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Background and Aim: Opportunities to participate in leadership and management with protected time can be limited for clinical trainees. The aim of this fellowship was to gain experience of gold standard healthcare management by becoming part of multidisciplinary teams working to deliver transformational change in the National Health Service (NHS)., Methods: A 6-month pilot fellowship, structured as an Out of Programme Experience was created for two registrars to be seconded to the healthcare division of Deloitte, a leading professional services firm. Competitive selection was jointly administered by the Director of Medical Education at St Bartholomew's Hospital and Deloitte., Results: The successful candidates worked on service-led and digital transformation projects, interfacing with senior NHS executives and directors. Trainees gained direct experience and understanding of high-level decision making in the NHS, tackling complex service delivery problems and the practical realities of delivering change within a constrained budget. One impact of this pilot has been completion of a business case to scale up the fellowship into an established programme that can allow other trainees to apply., Conclusion: This innovative fellowship has allowed interested trainees an opportunity to broaden the relevant skills and experience in leadership and management required in specialty training curriculum with real-life application in the NHS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Iron deficiency (ID) is prevalent and adverse in chronic heart failure (CHF) but few human studies have explored the myocardial mechanism(s) that potentially underlie this adversity. Because mitochondrial oxidative phosphorylation (OXPHOS) provides over 90% of the hearts adenosine triphosphate (ATP), and iron is critical for OXPHOS, we hypothesized that patients with CHF and ID would harbour greater cardiac energetic impairments than patients without ID., Methods and Results: Phosphorus magnetic resonance spectroscopy was used to quantify the phosphocreatine (PCr) to ATP (PCr/ATP) ratio, an index of in-vivo cardiac energetics, in CHF patients and healthy volunteers. Cardiac structure and function was assessed from magnetic resonance short stack cines. Patients with (n = 27) and without (n = 12) ID, and healthy volunteers (n = 11), were similar with respect to age and gender. The PCr/ATP ratio was lower in patients with ID (1.03 [0.83-1.38]) compared to those without ID (1.72 [1.51-2.26], p < 0.01) and healthy volunteers (1.39 [1.10-3.68], p < 0.05). This was despite no difference in cardiac structure and function between patients with and without ID, and despite adjustment for the presence of anaemia, haemoglobin levels, cardiac rhythm, or New York Heart Association (NYHA) class. In the total CHF cohort, the PCr/ATP ratio correlated with ferritin levels (rho = 0.4, p < 0.01), and was higher in NYHA class I than class II or III patients (p = 0.02)., Conclusion: Iron deficiency is associated with greater cardiac energetic impairment in patients with CHF irrespective of anaemia and cardiac structure and function. Suppression of cardiac mitochondrial function might therefore be a mechanism via which ID worsens human CHF., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Competing Interests: Competing interests: None declared.

Aims: Plasma volume (PV) expansion hallmarks worsening chronic heart failure (CHF) but no non-invasive means of quantifying volume status exists. Because weight and haematocrit are related to PV, they can be used to calculate relative PV status (PVS). We tested the validity and prognostic utility of calculated PVS in CHF patients., Methods and Results: First, we evaluated the agreement between calculated actual PV (aPV) and aPV levels measured using (125)Iodine-human serum albumin. Second, we derived PVS as: [(calculated aPV - ideal PV)/ideal PV] × 100%. Third, we assessed the prognostic implications of PVS in 5002 patients from the Valsartan in Heart Failure Trial (Val-HeFT), and validated this in another 246 routine CHF outpatients. On analysis, calculated and measured aPV values correlated significantly in 119 normal subjects and 30 CHF patients. In the Val-HeFT cohort, mean (+SD) PVS was -9 ± 8% and related to volume biomarkers such as brain natriuretic peptide (BNP). Over 2 years, 977 (20%) patients died. Plasma volume status was associated with death and first morbid events in a 'J-shaped' fashion with the highest risk seen with a PVS > -4%. Stratification into PVS quartiles confirmed that a PVS > -4% was associated with increased mortality (unadjusted hazard ratio 1.65, 95% confidence interval 1.44-1.88, χ(2)  = 54, P < 0.001) even after adjusting for 22 variables, including brain natriuretic peptide. These results were mirrored in the validation cohort., Conclusions: Relative PVS calculated from simple clinical indices reflects the degree to which patients have deviated from their ideal PV and independently relates to outcomes. The utility of PVS-driven CHF management needs further evaluation., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Platelet reactivity testing is important for the diagnosis of bleeding disorders, and increasingly to optimise anti-platelet therapy. Traditional light transmission aggregometry is considered the gold standard, whilst 96-well plate aggregometry, founded on similar principles, provides a higher throughput screening method. Despite the widespread use of both, methodologies and outputs vary widely between laboratories. We report a methodological approach towards providing a standardised optical detection of platelet aggregation (optimul method) based upon 96-well plate aggregometry. Individual wells of half-area 96-well plates were coated with gelatine and one of seven concentrations of arachidonic acid (AA), adenosine diphosphate (ADP), collagen, epinephrine (EPI), ristocetin, TRAP-6 amide or U46619, before being lyophilised, vacuum-sealed, foil-packed and stored at room temperature for up to 24 weeks. For platelet testing, 40 µl of platelet-rich plasma was added to each well. Platelet aggregation was determined by changes in light absorbance, release of ATP/ADP by luminescence and release of thromboxane (TX) A(2) by ELISA. Some experiments were conducted in the presence of aspirin (30 µM) or prasugrel active metabolite (PAM; 3 µM). Optimul plates stored for up to 12 weeks permitted reliable detection of concentration-dependent platelet aggregation, ATP/ADP release and TXA₂ production. PAM caused reductions in platelet responses to AA, ADP, collagen, EPI, TRAP-6 and U46619, whilst aspirin inhibited responses to AA, collagen and EPI. We conclude that the optimul method offers a viable, standardised approach, allowing platelet reactivity testing and could provide a broad platelet function analysis without the need for dedicated equipment.

Background: There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world., Methods: We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and either high-dose tirofiban or double-bolus eptifibatide (double AAD plus small molecules group, n=666). The primary end point (incidence of composite ischemic events within one year) included death, acute myocardial infarction, unstable angina, stent thrombosis or repeat PCI or coronary bypass surgery (related to the target vessel PCI failure) and was modelled by Cox's regression., Results: There were 89 composite ischemic events: 24 (11.6%) in double AAD alone and 65 (9.8%) in double AAD plus small molecules groups (log-rank test: p=0.36). Incidences by type of ischemic events were similar between the 2 groups. Based on 21 potential covariates fitted simultaneously, adjusted hazard ratios (HR and 95% confidence intervals) showed that age (HR 1.03, 1.01-1.06, p=0.01), diabetes (HR 1.68, 1.01-2.79, p=0.05) and intra aortic balloon pump (HR 5.12, 2.36-11.10, p=0.0001) were significant risk factors whereas thrombolysis by tenecteplase (HR 0.35, 0.13-0.98, p=0.05) and having had hypertension or anti-hypertensive treatment (HR 0.58, 0.36-0.93, p=0.03) were significant protectors for events. Whether small molecules were present provided a non significant additional benefit as compared to double AAD alone (HR 0.83, 0.51-1.36, p=0.46). Pre-PCI CK-MB were not useful to predict events (HR 1.01, 0.99-1.01, p=0.17)., Conclusions: In clinical world patients undergoing PCI (rescue plus primary <13%) while on double AAD, based on clopidogrel plus aspirin, small molecules (tirofiban or eptifibatide) provided no additive long-term protection against the occurrence of composite ischemic events whereas thrombolysis by tenecteplase did.

Background: The Sant'ANna TIrofiban Safety study (SANTISS) is an open-label investigator-initiated single-centre registry launched to assess the combination of bleeding and access site in-hospital complications (primary end-point) in patients undergoing percutaneous coronary intervention (PCI) by femoral approach only., Methods: We compared patients who were on oral single antiaggregating drug (AAD) and received, just prior to PCI, high-dose tirofiban and a second oral antiplatelet agent (triple AAD: group 1, n = 970) with those who were already on an oral double AAD regimen and did not receive tirofiban (double AAD: group 2, n = 608)., Results: Group 2 patients were slightly older, presented less frequently with unstable angina and had chronic renal failure more frequently. They were more than twice as frequently on rescue PCI, being more than three-fold less frequently on primary PCI (all: 0.01>P < 0.001). Overall, there were 87 in-hospital (average 4.7 days of stay) complications: 51 (5.3%) in group 1 and 36 (5.9%) in group 2 (not significant). Haemotransfusions were needed in 34 patients: 21 (2.2%) in group 1 and 13 (2.1%) in group 2 (not significant). Of the 16 hospital deaths, eight (0.8%) were seen in group 1 and eight (1.3%) in group 2 (not significant). Multivariate prediction showed a high predictive accuracy (areas under the curve >0.700) of female sex, rescue PCI and chronic renal failure to index complications, with highly significant odds ratios. The presence of high-dose tirofiban did not increase complication risk., Conclusion: In the real world, high-dose tirofiban is well tolerated by patients on elective, primary or rescue PCI, and the in-hospital complication rate, including major bleeding, is low. This may have pharmacoeconomic consequences.

Aim of this paper is to analyze the tools and working methods, used in the Lazio Region, to assess organizational appropriateness in the context of Inpatient Rehabilitation Facilities, and the results obtained. It illustrates also the regional experiences of Veneto and Lombardia, which characterized by dynamism and originality in an attempt to overcome the obvious place for the critical assessment of this area of care.

Compared to the previous one, the recently updated Italian version of the International Classification of Diseases - Clinical Modification (ICD-9-CM) includes new codes for the description of medical-related vaccinations procedures. In this work the new codes are described and the Classification is proposed as a possible tool for storing electronic information systems of immunization health services.

Nurses and physiotherapists who work in a Rehabilitation Centre are exposed to biologic hazards due to the close physical contact they have with their patients, who are often affected by contagious infectious diseases. The perceived risk amongst these workers is a significant element in establishing an effective prevention plan and in evaluating educational needs and was therefore investigated in this survey. An anonymous self-administered questionnaire, structured in four subsections for a total of twenty four multiple-choice questions was used. The evaluated variables included knowledge of pathogen transmission pathways, modes of exposure to such pathogens, knowledge of universal precautions and of ways in which to deal with known exposure. Physiotherapists, more so than nurses, have a partial and insufficient knowledge of biologic hazards. The main reason for this gap can be found in the school curriculum for such professionals, in which, in comparison to other graduate degree courses (medicine, nursing) a much smaller amount of course time is allotted to the topic of biologic hazards and risk prevention. In order to practice effective risk management it is therefore necessary for the employer to commit to providing specific on-site education and training to its workers. For this purpose, our centre has developed specific educational activities and internal procedures which can be shared on the topic of biologic hazards and risk management.

Often in Occupational Medicine doctors misunderstand or underestimate the occupational psychologic discomfort forms deriving from "transverse risks" of organizational kind. In this communication is shortly described a our study with in a "call center". We explain the several kinds of psychologic discomfort which we have here recognized and studied. We show, at last, some of job's organization modifications rose from the first outcome of our study.

Violence and aggression in health care settings is an ill-defined and under-reported problem. Early risk assessment, adequate training and information of health care workers, and specific monitoring tools (such as the Violent Incident Form, VIF) are necessary for risk management.

In the literature, several malformations of cortical development have been described as additional lesions in tuberous sclerosis complex. Among these lesions, a very large focal cortical dysplasia has peculiar magnetic resonance imaging features: a signal abnormality that extends radially inward toward the lateral ventricle from the pachygyric cortical surface plus a homogeneous clinical picture. Affected patients have early-onset drug-resistant epilepsy and severe developmental delay. We describe the clinical, genetic, neurophysiologic, and neuroradiologic characteristics of four patients affected by tuberous sclerosis and this type of cortical dysplasia these patients are of special interest because they have been operated on for their dysplastic lesions. Total control of seizures has been achieved in the three children who underwent a complete lesionectomy. This result cannot be permanent, however, because of the presence of other cortical tubers which could become epileptogenic. All things considered, our choice was to give these children at least temporary relief from severe epilepsy and possibly support for developmental progression.

In patients undergoing bone marrow transplantation cryptococcosis is rarely encountered. We report a fatal case of Cryptococcus meningitis in a 12-year-old girl with acute lymphoblastic leukemia (ALL) in second remission who had a transplant from a human leukocyte antigen (HLA)-identical unrelated bone marrow donor. The conditioning regimen was thiotepa, cyclophosphamide, and total body irradiation (TBI); graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A, methotrexate, and antilymphocyte globulin (ALG). The patient experienced stage III GVHD responsive to high-dose corticosteroids. On day +54 a thrombotic microangiopathy occurred. On day +64 neurological status worsened; a brain computed tomographic (CT) scan showed hyperdense lesions suggesting fungal infection. Detection of cryptococcal antigen by latex agglutination was positive but India ink stain and culture were negative. Despite treatment with amphotericin B, 5-flucytosine, and granulocyte-macrophage colony-stimulating factor, the patient died 13 days after the diagnosis.