Medication review and deprescribing in different healthcare settings: a position statement from an Italian scientific consortium.

Recent medical advancements have increased life expectancy, leading to a surge in patients affected by multiple chronic diseases and consequent polypharmacy, especially among older adults. This scenario increases the risk of drug interactions and adverse drug reactions, highlighting the need for medication review and deprescribing to reduce inappropriate medications and optimize therapeutic regimens, with the ultimate goal to improving patients' health and quality of life. This position statement from the Italian Scientific Consortium on medication review and deprescribing aims to describe key elements, strategies, tools, timing, and healthcare professionals to be involved, for the implementation of medication review and deprescribing in different healthcare settings (i.e., primary care, hospital, long-term care facilities, and palliative care). Challenges and potential solutions for the implementation of medication review and deprescribing are also discussed.

COVID-19 after 2 Years from Hospital Discharge: A Pulmonary Function and Chest Computed Tomography Follow-Up Study.

INTRODUCTION: Serial follow-up with pulmonary function testing (PFT) and chest computed tomography (CT) after severe COVID-19 are recommended. As a result, many longitudinal studies have been published on COVID-19 of different grade of severity up to 1-year follow-up. Therefore, we aimed at a long-term observational study throughout 2 years after severe COVID-19. METHODS: Severe COVID-19 patients were consecutively recruited after hospital discharge between March and June 2020 and prospectively followed up for 24 months, with mMRC dyspnea scale and PFT at 6, 12, and 24 months. Chest CT was performed when clinically indicated. RESULTS: One hundred one patients enrolled completed the observational study. At 24 months, those with reduced total lung capacity (TLC) were 16%, associated with fibrotic ground glass opacity (GGO) and mMRC score >1, respectively, in 75% and 69% of them. At 24 months, those with a reduced diffusing capacity of the lung for CO were 41%, associated with fibrotic GGO and mMRC score >1, respectively, in 53% and 22% of them. CONCLUSION: Two years after hospitalization for severe COVID-19, a non-negligible number of patients still suffer from "long COVID" due to respiratory damage.

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.

Italian good practice recommendations on management of persons with Long-COVID.

A significant number of people, following acute SARS-CoV-2 infection, report persistent symptoms or new symptoms that are sustained over time, often affecting different body systems. This condition, commonly referred to as Long-COVID, requires a complex clinical management. In Italy new health facilities specifically dedicated to the diagnosis and care of Long-COVID were implemented. However, the activity of these clinical centers is highly heterogeneous, with wide variation in the type of services provided, specialistic expertise and, ultimately, in the clinical care provided. Recommendations for a uniform management of Long-COVID were therefore needed. Professionals from different disciplines (including general practitioners, specialists in respiratory diseases, infectious diseases, internal medicine, geriatrics, cardiology, neurology, pediatrics, and odontostomatology) were invited to participate, together with a patient representative, in a multidisciplinary Panel appointed to draft Good Practices on clinical management of Long-COVID. The Panel, after extensive literature review, issued recommendations on 3 thematic areas: access to Long-COVID services, clinical evaluation, and organization of the services. The Panel highlighted the importance of providing integrated multidisciplinary care in the management of patients after SARS-CoV-2 infection, and agreed that a multidisciplinary service, one-stop clinic approach could avoid multiple referrals and reduce the number of appointments. In areas where multidisciplinary services are not available, services may be provided through integrated and coordinated primary, community, rehabilitation and mental health services. Management should be adapted according to the patient's needs and should promptly address possible life-threatening complications. The present recommendations could provide guidance and support in standardizing the care provided to Long-COVID patients.

COVID-19 6 months after hospital discharge: pulmonary function impairment and its heterogeneity.

After 6 months, about half of #COVID19 discharged subjects present impaired respiratory function with exertional dyspnoea, mainly due a reduced CO diffusion (34%), followed by pulmonary restriction (19%) https://bit.ly/3vcnbdR.

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.

Italian intersociety consensus on prevention, diagnosis, and treatment of delirium in hospitalized older persons.

Delirium is a severe neuropsychiatric syndrome characterized by inattention and global cognitive dysfunction in the setting of an acute medical illness, medical complication, drug intoxication, or drug withdrawal. The most important risk factors are advanced age and dementia, whereas pain, dehydration, infections, stroke, metabolic disturbances, and surgery are the most common triggering factors. Although delirium is a common clinical syndrome in different settings of care (acute care hospitals, inpatient rehabilitation facilities, nursing homes, and hospices), it often remains under-recognized, poorly understood, and inadequately managed. There exists a clear need for improved understanding to overcome cultural stereotypes, and for the development and dissemination of a comprehensive model of implementation of general good practice points. A network of Italian national scientific societies was thus convened (1) to develop a collaborative multidisciplinary initiative report on delirium in elderly hospitalized patients, (2) to focus the attention of health care personnel on prevention, diagnosis, and therapy of patients suffering from delirium, and (3) to make the health services research community and policy-makers more aware of the potential risks of this condition providing a reference for training activities and data collection.

Pulmonary embolism prognostic factors and length of hospital stay: A cohort study.

INTRODUCTION: Patients with pulmonary embolism (PE) are commonly admitted to hospital for their initial treatment. We aimed to assess the association of length of hospital stay with commonly available clinical variables and their combinations. METHODS: A retrospective multicenter cohort study was conducted on consecutive PE patients admitted to eight Italian centers. Logistic regression analysis was performed to evaluate the association between the length of hospital stay and the Pulmonary Embolism Severity Index (PESI) parameters, National Early Warning Score (NEWS) and other possible determinants. RESULTS: We enrolled 391 patients, with a median hospital stay of 10days (IQR 7-14). Among PESI parameters, only oxygen saturation <90% was significantly associated with length of hospital stay at univariable analysis (OR 1.99; 95% CI 1.3-3.2). At multivariable analysis, NEWS ≥5 was associated with prolonged hospitalization (OR 3.14; 95% CI 1.2-8.3). A difference of median hospital stay was found between simplified PESI high and low risk groups (10 and 9days, respectively, p=0.027). DISCUSSION: The median duration of hospital stay was generally long and not influenced by single parameters of PESI or common prognostic factors. The difference of one day between the low- and high-risk groups according to simplified PESI was not clinically significant.

Nephrotic syndrome in a patient with IgM myeloma with associated neutrophilia.

An unusual case having IgM monoclonal gammopathy with clinical and pathologic features of multiple myeloma (MM) in association with neutrophilia and nephrotic syndrome is reported. The patient showed lytic bone lesions, decreased IgG and IgA levels, Bence-Jones proteinuria, nephrotic proteinuria with edema, and histological plasma cell infiltration typical of MM. Moreover, mature neutrophilic leukocytosis, hepatomegaly, high leukocyte alkaline phosphatase score (LAP), absence of Philadelphia (Ph) chromosome and bcr gene rearrangement were also evidenced, all these features representing findings typical of the recently described plasma cell dyscrasia-associated neutrophilia. After the diagnosis, the patient was treated with melphalan and prednisone, with an excellent response to the treatment. Different from the 30 cases so far reported, this is the first case of plasma-cell dyscrasia with associated neutrophilia due to IgM-producing monoclonal gammopathy. At the same time, this is the first reported case of nephrotic syndrome secondary to IgM myeloma.

Induction of neutrophil chemotaxis by leptin: crucial role for p38 and Src kinases.

Leptin is involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Although hypoleptinemia characterizing malnutrition has been strictly related to increased susceptibility to infection, other hyperleptinemic conditions, such as end-stage renal disease (ESRD), are highly susceptible to bacterial infections. On the other hand, ESRD is characterized by neutrophil functional defects crucial for infectious morbidity, and several uremic toxins capable of depressing neutrophil functions have been identified. In the present study, we investigated leptin's effects on neutrophil function. Our results show that leptin inhibits neutrophil migration in response to classical chemoattractants. Otherwise, leptin is endowed with chemotactic activity toward neutrophils. The two activities, inhibition of the cell response to chemokines and stimulation of neutrophil migration, could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca2+]i mobilization, oxidant production, or beta2-integrin upregulation. The results demonstrate that leptin is a pure chemoattractant devoid of secretagogue properties but capable of inhibiting neutrophil chemotaxis to classical neutrophilic chemoattractants. This effect is dependent on the activation of intracellular kinases involved in F-actin polymerization and neutrophil locomotion. Indeed, p38 mitogen-activated protein kinase (MAPK) and Src kinase, but not extracellular-regulated kinase (ERK), were activated by short-term incubation with leptin. Moreover, p38 MAPK inhibitor SB203580 and Src kinase inhibitor PP1, but not MEK inhibitor PD98059, blocked neutrophil chemotaxis toward leptin. Serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionine-leucyl-phenylalanine (FMLP) with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion. The serum inhibitory activity can be effectively prevented by immune-depletion of leptin. Taking into account the crucial role of neutrophils in host defense, we show that leptin-mediated ability of ERSD serum to inhibit neutrophil chemotaxis appears to be a mechanism contributing to neutrophil dysfunction in ESRD.

Leptin as a uremic toxin interferes with neutrophil chemotaxis.

Leptin is a pleiotropic molecule involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Hypoleptinemia characterizing starvation has been strictly related to increased susceptibility to infection secondary to malnutrition. Nevertheless, ESRD is characterized by high susceptibility to bacterial infection despite hyperleptinemia. Defects in neutrophils play a crucial role in the infectious morbidity, and several uremic toxins that are capable of depressing neutrophil functions have been identified. Only a few and contrasting reports about leptin and neutrophils are available. This study provides evidence that leptin inhibits neutrophil migration in response to classical chemoattractants. Moreover, serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion. Finally, the serum inhibitory activity can be effectively prevented by immune depletion of leptin. The results also show, however, that leptin by itself is endowed with chemotactic activity toward neutrophils. The two activities-inhibition of the cell response to chemokines and stimulation of neutrophil migration-could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca(2+)](i) mobilization, oxidant production, or beta(2)-integrin upregulation. The results demonstrate that leptin is a pure chemoattractant devoid of secretagogue properties that are capable of inhibiting neutrophil chemotaxis to classical neutrophilic chemoattractants. Taking into account the crucial role of neutrophils in host defense, the leptin-mediated ability of ERSD serum to inhibit neutrophil chemotaxis appears as a potential mechanism that contributes to the establishment of infections in ERSD.