Showing papers by "University of Milano-Bicocca published in 2021"

Population Properties of Compact Objects from the Second LIGO-Virgo Gravitational-Wave Transient Catalog

Abstract: We report on the population of 47 compact binary mergers detected with a false-alarm rate of 0.01 are dynamically assembled. Third, we estimate merger rates, finding RBBH = 23.9-+8.614.3 Gpc-3 yr-1 for BBHs and RBNS = 320-+240490 Gpc-3 yr-1 for binary neutron stars. We find that the BBH rate likely increases with redshift (85% credibility) but not faster than the star formation rate (86% credibility). Additionally, we examine recent exceptional events in the context of our population models, finding that the asymmetric masses of GW190412 and the high component masses of GW190521 are consistent with our models, but the low secondary mass of GW190814 makes it an outlier.

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

Abstract: Background The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. Methods The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Results The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. Conclusion The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.

An immune-based biomarker signature is associated with mortality in COVID-19 patients.

Abstract: Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients' first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

Knowledge Graphs

Abstract: In this article, we provide a comprehensive introduction to knowledge graphs, which have recently garnered significant attention from both industry and academia in scenarios that require exploiting diverse, dynamic, large-scale collections of data. After some opening remarks, we motivate and contrast various graph-based data models, as well as languages used to query and validate knowledge graphs. We explain how knowledge can be represented and extracted using a combination of deductive and inductive techniques. We conclude with high-level future research directions for knowledge graphs.

Preliminary predictive criteria for COVID-19 cytokine storm

Abstract: Objectives To develop predictive criteria for COVID-19-associated cytokine storm (CS), a severe hyperimmune response that results in organ damage in some patients infected with COVID-19. We hypothesised that criteria for inflammation and cell death would predict this type of CS. Methods We analysed 513 hospitalised patients who were positive for COVID-19 reverse transcriptase PCR and for ground-glass opacity by chest high-resolution CT. To achieve an early diagnosis, we analysed the laboratory results of the first 7 days of hospitalisation. We implemented logistic regression and principal component analysis to determine the predictive criteria. We used a ‘genetic algorithm’ to derive the cut-offs for each laboratory result. We validated the criteria with a second cohort of 258 patients. Results We found that the criteria for macrophage activation syndrome, haemophagocytic lymphohistiocytosis and the HScore did not identify the COVID-19 cytokine storm (COVID-CS). We developed new predictive criteria, with sensitivity and specificity of 0.85 and 0.80, respectively, comprising three clusters of laboratory results that involve (1) inflammation, (2) cell death and tissue damage, and (3) prerenal electrolyte imbalance. The criteria identified patients with longer hospitalisation and increased mortality. These results highlight the relevance of hyperinflammation and tissue damage in the COVID-CS. Conclusions We propose new early predictive criteria to identify the CS occurring in patients with COVID-19. The criteria can be readily used in clinical practice to determine the need for an early therapeutic regimen, block the hyperimmune response and possibly decrease mortality.

Forced Social Isolation and Mental Health: A Study on 1,006 Italians Under COVID-19 Lockdown

Abstract: Most countries have been struggling with the spread of the COVID-19 pandemic imposing social isolation on their citizens. However, this measure carried risks for people's mental health. This study evaluated the psychological repercussions of objective isolation in 1,006 Italians during the first, especially strict, lockdown in spring 2020. Although varying for the regional spread-rate of the contagion, results showed that the longer the isolation and the less adequate the physical space where people were isolated, the worse the mental health (e.g., depression). Offline social contacts buffered the association between social isolation and mental health. However, when offline contacts were limited, online contacts seemed crucial in protecting mental health. The findings inform about the potential downsides of the massive social isolation imposed by COVID-19 spread, highlighting possible risk factors and resources to account for implementing such isolation measures. Specifically, besides some known factors such as physical space availability, the local contagion rate is critical in moderating the link between social isolation and mental health issues, supporting national policies implementing regional tiers of restriction severity.

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries.

Abstract: Importance Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures Tracheal intubation. Main Outcomes and Measures The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation Results Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events—in particular cardiovascular instability—were observed frequently.

The release process of microfibers: from surgical face masks into the marine environment

Abstract: Due to the Covid-19 pandemic, the use of disposable face masks has been adopted worldwide as a precautionary measure to slow down the transmission of the virus. This has determined an unprecedented rise in the production of these protective equipments, and unfortunately to a new form of environmental contamination due to the improper disposal. To provide a preliminary estimation of the release of microfibers by a surgical mask dumped in the marine environment, we carried out artificial weathering experiments. Results indicated that a single surgical mask submitted to 180 hours UV-light irradiation and vigorous stirring in artificial seawater may release up to 173,000 fibers/ day. Moreover, SEM and micro-FTIR analysis carried out onto surgical masks collected from Italian beaches highlighted the same morphological and chemical degradation signature observed in the masks subjected to the artificially weathering experiments, confirming the risks of a similar microfiber release into the marine environment.

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA).

Abstract: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.

Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial

Abstract: Importance Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule with efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Objective To evaluate event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant. Design, setting, and participants In this randomized phase 3 clinical trial, patients were enrolled November 2015 to July 2019 (data cutoff, July 17, 2019). Investigators at 47 centers in 13 countries enrolled children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow, Intervention Patients were randomized to receive 1 cycle of blinatumomab (n = 54; 15 μg/m2/d for 4 weeks, continuous intravenous infusion) or chemotherapy (n = 54) for the third consolidation. Main outcomes and measures The primary end point was event-free survival (events: relapse, death, second malignancy, or failure to achieve complete remission). The key secondary efficacy end point was overall survival. Other secondary end points included minimal residual disease remission and incidence of adverse events. Results A total of 108 patients were randomized (median age, 5.0 years [interquartile range {IQR}, 4.0-10.5]; 51.9% girls; 97.2% M1 marrow) and all patients were included in the analysis. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. After a median of 22.4 months of follow-up (IQR, 8.1-34.2), the incidence of events in the blinatumomab vs consolidation chemotherapy groups was 31% vs 57% (log-rank P Conclusions and relevance Among children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab compared with standard intensive multidrug chemotherapy before allogeneic hematopoietic stem cell transplant resulted in an improved event-free survival at a median of 22.4 months of follow-up. Trial registration ClinicalTrials.gov Identifier: NCT02393859.

Common-red-signal analysis with 24-yr high-precision timing of the European Pulsar Timing Array: Inferences in the stochastic gravitational-wave background search

Abstract: We present results from the search for a stochastic gravitational-wave background (GWB) as predicted by the theory of General Relativity using six radio millisecond pulsars from the Data Release 2 (DR2) of the European Pulsar Timing Array (EPTA) covering a timespan up to 24 years. A GWB manifests itself as a long-term low-frequency stochastic signal common to all pulsars, a common red signal (CRS), with the characteristic Hellings-Downs (HD) spatial correlation. Our analysis is performed with two independent pipelines, \eprise and \tn+\ftwo, which produce consistent results. A search for a CRS with simultaneous estimation of its spatial correlations yields spectral properties compatible with theoretical GWB predictions, but does not result in the required measurement of the HD correlation, as required for GWB detection. Further Bayesian model comparison between different types of CRSs, including a GWB, finds the most favoured model to be the common uncorrelated red noise described by a power-law with $A = 5.13_{-2.73}^{+4.20} \times 10^{-15}$ and $\gamma = 3.78_{-0.59}^{+0.69}$ (95% credible regions). Fixing the spectral index to $\gamma=13/3$ as expected from the GWB by circular, inspiralling supermassive black-hole binaries results in an amplitude of $A =2.95_{-0.72}^{+0.89} \times 10^{-15}$. We implement three different models, BAYESEPHEM, LINIMOSS and EPHEMGP, to address possible Solar-system ephemeris (SSE) systematics and conclude that our results may only marginally depend on these effects. This work builds on the methods and models from the studies on the EPTA DR1. We show that under the same analysis framework the results remain consistent after the data set extension.

Trust predicts COVID-19 prescribed and discretionary behavioral intentions in 23 countries.

Abstract: The worldwide spread of a new coronavirus (SARS-CoV-2) since December 2019 has posed a severe threat to individuals’ well-being. While the world at large is waiting that the released vaccines immunize most citizens, public health experts suggest that, in the meantime, it is only through behavior change that the spread of COVID-19 can be controlled. Importantly, the required behaviors are aimed not only at safeguarding one’s own health. Instead, individuals are asked to adapt their behaviors to protect the community at large. This raises the question of which social concerns and moral principles make people willing to do so. We considered in 23 countries (N = 6948) individuals’ willingness to engage in prescribed and discretionary behaviors, as well as country-level and individual-level factors that might drive such behavioral intentions. Results from multilevel multiple regressions, with country as the nesting variable, showed that publicized number of infections were not significantly related to individual intentions to comply with the prescribed measures and intentions to engage in discretionary prosocial behaviors. Instead, psychological differences in terms of trust in government, citizens, and in particular toward science predicted individuals’ behavioral intentions across countries. The more people endorsed moral principles of fairness and care (vs. loyalty and authority), the more they were inclined to report trust in science, which, in turn, statistically predicted prescribed and discretionary behavioral intentions. Results have implications for the type of intervention and public communication strategies that should be most effective to induce the behavioral changes that are needed to control the COVID-19 outbreak.

Prevalence of NAFLD, MAFLD and associated advanced fibrosis in the contemporary United States population.

Abstract: Data are limited on the epidemiological implications of the recent change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD). We therefore performed a cross-sectional study of adults recruited in the 2017-2018 National Health and Nutrition Examination Survey, a representative sample of the general US population. The prevalence of NAFLD and MAFLD based on controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) obtained through vibration-controlled transient elastography (VCTE) were 37.1% (95% CI 34.0-40.4) and 39.1% (95% CI 36.3-42.1), respectively, with higher rates among Hispanic individuals. Agreement between the two definitions was high (Cohen's κ 0.92). Patients with NAFLD and MAFLD also showed similar risk of advanced liver fibrosis (7.5% and 7.4% respectively). Our results suggest that the recent change in diagnostic criteria did not affect the prevalence of the condition in the general United States population.

Genetic analyses identify widespread sex-differential participation bias

Abstract: Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index–increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10−36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow. Genetic analyses identify widespread sex-differential participation bias in population-based studies and show how this bias can lead to incorrect inferences. These findings highlight new challenges for association studies as sample sizes continue to grow.

Classification and Personalized Prognostic Assessment on the Basis of Clinical and Genomic Features in Myelodysplastic Syndromes

Abstract: PURPOSERecurrently mutated genes and chromosomal abnormalities have been identified in myelodysplastic syndromes (MDS). We aim to integrate these genomic features into disease classification and pr...

How the COVID-19 pandemic will change the future of critical care.

Abstract: Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.

The Atacama cosmology telescope: a catalog of >4000 sunyaev–zel'dovich galaxy clusters

Abstract: We present a catalog of 4195 optically confirmed Sunyaev–Zel’dovich (SZ) selected galaxy clusters detected with signal-to-noise ratio >4 in 13,211 deg2 of sky surveyed by the Atacama Cosmology Telescope (ACT). Cluster candidates were selected by applying a multifrequency matched filter to 98 and 150 GHz maps constructed from ACT observations obtained from 2008 to 2018 and confirmed using deep, wide-area optical surveys. The clusters span the redshift range 0.04 1 clusters, and a total of 868 systems are new discoveries. Assuming an SZ signal versus mass-scaling relation calibrated from X-ray observations, the sample has a 90% completeness mass limit of M500c > 3.8 × 1014 Me, evaluated at z = 0.5, for clusters detected at signal-to-noise ratio >5 in maps filtered at an angular scale of 2 4. The survey has a large overlap with deep optical weak-lensing surveys that are being used to calibrate the SZ signal mass-scaling relation, such as the Dark Energy Survey (4566 deg2), the Hyper Suprime-Cam Subaru Strategic Program (469 deg2), and the Kilo Degree Survey (825 deg2). We highlight some noteworthy objects in the sample, including potentially projected systems, clusters with strong lensing features, clusters with active central galaxies or star formation, and systems of multiple clusters that may be physically associated. The cluster catalog will be a useful resource for future cosmological analyses and studying the evolution of the intracluster medium and galaxies in massive clusters over the past 10 Gyr.

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

Adherence to Single-Pill Versus Free-Equivalent Combination Therapy in Hypertension: A Systematic Review and Meta-Analysis.

Abstract: Poor adherence to antihypertensive therapy is a major cause of poor blood pressure (BP) control in patients with hypertension. Regimen simplification may improve adherence and BP control. This systematic review assessed whether single-pill combination (SPC) therapy led to improved adherence, persistence, and better BP control compared with free-equivalent combination (FEC) therapy in patients with hypertension. PubMed, Medline, Embase, and the Cochrane Library were searched until July 2020, in addition to manual searching of relevant congress abstracts from 2014 to 2020 for studies including adults with hypertension aged ≥18 years receiving SPC or FEC antihypertensive therapy measuring any of the following: adherence, persistence, and reductions in systolic BP and/or diastolic BP. Adherence and persistence were summarized in a narrative analysis; direct pair-wise meta-analysis was conducted to compare BP reductions with SPC therapy versus FEC therapy using fixed-effect and random-effects models. Following screening, 44 studies were included. The majority (18 of 23) of studies measuring adherence showed adherence was significantly improved in patients receiving SPCs versus FECs. Overall, 16 studies measured persistence, of which 14 showed that patients receiving SPCs had significantly improved persistence or were significantly less likely to discontinue therapy than patients receiving FECs. Systolic BP (mean difference, -3.99 [95% CI, -7.92 to -0.07]; P=0.05) and diastolic BP (-1.54 [95% CI, -2.67 to -0.41]; P=0.0076) were both significantly reduced with SPC therapy compared with FEC therapy at week 12. SPC therapy leads to improved adherence and persistence compared with FEC therapy and may lead to better BP control in patients with hypertension.