Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also for the risk prediction of combination therapies with QT-prolonging drugs

Roller Speed Skating Kinematics and Electromyographic Analysis: A Methodological Approach

Roller speed skating is a discipline similar to hockey and ice skating from a biomechanical point of view, but there are no specific functional protocols for rehabilitation and performance improvement for these athletes. The aim of the study is to create a dedicated functional, kinematic and electromyographic protocol to be used as a tool for future studies on the subject. The protocol was created, starting from a correct and repeatable movement as a case study, on a world speed skating champion, using an inertial sensor positioned at the level of the first sacral vertebra, eight electromyographic probes positioned on one or the other lower limb, and a high-definition camera at 50 Hz. The results show the electromyographic activity of the muscles investigated, the degree of absolute muscle activation and compared to their maximum voluntary isometric contraction (MVIC), the level of co-activation of the agonist/antagonist muscles, and the accelerations of the body on the three axes of space. The results will represent the basis for physiotherapy and specific training use. Future developments will include the analysis of a sample of elite athletes to be able to build a normal range on the parameters investigated, and the possibility of treating in the most appropriate way possible muscle injuries (which mostly occur in the groin in such athletes) once they have occurred, even with oriented MVIC or co-activation oriented exercises

Streptococcus pneumoniae colonisation in children and adolescents with asthma: Impact of the heptavalent pneumococcal conjugate vaccine and evaluation of potential effect of thirteen-valent pneumococcal conjugate vaccine

none14noBackground: The main aim of this study was to evaluate Streptococcus pneumoniae carriage in a group of school-aged children and adolescents with asthma because these results might indicate the theoretical risk of invasive pneumococcal disease (IPD) of such patients and the potential protective efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods: Oropharyngeal samples were obtained from 423 children with documented asthma (300 males, 70.9 %), and tested for the autolysin-A-encoding (lytA) and the wzg (cpsA) gene of S. pneumoniae by means of real-time polymerase chain reaction. Results: S. pneumoniae was identified in the swabs of 192 subjects (45.4 %): 48.4 % of whom were aged = 15 years (p < 0.001). Carriage was significantly less frequent among the children who had received recent antibiotic therapy (odds ratio [OR 0.41]; 95 % confidence interval [95 % CI] 0.22-0.76). Multivariate analyses showed no association between carriage and vaccination status, with ORs of 1.05 (95 % CI 0.70-1.58) for carriers of any pneumococcal serotype, 1.08 (95 % CI 0.72-1.62) for carriers of any of the serotypes included in 7-valent pneumococcal conjugate vaccine (PCV7), and 0.76 (95 % CI 0.45-1.28) for carriers of any of the six additional serotypes of PCV13. Serotypes 19 F, 4 and 9 V were the most frequently identified serotypes in vaccinated subjects. Conclusions: These results showed that carriage of S. pneumoniae is relatively common in all school-aged children and adolescents with asthma, regardless of the severity of disease and the administration of PCV7 in the first years of life. This highlights the problem of the duration of the protection against colonisation provided by pneumococcal conjugate vaccine, and the importance of re-colonization by the same pneumococcal serotypes included in the previously used vaccine.Esposito, Susanna; Terranova, Leonardo; Patria, Maria Francesca; Marseglia, Gian Luigi; Miraglia del Giudice, Michele; Bodini, Alessandro; Martelli, Alberto; Baraldi, Eugenio; Mazzina, Oscar; Tagliabue, Claudia; Licari, Amelia; Ierardi, Valentina; Lelii, Mara; Principi, NicolaEsposito, Susanna; Terranova, Leonardo; Patria, Maria Francesca; Marseglia, GIAN LUIGI; Miraglia del Giudice, Michele; Bodini, Alessandro; Martelli, Alberto; Baraldi, Eugenio; Mazzina, Oscar; Tagliabue, Claudia; Licari, Amelia; Ierardi, Valentina; Lelii, Mara; Principi, Nicol

The dramatic COVID-19 outbreak in italy is responsible of a huge drop in urological surgical activity: A multicenter observational study

OBJECTIVE: Italy is facing the COVID-19 outbreak with an abrupt reorganization of its national health-system, in order to augment care provision to symptomatic patients. The sudden shift of personnel and resources towards COVID-19 care has led to the reduction of surgery, with possible severe drawbacks. The aim of the study is to describe the trend in surgical volume in urology, in Italy. MATERIALS AND METHODS: Thirty-three urological units with physicians affiliated to the AGILE consortium were involved in a survey. Urologists were asked to report the amount of surgical elective procedures week-by-week, from the beginning of the emergency to the following month. RESULTS: The 33 hospitals involved in the study account, globally, for 22,945 beds and are distributed in 13/20 Italian regions. Before the outbreak, the involved urology units performed an overall amount of 1,213 procedures per week, half of which were oncological. One month later, the amount of surgery declined by 78%. Lombardy, the first region with positive-cases, experienced a 94% reduction. The decrease in oncological and non-oncological surgical activity was 35,9% and 89%, respectively. The trend of the decline showed a delay of roughly 2 weeks for the other regions. CONCLUSION: Italy, the country with the highest fatality rate from COVID-19, is experiencing a sudden decline in surgical activity. It is inversely related to the increase in COVID-19 care, with potential harm particularly in the oncological field. The Italian experience can be helpful for future surgical pre-planning in other countries not so hardly hit by the disease yet

Feasibility and Accuracy of Transduodenal Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Solid Lesions Using a 19-Gauge Flexible Needle: A Multicenter Study

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Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age.Methods: From the Italian LIPIGEN cohort, we selected 1188 (&gt;= 18 years) and 708 (&lt;18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation.Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives.Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age

Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and pharmacodynamic effects in their potentially additive nature

Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug-drug interactions

Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aims: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age. Methods: From the Italian LIPIGEN cohort, we selected 1188 (≥18 years) and 708 (&lt;18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation. Results: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives. Conclusions: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age

Evaluation of muscle energy in isometric maintenance as an index of muscle fatigue in roller speed skating

Roller speed skating is a discipline in which muscle fatigue plays an important role in athletes; in this work, we wanted to evaluate whether a methodological approach based on the energy required to maintain an isometric muscle contraction for one minute, indexed on the MVIC (maximum voluntary isometric contraction), i.e. % RMS/MVIC can give results similar to the frequency decay analysis/time in terms of usability for athlete training and injury prevention. Right and left gluteus maximus and vastus lateralis muscles (involved in the propulsive phase of skating ) were examined separately by surface electromyography in three competitive athletes in short-track speed skating on asphalt. The results showed an asymmetry between the right (less resistant) and left (more resistant) lower limb, in all three athletes, from the point of view of fatigue, in both investigated muscles. Furthermore, a trend in terms of fatigue resistance was found that was directly proportional to skill in both muscles studied. This can be of help in better planning the training of street speed skaters (which although similar to the discipline on ice is not completely superimposable) with the dual purpose of improving their performance and preventing injuries, often linked to the degree of right-left muscle asymmetry

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network)