Risultati per: Analisi sull’uso dei farmaci anti-osteoporotici in sette database europei

A rischio settore dei farmaci generici-equivalenti e biosimilari

Background
Inflammation is indicated as one of the factors that play a role in the development of schizophrenia, with several studies having found considerable inconsistencies in their results. Few have investigated the role of inflammation in primary psychosis in blood and cerebrospinal fluids simultaneously, the aim of this study being to investigate the expression of blood and cerebrospinal fluid inflammatory cytokines in treatment-naive first-episode psychotic participants.

Methods and analysis
This is a combined cross-sectional and prospective observational study, which is currently taking place in Durban, South Africa, will recruit 60 participants (30 cases and 30 matched controls). The primary objective is to describe baseline CSF and longitudinal expression/levels of inflammatory cytokines in the blood in persons diagnosed with first-episode psychosis (FEP) for 12 months. The secondary objective is to describe the associations between inflammatory cytokines and psychosis severity, neurocognitive performance, antipsychotic response and metabolic changes at different time points (baseline, 3, 6 and 12 months).

Interventions
We will collect the sociodemographic details of all participants, and the Positive and Negative Symptoms Scale, Patient Health Questionnaire-9, Childhood Trauma Scale, Repeatable Battery for the Assessment of Neuropsychological Status Update, metabolic markers and inflammatory markers (venous blood and lumbar puncture cerebrospinal fluid) for those with FEP. Data from matched controls will only be collected at one point and no follow-ups (cross-sectional).

Ethics and dissemination
The study protocol has been approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00004714/2022). The study is nested in an ongoing study titled the burden of HIV and Psychosis in an African setting: a longitudinal study of HIV-infected and non-infected patients with First-Episode Psychosis (BREC 571/18). The results will be actively disseminated through peer-reviewed journal publications and conference presentations.

Cattani, serve una risposta politica ai dazi, siamo in una posizione di forza

Farmindustria: ‘Scenario da evitare, fiducia nell’Ue e nel Governo’

Comunicato del 13/03/2025 n°10

Un anno fa la norma per dispensarne alcuni dall’ospedale alle farmacie

Objectives
While there is growing evidence that physical activity reduces the risk of hepatocellular carcinoma (HCC), the impact of occupational physical activity and sedentary behaviour remains unclear. This study aimed to investigate the associations between occupational physical activity and sedentary behaviour and HCC risk.

Design
Matched case-control study.

Setting
Nationwide multicentre, hospital-inpatient data set in Japan, from 2005 to 2021.

Participants
The study included 5625 inpatients diagnosed with HCC and 27 792 matched controls without liver disease or neoplasms. Participants were matched based on sex, age, admission date, and hospital.

Primary measures
The association between levels of occupational physical activity (low, medium, high) and sedentary time (short, medium, long) with the risk of HCC.

Secondary measures
Stratification of HCC risk by viral infection status (hepatitis B/C virus), alcohol consumption levels and the presence of metabolic diseases (hypertension, diabetes, dyslipidaemia, obesity).

Results
High occupational physical activity was not associated with HCC caused by hepatitis B/C virus infection in men. In women, high occupational physical activity was associated with a reduced risk of non-viral HCC, with ORs (95% CIs) of 0.65 (0.45–0.93). Among patients with non-viral HCC, medium occupational physical activity combined with medium alcohol intake further decreased the HCC risk in men with an OR of 0.70 (0.50–0.97), while high occupational physical activity combined with lowest alcohol intake decreased the HCC risk in women with an OR of 0.69 (0.48–0.99). Men and women with medium sedentary time had a lower HCC risk compared with those with long sedentary time, with ORs of 0.88 (0.79–0.98) in men and 0.77 (0.62–0.97) in women, respectively. In patients without viral infection or alcohol use, medium sedentary time reduced the HCC risk associated with fatty liver disease without comorbid metabolic diseases in women.

Conclusions
High levels of occupational physical activity and/or medium periods of sedentary time are associated with a reduced risk of HCC, particularly non-alcoholic steatohepatitis.

Obbliga le aziende a contribuire a costi di trattamento delle acque

TNF-like cytokine 1A (TL1A) and its functional receptor, death-domain receptor 3 (DR3), are members of the TNF and TNFR superfamilies, respectively, with recognised roles in regulating innate and adaptive immune responses; additional existence of a decoy receptor, DcR3, indicates a tightly regulated cytokine system. The significance of TL1A:DR3 signalling in the pathogenesis of inflammatory bowel disease (IBD) is supported by several converging lines of evidence. Herein, we aim to provide a comprehensive understanding of what is currently known regarding the TL1A/DR3 system in the context of IBD. TL1A and DR3 are expressed by cellular subsets with important roles for the initiation and maintenance of intestinal inflammation, serving as potent universal costimulators of effector immune responses, indicating their participation in the pathogenesis of IBD. Recent evidence also supports a homoeostatic role for TL1A:DR3 via regulation of Tregs and innate lymphoid cells. TL1A and DR3 are also expressed by stromal cells and may contribute to inflammation-induced or inflammation-independent intestinal fibrogenesis. Finally, discovery of genetic polymorphisms with functional consequences may allow for patient stratification, including differential responses to TL1A-targeted therapeutics. In conclusion, TL1A:DR3 signalling plays a central and multifaceted role in the immunological pathways that underlie intestinal inflammation, such as that observed in IBD. Such evidence provides the foundation for developing pharmaceutical approaches targeting this ligand-receptor pair in IBD.

Objectives
To investigate the long-term safety and efficacy of otilimab, an antigranulocyte-macrophage colony-stimulating factor monoclonal antibody, for patients with rheumatoid arthritis (RA).

Methods
ContRAst X (NCT04333147) was a phase 3, multicentre, long-term extension trial. Patients with RA aged ≥18 years who completed a qualifying contRAst trial (contRAst 1–3) and who the investigator thought might benefit from long-term otilimab treatment were eligible to enter contRAst X. Patients who received otilimab (90 mg/150 mg) in their qualifying trial maintained the same dose; patients who received tofacitinib or sarilumab were rerandomised 1:1 to either otilimab dose. Patients could continue background conventional synthetic disease-modifying antirheumatic drugs. The primary objective was long-term safety (up to 4 years).

Results
Of the 2916 patients who entered contRAst X, 2915 received otilimab (exposure range: 7–896 days); the majority were withdrawn due to early trial termination. For otilimab 90 mg and 150 mg, the incidence of adverse events (AEs) was 62% (n=902/1456) and 64% (n=931/1459), the incidence of AEs of special interest was 8% (n=120/1456) and 7% (n=95/1459) and the incidence of serious AEs was 8% (n=123/1456) and 8% (n=114/1459), respectively. There were no instances of pulmonary alveolar proteinosis (PAP), active tuberculosis (TB), TB reactivation or serious hypersensitivity reactions. The proportions of clinical disease activity index low disease activity responders remained relatively stable throughout, with no apparent reduction following the switch from tofacitinib/sarilumab to otilimab.

Conclusion
No new safety signals or instances of PAP were associated with long-term (≤2.5 years) treatment with otilimab.

Trial registration number
ClinicalTrials.gov: NCT04333147.

Molecola lonafarnib indicata contro rischio morte per progeria

A disposizione dei medici ma consultabile anche dai cittadini

This randomized clinical trial assessed the safety, pharmacokinetics, and efficacy of the humanized anti–IL-23 monoclonal antibody QX004N for patients with moderate to severe plaque psoriasis.

This cohort study examines the response and survival rates associated with ipilimumab-nivolumab therapy in patients with progressive melanoma brain metastases after anti–programmed cell death 1 (anti–PD-1) therapy.

Studio di Università Milano-Bicocca e Brescia su 6.609 studenti

Objective
This study developed and validated a stacked ensemble machine learning model to predict the risk of acute kidney injury in patients with acute pancreatitis complicated by sepsis.

Design
A retrospective study based on patient data from public databases.

Participants
This study analysed 1295 patients with acute pancreatitis complicated by septicaemia from the US Intensive Care Database.

Methods
From the MIMIC database, data of patients with acute pancreatitis and sepsis were obtained to construct machine learning models, which were internally and externally validated. The Boruta algorithm was used to select variables. Then, eight machine learning algorithms were used to construct prediction models for acute kidney injury (AKI) occurrence in intensive care unit (ICU) patients. A new stacked ensemble model was developed using the Stacking ensemble method. Model evaluation was performed using area under the receiver operating characteristic curve (AUC), precision-recall (PR) curve, accuracy, recall and F1 score. The Shapley additive explanation (SHAP) method was used to explain the models.

Main outcome measures
AKI in patients with acute pancreatitis complicated by sepsis.

Results
The final study included 1295 patients with acute pancreatitis complicated by sepsis, among whom 893 cases (68.9%) developed acute kidney injury. We established eight base models, including Logit, SVM, CatBoost, RF, XGBoost, LightGBM, AdaBoost and MLP, as well as a stacked ensemble model called Multimodel. Among all models, Multimodel had an AUC value of 0.853 (95% CI: 0.792 to 0.896) in the internal validation dataset and 0.802 (95% CI: 0.732 to 0.861) in the external validation dataset. This model demonstrated the best predictive performance in terms of discrimination and clinical application.

Conclusion
The stack ensemble model developed by us achieved AUC values of 0.853 and 0.802 in internal and external validation cohorts respectively and also demonstrated excellent performance in other metrics. It serves as a reliable tool for predicting AKI in patients with acute pancreatitis complicated by sepsis.