Disease-modifying therapies for diabetic peripheral neuropathy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Alpha-lipoic acid, epalrestat, and mecobalamin are widely used as monotherapies for diabetic peripheral neuropathy. However, whether a triple-combination therapy with these three drugs is superior to monotherapy or dual therapy remains debatable. METHODS: Nine randomized controlled trials were identified through a search on electronic databases such as PubMed, Web of Science, and Cochrane Library. The trial participants (N = 1153) were divided into the experimental group who received the triple-combination therapy and the control group who received conventional or dual therapy with the aforementioned drugs. RESULTS: Therapeutic outcomes were better in the experimental group than in the control group (odds ratio: 3.74; 95 % confidence interval: 2.57-5.45; I2 = 0 %; p < 0.00001). No statistic difference was noted in adverse effects. Compared with the control group, the experimental group exhibited significant improvements in median motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and vibration perception thresholds (VPT) in the left and right lower limbs. In the control group, a subgroup analysis by treatment strategy revealed similar improvements in total efficacy, MNCV, and SNCV. CONCLUSIONS: For diabetic peripheral neuropathy, the triple-combination therapy may be more effective than monotherapy or dual therapy.

Clinical efficacy and safety of interleukin-1 blockade in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study evaluated the clinical efficacy and safety of interleukin-1 (IL-1) blockade for patients with COVID-19. METHODS: The PubMed, Web of Science, Ovid Medline, Embase and Cochrane Library databases were searched for relevant articles from their inception to 25 September 2022. Only randomized clinical trials (RCTs) that assessed the clinical efficacy and safety of IL-1 blockade in the treatment of patients with COVID-19 were included. RESULTS: This meta-analysis included seven RCTs. No significant difference in the all-cause mortality rate of patients with COVID-19 was observed between the IL-1 blockade and control groups (7.7 vs. 10.5%, odds ratio [OR] = 0.83, 95% confidence interval [CI] 0.57-1.22; I2 = 18%). However, the study group was at significantly lower risk of requiring mechanical ventilation (MV) compared with the control group (OR = 0.53, 95% CI 0.32-0.86; I2 = 24%). Finally, the risk of adverse events was similar between the two groups. CONCLUSIONS: IL-1 blockade does not provide increased survival benefits in hospitalized patients with COVID-19, but it may reduce the need for MV. Furthermore, it is a safe agent for use in the treatment of COVID-19.>.

This systematic review and meta-analysis of randomized clinical trials (RCTs) evaluated the clinical efficacy and safety of interleukin-1 (IL-1) blockade for patients with COVID-19.Based on the analysis of six RCTs, no significant difference in the all-cause mortality rate of patients with COVID-19 was observed between the IL-1 blockade and control groups.The study group using IL1 was associated with a significantly lower risk of requiring mechanical ventilation compared with the control group.The risk of adverse events was similar between the study and the control groups.

Effect of fluvoxamine on outcomes of nonhospitalized patients with COVID-19: A systematic review and meta-analysis.

OBJECTIVES: This meta-analysis investigated the use of fluvoxamine for the treatment of nonhospitalized patients with COVID-19. METHODS: PubMed, Web of Science, Ovid medline, Embase, Scopus, Cochrane Library databases, and ClinicalTrials.gov were searched for studies published before June 25, 2022. Only clinical studies that compared the efficacy and safety of fluvoxamine with other alternatives or placebos in the treatment of nonhospitalized patients with COVID-19 were included. RESULTS: Four studies with 1814 patients, of whom 912 received fluvoxamine, were included in this study. Compared with the control group receiving placebo or no therapy, the study group receiving fluvoxamine demonstrated a lower risk of hospitalization and emergency department (ED) visits (odds ratio [OR], 0.59; 95 % CI, 0.44-0.79; I2 = 26 %). In addition, the rate of hospitalization remained significantly lower in patients who received fluvoxamine than in the control group (OR, 0.69; 95 % CI, 0.51-0.94; I2 = 36 %). Although the study group demonstrated a lower risk of requirement of mechanical ventilation and intensive care unit admission, and mortality than the control group, these differences were nonsignificant. Finally, fluvoxamine use was associated with a similar risk of adverse events as that observed in the control group. CONCLUSION: Fluvoxamine can be safely used in nonhospitalized patients with COVID-19 and can reduce the hospitalization rate or ED visits in these patients.

Clinical efficacy and safety of topical difamilast in the treatment of patients with atopic dermatitis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the clinical efficacy and safety of topical difamilast in mild-to-moderate atopic dermatitis (AD). METHODS: 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. RESULTS: 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. CONCLUSIONS: This meta-analysis suggests that topical difamilast is an effective and safe treatment for mild-to-moderate AD.

Accelerated-strategy renal replacement therapy for critically ill patients: A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to investigate the clinical effect and safety of accelerated-strategy initiation of renal replacement therapy (RRT) in critically ill patients. METHODS: PubMed, Embase, OVID, EBSCO, and the Cochrane Library databases were searched for relevant articles from inception to December 30, 2020. Only RCTs that compared the clinical efficacy and safety between accelerated-strategy RRT and standard-strategy RRT among critically ill adult patients with acute kidney injury (AKI) were included. The primary outcome was 28-day mortality. RESULTS: A total of 5279 patients in 12 RCTs were included in this meta-analysis. The 28-day mortality rates of patients treated with accelerated and standard RRT were 37.3% (969/2596) and 37.9% (976/2573), respectively. No significant difference was observed between the groups (OR, 0.92; 95% CI, 0.70-1.12; I2 = 60%). The recovery rates of renal function were 54.5% and 52.5% in the accelerated- and standard-RRT groups, respectively, with no significant difference (OR, 1.03; 95% CI, 0.89-1.19; I2 = 56%). The rate of RRT dependency was similar in the accelerated- and standard-RRT strategies (6.7% vs 5.0%; OR, 1.11; 95% CI, 0.71-1.72; I2 = 20%). The accelerated-RRT group displayed higher risks of hypotension, catheter-related infection, and hypophosphatemia than the standard-RRT group (hypotension: OR, 1.26; 95% CI, 1.10-1.45; I2 = 36%; catheter-related infection: OR, 1.90; 95% CI, 1.17-3.09; I2 = 0%; hypophosphatemia: OR, 2.11; 95% CI, 1.43-3.15; I2 = 67%). CONCLUSIONS: Accelerated RRT does not reduce the risk of death and does not improve the recovery of kidney function among critically ill patients with AKI. In contrast, an increased risk of adverse events was observed in patients receiving accelerated RRT. However, these findings were based on low quality of evidence. Further large-scale RCTs is warranted.

Effect of colchicine on the outcomes of patients with COVID-19: a systematic review and meta-analysis of randomised controlled trials.

AIM: This meta-analysis aimed to assess the usefulness of colchicine in patients with COVID-19. METHODS: PubMed, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Clinicaltrials.gov were searched for relevant randomised controlled trials (RCTs) published between database inception and November 12, 2021. Only RCTs that compared the clinical efficacy and safety of colchicine with other alternative treatments or placebos in patients with COVID-19 were included. RESULTS: Overall, 7 RCTs involving 16,024 patients were included; 7,794 patients were in the study group receiving colchicine and 8,230 were in the control group receiving placebo or standard treatment. The study and control groups had similar risk of mortality (odds ratio [OR], 1.00; 95% CI, 0.91-1.09; I2 = 0%). No significant difference was observed between the study and control groups in terms of the need for non-invasive ventilation (OR, 0.92; 95% CI, 0.83-1.03; I2 = 0%), the need for mechanical ventilation (OR, 0.64; 95% CI, 0.32-1.32; I2 = 58%), and length of hospital stay (mean difference, -0.42 days; 95% CI, -1.95 to 1.11; I2 = 62%). In addition, colchicine was associated with significantly higher risks of gastrointestinal adverse events (OR, 1.81; 95% CI, 1.56-2.11; I2 = 0%) and diarrhoea (OR, 2.12; 95% CI, 1.75-2.56; I2 = 9%). CONCLUSIONS: Colchicine does not improve clinical outcomes in patients with COVID-19, so it did not support the additional use of colchicine in the treatment of patients with COVID-19.Key messageColchicine could not reduce the mortality of patients with COVID-19.No significant difference was observed between the colchicine and comparators in terms of the need for non-invasive ventilation, need for mechanical ventilation, and length of hospital stay.Colchicine was associated with a higher risk of gastrointestinal adverse events.

Pro-, pre- and synbiotics for the prevention of incidental ventilator-associated pneumonia among critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study investigated the preventive effects of pro-, pre- and synbiotics on ventilator-associated pneumonia (VAP) among critically ill patients. METHODS: 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. RESULTS: 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; I2 = 67%). The duration of mechanical ventilation was significantly shorter in the study group than in the control group (mean difference [MD], -1.61 days; 95% CI, -2.72 to -0.50; I2 = 86%), and the study group had a shorter duration of stay in the intensive care unit than the control group did (MD, -1.72 days; 95% CI, -3.22 to -0.23; I2 = 87%). CONCLUSIONS: Pro-, pre- and synbiotics can prevent VAP and the use of probiotics for patients who are critically ill should be supported.

Favipiravir-based treatment for outcomes of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis of randomized controlled trials (RCTs) investigated the clinical efficacy and safety of favipiravir for patients with mild-to-critical COVID-19. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Efficacy of melatonin in the treatment of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

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; I2 = 0%, p = 0.02). The risk of intensive care unit admission was numerically lower in the melatonin group than in the control group (8.3% [6/72] vs. 17.6% [12/68], OR: 0.45; 95% CI: 0.16-1.25; I2 = 0%, p = 0.13), and the risk of mortality was numerically lower in the melatonin group than in the control group (1.4% [1/72] vs. 4.4% [3/68], OR: 0.32; 95% CI: 0.03-3.18; I2 = 0%, p = 0.33). In conclusion, melatonin may help improve the clinical outcomes of patients with COVID-19.

Effectiveness of intergenerational participation on residents with dementia: A systematic review and meta-analysis.

AIM: This meta-analysis evaluated the effectiveness of intergenerational program participation for long-term care institution residents with dementia. DESIGN: A systematic review and meta-analysis. METHODS: Ten electronic databases were systematically searched until August 2020: CINAHL, the Cochrane Library, EBSCO, EMBASE, Ovid Medline, ProQuest, Psychology and Behavioral Sciences Collection, PubMed, Scopus, and Web of Science. The Joanna Briggs Institute tool (JBI tool) was used for the quality appraisal of the included publications, and Review Manager 5.3 was used for the meta-analysis. RESULTS: Thirteen articles were identified (1993-2015). Intergenerational program participation could improve the pleasure level and significantly reduce disengagement behaviours of residents with dementia. The intergenerational program intervention caused no apparent improvement in their quality of life, depression levels, and engagement levels.

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

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 25 December 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. 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.

Janus kinase inhibitors for hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials.

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.

Effectiveness and Safety of Compound Polymyxin B Ointment in Treatment of Burn Wounds: A Meta-analysis.

Burn injuries represent a global public health concern. The guidelines for burn care mention that the treatment of burn injuries depends on the type of burn injury, depth of tissue, area of wounds, and site on the body. At present, several topical antimicrobial agents are used in the treatment of burn wounds as a first choice. This study aims to investigate the effectiveness of the compound polymyxin B topical agents for the treatment of burn wounds. PubMed, Web of Science, ProQuest, and China National Knowledge Infrastructure databases were searched for articles published until January 2021. The studies that conducted clinical trials comparing compound polymyxin B ointment with other treatment reagents for burn wound treatment were included. A total of three outcomes, which were investigator-assessed clinical response, including mortality, bacterial counts, efficacy and safety were included for analysis in this study. In total, 12 randomized controlled trials, 1 clinical trial, 2 prospective studies, and 1 retrospective study were extracted. The result of mortality showed no significant difference (risk ratio [RR]: 0.70, 95% CI: 0.21-2.31, P = .56); wound healing revealed an RR of 1.59 (95% CI: 1.40-1.81, P < .001); time to heal revealed a mean difference of -5.09 (95% CI: -6.31 to -3.86) days (P < .001); scar incidence was not significantly lower in the treatment group (RR: 0.70, 95% CI: 0.38-1.30, P = .26); and adverse event incidence was significantly lower in the treatment group (RR: 0.26, 95% CI: 0.09-0.72, P < .01). The compound polymyxin B ointment shows the effectiveness of increase in the wound healing and accelerates the time of healing with fewer adverse effects.

Novel ß-lactam/ß-lactamase inhibitor combinations versus alternative antibiotics in adults with hospital-acquired pneumonia or ventilator-associated pneumonia: an integrated analysis of three randomised controlled trials.

OBJECTIVES: This study assessed the efficacy and safety of novel ß-lactam/ß-lactamase inhibitor (BL/BLI) combinations in adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). METHODS: PubMed, Web of Science, the Cochrane Library, Ovid MEDLINE, Embase and EBSCO databases were searched for randomised controlled trials (RCTs) published before 13 September 2020. Only RCTs comparing the treatment efficacy of novel BL/BLI combinations with other antibiotics for HAP/VAP in adult patients were included in this integrated analysis. RESULTS: Three RCTs were included and no significant difference in clinical cure rate of test of cure was observed between the novel BL/BLI combinations and comparators [odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.81-1.27; I2 = 35%]. The 28-day all-cause mortality was 16.2% and 17.6% for patients receiving novel BL/BLI combinations and comparators, respectively, and no significant difference was noted (OR = 0.90, 95% CI 0.69-1.16; I2 = 11%). Compared with comparators, novel BL/BLI combinations were associated with a similar microbiological response (OR = 1.06, 95% CI 0.73-1.54; I2 = 64%) and a similar risk of adverse events (AEs) [treatment-emergent AEs (TEAEs): OR = 1.04, 95% CI 0.83-1.30; I2 = 0%; serious AEs: OR = 1.14, 95% CI 0.79-1.63; I2 = 68%; treatment discontinuation for TEAE: OR = 0.90, 95% CI 0.62-1.31; I2 = 11%). CONCLUSION: Clinical and microbiological responses of novel BL/BLI combinations in the treatment of HAP/VAP were similar to those of other available antibiotics. These combinations also shared a similar safety profile to comparators.

Effectiveness of Companion Robot Care for Dementia: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Dementia and central nervous system degeneration are common problems in aging societies with regard to the number of people affected and total medical expenses. Socially assistive robotic technology has gradually matured; currently, most scholars believe it can be used as companions in long-term care facilities and to work as caregivers alongside staff to improve the social interaction and mental state of older adults and patients with dementia. Therefore, this study measured the effect of the duration of exposure to socially assistive robots in older adults with dementia. RESEARCH DESIGN AND METHODS: Seven databases were searched up to February 2019 through the consultation of appropriate Internet sites and the use of criteria lists recommended by relevant experts. Randomized controlled trials comparing socially assistive robot use with a control group in older adults with dementia and using at least one of the primary outcomes of agitation, depression, and quality of life were included. RESULTS: Thirteen randomized controlled trials were identified from 873 articles, 7 of which were included in the meta-analysis. The pooled effect estimate from 3 trials with 214 participants revealed that the pet-type robot improved patients' agitation level, with a standardized mean difference of -0.37 (95% CI: -0.64 to -0.10, p < .01) and no heterogeneity (I 2 = 0%). The results also revealed that length of each session and pet-type robot exposure time per week were associated with reduced depression levels (ß = -0.06, Q = 21.213, df = 1, p < .001 and ß = -0.019, Q = 7.532, df = 1, p < .01, respectively). However, the results for quality of life were nonsignificant. DISCUSSION AND IMPLICATIONS: Pet-type robot systems seem to be a potential activity in long-term care facilities for dementia care. Further research is warranted to establish a comprehensive intervention plan related to the use of pet-type robots.

Clinical Efficacy and Safety of Cefoperazone-Sulbactam in Treatment of Intra-Abdominal Infections: A Systematic Review and Meta-Analysis.

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-abdominal infections. Methods: The PubMed, Cochrane, Web of Science, Ovid Medline, and CKNI databases were searched for relevant articles up to November 25, 2020. The primary outcome was clinical efficacy rate, and the secondary outcomes were microbiologic eradication rate, mortality rate, and adverse event (AE) risk. Results: Twelve studies involving 1,674 patients were included. Overall, the clinical efficacy rate of cefoperazone-sulbactam and comparators was 87.7% and 81.7%, respectively, and cefoperazone-sulbactam was associated with a higher clinical efficacy rate than that the comparator (odds ratio [OR] 1.98; 95% confidence interval [CI] 1.31-3.00; I2 = 36%). Additionally, cefoperazone-sulbactam was associated with a lower clinical failure rate (OR 0.40; 95% CI 0.28-0.57; I2 = 0) and a higher clinical cure rate (OR 1.54; 95% CI 1.17-2.03; I2 = 0) than the comparators. Cefoperazone-sulbactam was associated with a higher microbiologic eradication rate than the comparator (OR 2.54; 95% CI 1.72-3.76; I2 = 0). Finally, there was no significant difference between cefoperazone-sulbactam and the comparators in terms of mortality rate (OR 090; 95% CI 0.38-2.16; I2 = 0) and AE risk (OR 1.07; 95% CI 0.74-1.55; I2 = 0). Conclusions: The clinical efficacy and safety of cefoperazone-sulbactam were similar to those of alternative antibiotics in the treatment of intra-abdominal infections. Therefore, cefoperazone-sulbactam could be recommended as an effective and safe antibiotic for treating intra-abdominal infections.

Vitamin D supplementation and the outcomes of critically ill adult patients: a systematic review and meta-analysis of randomized controlled trials.

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.

Five-day antibiotic treatment for community-acquired bacterial pneumonia: A systematic review and meta-analysis of randomized controlled trials.

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.

Tocilizumab for severe COVID-19: a systematic review and meta-analysis.

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.

Novel ß-Lactam/ß-Lactamase inhibitor combinations vs alternative antibiotics in the treatment of complicated urinary tract infections: A meta-analysis of randomized controlled trials.

OBJECTIVES: This meta-analysis assessed the efficacy and safety of novel ß-lactam/ß-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 ß-lactam/ß-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 ß-lactam/ß-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 ß-lactam/ß-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; I = 28%) and the microbiologically evaluable population (95.2% vs 94.7%, OR, 1.12; 95% CI, 0.68-1.84; I = 0%). Additionally, the novel ß-lactam/ß-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; I = 45%) and microbiologically evaluable population (80.1% vs 72.5%, OR, 1.49; 95% CI, 1.06-2.10; I = 58%). Finally, the risk of AEs associated with the novel ß-lactam/ß-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; I = 19%; serious AEs, OR, 1.21; 95% CI, 0.82-1.76; I = 0%; treatment discontinuation for drug-related TEAE, OR, 077; 95% CI, 0.38-1.56, I = 5%). The all-cause mortality did not differ between the novel ß-lactam/ß-lactamase inhibitor combination and comparators (OR, 1.19; 95% CI, 0.37-3.81; I = 0%). CONCLUSIONS: The clinical and microbiological responses of novel ß-lactam/ß-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.