Background: Little is known about pneumococcal carrier states in older adults. The main aim of th... more Background: Little is known about pneumococcal carrier states in older adults. The main aim of this study was to evaluate pneumococcal colonization patterns among older adults in two centres in Milan, Italy, before the widespread use of the 13-valent pneumococcal vaccine (PCV13) in this age group, to investigate demographic and clinical features that are associated with pneumococcal colonization and to estimate the potential coverage offered by PCV13. Results: Among 417 adults ≥65 years old (171, 41.1 %, ≥75 years), 41 (9.8 %) were pneumococcal carriers. Univariate and multivariate analyses revealed that pneumococcal colonization was significantly less common among individuals with underlying co-morbidities than among those without (odds ratio [OR] 0.453, 95 % confidence interval [CI] 0.235–0.875, p = 0.018; adjusted OR 0.503, 95 % CI 0.255–0.992, p = 0.047). Moreover, among these patients, those with cardiac disease had a significantly lower risk of colonization (OR 0.308, 95 % CI ...
. The assessment of planned discharges: agreement between BRASS index and clinical judgement. Int... more . The assessment of planned discharges: agreement between BRASS index and clinical judgement. Introduction: The BRASS (Blaylock Risk Assessment Screening Score) index is a risk screening tool for identification of patients at risk of difficult discharge. Objective: To assess the agreement of discharge options between the BRASS classification and the nurses' clinical judgement. Methods: Consecutive patients admitted to surgical wards of a large Italian hospital from November 2016 to June 2017 were assessed with the BRASS index within 48 hours from admission and 24 hours before discharge. After discharge a group of expert nurses, blind to the BRASS score and patient effective destination, planned the patients' discharge reviewing the clinical records. Patients were classified as needing ordinary discharge, with support or to hospital. Results: The 90% of the 428 included patients remained in the same BRASS risk class; the agreement between BRASS score (K Cohen) at admission and clinical judgement was 0.474 and 0.533 at discharge. Of the 96 subject at need of discharge with support or to hospital, 60 were classified in the same class by the BRASS Index. Factors that impacted on the different classification were patients' age, presence of devices and availability and appropriateness of social support. Conclusions: Most patients remained in the same BRASS class. There is moderate agreement between BRASS index and clinical judgement, specifically for patients at medium/high risk of difficult discharge. Our data confirm the need for including new items in the Brass scale.
Our randomized trial found no survival advantage for axillary dissection (AD) compared observatio... more Our randomized trial found no survival advantage for axillary dissection (AD) compared observation only (no AD) in older patients with early breast cancer and a clinically negative axilla, indicating that AD is unnecessary. We compared characteristics and outcomes in out-trial patients with those in trial patients to provide indications as to whether AD can be safely omitted outside the trial setting. The trial started in 1996, recruiting 238 patients age 65-80 years with cT1cN0 breast cancer, randomized to conservative surgery with or without AD. Over the recruitment period, 109 eligible patients who refused to participate in the trial, also received conservative breast surgery with or without AD depending on patient preference/surgeon opinion. Trial and out-trial patients received conventionally-fractioned whole breast radiation and tamoxifen for five years. Endpoints were breast cancer mortality, overall survival, and cumulative incidence of axillary disease in patients not receiving AD. After 15 years of follow-up, breast cancer mortality and overall survival did not differ between the AD and no AD arms, in either the trial or out-trial cohorts. The 15-year cumulative incidence of axillary relapse was 6% in the no AD arm of the trial group, and zero in the no AD arm of the out-trial group. Outside the trial setting, older patients with T1N0 breast cancer can be safely treated by conservative surgery, postoperative radiotherapy and tamoxifen for five years (if ER-positive). Axillary surgery is appropriate only for the small proportion of patients who develop overt axillary disease during follow-up.
Real-time PCR is a laboratory technique which is used to amplify and simultaneously quantify the ... more Real-time PCR is a laboratory technique which is used to amplify and simultaneously quantify the concentration of biological markers based on sequences of nucleic acid (DNA or RNA). We investigated data from an external quality control of real-time PCR and we observed the presence of outliers. The aim of this work is to compare the performance of L2-norm (OLS) regression method with L1-norm (LAD) robust regression method in estimating the nucleic acid concentration in the presence of outliers. For this purpose a simulation study was planned and two different procedures (OLS and LAD) were applied to the simulated data. Both non contaminated and contaminated (with outliers) situations were considered. In the absence of outliers OLS procedure enables obtaining a precise and accurate estimate of the nucleic acid concentration, whereas the presence of outliers leads to a biased estimate, which can be improved by using LAD robust method
BackgroundVascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors... more BackgroundVascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population.Patients and methodsIn this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs.ResultsA total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001).ConclusionsMACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.
In several experimental or observational clinical studies, the evaluation of the effect of a ther... more In several experimental or observational clinical studies, the evaluation of the effect of a therapy and the impact of prognostic factors is based on relapse-free survival and the suited regression models. Relapse free survival is a net survival and needs to be interpreted as the survival probability that would be observed if all patients experienced relapse sooner or later. Death without evidence of relapse prevents the subsequent observation of relapse, acting in a competing risks framework. Relapse free survival is often estimated by standard regression models after censoring times to death. The association between relapse and death is thus ignored. However to better estimate relapse free survival a bivariate distribution of times to events needs to be considered, for example by means of copula models, with ad hoc estimating procedures. We concentrate here on the copula graphic estimator, for which a pertinent regression model has been developed (Lo and Wilke). The advantage of this approach is based on the relationship between net survival, overall survival and cause specific hazard. Regression models can be fitted for the latter quantity by standard statistical methods and the estimates can be used to compute net survival through a copula structure. Parametric models are preferred. To avoid the constraint of parametric distribution, we propose piecewise regression models. A consistent estimate of the association parameter for the copula model can be obtained by considering the semi-competing risks framework, because death can be observed after relapse. The drawback of the copula graphic regression model is that no direct parametric estimation of the regression coefficient for the covariates is available. To obtain an overall view of the association between covariate levels and net relapse free survival we propose a multivariate visualisation approach through Multiple Correspondence Analysis. This approach has been applied to two case series of patients with breast cancer and extremity soft tissue sarcoma respectively, in order to compare the results obtained by piecewise exponential model on cause specific hazard and net relapse free survival computed through copula graphic estimator
AimTo examine the trajectory of forced expiratory volume in 1 s (FEV1) using data from the Europe... more AimTo examine the trajectory of forced expiratory volume in 1 s (FEV1) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to 2016,i.e.the era before highly effective modulator therapy (HEMT). We evaluated risk factors for FEV1decline.MethodsThe study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008–2016). The evolution of FEV1% predicted (%FEV1) with age, and the yearly change in %FEV1were evaluated. Risk factors considered were cystic fibrosis transmembrane conductance regulator (CFTR) mutation class, gender, age at diagnosis, neonatal screening, meconium ileus, sweat chloride concentration at diagnosis and country's income level.ResultsWe used 199 604 FEV1recordings from 38 734 patients. The fastest decline was seen during puberty and in patients diagnosed before the age of 10 years. Males had a higher %FEV1, but a higher yearly %FEV1loss between the ages of 15 and 25 years. W...
Background: Little is known about pneumococcal carrier states in older adults. The main aim of th... more Background: Little is known about pneumococcal carrier states in older adults. The main aim of this study was to evaluate pneumococcal colonization patterns among older adults in two centres in Milan, Italy, before the widespread use of the 13-valent pneumococcal vaccine (PCV13) in this age group, to investigate demographic and clinical features that are associated with pneumococcal colonization and to estimate the potential coverage offered by PCV13. Results: Among 417 adults ≥65 years old (171, 41.1 %, ≥75 years), 41 (9.8 %) were pneumococcal carriers. Univariate and multivariate analyses revealed that pneumococcal colonization was significantly less common among individuals with underlying co-morbidities than among those without (odds ratio [OR] 0.453, 95 % confidence interval [CI] 0.235–0.875, p = 0.018; adjusted OR 0.503, 95 % CI 0.255–0.992, p = 0.047). Moreover, among these patients, those with cardiac disease had a significantly lower risk of colonization (OR 0.308, 95 % CI ...
. The assessment of planned discharges: agreement between BRASS index and clinical judgement. Int... more . The assessment of planned discharges: agreement between BRASS index and clinical judgement. Introduction: The BRASS (Blaylock Risk Assessment Screening Score) index is a risk screening tool for identification of patients at risk of difficult discharge. Objective: To assess the agreement of discharge options between the BRASS classification and the nurses' clinical judgement. Methods: Consecutive patients admitted to surgical wards of a large Italian hospital from November 2016 to June 2017 were assessed with the BRASS index within 48 hours from admission and 24 hours before discharge. After discharge a group of expert nurses, blind to the BRASS score and patient effective destination, planned the patients' discharge reviewing the clinical records. Patients were classified as needing ordinary discharge, with support or to hospital. Results: The 90% of the 428 included patients remained in the same BRASS risk class; the agreement between BRASS score (K Cohen) at admission and clinical judgement was 0.474 and 0.533 at discharge. Of the 96 subject at need of discharge with support or to hospital, 60 were classified in the same class by the BRASS Index. Factors that impacted on the different classification were patients' age, presence of devices and availability and appropriateness of social support. Conclusions: Most patients remained in the same BRASS class. There is moderate agreement between BRASS index and clinical judgement, specifically for patients at medium/high risk of difficult discharge. Our data confirm the need for including new items in the Brass scale.
Our randomized trial found no survival advantage for axillary dissection (AD) compared observatio... more Our randomized trial found no survival advantage for axillary dissection (AD) compared observation only (no AD) in older patients with early breast cancer and a clinically negative axilla, indicating that AD is unnecessary. We compared characteristics and outcomes in out-trial patients with those in trial patients to provide indications as to whether AD can be safely omitted outside the trial setting. The trial started in 1996, recruiting 238 patients age 65-80 years with cT1cN0 breast cancer, randomized to conservative surgery with or without AD. Over the recruitment period, 109 eligible patients who refused to participate in the trial, also received conservative breast surgery with or without AD depending on patient preference/surgeon opinion. Trial and out-trial patients received conventionally-fractioned whole breast radiation and tamoxifen for five years. Endpoints were breast cancer mortality, overall survival, and cumulative incidence of axillary disease in patients not receiving AD. After 15 years of follow-up, breast cancer mortality and overall survival did not differ between the AD and no AD arms, in either the trial or out-trial cohorts. The 15-year cumulative incidence of axillary relapse was 6% in the no AD arm of the trial group, and zero in the no AD arm of the out-trial group. Outside the trial setting, older patients with T1N0 breast cancer can be safely treated by conservative surgery, postoperative radiotherapy and tamoxifen for five years (if ER-positive). Axillary surgery is appropriate only for the small proportion of patients who develop overt axillary disease during follow-up.
Real-time PCR is a laboratory technique which is used to amplify and simultaneously quantify the ... more Real-time PCR is a laboratory technique which is used to amplify and simultaneously quantify the concentration of biological markers based on sequences of nucleic acid (DNA or RNA). We investigated data from an external quality control of real-time PCR and we observed the presence of outliers. The aim of this work is to compare the performance of L2-norm (OLS) regression method with L1-norm (LAD) robust regression method in estimating the nucleic acid concentration in the presence of outliers. For this purpose a simulation study was planned and two different procedures (OLS and LAD) were applied to the simulated data. Both non contaminated and contaminated (with outliers) situations were considered. In the absence of outliers OLS procedure enables obtaining a precise and accurate estimate of the nucleic acid concentration, whereas the presence of outliers leads to a biased estimate, which can be improved by using LAD robust method
BackgroundVascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors... more BackgroundVascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population.Patients and methodsIn this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs.ResultsA total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001).ConclusionsMACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.
In several experimental or observational clinical studies, the evaluation of the effect of a ther... more In several experimental or observational clinical studies, the evaluation of the effect of a therapy and the impact of prognostic factors is based on relapse-free survival and the suited regression models. Relapse free survival is a net survival and needs to be interpreted as the survival probability that would be observed if all patients experienced relapse sooner or later. Death without evidence of relapse prevents the subsequent observation of relapse, acting in a competing risks framework. Relapse free survival is often estimated by standard regression models after censoring times to death. The association between relapse and death is thus ignored. However to better estimate relapse free survival a bivariate distribution of times to events needs to be considered, for example by means of copula models, with ad hoc estimating procedures. We concentrate here on the copula graphic estimator, for which a pertinent regression model has been developed (Lo and Wilke). The advantage of this approach is based on the relationship between net survival, overall survival and cause specific hazard. Regression models can be fitted for the latter quantity by standard statistical methods and the estimates can be used to compute net survival through a copula structure. Parametric models are preferred. To avoid the constraint of parametric distribution, we propose piecewise regression models. A consistent estimate of the association parameter for the copula model can be obtained by considering the semi-competing risks framework, because death can be observed after relapse. The drawback of the copula graphic regression model is that no direct parametric estimation of the regression coefficient for the covariates is available. To obtain an overall view of the association between covariate levels and net relapse free survival we propose a multivariate visualisation approach through Multiple Correspondence Analysis. This approach has been applied to two case series of patients with breast cancer and extremity soft tissue sarcoma respectively, in order to compare the results obtained by piecewise exponential model on cause specific hazard and net relapse free survival computed through copula graphic estimator
AimTo examine the trajectory of forced expiratory volume in 1 s (FEV1) using data from the Europe... more AimTo examine the trajectory of forced expiratory volume in 1 s (FEV1) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to 2016,i.e.the era before highly effective modulator therapy (HEMT). We evaluated risk factors for FEV1decline.MethodsThe study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008–2016). The evolution of FEV1% predicted (%FEV1) with age, and the yearly change in %FEV1were evaluated. Risk factors considered were cystic fibrosis transmembrane conductance regulator (CFTR) mutation class, gender, age at diagnosis, neonatal screening, meconium ileus, sweat chloride concentration at diagnosis and country's income level.ResultsWe used 199 604 FEV1recordings from 38 734 patients. The fastest decline was seen during puberty and in patients diagnosed before the age of 10 years. Males had a higher %FEV1, but a higher yearly %FEV1loss between the ages of 15 and 25 years. W...
Uploads
Papers by Annalisa Orenti