Is moderate resistance training adequate for older adults with sarcopenia? A systematic review and network meta-analysis of RCTs.

BACKGROUND: Resistance training (RT) and nutritional supplementation are recommended for the management of sarcopenia in older adults. However, optimal RT intensity for the treatment of sarcopenia has not been well investigated. METHODS: This network meta-analysis aims to determine the comparative effectiveness of interventions for sarcopenia, taking RT intensity into consideration. RT intensity was classified into light-to-moderate intensity RT(LMRT), moderate intensity RT(MRT), and moderate-to-vigorous intensity RT(MVRT) based on percentage of one repetition maximum (%1RM) and/or rating of perceived exertion. RESULTS: A total of 50 RCTs (N = 4,085) were included after screening 3,485 articles. The results confirmed that RT with or without nutrition was positively associated with improved measures of muscle strength and physical performance. Regarding RT intensity, LMRT only demonstrated positive effects on hand grip (aerobic training + LMRT + nutrition: mean difference [MD] = 2.88; 95% credential intervals [CrI] = 0.43,5.32). MRT provided benefits on improvement in the 30-s chair stand test (repetitions) (MRT: MD = 2.98, 95% CrI = 0.35,5.59), timed up and go test (MRT: MD = -1.74, 95% CrI: = -3.34,-0.56), hand grip (MRT: MD = 2.44; 95% CrI = 0.03,5.70), and leg press (MRT: MD = 8.36; 95% CrI = 1.87,13.4). MVRT also improved chair stand test repetitions (MVRT: MD = 5.64, 95% CrI = 0.14,11.4), gait speed (MVRT + nutrition: MD = 0.21, 95% CrI = 0.003,0.48), appendicular skeletal muscle index (MVRT + nutrition: MD = 0.25, 95% CrI = 0.01,0.5), and leg press (MVRT: MD = 14.7, 95% CrI: 5.96,22.4; MVRT + nutrition: MD = 17.8, 95% CrI: 7.55,28.6). CONCLUSION: MVRT had greater benefits on muscle mass, lower extremity strength, and physical performance compared to MRT. Increasing RT intensity may be recommended for sarcopenic older adults.

Comparison of clinically indicated replacement and routine replacement of peripheral intravenous catheters: A systematic review and meta-analysis of randomized controlled trials.

Background: It is unknown whether clinically indicated replacement of peripheral intravenous catheters (PIVCs) increases the risks of PIVC-associated complications and infections compared to routine replacement of PIVCs. Methods: We searched PubMed, the Web of Science, the Cochrane Library, Ovid MEDLINE, and Clinicaltrials.gov for randomized controlled trials (RCTs) that compare the safety outcomes of routine replacement and clinically indicated replacement of PIVCs were included for meta-analysis. The primary outcome was the incidence of phlebitis, and secondary outcomes included the risks of occlusion, local infection, infiltration, catheter-related bloodstream infection (CRBSI), and accidental removal of the PIVC. Results: A total of 9 RCTs involving 10 973 patients were included in this meta-analysis, of whom 5,546 and 5,527 were assigned to the study group (clinically indicated replacement of PIVCs) and control group (routine replacement of PIVCs every 72-96 h), respectively. The incidence of phlebitis in the study group was significantly higher than that in the control group [risk ratio (RR), 1.20; 95% confidence interval (CI), 1.01-1.44, P = 0.04, I2 = 49%]. In addition, the study group was associated with a higher risk of occlusion (RR, 1.45; 95% CI, 1.08-1.95, P = 0.01, I2 = 82%) and infiltration (fluid leaks) (RR, 1.27; 95% CI, 1.06-1.53, P = 0.01, I2 = 72%) than the control group. However, no significant differences were observed in the risks of local infection (RR, 1.75; 95% CI, 0.38-8.16, P = 0.48, I2 = 0%) and CRBSI (RR, 0.61; 95% CI, 0.08-4.68, P = 0.64, I2 = 0%) between the study and control groups. Conclusion: The clinically indicated replacement of PIVCs may increase the risks of PIVC-associated phlebitis, infiltration, and occlusion compared to the routine replacement of PIVCs, but did not increase the risk of PIVC-associated infections. Based on these findings, routine replacement of PIVCs every 72-96 h maybe a preferred option than clinically indicated replacement of PIVCs. Systematic review registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022302021].

The effect of intravenous immunoglobulins on the outcomes of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Severe-to-critical COVID-19 has been associated with exaggerated immune responses, and anti-inflammatory agents including corticosteroid and interleukin-6 antagonist have been repurposed as the treatment modality against severe SARS-CoV-2 infections. However, the clinical efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of patients with COVID-19 was controversial. METHODS: This meta-analysis of randomized controlled trials (RCTs) investigated the effectiveness of IVIG in patients with COVID-19. Electronic databases were searched for RCTs that compared the clinical efficacy of IVIG with standard of care or placebo in the hospitalized patients with COVID-19 were included. RESULTS: Six RCTs involving 472 patients were included. Patients who received IVIG had a similar mortality rate to the controls (25.3% vs 27.0%, odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27-1.31). Compared with the control group, the study group demonstrated a similar incidence of receiving mechanical ventilation (OR, 0.70; 95% CI, 0.45-1.11), intensive care unit (ICU) admission (OR, 0.58; 95% CI, 0.22-1.53), length of hospital stay (mean difference [MD], -1.81 days; 95% CI, -8.42 to 4.81) and ICU stay (MD, -0.61 days; 95% CI, -2.80 to 1.58). CONCLUSIONS: The administration of IVIG in hospitalized patients with COVID-19 does not improve clinical outcomes.

The clinical efficacy and safety of mesenchymal stromal cells for patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This meta-analysis of randomized controlled trials (RCTs) investigated the usefulness of mesenchymal stromal cells (MSCs) to treat patients with COVID-19. METHODS: PubMed, Embase, Ovid MEDLINE, the Cochrane Library, and Clinicaltrials.gov were searched for RCTs published before November 7, 2021. Only RCTs that compared the clinical efficacy and safety of MSCs with other alternative treatments or placebos in the treatment of patients with COVID-19 were included. RESULTS: Six RCTs were included, in which the MSC and control groups consisted of 158 and 135 patients, respectively. The patients who received MSCs had a significantly lower 28-day mortality rate (7.6% vs 21.5%; OR, 0.18; 95% CI, 0.06-0.52; I2 = 0%) and significantly higher clinical improvement rate (OR, 6.05; 95% CI, 2.31-15.83; I2 = 0%) than the controls. The patients who received MSCs were associated with a similar risk of adverse events (AEs) and serious AEs to the control group (AEs: OR, 33; 95% CI, 0.09-1.18; I2 = 59%; serious AEs: OR, 0.30; 95% CI, 0.02-4.41; I2 = 53%). CONCLUSIONS: MSC treatment may help to improve the clinical outcomes of patients with COVID-19. In addition, MSC treatment appears to be a safe therapeutic option for patients with COVID-19.

Comparative safety of immune checkpoint inhibitors and chemotherapy in advanced non-small cell lung cancer: A systematic review and network meta-analysis.

BACKGROUNDS: Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy (CT) are the standard of care for first-line therapy in metastatic non-small cell lung cancer (NSCLC) patients without actionable mutations. The safety ranking of different ICI and CT combination regimens has not been investigated. This study was aimed to provide a toxicity profile and safety ranking of different ICI and CT combination regimens. METHODS: We performed comprehensive searches of phase 2 and 3 randomized clinical trials (RCTs) comparing different ICI regimens (alone or combination) or CT for the first-line treatment of advanced NSCLC. Outcomes of interest were the cumulative incidence of any treatment-related adverse events (TRAEs), grade 3-5 TRAEs (grade 3-5), any immune-related adverse events (irAEs), and grade 3-5 irAEs (grade 3-5). Odds ratios and 95% credible intervals were calculated as summary statistics to quantify the effect of different ICI combination regimens. RESULTS: We included 21 RCTs from 2016 to 2021 with a total of 12,626 patients. The incidence of any TRAEs and grade 3-5 TRAEs ranked from high to low were ICI-CT (probability: 88.3% and 87.1%), ICI-ICI-CT (66.2% and 73.9%), CT alone (77.7% and 86.6%), ICI-ICI (98.9% and 99.2%), and ICI monotherapy (99.7% and 100%). Adding CT to ICI regimens resulted in a higher incidence of any grade or grade 3-5 TRAEs compared to ICI-ICI combinations or ICI monotherapy. However, ICI-ICI-CT combinations did not result in a higher incidence of TRAEs than ICI-CT combinations. For any irAEs and grade 3-5 irAEs, the ranking was ICI-ICI (probability: 97.6% and 99.8%), ICI monotherapy (97.2% and 99.8%), ICI-CT (99.5% and 99.9%), and CT alone (99.9% and 100%). Notably, the incidence of any grade and grade 3-5 irAEs was lower when adding CT to ICI monotherapy. CONCLUSION: Lack of head-to-head comparisons, these findings provide evidence for clinical decision-making when considering different ICI combination regimens for advanced NSCLC patients.

Effect of sofosbuvir-based treatment on clinical outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials.

This systematic review and meta-analysis examined the efficacy of sofosbuvir-based antiviral treatment against COVID-19 (coronavirus disease 2019). PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched from inception to 15 August 2021. Studies comparing the clinical efficacy and safety of sofosbuvir-based antiviral regimens (study group) with other antivirals or standard of care (control group) in patients with COVID-19 were included. Overall, 687 patients with COVID-19 were included, of which 377 patients received sofosbuvir-based treatment. Mortality was lower in the study group than in the control group [odds ratio (OR) = 0.49, 95% confidence interval (CI) 0.30-0.79; I2 = 0%]. The overall clinical recovery rate was higher in the study group than in the control group (OR = 1.82, 95% CI 1.20-2.76; I2 = 28%). The study group presented a lower requirement for mechanical ventilation (OR = 0.33, 95% CI 0.13-0.89; I2 = 0%) and intensive care unit admission (OR = 0.42, 95% CI 0.25-0.70; I2 = 0%) than the control group. Furthermore, the study group exhibited a shorter hospital length of stay [mean deviation (MD), -1.49, 95% CI -2.62 to -0.37; I2 = 56%] and recovery time (MD, -1.34, 95% CI -2.29 to -0.38; I2 = 46%) than the control group. Sofosbuvir-based treatment may help reduce mortality in patients with COVID-19 and improve associated clinical outcomes. Furthermore, sofosbuvir-based treatment was as safe as the comparator in patients with COVID-19. However, further large-scale studies are warranted to validate these findings.

Clinical efficacy and safety of novel lipoglycopeptides in the treatment of acute bacterial skin and skin structure infections: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of novel lipoglycopeptides in treating acute bacterial skin and skin structure infections (ABSSSIs). RESEARCH DESIGN AND METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov were searched from inception to 20 May 2021. Randomized controlled trials (RCTs) comparing the clinical efficacy and safety of lipoglycopeptides with other comparators in treating adult patients with ABSSSIs were included. The primary outcome was clinical response. RESULTS: Eight RCTs (6416 patients; lipoglycopeptides: 3359, comparators: 3057) were enrolled. Clinical response rate was not significantly different between lipoglycopeptides and comparators at early-clinical-evaluation (odds ratio [95% confidence interval]: 1.01 [0.85-1.20], I2 = 34%), end-of-treatment (0.94 [0.80-1.11], I2 = 0%), and test-of-cure (1.05 [0.85-1.30], I2 = 0%). Lipoglycopeptides showed a similar overall microbiological eradication rate (1.12 [0.90-1.38], I2 = 21%) but a borderline higher microbiological eradication rate for methicillin-resistant Staphylococcus aureus (1.37 [1.00-1.86], I2 = 0%) than the comparators. Lipoglycopeptides were not associated with a higher risk than comparators. CONCLUSIONS: Lipoglycopeptides can achieve similar clinical and microbiological responses to other comparators in treating ABSSSIs. In addition, lipoglycopeptides are as tolerable as their comparators.

Clinical efficacy and safety of interferon-ß-containing regimens in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this systematic review and meta-analysis of randomized controlled trials(RCTs) was to investigate the efficacy of interferon (IFN)-ß-containing regimens in treating patients with COVID-19. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to 17 July 2021. RCTs comparing the clinical efficacy and safety of IFN-ß-containing regimens (study group) to other antiviral treatment options or placebo (control group) in treating patients with COVID-19 were included. RESULTS: Eight RCTs were included. No significant difference in the 28-day all-cause mortality rate was observed between the study and control groups (OR, 0.74; 95% CI, 0.44-1.24; I2 = 51%). The study groups had a lower rate of intensive care unit (ICU) admissions than the control groups (OR 0.58, 95% CI 0.36-0.95; I2 = 0%). Furthermore, INF-ß was not associated with an increased risk of any adverse event (AE) or serious AE when compared with the control group. CONCLUSIONS: IFN-ß does not appear to provide an increased survival benefit in hospitalized patients with COVID-19 but may help reduce the risk of ICU admission. Moreover, IFN-ß is a safe agent for use in the treatment of COVID-19.

Clinical efficacy and safety of Janus kinase inhibitors for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of Janus kinase (JAK) inhibitors for COVID-19 patients. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to July 12, 2021. RCTs comparing the clinical efficacy and safety of JAK inhibitors with a placebo or standard care in treating COVID-19 patients were included. The primary outcome was all-cause mortality rate at day 28. RESULTS: Three RCTs were included in this meta-analysis. The all-cause mortality rate at day 28 was lower among the patients receiving JAK inhibitors than among the controls (4.1% [28/647] versus 7.0% [48/684], OR, 0.57; 95% CI, 0.36-0.92, I2 = 0). The clinical recovery rate was higher among the patients receiving JAK inhibitors than among the controls (85.1% (579/680) versus 80.0% [547/684], OR, 1.45; 95% CI, 1.09-1.93, I2 = 0). Additionally, the use of JAK inhibitors was associated with a shorter time to recovery than among the controls (MD, -2.84; 95% CI, -5.56 to -0.12; I2 = 50%). The rate of invasive mechanical ventilation (MV) was lower in the patients who used JAK inhibitors than among the controls. Finally, no significant difference was observed between the patients who used JAK inhibitors and the controls in the risk of any adverse events (OR, 0.92; 95% CI, 0.64-1.34; I2 = 33%) and serious adverse events (OR, 0.80; 95% CI, 0.45-1.44; I2 = 46%). CONCLUSIONS: JAK inhibitors can lead to a better clinical outcome of hospitalized COVID-19 patients, and they are a safe agent in the treatment of COVID-19.

Anti-MRSA Cephalosporin versus Vancomycin-Based Treatment for Acute Bacterial Skin and Skin Structure Infection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis of randomized controlled trials (RCTs) compared the clinical efficacy and safety of anti-MRSA cephalosporin and vancomycin-based treatment in treating acute bacterial skin and skin structure infections (ABSSSIs). PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov databases were searched for relevant articles from inception to 15 June 2020. RCTs comparing the clinical efficacy and safety of anti-MRSA cephalosporin with those of vancomycin-based regimens in treating adult patients with ABSSSIs were included. The primary and secondary outcomes were clinical response at the test-of-cure assessments and risk of adverse events (AEs), respectively. Eight RCTs were enrolled. The clinical response rate was not significantly different between anti-MRSA cephalosporin and vancomycin-based treatments (odds ratio [OR], 1.05; 95% CI, 0.90-1.23; I2 = 0%). Except for major cutaneous abscesses in which anti-MRSA cephalosporin-based treatment was associated with a lower clinical response rate than vancomycin-based treatment (OR, 0.62; 95% CI, 0.40-0.97; I2 = 0%), other subgroup analyses according to the type of cephalosporin (ceftaroline or ceftobiprole), type of infection, and different pathogens did not show significant differences in clinical response. Anti-MRSA cephalosporin-based treatment was only associated with a higher risk of nausea than vancomycin-based treatment (OR, 1.41; 95% CI, 1.07-1.85; I2 = 0%). In treating ABSSSIs, the clinical efficacy of anti-MRSA cephalosporin is comparable to that of vancomycin-based treatment, except in major cutaneous abscesses. In addition to nausea, anti-MRSA cephalosporin was as tolerable as vancomycin-based treatment.

Chemotherapy or chemo-immunotherapy as first-line treatment for extensive-stage small-cell lung cancer: a meta-analysis.

This meta-analysis investigated the clinical benefits of chemo-immunotherapy in extensive-stage small-cell lung cancer (ES-SCLC). Seven randomized controlled trials with a total of 2862 patients were analyzed. Compared with chemotherapy alone, chemo-immunotherapy provided a better progression-free survival (PFS) with a hazard ratio (HR) of 0.81, p < 0.00001, and overall survival (OS) with a HR of 0.82, p < 0.0001; however, the incidence of treatment-related adverse effects (TRAEs) was significantly increased. Subgroup analyses showed that good performance status, cisplatin-based chemotherapy, without brain metastases at baseline and non-Asian populations were associated with greater benefits in OS from chemo-immunotherapy. Chemo-immunotherapy demonstrated better PFS and OS compared with chemotherapy alone as first line treatment in ES-SCLC, but additional TRAEs should be closely monitored.

Lung cancer is the leading cause of cancer deaths worldwide, of which small-cell lung cancer (SCLC) is an extremely lethal type, because most patients present with incurable, extensive-stage SCLC (ES-SCLC). The standard first-line treatment for ES-SCLC for the last 30 years has been chemotherapy. Immunotherapies have recently been introduced as cancer treatments, and have shown the potential to provide a higher and more durable treatment response with relatively tolerable toxicity. This study systematically assessed the results of previous research and provided evidence that add-on immunotherapy with standard chemotherapy as the first line treatment in ES-SCLC offered great improvement in survival, but patients should be closely monitor for additional side effects.

LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis.

BACKGROUND: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting ß2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. METHODS: We searched several databases and manufacturers' websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. RESULTS: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79-1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90-1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81-1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86-1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52-64 weeks). CONCLUSION: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

Long-acting beta2-agonists versus long-acting muscarinic antagonists in patients with stable COPD: A systematic review and meta-analysis of randomized controlled trials.

Several long-acting bronchodilators have been developed and are widely used as first-line treatment in patients with stable chronic obstructive pulmonary disease (COPD). However, the initial choice of therapy is still uncertain. The aim of this study was to examine the clinical efficacy and safety of long-acting muscarinic antagonist (LAMA) and long-acting beta2-agonist (LABA) in patients with stable COPD. We searched several databases and manufacturers' websites to identify relevant randomized clinical trials for meta-analysis. Outcomes of interest were trough forced expiratory volume in 1 s (FEV1 ), acute exacerbations, transitional dyspnoea index (TDI) score, St George's Respiratory Questionnaire (SGRQ) score and adverse events. Sixteen trials with a total of 22 872 patients were included in this study. Compared with LABA, LAMA were associated with a greater reduction in acute exacerbations (OR: 0.84, 95% CI: 0.74-0.94, P = 0.003) and fewer adverse events (OR: 0.92, 95% CI: 0.86-0.97, P = 0.005). There were no significant differences in trough FEV1 , TDI and SGRQ scores. In patients with stable COPD, LAMA were associated with a greater reduction in acute exacerbations and fewer adverse effects compared with LABA.