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1.
Comparison of two pharmacokinetic-pharmacodynamic models of rocuronium bromide during profound neuromuscular block: analysis of estimated and measured post-tetanic count effect.
Couto, M, Vide, S, Marco-Ariño, N, Troconiz, IF, Esteves, S, Nunes, CS, Amorim, P, Mendes, J
British journal of anaesthesia. 2022;(3):473-481
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Abstract
BACKGROUND Profound neuromuscular block (NMB) is important in surgeries where complete immobility is considered essential to improve tracheal intubation and surgical conditions. Rocuronium bromide is a commonly used NMB agent. This work describes a noninvasive approach for estimation of post-tetanic count (PTC) based on two pharmacokinetic (PK) models, the Saldien and the De Haes models. The aim was to investigate the rocuronium bromide PK-pharmacodynamic (PD) relationship in estimating the PTC effect during profound NMB. METHODS In this prospective, non-randomised, observational study, an induction bolus of rocuronium bromide was administered followed by continuous infusion for maintenance of a PTC of 1-2. measured every 3 min. Measurements were analysed as discrete categorical data and by applying the nonlinear mixed-effect modelling approach. Performance of the selected models was evaluated through simulation model-based diagnostics, further assessing the precision of the parameter estimates and the performance of the models at the individual level. RESULTS Data from 30 adult patients undergoing elective abdominal or neurosurgical procedures were included. Post-tetanic count response profiles during rocuronium bromide infusion were successfully characterised using the population PD analysis. The models showed a good performance for all PTC categories, albeit with a moderate over-prediction of PTC >6. CONCLUSIONS Our findings indicate that using plasma concentrations of rocuronium bromide estimated with either of the two models, combined with a PD model, provides equal model performance when predicting PTC. These promising results may provide an important advance in guiding rocuronium bromide administration when profound NMB in routine clinical practice is desired.
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Physical exercise, immune response, and susceptibility to infections-current knowledge and growing research areas.
Kurowski, M, Seys, S, Bonini, M, Del Giacco, S, Delgado, L, Diamant, Z, Kowalski, ML, Moreira, A, Rukhadze, M, Couto, M
Allergy. 2022;(9):2653-2664
Abstract
This review presents state-of-the-art knowledge and identifies knowledge gaps for future research in the area of exercise-associated modifications of infection susceptibility. Regular moderate-intensity exercise is believed to have beneficial effects on immune health through lowering inflammation intensity and reducing susceptibility to respiratory infections. However, strenuous exercise, as performed by professional athletes, may promote infection: in about half of athletes presenting respiratory symptoms, no causative pathogen can be identified. Acute bouts of exercise enhance the release of pro-inflammatory mediators, which may induce infection-like respiratory symptoms. Relatively few studies have assessed the influence of regularly repeated exercise on the immune response and systemic inflammation compared to the effects of acute exercise. Additionally, ambient and environmental conditions may modify the systemic inflammatory response and infection susceptibility, particularly in outdoor athletes. Both acute and chronic regular exercise influence humoral and cellular immune response mechanisms, resulting in decreased specific and non-specific response in competitive athletes. The most promising areas of further research in exercise immunology include detailed immunological characterization of infection-prone and infection-resistant athletes, examining the efficacy of nutritional and pharmaceutical interventions as countermeasures to infection symptoms, and determining the influence of various exercise loads on susceptibility to infections with respiratory viruses, including SARS-CoV-2. By establishing a uniform definition of an "elite athlete," it will be possible to make a comparable and straightforward interpretation of data from different studies and settings.
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Health effects of exposure to chlorination by-products in swimming pools.
Couto, M, Bernard, A, Delgado, L, Drobnic, F, Kurowski, M, Moreira, A, Rodrigues-Alves, R, Rukhadze, M, Seys, S, Wiszniewska, M, et al
Allergy. 2021;(11):3257-3275
Abstract
Concerns have been raised regarding the potential negative effects on human health of water disinfectants used in swimming pools. Among the disinfection options, the approaches using chlorine-based products have been typically preferred. Chlorine readily reacts with natural organic matter that are introduced in the water mainly through the bathers, leading to the formation of potentially harmful chlorination by-products (CBPs). The formation of CBPs is of particular concern since some have been epidemiologically associated with the development of various clinical manifestations. The higher the concentration of volatile CBPs in the water, the higher their concentration in the air above the pool, and different routes of exposure to chemicals in swimming pools (water ingestion, skin absorption, and inhalation) contribute to the individual exposome. Some CBPs may affect the respiratory and skin health of those who stay indoor for long periods, such as swimming instructors, pool staff, and competitive swimmers. Whether those who use chlorinated pools as customers, particularly children, may also be affected has been a matter of debate. In this article, we discuss the current evidence regarding the health effects of both acute and chronic exposures in different populations (work-related exposures, intensive sports, and recreational attendance) and identify the main recommendations and unmet needs for research in this area.
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Management of Intermittent and Persistent Asthma in Adolescent and High School Athletes.
Del Giacco, S, Couto, M, Firinu, D, Garcia-Larsen, V
The journal of allergy and clinical immunology. In practice. 2020;(7):2166-2181
Abstract
Asthma is the most common chronic condition during childhood and adolescence, affecting an estimated 8% of children and youngsters below 18 years in the United States and the United Kingdom. In adolescent athletes, asthma-like symptoms may represent a common consequence of regular sport practice. Asthma in young athletes poses several challenges, including the ambiguity of definitions and diagnosis of asthma resulting from exercise-induced symptoms, the best pharmacological treatments, and the nonpharmacological options for the management of disease and the challenges inherent to this age group. At a time when the regular practice of sports is increasingly being recommended for a healthy living, the support network around the young athletes is crucial to reduce the impact of asthma on their physical and emotional well-being. In this review, we examine the main issues around the definitions and clinical differentiations of asthma in young sport athletes. We discuss best practice approaches to improve the adherence to the clinical management, including nonpharmacological strategies directed at the family and trainers of athlete adolescents.
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Oxidative stress in asthmatic and non-asthmatic adolescent swimmers-A breathomics approach.
Couto, M, Barbosa, C, Silva, D, Rudnitskaya, A, Delgado, L, Moreira, A, Rocha, SM
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2017;(5):452-457
Abstract
UNLABELLED We hypothesize that oxidative stress induced by trichloramine exposure during swimming could be related to etiopathogenesis of asthma among elite swimmers. AIM: To investigate the effect of a swimming training session on oxidative stress markers of asthmatic compared to non-asthmatic elite swimmers using exhaled breath (EB) metabolomics. METHODS Elite swimmers annually screened in our department (n=27) were invited and those who agreed to participate (n=20, of which 9 with asthma) had EB collected (Tedlar® bags) before and after a swimming training session. SPME fiber (DVB/CAR/PDMS) was used to extract EB metabolites followed by a multidimensional gas chromatography analysis (GC×GC-ToFMS). Dataset comprises eight metabolites end products of lipid peroxidation: five aliphatic alkanes (nonane, 2,2,4,6,6-pentamethylheptane, decane, dodecane, and tetradecane) and three aldehydes (nonanal, decanal, and dodecanal). To assess exercise impact on lipid peroxidation markers, data were analyzed using principle component analysis (PCA), which was run on the original data set and on the data set constructed using differences in the metabolite total areas before and after exercise session. RESULTS Heatmap representation revealed that metabolites content decreased after exercise, both for control and asthma groups; however, the greater decrease was observed for controls. Asthmatics and controls did not form separated clusters; however, control swimmers demonstrated a more varied response to the exercise being dispersed along all score plot. CONCLUSION In well-trained athletes, swimming is associated with a decrease in oxidative stress markers independently of the presence of asthma, although a more pronounced decrease was seen in controls.
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Endovascular Intervention in the Treatment of Peripheral Artery Disease.
Couto, M, Figueróa, A, Sotolongo, A, Pérez, R, Ojeda, JM
Boletin de la Asociacion Medica de Puerto Rico. 2015;(3):47-51
Abstract
Endovascular therapy has emerged as an essential part of the management we can offer patients suffering from peripheral arterial disease. The AHA/ACCF guidelines deemed ballon angioplasty as a reasonable alternative for patients with limb threatening lower extremity ischemia who are not candidates for an autologus venous graft. Endovascular treatment is most useful for the treatment of critical limb ischemia and should ensure adequate proximal flow before engaging in interventions of distal disease.To increase procedure success rate, a thorough diagnostic evaluation is fundamental. This evaluation must take into account amount of calcium, no flow occlusion, length of occlusion, and presence of collaterals. There are different tools and procedure techniques available. Among these are the medicated ballon angioplasty and atherectomy by laser or high-speed drill, among others. Further studies may consolidate endovascular intervention as a safe and effective management for patients with lower extremity arterial disease and possibly cause a change in the actual practice guidelines.
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Acquired Von Willebrand Syndrome In Aortic Stenosis: Case Report And Review.
Alsidawi, S, Couto, M, López-Candales, A
Boletin de la Asociacion Medica de Puerto Rico. 2015;(2):86-8
Abstract
We present a case of a 61 year old man who presented with a 3 week history of easy bruising and ecchymoses in both thighs and right arm without significant trauma. Physical exam was remarkable for oozing gums, diminished second heart sound, a systolic ejection murmur at the aortic position with radiation to carotids, and delayed pulses. Laboratories were remarkable for iron deficiency anemia. Echocardiogram was consistent with severe aortic stenosis. Colonoscopy revealed several arteriovenous malformations throughout the colon. There is an association between severe aortic stenosis and gastrointestinal bleeding. The pathogenesis of Heyde's Syndrome involves iron deficiency anemia due to acquired von Willebrand factor (vWF) deficiency and ultimately gastrointestinal angiodysplasia. Correct diagnosis and management warrants a multidisciplinary approach.
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Low prealbumin is strongly associated with adverse outcome in heart failure.
Lourenço, P, Silva, S, Friões, F, Alvelos, M, Amorim, M, Couto, M, Torres-Ramalho, P, Guimarães, JT, Araújo, JP, Bettencourt, P
Heart (British Cardiac Society). 2014;(22):1780-5
Abstract
OBJECTIVE Prealbumin is one of the best indicators of nutritional status. We previously showed that prealbumin predicted in-hospital mortality in heart failure (HF) patients. We evaluated if a low discharge prealbumin after admission with acute HF would predict morbidity and mortality. METHODS We conducted a prospective observational study. Patients admitted with a primary diagnosis of HF were studied. Follow-up was up to 6 months. Endpoints analysed were: all-cause and HF-death; all-cause and worsening HF hospitalisation. Patients with discharge prealbumin ≤15.0 mg/dL and those with prealbumin >15 mg/dL were compared. A Cox-regression analysis was used to evaluate the prognostic impact of low prealbumin. RESULTS We studied 514 patients. Mean age was 78 years and 45.7% were male. During follow-up, 101 patients died (78 for HF) and 209 patients were hospital readmitted (140 for worsening HF). Median prealbumin was 20.1 (15.3-25.3) mg/dL. Patients with lower prealbumin were more often women, older aged and with non-ischaemic HF; they had lower albumin, haemoglobin and total cholesterol; and higher glomerular filtration rate, C-reactive protein, B-type natriuretic peptide and length of hospital stay. Lower prealbumin associated with less β-blocker and statin use. Patients with discharge prealbumin ≤15 mg/dL had a multivariate adjusted HR of 6-month all-cause and HF death of 1.67 (1.00 to 2.80) and 2.12 (1.19 to 3.79) respectively and of all-cause and HF readmission of 1.47 (1.01 to 2.14) and 1.58 (1.01 to 2.47). CONCLUSIONS Patients with discharge prealbumin ≤15 mg/dL have an higher risk of 6 months morbidity and mortality. The unbalance between protein-energy demands and its availability predicts ominous HF outcome.
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[Eosinophilic esophagitis].
Couto, M, Rodrigues, S, Piedade, S, Gaspar, Â, Morais-Almeida, M, Macedo, G
Acta medica portuguesa. 2011;:949-60
Abstract
Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus characterized by significant and isolated infiltration of the esophageal mucosa by eosinophils, associated with clinical symptoms of esophageal dysfunction, affecting children and adults. It is an increasingly frequent cause of symptoms similar to gastroesophageal reflux disease but refractory to anti-acid therapeutic. It is commonly associated with food allergies or other atopic diseases. Since there are no symptoms, signs, serological biomarkers or endoscopic findings pathognomonic of EE, the diagnosis requires a high degree of suspicion; moreover, due to its chronic relapsing nature the potential to cause major esophageal structural changes, its early recognition and close cooperation between gastroenterologists and immunoallergologists is essential for the timely institution of appropriate therapy. The treatment is based on two main strategies: diet and / or pharmacotherapy, depending on the co-existence of sensitization to food allergens. It is our aim to review this issue, considering recent guidelines, as well as propose a diagnostic and therapeutic algorithm.