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Francesco Zanatta,1 Ekaterina Nissanova,1 Natalia Świątoniowska-Lonc,2 Antonia Pierobon,1 Giovanna Callegari,3 Francesca Olmetti,4 Guido Felicetti,5 Piotr Karniej,2 Jacek Polański,6 Anna Giardini,7 Beata Jankowska-Polańska2 1Psychology Unit of Montescano Institute, Istituti Clinici Scientifici Maugeri IRCCS, Montescano (PV), Italy; 2Department of Clinical Nursing, Faculty of Health Science, Wroclaw Medical University, Wroclaw, Poland; 3Respiratory Rehabilitation Unit of Montescano Institute, Istituti Clinici Scientifici Maugeri IRCCS, Montescano (PV), Italy; 4Cardiological Rehabilitation Unit of Montescano Institute, Istituti Clinici Scientifici Maugeri IRCCS, Montescano (PV), Italy; 5Neuromotor Rehabilitation Unit of Montescano Institute, Istituti Clinici Scientifici Maugeri IRCCS, Montescano (PV), Italy; 6Department of Internal Diseases, Occupational Medicine, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, Poland; 7Information Technology Department, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, ItalyCorrespondence: Antonia PierobonIstituti Clinici Scientifici Maugeri IRCCS, Via S. Maugeri, 4, Pavia 27100, ItalyTel +39 385 247255Fax +39 385 61386Email antonia.pierobon@icsmaugeri.itPurpose: Non-adherence to clinical prescriptions is widely recognized as the most common cause of uncontrolled hypertension, contributing to develop acute and chronic cardiovascular diseases. Specifically, patients’ unintentional non-adherence is related to psychosocial factors as beliefs about medications, perceived physician’s communication effectiveness and medication-specific social support. The aim of this study was to observe the impact of these factors on self-efficacy in relation to pharmacological and non-pharmacological self-reported adherence among older chronic patients with hypertension.Patients and Methods: This research had a cross-sectional, observational and multicentre study design. Italian inpatients under rehabilitation, and Polish inpatients/outpatients were recruited. Following a cognitive screening, socio-demographic and clinical characteristics were obtained. Data on clinical and behavioral adherence (i.e., pharmacological adherence, adherence to refill medicines, intentional non-adherence) and psychosocial factors related to treatment adherence (i.e., beliefs about medicines, physician’s communication skills, medication-specific social support, psychological antecedents and self-efficacy) were collected with self-report questionnaires.Results: A total of 458 patients were recruited. Fischer’s LSD post hoc test revealed significant differences between Italian and Polish samples in all measures (p< 0.001). Multiple linear regression analysis showed low self-reported intentional non-adherence (β = − .02, p=0.031), high self-reported adherence to refill medications (β=− .05, p=0.017), high levels of perceived physician’s communication effectiveness (β=0.11, p< 0.001), positive beliefs about medications (β=0.13, p< 0.001), and high perceived medication-specific social support (β=0.05, p< 0.001) to predict significantly high patients’ self-efficacy in relation to pharmacological and non-pharmacological self-reported adherence.Conclusion: The observed psychosocial and behavioral factors revealed to positively impact on self-efficacy in relation to treatment adherence among older chronic patients dealing with hypertension. In a prevention framework, future studies and clinical practice may consider these factors in order to improve assessment and intervention on adherence in this population.Keywords: self-reported adherence, hypertension, chronicity, self-efficacy, older patients, psychosocial

Patrizia Steca,1 Dario Monzani,1 Antonia Pierobon,2 Giulia Avvenuti,2 Andrea Greco,1 Anna Giardini2 1Department of Psychology, University of Milano – Bicocca, Milan, 2Psychology Unit, Istituti Clinici Scientifici Maugeri Spa SB, IRCCS Montescano, Montescano, Italy Abstract: The Life Orientation Test-Revised (LOT-R) measures dispositional optimism (DO) – an individual difference promoting physical and psychological well-being in healthy adults (HAs) as well as in patients with chronic heart failure (CHF) and healthcare providers (HPs). Controversy has arisen regarding the dimensionality of the LOT-R. Whereas DO was originally defined as a one-dimensional construct, empirical evidence suggests two correlated factors in the LOT-R. This study was the first attempt to identify the best factor structure of the LOT-R in patients with CHF and HPs and to evaluate its measurement invariance among subsamples of patients with CHF, HPs, and a normative sample of HAs. Its validity was also evaluated in patients with CHF. The sample comprised 543 participants (34% HAs; 34% HPs; and 32% CHF patients). Congeneric, two correlated factor, and two orthogonal factor models for the LOT-R were compared by performing confirmatory factor analysis (CFA). Measurement invariance was evaluated by considering differential item functioning (DIF) among subsamples of HPs, patients with CHF, and HAs. In patients with CHF, validity was assessed by considering associations with anxiety and depression. The CFA demonstrated the superior fit of the two orthogonal factor model. Moreover, across patients with CHF, HPs, and HAs, the results highlighted a minimal DIF with only trivial consequences. Finally, negative but weak correlations of DO with anxiety and depression confirmed the validity of the LOT-R in patients with CHF. In summary, these findings supported the validity and suitability of the LOT-R for the assessment of DO in patients with CHF, HPs, and HAs. Keywords: Life Orientation Test-Revised, dispositional optimism, validity, measurement equivalence, chronic heart failure

Antonia Pierobon,1 Elisa Sini Bottelli,1 Laura Ranzini,1 Claudio Bruschi,2 Roberto Maestri,3 Giorgio Bertolotti,4 Marinella Sommaruga,5 Valeria Torlaschi,1 Simona Callegari,1 Anna Giardini1 1Psychology Unit, 2Department of Pulmonary Rehabilitation, 3Department of Biomedical Engineering, Istituti Clinici Scientifici Maugeri, IRCCS, Montescano, 4Psychology Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Tratate, 5Clinical Psychology and Social Support Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Camaldoli, Italy Abstract: In addition to clinical comorbidities, psychological and neuropsychological problems are frequent in COPD and may affect pulmonary rehabilitation delivery and outcome. The aims of the study were to describe a COPD population in a rehabilitative setting as regards the patients depressive symptoms, anxiety, mild cognitive impairment (MCI) and self-reported adherence and to analyze their relationships; to compare the COPD sample MCI scores with normative data; and to investigate which factors might predict adherence to prescribed physical exercise. This was a multicenter observational cross-sectional study. Of the 117 eligible stable COPD inpatients, 84 were enrolled according to Global initiative for chronic Obstructive Lung Disease (GOLD) criteria (mainly in Stage III–IV). The assessment included Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), anxiety, depression and self-reported pharmacological and nonpharmacological adherence. From the MMSE, 3.6% of patients were found to be impaired, whereas from the MoCA 9.5% had a likely MCI. Patients referred had mild-severe depression (46.7%), anxiety (40.5%), good pharmacological adherence (80.3%) and difficulties in following prescribed diet (24.1%) and exercise (51.8%); they struggled with disease acceptance (30.9%) and disease limitations acceptance (28.6%). Most of them received good family (89%) or social (53%) support. Nonpharmacological adherence, depression, anxiety and MCI showed significant relations with 6-minute walking test, body mass index (BMI) and GOLD. Depression was related to autonomous long-term oxygen therapy modifications, disease perception, family support and MCI. In the multivariate logistic regression analysis, higher BMI, higher depression and lower anxiety predicted lower adherence to exercise prescriptions (P=0.0004, odds ratio =0.796, 95% CI =0.701, 0.903; P=0.009, odds ratio =0.356, 95% CI =0.165, 0.770; and P=0.05, odds ratio =2.361, 95% CI =0.995, 5.627 respectively). In COPD patients, focusing on pharmacological and nonpharmacological adherence enhance the possibility of tailored pulmonary rehabilitation programs. Keywords: depression, anxiety, mild cognitive impairment, adherence, COPD, pulmonary rehabilitation

Anna Giardini,1 Marina Maffoni,2 Przemyslaw Kardas,3 Elisio Costa4 1Psychology Unit, Istituti Clinici Scientifici Maugeri Spa SB, IRCSS Montescano, Montescano (PV), Italy; 2Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy; 3Department of Family Medicine, Medical University of Lodz, Lodz, Poland; 4Elísio Costa, UCIBIO-REQUIMTE, Faculty of Pharmacy and Porto4Ageing EIP-AHA Reference Site, University of Porto, Porto, Portugal Abstract: Worldwide, the population is aging and this trend will increase in the future due to medical, technological and scientific advancements. To take care of the elderly is highly demanding and challenging for the health care system due to their frequent condition of chronicity, multimorbidity and the consequent complex management of polypharmacy. Nonadherence to medications and to medical plans is a well-recognized public health problem and a very urgent issue in this population. For this reason, some considerations to identify a new shared approach to integrated care of older people are described. The concept of adherence should be considered as a complex and continuous process where family, caregivers and patients’ beliefs come into play. Moreover, a new culture of adherence should contemplate the complexity of multimorbidity, as well as the necessity to renegotiate the medication regimen on the basis of each patient’s needs. Keywords: population aging, chronicity, multimorbidity, polypharmacy, nonadherence

Abstract Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is frequently associated with involvement of the kidneys (causing nephrotic syndrome), heart (cardiac failure and arrhythmia), and peripheral nervous system (sensorimotor polyneuropathy and autonomic dysfunction). This condition is important to the rheumatologist for several reasons, such as its systemic involvement that mimics autoimmune rheumatic diseases, its musculoskeletal manifestations, which when recognized can allow the diagnosis of amyloidosis, and also because reactive or secondary AA amyloidosis is a complication of rheumatic inflammatory diseases. The treatment of amyloidosis depends on the type of amyloid protein involved. Early recognition of this rare disease is fundamental for improved clinical outcomes.

Abstract Although the terms “rare diseases” (RD) and “orphan diseases” (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades.

Abstract Introduction Mental health professionals, teachers, families, and public administrators are concerned about suicide rates among young people, particularly in the university context. For every ten college students worldwide, three attempt suicide in their lifetime, and two experience suicidal ideation. Reducing these rates requires interventions that recognize the problem in terms of risk factors and protective factors. Objective The general aim of the study was to map the protective factors for suicide among college students, as perceived by them, mental health professionals, and coordinators of undergraduate courses in a public university in the North of Brazil. Methods The study followed an exploratory, mixed-method design. Data were collected through interviews and the application of a questionnaire with 54 participants, including college students (n = 20), mental health professionals (n = 22), and course coordinators (n = 12). Data were analyzed using Content Analysis and simple descriptive statistics. Results The findings show that the protective factors for suicide most cited among the three groups were social support, strengthening of internal resources, institutional support, and finding meaning about the change to enter the university. Although the three audiences did not converge, the protective factors also frequently reported were psychological treatment, leisure activities, religious engagement, medical treatment, civic engagement, employability, opportunities for social ascension offered by the university, and quality family relationships. Conclusion It is suggested that these protective factors are considered when formulating policies to promote mental health and suicide prevention in the university environment.

The 2020 update of the European Seismic Hazard Model (ESHM20) is the most recent and up-to-date assessment of seismic hazard for the Euro-Mediterranean region. The new model, publicly released in May 2022, incorporates refined and cross-border harmonized earthquake catalogues, homogeneous tectonic zonation, updated active fault datasets and geological information, complex subduction sources, updated area source models, a smoothed seismicity model with an adaptive kernel optimized within each tectonic region, and a novel ground motion characteristic model. ESHM20 supersedes the 2013 European Seismic Hazard Model (ESHM13; Woessner et al., 2015) and provides full sets of hazard outputs such as hazard curves, maps, and uniform hazard spectra for the Euro-Mediterranean region. The model provides two informative hazard maps that will serve as a reference for the forthcoming revision of the European Seismic Design Code (CEN EC8) and provides input to the first earthquake risk model for Europe (Crowley et al., 2021). ESHM20 will continue to evolve and act as a key resource for supporting earthquake preparedness and resilience throughout the Euro-Mediterranean region under the umbrella of the European Facilities for Seismic Hazard and Risk consortium (EFEHR Consortium).

Elísio Costa,1 Anna Giardini,2 Magda Savin,3 Enrica Menditto,4 Elaine Lehane,5 Olga Laosa,6 Sergio Pecorelli,7,8 Alessandro Monaco,7 Alessandra Marengoni9On behalf of the A1 Action group “Prescription and Adherence to Medical Plans”, European Innovation Partnership on Active and Healthy Ageing1UCIBIO, REQUIMTE, Faculty of Pharmacy, University of Porto, Porto, Portugal; 2Psychology Unit, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Montescano (PV), Pavia, Italy; 3European Association of Pharmaceutical Full-line Wholesalers, Brussels, Belgium; 4CIRFF/Center of Pharmacoeconomics, School of Pharmacy, University of Naples FedericoII, Nápoles, Italy; 5Catherine McAuley School of Nursing and Midwifery, Brookfield Health Sciences Complex, University College Cork, Cork, Ireland; 6Centro de Investigación Clínica del Anciano Fundación para la Investigación Biomédica, Hospital Universitario de Getafe, Madrid, Spain; 7Italian Medicines Agency – AIFA, Rome, Italy; 8University of Brescia, Brescia, Italy; 9Department of Clinical and Experimental Science, University of Brescia, Brescia, Italy Abstract: Medication adherence and persistence is recognized as a worldwide public health problem, particularly important in the management of chronic diseases. Nonadherence to medical plans affects every level of the population, but particularly older adults due to the high number of coexisting diseases they are affected by and the consequent polypharmacy. Chronic disease management requires a continuous psychological adaptation and behavioral reorganization. In literature, many interventions to improve medication adherence have been described for different clinical conditions, however, most interventions seem to fail in their aims. Moreover, most interventions associated with adherence improvements are not associated with improvements in other outcomes. Indeed, in the last decades, the degree of nonadherence remained unchanged. In this work, we review the most frequent interventions employed to increase the degree of medication adherence, the measured outcomes, and the improvements achieved, as well as the main limitations of the available studies on adherence, with a particular focus on older persons.Keywords: cognitive impairment, nonadherence, tools, compliance, chronic diseases, elderly

The sealing characteristics of the geological formation located above a CO2 storage reservoir, the so-called caprock, are essential to ensure efficient geological carbon storage. If CO2 were to leak through the caprock, temporal changes in fluid geochemistry can reveal fundamental information on migration mechanisms and induced fluid-rock interactions. Here, we present the results from a unique in-situ injection experiment, where CO2-enriched fluid was continuously injected in a faulted caprock analogue. Our results show that the CO2 migration follows complex pathways within the fault structure. The joint analysis of noble gases, ion concentrations and carbon isotopes allow us to quantify mixing between injected CO2-enriched fluid and resident formation water and to describe the temporal evolution of water-rock interaction processes. The results presented here are a crucial complement to the geophysical monitoring at the fracture scale highlighting a unique migration of CO2 in fault zones.

Performing stimulation experiments at approximately 1 km depth in the Bedretto Underground Laboratory for Geosciences and Geoenergies necessitates identifying and characterizing the target fault zone for on-fault monitoring of induced fault slip and seismicity, which presents a challenge when attempting to understand seismogenic processes. We discuss the multidisciplinary approach for selecting the target fault zone for experiments planned within the Fault Activation and Earthquake Ruptures (FEAR) project, for which the aim is to induce the fault slip and seismicity for an earthquake magnitude of up to 1.0 while enhancing the monitoring and control of fluid-injection experiments. Structural geological mapping, remote sensing, exploration drilling and borehole logging, ground-penetration radar, and laboratory investigations were employed to identify and characterize the target fault – a ductile–brittle shear zone several meters wide with an intensely fractured volume spanning over 100 m. Its orientation in the in situ stress field favors reactivation in normal to strike-slip regimes. Laboratory tests showed slight velocity strengthening of the fault gouge. The fault's architecture, typical for crystalline environments, poses challenges for fluid flow, necessitating detailed hydraulic and stress characterization before each of the FEAR experiments. This multidisciplinary approach was crucial for managing rock volume heterogeneity and understanding implications for the dense monitoring network. Successfully identifying the fault sets the stage for seismic activation experiments commencing in spring 2024.

BACKGROUND: Known genetic causes of congenital heart disease (CHD) explain

Objetivos: Investigar a eficácia terapêutica de um fármaco mimético da hepcidina, Rusfertide, que tem sido pesquisado como uma opção inovadora na restauração da homeostase em diversos distúrbios hematológicos, inclusive na Policitemia Vera (PV). Metodologia: Revisão de literatura realizada em junho de 2024, utilizando as plataformas Pubmed. Foi adotado como filtro, publicações de 2020 a 2024 e encontrados 100 artigos. Desses, foram utilizados 10 artigos, que estão disponíveis na íntegra e publicados em inglês. Resultados: Após análise de estudos com pacientes que possuem PV leve e severa, foi observado que a taxa de Flebotomia terapêutica (FT) decaiu após as primeiras semanas com o uso do fármaco. Todos os pacientes apresentaram efeitos adversos, variando em graus de severidade, onde os de grau leve apresentaram reações no local da injeção (eritema), mas foi controlada ao decorrer do tratamento, e a variação do número de leucócitos, onde parte dos pacientes apresentaram valores normais da série branca e outra apresentou uma leucocitose sem causa aparente. Já os pacientes com efeitos adversos graves, foi observado uma trombocitose assintomática, Leucemia Mieloide Aguda e infarto do miocárdio, em PV severa. Além disso, todos os pacientes em tratamento apresentaram uma redução do hematócrito (Ht) para 45% em que anteriormente apresentaram valores superiores a 55% e 43% dos indivíduos estudados tiveram uma redução da frequência de FT. Discussão: A PV é uma neoplasia mieloproliferativa crônica caracterizada por uma mutação pontual no gene JAK2, que resulta na produção excessiva de células sanguíneas e está associada a complicações graves, como trombose e hemorragia. Os tratamentos convencionais, como a FT e as terapias citorredutoras, causam limitações e não aliviam adequadamente os sintomas dos pacientes. Com o objetivo de proporcionar uma melhor qualidade de vida e um controle mais eficaz da doença, foi desenvolvido o Rusfertide, um fármaco injetável que mimetiza a hepcidina, responsável pela regulação do ferro no organismo. Está sendo testado em ensaios clínicos para pacientes que dependem de FT. Esta nova abordagem tem demonstrado resultados encorajadores, como a capacidade de controlar o Ht, diminuir a frequência de FT necessárias e aliviar sintomas. O tratamento tem benefícios, pois houve o controle da neoplasia da maioria dos pacientes em tratamento. Além disso, a FT diminuiu ou cessou em todos os pacientes após o início do tratamento com Rusfertide, independentemente da categoria de risco de PV ou de tratamentos concomitantes. Essa redução do número de FT, além de possuir vantagens terapêuticas, também pode aumentar a qualidade de vida do paciente, visto que a necessidade de monitoramento constante e procedimentos invasivos limita a sua autonomia. Portanto, é sugestivo que a terapia possa melhorar o controle do Ht e diminuir o uso da FT. Conclusão: Apesar das reações adversas e da necessidade de mais pesquisas, devido a melhora da qualidade de vida do paciente, o tratamento com o Rusfertide se mostra promissor. Este fármaco pode se tornar uma ferramenta adicional para o controle desta doença, a partir de seu mecanismo de ação, que irá atingir e sustentar o controle do Ht em pacientes com PV, reduzindo o uso de FT e a ocorrência de sintomas debilitantes relacionados à doença.

Objetivos: Realizar uma comparação entre a eficácia terapêutica do Tercartus, que tem sido uma descoberta para o tratamento de Leucemia Linfoblástica Aguda (LLA) em contrapartida com a já utilizada terapia com Mesilato de Imatinibe. Metodologia: Revisão de literatura realizada em junho de 2024, utilizando as plataformas Pubmed e Clinical Trials. Foi adotado como filtro, publicações de 2020 a 2024. Dessas, foram utilizados 10 artigos, que atendiam aos critérios de serem disponíveis gratuitamente na íntegra e publicados em inglês. Resultados: Atualmente, há em andamento 8 estudos clínicos no Clinical Trials e 23 artigos no PubMed sobre os efeitos do Tercartus em pacientes adultos com LLA do tipo B recidiva ou refratária. Em um estudo realizado com 55 pacientes, foram acompanhados por 26,8 meses e observado uma taxa de remissão completa (RC) de 56% e quando a RC associado a recuperação hematológica incompleta foi obtido uma taxa de 71%. Houve uma resposta por parte dos pacientes para o Tecartus independente da idade ou porcentagem de blastos, porém quando analisado pacientes com números maiores que 75% de blastos não houve essa resposta. Quando analisados os eventos adversos, não ocorreu nenhum de grau severo, como a síndrome de liberação de citocinas. Assim, é possível se analisar que a imunoterapia fornece um benefício de sobrevivência clinicamente significativo com toxicidade gerenciável. Discussão: No final de 2023, a ANVISA aprovou o Tecartus, seu princípio ativo é o Brexucabtagene autoleucel e promove a morte de células que expressam o CD19 (células B neoplásicas), a partir da ativação e proliferação de células T e a secreção de interleucinas, com o intuito de levar a morte da célula. Entre as neoplasias que visam tratar, destaca-se a LLA de células B precursoras recidivante ou refratária. Por mais que já existam terapias disponíveis no mercado que vêm sendo utilizadas para o tratamento dessa neoplasia, como o Imatinibe, o Tecartus vem buscando se mostrar promissor para ser um novo medicamento para o tratamento da LLA. Em comparação com o tratamento com Imatinibe, que é um inibidor da atividade de proteína tirosina quinase do gene de fusão BCR-ABL da LLA, foi observado em estudos que para obter melhores taxas de sucesso e entrar em remissão e posteriormente impedir uma recidiva, deve-se fazer a associação dele com quimioterapia agressiva. Foi observado também uma grande quantidade de reações adversas, como dor abdominal e hemorragia gastrointestinal. Entretanto, os benefícios foram muitos, cerca de 62% dos pacientes mostraram aumento na taxa de remissão clínica completa. A terapia com Tecartus, no geral, tem se mostrado bastante eficaz, porém a taxa de RC foi menor quando comparado ao uso de Imatinibe. Com isso, sugere-se que o Imatinibe traz maiores benefícios em relação ao novo tratamento, apesar de possuir um tratamento a longo prazo, devido sua administração via oral, enquanto para o Tecartus é necessário uma única infusão e é necessário a associação com quimioterapia. Conclusão: Apesar de ter apresentado menor taxa de RC ao Imatinibe, o Tecartus é uma terapia promissora que faz aumentar a sobrevida global mediana e promove uma RC da neoplasia em parte dos pacientes, mesmo sendo necessário realizar quimioterapia concomitante à infusão.