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  1. Article ; Online: Functional modeling of recurrent events on time-to-event processes.

    Spreafico, Marta / Ieva, Francesca

    Biometrical journal. Biometrische Zeitschrift

    2021  Volume 63, Issue 5, Page(s) 948–967

    Abstract: In clinical practice, it is often the case where the association between the occurrence of events and time-to-event outcomes is of interest; thus, it can be modeled within the framework of recurrent events. The purpose of our study is to enrich the ... ...

    Abstract In clinical practice, it is often the case where the association between the occurrence of events and time-to-event outcomes is of interest; thus, it can be modeled within the framework of recurrent events. The purpose of our study is to enrich the information available for modeling survival with relevant dynamic features, properly taking into account their possibly time-varying nature, as well as to provide a new setting for quantifying the association between time-varying processes and time-to-event outcomes. We propose an innovative methodology to model information carried out by time-varying processes by means of functional data, modeling each time-varying variable as the compensator of marked point process the recurrent events are supposed to derive from. By means of Functional Principal Component Analysis, a suitable dimensional reduction of these objects is carried out in order to plug them into a Cox-type functional regression model for overall survival. We applied our methodology to data retrieved from the administrative databases of Lombardy Region (Italy), related to patients hospitalized for Heart Failure (HF) between 2000 and 2012. We focused on time-varying processes of HF hospitalizations and multiple drugs consumption and we studied how they influence patients' overall survival. This novel way to account for time-varying variables allowed to model self-exciting behaviors, for which the occurrence of events in the past increases the probability of a new event, and to quantify the effect of personal behaviors and therapeutic patterns on survival, giving new insights into the direction of personalized treatment.
    MeSH term(s) Heart Failure ; Hospitalization ; Humans ; Italy ; Probability ; Proportional Hazards Models
    Language English
    Publishing date 2021-03-19
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 131640-0
    ISSN 1521-4036 ; 0323-3847 ; 0006-3452
    ISSN (online) 1521-4036
    ISSN 0323-3847 ; 0006-3452
    DOI 10.1002/bimj.202000374
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    In stock of ZB MED Bonn / Germany

    Z 1267: Show issues

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  2. Article ; Online: Dynamic monitoring of the effects of adherence to medication on survival in heart failure patients: A joint modeling approach exploiting time-varying covariates.

    Spreafico, Marta / Ieva, Francesca

    Biometrical journal. Biometrische Zeitschrift

    2020  Volume 63, Issue 2, Page(s) 305–322

    Abstract: Adherence to medication is the process by which patients take their drugs as prescribed, and represents an issue in pharmacoepidemiological studies. Poor adherence is often associated with adverse health conditions and outcomes, especially in case of ... ...

    Abstract Adherence to medication is the process by which patients take their drugs as prescribed, and represents an issue in pharmacoepidemiological studies. Poor adherence is often associated with adverse health conditions and outcomes, especially in case of chronic diseases such as heart failure (HF). This turns out in an increased request for health care services, and in a greater burden for the health care system. In recent years, there has been a substantial growth in pharmacotherapy research, aimed at studying effects and consequences of proper/improper adherence to medication both for the increasing awareness of the problem and for the pervasiveness of poor adherence among patients. However, the way adherence is computed and accounted for into predictive models is far from being informative as it may be. In fact, it is usually analyzed as a fixed baseline covariate, without considering its time-varying behavior. The purpose and novelty of this study is to define a new personalized monitoring tool exploiting time-varying definition of adherence to medication, within a joint modeling approach. In doing so, we are able to capture and quantify the association between the longitudinal process of dynamic adherence to medication with the long-term survival outcome. Another novelty of this approach consists of exploiting the potential of health care administrative databases in order to reconstruct the dynamics of drugs consumption through pharmaceutical administrative registries. In particular, we analyzed administrative data provided by Regione Lombardia - Healthcare Division related to patients hospitalized for HF between 2000 and 2012.
    MeSH term(s) Chronic Disease ; Heart Failure/drug therapy ; Humans ; Medication Adherence
    Language English
    Publishing date 2020-08-31
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 131640-0
    ISSN 1521-4036 ; 0323-3847 ; 0006-3452
    ISSN (online) 1521-4036
    ISSN 0323-3847 ; 0006-3452
    DOI 10.1002/bimj.201900365
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    In stock of ZB MED Bonn / Germany

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  3. Book ; Online: Causal effect of chemotherapy received dose intensity on survival outcome

    Spreafico, Marta / Ieva, Francesca / Fiocco, Marta

    a retrospective study in osteosarcoma

    2023  

    Abstract: This study aims to analyse the effects of reducing Received Dose Intensity (RDI) in chemotherapy treatment for osteosarcoma patients on their survival by using a novel approach. In this scenario, toxic side effects are risk factors for mortality and ... ...

    Abstract This study aims to analyse the effects of reducing Received Dose Intensity (RDI) in chemotherapy treatment for osteosarcoma patients on their survival by using a novel approach. In this scenario, toxic side effects are risk factors for mortality and predictors of future exposure levels, introducing post-assignment confounding. Chemotherapy administration data from BO03 and BO06 Randomized Clinical Trials (RCTs) in ostosarcoma are employed to emulate a target trial with three RDI-based exposure strategies: 1) standard, 2) reduced, and 3) highly-reduced RDI. Investigations are conducted between subgroups of patients characterised by poor or good Histological Responses (HRe). Inverse Probability of Treatment Weighting (IPTW) is first used to transform the original population into a pseudo-population which mimics the target randomized cohort. Then, a Marginal Structural Cox Model with effect modification is employed. Conditional Average Treatment Effects (CATEs) are ultimately measured as the difference between the Restricted Mean Survival Time of reduced/highly-reduced RDI strategy and the standard one. Confidence Intervals for CATEs are obtained using a novel IPTW-based bootstrap procedure. Significant effect modifications based on HRe were found. Increasing RDI-reductions led to contrasting trends for poor and good responders: the higher the reduction, the better (worsen) was the survival in poor (good) reponders. This study introduces a novel approach to (i) comprehensively address the challenges related to the analysis of chemotherapy data, (ii) mitigate the toxicity-treatment-adjustment bias, and (iii) repurpose existing RCT data for retrospective analyses extending beyond the original trials' intended scopes.
    Keywords Statistics - Applications
    Subject code 610
    Publishing date 2023-07-18
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Interaction between temperature and nutrients: How does the phytoplankton community cope with climate change?

    Dory, Flavia / Nava, Veronica / Spreafico, Morena / Orlandi, Valentina / Soler, Valentina / Leoni, Barbara

    The Science of the total environment

    2023  Volume 906, Page(s) 167566

    Abstract: Climate change and increasing nutrient concentrations are two major threats to lake ecosystems. Furthermore, warming is exacerbating the symptoms of eutrophication in freshwaters. Facing both environmental challenges simultaneously is more urgent than ... ...

    Abstract Climate change and increasing nutrient concentrations are two major threats to lake ecosystems. Furthermore, warming is exacerbating the symptoms of eutrophication in freshwaters. Facing both environmental challenges simultaneously is more urgent than ever to preserve and recover water quality and protect the remaining biodiversity. Here, we used long-term observational data to investigate the phytoplankton response to the interaction between temperature and nutrient variations in a deep mesotrophic subalpine lake (L. Iseo, Italy). Despite the existing management programs, we observed a deterioration of the physicochemical status of the lake between 1993 and 2021 in the water column. The average rate of temperature increase was 0.02 °C y
    MeSH term(s) Phytoplankton/physiology ; Ecosystem ; Climate Change ; Temperature ; Lakes/chemistry ; Eutrophication ; Nutrients ; China ; Phosphorus/analysis
    Chemical Substances Phosphorus (27YLU75U4W)
    Language English
    Publishing date 2023-10-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2023.167566
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 949: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Lombardy diagnostic and therapeutic network of thrombotic microangiopathy.

    Mancini, I / Agosti, P / Boscarino, M / Ferrari, B / Artoni, A / Palla, R / Spreafico, M / Crovetti, G / Volpato, E / Rossini, S / Novelli, C / Gattillo, S / Barcella, L / Salmoiraghi, M / Falanga, A / Peyvandi, F

    Orphanet journal of rare diseases

    2022  Volume 17, Issue 1, Page(s) 246

    Abstract: Background: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) requiring urgent treatment. Standardization of its diagnosis and optimal management is challenging. This study aimed to evaluate the role ... ...

    Abstract Background: Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA) requiring urgent treatment. Standardization of its diagnosis and optimal management is challenging. This study aimed to evaluate the role of centralized, rapid testing of ADAMTS13 in patients experiencing acute TMAs requiring plasma-exchange (PEX) and to estimate the incidence of TTP in a large Italian Region.
    Methods: We perfomed a cohort study in the frame of the project "Set-up of a Lombardy network for the study and treatment of patients undergoing apheresis", including 11 transfusion centers in the Region. Consecutive patients referred from 2014 to 2016 with acute TMAs requiring PEX were enrolled. Centralized ADAMTS13 activity testing was performed at the Milan Hemophilia and Thrombosis Center within 24 h.
    Results: Forty-three TMA patients (44 events) were enrolled, of whom 35 (81%) had severe ADAMTS13 deficiency. Patients with severe ADAMTS13 deficiency were younger, mainly women, with a higher prevalence of autoimmune disorders and a lower prevalence of cancer. Clinical and laboratory characteristics of patients with and without severe ADAMTS13 deficiency largely overlapped, with a lower platelet count being the only baseline marker that significantly differed between the two patient groups (ADAMTS13 activity < 10% vs ≥ 10%: median difference of -27 × 10
    Conclusions: Severe ADAMTS13 deficiency distinguished two groups of patients with largely overlapping clinical features but different treatment and disease course. This study provides a feasible model implemented in a large Italian region for the practical clinical approach to TMAs and underlines the importance of urgent ADAMTS13 activity testing for an accurate differential diagnosis and therapeutic approach.
    MeSH term(s) ADAMTS13 Protein/deficiency ; Cohort Studies ; Female ; Humans ; Plasma Exchange ; Purpura, Thrombotic Thrombocytopenic/diagnosis ; Purpura, Thrombotic Thrombocytopenic/epidemiology ; Purpura, Thrombotic Thrombocytopenic/therapy ; Thrombosis ; Thrombotic Microangiopathies/diagnosis ; Thrombotic Microangiopathies/epidemiology ; Thrombotic Microangiopathies/therapy
    Chemical Substances ADAMTS13 Protein (EC 3.4.24.87) ; ADAMTS13 protein, human (EC 3.4.24.87)
    Language English
    Publishing date 2022-06-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2225857-7
    ISSN 1750-1172 ; 1750-1172
    ISSN (online) 1750-1172
    ISSN 1750-1172
    DOI 10.1186/s13023-022-02400-y
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  6. Article ; Online: Personalized Timing for Allogeneic Stem-Cell Transplantation in Hematologic Neoplasms: A Target Trial Emulation Approach Using Multistate Modeling and Microsimulation.

    Gregorio, Caterina / Spreafico, Marta / D'Amico, Saverio / Sauta, Elisabetta / Asti, Gianluca / Lanino, Luca / Tentori, Cristina Astrid / Platzbecker, Uwe / Haferlach, Torsten / Diez-Campelo, Maria / Fenaux, Pierre / Komrokji, Rami / Della Porta, Matteo Giovanni / Ieva, Francesca

    JCO clinical cancer informatics

    2024  Volume 8, Page(s) e2300205

    Abstract: Purpose: Decision about the optimal timing of a treatment procedure in patients with hematologic neoplasms is critical, especially for cellular therapies (most including allogeneic hematopoietic stem-cell transplantation [HSCT]). In the absence of ... ...

    Abstract Purpose: Decision about the optimal timing of a treatment procedure in patients with hematologic neoplasms is critical, especially for cellular therapies (most including allogeneic hematopoietic stem-cell transplantation [HSCT]). In the absence of evidence from randomized trials, real-world observational data become beneficial to study the effect of the treatment timing. In this study, a framework to estimate the expected outcome after an intervention in a time-to-event scenario is developed, with the aim of optimizing the timing in a personalized manner.
    Methods: Retrospective real-world data are leveraged to emulate a target trial for treatment timing using multistate modeling and microsimulation. This case study focuses on myelodysplastic syndromes, serving as a prototype for rare cancers characterized by a heterogeneous clinical course and complex genomic background. A cohort of 7,118 patients treated according to conventional available treatments/evidence across Europe and United States is analyzed. The primary clinical objective is to determine the ideal timing for HSCT, the only curative option for these patients.
    Results: This analysis enabled us to identify the most appropriate time frames for HSCT on the basis of each patient's unique profile, defined by a combination relevant patients' characteristics.
    Conclusion: The developed methodology offers a structured framework to address a relevant clinical issue in the field of hematology. It makes several valuable contributions: (1) novel insights into how to develop decision models to identify the most favorable HSCT timing, (2) evidence to inform clinical decisions in a real-world context, and (3) the incorporation of complex information into decision making. This framework can be applied to provide medical insights for clinical issues that cannot be adequately addressed through randomized clinical trials.
    MeSH term(s) Humans ; Hematopoietic Stem Cell Transplantation/methods ; Hematologic Neoplasms/therapy ; Transplantation, Homologous/methods ; Male ; Middle Aged ; Female ; Precision Medicine/methods ; Adult ; Aged ; Retrospective Studies ; Myelodysplastic Syndromes/therapy ; Young Adult
    Language English
    Publishing date 2024-05-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2473-4276
    ISSN (online) 2473-4276
    DOI 10.1200/CCI.23.00205
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  7. Article ; Online: SARS-CoV-2 detection in the pericardial fluid of a patient with cardiac tamponade.

    Farina, Andrea / Uccello, Giuseppe / Spreafico, Marta / Bassanelli, Giorgio / Savonitto, Stefano

    European journal of internal medicine

    2020  Volume 76, Page(s) 100–101

    MeSH term(s) Acute Coronary Syndrome/diagnosis ; Acute Coronary Syndrome/surgery ; Betacoronavirus/isolation & purification ; COVID-19 ; Cardiac Tamponade/diagnosis ; Cardiac Tamponade/etiology ; Cardiac Tamponade/therapy ; Coronary Artery Bypass/adverse effects ; Coronary Artery Bypass/methods ; Coronavirus Infections/complications ; Coronavirus Infections/diagnosis ; Coronavirus Infections/physiopathology ; Coronavirus Infections/therapy ; Echocardiography/methods ; Humans ; Male ; Middle Aged ; Pandemics ; Patient Care Management/methods ; Pericardial Effusion/diagnosis ; Pericardial Effusion/etiology ; Pericardial Effusion/surgery ; Pericardial Effusion/virology ; Pericardiocentesis/methods ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/physiopathology ; Pneumonia, Viral/therapy ; Postoperative Complications/diagnosis ; Postoperative Complications/therapy ; Respiratory Insufficiency/diagnosis ; Respiratory Insufficiency/etiology ; Respiratory Insufficiency/therapy ; SARS-CoV-2 ; Treatment Outcome
    Keywords covid19
    Language English
    Publishing date 2020-04-23
    Publishing country Netherlands
    Document type Case Reports ; Letter
    ZDB-ID 1038679-8
    ISSN 1879-0828 ; 0953-6205
    ISSN (online) 1879-0828
    ISSN 0953-6205
    DOI 10.1016/j.ejim.2020.04.045
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2608: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Black blood matters.

    Berzuini, Alessandra / Foglieni, Barbara / Spreafico, Marta / Gerosa, Alessandro / Revelli, Nicoletta / Paccapelo, Cinzia / Prati, Daniele

    Blood transfusion = Trasfusione del sangue

    2021  Volume 19, Issue 5, Page(s) 363–365

    Language English
    Publishing date 2021-07-20
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2135732-8
    ISSN 2385-2070 ; 0041-1787 ; 1723-2007
    ISSN (online) 2385-2070
    ISSN 0041-1787 ; 1723-2007
    DOI 10.2450/2021.0144-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 798: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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