Quercetin for the treatment of COVID-19 patients: A systematic review and meta-analysis.

Currently approved therapies for COVID-19 are mostly limited by their low availability, high costs or the requirement of parenteral administration by trained medical personnel in an in-hospital setting. Quercetin is a cheap and easily accessible therapeutic option for COVID-19 patients. However, it has not been evaluated in a systematic review until now. We aimed to conduct a meta-analysis to assess the effect of quercetin on clinical outcomes in COVID-19 patients. Various databases including PubMed, the Cochrane Library and Embase were searched from inception until 5 October 2022 and results from six randomized controlled trials (RCTs) were pooled using a random-effects model. All analyses were conducted using RevMan 5.4 with odds ratio (OR) as the effect measure. Quercetin decreased the risk of intensive care unit admission (OR = 0.31; 95% confidence interval (CI) 0.10-0.99) and the incidence of hospitalisation (OR = 0.25; 95% CI 0.10-0.62) but did not decrease the risk of all-cause mortality and the rate of no recovery. Quercetin may be of benefit in COVID-19 patients, especially if administered in its phytosome formulation which greatly enhances its bioavailability but large-scale RCTs are needed to confirm these findings.

Expectant management of patent ductus arteriosus for preterm infants: A meta-analysis of randomized controlled trials.

We conducted this meta-analysis to compare expectant management of patent ductus arteriosus (PDA) with active treatment for PDA closure in preterm infants. Data from 7 randomized controlled trials (RCTs) showed that all-cause mortality and other clinical adverse outcomes did not differ between expectant management of PDA and active treatment. Future large-scale and double-blinded RCTs with a consistent definition for hemodynamically significant PDA, and focusing on clearly delineated high-risk subgroups or later selective treatment are needed to further evaluate the role of expectant management.

Perioperative prophylactic corticosteroids for cardiac surgery in children: A systematic review and meta-analysis.

OBJECTIVE: Perioperative corticosteroids have been used for pediatric cardiac surgery for decades, but the underlying evidence is conflicting. We aimed to investigate the efficacy and safety of perioperative prophylactic corticosteroids in pediatric heart surgeries. METHODS: We searched electronic databases until March 2023 to retrieve all randomized controlled trials (RCTs) that administered perioperative prophylactic corticosteroids to children undergoing heart surgery. We used RevMan 5.4 to pool risk ratios (RRs) and mean differences (MDs). RESULTS: A total of 12 RCTs (2,209 patients) were included in our review. Corticosteroids administration was associated with a nonsignificant reduction in all-cause mortality (RR 0.62; 95% CI: 0.37-1.02, I2 = 0%; moderate certainty); however, it was associated with a lower duration of mechanical ventilation (MV) (MD -0.63 days; 95% CI: -1.16 to -0.09 days, I2 = 41%; high certainty). Corticosteroids did not affect the length of ICU and hospital stay but significantly reduced the incidence of postoperative low cardiac output syndrome (LCOS) (RR 0.76; 95% CI: 0.60-0.96, I2 = 0%; moderate certainty) and reoperation (RR 0.37; 95% CI: 0.19-0.74, I2 = 0%; moderate certainty). There was no increase in adverse events except a higher risk of hyperglycemia and postoperative insulin use. CONCLUSIONS: The use of perioperative corticosteroids in pediatric heart surgeries is associated with a trend toward reduced all-cause mortality without attaining statistical significance. Corticosteroids reduced MV duration, and probably decrease the incidence of LCOS, and reoperations. The choice of corticosteroid agent and dose is highly variable and further larger studies may help determine the ideal agent, dose, and patient population for this prophylactic therapy.

Antiandrogens for the treatment of COVID-19 patients: A meta-analysis of randomized controlled trials.

Antiandrogens may carry a potential benefit as a therapeutic agent against COVID-19. However, studies have been yielding mixed results, thus hindering any objective recommendations. This necessitates a quantitative synthesis of data to quantify the benefits of antiandrogens. We systematically searched PubMed/MEDLINE, Cochrane Library, clinical trial registers, and reference lists of included studies to identify relevant randomized controlled trials (RCTs). Results from the trials were pooled using a random-effects model and outcomes were reported as risk ratios (RR) and mean differences (MDs) with 95% confidence intervals (CIs). Fourteen RCTs with a total sample size of 2593 patients were included. Antiandrogens yielded a significant mortality benefit (RR 0.37; 95% CI; 0.25-0.55). However, on subgroup analysis, only proxalutamide/enzalutamide and sabizabulin were found to significantly reduce mortality (RR 0.22, 95% CI: 0.16-0.30 and RR 0.42, 95% CI: 0.26-0.68, respectively), while aldosterone receptor antagonists and antigonadotropins did not show any benefit. No significant between-group difference was found in the early or late initiation of therapy. Antiandrogens also reduced hospitalizations and the duration of hospital stay, and improved recovery rates. Proxalutamide and sabizabulin may be effective against COVID-19, however, further large-scale trials are needed to confirm these findings.

Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A meta-analysis of randomized controlled trials.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) is a resuscitation method for patients with refractory out-of-hospital cardiac arrest (OHCA). However, evidence from randomized controlled trials (RCTs) is lacking. METHODS: We searched several electronic databases until March 2023 for RCTs comparing ECPR with conventional CPR in OHCA patients. RevMan 5.4 was used to pool risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: A total of four RCTs were included. The results of our meta-analysis showed no statistically significant benefit of ECPR regarding mid-term survival (RR 1.21; 95% CI 0.64 to 2.28; I2 = 48%; p = .55). We found a significant improvement with ECPR in mid-term favorable neurological outcome (RR 1.59; 95% CI 1.09 to 2.33; I2 = 0%; p = .02). There was no significant difference between ECPR and conventional CPR in long-term survival (RR 1.32; 95% CI 0.18 to 9.50; I2 = 64%; p = .79), and long-term favorable neurological outcome (RR 1.47; 95% CI 0.89 to 2.43; I2 = 25%; p = .13). There was an increased incidence of adverse events in the ECPR group (RR 3.22; 95% CI 1.18 to 8.80; I2 = 63%; p = .02). CONCLUSION: ECPR in OHCA patients was not associated with improved survival or long-term favorable neurological outcome but did improve favorable neurological outcome in the mid-term. However, these results are likely underpowered due to the small number of available RCTs. Large-scale confirmatory RCTs are needed to provide definitive conclusions.

Curcumin for the treatment of COVID-19 patients: A meta-analysis of randomized controlled trials.

Curcumin is a low-cost and easily accessible therapeutic option for COVID-19 patients. We aimed to conduct a meta-analysis to assess the effect of curcumin on clinical outcomes in COVID-19 patients. Various databases, including PubMed, the Cochrane Library and Embase were searched from inception until October 2022 for randomized controlled trials (RCTs) evaluating curcumin use in COVID-19 patients. Results from 13 RCTs were pooled using R software version 4.1.0. Curcumin reduced the risk of all-cause mortality (RR 0.38; 95% CI: 0.20-0.72; moderate certainty of evidence), and patients with no recovery status (RR 0.54; 95% CI: 0.42-0.70; moderate certainty of evidence) but had no effect on the incidence of mechanical ventilation and hospitalization, and the rate of a positive viral PCR test. The results of subgroup analysis suggested a higher benefit with early administration of curcumin (within 5 days of onset of symptoms) and with the use of combination regimens. Curcumin is likely to be of benefit in mild-to-moderate COVID-19 patients, but large-scale RCTs are needed to confirm these findings. The limitations of our meta-analysis include the small sample sizes of the included RCTs and the variable formulations of curcumin used across the studies.

Benvitimod for the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Benvitimod is a topical drug that has recently been approved for mild to moderate psoriasis and atopic dermatitis. The drug has just completed phase 3 trials for psoriasis, which calls for a systematic update of current evidence on the efficacy and safety of this drug. We searched MEDLINE (PubMed), EMBASE, Science Direct, International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials, and Google Scholar for all available randomized controlled trials concerning the topic. We included six randomized controlled trials evaluating the efficacy of benvitimod 1.0% with a total of 1925 patients. Our meta-analysis demonstrated that more patients in the benvitimod group achieved physician global assessment score of 0 or 1 (RR 6.53, 95% CI 4.39-9.71), psoriasis area and severity index (PASI) 75 (RR 4.34, 95% CI 2.96-6.36), PASI 90 (RR 8.83, 95% CI 5.22-14.95) and body surface area reduction (MD -3.85, 95% CI -4.83, -2.88) than placebo at week 12. Patient-reported outcomes were also analyzed, yielding a significant benefit in the benvitimod group for peak pruritus numerical rating scale (PP-NRS) score (MD -1.20, 95% CI -1.98, -0.42), ≥4-point decrease in PP-NRS score (RR 1.58, 95% CI, 1.24-2.03) and dermatology life quality index score (MD -2.54, 95% CI -4.00, -1.07). There was a significantly higher incidence of adverse events in the benvitimod group compared to placebo (RR 1.98, 95% CI 1.73-2.27), while the risk was found to be non-significant for serious adverse events. Benvitimod is an effective treatment of psoriasis as compared to a placebo. However, more large-scale, high-quality trials are needed to comment on the safety of this drug.

Outcomes in systemic sclerosis patients hospitalized with COVID-19: Insight from the National Inpatient Sample.

Objective: COVID-19, a respiratory infection caused by the novel coronavirus SARS-CoV-2, can cause varying degrees of illness ranging from mild respiratory illness to severe respiratory failure. Systemic sclerosis is a chronic autoimmune disease, with an increased prevalence of infections as compared to the general population. In this study, we compare the clinical outcomes and resource utilization for COVID-19 hospitalizations in patients with and without systemic sclerosis. Methods: We used the National Inpatient Sample database, 2020, to study the characteristics, morbidity, mortality, cost, and resource utilization among primary COVID-19 hospitalizations with and without systemic sclerosis. Results: There were 1,050,040 patients aged ⩾ 18 years with a diagnosis of COVID-19. Of these, 775 (0.07%) patients had a secondary diagnosis of systemic sclerosis. Although there was no statistically significant difference regarding individual outcomes; in-hospital mortality, vasopressor use, cardiac arrest, acute kidney injury, and disposition to facility were numerically higher in hospitalizations with systemic sclerosis. The composite endpoint of major adverse events was higher in the systemic sclerosis cohort (adjusted odds ratio 1.52, 95% confidence interval: 1.06-2.17, p = 0.022). Conclusion: COVID-19 patients with systemic sclerosis had worse outcomes (i.e. higher composite endpoint of major adverse events) than those without systemic sclerosis. Further studies are needed to establish a better understanding of the relationship between COVID-19 and systemic sclerosis.

Long-term outcome of microvascular decompression for typical trigeminal neuralgia with autologous muscle: an analysis of 1025 patients from a developing country.

OBJECTIVE: The objective was to evaluate the long-term outcome of microvascular decompression (MVD) utilizing autologous muscle for trigeminal neuralgia (TGN). METHODS: A retrospective review was performed of all first-time MVD patients for typical classic TGN without prior surgical intervention who were treated between 2000 and 2019 at a tertiary supraregional neurosurgery practice. Demographic characteristics, surgical findings, operative results, complications, and recurrence rates at 1 year, 5 years, and last follow-up were collected. Pain outcome was assessed using the Barrow Neurological Institute (BNI) pain score. The chi-square test with continuity correction was used to compare categorical variables, and Kaplan-Meier curves and Cox regression were used to identify factors associated with recurrence. RESULTS: In total, 1025 patients were studied with a median (interquartile range [IQR]) (range) follow-up of 8 (5-13) (3-20) years. In the immediate postoperative period, 889 patients (86.7%) had complete pain relief and 106 (10.3%) had partial pain relief; neither group required medication, and 30 patients (2.9%) had no relief. One hundred forty-one recurrences (13.8%) occurred over a median (IQR) of 3 (2-6) years after surgery. The proportion of patients without recurrence was 97% at 1 year, 90% at 5 years, 85% at 10 years, 82% at 15 years, and 81% at 20 years. There was no significant difference in the probability of recurrence between patients with complete (114/907 [12.6%] recurrences) or partial (19/106 [17.9%] recurrences) postoperative pain relief (p = 0.124, log-rank test). Patients with venous compression (n = 322) had a significantly higher rate of MVD failure (n = 16 [5%]) compared to those with arterial compression (14/703 [2%]) (p = 0.015, chi-square test). In the Cox proportional hazards model, venous compression and lack of immediate postoperative pain relief had hazard ratios of 1.62 (95% CI 1.16-2.27) and 2.65 (95% CI 1.45-4.82) for recurrence, respectively. One hundred twenty-four (12.1%) complications were documented, including facial numbness (44 [4.3%]), facial nerve palsy (37 [3.6%]), CSF leak (13 [1.3%]), and diplopia (5 [0.5%]), which resolved in all patients. CONCLUSIONS: MVD with autologous muscle provides long-lasting pain relief in TGN patients with vascular compression with minimum morbidity and is a viable alternative to synthetic materials.

Molnupiravir for the treatment of COVID-19 outpatients: An updated meta-analysis.

BACKGROUND: The majority of available data on molnupiravir come from an unvaccinated COVID-19 population. Therefore, we conducted this meta-analysis to integrate evidence from recent randomized controlled trials (RCTs) as well as observational studies stratified by vaccination status to determine the clinical efficacy and safety of molnupiravir in COVID-19 outpatients. METHODS: We searched PubMed, Embase, the Cochrane Library, medRxiv, and ClinicalTrials.gov from inception to November 2023. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) as the effect measure. RESULTS: We included 8 RCTs and 5 observational studies in our meta-analysis. Molnupiravir reduced the risk of all-cause mortality (RR 0.28; 95% CI: 0.20-0.79, I2 = 0%) but did not decrease the hospitalization rate (RR 0.67; 95% CI: 0.45-1.00, I2 = 53%) in the overall population; in the immunized population, no benefits were observed. Molnupiravir lowered the rate of no recovery (RR 0.78; 95% CI: 0.76-0.81, I2 = 0%) and increased virological clearance at day 5 (RR 2.68; 95% CI: 1.94-4.22, I2 = 85%). There was no increase in the incidence of adverse events. CONCLUSIONS: Molnupiravir does not decrease mortality and hospitalization rates in immunized patients with COVID-19. However, it does shorten the disease course and increases the recovery rate. The use of molnupiravir will need to be considered on a case-by-case basis in the context of the prevailing social circumstances, the resource setting, drug costs, and the healthcare burden.

Colchicine for the treatment of patients with COVID-19: an updated systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: We conducted an updated systematic review and meta-analysis to investigate the effect of colchicine treatment on clinical outcomes in patients with COVID-19. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We searched PubMed, Embase, the Cochrane Library, medRxiv and ClinicalTrials.gov from inception to January 2023. ELIGIBILITY CRITERIA: All randomised controlled trials (RCTs) that investigated the efficacy of colchicine treatment in patients with COVID-19 as compared with placebo or standard of care were included. There were no language restrictions. Studies that used colchicine prophylactically were excluded. DATA EXTRACTION AND SYNTHESIS: We extracted all information relating to the study characteristics, such as author names, location, study population, details of intervention and comparator groups, and our outcomes of interest. We conducted our meta-analysis by using RevMan V.5.4 with risk ratio (RR) and mean difference as the effect measures. RESULTS: We included 23 RCTs (28 249 participants) in this systematic review. Colchicine did not decrease the risk of mortality (RR 0.99; 95% CI 0.93 to 1.05; I2=0%; 20 RCTs, 25 824 participants), with the results being consistent among both hospitalised and non-hospitalised patients. There were no significant differences between the colchicine and control groups in other relevant clinical outcomes, including the incidence of mechanical ventilation (RR 0.75; 95% CI 0.48 to 1.18; p=0.22; I2=40%; 8 RCTs, 13 262 participants), intensive care unit admission (RR 0.77; 95% CI 0.49 to 1.22; p=0.27; I2=0%; 6 RCTs, 961 participants) and hospital admission (RR 0.74; 95% CI 0.48 to 1.16; p=0.19; I2=70%; 3 RCTs, 8572 participants). CONCLUSIONS: The results of this meta-analysis do not support the use of colchicine as a treatment for reducing the risk of mortality or improving other relevant clinical outcomes in patients with COVID-19. However, RCTs investigating early treatment with colchicine (within 5 days of symptom onset or in patients with early-stage disease) are needed to fully elucidate the potential benefits of colchicine in this patient population. PROSPERO REGISTRATION NUMBER: CRD42022369850.

Nigella sativa for the treatment of COVID-19 patients: A rapid systematic review and meta-analysis of randomized controlled trials.

Nigella sativa is an herbal therapy for various afflictions. It has some potential to be a promising option as an efficacious treatment for COVID-19 patients that can contribute to global healthcare as a relatively cheap therapy but evidence of its use from randomized controlled trials (RCTs) is limited. Therefore, to explore the effect of N. sativa in combating COVID-19, we undertook this meta-analysis. We searched several databases to retrieve all RCTs investigating N. sativa for the treatment of COVID-19 as compared to placebo or standard care. We used RevMan 5.4 for all analyses with risk ratio (RR) or odds ratio (OR) as the effect measures. We included a total of seven RCTs in this review. N. sativa significantly reduced the risk of all-cause mortality in patients with COVID-19 compared to the control group (RR 0.27, 95% CI: 0.10 to 0.72; I 2 = 0%). N. sativa significantly reduced the rate of viral PCR positivity (RR 0.62, 95% CI: 0.39 to 0.97; I 2 = 0%). We did not find any significant difference in the risk of hospitalization (RR 0.26, 95% CI: 0.04 to 1.54; I 2 = 0%) and the rate of no recovery (OR 0.48, 95% CI: 0.20 to 1.15; I 2 = 84%) between the two groups. N. sativa is an easily available herbal medicine that may decrease the risk of mortality and improve virological clearance in COVID-19 patients. However, our results are limited by the small number of RCTs available. Further large-scale RCTs are needed to better understand the anti-inflammatory and antiviral effects of N. sativa in COVID-19 patients.

Efficacy and safety of corticosteroids for the treatment of community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the effectiveness and potential effect modifiers of adjunctive corticosteroids in patients with CAP. METHODS: The protocol of this meta-analysis was registered with PROSPERO (CRD42022354920). We searched MEDLINE, Embase, the Cochrane Library and trial registers from inception till March 2023 to identify randomized controlled trials (RCTs) investigating corticosteroids in adult patients with CAP. Our primary outcome was the risk of all-cause mortality within 30 days after randomization (if not reported at day 30, we extracted the outcome closest to 30 days). Risk ratios (RR) and mean differences (MDs) were pooled under a random-effects model. RESULTS: Fifteen RCTs (n = 3252 patients) were included in this review. Corticosteroids reduced the risk of all-cause mortality in CAP patients (RR: 0.69, 95% CI: 0.53-0.89; high certainty). This significant result was restricted to hydrocortisone therapy and patients with severe CAP. Additionally, younger patients demonstrated a greater reduction in mortality. Corticosteroids reduced the incidence of shock and the need for mechanical ventilation (MV), and decreased the length of hospital and ICU stay (moderate certainty). CONCLUSIONS: Corticosteroids reduce the risk of all-cause mortality, especially in younger patients receiving hydrocortisone, and probably decrease the need for MV, the incidence of shock, and the length of hospital and ICU stay in patients with CAP. Our findings indicate that patients with CAP, especially severe CAP, will benefit from adjunctive corticosteroid therapy.

Efficacy and Safety of Enteral Human Recombinant Insulin to Reduce the Time to Full Enteral Feeding in Preterm Infants: A Meta-Analytical Study.

Recombinant human insulin plays an important role in the gut maturation of preterm infants. This meta-analysis was carried out to assess the efficacy and safety of enteral recombinant human insulin in decreasing the time to full enteral feeding in preterm infants. The pooling of data from four clinical trials yielded a significant decrease in the time to full enteral feeding in preterm infants under both low (Mean difference [MD] -3.43 days; 95% CI: -6.18 to -0.69 days; I2 = 48%) and high doses of insulin (MD -7.10 days; 95% CI: -10.02 to -4.18 days; I2 = 0%). These findings require confirmation by further large trials that evaluate the efficacy and safety of enteral insulin, especially at supraphysiological doses.