86, 95% CI, 0.75&ndash, 0.95, I2 = 0%) and NIV (RR, 0.59, 95% CI, 0.40&ndash, 0.86, I2 = 0%), respectively. However, there was no significant difference between HFNC and control groups in terms of 28-day mortality (RR, 0.78, 95% CI, 0.58&ndash, 1.04, I2 = 48%), and intensive care unit (ICU) mortality (RR, 0.87, 95% CI, 0.73&ndash, 1.05, I2 = 57%). The ICU and hospital LOS were similar between HFNC and control groups (ICU LOS: mean difference, 0.49 days, 95% CI, &minus, 0.25&ndash, 1.23, I2 = 69%, hospital LOS: mean difference, &minus, 0.12 days, 1.86&ndash, 1.61, I2 = 64%). Conclusions: Use of HFNC may decrease the intubation rate in immunocompromised patients with ARF compared with the control group, including COT and NIV. However, HFNC could not provide additional survival benefit or shorten the LOS. Further large, randomized controlled trials are needed to confirm these findings.

“Physical restraint” formerly used as a measure of protection for psychiatric patients is now widely used. However, existing studies showed that physical restraint not only has inadequate effect of protection but also has negative effects on residents. To analyzes the impact of educational program on the physical restraint use in long-term care facilities. Design: A systematic review with meta-analysis and meta-regression. Eight databases, including Cochrane Library, ProQuest, PubMed, EMBASE, EBSCO, Web of Science, Ovid Medline and Physiotherapy Evidence Database (PEDro), were searched up to January 2017. Eligible studies were classified by intervention and accessed for quality using the Quality Assessment Tool for quantitative studies. Sixteen research articles were eligible in the final review; 10 randomize control trail studies were included in the analysis. The meta-analysis revealed that the use of physical restraint was significantly less often in the experimental (education) group (OR = 0.55, 95% CI: 0.39 to 0.78, p < 0.001) compared to the control group. Meta-regression revealed the period of post education would have decreased the effect of the restraint educational program (β: 0.08, p = 0.002); instead, the longer education period and more times of education would have a stronger effect of reducing the use of physical restraint (β: −0.07, p < 0.001; β: −0.04, p = 0.056). The educational program had an effect on the reduced use of physical restraint. The results of meta-regression suggest that long-term care facilities should provide a continuous education program of physical restraint for caregivers.

This study aims to assess the clinical efficacy and safety of ceftaroline for the treatment of complicated skin and skin structure infections (cSSSIs) in adult patients through meta-analysis. PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched up to April 2019. Only randomized controlled trials (RCTs) that evaluated ceftaroline and other comparators for treating cSSSIs in adult patients were included. The primary outcome was the clinical cure rate, whereas the secondary outcomes were clinical failure rate, microbiological eradication rate, relapse rate, and risk of an adverse event (AE). Five RCTs were included. Overall, ceftaroline had a clinical cure rate similar to comparators in the treatment of cSSSIs in the modified intent-to-treat population (risk ratio (RR), 1.00, 95% confidence interval (CI), 0.97&ndash, 1.04, I2 = 0%) and in the clinically evaluable population (RR, 1.00, 95% CI, 0.97&ndash, 1.03, I2 = 0%). In addition, no significant difference was observed between ceftaroline and comparators for the treatment of infection with Staphylococcus aureus (RR, 1.01, 95% CI, 0.98&ndash, 1.05, I2 = 0%), methicillin-resistant S. aureus (RR, 0.99, 95% CI, 0.94&ndash, I2 = 0%), methicillin-susceptible S. aureus (RR, 1.01, 95% CI, 0.96&ndash, 1.06, I2 = 26%), Streptococcus spp. (RR, 1.07, 95% CI, 0.92&ndash, 1.24, I2 = 73%), and Gram-negative bacteria (RR, 0.94, 95% CI, 0.83&ndash, 1.08, I2 = 0%). Furthermore, ceftaroline had a similar rate of microbiological eradication (92.2% vs. 92.6%, RR, 1.00, I2 = 9%) and relapse (6.9% vs. 9.1%, RR, 0.48, 95% CI, 0.14&ndash, 1.74, I2 = 0%) as comparators. Finally, the risks of treatment-emergent AEs (RR, 0.96, 95% CI, 0.88&ndash, I2 = 0%), serious AEs (RR, 1.03, 95% CI, 0.63&ndash, 1.68, I2 = 0%), and discontinuation of study drug due to an AE (RR, 0.86, 95% CI, 0.50&ndash, 1.49, I2 = 34%) did not differ significantly between ceftaroline and comparators. In conclusion, the clinical efficacy of ceftaroline is as high as that of comparators in the treatment of cSSSIs in adult patients, and this antibiotic is well tolerated like the comparators.

Shao-Huan Lan,1 Chih-Cheng Lai,2 Li-Chin Lu,3 Shen-Peng Chang,4 Hui-Ting Huang41School of Pharmaceutical Sciences and Medical Technology, Putian University, Putian, People’s Republic of China; 2Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan; 3School of Management, Putian University, Putian, People’s Republic of China; 4Department of Pharmacy, Chi Mei Medical Center, Liouying, TaiwanPurpose: To assess the clinical efficacy and safety of delafloxacin for treating acute bacterial skin and skin structure infections (ABSSSIs) in adult patients.Patients and methods: The Cochrane Library, EBSCO, EMBASE, Ovid Medline, PubMed, and Web of Science databases were searched up to November 2018. Only randomized controlled trials (RCTs) that evaluated delafloxacin and other comparators for the treatment of ABSSSIs were included. The primary outcome was the clinical cure rate and the secondary outcomes were microbiological response and the risk of adverse events.Results: Four RCTs were included. Overall, delafloxacin exhibited a clinical cure rate similar to the rates of the comparator drugs in the treatment of ABSSSI (OR, 1.05; 95% CI, 0.87–1.27, I2,=16%) and methicillin-resistant Staphylococcus aureus (MRSA)-associated ABSSSI (OR, 1.12; 95% CI, 0.71–1.77, I2,=0%). Delafloxacin had a microbiological eradication (documented and presumed) rate similar to the rates of the comparators in the treatment of ABSSSI (OR, 1.21; 95% CI, 0.58–2.50, I2,=0%) and MRSA-associated ABSSSIs (OR, 1.16; 95% CI, 0.37–3.60, I2,=0%). Delafloxacin and the comparators did not differ significantly in the risk of serious adverse events (AEs), treatment-emergent adverse events (TEAEs), and TEAEs related to the study drug. However, the risk of discontinuation of the study drug due to an AE was lower for delafloxacin than for the comparators (OR, 0.33; 95% CI, 0.15–0.74, I2,=0%).Conclusion: The clinical efficacy of delafloxacin is as high as that of the comparator drugs in the treatment of ABSSSI, including MRSA-associated infections; furthermore, this antibiotic is as well-tolerated as the comparators.Keywords: delafloxacin, acute bacterial skin and skin structure infections, MRSA, efficacy, safety

Purpose This meta-analysis assessed the clinical efficacy and safety of cefoperazone-sulbactam for empiric therapy febrile neutropenia. Methods The PubMed, Web of Science, EBSCO, Cochrane Library, Ovid Medline, EMBASE, and ClinicalTrial.gov database were searched through May 10, 2019. Only clinical trials comparing cefoperazone-sulbactam with other antibiotics for empiric treatment of febrile neutropenia were included. The primary outcome was treatment success without modification, and the secondary outcomes were all-cause mortality and adverse events (AEs). Results Ten randomized controlled trials (RCTs) and 1 retrospective cohort study were included. Overall, cefoperazone-sulbactam exhibited a treatment success rate similar to those of comparator drugs for the treatment of febrile neutropenia (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.85 to 1.24, I = 0%). A similar finding was noted in pooled analysis of 10 RCTs (OR, 1.07; 95% CI, 0.88 to 1.30, I = 0%). Subgroup analysis showed that cefoperazone-sulbactam had a treatment success rate similar to the rates of comparators for adults (OR, 1.10; 95% CI, 0.88 to 1.38, I = 0%) and children (OR, 0.96; 95% CI, 0.63 to 1.46, I = 0%). Cefoperazone-sulbactam did not differ significantly from comparators in the risks of all-cause mortality (OR, 0.96; 95% CI, 0.58 to 1.58, I = 0%) or common AEs, namely rash, nausea/vomiting, and superinfection. Conclusion The clinical efficacy and tolerability of cefoperazone-sulbactam are comparable to those of comparator drugs in the treatment of febrile neutropenia.

A majority of patients with diabetes have trigger digits. Initial management of symptomatic trigger digits commonly involves corticosteroid injection. However, varying outcomes have been reported for patients with diabetes who receive corticosteroid injections. The authors conducted a meta-analysis to evaluate the effect of diabetes on outcome after corticosteroid injection for trigger digit. PubMed and other Internet databases were searched for the period 1977 to 2015. Five articles, involving 381 diabetic digits and 449 non-diabetic digits, were included in the meta-analysis. The authors found treatment failure rates of 78% for patients with insulin-dependent diabetes, 47% for patients with non–insulin-dependent diabetes, and 49% for patients without diabetes when a single injection of corticosteroid was administered for trigger digit. After 3 injections, the failure rates were 57%, 39%, and 30%, respectively. The pooled data showed that patients with insulin-dependent diabetes and patients with non–insulin-dependent diabetes had worse prognoses after corticosteroid injection for trigger digit than patients without diabetes. Furthermore, the patients with insulin-dependent diabetes had a trend toward multiple digit involvement and much worse treatment outcomes than the patients with non–insulin-dependent diabetes. The authors conclude that more aggressive treatment, such as surgical intervention, should be considered for those patients expected to have high failure rates after injection. [ Orthopedics. 2018; 41(1):e8–e14.]

This meta-analysis aims to assess the efficacy and safety of tedizolid, compared to linezolid, in the treatment of acute bacterial skin and skin structure infection (ABSSSI). PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid Medline and Embase databases were accessed until 18 July 2019. Only randomized controlled trials (RCTs) comparing the efficacy of tedizolid with linezolid for adult patients with ABSSSIs were included. The outcomes included the clinical response, microbiological response, and risk of adverse events (AEs). A total of four RCTs involving 2056 adult patients with ABSSSI were enrolled. The early clinical response rate was 79.6% and 80.5% for patients receiving tedizolid and linezolid, respectively. The pooled analysis showed that tedizolid had a non-inferior early clinical response rate to linezolid (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.77&ndash, 1.19, I2 = 0%). The early response rate was similar between tedizolid and linezolid among patients with cellulitis/erysipelas (75.1% vs. 77.1%, OR = 0.90, 95% CI = 0.64&ndash, 1.27, I2 = 25%), major cutaneous abscess (85.1% vs. 86.8%, OR = 0.93, 95% CI = 0.42&ndash, 2.03, I2 = 37%) and wound infection (85.9% vs. 82.6%, OR = 1.29, 95% CI = 0.66&ndash, 2.51, I2 = 45%). For methicillin-resistant Staphylococcus aureus patients, tedizolid had a favorable microbiological response rate of 95.2% which was comparable to linezolid (94%) (OR = 1.19, 95% CI = 0.49&ndash, 2.90, I2 = 0%). In addition to the similar risk of treatment-emergent AEs (a serious event, the discontinuation of the study drug due to AEs and mortality between tedizolid and linezolid), tedizolid was associated with a lower risk of nausea, vomiting and abnormal neutrophil count than linezolid. In conclusion, once-daily tedizolid (200 mg for six days) compared to linezolid (600 mg twice-daily for 10 days) was non-inferior in efficacy in the treatment of ABSSSI. Besides, tedizolid was generally as well tolerated as linezolid, and had a lower incidence of gastrointestinal AEs and bone marrow suppression than linezolid.

This study aims to assess the clinical efficacy and safety of eravacycline for treating complicated intra-abdominal infection (cIAI) in adult patients. The PubMed, Web of Science, EBSCO, Cochrane databases, Ovid Medline, Embase, and ClinicalTrials.gov were searched up to May 2019. Only randomized controlled trials (RCTs) that evaluated eravacycline and other comparators for the treatment of cIAI were included. The primary outcome was the clinical cure rate at the test-of-cure visit based on modified intent-to-treat population, microbiological intent-to-treat population, clinically evaluable population, and microbiological evaluable population, and the secondary outcomes were clinical failure rate and the risk of adverse event. Three RCTs were included. Overall, eravacycline had a clinical cure rate (88.7%, 559/630) at test-of-cure in modified intent-to-treat population similar to comparators (90.1%, 492/546) in the treatment of cIAIs (risk ratio (RR), 0.99, 95% confidence interval (CI), 0.95&ndash, 1.03, I2 = 0%, Figure 3). In the microbiological intent-to-treat, clinically evaluable, and microbiological evaluable populations, no difference was found between eravacycline and comparators in terms of clinical cure rate at test-of-cure (microbiological intent-to-treat population, RR, 0.99, 95% CI, 0.95&ndash, 1.04, I2 = 0%, clinically evaluable population, RR, 1.00, 95% CI, 0.97&ndash, I2 = 0%, microbiological evaluable population, RR, 0.98, 1.02, I2 = 0%). In addition, eravacycline had clinical failure rate similar to comparators at test-of-cure in modified intent-to-treat population (RR, 1.01, 95% CI, 0.61&ndash, 0.69, I2 = 0%), microbiological intent-to-treat population (RR, 1.34, 95% CI, 0.77&ndash, 2.31, I2 = 16%), clinically evaluable population (RR, 1.03, 1.76, I2 = 0%), and microbiological evaluable population (RR, 1.32, 95% CI, 0.75&ndash, 2.32, I2 = 10%). Although eravacycline was associated with higher risk of treatment-emergent adverse event than comparators (RR, 1.34, 95% CI, 1.13&ndash, 1.58, I2 = 0%), no significant differences were found between eravacycline and comparators for the risk of serious adverse event (RR, 1.04, 95% CI, 0.65&ndash, 1.65, I2 = 0%), discontinuation of study drug because of adverse event (RR, 0.68, 95% CI, 0.23&ndash, 1.99, I2 = 13%), and all-cause mortality (RR, 1.09, 95% CI, 0.41&ndash, 2.9, I2 = 28%). In conclusion, the clinical efficacy of eravacycline is as high as that of the comparator drugs in the treatment of cIAIs and this antibiotic is as well tolerated as the comparators.

This study aimed to compare the clinical efficacy and safety of ceftaroline with those of ceftriaxone for treating community-acquired pneumonia (CAP). The PubMed, Cochrane Library, Embase, and clinicalTrials.gov databases were searched until April 2019. This meta-analysis only included randomized controlled trials (RCTs) that evaluated ceftaroline and ceftriaxone for the treatment of CAP. The primary outcome was the clinical cure rate, and the secondary outcome was the risk of adverse events (AEs). Five RCTs were included. Overall, at the test of cure (TOC), the clinical cure rate of ceftaroline was superior to the rates of ceftriaxone for the treatment of CAP (modified intent-to-treat population (MITT) population, odds ratio (OR) 1.61, 95% confidence interval (CI) 1.31&ndash, 1.99, I2 = 0%, clinically evaluable (CE) population, OR 1.38, 95% CI 1.07&ndash, 1.78, I2 = 14%). Similarly, the clinical cure rate of ceftaroline was superior to that of ceftriaxone at the end of therapy (EOT) (MITT population, OR 1.57, 95% CI 1.16&ndash, 2.11, I2 = 0%, CE population, OR 1.64, 95% CI 1.15&ndash, 2.33, I2 = 0%). For adult patients, the clinical cure rate of ceftaroline remained superior to that of ceftriaxone at TOC (MITT population, OR 1.66, 95% CI 1.34&ndash, 2.06, I2 = 0%, CE population, OR 1.39, 95% CI 1.08&ndash, 1.80, I2 = 30%) and at EOT (MITT population, OR 1.64, 95% CI 1.20&ndash, 2.24, I2 = 0%, CE population, OR 1.65, 95% CI 1.15&ndash, 2.36, I2 = 0%). Ceftaroline and ceftriaxone did not differ significantly in the risk of serious AEs, treatment-emergent AEs, and discontinuation of the study drug owing to an AE. In conclusion, the clinical efficacy of ceftaroline is similar to that of ceftriaxone for the treatment of CAP. Furthermore, this antibiotic is as tolerable as ceftriaxone.

Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is one of the active constituents from the root and rhizome of Rheum palmatum. Our previous study has demonstrated that aloe-emodin induced a significant change in the expression of lung cancer cell apoptosis-related proteins compared to those of control cells. However, the molecular mechanisms underlying the biological effects of aloe-emodin still remain unknown. Based on these reasons, we were interested in the change of aloe-emodin–induced total protein expression by the proteomics technique during aloe-emodin–induced lung cancer cell apoptosis. Our study applied 2D electrophoresis to analyze the proteins involved in aloe-emodin–induced apoptosis in H460 cells. We found that the release of nucleophosmin from the nucleus to the cytosol and the degradation of nucleophosmin were associated with aloe-emodin–induced H460 cell apoptosis. Our study also demonstrated that the gene expression of nucleophosmin remained unchanged after treatment with aloe-emodin. The aloe-emodin–caused increase in the amount of proform and fragment of nucleophosmin in cytoplasm may be one of the important events for aloe-emodin–induced H460 cell apoptosis. © 2004 Wiley-Liss, Inc.