Claudio Cimminiello

Risk factors for catheter-related thrombosis (CRT) in cancer patients: a patient-level data (IPD) meta-analysis of clinical trials and prospective studies

Background: Knowledge of independent, baseline risk factors for catheter‐related thrombosis (CRT) may help select adult cancer patients who are at high risk to receive thromboprophylaxis. Objectives: We conducted a meta‐analysis of individual patient‐level data to identify these baseline risk factors. Patients/Methods: MEDLINE, EMBASE, CINAHL, CENTRAL, DARE and the Grey literature databases were searched in all languages from 1995 to 2008. Prospective studies and randomized controlled trials (RCTs) were eligible. Studies were included if original patient‐level data were provided by the investigators and if CRT was objectively confirmed with valid imaging. Multivariate logistic regression analysis of 17 prespecified baseline characteristics was conducted. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results: A total sample of 5636 subjects from five RCTs and seven prospective studies was included in the analysis. Among these subjects, 425 CRT events were observed. In multivariate logistic regression, the use of implanted ports as compared with peripherally implanted central venous catheters (PICCs), decreased CRT risk (OR,u20030.43; 95% CI, 0.23–0.80), whereas past history of deep vein thrombosis (DVT) (OR,u20032.03; 95% CI, 1.05–3.92), subclavian venipuncture insertion technique (OR,u20032.16; 95% CI, 1.07–4.34) and improper catheter tip location (OR,u20031.92; 95% CI, 1.22–3.02), increased CRT risk. Conclusions: CRT risk is increased with use of PICCs, previous history of DVT, subclavian venipuncture insertion technique and improper positioning of the catheter tip. These factors may be useful for risk stratifying patients to select those for thromboprophylaxis. Prospective studies are needed to validate these findings.

Implementing an evidence-based computerized decision support system to improve patient care in a general hospital: the CODES study protocol for a randomized controlled trial

BackgroundComputerized decision support systems (CDSSs) are information technology-based software that provide health professionals with actionable, patient-specific recommendations or guidelines for disease diagnosis, treatment, and management at the point-of-care. These messages are intelligently filtered to enhance the health and clinical care of patients. CDSSs may be integrated with patient electronic health records (EHRs) and evidence-based knowledge.Methods/designWe designed a pragmatic randomized controlled trial to evaluate the effectiveness of patient-specific, evidence-based reminders generated at the point-of-care by a multi-specialty decision support system on clinical practice and the quality of care. We will include all the patients admitted to the internal medicine department of one large general hospital. The primary outcome is the rate at which medical problems, which are detected by the decision support software and reported through the reminders, are resolved (i.e., resolution rates). Secondary outcomes are resolution rates for reminders specific to venous thromboembolism (VTE) prevention, in-hospital all causes and VTE-related mortality, and the length of hospital stay during the study period.DiscussionThe adoption of CDSSs is likely to increase across healthcare systems due to growing concerns about the quality of medical care and discrepancy between real and ideal practice, continuous demands for a meaningful use of health information technology, and the increasing use of and familiarity with advanced technology among new generations of physicians. The results of our study will contribute to the current understanding of the effectiveness of CDSSs in primary care and hospital settings, thereby informing future research and healthcare policy questions related to the feasibility and value of CDSS use in healthcare systems. This trial is seconded by a specialty trial randomizing patients in an oncology setting (ONCO-CODES).Trial registrationClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02577198?term=NCT02577198&rank=1

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 (RDxa0=xa00.040%, 95% CI 0.001–0.080%, pxa0=xa00.0434). Subgroup analysis shows an incidence of MB (RDxa0=xa00.181%, 95% CI 0.029–0.332%, pxa0=xa00.0033) and CRNMB (RDxa0=xa00.546%, 95% CI 0.009–1.082%, pxa0=xa00.0462) in patients treated with 40xa0mg 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 40xa0mg, is statistically significant, but small in terms of clinical relevance.

Thromboprophylaxis with Low-Molecular-Weight Heparins: An Assessment of the Methodological Quality of Studies

Low-molecular-weight heparin (LMWH) represents the standard of care for prophylaxis of venous thromboembolism (VTE). We conducted a review of the evidence supporting the use of the different LMWHs employed in VTE prophylaxis, in different clinical settings, and analyzed its progression over time. To evaluate the standards of methodological quality of studies, we elaborated a quality assessment tool. By electronic databases, PubMed, MEDLINE, and Scopus databases, 249 articles deemed eligible for the analysis were selected. Several LMWHs did not have publications in all clinical settings. Extended duration of prophylaxis was documented only for a few LMWH. The quality score yielded statistically significant differences between the medians of the four settings (pu2009=u20090.0021) with a higher score in major orthopedic surgery (median, 16; 95% confidence interval [CI], 15-16) when compared with general surgery (median, 14; 95% CI, 13-14; pu2009<u20090.001). Median score for studies published after the year 1990 was higher than for those published earlier (pu2009<u20090.001). We conclude that the quality of the studies supporting LMWH for VTE prophylaxis in the different clinical settings is not homogeneous and inferior for studies performed before the year 1990. Clinical interchangeability of LMWHs in clinical practice remains a critical issue, and the selection of a product should be based on evidence available for each agent, and for each clinical indication derived from clinical trials.

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 >65xa0years 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 sPESIu2009>u20091 and 61.1% a CCIu2009>u20091. 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-valueu2009<u20090.001), and sPESI a HRu2009=u2009NS(p-valueu2009=u20090.267). 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-valueu2009<u20090.001) and sPESI a HRu2009=u2009NS(p-valueu2009=u20090.353). 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.

What intervention trials don't tell us: the residual risk in primary prevention.

A number of epidemiological studies and intervention clinical trials demonstrated that the in spite of the achievement of recommended targets of low-density lipoprotein (LDL)-cholesterol in subjects not yet affected by cardiovascular diseases, a substantial percentage of them still remain at risk of acute events. Beyond LDL-c, additional abnormalities of lipid profile, consisting of low high-density lipoprotein (HDL)-cholesterol and high levels of triglycerides or the combination of the two, may play a role in determining the cardiovascular prognosis. The mentioned lipid abnormalities, together with elevated apolipoprotein B and non-HDL cholesterol, do represent the burden of the so-called residual cardiovascular risk of lipid nature. Although it is plausible that there is benefit in normalizing lipid abnormalities other than LDL-C in primary prevention, it is still controversial that this actually reduces clinical events. Recent attempts to further reduce the risk of patients already given statin therapy with drugs raising HDL-c or lowering triglycerides levels failed to demonstrate a favorable impact on secondary prevention. Of importance, evidence is completely lacking for people at lower risk such as those requiring primary prevention. New and more safe/effective drugs are currently under investigation in this field. Until further information is available on the efficacy and safety of interventions aimed at restoring normal levels of triglycerides and HDL, we have to continue to implement safe and effective methods we already have to blunt the cardiovascular risk, consisting mainly of lifestyle changes and statin therapy.

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.

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.

Barriere e facilitatori all’implementazione dei sistemi di supporto decisionale computerizzati in ospedale: uno studio “grounded theory”

INTRODUCTION Computerized Decision Support Systems (CDSSs) connect health care professionals with high-quality, evidence-based information at the point-of-care to guide clinical decision-making. Current research shows the potential of CDSSs to improve the efficiency and quality of patient care. The mere provision of the technology, however, does not guarantee its uptake. This qualitative study aims to explore the barriers and facilitators to the use of CDSSs as identified by health providers. METHODS The study was performed in three Italian hospitals, each characterized by a different level of familiarity with the CDSS technology. We interviewed frontline physicians, nurses, information technology staff, and members of the hospital board of directors (n=24). A grounded theory approach informed our sampling criteria as well as the data collection and analysis. RESULTS The adoption of CDSSs by health care professionals can be represented as a process that consists of six positionings, each corresponding to an individuals use and perceived mastery of the technology. In conditions of low mastery, the CDSS is perceived as an object of threat, an unfamiliar tool that is difficult to control. On the other hand, individuals in conditions of high mastery view the CDSS as a helpful tool that can be locally adapted and integrated with clinicians competences to fulfil their needs. In the first positionings, the uptake of CDSSs is hindered by representational obstacles. The last positionings, alternatively, featured technical obstacles to CDSS uptake. DISCUSSION Our model of CDSS adoption can guide hospital administrators interested in the future integration of CDSSs to evaluate their organizational contexts, identify potential challenges to the implementation of the technology, and develop an effective strategy to address them. Our findings also allow reflections concerning the misalignment between most Italian hospitals and the current innovation trends toward the uptake of computerized decision support technologies.