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.

Real-world use of remdesivir for the treatment of patients admitted to Italian hospitals with COVID-19: the nationwide retrospective FADOI-RECOVER study.

BACKGROUND: Remdesivir is widely used for treatment of SARS-CoV-2 pneumonia. The aim of this study was to evaluate the characteristics of patients with moderate-to-severe COVID-19 treated with remdesivir, and their outcomes during hospitalization. METHODS: This retrospective observational multicenter study included consecutive patients, hospitalized for moderate-to-severe COVID-19 (September 2020-September 2021), who were treated with remdesivir. RESULTS: One thousand four patients were enrolled, all with onset of symptoms occurring less than 10 days before starting remdesivir; 17% of patients had 4 or more concomitant diseases. Remdesivir was well tolerated, adverse drug reactions (ADRs) being reported in 2.3% of patients. In-hospital death occurred in 80 patients (8.0%). The median timing of the first remdesivir dose was 5 days after symptom onset. The following endpoints did not differ according to the time span from the onset of symptoms to the first dose: length of hospitalization, in-hospital death, composite outcome (in-hospital death and/or endotracheal intubation). Advanced age, number of comorbidities ≥ 4, and severity of respiratory failure at admission were associated with poor in-hospital outcomes. CONCLUSION: In a real-world setting, remdesivir proved to be a safe and well-tolerated treatment for moderate-to-severe COVID-19. In patients receiving remdesivir less than 3 or 5 days from the onset of SARS-CoV-2 symptoms, mortality and the need for mechanical ventilation did not differ from the rest of the sample.

Green Line Hospital-Territory Study: A Single-Blind Randomized Clinical Trial for Evaluation of Technological Challenges of Continuous Wireless Monitoring in Internal Medicine, Preliminary Results.

BACKGROUND: Wireless vital parameter continuous monitoring (WVPCM) after discharge is compared to regular monitoring to provide data on the clinical-economic impact of complex patients (CPs) discharged from Internal Medicine Units of Ospedale dei Castelli, Lazio. PRIMARY OUTCOME: Major complications (MC) reduction. SECONDARY OUTCOMES: Patients who reached discharge criteria within the 7th day from admission; difference in MC incidence at the conclusion of the standard telemonitoring/clinical monitoring phase, 5 and 30 days after discharge; and conditions predisposing to MC occurrence. METHODS: Open label randomized controlled trial with wearable wireless system that creates alerts on portable devices. Continuous glycemic monitoring is performed for patients with diabetes mellitus. RESULTS: There were 110 patients enrolled (mean age: 76.2 years). Comorbidity: Cumulative Illness Rating Scale CIRS-CI (comorbidities index): 3.93, CIRS SI (severity index): 1.93. About 19% scored a BRASS (Blaylock Risk Assessment Screening Score) ≥20 indicating need for discharge planning requiring step-down care. Globally, 48% of patients in the control group had major complications (27 out of 56 patients), in contrast to 22% in the intervention group (12 out of 54 patients). CONCLUSIONS: Since WVPCM detects early complications during the post-discharge CPs monitoring, it increases safety and reduces inappropriate access to the Emergency Room, preventing avoidable re-hospitalizations.

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.

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.

Misdiagnosis of vertebral fractures on local radiographic readings of the multicentre POINT (Prevalence of Osteoporosis in INTernal medicine) study.

BACKGROUND: Osteoporotic vertebral fractures (VFs) are often misdiagnosed because asymptomatic and occurring in the absence of specific trauma. Further, diagnostic assessment of VFs may be suboptimal. AIM OF THE STUDY: To assess the misdiagnosis of vertebral fractures on local radiographic readings in the cohort of patients enrolled in the POINT study. METHODS: We enrolled hospitalised patients, admitted for any cause to the Internal Medicine Units of 37 hospitals participating to the cross-sectional previously published POINT study. The assessment of VFs was performed both by local radiologists and by two expert skeletal radiologists, by using semiquantitative method (SQ). To better evaluate mild vertebral deformities, the two central radiologists also used the algorithm-based qualitative assessment (ABQ). RESULTS: The radiographs of 661 patients (401 females; mean age 75.8±8.0) were evaluated. The inter-reader percent agreement between two central expert radiologists per-vertebra assessment was excellent (99.78%; k=0.984; 95% CI, 0.977-0.991). Central reading identified 318/661 (48.1%) patients with at least one VF. Local and central readings agreed in 502/661 (75.9%) patients, resulting in a fair reproducibility (k=0.52; 95% confidence interval 0.44-0.59). Diagnostic performance parameters of local readings were: sensitivity 76.1%; specificity 75.8%; PPV 74.46%; NPV 77.38%). By examining 9254 vertebrae, central and local readers diagnosed 665 (7.2%) and 562 (6.1%) VFs respectively. Misdiagnosis (102 false positives and 205 false negatives) mainly occurred for mild VFs. Local readings identified correctly 460 out 665 VFs diagnosed by central readings, resulting in sensitivity of 69.2% and PPV of 81.8%. CONCLUSIONS: Following a standardized protocol of acquisition techniques and of interpretation criteria, an excellent agreement between local and central readings for moderate and severe vertebral fractures resulted. However a significant amount of mild vertebral fractures, that are the most of VFs, were misdiagnosed by local radiologists. In order to improve VFs assessment, the radiologists should be trained and sensitized in relation to the relevant clinical significance of osteoporotic VFs identification.

Evaluation of safety at work in a psychiatric setting: the "Workplace Safety Assessment".

OBJECTIVES: Workplace violence is a common risk for mental health professionals, and psychiatrists often encounter it in a variety of settings. The aim of this study was to estimate the prevalence and features of violent episodes toward psychiatrists in various mental healthcare system settings. METHODS: All psychiatrists from the Region of Puglia (Apulia) were contacted (N=285) via email and were administered an on-line standardized questionnaire. RESULTS: The response rate by psychiatrists was 57%. The main types of violence revealed were "threats" and "verbal aggression" and, of particular importance, "stalking". Female psychiatrists seemed to be at a higher risk of becoming victims of workplace violence, especially as regards verbal abuse (OR: 2.7, 95% CI: 1.2-6.5, c2 6.7, p=0.0095) and reported more serious psychological consequences with need for rest after the episode of aggression. CONCLUSIONS: Our data confirm that mental health workers, particularly psychiatrists, are healthcare professionals at high risk for workplace violence. Future implementation of preventive strategies with the aim of reducing aggressive episodes towards psychiatrists should be a high priority for managers and policy-makers operating in the Italian healthcare sector.

Prulifloxacin vs Levofloxacin for Exacerbation of COPD after Failure of Other Antibiotics.

The chronic course and evolution of chronic obstructive pulmonary disease (COPD) is often characterized by periods of exacerbation of symptoms, which have a negative impact on the quality of life of patients, as well as on the evolution of COPD, and represent a significant cause of medical intervention and hospitalization. Very few data are available on the efficacy of rescue antibiotics in patients with acute exacerbation of COPD (AECOPD) unresponsive to previous treatment. The aim of this study was to evaluate the efficacy of two fluoroquinolones in AECOPD previously treated without success. The FADOI-FLOR study is a randomized, single-blind, non-inferiority comparison between levofloxacin and prulifloxacin. Primary end-point was "therapeutic success" at Day 10 of treatment, defined as disappearance of signs/symptoms or decrease of at least three points of a global score of symptomatology (maximum score = 15). 258 patients were enrolled (128 levofloxacin and 130 prulifloxacin), in 25 centers. A very high proportion of patients in the two groups had therapeutic success at Day-10 (levofloxacin 93.0% vs prulifloxacin 96.7%, population intention-to-treat; 94.6% vs 99.1%, population per-protocol). Earlier therapeutic success (within 7 days) was achieved in 32.0% and 36.2% of patients receiving levofloxacin or prulifloxacin, respectively. At 3-month follow-up, re-exacerbations occurred in 17.8% of patients treated with levofloxacin and 14.2% of those receiving prulifloxacin (p = 0.44). In conclusion, fluoroquinolones are very effective in the treatment of AECOPD resistant to other antibiotics.

High prevalence of fragility vertebral fractures in patients hospitalised in Internal Medicine Units. Results of the POINT (Prevalence of Osteoporosis in INTernal medicine) study.

BACKGROUND: Osteoporotic vertebral fractures (VFs) often go unrecognised in both healthy individuals and in pathological conditions. Few data exist on VFs in patients hospitalised in Internal Medicine Units (IMUs), who often suffer from multiple concomitant chronic disorders. AIM OF THE STUDY: This multicentre cross-sectional study was aimed at assessing the prevalence of VFs in an unselected population of patients referring to IMUs. Correlations between VFs and the main coexisting diseases were also investigated. METHODS: Information on demographic, clinical and laboratory findings, and on the presence of known risk factors for osteoporosis was recorded. The Genant's semi-quantitative method was used to evaluate, in a central reading centre, the presence and severity of VFs in the thoracic and lumbar spine. RESULTS: A cohort of 995 patients was evaluated. At least one VF of any grade was found in 47.5% of patients, with similar prevalence between females (48.1%) and males (46.7%). Older age, chronic obstructive pulmonary disease, and previous diagnosis of osteoporosis showed a significant association with VFs in multivariable analysis. However, 79.7% of the VFs were observed in patients without previous diagnosis of osteoporosis. Moreover, a VF of grade 2 or greater was found in 20.8% of patients. CONCLUSIONS: Fragility VFs is a very frequent finding in patients hospitalised in IMUs. Consequently, more attention should be devoted in this clinical setting to this comorbidity, which is known to be an additional factor for mortality and, when localised in the thoracic part of the spine, may negatively influence a concomitant respiratory insufficiency.

Effects of iloprost on pain-free walking distance and clinical outcome in patients with severe stage IIb peripheral arterial disease: the FADOI 2bPILOT Study.

BACKGROUND: Patients with peripheral arterial disease (PAD) at stage IIb, pain-free walking distance (PFWD) less than 100 m and unsuitable for revascularization have both impaired quality of life and severe clinical outcome. Aim of the study was to evaluate the efficacy of the prostacyclin analogue iloprost, added to standard therapy, in these patients. MATERIAL AND METHODS: Patients were randomized to receive standard medical therapy (Group A) or standard therapy plus iloprost (Group B), for 1 year. Iloprost was administered for 10 days every 3 months. Treadmill test was performed every 3 months, in Group B before starting the 10-day iloprost cycle. RESULTS: Fifty patients in Group A and 51 in Group B were enrolled. Mean baseline and 12-month PFWD values were 75.4 ± 21.3 and 128.9 ± 62.9 for iloprost group and 70.3 ± 21.6 and 99.6 ± 62.6 m for controls. Patients treated with iloprost had significantly higher PFWD at 9 and 12 months. This finding was confirmed after carrying forward the last valid observation (124.7 ± 63.4 vs. 88.4 ± 63.1 m, P < 0.01). Major cardiovascular events occurred in 32.0% and 3.9% of patients in Group A and Group B, respectively (P < 0.001). Five patients in Group A died vs. none in Group B (P = 0.02). No serious unexpected adverse reactions occurred in patients receiving iloprost. CONCLUSIONS: Iloprost, added to standard therapy, significantly increases exercise capacity in patients with PAD at severe stage IIb. The percentage of patients who died or experienced major cardiovascular events was significantly lower in patients receiving iloprost. Future studies should focus on the effects of this therapy on clinical outcome.

Real-world management of atrial fibrillation in Internal Medicine units: the FADOI 'FALP' observational study.

BACKGROUND: Atrial fibrillation is the most frequent arrhythmia, but few data are available on patients' characteristics and management in the context of Internal Medicine wards. METHODS: Data were collected at the beginning of 2010 in 18 Internal Medicine units of the regions Liguria and Piemonte (Italy). Each centre reviewed the hospital charts of the last 50 patients discharged during the year 2009 in whom a diagnosis of atrial fibrillation had been made (patient's history or during the hospitalization). RESULTS: A total of 903 atrial fibrillation patients were evaluated. Prevalence of atrial fibrillation among patients hospitalized in Internal Medicine units was 18.2%. More than 85% of patients had at least two diseases other than atrial fibrillation, and 'lone' atrial fibrillation was rare (1.3%). During hospital stay, 80.5% of the patients received at least one treatment for atrial fibrillation: 55.5% received an antithrombotic and 61.8% a drug for arrhythmia, mostly aimed at rate control (47.2%). In-hospital all-cause mortality was 13.4%. At discharge, 70.2 and 68.9% of the patients received prescription of a drug for arrhythmia and for antithrombotic treatment, respectively. Prescription of oral anticoagulants was significantly associated with hypertension, while previous bleeding, age above 75 years, paroxysmal atrial fibrillation, male sex and a number of concomitant drugs of more than four were strong negative predictors. CONCLUSION: Data from our study confirm that atrial fibrillation is a common finding in patients hospitalized in Internal Medicine units, and this population is characterized by multiple comorbidities and severe prognosis. Discrepancies exist between recommendations by guidelines and real-world management, owing to the complexity of patients and limits of existing treatment strategies.

Incidence and predictors of venous thromboembolism in post-acute care patients. A prospective cohort study.

Few studies have addressed the topic of venous thromboembolism (VTE) in patients hospitalised in rehabilitation facilities. This patient population is rapidly growing, and data aimed to better define VTE risk in this setting are needed. Primary aim of this prospective observational study was to evaluate the frequency of symptomatic, objectively confirmed VTE in a cohort of unselected consecutive patients admitted to rehabilitation facilities, after medical diseases or surgery. Further objectives were to assess overall mortality, to identify risk factors for VTE and mortality, and to assess the attitude of physicians towards thromboprophylaxis. A total of 3,039 patients were included in the study, and the median duration of hospitalisation was 26 days. Seventy-two patients (2.4%) had symptomatic VTE. The median time to VTE from admission to the long-term care unit was 13 days. According to multivariable analysis, previous VTE (hazard ratio 5.67, 95% confidence interval 3.30-9.77) and cancer (hazard ratio 2.26, 95% confidence interval 1.36-3.75) were significantly associated to the occurrence of VTE. Overall in-hospital mortality was 15.1%. Age over 75 years, male gender, disability, cancer, and the absence of thromboprophylaxis were significantly associated to an increased risk of death (multivariable analysis). In-hospital antithrombotic prophylaxis was administered to 75.1% of patients, and low-molecular-weight heparin was the most widely used agent. According to our study, patients admitted to rehabilitation facilities remain at substantially increased risk for VTE. Because this applies to the majority of these patients, there is a great need for clinical trials assessing optimal prophylactic strategies.

In-hospital symptomatic venous thromboembolism and antithrombotic prophylaxis in Internal Medicine. Findings from a multicenter, prospective study.

Hospitalised medical patients are at increased risk of venous thromboembolism (VTE), but the incidence of hospitalisation-related VTE in unselected medical inpatients has not been extensively studied, and uncertainties remain about the optimal use of thromboprophylaxis in this setting. Aims of our prospective, observational study were to assess the prevalence of VTE and the incidence of symptomatic, hospitalisation-related events in a cohort of consecutive patients admitted to 27 Internal Medicine Departments, and to evaluate clinical factors associated with the use of thromboprophylaxis. Between March and September 2006, a total of 4,846 patients were included in the study. Symptomatic VTE with onset of symptoms later than 48 hours after admission ("hospital-acquired" events, primary study end-point) occurred in 26 patients (0.55%), while the overall prevalence of VTE (including diagnosis prior to or at admission) was 3.65%. During hospital stay antithrombotic prophylaxis was administered in 41.6% of patients, and in 58.7% of those for whom prophylaxis was recommended according to the 2004 Guidelines of the American College of Chest Physicians. The choice of administering thromboprophylaxis or not appeared qualitatively adherent to indications from randomised clinical trials and international guidelines, and bed rest was the strongest determinant of the use of prophylaxis. Data from our real-world study confirm that VTE is a relevant complication in patients admitted to Internal Medicine Departments, and recommended tromboprophylaxis is still under-used, in particular in some patients groups. Further efforts are needed to better define risk profile and to optimise prophylaxis in the heterogeneous setting of medical inpatients.

Genotyping of Pneumocystis jiroveci pneumonia in Italian AIDS patients. Clinical outcome is influenced by dihydropteroate synthase and not by internal transcribed spacer genotype.

BACKGROUND: Two Pneumocystis jiroveci independent genomic regions, internal transcribed spacer (ITS) 1 and ITS2, and dihydropteroate synthase (DHPS) gene have been used for typing a cohort of HIV-infected Italian patients with P jiroveci pneumonia (PcP). METHODS: Bronchoalveolar lavage samples isolated from 207 HIV-infected adults were ITS and DHPS genotyped by DNA sequencing and by restriction fragment length polymorphism analysis, respectively. Mutant DHPS samples were cloned and ITS typed. Data on severity, treatment, and outcome of PcP were obtained by chart review. RESULTS: High diversity with 46 different ITS genotypes was observed. At the DHPS locus, 9.1% of samples analyzed were found to be mutated. A correlation was observed between DHPS mutants and greater severity of PcP, as defined by higher lactate dehydrogenase (P = 0.015) and need for intubation (P = 0.002), and worse outcomes, as defined by failure of sulfa treatment (P = 0.04), death, and/or relapse of PcP (P = 0.008). There was a significant difference in ITS genotype patterns between DHPS wild-type and mutants (P = 0.028). CONCLUSIONS: The present data suggest the absence of a correlation between P jiroveci ITS types and specific clinical characteristics. DHPS mutations correlate with possible failure of anti-P jiroveci sulfa therapy, and a trend of association is shown between DHPS mutations and some clinical PcP features.

Assessment of immune reconstitution to Pneumocystis carinii in HIV-1 patients under different highly active antiretroviral therapy regimens.

The introduction of protease inhibitors (PIs) gave a dramatic drop in AIDS-related opportunistic events, mainly due to induced immune reconstitution. Discontinuation of prophylaxis against Pneumocystis carinii is considered safe when CD4 > 200 cells/mm(3). Ideally, we should have specific functional tests for HIV-1-related decisions. We examined viro-immunological profiles, clinical outcome and lymphocyte proliferation (LP) to P. carinii and other antigens in 108 subjects: 28 AIDS presenters with P. carinii pneumonia (PCP) (CD4 < 200 cells/mm(3)), 22 untreated asymptomatic HIV-1-infected patients (CD4 > 200 cells/mm(3)), 44 HIV-1-infected patients immune-reconstituted on antiretroviral regimens and 14 HIV-1-uninfected healthy controls. As regards viral load, there was no significant difference in therapy duration, nadir, or actual CD4, CD8, natural killer or B cell counts in immune-reconstituted patients receiving protease inhibitor (PI)-based versus those receiving PI-sparing antiretroviral regimens. Among subjects showing abnormally low P. carinii-specific LP, three patients receiving a non-nucleoside reverse transcriptase inhibitor (nNRTI) developed PCP despite having CD4 > 250 cells/mm(3). P. carinii-specific LP could be considered for doubtful situations, i.e. for a safer clinical decision of discontinuing or restarting prophylaxis in patients with a low CD4 nadir or experiencing a sudden CD4 decrease under highly active antiretroviral therapy (HAART). HIV-1 PIs, having in vitro aspecific effects against Pneumocystis, could play a clinically significant anti-opportunistic role, thus offering a further benefit in heavily immunosuppressed patients during early stages of antiretroviral therapy.