Machine learning and LACE index for predicting 30-day readmissions after heart failure hospitalization in elderly patients.

Machine learning (ML) techniques may improve readmission prediction performance in heart failure (HF) patients. This study aimed to assess the ability of ML algorithms to predict unplanned all-cause 30-day readmissions in HF elderly patients, and to compare them with conventional LACE (Length of hospitalization, Acuity, Comorbidities, Emergency department visits) index. All patients aged ≥ 65 years discharged alive between 2010 and 2019 after a hospitalization for acute HF were included in this retrospective cohort study. We applied MICE (Multivariate Imputation via Chained Equations) method to obtain a balanced, fully valued dataset and LASSO (Least Absolute Shrinkage and Selection Operator) algorithm to get the most significant features. Training (80% of records) and test (20%) cohorts were randomly selected. Study population: 3079 patients, 394 (12.8%) presented at least one readmission within 30 days, and 2685 (87.2%) did not. In the test cohort AUCs (IC95%) of XGBoost, Ada Boost Classifier, Random forest, and Gradient Boosting, and LACE Index were: 0.803 (0.734-0.872), 0.782 (0.711-0.854), 0.776 (0.703-0.848), 0.786 (0.715-0.857), and 0.504 (0.414-0.594), respectively, for predicting readmissions. A SHAP analysis was performed to offer a breakdown of the ML variables associated with readmission. Positive and negative predicting values estimates of the different ML models and LACE index were also provided, for several values of readmission rate prevalence. Among elderly patients, the rate of all-cause unplanned 30-day readmissions after hospitalization due to an acute HF was high. ML models performed better than the conventional LACE index for predicting readmissions. ML models can be proposed as promising tools for the identification of subjects at high risk of hospitalization in this clinical setting, enabling care teams to target interventions for improving overall clinical outcomes.

Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis.

AIMS: Patients with acute pulmonary embolism (PE) at low risk for short-term death are candidates for home treatment or short-hospital stay. We aimed at determining whether the assessment of right ventricle dysfunction (RVD) or elevated troponin improves identification of low-risk patients over clinical models alone. METHODS AND RESULTS: Individual patient data meta-analysis of studies assessing the relationship between RVD or elevated troponin and short-term mortality in patients with acute PE at low risk for death based on clinical models (Pulmonary Embolism Severity Index, simplified Pulmonary Embolism Severity Index or Hestia). The primary study outcome was short-term death defined as death occurring in hospital or within 30 days. Individual data of 5010 low-risk patients from 18 studies were pooled. Short-term mortality was 0.7% [95% confidence interval (CI) 0.4-1.3]. RVD at echocardiography, computed tomography or B-type natriuretic peptide (BNP)/N-terminal pro BNP (NT-proBNP) was associated with increased risk for short-term death (1.5 vs. 0.3%; OR 4.81, 95% CI 1.98-11.68), death within 3 months (1.6 vs. 0.4%; OR 4.03, 95% CI 2.01-8.08), and PE-related death (1.1 vs. 0.04%; OR 22.9, 95% CI 2.89-181). Elevated troponin was associated with short-term death (OR 2.78, 95% CI 1.06-7.26) and death within 3 months (OR 3.68, 95% CI 1.75-7.74). CONCLUSION: RVD assessed by echocardiography, computed tomography, or elevated BNP/NT-proBNP levels and increased troponin are associated with short-term death in patients with acute PE at low risk based on clinical models. RVD assessment, mainly by BNP/NT-proBNP or echocardiography, should be considered to improve identification of low-risk patients that may be candidates for outpatient management or short hospital stay.

Acute pulmonary embolism in patients presenting pulmonary deterioration after hospitalisation for non-critical COVID-19.

BACKGROUND: Emerging evidence suggests an association between COVID-19 and acute pulmonary embolism (APE). AIMS: To assess the prevalence of APE in patients hospitalised for non-critical COVID-19 who presented clinical deterioration, and to investigate the association of clinical and biochemical variables with a confirmed diagnosis of APE in these subjects. METHODS: All consecutive patients admitted to the internal medicine department of a general hospital with a diagnosis of non-critical COVID-19, who performed a computer tomography pulmonary angiography (CTPA) for respiratory deterioration in April 2020, were included in this retrospective cohort study. RESULTS: Study populations: 41 subjects, median (interquartile range) age: 71.7 (63-76) years, CPTA confirmed APE = 8 (19.51%, 95% confidence interval (CI): 8.82-34.87%). Among patients with and without APE, no significant differences were found with regards symptoms, comorbidities, treatment, Wells score and outcomes. The optimal cut-off value of d-dimer for predicting APE was 2454 ng/mL, sensitivity (95% CI): 63 (24-91), specificity: 73 (54-87), positive predictive value: 36 (13-65), negative predictive value: 89 (71-98) and AUC: 0.62 (0.38-0.85). The standard and age-adjusted d-dimer cut-offs, and the Wells score ≥2 did not associate with confirmed APE, albeit a cut-off value of d-dimer = 2454 ng/mL showed an relative risk: 3.21; 95% CI: 0.92-13.97; P = 0.073. Heparin at anticoagulant doses was used in 70.73% of patients before performing CTPA. CONCLUSION: Among patients presenting pulmonary deterioration after hospitalisation for non-critical COVID-19, the prevalence of APE is high. Traditional diagnostic tools to identify high APE pre-test probability patients do not seem to be clinically useful. These results support the use of a high index of suspicion for performing CTPA to exclude or confirm APE as the most appropriate diagnostic approach in this clinical setting.

Predictors of medium- and long-term mortality in elderly patients with acute pulmonary embolism.

INTRODUCTION: Data on medium- and long-term prognostic factors for death in elderly patients with acute Pulmonary Embolism (APE) are lacking. The present study aimed to assess sPESI score and the Charlson Comorbidity Index (CCI) as medium- and long-term predictors of mortality in elderly patients with haemodinamically stable APE. METHODS: All consecutive patients aged≥65 years old, evaluated at the emergency department (ED) of our hospital from 2010 through 2014, with a final diagnosis of APE, were included in this retrospective cohort study. RESULTS: Study population:162 patients, female:36.5%, median age:79 years old, 74% presented a sPESI score>0, and 61% a CCI≥ 1. All causes mortality: 19.8%, 23.5%, 26.5%, 32.1% and 48.2% at 3, 6 months, 1, 2 and 5 years after APE. Univariate regression analysis: CCI≥1 was associated with a higher mortality at 3, 6 months, 1, 2 and 5 years. Multivariate Cox analysis: CCI≥1 associated with increased mortality at 3 months (HR:4.29; IC95%:1.46-12.59), 6 months (HR:5.33; IC95%:1.84-15.44), 1 year (HR:4.87; IC95%:1.87-12.70), 2 years (HR:3.78; IC95%:1.74-8.25), and 5 years (HR:2.30; IC95%:1.33-3.99). sPESI score≥1 was not found to be related to an increased medium-or long-term mortality. Negative predictive values (IC95%) of CCI≥1 were 93.65% (87.61-99.69), 93.65% (87.61-99.69), 92.06% (85.37-98.76), 87.3% (79.05-95.55) and 71.61% (60.13-83.1) for mortality at 3, 6 months, 1, 2 and 5 years. CONCLUSION: In elderly patients with a confirmed normotensive APE, unlike sPESI score, CCI showed to be an independent prognostic factor for medium- and long-term mortality. In these patients, after the acute phase following a PE event, the assessment of the comorbidities burden represents the most appropriate approach for predicting medium- and long-term mortality.

Short and long-term mortality in elderly patients with suspected not confirmed pulmonary embolism.

INTRODUCTION: Most patients evaluated for suspected pulmonary embolism(PE) conclude the Emergency Department(ED) work-up with a diagnosis of PE not confirmed(PE excluded;PE-E). We aimed to investigate the clinical features, short and long-term mortality, and prognostic factors for death in elderly with PE-E, and to compare these figures with those of patients with PE confirmed(PE-C). METHODS: Consecutive patients ≥65 years old evaluated in the ED for clinically suspected hemodynamically stable acute PE were included in this retrospective cohort study. RESULTS: Study population: 657 patients with suspected PE, PE-C:162(24.65%). When compared with PE-C, patients with PE-E presented a higher prevalence of chronic cardiopulmonary disease (17.37% vs 8.02%, p = 0.003), a lower prevalence of pulse rate >110 (13.13% vs 25.93%; p<0.001), of arterial oxygen saturation <90% (16.16% vs. 25.93%; p = 0.007) and of hospitalized patients (52.93% vs 98.15%; p < 0.001). Thirty-day, 90-day, 1-year, 2-year and 5-year overall mortality was 8.83%, 15.98%, 23.59%, 29.68%, and 51.09%, respectively, differences between PE-E and PE-C non statistically significant. Among patients with PE-E, multivariate analysis showed that simplified Pulmonary Embolism Severity Index score>0 was associated with higher short and long-term mortality (30-day:HR:5.31,p = 0.029; 5 year:HR:2.18, p < 0.001), meanwhile comorbidity (Charlson Comorbidity Index>0) only with higher long-term mortality (30-day: HR:1.60, p = 0.342; 5 year: HR:1.41, p = 0.038). CONCLUSION: In real world haemodinamically stable elderly patients evaluated in the ED for suspected PE, short and long-term mortality was markedly high regardless whether PE was confirmed or excluded. At the time to set management and follow up strategies, elderly patients with PE excluded should not be considered a low-risk population.

Effectiveness of a Hospital-Based Computerized Decision Support System on Clinician Recommendations and Patient Outcomes: A Randomized Clinical Trial.

Importance: Sophisticated evidence-based information resources can filter medical evidence from the literature, integrate it into electronic health records, and generate recommendations tailored to individual patients. Objective: To assess the effectiveness of a computerized clinical decision support system (CDSS) that preappraises evidence and provides health professionals with actionable, patient-specific recommendations at the point of care. Design, Setting, and Participants: Open-label, parallel-group, randomized clinical trial among internal medicine wards of a large Italian general hospital. All analyses in this randomized clinical trial followed the intent-to-treat principle. Between November 1, 2015, and December 31, 2016, patients were randomly assigned to the intervention group, in which CDSS-generated reminders were displayed to physicians, or to the control group, in which reminders were generated but not shown. Data were analyzed between February 1 and July 31, 2018. Interventions: Evidence-Based Medicine Electronic Decision Support (EBMEDS), a commercial CDSS covering a wide array of health conditions across specialties, was integrated into the hospital electronic health records to generate patient-specific recommendations. Main Outcomes and Measures: The primary outcome was the resolution rate, the rate at which medical problems identified and alerted by the CDSS were addressed by a change in practice. Secondary outcomes included the length of hospital stay and in-hospital all-cause mortality. Results: In this randomized clinical trial, 20 563 patients were admitted to the hospital. Of these, 6480 (31.5%) were admitted to the internal medicine wards (study population) and randomized (3242 to CDSS and 3238 to control). The mean (SD) age of patients was 70.5 (17.3) years, and 54.5% were men. In total, 28 394 reminders were generated throughout the course of the trial (median, 3 reminders per patient per hospital stay; interquartile range [IQR], 1-6). These messages led to a change in practice in approximately 4 of 100 patients. The resolution rate was 38.0% (95% CI, 37.2%-38.8%) in the intervention group and 33.7% (95% CI, 32.9%-34.4%) in the control group, corresponding to an odds ratio of 1.21 (95% CI, 1.11-1.32; P < .001). The length of hospital stay did not differ between the groups, with a median time of 8 days (IQR, 5-13 days) for the intervention group and a median time of 8 days (IQR, 5-14 days) for the control group (P = .36). In-hospital all-cause mortality also did not differ between groups (odds ratio, 0.95; 95% CI, 0.77-1.17; P = .59). Alert fatigue did not differ between early and late study periods. Conclusions and Relevance: An international commercial CDSS intervention marginally influenced routine practice in a general hospital, although the change did not statistically significantly affect patient outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT02577198.

Investigation on Dabigatran Etexilate and Worsening of Renal Function in Patients with Atrial fibrillation: The IDEA Study.

BACKGROUND AND OBJECTIVES: Warfarin-related nephropathy is an unexplained acute kidney injury, and may occur in patients with supratherapeutic INR, in the absence of overt bleeding. Similar findings have been observed in rats treated with dabigatran etexilate. We conducted a prospective study in dabigatran etexilate-treated patients to assess the incidence of dabigatran-related nephropathy and to investigate the possible correlation between dabigatran plasma concentration (DPC) and worsening renal function. METHOD: One hundred and seven patients treated long term with dabigatran etexilate for non-valvular atrial fibrillation (NVAF) were followed up for 90 days. DPC, serum creatinine (SCr) and serum cystatin C were prospectively measured. Ninety five patients had complete follow-up data and were evaluable for primary endpoint. RESULTS: Eleven patients had supratherapeutic DPC, defined as DPC higher than 200 ng/ml at study enrolment, but at the end of follow-up no patient showed a persistent increase in SCr. No patients experienced acute kidney injury. CONCLUSIONS: Our study shows that no persistent renal detrimental effect is associated with dabigatran treatment. An increase in SCr during dabigatran treatment is reversible and it seems to be unrelated to dabigatran itself.

Comorbidity burden conditions the prognostic performance of D-dimer in elderly patients with acute pulmonary embolism.

INTRODUCTION: The prognostic accuracy of D-dimer for risk assessment in acute Pulmonary Embolism (APE) patients may be hampered by comorbidities. We investigated the impact of comorbidity burden (CB) by using the Charlson Comorbidity Index (CCI), on the prognostic ability of D-dimer to predict 30 and 90-day mortality in hemodynamically stable elderly patients with APE. METHODS: All patients aged >65 years with normotensive APE, consecutively evaluated in the Emergency Department since 2010 through 2014 were included in this retrospective cohort study. Area under the curve (AUC) and ½ Net Reclassification Improvement (NRI) were calculated. RESULTS: Study population: 162 patients, median age: 79.2 years. The optimal cut-off value of CCI score for predicting mortality was ≤1 (Low CB) and >1 (High CB), AUC = 0.786. Higher levels of D-dimer were associated with an increased risk death at 30 (HR = 1.039, 95%CI:1.000-1.080, p = 0.049) and 90 days (HR = 1.039, 95%CI:1.009-1.070, p = 0.012). When added to simplified Pulmonary Embolism Severity Index (sPESI) score, D-dimer increased significantly the AUC for predicting 30-day mortality in Low CB (AUC = 0.778, 95%CI:0.620-0.937, ½NRI = 0.535, p = 0.015), but not in High CB patients (AUC = 0.634, 95%CI:0.460-0.807, ½ NRI = 0.248, p = 0.294). Similarly, for 90-day mortality D-dimer increased significantly the AUC in Low CB (AUC = 0.786, 95%CI:0.643-0.929, ½NRI = 0.424, p-value = 0.025), but not in High CB patients (AUC = 0.659, 95%CI:0.541-0.778, ½NRI = 0.354, p-value = 0.165). CONCLUSION: In elderly patients with normotensive APE, comorbidities condition the prognostic performance of D-dimer, which was found to be a better predictor of death in subjects with low CB. These results support multimarker strategies for risk assessment in this population.

Patterns of treatment with antiplatelet therapy after an acute coronary syndrome: Data from a large database in a community setting.

AIMS: Current guidelines strongly recommend antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor (dual therapy) for patients with acute coronary syndrome (ACS). To better understand how antiplatelet treatment is prescribed in clinical practice, the aim of this study was to provide a more detailed description of real-world patients with and without antiplatelet treatment after an ACS, their outcomes at one-year follow-up and the related integrated cost. METHODS: The ReS database, including more than 12 million inhabitants, was evaluated. During the accrual period ACS patients discharged alive were identified on the basis of ICD-IX-CM code. Antiplatelet drug prescriptions and healthcare costs were analysed over one-year follow-up. RESULTS: In 2014, of the 25,129 patients discharged alive after an ACS, 5796 (23%) did not receive any antiplatelet therapy during the first month after hospital discharge. Among them, 3846 (66%) subjects were prescribed an antiplatelet drug subsequently, while 7.7% did not receive any antiplatelet treatment during the whole following year. Dual therapy in the subgroup of patients undergoing a revascularization procedure ( n = 8436) was prescribed to 79.2% of cases and to 46.1% ( n = 4009) of medically managed patients. The patients not treated with an antiplatelet treatment in the first month showed the highest one-year healthcare costs, mostly due to hospital re-admissions. CONCLUSIONS: This analysis of a large patient community shows that a considerable proportion of patients remained untreated with antiplatelet treatment after an ACS event. A clearer characterization of these subjects can help to improve the adherence to the current guidelines and recommendations.

Non-vitamin k antagonist oral anticoagulants in a European primary care physician survey.

BACKGROUND: Familiarity and competency in the options for stroke prevention in atrial fibrillation (AF) and the role of non-vitamin K antagonist oral anticoagulants (NOACs) may vary among primary care physicians (PCPs) from different European countries. AIMS: To investigate PCP views on prescribing and managing NOACs across Europe and identify perceived unmet needs. DESIGN & SETTING: Web-based survey including PCPs with particular interest in cardiovascular medicine. METHOD: A questionnaire was drawn up, containing 10 questions on initiation and ongoing management of NOACs; use of AF stroke guidelines on NOACs and anticoagulant switching; and perceived information needs. RESULTS: The overall response rate was 42%. The majority of PCPs declared they are responsible for and confident in both initiating and managing NOAC therapy. In some countries, PCPs are not able to initiate NOAC therapy due to administrative barriers (namely, Italy and Slovakia). No single set of guidelines is referred to across all countries and over a fifth of responders indicate they do not follow specific guidelines. The main learning needs reported were more related to initiation than to ongoing management of anticoagulant therapy. CONCLUSION: According to this self-assessment survey, the experience of most PCPs in management of different aspects of AF appears good and only some felt the need for further training. However, in the light of the importance of this topic as public health issue, intensified efforts aiming at better equipping PCPs to meet their key roles in an integrated service across Europe are overdue.

Antithrombotic therapy for venous thromboembolism in patients with cancer: expert guidance.

INTRODUCTION: Most of the current clinical guidelines recommend the use of Low-Molecular-Weight Heparins (LMWHs) for cancer-associated thrombosis (CAT). The Hokusai VTE-cancer trial reported the first results of a direct comparison between a direct oral anticoagulant (DOAC), edoxaban, and LMWH in this setting. AREAS COVERED: This review aims to critically appraise the currently available evidence on the efficacy and safety of anticoagulant agents for the long-term treatment of CAT and to provide an expert opinion and guidance in this field. EXPERT OPINION: Based on the available evidence, DOACs represent a valid alternative to LMWH for the treatment of CAT for the majority of patients with active cancer. Currently, most solid evidence comes from the Hokusai VTE-cancer study, which showed that edoxaban is non-inferior to the LMWH dalteparin, with a trend toward fewer recurrent venous thromboembolic events, but with more major bleeding events. Similar findings were reported with rivaroxaban, although the study was not sufficiently powered to allow definitive conclusions. The majority of bleeding events occurred in the upper gastrointestinal tract and in patients with gastrointestinal cancer. Thus, LMWH remains the preferred option for patients with gastrointestinal cancer. Additional studies aimed to confirm these findings with other DOACs are now warranted.

What hinders the uptake of computerized decision support systems in hospitals? A qualitative study and framework for implementation.

BACKGROUND: Advanced Computerized Decision Support Systems (CDSSs) assist clinicians in their decision-making process, generating recommendations based on up-to-date scientific evidence. Although this technology has the potential to improve the quality of patient care, its mere provision does not guarantee uptake: even where CDSSs are available, clinicians often fail to adopt their recommendations. This study examines the barriers and facilitators to the uptake of an evidence-based CDSS as perceived by diverse health professionals in hospitals at different stages of CDSS adoption. METHODS: Qualitative study conducted as part of a series of randomized controlled trials of CDSSs. The sample includes two hospitals using a CDSS and two hospitals that aim to adopt a CDSS in the future. We interviewed physicians, nurses, information technology staff, and members of the boards of directors (n = 30). We used a constant comparative approach to develop a framework for guiding implementation. RESULTS: We identified six clusters of experiences of, and attitudes towards CDSSs, which we label as "positions." The six positions represent a gradient of acquisition of control over CDSSs (from low to high) and are characterized by different types of barriers to CDSS uptake. The most severe barriers (prevalent in the first positions) include clinicians' perception that the CDSSs may reduce their professional autonomy or may be used against them in the event of medical-legal controversies. Moving towards the last positions, these barriers are substituted by technical and usability problems related to the technology interface. When all barriers are overcome, CDSSs are perceived as a working tool at the service of its users, integrating clinicians' reasoning and fostering organizational learning. CONCLUSIONS: Barriers and facilitators to the use of CDSSs are dynamic and may exist prior to their introduction in clinical contexts; providing a static list of obstacles and facilitators, irrespective of the specific implementation phase and context, may not be sufficient or useful to facilitate uptake. Factors such as clinicians' attitudes towards scientific evidences and guidelines, the quality of inter-disciplinary relationships, and an organizational ethos of transparency and accountability need to be considered when exploring the readiness of a hospital to adopt CDSSs.

Simultaneous validation of the SunTech CT40 automated blood pressure measurement device by the 1993 British Hypertension Society protocol and the Association for the Advancement of Medical Instrumentation/International Organization for Standardization 81060-2: 2013 standard.

OBJECTIVE: This study aimed to perform a simultaneous, third-party, independent validation of the oscillometric SunTech CT40 device for blood pressure (BP) measurement, according to the 1993 protocol of the British Hypertension Society and the standard of the Association for the Advancement of Medical Instrumentation (AAMI)/the International Organization for Standardization (ISO) 81060-2:2013. PARTICIPANTS AND METHODS: Patient recruitment, study procedures, and data analysis followed the recommendations stated by the protocols. The study was approved by the institutional review board. RESULTS: A total of 94 participants were included, 52 (55.3%) women, mean±SD age: 63.1±18.0 years, mean±SD arm circumference: 35.0±9.0 cm. The average of observers' entry BPs was 146.9±37.2 mmHg for systolic blood pressure (SBP) and 82.2±22.1 mmHg for diastolic blood pressure (DBP). Differences between the standard measurement and the test device within 5, 10, and 15 mmHg, for the better observer, were 79.4, 96.5, and 100.0% for SBP and 82.6, 97.5, and 100.0% for DBP, respectively. The mean±SD differences between the readings obtained using the test device and those obtained by the observers (AAMI/ISO 81060-2:2013 standard criterion 1) were 0.3±5.0 mmHg (SBP) and -0.8±4.3 mmHg (DBP), and the mean±SD differences between average of reference readings and average of test device readings in each patient (criterion 2) were 0.3±3.9 and -0.8±3.5 mmHg for SBP and DBP, respectively. CONCLUSION: The CT40 BP device achieved A/A grade of the British Hypertension Society protocol and fulfilled the requirements (criteria 1 and 2) of the AAMI/ISO standard. CT40 can be recommended for BP measurement in adults.

Comorbidity assessment as predictor of short and long-term mortality in elderly patients with hemodynamically stable acute pulmonary embolism.

Elderly patients presenting with acute pulmonary embolism (PE) frequently have significant underlying comorbidities which may condition the prognosis. The current study aimed to determine the ability of Charlson comorbidity index (CCI) score to predict short and long-term mortality in elderly patients with hemodynamically stable acute PE. All hemodynamically stable patients aged >65 years with acute PE, evaluated in the Emergency Department since 2010 through 2014, were included in this retrospective cohort study. CCI, simplified pulmonary embolism severity index (sPESI) scores and vital status were recorded. Were included 162 patients with confirmed PE, out of 657 suspected cases (24.7%). Median age: 79.2 years, 74.1% presented an sPESI > 1 and 61.1% a CCI > 1. The overall 30, 90-day and 2-year mortality was 11.7% (95%CI 6.6-16.6), 19.8% (95%CI 13.4-25.7) and 31.8% (95%CI 24.1-38.8). For 30-day mortality sPESI showed an AUC 0.642 (95%CI 0.511-0.772) and adding CCI as covariate did not increase its prognostic performance. For 90-day mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.282 (95%CI 1.151-1.429, p-value < 0.001), and sPESI a HR = NS(p-value = 0.267). For 2-year mortality, in an adjusted model including sPESI and CCI, CCI showed a HR 1.295 (95%CI 1.180-1.421, p-value < 0.001) and sPESI a HR = NS(p-value = 0.353). In elderly patients with hemodynamically stable PE, the CCI score was found to be an independent predictor of mortality. CCI shows a significantly better ability to predict 90-day and 2-year mortality than sPESI. The assessment of comorbidity burden by using the CCI score may be proposed as an useful tool to predict mortality in these patients.

Thromboprophylaxis with enoxaparin and direct oral anticoagulants in major orthopedic surgery and acutely ill medical patients: a meta-analysis.

Subjects undergoing major orthopedic surgery and acutely ill hospitalized medical patients represent a population at medium-high risk for venous thromboembolism (VTE). They are treated with low molecular weight heparin (LMWH) and direct oral anticoagulants [DOACs] for VTE prevention. We conducted a meta-analysis of phase III randomized clinical trials evaluating LMWH enoxaparin versus DOACs for prophylaxis of VTE by combining studies including patients undergoing elective total hip and knee replacement surgery, and acutely ill hospitalized medical subjects. Studies were searched using PubMed, MEDLINE, and EMBASE databases until December 2016. Differences in clinical outcomes for efficacy and safety endpoints between treatment groups were expressed as risk differences with 95% confidence intervals (95% CI), using random effects regression models. Fourteen RCTs were considered (60,467 subjects). Overall mortality, symptomatic deep venous thrombosis, non-fatal pulmonary embolism (PE) major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) are not different between treatment regimens. Treatment with LMWH enoxaparin is associated with a lower risk of fatal PE plus VTE-related death compared therapy with DOACs (RD = 0.040%, 95% CI 0.001-0.080%, p = 0.0434). Subgroup analysis shows an incidence of MB (RD = 0.181%, 95% CI 0.029-0.332%, p = 0.0033) and CRNMB (RD = 0.546%, 95% CI 0.009-1.082%, p = 0.0462) in patients treated with 40 mg OD enoxaparin compared to DOACs. In major orthopedic surgery and acutely ill hospitalized medical patients, DOACs do not offer clear advantages in terms of clinical efficacy compared to enoxaparin. The advantage of the latter in terms of major and CRNMB, when used at a dose of 40 mg, is statistically significant, but small in terms of clinical relevance.

The introduction of biosimilars of low molecular weight heparins in Europe: a critical review and reappraisal endorsed by the Italian Society for Haemostasis and Thrombosis (SISET) and the Italian Society for Angiology and Vascular Medicine (SIAPAV).

Recently, the European Medicines Agency (EMA) authorized the introduction and marketing of Thorinane® and Inhixa®, biosimilars of the Low Molecular Weight Heparin (LMWH) enoxaparin. The authorization path is considerably different from the guidelines published by the EMA in 2009, as well as from the recommendations from the International Society on Thrombosis and Haemostasis published in 2013. Indeed, both of them recommended that LMWHs biosimilars therapeutic equivalence should be demonstrated in at least one adequately designed clinical trial. Shortly after enoxaparin biosimilars approval, EMA published a revised version of its guideline, no longer requiring the execution of a clinical study in patients at risk of venous thromboembolism. Also the assessment of safety shows some relevant flaws, as it relies only on a 20 healthy volunteers study, clearly underpowered to draw any conclusions about the safety profile of the drug. In our opinion, the approach taken by EMA for approval of enoxaparin biosimilars raises serious concerns about their actual, clinical "similarity". On these grounds, with the endorsement of the Italian Society for Haemostasis and Thrombosis (SISET) and the Italian Society for Angiology and Vascular Medicine (SIAPAV), we elaborated the present document aimed at reviewing and reappraising some critical points regarding the introduction of biosimilars of LMWH in Europe. Moreover, we would strongly advise the Italian National Health Authorities not to entrust safety assessment to the post-marketing surveillance only, but to promote well designed and powered studies aimed at establish the actual efficacy and safety of LMWH biosimilars.

Patterns and determinants of use of pharmacological therapies for intermittent claudication in PAD outpatients: results of the IDOMENEO study.

BACKGROUND: Peripheral arterial disease (PAD) usually presents with intermittent claudication (IC). The aim of the present study was to assess, in clinical practice, the pattern of use of pharmacological therapies for IC in stable PAD outpatients. METHODS: A propensity analysis was performed using data from the IDOMENEO study, an observational prospective multicenter cohort study. The association between any pharmacological symptomatic IC therapy with different variables was investigated using generalized linear mixed models with pharmacological therapy as response variable and binomial error. RESULTS: Study population: 213 patients, male sex 147 (69.0%), mean age 70.0±8.6 years. Only 36.6% was under pharmacological treatment for IC, being cilostazol the most used medication (21.6%). Univariate analysis showed a probability of a patient of being assigned to any pharmacological symptomatic IC therapy of 67.0% when Ankle-Brachial Index (ABI) <0.6 and 29.8% when ABI>0.6 (P=0.0048), and a propensity to avoid pharmacological treatment for patients with a high number of drugs to treat cardiovascular risk factors (probability of 55.2% for <4 drugs and 19.6% for >4 drugs, P=0.0317). Multivariate analysis confirmed a higher probability of assigning treatment for ABI<0.6 (P=0.0274), and a trend to a lower probability in patients under polypharmacy (>4 drugs: OR=0.13, P=0.0546). CONCLUSIONS: In clinical practice, only one third of stable outpatients with IC used symptomatic pharmacological therapy for IC. We found a propensity of clinicians to assign any symptomatic pharmacological IC therapy to patients with lower values of ABI and a propensity to avoid this kind of treatment in patients under polypharmacy.

[Computerized decision support systems: EBM at the bedside]. / Sistemi computerizzati di supporto alle decisioni cliniche: l'EBM al letto del malato.

INTRODUCTION: One of the aims of Evidence-Based Medicine is to improve quality and appropriateness of care by the expedition of the knowledge transfer process. Computerized Decision Support Systems (CDSSs) are computer programs that provide alerts to the prescribing doctor directly at the moment of medical examination. In fact, alerts are integrated within the single patient electronic health record. CDSS based on the best available and updated evidence and guidelines may be an efficient tool to facilitate the transfer of the latest results from clinical research directly at the bedside, thus supporting decision-making. OBJECTIVES: The CODES (COmputerized DEcision Support) trial is a research program funded by the Italian Ministry of Health and the Lombardy Region. It aims to evaluate the feasibility of the implementation of a CDSS at the hospital level and to assess its efficacy in daily clinical practice. METHODS: The CODES project includes two pragmatic RCTs testing a CDSS (i.e. the EBMeDS - MediDSS) in two large Italian hospitals: the first is a general hospital in Vimercate (Lombardy), the second is an oncologic research center in Meldola (Emilia Romagna). The CDSS supports a full spectrum of decisions: therapy, drug interactions, diagnosis, and management of health care services are covered by a hundreds of reminders. However only few reminders are activated per patient, highlighting crucial problems in the delivery of high-quality care. The two trials have similar design and primary outcome, the rate at which alerts detected by the software are resolved by a decision of the clinicians. The project also includes the assessment of barriers and facilitators in the adoption of these new technologies by hospital staff members and the retrospective evaluation of the repeated risks in prescription habits. RESULTS: The trials are ongoing and currently more than 10,000 patients have been randomized. The qualitative analysis revealed a progressive shift in the perception of the tool. Doctors are now seeing it as a trusted second opinion, available 24/7, which is tailored to the needs of the patient. The retrospective analysis showed the opportunity to achieve a better healthcare quality through an active risk management. Aggregating data from whole hospitals emerge rare drug interactions that otherwise would not be recognizable. DISCUSSION: CDSS are promising tools to support clinicians in everyday practice. They can be used as a real time app or to perform retrospective analyses. These data can provide unique resources to hospital management.

Prognostic value of D-dimer in elderly patients with Pulmonary Embolism.

In a general population with acute Pulmonary Embolism (PE) elevated D-dimer concentrations associate with increased mortality. The aim of the study was to assess the ability of D-dimer to predict 30 and 90-days mortality in elderly patients with acute PE. Hemodynamically stable patients aged ≥65 years old with confirmed PE were included in this retrospective cohort study. A pulmonary computerized tomography angiography scan, D-dimer concentrations, simplified Pulmonary Embolism Severity Index (sPESI) variables and vital status were available for all patients. The study included 154 confirmed cases of PE (23.5 % of suspected), median age 79.1 years. D-dimer was higher in patients dead than in those alive at 30 (median 14,547 vs. 8340 ng/mL, p = 0.05) and 90 days (13,604 vs. 7973 ng/mL, p = 0.013). When adding D-dimer to sPESI, the discriminant capacity to predict mortality within 30 and 90 days was increased by 0.080 and 0.089, respectively. The contribution of D-dimer to the discriminating ability was NRI = 0.286 (95 % CI -0.198 to 0.770, p value: 0.247) at 30 days and NRI = 0.605 (95 % CI 0.223-0.988, p-value: 0.002) at 90 days.D-dimer concentration was associated with 30 and 90-days mortality and showed a higher discriminant capacity than sPESI alone to predict 90-days mortality. Adding D-dimer concentrations to sPESI score seems to improve its prognostic ability, supporting multivariable risk models as the best approach to estimate prognosis in elderly patients with PE.