Menthol can be safely applied to improve thermal perception during physical exercise : a meta-analysis of randomized controlled trials

Menthol is often used as a cold-mimicking substance to allegedly enhance performance during physical activity, however menthol-induced activation of cold-defence responses during exercise can intensify heat accumulation in the body. This meta-analysis aimed at studying the effects of menthol on thermal perception and thermophysiological homeostasis during exercise. PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched until May 2020. Menthol caused cooler thermal sensation by weighted mean difference (WMD) of - 1.65 (95% CI, - 2.96 to - 0.33) and tended to improve thermal comfort (WMD = 1.42; 95% CI, - 0.13 to 2.96) during physical exercise. However, there was no meaningful difference in sweat production (WMD = - 24.10 ml; 95% CI, - 139.59 to 91.39 ml), deep body temperature (WMD = 0.02 °C; 95% CI, - 0.11 to 0.15 °C), and heart rate (WMD = 2.67 bpm; 95% CI - 0.74 to 6.09 bpm) between the treatment groups. Menthol improved the performance time in certain subgroups, which are discussed. Our findings suggest that different factors, viz., external application, warmer environment, and higher body mass index can improve menthol's effects on endurance performance, however menthol does not compromise warmth-defence responses during exercise, thus it can be safely applied by athletes from the thermoregulation point of view

The quadrivalent HPV vaccine is protective against genital warts: a meta-analysis

The quadrivalent human papillomavirus (HPV) vaccine has been assumed to give protection against genital warts (GW) as well as cervical cancer. Our main question was whether HPV vaccine has any effects on the prevention of GW reported in randomised controlled clinical trials (RCTs) and time-trend analyses.This meta-analysis was performed according to the PRISMA guidelines using the PICO format. We searched in three electronic databases (PubMed, Embase, Cochrane Trials), and assessed heterogeneity using the Q-test and I-squared statistics, meta-regression was also performed. Odds ratios (OR) and their confidence intervals (CI) were calculated. The sensitivity was tested by leave-one-out method. We evaluated the presence of publication bias using the funnel plot graph and the Copas selection model. The strength of evidence was assessed using the GRADE approach.Eight RCTs (per-protocol populations) and eight time-trend ecological studies were included in this meta-analysis. A significant reduction (pooled OR = 0.03, 95% CI: 0.01-0.09; I-squared = 53.6%) of GW in young women was recorded in RCTs, and in time-trend analyses both in young women (pooled OR = 0.36, CI 95% = 0.26-0.51; I-squared = 98.2%), and in young men (pooled OR = 0.69, 95% CI = 0.61-0.78; I-squared = 92.7%). In subgroup analysis, a significant reduction of the number of GW events was observed especially in women under 21 years (pooled OR = 0.33, 95% CI = 0.17-0.63). Leave-one-out analysis showed that similar results could be obtained after excluding one study, meta-regression did not show significant difference.Prophylactic, quadrivalent HPV vaccination can prevent GW in healthy women and men, therefore, it should be included in routine immunization programme

Relative performance of various biomaterials used for maxillary sinus augmentation. A Bayesian network meta-analysis.

To assess the histomorphometric outcomes obtained in randomized clinical trials (RCTs) with different biomaterials used for maxillary sinus augmentation (MSA).A search of the existing medical literature until October 1, 2019 was performed. Inclusion criteria were (1) RCTs assessing a two-stage MSA from the lateral approach using autologous bone or biomaterials for grafting, (2) reported histomorphometric outcomes based on crestal bone core biopsy samples. The Bayesian method was used to perform pairwise meta-analyses and network meta-analysis (NMA). The primary outcome, the new bone percentage (NB%), was calculated as mean differences with 95% credible intervals. The interventions were ranked by their posterior probability by calculating the Surface Under the Cumulative Ranking curve values.Thirty-four RCTs (842 MSAs) were included in the analysis with a normal healing period (5-8 months). All comparisons were presented in a league table. On the basis of the ranking probability, the most effective bone grafting material for NB% was bovine xenograft + bone marrow concentrate (BMC) (81%), followed by bovine xenograft + platelet-rich plasma (PRP) (77%), bioactive glass ceramic + autologous bone 1:1 (70 %), nanocrystalline hydroxyapatite in silica gel (70%), and bioactive glass ceramic (70%). Autologous bone graft alone took the twelfth position with 57%.Within the limitations of the present NMA, the analysis did not confirm autologous bone alone as the gold standard for MSA and showed superiority of composite grafts such as bovine xenograft + BMC after 5-8 months of healing

Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: Insights from mathematical modeling and meta-analysis

Antagonists of the transient receptor potential vanilloid-1 (TRPV1) channel alter body temperature (Tb) in laboratory animals and humans: most cause hyperthermia; some produce hypothermia; and yet others have no effect. TRPV1 can be activated by capsaicin (CAP), protons (low pH), and heat. First-generation (polymodal) TRPV1 antagonists potently block all three TRPV1 activation modes. Second-generation (mode-selective) TRPV1 antagonists potently block channel activation by CAP, but exert different effects (e.g., potentiation, no effect, or low-potency inhibition) in the proton mode, heat mode, or both. Based on our earlier studies in rats, only one mode of TRPV1 activation - by protons - is involved in thermoregulatory responses to TRPV1 antagonists. In rats, compounds that potently block, potentiate, or have no effect on proton activation cause hyperthermia, hypothermia, or no effect on Tb, respectively. A Tb response occurs when a TRPV1 antagonist blocks (in case of hyperthermia) or potentiates (hypothermia) the tonic TRPV1 activation by protons somewhere in the trunk, perhaps in muscles, and - via the acido-antithermogenic and acido-antivasoconstrictor reflexes - modulates thermogenesis and skin vasoconstriction. In this work, we used a mathematical model to analyze Tb data from human clinical trials of TRPV1 antagonists. The analysis suggests that, in humans, the hyperthermic effect depends on the antagonist's potency to block TRPV1 activation not only by protons, but also by heat, while the CAP activation mode is uninvolved. Whereas in rats TRPV1 drives thermoeffectors by mediating pH signals from the trunk, but not Tb signals, our analysis suggests that TRPV1 mediates both pH and thermal signals driving thermoregulation in humans. Hence, in humans (but not in rats), TRPV1 is likely to serve as a thermosensor of the thermoregulation system. We also conducted a meta-analysis of Tb data from human trials and found that polymodal TRPV1 antagonists (ABT-102, AZD1386, and V116517) increase Tb, whereas the mode-selective blocker NEO6860 does not. Several strategies of harnessing the thermoregulatory effects of TRPV1 antagonists in humans are discussed

Noninvasive ventilation improves the outcome in patients with pneumonia-associated respiratory failure: Systematic review and meta-analysis

Noninvasive ventilation (NIV) is beneficial in exacerbations of chronic obstructive pulmonary disease (COPD), but its effectiveness in pneumonia-associated respiratory failure is still controversial. In the current meta-analysis, we aimed to investigate whether the use of NIV before intubation in pneumonia improves the mortality and intubation rates of respiratory failure as compared to no use of NIV in adults.We searched three databases from inception to December 2019. We included studies, in which pneumonia patients were randomized initially into either NIV-treated or non-NIV-treated groups. Five full-text publications, including 121 patients, reported eligible data for statistical analysis.With NIV the overall hospital mortality rate seemed lower in patients with pneumonia-associated respiratory failure, but this was not significant [odds ratio (OR) = 0.39; 95% confidence interval (CI): 0.13-1.14; P = 0.085]. In the intensive care unit, the mortality was significantly lower when NIV was applied compared to no NIV treatment (OR = 0.22; 95% CI: 0.07-0.75; P = 0.015). NIV also decreased mortality compared to no NIV in patient groups, which did not exclude patients with COPD (OR = 0.25; 95% CI: 0.08-0.74; P = 0.013). The need for intubation was significantly reduced in NIV-treated patients (OR = 0.22; 95% CI: 0.09-0.53; P = 0.001), which effect was more prominent in pneumonia patient groups not excluding patients with pre-existing COPD (OR = 0.13; 95% CI: 0.03-0.46; P = 0.002).NIV markedly decreases the death rate in the intensive care unit and reduces the need for intubation in patients with pneumonia-associated respiratory failure. The beneficial effects of NIV seem more pronounced in populations that include patients with COPD. Our findings suggest that NIV should be considered in the therapeutic guidelines of pneumonia, given that future clinical trials confirm the results of our meta-analysis.All data and materials generated during the current study are available from the corresponding author on reasonable request

Macrophage migration inhibitory factor as a diagnostic and predictive biomarker in sepsis: meta-analysis of clinical trials

The hunt for useful sepsis biomarkers is ongoing. Macrophage migration inhibitory factor (MIF) was implicated as a biomarker in sepsis, but its diagnostic and prognostic value has remained unclear in human studies. Here, we aimed at clarifying the value of MIF as a sepsis biomarker with the meta-analysis of clinical trials. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched until December 2019. From the included studies, blood MIF levels and indicators of disease severity were extracted in septic and control patient groups. Twenty-one eligible studies were identified, including data from 1876 subjects (of which 1206 had sepsis). In the septic patients, blood MIF levels were significantly higher than in healthy controls with a standardized mean difference (SMD) of 1.47 (95% confidence interval, CI: 0.96-1.97; p < 0.001) and also higher than in patient groups with nonseptic systemic inflammation (SMD = 0.94; CI: 0.51-1.38; p < 0.001). Markedly greater elevation in blood MIF level was found in the more severe forms of sepsis and in nonsurvivors than in less severe forms and in survivors with SMDs of 0.84 (CI: 0.45-1.24) and 0.75 (CI: 0.40-1.11), respectively (p < 0.001 for both). In conclusion, blood MIF level is more elevated in systemic inflammation caused by infection (i.e., sepsis) compared to noninfectious causes. In more severe forms of sepsis, including fatal outcome, MIF levels are higher than in less severe forms. These results suggest that MIF can be a valuable diagnostic and prognostic biomarker in sepsis given that well-designed clinical trials validate our findings

Dietary supplementation of transient receptor potential vanilloid-1 channel agonists reduces serum total cholesterol level: a meta-analysis of controlled human trials

Abnormal cholesterol level is a major risk factor in the development of atherosclerosis, which is a fundamental derangement in cardiovascular diseases. Any efforts should be undertaken to lower blood cholesterol levels. Among dietary interventions, capsaicinoid supplementation is also considered as a novel cholesterol-lowering approach, but human studies concluded contradictory results about its effectiveness. The present meta-analysis aimed at determining the effects of capsaicinoids on serum lipid profile in humans. We searched the PubMed, EMBASE, and CENTRAL databases from inception to February 2021. We included 10 controlled studies, which involved 398 participants. We found that dietary capsaicinoid supplementation alone or in combination with other substances significantly (p = 0.004 and 0.001, respectively) reduced serum total cholesterol level compared to controls with an overall standardized mean difference of -0.52 (95% confidence interval: -0.83, -0.21). Capsaicinoids also decreased low-density lipoprotein level significantly (p = 0.035), whereas no effect was observed on serum levels of high-density lipoprotein and triglycerides. Our findings provide novel quantitative evidence for the efficacy of dietary capsaicin supplementation in lowering serum total cholesterol and low-density lipoprotein levels in humans. To validate our conclusion, further randomized controlled trials in a diverse population of adult humans receiving dietary capsaicinoid supplementation are warranted