Papers by massimo baraldo
EFFECTS OF SMOKELESS TOBACCO (SNUS) ADMINISTRATION ON EXERCISE ENDURANCE IN MEN Thomas Zandonai*1... more EFFECTS OF SMOKELESS TOBACCO (SNUS) ADMINISTRATION ON EXERCISE ENDURANCE IN MEN Thomas Zandonai*1, Massimo Baraldo2, Loretta Franceschi2, Tanja Zappamiglio2, and Cristiano Chiamulera1, 1Neuropsychopharmacology Laboratory, Public Health & Community Medicine Department, University of Verona, Italy; 2Experimental Clinical Medicine Department, University of Udine, Italy SOC Institute of Clinical Pharmacology, S. Maria della Misericordia University-Hospital, Udine, Italy There are anecdotal reports that some winter sport athletes used smokeless tobacco (Snus). However, there are no studies whether this is a socio-cultural habit or a sought psychobiological effect. The aim of this study was to investigate the effects of Snus (SS) on the perception of fatigue during an endurance exercise The study was a double-blind placebo controlled (SP) crossover design study. We recruited 14 non-smokers (breath CO confirmed) men (age 22.8 \ub1 4.6 years; means \ub1 SD). Subjects were studied during three sessions on cycle ergometer: experimental session 1 (EXP1) consisted on an incremental exercise test to determine VO2max (maximal oxygen uptake) and Wmax (maximal aerobic power output); EXP2 and EXP3 consisted on SS or SP administration followed by an exercise at 65% Wmax until exhaustion. During the EXP2 and EXP3 the global rating of perceived exertion (RPE) was recorded, using the 15-point Borg scale every 5min until the end of the session. Blood samples were taken in order to assess nicotine plasma levels during the session. Detected plasma nicotine level was 7.31 \ub1 1.78 ng/ml (means \ub1 SD) in 7 subjects for SS and 3.26 \ub1 0.12 ng/ml (means \ub1 SD) in 3 subjects for SP. In three subjects nicotine was no detectable. Seven out 13 subjects cycled for longer during the SS vs. SP session: time to exhaustion was 60.4 \ub1 41.5 min after SS and 48.8 \ub1 19.4 min after SP; paired Student\u2019s t-test showed that a 18.6% increase was not significant. RPE at 25%, 50%, 75% and 100% of exhaustion time increased during both session; however, no differences were observed between the two conditions. In conclusion, the study showed that SS does not change RPE compared to placebo condition; this means that the sought effect could not be an improvement of fatigue during an endurance exercise until exhaustion. No funding. CORRESPONDING AUTHOR: Thomas Zandonai, University of Verona, Neuropsychopharmacology Lab - Public Health and Community Medicine Dep., P.le Scuro 10, Verona, 37134, Italy
Tabaccologia, May 20, 2022
Dato l'enorme impatto sociosanitario che il fumo di sigaretta continua ad avere sulla popolazione... more Dato l'enorme impatto sociosanitario che il fumo di sigaretta continua ad avere sulla popolazione mondiale, individuare nuove terapie per combattere il tabagismo è una necessità sempre attuale. Una possibile soluzione al problema proviene dal mondo tecnologico, grazie al quale è possibile sviluppare nuove sinergie con le terapie attualmente in uso. In particolare, la realtà virtuale è una tecnologia di recente sviluppo che bene si presta a essere impiegata anche in ambiente medico-sanitario, soprattutto in un settore complesso come le dipendenze comportamentali e da sostanze. Si sono quindi valutate le possibili applicazioni della realtà virtuale nello specifico contesto del tabagismo, soffermandosi sull'efficacia delle metodiche utilizzate e i possibili sviluppi in questo ambito.
Tabaccologia, 2021
La diffusione pandemica del tabagismo (1,2 miliardi di fumatori nel mondo e più di 7 milioni di d... more La diffusione pandemica del tabagismo (1,2 miliardi di fumatori nel mondo e più di 7 milioni di decessi tabacco-correlati) fa del fumo di tabacco la prima causa di morte evitabile nel mondo. Lungi dall'essere un semplice "vizio" o "abitudine", il tabagismo è riconosciuto dall'International Classification of Diseases (ICD-10) e dal Diagnostic and Statistical Manual of Mental Disorder (DSM) come una patologia da dipendenza. Esso infatti soddisfa i criteri psicobiologici per definire, come tutte le altre tossicodipendenze, uno stato di addiction. Inoltre, il tabagismo funge da gateway per altre droghe. Gli interventi di cessazione del fumo presuppongono oggi competenze integrate e devono diventare pratica comune di tutti gli operatori della salute. I punti fermi evidenziati scientificamente sono il counselling, il trattamento farmacologico con i farmaci di prima fascia come i sostituti nicotinici in tutte le sue forme, il bupropione e la vareniclina (e citisina). La combinazione di questi trattamenti, non farmacologico e farmacologico risulta essere di maggiore validità per la cessazione del fumo di tabacco. In questa review si discute sui vari trattamenti alla luce delle linee guida internazionali e nazionali.
Antibiotics, May 9, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Transplant International, Apr 12, 2014
PubMed, May 26, 2015
Individualized drug therapy with immunosuppressants is an hot topic in transplantation. Therapeut... more Individualized drug therapy with immunosuppressants is an hot topic in transplantation. Therapeutic drug monitoring (TDM) is currently utilized to guide therapy, but toxic or subtherapeutic concentrations can only be identified after the drug is administered. Pharmacogenetics, by studying the relationship between a human genetic difference and drug response, holds great promises in optimizing immunosuppressive drug prescribing for solid organ transplantation.Nevertheless, a complete translation in the clinic has lagged behind,due to the overall complexity of the genetic approach, and the lack of sound evidence of identified genetic polymorphisms in ultimately explaining drug exposure. However, for tacrolimus it is likely that a genotype-based drug dosage can benefit patient outcome, while for cyclosporine data appear less convincing. Mycophenolic acid undergoes a complex metabolic pathway and various genes affecting drug disposition are under investigations, with promising results for some of them of being of value in aiding clinicians in decision making. Finally, for sirolimus and everolimus the lack of data and the absence of large prospective studies do not allow to draw any conclusion.
International Journal of Antimicrobial Agents, Oct 1, 2021
Continuous infusion (CI) piperacillin/tazobactam is frequently used to treat infections in very e... more Continuous infusion (CI) piperacillin/tazobactam is frequently used to treat infections in very elderly patients. The aims is to conduct a population pharmacokinetic analysis of CI piperacillin/tazobactam and to identify optimal dosages for safe and effective probability of target attainment (PTA) against Enterobacterales and P. aeruginosa. A non-linear mixed-effects modelling was performed with Pmetrics. Monte Carlo simulations assessed the steady-state concentration (Css) of increasing piperacillin/tazobactam regimens (from 2.25 to 18g daily by CI). Permissible doses were defined as those associated with <10% probability of Css>157.2 mg/L. PTAs at the pharmacodynamic targets of fCss/MIC≥1 and ≥4 and cumulative fraction of response (CFR) against EUCAST MIC distribution were also calculated. A total of 141 patients, whose median age was 85 years, provided 217 plasma piperacillin Css. Most patients (55.2%) had hospital-acquired pneumonia and intra-abdominal infections. A one-compartment pharmacokinetic model with parallel linear and Michaelis-Menten elimination best described piperacillin data. Creatinine clearance (CLCR) was the covariate retained by the model. Pharmacokinetic estimates were 6.05L/h for clearance (CL) and 3.09mg/h for Michaelis-Menten saturative constant (Km). Permissible doses were up to 4.5, 9, 11.25 and 13.5g daily by CI for patients with CLCR of 0-19, 20-39, 40-59 and 60-79 mL/min/1.73m2, respectively. At the clinical breakpoint of 8 mg/L, the permissible doses achieved optimal PTA only for fCss/MIC≥1 in patients with CLCR 20-79mL/min/1.73m2. Optimal CFRs with the permissible doses were attained only against E. coli and P. mirabilis. Permissible dosages and CLCR should be considered for prescribing CI piperacillin/tazobactam in very elderly patients.
Heart Transplantation [Working Title], 2022
Mycophenolate mofetil (MMF) represents a cornerstone in heart transplant (HTx) treatment. The are... more Mycophenolate mofetil (MMF) represents a cornerstone in heart transplant (HTx) treatment. The area under the 12-hour concentration-time curve (AUC0-12h) of mycophenolic acid (MPA) -MMF’s active drug- is associated with treatment outcome. Nonetheless, therapeutic drug monitoring (TDM) of MPA AUC0-12h is impractical to assess in clinical practice and Limited Sampling Strategies (LSSs) represent a consolidated tool to estimate AUC0-12h. Two LSSs were previously generated in a selected cohort of HTx recipients treated with MMF and cyclosporine (CsA). This pilot study aimed to test these LSSs in a cohort of non-selected HTx recipients treated with MMF combined with CsA or tacrolimus (TAC). Complete PK profile was performed in 40 adults HTx recipients. MPA-AUC0-12h was estimated by two algorithms, LSS3 and LSS4, based on 3 and 4 time-points. The evaluation was made through linear regression and Bland-Altman analyses. Both LSS3 and LSS4 tended to underestimate the value of MPA-AUC0-12h (me...
Pharmaceutics
Background: Meropenem is a carbapenem antibiotic widely employed for serious bacterial infections... more Background: Meropenem is a carbapenem antibiotic widely employed for serious bacterial infections. Therapeutic drug monitoring (TDM) is a strategy to optimize dosing, especially in critically ill patients. This study aims to show how TDM influences the management of meropenem in a real-life setting, not limited to intensive care units. Methods: From December 2021 to February 2022, we retrospectively analyzed 195 meropenem serum concentrations (Css). We characterized patients according to meropenem exposure, focusing on the renal function impact. Results: A total of 36% (n = 51) of the overall observed patients (n = 144) were in the therapeutic range (8–16 mg/L), whereas 64% (n = 93) required a meropenem dose modification (37 patients (26%) underexposed; 53 (38%) overexposed). We found a strong relationship between renal function and meropenem concentrations (correlation coefficient = −0.7; p-value < 0.001). We observed different dose-normalized meropenem exposure (Css/D) among re...
Biomedicine & Pharmacotherapy
Transplantation Proceedings, 2019
The posology of tacrolimus (TAC) is usually guided by its therapeutic drug monitoring. Some patie... more The posology of tacrolimus (TAC) is usually guided by its therapeutic drug monitoring. Some patients reach target concentrations (CTs) quickly, others more slowly. In a retrospective study, 20 kidney transplant recipients were included (mean age, 50.7 AE 14.1 years; weight 64.0 AE 14.2 kg; patients clinically stable for over a year). We studied cytochrome CYP3A5 genotype, in particular CYP3A5 6986A>G, the most important polymorphism related to the metabolism of TAC (wild genotype CYP3A5 *1 genotype, and CYP3A5 *3 variants). One year after transplantation, the CTs were 5.0 to 8.0 ng/mL. The patients were divided into group A (TAC doses < 6.0 mg/d) and group B (TAC doses > 6.0 mg/d). All were tested for the CYP3A5 gene sequence to characterize their polymorphism. Patients with CYP3A5 *1/*1 and *1/*3 were extensive metabolizers, and those with CYP3A5 *3/*3 were poor metabolizers. In group A and group B, the average TAC doses at the time of therapeutic drug monitoring were 3.0 AE 1.4 ng/mL (0.05 AE 0.03 mg/kg) and 12.8 AE 3.7 ng/mL (0.2 AE 0.1 mg/kg), respectively (P < .001). Group A was the poor metabolizers genotype, while in group B, the extensive metabolizers genotype was present. Patients with the CYP3A5 *1/*1 or *1/*3 genotype required 1.5 to 2 times higher doses than patients *3/*3 to reach CT. This genetic test allows clinicians to know, before the kidney transplant, the patient's TAC metabolism pattern and then to optimize the drug exposure.
Transplant Infectious Disease, 2015
F. Pea, P. Cojutti, V. Tursi, U. Livi, M. Baraldo. Everolimus overexposure in a heart transplant ... more F. Pea, P. Cojutti, V. Tursi, U. Livi, M. Baraldo. Everolimus overexposure in a heart transplant patient receiving clarithromycin for the treatment of pneumonia. Transpl Infect Dis 2015: 17: 926–928. All rights reserved F. Pea, P. Cojutti, V. Tursi, U. Livi, M. Baraldo Institute of Clinical Pharmacology, Azienda OspedalieroUniversitaria Santa Maria della Misericordia, Udine, Italy, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy, Cardiothoracic Department, Azienda OspedalieroUniversitaria Santa Maria della Misericordia, Udine, Italy
The Messina's War. triBUNa L'odore del denaro. [B. Tinghino] The smell of money. FoCUS oN Nicotin... more The Messina's War. triBUNa L'odore del denaro. [B. Tinghino] The smell of money. FoCUS oN Nicotina come "gateway drug". [D.L Amram, V. Zagà] Nicotine as a "gateway drug".
Pharmaceutics
In the clinical practice management of heart transplant (HTx), the impact of calcineurin inhibito... more In the clinical practice management of heart transplant (HTx), the impact of calcineurin inhibitors co-administration on pharmacokinetics (PKs) of mycophenolic acid (MPA), mycophenolate mofetil (MMF) active drug, is not adequately considered. This retrospective study investigated full MPA-PK profiles by therapeutic drug monitoring (TDM) in 21 HTx recipients treated with MMF combined with cyclosporine (CsA) or tacrolimus (TAC) at a median time of 2.6 months post-transplant. The two treatment groups were compared. We described the main MPA-PK parameters in patients developing acute cellular rejection (ACR) and those who did not. Median dose-adjusted MPA-trough levels and MPA-AUC0–12h were higher in patients co-treated with TAC than with CsA (p = 0.0001 and p = 0.006, respectively). MPA-Cmax and Tmax were similar between the two groups, whereas the enterohepatic recirculation biomarker of MPA (MPA-AUC4–12h) was higher in the MMF and TAC group (p = 0.004). Consistently, MPA clearance wa...
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Papers by massimo baraldo