QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

BACKGROUND: Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. METHOD: We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine) and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine) with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine) or lithium. An Electrocardiogram (ECG) was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. RESULTS: Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms) however this was not the case in Group 1 (-1 ± 30 ms) (Repeated measures ANOVA p < 0,01). Furthermore we found a significant difference in the number of patients who exceeded the threshold of borderline QTc interval value (450 ms) between the two groups, with seven patients in Group 2 (38%) compared to one patient in Group 1 (7%) (Fisher Exact Text, p < 0,05). CONCLUSIONS: No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a combined treatment of antipsychotic and antidepressant agents

Health impact of the emissions from a refinery: case-control study on the adult population living in two municipalities in Lomellina, Italy

Background: In the municipalities of Sannazzaro de’ Burgondi and Ferrer Erbognone (District of Lomellina, Pavia, Lombardy, Italy), an oil refinery is operating since 1963. In 2008, the company running the plant (eni S.p.A.) asked the competent bodies the permission for building a new facility (“EST”). The present work is aimed at evaluating the ante-operam health impacts of the existing facility refinery. Methods: A case-control study design was implemented. Cases were subjects admitted to hospital in 2002-2014 due to acute respiratory, cardiovascular or gastrointestinal conditions. Controls were selected among those who had not been hospitalised in that timespan. Cases and controls had to be alive at enrolment, aged 20-64 years, and were frequency-matched by age, gender and municipality. Data were extracted from the health insurance registry and from Hospital Discharge Records (ATS Pavia). Enrolled subjects were asked to complete a mailed survey. Environmental exposure was the fallout of refinery emissions (PM10) at participants’ homes, as predicted by an AERMOD model. Results: 541 respondents (125 cases, 416 controls) were included in the analyses. Response bias was excluded. Individual PM10 exposure was not significantly different between cases and controls, while it was significantly associated with municipality (being higher in Sannazzaro). The crude effect estimate of PM10 over case/control status indicated a not-significant excess of hospitalisation with the increase in PM10 exposure. Multivariate analyses confirmed those results. Conclusion: Findings indicate a possible excess of hospitalisation risk in most exposed people, but the effect is not statistically significant and may be affected by bias

Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

SARS-CoV-2-spike antibody and T-cell responses elicited by a homologous third mRNA COVID-19 dose in hemodialysis and kidney transplant recipients

This article belongs to the Section Medical Microbiology.The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.This research work was supported by funding from the Instituto de Salud Carlos III, Madrid, Spain (FIS, PI21/00563) to DN and by funding from the European Commission NextGenerationEU fund (EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global), to RG, and funding from the Valencian Society of Neprology. The project received the Isabel Burches grant from the Valencian Society of Nephrology (2/2/21).Peer reviewe

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza a(H1N1)pdm09 and B among elderly people in Europe: Results from the I-MOVE+ project

We conducted a multicentre test-negative caseâ\u80\u93control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged â\u89¥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases

Studio sul rilascio di istamina e triptasi da cisatracurio in pazienti allergici e non

Diversi studi concordano sulla pericolosità ed imprevedibilità delle reazioni di ipersensibilità ad alcuni farmaci in anestesia. Nonostante la letteratura riporti lo shock anafilattico, l’evento più drammatico di una reazione allergica, come un fenomeno raro, molti autori concordano come questo sia in parte ancora sottovalutato e sottostimato. Non esistono particolari fattori di rischio predittivi lo scatenarsi di una reazione immunitaria, ad eccezione di un rischio generalmente aumentato nei pazienti aventi ipersensibilità accertate. I farmaci più comunemente responsabili di possibili reazioni allergiche, anche se non tutti gli studi concordano, risultano essere i miorilassanti ed in particolar modo i bloccanti neuromuscolari non depolarizzanti. Il nostro studio avrà la finalità di indagare il fenomeno, in particolare analizzando il cisatracurio, uno degli ultimi farmaci introdotti in commercio ed uno dei più utilizzati in sala operatoria. Abbiamo analizzato i livelli plasmatici di istamina e triptasi di 22 pazienti sottoposti ad interventi in anestesia generale, tramite tre prelievi: il primo, valore basale, effettuato prima della somministrazione di farmaci; il secondo dopo l’induzione con proprofol e fentanyl ed il terzo dopo somministrazione del curaro. I pazienti erano stati selezionati in modo di averne 11, che riferivano una storia personale di allergia ed 11 privi di atopie; questa suddivisione ci ha dato la possibilità di eseguire uno studio comparativo. Nei soggetti analizzati non c’è stato nessun rilascio di istamina; comparando le due classi, i risultati non dimostrano grandi variazioni, tenuto conto di un valore delle triptasi sia basale che dopo somministrazione di farmaci, generalmente più elevato nei pazienti allergici; valori comunque non associabili ad una reazione immunitaria. In un caso, una donna di 38 aa, con anamnesi positiva per allergie e sottoposta a ripetuti interventi di laparocele post-colecistectomia ( 4-5 vv), abbiamo riscontrato un’istaminemia dopo somministrazione di curaro 4 volte superiore rispetto al proprio valore basale e 6 volte superiore rispetto all’induzione con il propofol e fentanest. Il valore è ragguardevole tenuto conto che la paziente era sottoposta ad una terapia per asma, che includeva farmaci antistaminici. Il dato può far supporre una reazione di ipersensibilità al cisatracurio. Questa non è stata accompagnata a manifestazioni cliniche evidenti mentre si è notato una lieve riduzione della pressione arteriosa sistemica durante il monitoraggio intraoperatorio. Pare che le reazioni allergiche subcliniche,che restano misconosciute,potrebbero avere una percentuale considerevole,visto che noi ne abbiamo isolata 1 su 11 casi

The burden of influenza and the role of influenza vaccination in adults aged 50-64 years: A summary of available evidence

Influenza is a vaccine-preventable disease and a global public health problem. Although most national influenza vaccination recommendations focus on subjects aged &amp; GE;65 years, an extensive burden of influenza has also been reported in those aged &amp; GE;50 years and is exacerbated by immune system aging. The main purpose of this review is to provide an overview of the burden of influenza and its potential prevention within the 50-64 age-group. These subjects account for a large proportion of the workforce, and play a central economic and social role. Individuals aged 50-64 years had a 3-times higher rate of hospitalization and a 9-fold higher mortality rate attributable to influenza than those aged 18-49-years, generating higher influenza-related hospitalization costs. Available data suggest that including healthy subjects aged 50-64 years in influenza vaccination recommendations would allow a broader population to be reached, reducing the economic and social burden of influenza

Crossing the AI Chasm in Neurocritical Care

Despite the growing interest in possible applications of computer science and artificial intelligence (AI) in the field of neurocritical care (neuro-ICU), widespread clinical applications are still missing. In neuro-ICU, the collection and analysis in real time of large datasets can play a crucial role in advancing this medical field and improving personalized patient care. For example, AI algorithms can detect subtle changes in brain activity or vital signs, alerting clinicians to potentially life-threatening conditions and facilitating rapid intervention. Consequently, data-driven AI and predictive analytics can greatly enhance medical decision making, diagnosis, and treatment, ultimately leading to better outcomes for patients. Nevertheless, there is a significant disparity between the current capabilities of AI systems and the potential benefits and applications that could be achieved with more advanced AI technologies. This gap is usually indicated as the AI chasm. In this paper, the underlying causes of the AI chasm in neuro-ICU are analyzed, along with proposed recommendations for utilizing AI to attain a competitive edge, foster innovation, and enhance patient outcomes. To bridge the AI divide in neurocritical care, it is crucial to foster collaboration among researchers, clinicians, and policymakers, with a focus on specific use cases. Additionally, strategic investments in AI technology, education and training, and infrastructure are needed to unlock the potential of AI technology. Before implementing a technology in patient care, it is essential to conduct thorough studies and establish clinical validation in real-world environments to ensure its effectiveness and safety. Finally, the development of ethical and regulatory frameworks is mandatory to ensure the secure and efficient deployment of AI technology throughout the process

Strain softening mechanisms in a regional scale shear zone: the Main Central Thrust Zone in the Mt. Makalu area (Eastern Nepal)

Deformation in mountain belt at middle/deep crustal levels is quite often heterogeneous and localized in high-strain zone, i.e. ductile shear zones, with the development of mylonites. One of the largest worldwide shear zones is exposed in the Himalaya where the Main Central Thrust Zone (MCTZ), a km thick ductile (to brittle) shear zone, tectonically juxtaposes the medium- to high grade metamorphic rocks of the Greater Himalaya Sequence structurally above the lowto medium- grade metamorphic rocks of the Lesser Himalaya Sequence (Hodges, 2000). In this contribution we investigate the processes active during the MCTZ evolution in the Makalu area (Eastern Nepal) where Precambrian orthogneiss, locally known as Num-orthogneiss, are ductile sheared and structural analysis testifies how a progressive transformation from orthogneiss to micaschist, trough a transitional zone, is present. Quantitative textural evolution, bulk-rock major and trace element chemical changes and mineral phases chemical changes have been characterized studying representative samples from “pristine” orthogneiss, transitional zone and micaschist. Kinematic indicators developed both at the meso and microscales, such as S-C fabric, rotated porphyroclasts and mica fishes point to a top-to the-south sense of shear. Kinematic indicators are progressively much more developed associated with changes of foliation morphology (from a spaced anastomosing schistosity to a continuous) starting from orthogneisses to micaschist. ICP-MS trace elements data confirm the common protolith origin of the studied rocks. Quantitative modal phase variations have been investigated with image analysis techniques (on BSE-SEM images) pointing to a progressive disappearance of feldspars balanced by increasing of micas. This latter process is assisted by progressive increasing of XMg in white micas and of a transition from biotite to phlogopite. Major and trace elements comparison between less deformed rocks (“pristine orthogneiss”) and higher deformed ones (micaschist) have been computed using the Isocon method (Grant, 2005). In summary, microstructural and geochemical analyses led to recognize a non-isochemical process of strain softening related to phase transformation (feldspar replaced by micas) enhanced by fluids infiltration and Mg metasomatism, which progressively favoured deformation localization within the MCTZ