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The aim of the present study was to analyze the effect of neuromuscular electrical stimulation (NMES) and photobiomodulation (PBMT) on the cardiovascular parameters, hemodynamic function, arterial baroreflex sensitivity (BRS), and autonomic balance (ANS) of rats with heart failure (HF). Male Wistar rats (220-290 g) were organized into five groups: Sham (n = 6), Control-HF (n = 5), NMES-HF (n = 6), PBMT-HF (n = 6), and NMES + PBMT-HF (n = 6). Myocardial infarction (MI) was induced by left coronary artery ligation. Animals were subjected to an eight-week NMES and PBMT protocol. Statistical analysis included the General Linear Model (GLM) followed by a Bonferroni post-hoc test. Rats of the NMES-HF group showed a higher MI area than the Control-HF (P = 0.003), PBMT-HF (P = 0.002), and NMES + PBMT-HF (P = 0.012) groups. NMES-HF and NMES + PBMT-HF showed higher pulmonary congestion (P = 0.004 and P = 0.02) and lower systolic pressure (P = 0.019 and P = 0.002) than the Sham group. NMES + PBMT-HF showed lower mean arterial pressure (P = 0.02) than the Sham group. Control-HF showed a higher heart rate than the NMES-HF and NMES + PBMT-HF (P = 0.017 and P = 0.013) groups. There was no difference in the BRS and ANS variables between groups. In conclusion, eight-week NMES isolated or associated with PBMT protocol reduced basal heart rate, systolic and mean arterial pressure, without influence on baroreflex sensibility and autonomic control, and no effect of PBMT was seen in rats with HF.
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Insuficiencia Cardíaca , Animales , Barorreflejo , Frecuencia Cardíaca , Hemodinámica , Masculino , Ratas , Ratas WistarRESUMEN
INTRODUCTION: Brazil is one of the countries with the largest population of people with hemophilia (PwH) worldwide. In this scoping review, we aim to investigate the Brazilian context for hemophilia regarding three predefined concepts: (i) clinical-epidemiological profile, (ii) burden of disease and (iii) patient journey and unmet needs. METHODS: Three questions in each concept guided the screening of references retrieved by systematic searches carried out in MEDLINE, LILACS and the Digital Library of Theses and Dissertations. Quantitative and qualitative studies conducted in Brazil from 2002 onwards were assessed for eligibility. MAIN RESULTS: Ninety-two studies were included. A total of 66 studies addressed the concept "Clinical-epidemiological profile", 31 investigated the concept of "Burden of disease" and 26 addressed the concept "Patient journey and unmet needs". Based on these studies, pain and arthropathy affect a substantial proportion of the PwH, with physical functioning, pain and school or work being the domains of quality of life with the greatest impact. About 43 % to 82.6 % of the PwH are unemployed. Rates of inhibitor development are highly variable across studies, especially in hemophilia A. Adherence to prophylactic treatment ranges from 25 % to 72 %. The annualized bleeding rate is estimated at 2.4 ± 4.1. The barriers to treatment identified include distance to reference centers, lack of coordination of specialized and emergency care and restricted access to rehabilitation. CONCLUSIONS: Hemophilia poses a considerable burden on the PwH. Despite the available modalities of treatment, there are remaining unmet needs that should be addressed by researchers and policy makers in the future.
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AIM: This study aimed to investigate the acute effects of dietary nitrate ingestion through l-arginine supplementation or dehydrated beet consumption on endothelial function in chronic obstructive pulmonary disease (COPD) patients. The secondary outcome was to analyze arterial stiffness, plasma nitrate, and nitrate/protein concentration. METHODS: In this randomized crossover study, subjects with COPD underwent three series of supplementation: (1) l-arginine, (2) dehydrated beetroot, and (3) a placebo that appeared like the other supplements. Each intervention lasted 14 days, with a 7-day washout period between series. Participants underwent endothelial function assessment using flow-mediated dilatation (FMD), and plasma nitrate levels were measured at the end of each supplementation series. RESULTS: Seventeen subjects (twelve male) completed the study protocol. Only five subjects presented endothelial dysfunction (RHI ≤0.51) at baseline. The mean baseline characteristics included age 66.5 ± 9.4 years, BMI 27.5 ± 4.5 kg/m2, FEV1, 0.79 (0.67-1.06) L. There were no differences (p > 0.05) between the groups or from pre-to post-interventions for RHI and arterial stiffness index (AIx) values, as well as parameters of endothelium-dependent vasodilation, such as blood flow velocity (BFV), shear stress, shear rate, FMD (mm), and FMD%. There was also no differences (p > 0.05) between the groups or from pre-to post-interventions plasma nitrate levels. CONCLUSIONS: Acute dietary supplementation with nitrates, at the doses provided, did not show a significant improvement in endothelial function assessed by FMD, EndoPAT, or plasma nitrate levels in COPD. These findings suggest that a higher dose or prolonged supplementation might be required to achieve a therapeutic effect.
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OBJECTIVE: To estimate original wild-type BNT162b2 effectiveness against symptomatic Omicron infection among children 5-11 years of age. METHODS: This prospective test-negative, case-control study was conducted in Toledo, southern Brazil, from June 2022 to July 2023. Patients were included if they were aged 5-11 years, sought care for acute respiratory symptoms in the public health system, and were tested for SARS-CoV-2 using reverse transcription polymerase chain reaction. In the primary analysis, we determined the effectiveness of two doses of original wild-type BNT162b2 against symptomatic COVID-19. The reference exposure group was the unvaccinated. RESULTS: A total of 757 children were enrolled; of these, 461 (25 cases; 436 controls) were included in the primary analysis. Mean age was 7.4 years, 49.7 % were female, 34.6 % were obese, and 14.1 % had chronic pulmonary disease. Omicron accounted for 100 % of all identified SARS-CoV-2 variants with BA.5, BQ.1, and XBB.1 accounting for 35.7 %, 21.4 % and 21.4 %, respectively. The adjusted estimate of two-dose vaccine effectiveness against symptomatic Omicron was 3.1 % (95 % CI, -133.7 % to 61.8 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 192.5 days (interquartile range, 99 to 242 days). CONCLUSION: In this study with children 5-11 years of age, a two dose-schedule of original wild-type BNT162b2 was not associated with a significant protection against symptomatic Omicron infection after a median time between the second dose and the beginning of COVID-19 symptoms of 192 days, although the study may have been underpowered to detect a clinically important difference. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05403307 (https://classic. CLINICALTRIALS: gov/ct2/show/NCT05403307).
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BACKGROUND: Cardiovascular diseases are a leading cause of mortality worldwide. A significant contributing factor to this mortality is the lack of engagement in preventive activities. Consequently, strategies for enhancing adherence to and duration of physical activity (PA) have become pivotal. This project aims to create and validate innovative, disruptive, and secure technologies that ensure appropriate exercise intensity, bolster adherence to PA, and monitor health biomarker responses pre-, during, and post-physical activity. METHODS: This exploratory study, followed by a noninferiority, investigator-blinded randomized clinical trial, will be divided into three phases: (1) development and validation of a sensor for real-time biofeedback during a functional assessment test; (2) integration of biofeedback and gamification into an app for the structured prescription of physical training within a controlled setting; and (3) implementation of biofeedback and gamification into an app for the prescription and monitoring of physical training in an uncontrolled setting. Phase 1 entails a validation test of a biosensor-monitoring heart rate (HR) and steps-during a modified shuttle walk test. In phase 2, the biosensor interfaces with a gamified smartphone application. The training regimen spans 6 weeks, 5 days weekly, with each session lasting 60 min: a five-min warm-up involving stationary gait, followed by 50 min of training at the target HR on the step and concluding with a five-min cool-down at a stationary pace. After 6 weeks of training, a new functional capacity test is conducted. Phase 3 involves an investigator-blinded, randomized clinical trial to demonstrate noninferiority. Participants are randomly assigned to either the intervention group (IG) or the control group (CG). IG participants practice exercise using the gamified application in an uncontrolled environment according to the prescribed method outlined in phase 2. CG participants receive PA practice guidelines exclusively. DISCUSSION: Anticipated outcomes include improved exercise adherence through the gamified application, better maintenance of prescribed exercise intensity, and enhanced health biomarkers. The results of this study will inform health-related decision-making. TRIAL REGISTRATION: The study protocol received approval from the Ethics Committee of Universidade Federal de Ciências da Saúde de Porto Alegre (54,492,221.80000.5345) and has been registered with the Brazilian Registry of Clinical Trials (ReBEC, RBR-359p69v).
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Tecnología Disruptiva , Aplicaciones Móviles , Humanos , Adulto , Ejercicio Físico/fisiología , Electrocardiografía , Proyectos de Investigación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Evidence regarding effectiveness of BNT162b2 mRNA COVID-19 vaccine against Omicron in Latin America is limited. We estimated BNT162b2 effectiveness against symptomatic COVID-19 in Brazil when Omicron was predominant. METHODS: This prospective test-negative, case-control study was conducted in Toledo, Brazil, following a mass COVID-19 vaccination with BNT162b2. Patients were included if they were aged ≥12 years, sought care for acute respiratory symptoms in the public health system between November 3, 2021 and June 20, 2022, and were tested for SARS-CoV-2 using RT-PCR. In the primary analysis, we determined the effectiveness of two doses of BNT162b2 against symptomatic COVID-19. RESULTS: A total of 4,574 were enrolled; of these, 1,758 patients (586 cases and 1,172 controls) were included in the primary analysis. Mean age was 27.7 years, 53.8 % were women, and 90.1 % had a Charlson comorbidity index of zero. Omicron accounted for >97 % of all identified SARS-CoV-2 variants, with BA.1 and BA.2 accounting for 84.3 % and 12.6 %, respectively. Overall adjusted estimate of two-dose vaccine effectiveness against symptomatic COVID-19 was 46.7 % (95 %CI, 19.9 %-64.6 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 94 days (IQR, 60-139 days). Effectiveness waned from 77.7 % at 7-29 days after receipt of a second dose to <30 % (non-significant) after ≥120 days. CONCLUSION: In a relatively young and healthy Brazilian population, two doses of BNT162b2 provided protection against symptomatic Omicron infection. However, this protection waned significantly over time, underscoring the need for boosting with variant-adapted vaccines in this population prior to waves of disease activity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT05052307 (https://clinicaltrials.gov/ct2/show/NCT05052307).
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COVID-19 , Humanos , Femenino , Adulto , Masculino , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Vacunas contra la COVID-19 , Vacuna BNT162 , Brasil/epidemiología , Estudios de Casos y Controles , Estudios Prospectivos , Programas de InmunizaciónRESUMEN
INTRODUCTION: Real-world data on COVID-19 vaccine effectiveness are needed to validate evidence from randomized clinical trials. Accordingly, this study aims to evaluate, in a real-world setting in Brazil, the effectiveness of Pfizer-BioNTech BNT162b2 against symptomatic COVID-19 and COVID-19-related complications across diverse populations. MATERIALS AND METHODS: A test-negative case-control study with follow-up of cases is currently being conducted in Toledo, a city in southern Brazil, following a mass COVID-19 vaccination campaign with BNT162b2. The study is being conducted among patients aged 12 years or older seeking care in the public health system with acute respiratory symptoms and tested for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). Cases are RT-PCR positive and controls RT-PCR negative. Test-positive cases are prospectively followed through structured telephone interviews performed at 15 days post-enrollment, and at 1, 3, 6, 9 and 12 months. Baseline demographic, clinical, and vaccination data are being collected by means of structured interviews and medical registry records reviews at the time of enrollment. All RT-PCR-positive samples are screened for mutations to identify SARS-CoV-2 variants. ETHICS AND DISSEMINATION: The study protocol has been approved by the research ethics committee of all participant sites. Study findings will be disseminated through peer-reviewed publications and conference presentations. TRAIL REGISTRATION: Clinicatrials.gov: NCT05052307.
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COVID-19 , SARS-CoV-2 , Humanos , Vacuna BNT162 , Brasil/epidemiología , Estudios de Casos y Controles , COVID-19/epidemiología , Vacunas contra la COVID-19 , SARS-CoV-2/genética , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES: To determine the minimal important difference (MID) for the London Chest Activity of Daily Living scale (LCADL) in patients with chronic obstructive pulmonary disease (COPD), focusing on the percentage of the total score (LCADL%total), using an anchor-based method in addition to distribution-based methods. DESIGN: Non-controlled before-and-after study. SETTING: Two outpatient centres. PARTICIPANTS: Seventy-seven patients with COPD (GOLD II-IV, 47 males, forced expiratory volume in 1second mean 37 (SD 14) % predicted). INTERVENTIONS: Aerobic training and localised training for upper and lower limbs was conducted for 24 sessions, three times per week. MAIN OUTCOME MEASURES: The main outcome was LCADL score pre- and post-exercise training. The MID was established using distribution and anchor-based methods. The modified Saint George Respiratory Questionnaire was the anchor for the analysis of sensitivity and specificity of the MID. RESULTS: The established MIDs ranged from -2.1 to -5.9 points for LCADLtotal and from -2 to -6 points for LCADL%total. The receiver operating characteristic curve indicated a cut-off point of -3 points for LCADLtotal (sensitivity 51%, specificity 82%; P=0.01) and -4 points for LCADL%total (sensitivity 56%, specificity 82%; P=0.04). CONCLUSIONS: The present findings suggest -3 points and -4 points as the MIDs for LCADLtotal and LCADL%total, respectively. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03251781.
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Actividades Cotidianas , Terapia por Ejercicio , Diferencia Mínima Clínicamente Importante , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Encuestas y Cuestionarios/normas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Sensibilidad y Especificidad , Prueba de PasoRESUMEN
BACKGROUND: COPD physiopathology involves multiple pathways and evidence indicates that brain-derived neurotrophic factor (BDNF) is an important biomarker associated with parameters of COPD severity. This study aimed to analyze the time course of the effects of a pulmonary rehabilitation program (PRP) on BDNF levels and on functional status in COPD patients. METHODS: Patients were enrolled in a 24-session PRP. Exercise capacity, dyspnea, health-related quality of life, and the BODE index were assessed at baseline and after the PRP. BDNF plasma levels were measured at baseline (immediately before the 1st session), after the 1st session, and before and after the 24th session. RESULTS: Sixteen patients were included. A reduction in BDNF levels was observed after the 1st session and an increase was observed between the end of the 1st session and the beginning of the 24th session. The PRP promoted an improvement in exercise capacity and health-related quality of life and a reduction in dyspnea and the BODE index. CONCLUSION: Exercise acutely reduced BDNF levels, an effect that was nullified by the overall intervention.
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Factor Neurotrófico Derivado del Encéfalo/sangre , Terapia por Ejercicio/métodos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Anciano , Índice de Masa Corporal , Depresión/etiología , Tolerancia al Ejercicio , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/psicología , Calidad de Vida , EspirometríaRESUMEN
BACKGROUND: Pursed-lips breathing (PLB) is a ventilatory strategy frequently adopted spontaneously by patients with chronic obstructive pulmonary disease (COPD) to relieve dyspnoea, and its practice is widely taught as a respiratory strategy to increase exercise tolerance. OBJECTIVE: To investigate the effects of acute use of PLB in exercise performance, dyspnoea, ventilatory parameters and oxygen saturation during exercise in patients with COPD. DATA SOURCES: PEDro, EMBASE, MEDLINE via OVID, and EBSCO up to May 2016. STUDY SELECTION: Crossover, randomized and quasi-randomized controlled trials that studied PLB as a ventilatory strategy for patients with COPD during exercise. DATA EXTRACTION AND SYNTHESIS: Data extraction included background characteristics of the research reports; participant characteristics; description of the analyzed variables and corresponding instruments; exercise protocol; exercise performance; outcomes and corresponding results; data for "responder" and "non-responder" outcomes. RESULTS: Eight studies were selected. The meta-analysis demonstrated that the use of PLB during exercise reduces minute ventilation and respiratory rate compared to exercise without PLB. No statistically significant differences were found in the 6-minute walk test distance. LIMITATIONS: The sample characteristics, exercise protocols, and criteria for "responders" and "non-responders" differed among studies. CONCLUSION: PLB is effective in reducing minute ventilation and respiratory rate during exercise in patients with COPD. It is still unclear who responds to PLB and how these responders benefit from its use. Further studies with better methodological quality are necessary to understand the implications of its acute use on the functional capacity and symptoms of patients with COPD. Systematic review registration number: PROSPERO CRD42015025903.
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Tolerancia al Ejercicio/fisiología , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Respiración , Terapia Respiratoria/métodos , Ensayos Clínicos como Asunto , Disnea/rehabilitación , Ejercicio Físico/fisiología , Humanos , Oxígeno/sangreRESUMEN
The study investigated the effects of exercise on epigenetic signals and systemic cytokine levels in chronic obstructive pulmonary disease (COPD) individuals. Ten participants of a pulmonary rehabilitation program were submitted to 24 sessions of a supervisioned exercise protocol thrice-weekly (90min/session). Blood samples were collected at baseline, after the 1st session, before and after the 24th session. A DNA hypomethylation status was observed after the 1st session when compared at baseline, while global histone H4 acetylation status was unaltered in any time-points evaluated. No significant changes were observed on cytokine levels after the 1st session. A significant enhancement on interleukin 6 (IL-6) and a decrease on transforming growth factor-beta (TGF-ß) levels were found after the 24th session when compared to the pre 24th session. Moreover, 23 sessions of exercise were able to diminish significantly the basal levels of IL-6 and interleukin 8 (IL-8). These data suggest a potential role of epigenetic machinery in mediating the anti-inflammatory effects of exercise in COPD patients.
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Epigénesis Genética , Terapia por Ejercicio , Ejercicio Físico/fisiología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Acetilación , Anciano , Biomarcadores/sangre , Citocinas/sangre , Metilación de ADN , Disnea/sangre , Disnea/genética , Disnea/inmunología , Disnea/rehabilitación , Femenino , Histonas/sangre , Humanos , Masculino , Proyectos Piloto , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Calidad de Vida , Conducta Sedentaria , Resultado del TratamientoRESUMEN
BACKGROUND: Dynamic hyperinflation leads to dyspnoea and consequent limitations in functional capacity in chronic obstructive pulmonary disease. It has been shown that the response to pursed-lips breathing in terms of dynamic hyperinflation and lower-limb exercise capacity is variable, and its effects on activities of daily living are unknown. This study aimed to evaluate the effect of pursed-lips breathing on dynamic hyperinflation and functional capacity in patients with chronic obstructive pulmonary disease in a lower-limb exercise test and in a multiple-task activities of daily living test. DESIGN: Randomized cross-over study. PATIENTS: Twenty-five patients with chronic obstructive pulmonary disease (16 men, mean age 64 ± 7 years, forced expiratory volume in 1 s (FEV1) = 41.7 ± 14.7% predicted). METHODS: Patients randomly performed two 6-min walk tests (6MWT) with and without pursed-lips breathing (6MWT(PLB) and 6MWT(Non-PLB)) and two Glittre-ADL tests with and without pursed-lips breathing (TGlittre(PLB) and TGlittre(Non-PLB)). Inspiratory capacity was assessed at baseline and immediately after the tests. RESULTS: The 6MWT(Non-PLB) and TGlittre(Non-PLB) induced similar magnitude dynamic hyperinflation (0.22 ± 0.24 l and 0.31 ± 0.23 l, respectively; p > 0.05). Pursed-lips breathing did not improve dynamic hyperinflation induced by the 6MWT (0.24 ± 0.20 and 0.22 ± 0.24 l, respectively, with and without pursed-lips breathing; p > 0.05). Dynamic hyperinflation in the TGlittre(PLB) was significantly lower than in the TGlittre(Non-PLB) (0.19 ± 0.20 l and 0.31 ± 0.23 l, respectively; p = 0.02). Pursed-lips breathing did not improve 6MWT or TGlittre performance. CONCLUSION: Pursed-lips breathing reduced dynamic hyperinflation in the TGlittre, but not in the 6MWT. However, pursed-lips breathing did not improve functional capacity.