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Purpose: Increasing prevalence of candidemia in Internal Medicine wards (IMWs) has been reported in recent years, but risk factors for candida bloodstream infection in patients admitted to IMW may differ from those known in other settings. The aim of this study was to identify risk factors and define a prediction rule for the early recognition of the risk of candidemia in IMW inpatients., Methods: This was a multicentric, retrospective, observational case-control study on non-neutropenic patients with candidemia admitted to IMWs of four large Italian Hospitals. Each eligible patient with candidemia (case) was matched to a control with bacteremia. Stepwise logistic regression analyses were performed., Results: Overall, 300 patients (150 cases and 150 controls) were enrolled. The following factors were associated with an increased risk of candidemia and weighted to build a score: total parenteral nutrition (OR 2.45, p = 0.008; 1 point); central venous catheter (OR 2.19, p = 0.031; 1 point); peripherally inserted central catheter (OR 5.63, p < 0.0001; 3 points), antibiotic treatment prior (OR 2.06; p = 0.059; 1 point) and during hospitalization (OR2.38, p = 0.033; 1 point); neurological disability (OR 2.25, p = 0.01; 1 point); and previous hospitalization within 3 months (OR 1.56, p = 0.163; 1 point). At ROC curve analysis, a final score ≥ 4 showed 84% sensitivity, 76% specificity, and 80% accuracy in predicting the risk of candidemia., Conclusions: The proposed scoring system showed to be a simple and highly performing tool in distinguishing bloodstream infections due to Candida and bacteria in patients admitted to IMW. The proposed rule might help to reduce delay in empirical treatment and improve appropriateness in antifungal prescription in septic patients.

Background: The number of human immunodeficiency virus (HIV)-related hospitalizations has decreased worldwide in recent years, due to the availability of combined antiretroviral therapies (cART). The present analysis aimed to analyse the economic, and clinical burden of HIV management, after the introduction of systematic use of cART., Methods: Data from HIV-infected patients, treated at Policlinico San Martino Hospital in Genova (Italy) were retrospectively collected. A comparison between years 2009 and 2015 was performed. HIV-related admissions were identified by using the Diagnosis-Related Group (DRG) codes. The resource consumption of outpatient services was derived by using a modelling approach. Expenditure for drugs was also analysed, as aggregate data., Results: The number of HIV-infected patients was 898 in 2009 and 1006 in 2015. Overall, the virological success rate improved from 2009 to 2015, as the percentage of patients with HIV-RNA < 50 copies/mL increased from 79 to 89% (P < 0.05). The average incidence of hospitalizations per-patient decreased from 0.30 in 2009, to 0.13 in 2015. Average expenditure per-patient decreased from €10,107 in 2009 to €9063 in 2015., Conclusions: The present analysis confirmed the role of cART in controlling HIV viral load and, consequently, in reducing hospitalizations, admissions to day-hospital and the use of outpatient services. Clinical improvements and economic savings more than compensated the investments required to treat HIV-infected patients with cART. Health Authorities should invest in modern cART supply and universal treatment, to use at best the available resources and obtain a cost-effective improvement of health in people living with HIV. Additional research, with the involvement of different centers and the use of patient-specific data, are recommended to consolidate the findings of this analysis.

Background: To ensure identification of anaplastic lymphoma kinase-positive (ALK + ) patients, the Italian Drug Agency suggested a testing algorithm based on the use of fluorescence in situ hybridization (FISH) and/or immunohistochemistry. The aim was to evaluate the clinical and economic effects of adopting an immunohistochemical test (Ventana ALK D5F3) as an option for detecting ALK protein expression in advanced non-small cell lung cancer (NSCLC) patients., Materials and Methods: A budget impact model was developed by adopting the Italian National Health Service (NHS) perspective and a 5-year period to compare 2 scenarios: the current use of D5F3 (28%; current scenario) and increased use of D5F3 (60%; alternative scenario). The testing cost and the number and cost of the identified ALK + patients were evaluated., Results: A more extensive use of D5F3 in the alternative scenario showed a decrease in diagnostic costs of ∼€468,000 compared with current scenario when considering all advanced NSCLC patients. If these savings were allocated to test more NSCLC patients (75% vs. 53%), an incremental cost per identified ALK + patient of €63 would be required, leading to an overall survival gain for the alternative scenario compared with the current scenario (32.4 vs. 27.1 months; relative increase, 20%)., Conclusion: The use of D5F3 would provide a cost savings for the NHS owing to a lower acquisition cost than FISH and a comparable detection rate. The savings could be reinvested to test a greater number of patients, leading to more efficient identification, use of targeted therapy, and improvement in clinical outcomes of ALK + patients., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Study Aim: Conventional endoscopic retrograde cholangiopancreatography (ERCP) combines endoscopy and radiography to diagnose and treat pathological conditions of the bile duct. The aim of the present analysis was to evaluate the clinical and economic impact of the use of single-operator intraductal cholangioscopy (IDC), which allows for direct visualization of the bile duct, as an alternative to ERCP for the treatment of difficult bile duct stones and the diagnosis of bile duct strictures., Patients and Methods: The clinical and economic consequences of single-operator IDC use were evaluated using two decision-tree models, one for management of difficult-to-remove stones and one for stricture diagnosis. A hospital perspective was adopted. Data to populate the models were derived from two Belgian hospitals that specialize in endoscopic procedures of the bile duct. Overall, the examined population consisted of 62 patients with difficult stones and 49 patients with indeterminate strictures., Results: In the model for difficult stone management, the use of IDC determined a decrease in the number of procedures (- 27 % relative reduction) and costs (- €73 000; - 11 % relative reduction) when compared with ERCP. In the model for stricture diagnosis, the use of IDC determined a decrease in the number of procedures (- 31 % relative reduction) and costs (- €13 000; - 5 % relative variation) when compared with ERCP., Conclusions: The single-operator IDC system performed better than ERCP for the treatment of difficult bile duct stones and the diagnosis of bile duct strictures, and reduced the overall expenditure in hospitals in Belgium., Competing Interests: Pierre Deprez has a consultant agreement with Boston Scientific, (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Chronic inflammatory rheumatic diseases (RDs) trigger high costs for healthcare systems and society due to the disability and comorbidity associated with these disease entities. The aim of this study was to analyze patients with RD, assess the use of conventional synthetic and biologic therapies, and estimate the overall cost of treatment in Italy., Methods: Administrative healthcare claims from the Piedmont region in Northwest Italy were reviewed to identify patients who received disease-modifying antirheumatic drugs (DMARDs) between 2007 and 2010. Confirmation of RD was based on: (1) diagnosis-specific exemption code; (2) hospitalization or emergency care events characterized by disease-specific ICD9 codes; (3) inclusion in the regional registry of biologic drugs. The follow-up period was 3 years., Results: A total of 9560 subjects, of whom the majority were women (58.1%), were entered into the study; the average age of the study population was 55.3 years. On the index date 12.9% of patients were receiving a biologic DMARD, with adalimumab the most frequently prescribed biologic DMARD (4.7%), followed by etanercept (4.4%). The average total healthcare expenditure was €377.98 per patient per month (patient-month). In the subgroup analysis of healthcare costs according to use of biologics, the total expenditure was €1037.97/€230.86 patient-month for those receiving/not receiving at least one biologic DMARD. In the subgroup analysis of healthcare costs according to type of biologic used, the total expenditure ranged from €657.61 (golimumab) to €1384.15 (rituximab) patient-month., Conclusions: A substantial difference in the total costs according to treatment/no treatment with a biologic and the specific biologic DMARD prescribed was identified. However, this result should be interpreted with caution as a bias in terms of patient selection was most likely present. The results of this study shed some light on RD in an relevant sample of Italian patients. The preliminary conclusions need to be confirmed by further analysis.

Background: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families., Methods: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community., Results: The societal burden of AD, composed of public, patient, and informal care costs, was about €20,000/yr. Out of this, the cost borne by the public sector was €4,534/yr. The main driver of public cost was the national cash-for-care allowance (€2,324/yr), followed by drug prescriptions (€1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at €13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure., Conclusion: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org (, Trial Registration Number: NCT01700556).

Nitroglycerin has been the mainstay of the medical management of angina pectoris for over 100 years. The long-held clinical impression of the efficacy of nitroglycerin has now been clearly documented in controlled clinical trials designed to evaluate objective response to antianginal agents. Advances in scientific methodology and improved experimental design have contributed to continuing interest in nitrates. Newer uses of nitroglycerin and other nitrates in congestive heart failure and acute myocardial infarction are the result of a developing understanding of the pharmacology of nitrates.

The hemodynamic effects of a new transdermal preparation of nitroglycerin were evaluated in 9 patients with chronic congestive heart failure (CHF). A graded infusion of nitroglycerin was administered initially to establish the dose-response relation for nitroglycerin and estimate the dose of topical nitroglycerin to be applied. Significant hemodynamic improvement was observed 0.5 to 1.0 hour after the cutaneous application of the nitroglycerin-impregnated polymer. The peak effect occurred at 6 hours, with the left ventricular filling pressure decreasing from 24 +/- 2 to 18 +/- 1 mm Hg (mean +/- standard error of the mean) (p less than 0.01) and the cardiac index increasing from 2.0 +/- 0.2 to 2.6 +/- 0.2 liters/min/m2 (p less than 0.01). The systemic vascular resistance decreased from 1,860 +/- 198 to 1,531 +/- 162 dynes s cm-5 (p less than 0.01). Heart rate and mean arterial pressure were unchanged. Significant hemodynamic benefit was observed for 24 hours, and no rebound deterioration occurred upon withdrawal of the drug. The average dose of transdermal nitroglycerin applied was 51 +/- 6 cm2 (1.7 +/- 0.2 mg/kg; 6 of the 9 patients received 64 cm2). Thus, topical application of a new nitroglycerin-impregnated polymer induces an improvement in cardiac performance that is sustained for 24 hours in patients with chronic CHF. However, substantial doses of the drug may be required to produce a satisfactory hemodynamic response in most patients with CHF.