The Fenice project to evaluate and improve the quality of healthcare in high-dependency care units: results after the first year.

High-Dependency care Units (HDUs) have been introduced worldwide as intermediate wards between Intensive Care Units (ICUs) and general wards. Performing a comparative assessment of the quality of care in HDU is challenging because there are no uniform standards and heterogeneity among centers is wide. The Fenice network promoted a prospective cohort study to assess the quality of care provided by HDUs in Italy. This work aims at describing the structural characteristics and admitted patients of Italian HDUs. All Italian HDUs affiliated to emergency departments were eligible to participate in the study. Participating centers reported detailed structural information and prospectively collected data on all admitted adult patients. Patients' data are presented overall and analyzed to evaluate the heterogeneity across the participating centers. A total of 12 HDUs participated in the study and enrolled 3670 patients. Patients were aged 68 years on average, had multiple comorbidities and were on major chronic therapies. Several admitted patients had at least one organ failure (39%). Mortality in HDU was 8.4%, raising to 16.6% in hospital. While most patients were transferred to general wards, a small proportion required ICU transfer (3.9%) and a large group was discharged directly home from the HDU (31%). The expertise of HDUs in managing complex and fragile patients is supported by both the available equipment and the characteristics of admitted patients. The limited proportion of patients transferred to ICUs supports the hypothesis of preventing of ICU admissions. The heterogeneity of HDU admissions requires further research to define meaningful patients' outcomes to be used by quality-of-care assessment programs.

Upper extremities deep vein thrombosis treated with oral direct anticoagulants: A prospective cohort study.

BACKGROUND: Limited data are available on the role of direct oral anticoagulants (DOACs) for the treatment of upper extremities deep vein thrombosis (UEDVT). OBJECTIVES: The aim of this study was to assess the effectiveness and safety of DOACs in the treatment of UEDVT. METHODS: Patients with an objectively confirmed acute UEDVT treated with DOACs were merged from prospective cohorts to a collaborative database. Primary study outcomes were recurrent venous thromboembolism (VTE) and major bleeding occurring during DOAC treatment. RESULTS: Overall, 188 patients were included in the study: mean age 52.4 ± 20.4 years, males 43.6%, patients with active cancer 29.2%. Twenty-nine percent of patients had 2 or more risk factors for VTE, 33.0% had catheter-related or pacemaker-related UEDVT. In 13.8% of patients, DOACs were started one month after UEDVT diagnosis or later. Active cancer was an independent predictor for delayed initiation of DOACs (OR 8.1, 95% CI 3.0-22.2). Mean duration of treatment with DOACs was 5.1 ± 2.8 months. During treatment with DOACs, recurrent VTE occurred in 0.9 per 100 patient-year, major bleeding in 1.7 and all-cause deaths in 6.0 per 100 patient-year. No fatal bleeding or fatal VTE recurrence were observed. During 232.1 patient-years of follow-up after DOAC withdrawal, recurrent VTE occurred in 3.0 per 100 patient-year. The 2019 ESC categories for risk of VTE recurrences were able to discriminate patient groups at different risk of events in the on and off-treatment periods. CONCLUSIONS: Our data support the feasibility as well as the effectiveness and safety of DOACs for the treatment of acute UEDVT.

Prognostic value of respiratory index in haemodynamically stable patients with acute pulmonary embolism: The Respiratory Index model study.

BACKGROUND: Current strategies for prognostic stratification in haemodynamically stable patients with acute pulmonary embolism require improvement. The aims of this study in haemodynamically stable patients with acute pulmonary embolism were (a) to evaluate the prognostic value of a novel respiratory index (oxygen saturation in air to respiratory rate ratio) and (b) to derive a risk model which includes the respiratory index and evaluate its value in predicting 30-day mortality. METHODS: Prospective cohorts of haemodynamically stable patients with acute pulmonary embolism were merged to a collaborative database that served to create two subsequent derivation and validation cohorts based on a temporal criterion. The study outcome was 30-day all-cause death. RESULTS: Thirty-day all-cause death occurred in 7.5% and in 6.9% of patients in the derivation and validation cohorts (each composed of 319 patients). In the derivation cohort, the respiratory index (odds ratio 0.66, 95% confidence interval 0.48-0.90) and simplified Pulmonary Embolism Severity Index (odds ratio 9.16, 95% confidence interval 1.22-68.89) were predictors of 30-day mortality. The cut-off value of the respiratory index ⩽3.8 was identified to best predict 30-day all-cause death (15.4% vs 5.0%, odds ratio 2.94, 95% confidence interval 1.22-7.11). The respiratory index ⩽3.8 was combined with the simplified Pulmonary Embolism Severity Index to create the Respiratory Index model that showed a good discriminatory power in the derivation (c-statistic 0.703, 95% confidence interval 0.60-0.80) and in the validation cohort (c-statistic 0.838, 95% confidence interval 0.768-0.907). CONCLUSION: In hemodynamically stable patients with acute pulmonary embolism, the respiratory index was an independent predictor of 30-day all-cause death. The Respiratory Index model which includes the simplified Pulmonary Embolism Severity Index and the respiratory index, provides a good risk stratification of haemodynamically stable patients with acute pulmonary embolism.

Prediction of major bleeding in patients receiving DOACs for venous thromboembolism: A prospective cohort study.

BACKGROUND: In the direct oral anticoagulants (DOACs) era, extended anticoagulation is an attractive strategy after venous thromboembolism (VTE). The role of currently available bleeding risk scores for VTE patients treated with DOACs in clinical practice is undefined. METHODS: Consecutive patients with VTE were included in a prospective multicenter cohort at the initiation of treatment with DOACs. The role of ATRIA, HAS-BLED, Kuijer, ORBIT, RIETE and VTE-BLEED scores in predicting major bleeding (ISTH definition) while on DOAC treatment was assessed. RESULTS: Overall, 1034 patients were included and followed for one year or until the end of treatment or the occurrence of major bleeding. During study period, 26 major bleedings occurred in 25 patients (2.8% patient-year). Anemia, bleeding history and creatinine clearance <60 ml/min were significant predictors of major bleedings. The predictive value of bleeding risk scores was modest. In the 12-month study period, ORBIT (HR intermediate-high vs. low risk patients 3.62, 95% CI 1.65-7.94 and c-statistics 0.645, 95% CI 0.523-0.767) and VTE-BLEED (HR high vs. low 16.11, 95% CI 2.18-119.09 and c-statistics 0.674, 95% CI 0.593-0.755) score significantly predicted major bleeding. The lowest incidence of major bleeding (0.3%) was observed in the low-risk category of VTE-BLEED, while the highest (7.1%) in the high-risk category of ORBIT. CONCLUSIONS: In a real-life cohort of patients with VTE treated with DOACs, the predictive value of currently available bleeding risk scores was modest and not statistically different. Whether these scores can be used for decision making on anticoagulation should be assessed in management studies.

Data on the use of oral anticoagulants in nonagenarians with atrial fibrillation.

The data presented in this article are related to the research article entitled "Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study" [1]. This article unveils original data of a cohort of 546 patients aged 90 years or older with non-valvular atrial fibrillation treated with oral anticoagulants. Here, we describe the time course of ischemic stroke and systemic embolism and of major bleeding according to the presence of outcome predictors and report the causes of permanent discontinuation and of death. Furthermore, we report data on the incidence of ischemic stroke and systemic embolism, of major bleeding, of permanent discontinuation and of all-cause death comparing i) oral anticoagulant naïve users vs. long-term oral anticoagulant users, ii) patients on anticoagulant therapy for less than 2 years (new users) vs. patients on anticoagulant therapy for more than 2 years. The material of this data article provides a better understanding on the use of oral anticoagulants in this fragile population and facilitates further critical analysis. Moreover, it aims at highlighting the importance of increasing knowledge in patients aged 90 years or older. These patients are often excluded from or under-represented in clinical trials and cohort studies.

Patients aged 90 years or older with atrial fibrillation treated with oral anticoagulants: A multicentre observational study.

BACKGROUND: Patients aged 90 years or older are often excluded from or under-represented in clinical trials and cohort studies. The clinical benefit of anticoagulation in nonagenarians with atrial fibrillation (AF) remains undefined. OBJECTIVES: To assess the effectiveness and safety of oral anticoagulants in AF patients aged 90 years or older. METHODS: Non-valvular AF patients aged 90 years or older receiving direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) were included in this observational multicentre study. The primary outcome was the composite of ischaemic stroke/transient ischemic attack (TIA) and systemic embolism (SE). Major bleeding (MB), anticoagulant discontinuation and all-cause death were also assessed. Results are reported as sub-distribution hazard ratios (SHR) with 95% CI, taking death as competing risk. RESULTS: 546 patients were included (301 VKAs retrospective cohort and 245 DOACs prospective cohort; median follow-up 404 days). The rate of ischaemic stroke/TIA/SE was 2.4% patient-year and that of MB 5.5% patient-year. Previous ischaemic stroke/TIA (SHR 3.47; 95% CI 1.54-7.81) and vascular disease (SHR 2.89; 95% CI 1.27-6.60) were independent predictors of ischaemic stroke/TIA/SE. Previous bleeding (SHR 2.53; 95% CI 1.37-4.64) was an independent predictor of MB. The risk of ischaemic stroke/TIA/SE (SHR 0.78, 95% CI 0.30-2.04) or MB (SHR 1.43, 95% CI 0.77-2.65) was not significantly different with DOACs or VKAs. CONCLUSIONS: In AF nonagenarians receiving anticoagulant treatment, the rate of ischaemic stroke/TIA/SE is relatively low with the drawback of a not negligible rate of MB. DOACs seem a reasonable option for prevention of ischaemic stroke/TIA/SE in this setting.

Patients with cancer and atrial fibrillation treated with doacs: A prospective cohort study.

BACKGROUND: Limited data are available on the use of direct oral anticoagulants (DOACs) in patients with cancer and atrial fibrillation (AF). METHODS: Consecutive patients with non-valvular AF treated with DOACs were enrolled in a prospective cohort with the aim of evaluating thromboembolic (ischemic stroke or transient ischemic attack or systemic embolism) and major bleeding (MB) events according to presence and type of cancer. The risk of study outcomes over time was compared using Kaplan-Meier method and log-rank test or Cox proportional hazards regression. RESULTS: 2304 patients with non-valvular AF receiving DOACs were enrolled and 16 excluded: 2288 analysed of whom 289 (12.6%) had cancer. Gastrointestinal (21%), genitourinary (15%), prostate (15%), haematological (14%), breast (13%), and lung (8%) were the more frequent sites of cancer. After a mean follow-up of 451 days, thromboembolic events occurred in 2.1% and 0.8% patient-year of cancer and non-cancer patients (adjusted-HR 2.58, 95% CI 1.08-6.16, p = 0.033). The rate of MB was 6.6% and 3.0% patient-year in cancer and non-cancer patients (adjusted-HR 2.02, 95% CI 1.25-3.27, p = 0.004). The differences in bleeding were mainly accounted for by bleeding at gastrointestinal and genitourinary sites. No significant differences were found concerning the rates of non-cancer-related mortality, fatal bleeding or fatal thrombotic events. CONCLUSIONS: In this study, the higher bleeding risk found in cancer compared to non-cancer patients was mainly due to an excess of bleeding at gastrointestinal and at genitourinary sites. Larger studies on the optimal management of cancer patients with AF are needed.

Permanent discontinuation of non vitamin K oral anticoagulants in real life patients with non-valvular atrial fibrillation.

BACKGROUND: Persistence to treatment affects clinical outcomes in patients with chronic disease such as atrial fibrillation (AF). METHODS: This prospective cohort study included consecutive non-valvular AF patients prescribed with non-vitamin K oral anticoagulants (NOACs) and investigated for any permanent discontinuation at 1-year of this therapy, as well as any reasons for discontinuation. RESULTS: Overall, 1305 patients were prescribed with dabigatran (N=473), rivaroxaban (N=425) or apixaban (N=407). Of these, 201 patients (15.4%) discontinued NOACs during the first year of treatment. More than 60% of these discontinuations occurred during the first 6months. Reasons for discontinuation included: dyspepsia or abdominal pain in 38 patients (2.9%) and bleeding in 59 (4.5%). Discontinuation for the former occurred earlier (50% within 2months) compared to the latter (66% after the first 4months). The prescription of reduced NOAC doses resulted being an independent predictor of discontinuation (OR 1.74, 95% CI 1.23-2.45, p=0.002). Regarding the use of dabigatran, rivaroxaban and apixaban, the following were observed: discontinuers were 22.0% (95% CI 18.5-25.9), 14.4% (95% CI 11.3-18.0) and 8.8% (95% CI 6.5-12.0), the risk of discontinuation associated with bleeding was 20.2%, 44.3% and 30.6% and dyspepsia or abdominal pain was 35.6%, 1.6% and 0%, respectively. CONCLUSION: Discontinuation of NOACs in AF patients was relatively common and more than often occurred in the first six months after prescription. Patients treated with reduced doses of NOACs had a higher probability to discontinue compared to those who were prescribed conventional doses.

Vitamin K and non-vitamin K antagonist oral anticoagulants for non-valvular atrial fibrillation in real-life.

BACKGROUND: Current guidelines recommend vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with non-valvular atrial fibrillation (AF). METHODS: We compared the clinical features of consecutive in- and out-patients with non-valvular AF newly-treated with NOACs or on treatment with VKAs. RESULTS: Overall, 1314 patients newly-treated with NOACs and 1024 on treatment with VKAs were included in the study. The mean CHA2DS2-VASc score was 4.3±1.5 and 4.0±1.5 and the mean HAS-BLED score was 2.8±1.2 and 2.2±1.1 in the two groups, respectively (both p<0.001). Hypertension, previous stroke, female gender, vascular diseases and previous bleeding were more prevalent in NOACs patients. Renal failure, age ≥75years and congestive heart failure were more prevalent in VKAs patients. Among NOACs patients, 438 were given dabigatran, 463 rivaroxaban and 413 apixaban (33%, 35% and 31%, respectively). The mean CHA2DS2-VASc and HAS-BLED scores were higher in rivaroxaban or apixaban patients compared with dabigatran (both p<0.001) and VKAs patients (both p<0.001). A lower mean age was observed in patients newly-treated with dabigatran. Patients newly-treated with reduced doses of NOACs (599 patients, 45.5%) had a higher CHA2DS2-VASc (4.8±1.4 vs. 3.9±1.5 vs. 4.0±1.5) and HAS-BLED (2.9±1.1 vs. 2.8±1.2 vs. 2.2±1.1) scores compared with those treated with regular doses of NOACs or VKAs. CONCLUSION: Patients given rivaroxaban and apixaban in clinical practice have a higher thrombotic and hemorrhagic risk in comparison with patients given dabigatran or VKAs. A considerable proportion of patients receive reduced doses of NOACs.

Liver hemangioma and vascular liver diseases in patients with systemic lupus erythematosus.

AIM: To investigate whether systemic lupus erythematosus (SLE) is associated with benign focal liver lesions and vascular liver diseases, since these have been occasionally reported in SLE patients. METHODS: Thirty-five consecutive adult patients with SLE and 35 age- and sex-matched healthy controls were evaluated. Hepatic and portal vein patency and presence of focal liver lesions were studied by colour-Doppler ultrasound, computerized tomography and magnetic resonance were used to refine the diagnosis, clinical data of SLE patients were reviewed. RESULTS: Benign hepatic lesions were common in SLE patients (54% vs 14% controls, P < 0.0001), with hemangioma being the most commonly observed lesion in the two groups. SLE was associated with the presence of single hemangioma [odds ratios (OR) 5.05; 95% confidence interval (CI) 1.91-13.38] and multiple hemangiomas (OR 4.13; 95% CI 1.03-16.55). Multiple hemangiomas were associated with a longer duration of SLE (9.9 ± 6.5 vs 5.5 ± 6.4 years; P = 0.04). Imaging prior to SLE onset was available in 9 patients with SLE and hemangioma, showing absence of lesions in 7/9. The clinical data of our patients suggest that SLE possibly plays a role in the development of hemangioma. In addition, a Budd-Chiari syndrome associated with nodular regenerative hyperplasia (NRH), and a NRH associated with hepatic hemangioma were observed, both in patients hospitalized for abdominal symptoms, suggesting that vascular liver diseases should be specifically investigated in this population. CONCLUSION: SLE is associated with 5-fold increased odds of liver hemangiomas, suggesting that these might be considered among the hepatic manifestations of SLE.

Prognostic value of a single HVPG measurement and Doppler-ultrasound evaluation in patients with cirrhosis and portal hypertension.

BACKGROUND: In patients with cirrhosis the onset of clinically significant portal hypertension (CSPH; i.e., hepatic venous pressure gradient (HVPG) ≥ 10 mmHg) is associated with an increased risk of complications. However, most cirrhotic patients already have CSPH at presentation, and limited information is available on further risk stratification in this population. This study assessed the prognostic value of a single HVPG measurement and Doppler-ultrasound (US) evaluation in patients with cirrhosis and CSPH. METHODS: Eighty-six consecutive patients with cirrhosis (73% compensated) and untreated CSPH (mean HVPG 17.8 ± 5.1 mmHg) were included. All were studied by paired HVPG and US, and followed up for a minimum of 12 months (mean 28 ± 20 months). RESULTS: Sixteen (25.3%) patients developed a first decompensation, and 11.6% died on follow-up. HVPG (per 1 mmHg increase OR 1.22, 95% CI 1.05-1.40, p = 0.007) and bilirubin (per 1 mg/ml increase OR 2.42, 95% CI 0.93-6.26, p = 0.06) independently predicted first decompensation, and Model for End-Stage Liver Disease (MELD) score (per 1 point increase OR 1.24, 95% CI 1.03-1.51, p = 0.03) and HVPG (per 1 mmHg increase OR 1.08, 95% CI 1.01-1.26, p = 0.05) independently predicted mortality. The best HVPG cutoff predicting these events was 16 mmHg. Ultrasonographic parameters lacked independent predictive value. The ultrasonographic detection of abdominal collaterals had a high positive likelihood ratio (7.03, 95% CI 2.23-22.16) for the prediction of HVPG ≥ 16 mmHg, implying an increase of the probability of belonging to this higher-risk population from 58 to 91%. CONCLUSIONS: HVPG holds an independent predictive value for first decompensation and death in patients with CSPH. The ultrasonographic detection of collaterals allows the non-invasive identification of patients with HVPG ≥ 16 mmHg, who are at higher risk.

Chronic endurance exercise training prevents aging-related cognitive decline in healthy older adults: a randomized controlled trial.

OBJECTIVE: To evaluate the effects of endurance exercise training (EET) on the cognitive status of healthy community-dwelling older adults. METHODS: A randomized controlled trial was conducted involving community-dwelling older adults from the town of Pianoro (northern Italy). We randomized 120 healthy subjects aged 65-74 years, both genders, to treatment (N = 60) and control (N = 60) groups. The treatment consisted of 12 months of supervised EET in a community gym, 3 h a week. All participants were assessed both at baseline and after 12 months on an intention-to-treat analysis. Cognitive status was assessed by one single test (Mini Mental State Examination, MMSE). Anthropometric indexes, routine laboratory measurements and C-reactive protein (CRP) were also assessed. RESULTS: The control group showed a significant decrease in MMSE score (mean difference -1.21, 95% CI -1.83/-0.60, p = 0.0002), which differed significantly (p = 0.02) from the treatment group scores (-0.21, 95% CI -0.79/0.37, p = 0.47). The odds ratio for the treated older adults to have a stable cognitive status after 1 year, as compared to the control group, was 2.74 (95% CI 1.16/6.48) after adjustment for age, gender, educational level and several other possible confounders. Blood pressure, body mass index, waist circumference and serum cholesterol did not differ significantly between the two groups, while CRP decreased only in the treatment group. CONCLUSIONS: A 12-month EET intervention may reduce the progression of age-related cognitive decline in healthy older adults.