Comparative effectiveness of continuous positive airway pressure and glucagon-like peptide-1 receptor agonists in obstructive sleep apnea: A network meta-analysis of randomised trials Gaspar R. Chiappa, Paula C N Santos, Deivyd Vieira Silva Calvacante, Alberto Souza Sá Filho, Natalia Prado, et al. Diabetes Obesity and Metabolism, 2026 Abstract To compare the effects of continuous positive airway pressure (CPAP), glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), their combination, and no active intervention on respiratory, sleepiness, and metabolic outcomes in adults with obstructive sleep apnea (OSA). We searched PubMed, Embase, and CENTRAL through August 2025 for randomised trials of CPAP, exenatide, liraglutide, tirzepatide, or their combinations. The primary endpoint was apnea–hypopnea index (AHI). Secondary endpoints were Epworth Sleepiness Scale (ESS), body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), fasting glucose, and glycated haemoglobin (HbA1c). Random‐effects network meta‐analyses estimated mean differences (MDs) with 95% confidence intervals (CIs). Treatments were ranked using SUCRA, and certainty of evidence was assessed with GRADE. Thirty‐four trials including 3964 participants were eligible. CPAP produced the largest reduction in AHI versus no active intervention (MD −22.17 events/h; 95% CI −38.01 to −6.33) and improved ESS (MD −2.75; 95% CI −3.71 to −1.79). Liraglutide reduced BMI (MD −1.60 kg/m 2 ; 95% CI −2.04 to −1.16) and HbA1c (MD −0.19%; 95% CI −0.25 to −0.13), whereas CPAP showed no meaningful metabolic effect. Liraglutide plus CPAP achieved the greatest BMI reduction (MD −2.00 kg/m 2 ; 95% CI −3.49 to −0.51). No intervention significantly changed SBP, DBP, or fasting glucose. According to GRADE, certainty of evidence was moderate for CPAP effects on respiratory and sleepiness outcomes and for GLP‐1 receptor agonists on BMI and HbA1c, and low for blood pressure and fasting glucose. CPAP is the most effective therapy for respiratory control, while GLP‐1 receptor agonists primarily improve weight and glycaemic indices, supporting an integrated airway–metabolic approach to OSA management.
Liraglutide and Exenatide in Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Cognitive Outcomes Paula Santos, Alberto Souza Sá Filho, Vicente Aprigliano, Amanda G. Duarte, Natã Alegransi Ribeiro, Katia Marques Lombardo, James Oluwagbamigbe Fajemiroye, Artur Prediger Buchholz, Victor Renault Vaz, Gaspar R. Chiappa Pharmaceutics, 2026 Background/Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) exhibit neuroprotective properties in preclinical models of Alzheimer’s disease (AD), reducing amyloid accumulation, neuroinflammation, and insulin resistance within the brain. However, clinical evidence regarding their cognitive effects in AD and mild cognitive impairment (MCI) remains inconclusive. To evaluate the effects of GLP-1 RAs on cognitive outcomes in patients with AD or MCI due to AD. Methods: A systematic review was conducted according to PRISMA 2020 and registered in PROSPERO (CRD420251143171). Although the original registry was broad, the identification of a small set of homogeneous randomized controlled trials (RCTs) during screening, prior to data extraction, allowed for a random-effects meta-analysis of cognitive outcomes. RCTs enrolling adults with clinically or biomarker-confirmed AD or MCI were included. Interventions comprised liraglutide or exenatide compared with placebo. Standardized mean differences (SMD) in global cognitive scores were pooled using a random-effects model (restricted maximum likelihood [REML] estimator with Hartung–Knapp adjustment). Results: Three randomized trials (n = 278 participants; 51% women; mean age 68 ± 7 years) met inclusion criteria. Treatment duration ranged from 26 weeks to 18 months. Pooled analysis revealed no significant effect of GLP-1 RAs on global cognition compared with placebo −0.21 (95% CI −0.81 to 0.38; I2 = 47%; τ2 = 3.77). Sensitivity analyses restricted to liraglutide or studies ≥ 12 months yielded similar results. Conclusions: Current randomized evidence does not support cognitive improvement with GLP-1 RAs in AD or MCI.
“Attacking” the Gut–Brain Axis with Psychobiotics: An Umbrella Review of Depressive and Anxiety Symptoms Alberto Souza Sá Filho, Tatiane Bastos Souza, José Luís Rodrigues Martins, Gunnar P. H. Dietz, Katia Flávia Fernandes, Stone de Sá, Pedro Augusto Inacio, Iransé Oliveira-Silva, Gustavo Pedrino, Vicente Aprigliano, Gaspar R. Chiappa, James Oluwagbamigbe Fajemiroye Pharmaceuticals, 2026 Background/Objectives: This umbrella review critically evaluates the available evidence on psychobiotics for depressive and anxiety symptoms, emphasizing methodological quality, consistency of findings, and persistent gaps in the literature. Methods: A comprehensive search was conducted across PubMed/MEDLINE, Scopus, Web of Science, SciELO, Cochrane, and EBSCO (May–June 2025) to identify systematic reviews with meta-analyses of randomized controlled trials examining probiotic, prebiotic, and synbiotic interventions in adults with depressive and/or anxiety symptoms or diagnoses. Two reviewers independently screened studies, extracted data, and evaluated methodological quality using AMSTAR-2. Additional bibliometric, conceptual, and psychometric features were mapped, including geographical origin, publication timeline, scale distribution, and citation-based connectivity. Results: Thirty systematic reviews and meta-analyses were included. Methodological quality was predominantly moderate, low, or critically low in 76.6% of reviews. Probiotic interventions demonstrated consistent benefits for MDD (SMD = −0.50 [95% CI: −0.58 to −0.42], p = 0.0001). However, findings for anxiety were markedly inconsistent, despite the modest improvements in specific subgroups (SMD = −0.19 [95% CI: −0.28 to −0.10]; p < 0.01). Prebiotics for MDD interventions showed limited positive results (SMD = −0.25 [95% CI: −0.47 to −0.03]; p = 0.03). For anxiety, the effects are inconclusive (SMD = −0.07 [95% CI: −0.30 to 0.10]; p = 0.18). Evidence for synbiotics was scarce. Citation-mapping revealed a fragmented and unevenly connected evidence base. Conclusions: The current evidence suggests that probiotics may confer beneficial effects on depressive and anxiety symptoms; however, the same cannot be said for prebiotics and synbiotics. Evidence for the efficacy of prebiotics and synbiotics to treat depression and anxiety is still insufficient or heterogeneous. Registration: CRD420251164884.
Acute Effects of High-Intensity Interval Training (HIIT) on Heart Rate Variability and Psychoaffective Responses Among Bipolar Patients and their Control Peers: A Randomized Crossover Trial Alberto Souza Sá Filho, Marcelo Magalhães Sales, Pedro Augusto Inacio, Gaspar R. Chiappa, Vicente Aprigliano, Rodolfo P. Vieira, Iransé Oliveira-Silva, James Oluwagbamigbe Fajemiroye, Adrielle Beze Peixoto, Antônio Sérgio Nakao de Aguiar, Rodrigo Alvaro Brandão Lopes-Martins, Sergio Machado CNS and Neurological Disorders Drug Targets, 2026 Introduction: to evaluate the acute effects of continuous moderate-intensity aerobic exercise and high-intensity interval training (HIIT) on heart rate variability (HRV) and psychoaffective responses in patients with bipolar disorder (BD) and healthy controls. Methods: Eight BD patients and eight controls underwent baseline assessments, including anthropometric measurements and a submaximal exercise test to determine VO2Max, followed by two randomized exercise sessions. In one session, participants performed 12 min of continuous exercise at 65%VO2Max, and in the other, during the HIIT protocol, participants engaged in six 45-s bouts at 100%VO2Max, each followed by a 1-min and 15-s recovery period at 40%VO2Max. Pre- and postexercise measurements included psychoaffective scales (feeling scale - FS, felt arousal scale - FAS, and SUDs anxiety scale) and HRV assessments recorded during a 10-minute rest period under controlled conditions. Results: Regarding RMSSD, both participants and sessions demonstrated a significant increase in this indicator (p=0.012). The BD significantly increased VLF and LF values and reduced HF values for both exercise sessions. Meanwhile, the LF/HF ratio showed a significant increase only in the HIIT session. For the control group, only a significant reduction in the HF index in both sessions and an increase in the LF/HF ratio only in the HIIT session. The FAS showed significant increases in bodily activation post-exercise across groups and modalities, while the FS demonstrated significant positive shifts in affective valence, with larger improvements following HIIT. Both exercise protocols produced significant reductions in anxiety levels (p=0.001), with HIIT showing a trend toward superior anxiolytic effects in BD patients. Discussion: The improvement in vagal tone and HRV modulates the function of critical brain regions involved in emotional regulation, such as the prefrontal cortex, amygdala, and anterior cingulate cortex. This modulation reduces limbic hyperactivity and impulsivity while influencing monoaminergic pathways, attenuating excessive dopaminergic signaling, thereby contributing to enhanced mood stability and the reduction of affective disturbances in individuals with BD. Conclusion: Both continuous moderate-intensity exercise and HIIT elicited favorable acute autonomic and psychoaffective responses in BD patients and healthy controls. Notably, HIIT tended to produce greater affective and anxiolytic benefits in individuals with BD.
Caffeine Combined with Excitatory Neuromodulation Based on Transcranial Direct Current Stimulation (tDCS) Enhances Performance in a Time-Trial CrossFit® Workout: A Randomized, Placebo-Controlled, Double-Blind Study Alberto Souza Sá Filho, Thiago Albernaz-Silva, Pedro Augusto Inacio, Vicente Aprigliano, Iransé Oliveira-Silva, Gaspar R. Chiappa, Rodolfo P. Vieira, Antônio Sérgio Nakao de Aguiar, Raphael Martins Cunha, James Oluwagbamigbe Fajemiroye, Marcelo Magalhães Sales Nutrients, 2025 Background: Caffeine (CAF) and transcranial direct current stimulation (tDCS) are ergogenic strategies with potential benefits for performance, yet their combined effects remain underexplored, particularly in high-intensity functional training contexts such as CrossFit®. This randomized, double-blind, placebo-controlled crossover study aimed to investigate the impact of tDCS, with and without CAF, on performance time in the Clean & Jerk (C&J) during the benchmark WOD GRACE among competitive CrossFit® athletes. Secondarily, we aimed to compare the RPE across the different experimental conditions, as well as to establish the relationship between personal record (PR) values adjusted for body mass and the execution time of the WOD GRACE, considering different athletes’ classification levels (RX Elite and RX Intermediate). Methods: Twenty participants completed four experimental conditions: CAF ingestion (400 mg) combined with anodal tDCS (CAF + a-tDCS), CAF with Sham tDCS (CAF + Sham-tDCS), placebo (PLA) with a-tDCS (PLA + a-tDCS), and PLA with Sham tDCS (PLA + Sham-tDCS). Results: The results indicated that the combination of CAF + a-tDCS significantly improved performance, reducing execution time (205.5 ± 58.0 s) compared to CAF + Sham-tDCS (218.3 ± 61.2 s; p = 0.034), PLA + a-tDCS (231.7 ± 64.1 s; p = 0.012), and PLA + Sham-tDCS (240.9 ± 66.4 s; p = 0.002). However, no significant differences were observed between CAF + Sham-tDCS and PLA + a-tDCS (p = 0.690), CAF + Sham-tDCS and PLA + Sham-tDCS (p = 0.352), or PLA + a-tDCS and PLA + Sham-tDCS (p = 0.595). Conclusions: The responder analysis revealed that 45% of participants improved performance with isolated tDCS, while 60% responded positively to CAF. No significant differences were found in RPE scores among conditions (p = 0.145). Additionally, no correlations were identified between PR values adjusted for body mass and execution time in both RX Elite (r = 0.265; p = 0.526) and RX Intermediate (r = 0.049; p = 0.901) groups, nor between training experience and performance across interventions. These findings suggest that tDCS, when combined with CAF, may serve as an effective ergogenic aid for improving performance in high-intensity functional training, whereas its isolated use does not yield meaningful benefits.
Exploring the Clinical Utility of Cardiorespiratory Optimal Point in Heart Failure Patients: Creating a New Research Gap Weder A. Silva, Alberto Souza Sá Filho, Plinio S. Ramos, Adriana M. Güntzel Chiappa, Vicente Aprigliano, Iransé Oliveira-Silva, Raphael Martins Cunha, James Oluwagbamigbe Fajemiroye, Rodolfo P. Vieira, Gerson Ferrari, Gaspar R. Chiappa Applied Sciences Switzerland, 2025 The cardiorespiratory optimal point (COP) is an emerging submaximal parameter from cardiopulmonary exercise testing (CPET) that reflects the optimal balance between cardiac workload and pulmonary ventilation. Recent studies have explored the clinical utility and prognostic value of the COP in various populations, particularly in patients with heart failure (HF). This comprehensive literature review evaluated the current evidence on the COP and its potential as an independent risk factor for cardiovascular disease and mortality. The COP has been identified as a predictor of all-cause and cardiovascular mortality, with elevated values being significantly associated with an increased risk. Studies have demonstrated that higher COP values correlate with greater mortality risk independent of traditional risk factors, with significant sex-based differences. Evidence suggests that COP values greater than 26 significantly influence mortality rates and lead to a worse prognosis in patients with HF. For example, individuals with a COP > 30 had an approximately six-fold higher mortality risk (17.1%) than those with a COP < 22, and the combination of a high COP (>30) + low VO2max leads to a significant increase in the risks of adverse effects (30.9%). This underscores the importance of the COP in the clinical management and risk stratification of HF patients. While the COP shows promise as a valuable submaximal marker with significant prognostic implications, further research is needed to establish its superiority over other established prognostic markers and elucidate the underlying mechanisms linking the COP to health outcomes. Nonetheless, the ability of the COP to predict mortality and enhance risk stratification in diverse populations makes it a promising tool in clinical practice.
Differential impacts of body composition on oxygen kinetics and exercise tolerance of HFrEF and HFpEF patients Gerson Cipriano, Cássia da Luz Goulart, Gaspar R. Chiappa, Marianne Lucena da Silva, Natália Turri Silva, Amanda Oliveira do Vale Lira, Edson Marcio Negrão, Luciana Bartolomei Orru DÁvila, Sergio Henrique Rodolpho Ramalho, Fausto Stauffer Junqueira de Souza, Graziella França Bernardelli Cipriano, Daniel Hirai, Dominique Hansen, Lawrence Patrick Cahalin Scientific Reports, 2024
Skeletal muscle metaboreflex in patients with chronic renal failure Paulo J. C. Vieira, Leonardo R. Silva, Vinicius Z. Maldamer, Gerson Cipriano, Adriana M. G. Chiappa, Rodrigo Schuster, Victor H. F. Boni, Tatiani Grandi, Andiara Wolpat, Bruno T. Roseguini, Gaspar R. Chiappa Clinical Physiology and Functional Imaging, 2017
