The Use of Risk Scores for Thromboprophylaxis in Medically Ill Patients-Rationale and Design of the RICO trial.

Background Venous thromboembolism (VTE) in hospitalized medically ill patients is a significant cause of morbidity and mortality. Guidelines suggest that VTE and bleeding risk assessment models (RAMs) should be integrated into the clinical decision-making process on thromboprophylaxis. However, poor evidence is available comparing the use of a RAM versus clinical judgement in evaluating VTE and bleeding occurrence. Methods Reducing Important Clinical Outcomes in hospitalized medical ill patients (RICO) is a multicenter, cluster-randomized, controlled clinical trial (ClinicalTrials.gov Identifier: NCT04267718). Acutely ill patients hospitalized in Internal Medicine wards are randomized to the use of RAMs-namely the Padua Prediction Score and the International Medical Prevention Registry on Venous Thromboembolism Bleeding Score-or to clinical judgement. The primary study outcome is a composite of symptomatic objectively confirmed VTE and major bleeding at 90-day follow-up. Secondary endpoints include the evaluation of clinical outcomes at hospital discharge and the assessment of VTE prophylaxis prescription during the study period. In order to demonstrate a 50% reduction in the primary outcome in the experimental group and assuming an incidence of the primary outcome of 3.5% in the control group at 90-day; 2,844 patients across 32 centers will be included in the study. Discussion The RICO trial is a randomized study of clinical management assessing the role of RAMs in hospitalized medical ill patients with the aim of reducing VTE and bleeding occurrence. The study has the potential to improve clinical practice since VTE still represents an important cause of morbidity and mortality in this setting.

Risk factors for recurrence and major bleeding in patients with cancer-associated venous thromboembolism.

Risks of recurrence and treatment-emergent bleeding are high in patients with cancer-associated venous thromboembolism (VTE) but factors associated with these risks remain substantially undefined. The aim of this analysis in patients with cancer-associated VTE included in the Caravaggio study was to identify risk factors for recurrent VTE and major bleeding. Variables potentially predictive for recurrent VTE or major bleeding were evaluated in a Cox proportional hazard multivariable analysis with backward variable selection. Recurrent VTE occurred in 78 patients (6.8%) and major bleeding in 45 (3.9%). Independent risk factors for recurrent VTE were deep vein thrombosis (DVT) as index event (Hazard ratio (HR) 1.84, 95% CI 1.17-2.88), ECOG status of 1 or more (HR 1.95, 95% CI 1.11-3.43), pancreatic or hepatobiliary cancer site (HR 2.20, 95% CI 1.19-4.06), concomitant anti-cancer treatment (HR 1.98, 95% CI 1.03-3.81) and creatinine clearance (HR 1.10, 95% CI 1.00-1.20 for every 10 ml/min absolute increase). Independent risk factors for major bleeding were ECOG status of 2 (HR 2.31, 95% CI 1.24-4.29), genitourinary cancer site (HR 2.72, 95% CI 1.28-5.77), upper gastrointestinal cancer site (HR 3.17, 95% CI 1.22-8.23), and non-resected luminal gastrointestinal cancer (HR 2.77, 95% CI 1.38-5.56). This analysis of the Caravaggio study in patients with cancer-associated VTE who were on standardized anticoagulant treatment identified five independent predictors for recurrent VTE and four independent predictors of treatment-emergent major bleeding. Considering these risks could help clinicians to optimize the anticoagulant treatment in patients with cancer-associated VTE.

One-Year Follow up of Noninvasive Respiratory Support in General Wards.

BACKGROUND: Noninvasive respiratory support (NRS) has been used to treat acute respiratory failure outside the ICU, but existing data have left many knowledge gaps for managing NRS in general wards. The primary objective of this study was to describe indications, duration of treatment, and outcomes of subjects treated with NRS outside the ICU. The secondary objective was to compare outcomes based on age < 80 or ≥ 80 y. METHODS: This retrospective observational study was conducted at Maggiore della Carità University Hospital in Novara, Italy, and included all patients treated with noninvasive ventilation (NIV) or CPAP outside the ICU from November 2017 to October 2018, with 1 year of follow-up. RESULTS: Of the 570 treatments performed, 383 subjects were analyzed, 136 NIV and 247 CPAP. Subjects' median (interquartile range [IQR]) age was 79 (72-85) y, and the main diagnoses of respiratory failure were cardiogenic pulmonary edema in 128 subjects (33%), pneumonia in 99 (26%), and COPD exacerbation in 52 (14%), with a median (IQR) treatment duration of 38 (16-74) h. Rapid response team visits lasted a median (IQR) 3 (2-6) d. Interface-related pressure lesions occurred in 13% of the subjects, in no case leading to definitive treatment discontinuation. Compared with the subjects ≥ 80 y old, the younger subjects had a median (IQR) longer hospitalization (16 [10-24] d vs 13 [9-20] d; P = .003) but slightly decreased in-hospital mortality (21% vs 30%; P = .061) and a decreased post-discharged 1-year mortality in hospital survivors (25% vs 41%; P = .002), differences observed only in the subjects treated with NIV. CONCLUSIONS: In a real-life setting outside the ICU, NIV and CPAP managed by a rapid response team with a daily visit in collaboration with ward staff highly experienced in NRS allowed us to treat the subjects without major complications. Post-discharge 1-year mortality was higher in the subjects ≥ 80 y old treated with NIV for acute hypercapnic respiratory failure.

Rivaroxaban vs placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer.

The clinical benefit of extended prophylaxis for venous thromboembolism (VTE) after laparoscopic surgery for cancer is unclear. The efficacy and safety of direct oral anticoagulants for this indication are unexplored. PROphylaxis of venous thromboembolism after LAParoscopic Surgery for colorectal cancer Study II (PROLAPS II) was a randomized, double-blind, placebo-controlled, investigator-initiated, superiority study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban after laparoscopic surgery for colorectal cancer. Consecutive patients who had laparoscopic surgery for colorectal cancer were randomized to receive rivaroxaban (10 mg once daily) or a placebo to be started at 7 ± 2 days after surgery and given for the subsequent 3 weeks. All patients received antithrombotic prophylaxis with low-molecular-weight heparin from surgery to randomization. The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT), or VTE-related death at 28 ± 2 days after surgery. The primary safety outcome was major bleeding. Patient recruitment was prematurely closed due to study drug expiry after the inclusion of 582 of the 646 planned patients. A primary study outcome event occurred in 11 of 282 patients in the placebo group compared with 3 of 287 in the rivaroxaban group (3.9 vs 1.0%; odds ratio, 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank P = .032). Major bleeding occurred in none of the patients in the placebo group and 2 patients in the rivaroxaban group (incidence rate 0.7%; 95% CI, 0-1.0). Oral rivaroxaban was more effective than placebo for extended prevention of VTE after laparoscopic surgery for colorectal cancer without an increase in major bleeding. This trial was registered at www.clinicaltrials.gov as #NCT03055026.

Clinical nutrition in internal medicine: An Italian survey by the scientific societies FADOI and SINPE.

OBJECTIVES: Patients hospitalized in internal medicine are frequently malnourished or at risk for malnutrition. The aim of this study, conducted by the Federation of Associations of Hospital Internists (FADOI) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) was to assess the nutritional management of internal medicine inpatients in Italy, to identify critical issues and formulate practical proposals to improve nutritional treatment. METHODS: From February to April 2021, FADOI and SINPE conducted a national web-based survey, including a 13 multiple-choice item questionnaire related to three key areas: screening and assessment of malnutrition and associated/overlapping sarcopenia and dysphagia; specialist consultations; and management of nutritional support. RESULTS: Responding to the questionnaire were 266 physicians among FADOI members (10.76%). Screening for malnutrition is performed with validated tests, within standardized care pathways, or routinely, only by 22% of participants. Global Leadership Initiative on Malnutrition criteria for diagnosis of malnutrition are little used (20%). Screening for sarcopenia was insufficient as the systematic use of assessment tools (handgrip/chair test) was minimal (3%). Screening for dysphagia is not a routine procedure for at-risk patients according to 33% of participants. Systematic involvement of clinical nutrition services/units in the management of malnourished/sarcopenic patients was reported by only 17% of internists. CONCLUSIONS: To overcome the critical issues that emerged from the present study, FADOI and SINPE experts proposed practical solutions to promote the application of the most recent guidelines and to improve awareness and sensitivity to nutritional management in internal medicine real-life settings.

Hospitalization and mortality for acute exacerbation of asthma: an Italian population-based study.

Asthma is an ever-increasing disease with a highly variable prevalence among different ethnic groups. Information on hospital admission for acute exacerbation of asthma in adult patients and data regarding short-term prognosis of these patients are limited. We, thus, performed an epidemiological study on hospital admission for asthma acute exacerbation in Italy using hospital discharge database records derived from all Italian hospitals. Patients > 15 years old were identified using clinical Modification (ICD-9-CM) codes. Information on baseline characteristics, vital status at discharge, duration of hospitalization, and up to five secondary discharge diagnoses was collected. Comorbidity was evaluated using the Charlson comorbidity index (CCI). During the observation period (2013-2014), 20,056 patients with asthma acute exacerbation were hospitalized. Median length of hospitalization was 7.9 days (interquartile range 4-10) and mean in-hospital mortality was 0.8%. In-hospital mortality and length of hospitalization varied among different regions (from 0 to 2.9% and from 6.5 to 8.9 days, respectively). Old age, invasive and non-invasive mechanical ventilation, and CCI resulted as significantly associated with higher in-hospital mortality. Our study results, on a large sample of patients, confirm that hospitalization for asthma acute exacerbation is not uncommon among Italian current population. Older age, high CCI, and use of ventilator support were associated with a higher mortality rate. These findings should be analyzed to set up appropriate health care policies on patients with asthma.

Acute cardiovascular events in patients with community acquired pneumonia: results from the observational prospective FADOI-ICECAP study.

BACKGROUND: The burden of cardiovascular (CV) complications in patients hospitalised for community-acquired pneumonia (CAP) is still uncertain. Available studies used different designs and different criteria to define CV complications. We assessed the cumulative incidence of acute of CV complications during hospitalisation for CAP in Internal Medicine Units (IMUs). METHODS: This was a prospective study carried out in 26 IMUs, enrolling patients consecutively hospitalised for CAP. Defined CV complications were: newly diagnosed heart failure, acute coronary syndrome, new onset of supraventricular or ventricular arrhythmias, new onset hemorrhagic or ischemic stroke or transient ischemic attack. Outcome measures were: in-hospital and 30-day mortality, length of hospital stay and rate of 30-day re-hospitalisation. RESULTS: A total of 1266 patients were enrolled, of these 23.8% experienced at least a CV event, the majority (15.5%) represented by newly diagnosed decompensated heart failure, and 75% occurring within 3 days. Female gender, a history of CV disease, and more severe pneumonia were predictors of CV events. In-hospital (12.2% vs 4.7%, p < 0.0001) and 30-day (16.3% vs 8.9%, p = 0.0001) mortality was higher in patients with CV events, as well as the re-hospitalisation rate (13.3% vs 9.3%, p = 0.002), and mean hospital stay was 11.4 ± 6.9 vs 9.5 ± 5.6 days (p < 0.0001). The occurrence of CV events during hospitalisation significantly increased the risk of 30-day mortality (HR 1.69, 95% CI 1.14-2.51; p = 0.009). CONCLUSION: Cardiovascular events are frequent in CAP, and their occurrence adversely affects outcome. A strict monitoring might be useful to intercept in-hospital CV complications for those patients with higher risk profile. TRIAL REGISTRATION: NCT03798457 Registered 10 January 2019 - Retrospectively registered.

Derivation and Validation of a Prediction Model for Venous Thromboembolism in Primary Care.

BACKGROUND: Most episodes of venous thromboembolism (VTE) occurred in primary care. To date, no score potentially able to identify those patients who may deserve an antithrombotic prophylaxis has been developed. AIM: The objective of this study is to develop and validate a prediction model for VTE in primary care. METHODS: Using the Health Search Database, we identified a cohort of 1,359,880 adult patients between 2002 and 2013. The date of the first General Practitioner's (GP) visit was the cohort entry date. All VTE cases (index date) observed up to December 2014 were identified. The cohort was randomly divided in a development and a validation cohort. According to nested case-cohort analysis, up to five controls were matched to their respective cases on month and year of cohort entry and duration of follow-up.The score was evaluated according to explained variance (pseudo R2) as a performance measure, ratio of predicted to observed cases as model calibration and area under the curve (AUC) as discrimination measure. RESULTS: The score was able to explain 27.9% of the variation for VTE occurrence. The calibration measure revealed a margin of error lower than 10% in 70% of the population. In terms of discrimination, AUC was 0.82 (95% confidence interval: 0.82-0.83). Results of sensitivity analyses substantially confirmed these findings. CONCLUSION: The present score demonstrated a very good accuracy in predicting the risk of VTE in primary care. This score may be therefore implemented in clinical practice so aiding GPs in making decision on patients potentially at risk of VTE.

Apixaban for the Treatment of Venous Thromboembolism Associated with Cancer.

BACKGROUND: Recent guidelines recommend consideration of the use of oral edoxaban or rivaroxaban for the treatment of venous thromboembolism in patients with cancer. However, the benefit of these oral agents is limited by the increased risk of bleeding associated with their use. METHODS: This was a multinational, randomized, investigator-initiated, open-label, noninferiority trial with blinded central outcome adjudication. We randomly assigned consecutive patients with cancer who had symptomatic or incidental acute proximal deep-vein thrombosis or pulmonary embolism to receive oral apixaban (at a dose of 10 mg twice daily for the first 7 days, followed by 5 mg twice daily) or subcutaneous dalteparin (at a dose of 200 IU per kilogram of body weight once daily for the first month, followed by 150 IU per kilogram once daily). The treatments were administered for 6 months. The primary outcome was objectively confirmed recurrent venous thromboembolism during the trial period. The principal safety outcome was major bleeding. RESULTS: Recurrent venous thromboembolism occurred in 32 of 576 patients (5.6%) in the apixaban group and in 46 of 579 patients (7.9%) in the dalteparin group (hazard ratio, 0.63; 95% confidence interval [CI], 0.37 to 1.07; P<0.001 for noninferiority). Major bleeding occurred in 22 patients (3.8%) in the apixaban group and in 23 patients (4.0%) in the dalteparin group (hazard ratio, 0.82; 95% CI, 0.40 to 1.69; P = 0.60). CONCLUSIONS: Oral apixaban was noninferior to subcutaneous dalteparin for the treatment of cancer-associated venous thromboembolism without an increased risk of major bleeding. (Funded by the Bristol-Myers Squibb-Pfizer Alliance; Caravaggio ClinicalTrials.gov number, NCT03045406.).

Acquired Factor XIII Deficiency Inducing Recurrent and Fatal Bleeding, Description of a Case.

Factor XIII deficiency may be inherited or acquired. Inherited deficiency is associated with signs and symptoms of minor bleeding from a young age, and possible major bleeding complications, in particular during pregnancy. On the other hand, acquired factor XIII deficiency is usually associated with severe symptoms of major bleeding, in particular during surgery. In this paper, we report an interesting case of recurrent major bleeding with subsequent fatal bleeding in an adult man diagnosed with acquired factor XIII deficiency.

Prophylaxis of Venous Thromboembolism after Hospital Discharge in Internal Medicine: Findings from the Observational FADOI-NoTEVole Study.

BACKGROUND AND AIM: Post-discharge prophylaxis for venous thromboembolism (VTE) is a challenging issue in patients hospitalised in Internal Medicine Units (IMUs). The aim of this study was to evaluate the frequency and the factors associated with post-discharge prophylaxis for VTE in IMUs. METHODS: Multi-centre, retrospective study including consecutive patients who were admitted for any cause and discharged from an IMU. RESULTS: Overall, 3,740 patients (mean age 74.1 ± 15.7 years) were included in the study at 38 IMUs in Italy. At discharge, the percentage of patients receiving pharmacological thromboprophylaxis was 16.0% (20.1% after excluding patients treated with anticoagulants for indications other than VTE prophylaxis). At multivariable analysis, history of ischaemic stroke, hypomobility ≥ 7 days, central venous catheter, ≥ 10 versus ≤ 5 days of hospital stay, use of corticosteroids, cancer, history of falls, availability of a caregiver, infections and age were significantly associated with thromboprophylaxis, while an inverse correlation was observed with concomitant anti-platelet drugs and platelet count < 70,000/mm3. Patients with a Padua Prediction Score ≥ 4 versus < 4 and with an IMPROVE bleeding score ≥ 7 versus < 7 more frequently received prophylaxis at discharge (31.2% vs. 10.6%, p < 0.0001, and 25.7% vs. 19.6%, p = 0.028, respectively). CONCLUSION: In this study, one in five patients discharged from an Italian IMU received prophylaxis for VTE. The perceived thrombotic risk is significantly related to the use of prophylaxis.

Prognostic value for mortality of the new FADOI-COMPLIMED score(s) in patients hospitalized in medical wards.

BACKGROUND: Recently we defined a user-friendly tool (FADOI-COMPLIMED scores-FCS) to assess complexity of patients hospitalized in medical wards. FCS-1 is an average between the Barthel Index and the Exton-Smith score, while FCS-2 is obtained by using the Charlson score. The aim of this paper is to assess the ability of the FCS to predict mortality in-hospital and after 1-3-6-12-months. In this perspective, we performed comparisons with the validated Multidimensional Prognostic Index (MPI). METHODS: It is a multicenter, prospective observational study, enrolling patients aged over 40, suffering from at least two chronic diseases and consecutively admitted to Internal Medicine departments. For each patient, data from 13 questionnaires were collected. Survival follow-up was conducted at 1-3-6-12 months after discharge. The relationships between cumulative incidences of death with FCS were investigated with logistic regression analyses. ROC curve analyses were performed in order to compare the predictiveness of the logistic models based on FCS with respect to those with MPI taken as reference. RESULTS: A cohort of 541 patients was evaluated. A 10-point higher value for FCS-1 and FCS-2 leads to an increased risk of 1-year death equal to 25.0% and 27.1%, respectively. In case of in-hospital mortality, the relevant percentages were 63.1% and 15.3%. The logistic model based on FCS is significantly more predictive than the model based on MPI (which requires an almost doubled number of items) for all the time-points considered. CONCLUSIONS: Assessment of prognosis of patients has the potential to guide clinical decision-making and lead to better care. We propose a new, efficient and easy-to-use instrument based on FCS, which demonstrated a good predictive power for mortality in patients hospitalized in medical wards. This tool may be of interest for clinical practice, since it well balances feasibility (requiring the compilation of 34 items, taking around 10 minutes) and performance.

[ANMCO/FADOI/SIAARTI/SIC/SIMG/SIMI/SIMEU consensus document: The clinical care pathway of acute heart failure patients from symptom onset to discharge from the emergency department]. / Documento di consenso ANMCO/FADOI/SIAARTI/SIC/SIMG/SIMI/SIMEU: Il percorso clinico-diagnostico e terapeutico del paziente con scompenso cardiaco acuto dal domicilio alla dimissione dal Pronto Soccorso/ Dipartimento di Emergenza-Accettazione.

Acute heart failure (AHF) represents a relevant burden for emergency departments worldwide. AHF patients have markedly worse long-term outcomes than patients with other acute cardiac diseases (e.g. acute coronary syndromes); mortality or readmissions rates at 3 months approximate 33%, whereas 1-year mortality from index discharge ranges from 25% to 50%.The multiplicity of healthcare professionals acting across the care pathway of AHF patients represents a critical factor, which generates the need for integrating the different expertise and competence of general practitioners, emergency physicians, cardiologists, internists, and intensive care physicians to focus on care goals able to improve clinical outcomes.This consensus document results from the cooperation of the scientific societies representing the different healthcare professionals involved in the care of AHF patients and describes shared strategies and pathways aimed at ensuring both high quality care and better outcomes. The document describes the patient journey from symptom onset to the clinical suspicion of AHF and home management or referral to emergency care and transportation to the hospital, through the clinical diagnostic pathway in the emergency department, acute treatment, risk stratification and discharge from the emergency department to ordinary wards or home. The document analyzes the potential role of a cardiology fast-track and Observation Units and the transition to outpatient care by general practitioners and specialist heart failure clinics.The increasing care burden and complex problems generated by AHF are unlikely to be solved without an integrated multidisciplinary approach. Efficient networking among emergency departments, intensive care units, ordinary wards and primary care settings is crucial to achieve better outcomes. Thanks to the joint effort of qualified scientific societies, this document aims to achieve this goal through an integrated, shared and applicable pathway that will contribute to a homogeneous care management of AHF patients across the country.

What Quality and Safety of Care for Patients Admitted to Clinically Inappropriate Wards: a Systematic Review.

BACKGROUND: In countries with public health system, hospital bed reductions and increasing social and medical frailty have led to the phenomenon of "outliers" or "outlying hospital in-patients." They are often medical patients who, because of unavailability of beds in their clinically appropriate ward, are admitted wherever unoccupied beds are. The present work is aimed to systematically review literature about quality and safety of care for patients admitted to clinically inappropriate wards. METHODS: We performed a systematic review of studies investigating outliers, published in peer-reviewed journals with no time restrictions. Search and screening were conducted by two independent researchers (MLR and ER). Studies were considered potentially eligible for this systematic review if aimed to assess the quality and/or the safety of care for patients admitted to clinically inappropriate units. Our search was supplemented by a hand search of references of included studies. Given the heterogeneity of studies, results were analyzed thematically. We used PRISMA guidelines to report our findings. RESULTS: We collected 17 eligible papers and grouped them into six thematic categories. Despite their methodological limits, the included studies show increased trends in mortality and readmissions among outliers. Quality of care and patient safety are compromised as patients and health professionals declare and risk analysis displays. Reported solutions are often multicomponent, stress early discharge but have not been investigated in the control group. CONCLUSIONS: Published literature cannot definitely conclude on the quality and safety of care for patients admitted to clinically inappropriate wards. As they may represent a serious threat for quality and safety, and moreover often neglected and under valued, well-designed and powered prospective studies are urgently needed.

Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016.

OBJECTIVE: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. METHODS: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. RESULTS: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P = .009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. CONCLUSIONS: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship.

Delirium, Dementia, and In-Hospital Mortality: The Results From the Italian Delirium Day 2016, A National Multicenter Study.

BACKGROUND: There is little evidence about the prevalence of cognitive disorders and their effect on in-hospital mortality in large multicenter studies. The objectives of the 2016th edition of the "Italian Delirium Day," a large multicenter study on in-hospital older patients, were to assess (i) the point prevalence of cognitive impairment/no dementia, dementia, delirium, and delirium superimposed on dementia and (ii) the effect of these conditions on in-hospital mortality. METHODS: This multicenter study and included 2,037 older patients (aged ≥65 years) admitted to acute medical and surgical wards across 205 acute hospitals. The four cognitive disorders groups were defined with a structured approach including the four AT and the presence of a documented diagnosis of dementia. The outcome measure was in-hospital mortality, as reported by the researchers involved in the study in each center. RESULTS: The mean age was 81.17 ± 7.7 years. Overall, 893 patients (43.8%) had neither delirium nor dementia nor cognitive impairment, 483 (23.7%) had cognitive impairment/no dementia, 230 (11.3%) dementia alone, 187 (9.2%) delirium alone, and 244 (12.0%) delirium superimposed on dementia. Overall, 99 (4.8%) patients died. Participants with delirium alone (odds ratio 2.56; 95% confidence interval: 1.29-5.09) and those with delirium superimposed on dementia (odds ratio 2.60; 95% confidence interval: 1.39-4.85) had higher mortality risk compared with the reference group of patients with "no cognitive impairment." CONCLUSIONS: Delirium and delirium superimposed on dementia were highly prevalent among older hospitalized patients and significantly increased in-hospital mortality. Clinicians should systematically assess these conditions and recognize them as markers of critical conditions and predictors of imminent death.

Apixaban versus Dalteparin for the Treatment of Acute Venous Thromboembolism in Patients with Cancer: The Caravaggio Study.

International and national guidelines recommend low-molecular-weight heparin for the treatment of venous thromboembolism (VTE) in patients with cancer. The aim of the Caravaggio study is to assess whether oral apixaban is non-inferior to subcutaneous dalteparin for the treatment of acute proximal deep vein thrombosis and/or pulmonary embolism in patients with cancer. The study is an investigator-initiated, multi-national, prospective, randomized, open-label with blind end-point evaluation (PROBE), non-inferiority clinical trial (NCT03045406). Consecutive patients are randomized to receive oral apixaban or subcutaneous dalteparin for 6 months. Apixaban is given at a dose of 10 mg twice daily for the first 7 days and then 5 mg twice daily; dalteparin is given at a dose of 200 IU/kg for the first month and then 150 IU/kg once daily. The primary outcome of the study is objectively confirmed recurrent VTE as assessed by a central independent adjudication committee unaware of study treatment allocation. The primary safety outcome is major bleeding defined according to the guidelines of the International Society of Thrombosis and Haemostasis. Assuming a 6-month incidence of the primary outcome of 7% with dalteparin and an upper limit of the two-sided 95% confidence interval of the hazard ratio below the pre-specified margin of 2.00, 1,168 patients will be randomized considering an up to 20% loss in total patient-years (ß = 80%; α one-sided = 0.025). The Caravaggio study has the potential, along with other recently performed or on-going studies, to make less cumbersome the management of VTE in patients with cancer by replacing parenteral with oral anticoagulation.

The complexity of patients hospitalized in Internal Medicine wards evaluated by FADOI-COMPLIMED score(s). A hypothetical approach.

OBJECTIVES: The aim of this study is to develop a new predictive model to measure complexity of patients in medical wards. SETTING: 29 Internal Medicine departments in Italy. MATERIALS AND METHODS: The study cohort was made of 541 consecutive patients hospitalized for any cause, aged more than 40 years and with at least two chronic diseases. First, we applied a hierarchical cluster analysis and the principal component analysis (PCA) to a panel of questionnaires [comorbidity (Charlson, CIRS), clinical stability (MEWS), social frailty (Flugelman), cognitive dysfunction (SPSMQ), depression (5-item GDS), functional dependence (ADL, IADL, Barthel), risk of sore threats (Exton-Smith scale), nutrition (MNA), pain (NRPS), adherence to therapy (Morisky scale)], in order to select domains informative for the definition of complexity. The following step was to create the score(s) needed to quantify it. RESULTS: Two main clusters were identified: the first includes 7 questionnaires whose common denominator is dependence and frailty, the second consists of 3 questionnaires representative of comorbidity. Globally, they account for about 70% of the total variance (55.2% and 13.8%, respectively). The first principal component was simplified in "Complimed Score 1" (CS1) as a recalibrated average between the Barthel Index and the Exton Smith score, whereas the second cluster was approximated to "Complimed Score 2" (CS2), by using the Charlson score only. CONCLUSIONS: Complexity is a two-dimensional clinical phenomenon. The FADOI-Complimed Score(s) is a new tool useful for the routine evaluation of complexity in medical patients, simple to use and taking around 10 minutes to complete.