High-dose vitamin D supplementation in patients with COVID-19: A meta-analysis of randomized controlled trials.

The efficacy of administering high doses of vitamin D to patients diagnosed with COVID-19 remains uncertain. We conducted a comprehensive search across multiple databases (PubMed, EMBASE, Cochrane Library, and ISI Web of Science) from inception until August 2022, with no limitations on language, to locate randomized controlled trials (RCTs) that investigated the impact of high-dose vitamin D supplementation (defined as a single dose of ≥100,000 IU or daily dose of ≥10,000 IU reaching a total dose of ≥100,000 IU) on COVID-19 patients. Risk ratios (RR) with 95% confidence intervals (CI) and weighted mean differences (WMD) with 95% CI were calculated. Our meta-analysis included 5 RCTs with a total of 834 patients. High-dose vitamin D supplementation did not show any significant benefits for mortality (I 2 = 0.0%, p = .670; RR 1.092, 95% CI 0.685-1.742, p = .711) or intensive care unit (ICU) admission (I 2 = 0.0%, p = .519; RR 0.707, 95% CI 0.454-1.102, p = .126) in COVID-19 patients compared to the control group. However, it was found to be safe and well-tolerated (I 2 = 0.0%, p = .887; RR 1.218, 95% CI 0.930-1.594, p = .151). Subgroup analysis also showed no benefits in overall mortality, including for patients with vitamin D deficiency (I 2 = 0.0%, p = .452; RR 2.441, 95% CI 0.448-13.312, p = .303) or compared to the placebo (I 2 = 0.0%, p = .673; RR 1.666, 95% CI 0.711-3.902, p = .240). Our research indicates that there is no evidence to support the efficacy of high-dose vitamin D supplementation in improving clinical outcomes among individuals with COVID-19, in line with previous studies focused on contexts including rickets. Considering the limitations of the study, additional research may be required.

Effects of doxofylline as an adjuvant on severe exacerbation and long-term prognosis for COPD with different clinical subtypes.

OBJECTIVE: This study aimed to investigate the effectiveness of doxofylline as an adjuvant in reducing severe exacerbation for different clinical subtypes of chronic obstructive pulmonary disease (COPD). METHODS: The clinical trial was an open-label non-randomized clinical trial that enrolled patients with COPD. The patients were divided into two groups (doxofylline group[DG] and non-doxofylline group[NDG]) according to whether the adjuvant was used. Based on the proportion of inflammatory cells present, the patients were divided into neutrophilic, eosinophilic, and mixed granulocytic subtypes. The rates of severe acute exacerbation, use of glucocorticoids, and clinical symptoms were followed up in the first month, the third month, and the sixth month after discharge. RESULTS: A total of 155 participants were included in the study. The average age of the participants was 71.2 ± 10.1 years, 52.3% of the patients were male, and 29.7% of the participants had extremely severe cases of COPD. In the third month after discharge the numbers of patients exhibiting severe exacerbation among the neutrophilic subtype were 5 (6.6%) in the DG versus 17 (22.4%) in the NDG (incidence rate ratio[IRR] = 0.4 [95% CI: 0.2-0.9] P = 0.024). In the sixth month after discharge, the numbers were 3 (3.9%) versus 13 (17.1%; IRR = 0.3 [95%; CI: 0.1-0.9], P = 0.045), and those for the eosinophilic subtype were 0 (0.0%) versus 4 (14.8%), P = 0.02. In the eosinophilic subtype, the results for forced expiratory volume in the first second and maximal mid-expiratory flow were significantly higher in the DG. The mean neutrophil and eosinophil levels were significantly lower than in the NDG among the neutrophilic subtype, and the neutrophil percentage was lower than in the NDG among the eosinophilic subtype. At the six-month follow-up, the dose adjustment rates of the neutrophilic and eosinophilic subtypes showed a significant difference (P< 0.05). CONCLUSIONS: As an adjuvant drug, doxofylline has a good therapeutic effect on patients with the neutrophilic and eosinophilic clinical subtypes of COPD. It can reduce the incidence of severe exacerbation, the use of glucocorticoids, and inflammatory reactions in the long term (when used for a minimum of 3 months).

Comparison of high flow nasal cannula and non-invasive positive pressure ventilation in children with bronchiolitis: A meta-analysis of randomized controlled trials.

Background: The effects of high-flow nasal cannula (HFNC) compared to non-invasive positive pressure ventilation (NIPPV) on children with bronchiolitis remain unclear. Methods: This meta-analysis was performed following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Randomized controlled trials (RCTs) were identified from a comprehensive search in PubMed, EMBASE, Cochrane Library, and Web of Science without time and language limitations. Primary endpoints include the rate of treatment failure, the rate of need for intubation, and the pediatric intensive care unit (PICU) length of stay. Results: Five RCTs including 541 children of less than 24 months were enrolled in the meta-analysis. Compared to the NIPPV group, the rate of treatment failure was significantly higher in the HFNC treatment group (I 2 = 0.0%, P = 0.574; RR 1.523, 95% CI 1.205 to 1.924, P < 0.001). No significant difference was noted in the need for intubation (I 2 = 0.0%, P = 0.431; RR 0.874, 95% CI 0.598 to 1.276, P = 0.485) and the PICU length of stay (I 2 = 0.0%, P = 0.568; WMD = -0.097, 95% CI = -0.480 to 0.285, P = 0.618) between the HFNC group and the NIPPV treatment. Conclusion: Compared to the NIPPV group, HFNC therapy was associated with a significantly higher treatment failure rate in children suffering from bronchiolitis. The intubation rate and the PICU length of stay were comparable between the two approaches.

The Clinical Effects of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients with Chronic Total Occlusion: A Meta-Analysis.

Background: The clinical effects of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) lesions remain unclear. Methods: We identified all full-text published studies that compared the effects of IVUS-guided CTO-PCI with angiography-guided CTO-PCI by searching electric databases including PubMed, Embase, Cochrane Library, and ISI Web of Science from the establishment to Nov 2021. There was no language limitation. The endpoints included the incidence of major adverse cardiac events (MACE), cardiac death, all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR). Results: Five studies involving a total of 2320 patients were included in this meta-analysis. Compared to the angiography-guided group, IVUS-guided PCI showed no significant reduction in the incidence of MACE (I 2 = 27.4%, P = 0.239; RR 0.929, 95% CI 0.765 to 1.128, P = 0.457), cardiac death (I 2 = 0.0%, P = 0.459; RR 0.574, 95% CI 0.299 to 1.103, P = 0.096), all-cause death (I 2 = 0.0%, P = 0.964; RR 0.677, 95% CI 0.395 to 1.163, P = 0.158), MI (I 2 = 46.7%, P = 0.131; RR0.836, 95% CI 0.508 to 1.377, P = 0.482), and TVR (I 2 = 21.2%, P = 0.279; RR 0.929, 95% CI 0.679 to 1.272, P = 0.648). Conclusions: IVUS-guided PCI demonstrated no significant benefit on MACE, cardiac death, all-cause death, MI, and TVR in patients with CTO lesions. However, given the study's limitations, additional high-quality RCTs are needed.

Effects of Liraglutide on Left Ventricular Function: A Meta-Analysis of Randomized, Placebo-Controlled Trials.

BACKGROUND: The effects of liraglutide treatment on the left ventricular systolic and diastolic function remain unclear. METHODS: This meta-analysis was conducted according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. All relevant randomized, placebo-controlled trials (RCTs) were identified by searching PubMed, EMBASE, Cochrane Library, and ISI Web of Science from the establishment to January 2021 without language limitations. The weighted mean difference (WMD) with 95% confidence intervals (CIs) was calculated. RESULTS: Ten placebo-controlled RCTs involving a total of 732 cases were included in the meta-analysis. Compared with the placebo group, liraglutide therapy showed no beneficial effect on the left ventricular ejection fraction (LVEF) at the end of the study (WMD: 2.120, 95% CI: -0.688 to 4.929, P=0.139) and ΔLVEF during the trial period (WMD: -0.651, 95% CI: -1.649 to 0.348, P=0.202). Similarly, no statistical differences were noted in diastolic function parameters between the two groups, including the value early diastolic filling velocity (E)/the mitral annular early diastolic velocity (e') (WMD: -0.763, 95% CI: -2.157 to 0.630, P=0.283), Δe' (WMD: -0.069, 95% CI: -0.481 to 0.343, P=0.742), and ΔE/e' (WMD: -0.683, 95% CI: -1.663 to 0.298, P=0.172). CONCLUSIONS: Liraglutide treatment did not improve the left ventricular systolic and diastolic function. Given the study's limitations, further investigation may be warranted.

Combination therapy of varenicline and bupropion in smoking cessation: A meta-analysis of the randomized controlled trials.

BACKGROUND: The effects of the combination therapy of varenicline and bupropion in smoking cessation are still controversial. METHODS: Databases including PubMed, EMBASE, Cochrane Library and Web of Science were scanned without time and language limitation. Subgroup analysis was performed to assess the effect of combination therapy in smokers with different level of nicotine dependence and cigarette consumption. RESULTS: Four randomized controlled trials involving a total of 1230 smokers were included. Compared with varenicline monotherapy, combination treatment with varenicline and bupropion could significantly improve the abstinence rate at the end of treatment (RR 1.153, 95% CI 1.019 to 1.305, P=0.024). The benefit existed at 6months follow-up (RR 1.231, 95% CI 1.017 to 1.490, P=0.033), disappeared at 12months follow-up (RR 1.130, 95% CI 0.894 to 1.428, P=0.305), and mainly concentrated in highly dependent smokers (RR 1.631, 95% CI 1.290 to 2.061, P<0.001) and heavy smokers (RR 1.515, 95% CI 1.226 to 1.873, P<0.001) rather than individuals with low nicotine dependence (RR 0.989, 95% CI 0.815 to 1.199, P=0.907) or low cigarette consumption (RR 0.985, 95% CI 0.800 to 1.212, P=0.252). For safety outcomes, the combination treatment was associated with more anxiety (RR 1.717, 95% CI 1.176 to 2.505, P=0.005) and insomnia (RR 1.268, 95% CI 1.076 to 1.494, P=0.005) symptoms compared with varenicline monotherapy. CONCLUSION: Compared with varenicline monotherapy, combination treatment with varenicline and bupropion can significantly improve the abstinence rate at the end of treatment and 6months follow-up, mainly in highly dependent smokers and heavy smokers.

Effects of Cilostazol-Based Triple Antiplatelet Therapy Versus Dual Antiplatelet Therapy After Coronary Drug-Eluting Stent Implantation: An Updated Meta-Analysis of the Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: The results of studies on cilostazol-based triple antiplatelet therapy (TAT) after drug-eluting stent (DES) implantation were inconsistent. To assess the effects of TAT compared with dual antiplatelet therapy (DAT) after DES/second-generation DES implantation, we performed a meta-analysis of randomized controlled trials (RCTs). METHODS: All relevant studies evaluated were identified by searching the PubMed, EMBASE, Cochrane Library, and ISI Web of Science databases without time and language limitation. Subgroup analyses were performed to evaluate the efficacy and safety of TAT after second-generation DES implantation. RESULTS: Eleven RCTs involving a total of 4684 patients were included. The meta-analysis showed TAT was associated with significant beneficial effects on angiographic findings of in-stent restenosis [risk ratio (RR) 0.645, 95% confidence interval (CI) 0.470-0.885; P = 0.007], in-segment restenosis (RR 0.606, 95% CI 0.450-0.817; P = 0.001), in-stent late loss (RR - 0.095, 95% CI - 0.136 to - 0.054; P < 0.0001), in-segment late loss (RR - 0.100, 95% CI - 0.139 to - 0.061; P < 0.0001), target lesion revascularization (TLR) (RR 0.570, 95% CI 0.430-0.755; P < 0.0001), and target vessel revascularization (TVR) (RR 0.523, 95% CI 0.380-0.719; P < 0.0001). No significant difference was found in outcomes of all-cause death, cardiac death, definite/probable stent thrombosis (ST), non-fatal myocardial infarction (MI), overall bleeding, and major bleeding between the two groups, as well as some minor adverse effects including palpitations, thrombocytopenia, neutropenia, and hepatic dysfunction. However, the incidence rate of rash, gastrointestinal disorders, and headache was significantly higher in TAT. The second-generation DES subgroup showed similar results, except for the indicators of all-cause death (RR 2.161, 95% CI 1.007-4.635; P = 0.048) and hepatic dysfunction (RR 0.176, 95% CI 0.031-0.995; P = 0.049). CONCLUSIONS: Compared with DAT, cilostazol-based TAT can significantly improve the angiographic findings of in-stent and in-segment late loss, in-stent and in-segment restenosis, TLR, and TVR after DES/second-generation DES implantation. However, no benefits were observed in outcomes of all-cause death, cardiac death, ST, and MI.

The efficacy of N-acetylcysteine plus sodium bicarbonate in the prevention of contrast-induced nephropathy after cardiac catheterization and percutaneous coronary intervention: A meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of combining use of N-acetylcysteine (NAC) and sodium bicarbonate (SOB) in the prevention of contrast-induced nephropathy (CIN) after cardiac catheterization and percutaneous coronary intervention (PCI) is unclear. METHODS: All relevant studies that compared the effect of combining the use of NAC and SOB with individual use on CIN in patients undergoing cardiac catheterization and PCI were identified by searching the databases including Pubmed, Embase, Cochrane Library, and Web of Science without time and language limitation. Only randomized controlled trials (RCTs) with full-text published were considered. RESULTS: Sixteen RCTs involving 4432 cases were included into this meta-analysis. The results showed there were no additional benefit in reduction of CIN in COM group (COM versus NAC: RR 0.85, 95% CI 0.70-1.03, P=0.103; COM versus SOB: RR 0.91, 95% CI 0.71-1.16, P=0.449), even in patients with diabetes mellitus (COM versus NAC: RR 1.11, 95% CI 0.71-1.75, P=0.646; COM versus SOB: RR 1.06, 95% CI 0.45-2.47, P=0.893), undergoing PCI procedure (COM versus NAC: RR0.76, 95% CI 0.39-1.47, P=0.411; COM versus SOB: RR0.96, 95% CI 0.65-1.40, P=0.814), or with baseline renal dysfunction (COM versus NAC: RR 0.89, 95% CI 0.70-1.14, P=0.366; COM versus SOB: RR 0.95, 95% CI 0.67-1.36, P=0.788). CONCLUSIONS: The present study demonstrated combining use of NAC and SOB was not significantly superior to individual use method in the prevention of CIN after cardiac catheterization and PCI.

Effect of Pioglitazone in Preventing In-Stent Restenosis after Percutaneous Coronary Intervention in Patients with Type 2 Diabetes: A Meta-Analysis.

BACKGROUND: The benefits of pioglitazone in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention (PCI) is unclear. OBJECTIVES: To evaluate the effect of pioglitazone on prevention of in-stent restenosis (ISR) in patients with T2DM after PCI. METHODS: All full-text published relevant studies compared the effect of pioglitazone with control group (placebo or no pioglitazone treatment) on ISR in patients with T2DM after PCI were identified by searching the databases including PubMed, EMBASE, Cochrane Library and ISI Web of Science through October 2015. The endpoints were defined as the rate of ISR, late lumen loss, in-stent neointimal volume, target lesion revascularization (TLR) and major adverse cardiac events (MACE). RESULTS: Six studies (5 RCTs and 1 retrospective study), comprising 503 patients, were included into this meta-analysis. In the pioglitazone group, as compared with the control group, the risk ratio for ISR was 0.48 (I2 = 14.5%, P = 0.322; 95%CI 0.35 to 0.68, P<0.001), the risk ratio for TLR was 0.58 (I2 = 6.0%, P = 0.363; 95%CI 0.38 to 0.87, P = 0.009). The result showed there was no association between the use of pioglitazone and the events of MACE (I2 = 36.7%, P = 0.209; RR 0.56, 95%CI 0.30 to 1.05, P = 0.071). For the considerable heterogeneity, further analysis was not suitable for the endpoints of late lumen loss (I2 = 81.9%, P<0.001) and neointimal volume (I2 = 75.9%, P = 0.016). CONCLUSIONS: The treatment of pioglitazone was associated with a reduction in ISR and TLR in T2DM patients suffering from PCI, except the incidence of MACE.

A novel external esophageal perfusion model for reflux-associated respiratory symptoms.

BACKGROUND AND OBJECTIVE: Gastroesophageal reflux disease (GERD) has been linked to a number of extra-esophageal symptoms and disorders, primarily in the respiratory tract. Current animal models of reflux esophagitis are adapted to diseases of the digestive system, rather than to reflux-associated respiratory symptoms. The aim of this study was to evaluate a novel external esophageal perfusion model to induce esophageal, tracheal and pneumonic histological injury similar to that associated with GERD. METHODS: Twenty guinea pigs were randomized to the acid-treated or PBS-treated group. Esophageal catheters were used to perfuse the esophageal lumen of guinea pigs with hydrochloric acid containing 1 g/l pepsin or PBS for 14 days. The total cell number and cell differential counts in bronchoalveolar lavage fluid (BALF) were determined 24 h after the last perfusion. Histological changes in the esophageal, tracheal and pneumonic tissues were observed by hematoxylin-eosin staining. RESULTS: The numbers of lymphocytes, eosinophils and total inflammatory cells in the BALF were significantly higher in acid-perfused than PBS-perfused animals. Histological evidence suggested esophageal and pneumonic inflammations were prominent in acid-treated animals. CONCLUSION: Repetitive, acid-perfused, esophageal events copied the animal models of reflux esophagitis, and elicited inflammatory responses in the airways and lungs of guinea pigs.

[The expression of substance P in airway mucosa of guinea pigs with repetitive esophageal stimulation by hydrochloric acid].

OBJECTIVE: To observe the expression of substance P (SP) in the airway mucosa of guinea pigs with repetitive esophageal stimulation by hydrochloric acid (HCL). METHODS: Twenty adult guinea pigs were randomly divided into 2 groups (n = 10 each): (1) The HCL model group: On the day of experimentation, guinea pigs were maintained under ketamine anesthesia. A 5F catheter was inserted orally into the lumen of the middle and lower esophagus. The esophagus of each animal was perfused with HCl-P for 20 min/d for 14 d. (2) The PBS control group: The esophagus of each animal was perfused with PBS instead. The bronchial responsiveness to Ach given intravenously with increasing doses (3.125, 6.25, 12.5, 25, 50, 100 microg/kg) was measured after the last perfusion. The left lung was isolated for pathological examination. Lung sections were stained with hematoxylin and eosin, and other sections were prepared for immunohistochemistry using monoclonal antibodies against SP. RESULTS: In response to increasing doses of ACh, all guinea pigs showed dose-dependent increases in R(L). However, when the dose of ACh was increased to 25 microg/kg, the airway responsiveness increased significantly in the HCl-P model animals compared with the PBS control group (t values = 43.057, 51.410, 57.359 respectively, all P<0.01). The mean gray values of SP decreased significantly in the tracheal epithelia and the distal airway walls of the model group compared with the PBS control group (t values = 3.44, 2.16 respectively, all P<0.01). CONCLUSION: There was airway neurogenic inflammation in guinea pigs with repetitive esophageal stimulation by HCL, which maybe closely related to the pathogenesis of gastro-esophageal reflux disease.

SH2-B beta expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF-TrkA-mediated asthma.

BACKGROUND AND OBJECTIVE: Nerve growth factor (NGF)/tyrosine kinase receptor A (TrkA) signalling may play an important role in the pathogenesis of asthma, and SH2-B beta, a TrkA-binding protein, modulates the NGF signalling pathway. In this study, SH2-B beta expression in alveolar macrophages (AM) in guinea pig BAL fluid and its role in asthma pathogenesis through the NGF-TrkA signalling pathway were investigated. METHODS: Guinea pigs were randomized into five groups: control, a model of asthma, anti-SH2-B beta antibody treatment, anti-NGF antibody treatment and anti-TrkA antibody treatment. The asthmatic model was established in guinea pigs by inhalation of ovalbumin. Specific anti-SH2-B beta, anti-NGF and anti-TrkA antibodies were administered and AM were isolated from BAL fluid to assess SH2-B beta expression using an immunofluorescence assay. SH2-B beta and TrkA protein expression were determined by western blotting, IL-1 beta and IL-4 levels in the BAL fluid supernatants were determined by ELISA, and pathological changes in the bronchi and lung tissues were examined by HE staining. RESULTS: Lymphocyte, eosinophil and total inflammatory cell numbers in BAL fluid were significantly higher in the asthma model group than in the other groups (P < 0.01). NGF expression in the asthma model group was significantly higher than that in the PBS control group (P < 0.01). SH2-B beta was expressed in AM of control animals and expression was significantly higher in the asthma model than in the other groups (P < 0.01). TrkA protein expression was significantly higher in the asthma model group than in the PBS group (P < 0.01), and treatment with anti-NGF antibody resulted in significant reduction of TrkA expression (P < 0.01). CONCLUSIONS: SH2-B beta is expressed in AM of normal guinea pigs, and SH2-B beta may participate in asthma pathogenesis through the NGF-TrkA signalling pathway.