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Aims In breast cancer (BC) patients treated with anthracyclines-based therapies, we aim at assessing whether adjuvant drugs impact cardiac function differently and whether their cardiotoxicity has a regional pattern. Methods and results In a multicentre study, 146 BC patients (56 ± 11 years) were prospectively enrolled and divided into three groups according to the received treatments: AC/EC-Group (doxorubicin or epirubicin + cyclophosphamide), AC/EC/Tax-Group (AC/EC + taxanes), FEC/Tax-Group (fluorouracil + EC + taxanes). Fifty-six patients of the total cohort also received trastuzumab. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were calculated before starting chemotherapy (T0), at 3 months (T3), at 6 (T6), and 12 months (T12). A ≥10% drop of EF, while remaining within the normal range, was reached at T6 in 25.3% of patients from the whole cohort with an early decrease only in FEC/Tax-Group (P = 0.04). A ≥15% GLS reduction was observed in many more (61.6%) patients. GLS decreased early both in the whole population (P Conclusions The decrease of GLS is more precocious and pronounced in BC patients who received FEC + taxanes. Cardiac function further worsens after 6 months of adjuvant trastuzumab. All LV segments are damaged, with the anterior septum and the apex showing the greatest impairments.

This study aims to assess the determinants of employment probabilities among people living with Human Immunodeficiency Virus (HIV) during a 15-year period (2001–2016) in Spain, focusing on the possible effects of occurrences such as the 2008 economic crisis. The probability of people living with HIV having a job was evaluated by applying several multivariate probit regression models. Differences between the employment status of people living with HIV and that of the general population were evaluated by applying genetic matching regression models. With respect to the former evaluation, for people living with HIV, the period before the crisis (2001–2007) was associated with a probability of being employed that was 2.43 percentage points (p.p.) higher than during the crisis, and the period after the crisis (2014–2016) with a probability that was 7.58 p.p. lower than during the crisis. Greater effects were also observed among males, the probability of being in employment before the economic crisis being higher (by 2.26 p.p.) and lower after the crisis (− 3.41 p.p.) than among women, and among those infected through drug use (6.18 p.p. and − 7.34 p.p. before and after the crisis, respectively), than among those infected through sex. When analysing the differences with respect to the general population, people living with HIV reported lower probabilities of being employed: by − 18 p.p. before the crisis, by − 15 p.p. during the crisis (years 2008–2013) and by − 10 p.p. after the crisis, implying a convergence in the prospects of employment with the passage of the years. Those differences were greater for people of basic educational level (− 23 to − 16 p.p.), a weaker immune system (− 34 p.p. to − 21 p.p.) and those infected through the use of drugs (− 31 p.p. to − 26 p.p.). Although the results suggest that the economic crisis had a greater effect on the employment prospects of people living with HIV, and that effect is still felt by that group, our findings also point towards a convergence of their employment prospects with those of the general population, over the 15-year period assessed. An analysis of the employment situation of people living with HIV might have helped when designing job-seeking methods and policies on the working environment, especially through the 15-year period considered, when the economic crisis had a greater effect on the job market.

Stage A and B heart failure (HF) include asymptomatic patients without and with structural cardiac disorder, respectively. Asymptomatic left ventricular (LV) dysfunction represents an early stage of HF that should be recognized to prevent overt HF development. Echocardiography plays a pivotal role in assessment of cardiac structure and function and represents the ideal imaging technique for screening in the general population, thanks to its availability, feasibility, and low cost. Traditional echocardiography, with LV systolic and diastolic function and cardiac remodeling assessment, is usually performed. Development of new technologies may offer additional information and insights in detection of early LV dysfunction.

Aims Bicuspid aortic valve (BAV) may be complicated by aortic aneurysms and dissection. This study aimed to evaluate the prognostic efficacy of markers from cardiac imaging, as well as genetic and new biomarkers, to early predict aortic complications. Methods and results We re-evaluated after a mean time of 48 ± 11 months 47 BAV patients who had undergone previous echocardiography for evaluation of aortic stiffness and 2D aortic longitudinal strain (LS) (by speckle-tracking analysis), and who had given a blood sample for the assessment of a single-nucleotide polymorphism of elastin gene (ELN rs2 071307) and quantification of elastin soluble fragments (ESF). Surgical treatment of aortic aneurysm/dissection was the primary endpoint, and an aortic dimension increase (of one or more aortic segments) ≥1 mm/year was the secondary endpoint. Nine patients underwent surgical treatment of ascending aorta (AA) aneurysms. Out of the 38 patients who did not need surgical intervention, 16 showed an increase of aortic root and/or AA dimension ≥1 mm/year. At multivariate Cox regression analysis, an impaired AA LS was an independent predictor of aortic surgery [P = 0.04; hazard ratio (HR) 0.961; 95% confidence interval (CI) 0.924–0.984] and aortic dilatation (P = 0.007; HR 0.960; 95% CI 0.932–0.989). An increased quantity of ESF was correlated (P = 0.015) with the primary endpoint at univariate Cox regression analysis but it did not keep statistical significance at multivariate analysis. Conclusion In BAV patients, impairment of elastic properties of the AA, as assessed by 2D LS, is an effective predictor of aortic complications.

To carry out a cost-effectiveness analysis of the use of Neuropad as a screening test for diabetic neuropathy together with the standard care tool, the 10-g monofilament, in people with diabetes. A cost-effectiveness analysis using a Markov model was developed to assess the impact on costs and outcomes of using Neuropad as a test for diabetic neuropathy (1) as a complement to the standard test, the 10-g monofilament (Neuropad + monofilament vs. monofilament); and (2) as a substitute for the monofilament (Neuropad vs. monofilament); from the healthcare provider perspective. The time horizon was 3 years. Data on costs and health gains were extracted from the literature. The incremental cost–utility ratio was calculated. Deterministic and probabilistic sensitivity analyses were also performed. Compared with standard care, Neuropad, in combination with the 10-g monofilament tool, is the dominant strategy as it leads to higher health gains and lower costs. In practice, compared with using the monofilament alone, performing both tests would lead to a savings of £1049.26 per patient and 0.044 QALY gain. Results were found to be consistent across the sensitivity analyses. Using both screening tools (Neuropad + monofilament) is a cost-effective strategy and the dominant alternative, when compared against using the 10-g monofilament alone. The results would be of special relevance in the early detection of diabetic peripheral neuropathy and to ensure the efficient allocation of resources and, thus, the sustainability of healthcare systems.

Objectives Recent studies have demonstrated mortality benefits from corticosteroid use in COVID-19 patients requiring respiratory support. However, clinical practice may warrant the use of corticosteroids outside the context of a clinical trial. Such data are rarely, if ever, reported. We explored the use of corticosteroids for adult respiratory distress syndrome (ARDS) indications in patients with non-COVID ARDS. Methods We retrospectively studied patients with moderate-to-severe ARDS, admitted to our intensive care unit (ICU) between January 2018 and March 2020. Key findings Of the 91 patients with ARDS identified, 80% were treated with a corticosteroid during their ICU admission. Of these, 73 (82%) had corticosteroids administered for reasons other than ARDS. Conclusions Corticosteroid use for non-ARDS indications is commonplace in ARDS patients in our ICU. The use of corticosteroids outside a randomisation process in randomised clinical trials may be more common than appreciated and needs to be routinely reported.

Background Tenosynovial Giant-Cell Tumour (TGCT) is a benign clonal neoplastic proliferation arising from the synovium, causing a variety of symptoms and often requiring repetitive surgery. This study aims to define the economic burden—from a societal perspective—associated with TGCT patients and their health-related quality of life (HRQOL) in six European countries. Methods This article analyses data from a multinational, multicentre, prospective observational registry, the TGCT Observational Platform Project (TOPP), involving hospitals and tertiary sarcoma centres from six European countries (Austria, France, Germany, Italy, the Netherlands, and Spain). It includes information on TGCT patients’ health-related quality of life and healthcare and non-healthcare resources used at baseline (the 12-month period prior to the patients entering the registry) and after 12 months of follow-up. Results 146 TGCT patients enrolled for the study, of which 137 fulfilled the inclusion criteria. Their mean age was 44.5 years, and 62% were female. The annual average total costs associated with TGCT were €4866 at baseline and €5160 at the 12-month follow-up visit. The annual average healthcare costs associated with TGCT were €4620 at baseline, of which 67% and 18% corresponded to surgery and medical visits, respectively. At the 12-month follow-up, the mean healthcare costs amounted to €5094, with surgery representing 70% of total costs. Loss of productivity represented, on average, 5% of the total cost at baseline and 1.3% at follow-up. The most-affected HRQOL dimensions, measured with the EQ-5D-5L instrument, were pain or discomfort, mobility, and the performance of usual activities, both at baseline and at the follow-up visit. Regarding HRQOL, patients declared a mean index score of 0.75 at baseline and 0.76 at the 12-month follow-up. Conclusion The results suggest that TGCT places a heavy burden on its sufferers, which increases after one year of follow-up, mainly due to the healthcare resources required—in particular, surgical procedures. As a result, this condition has a high economic impact on healthcare budgets, while the HRQOL of TGCT patients substantially deteriorates over time.

Patients with COVID-19 ARDS have distinct physiological and immunological phenotypes compared to patients with non-COVID ARDS. Patients with COVID-19 ARDS (n = 32) had a significant improvement in PaO2: FiO2 ratio (p = 0.046) following low-dose steroid treatment, unlike patients with non-COVID ARDS (n = 16) (p = 0.529). Patients with COVID-19 ARDS had a greater fall in CRP compared to patients with non-COVID ARDS, albeit not statistically significant (p = 0.07). Our novel findings highlight differences in the underlying physiological and immunological phenotypes between COVID-19 and non-COVID ARDS, with implications for future ARDS studies.

Coronary artery bifurcation lesions remain challenging despite significant advancements in stent technology and development of specific bifurcation stenting approaches. Optical coherence tomography (OCT) is the intracoronary imaging technique with the highest resolution and can generate automatically contoured lumen areas across the variable geometry of bifurcation lesions. Knowledge of plaque severity and composition facilitates planning of the best strategy for percutaneous coronary intervention (PCI) and stenting. In particular, the provisional stent strategy preferred in this context can be modified when there is high risk of side-branch compromise at the ostium after main vessel stenting. OCT is unique because it allows the identification of the site of guide wire crossing, an important determinant of the final result. OCT can also be used to assess the procedural success of new dedicated bifurcation stent technologies and for the evaluation at follow-up of potential predictors of stent thrombosis, including stent malapposition, stent under-expansion and stent-edge dissection. Finally, the development of 3D OCT allows a better evaluation of coronary anatomy – particularly of side branch ostium that is difficult to visualise by 2D OCT – further improving the value of this technique in guiding PCI in these patients.

Introduction Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. We undertook a meta-analysis of randomized controlled trials (RCTs) to determine the mortality benefit of non-specialist therapeutic interventions for ARDS available to general critical care units. Evidence acquisition A systematic search of MEDLINE, Embase, and the Cochrane Central Register for RCTs investigating therapeutic interventions in ARDS including corticosteroids, fluid management strategy, high PEEP, low tidal volume ventilation, neuromuscular blockade, prone position ventilation, or recruitment maneuvers. Data was collected on demographic information, treatment strategy, duration and dose of treatment, and primary (28 or 30-day mortality) and secondary (PaO2:FiO2 ratio at 24-48 hours) outcomes. Evidence synthesis No improvement in 28-day mortality could be demonstrated in three RCTs investigating high PEEP (28.0% vs. 30.2% control; risk ratio [confidence interval] 0.93 [0.82-1.06]; eight assessing prone position ventilation (39.3% vs. 44.5%; RR 0.83 [0.68-1.01]; seven investigating neuromuscular blockade (37.8% vs. 42.0%; RR 0.91 [0.81-1.03]); ten investigating recruitment maneuvers (42.4% vs. 42.1%; RR 1.01 [0.91-1.12]); eight investigating steroids (34.8% vs. 41.1%; RR 0.81 [0.59-1.12]); and one investigating conservative fluid strategies (25.5% vs. 28.4%; RR 0.90 [0.73-1.10]). Three studies assessing low tidal volume ventilation (33.1% vs. 41.9 %; RR 0.79 (0.68-0.91); p=0.001), and subgroup analyses within studies investigating prone position ventilation greater than 12 hours (33.1% vs. 44.4%; RR 0.75 [0.59-0.95), p=0.02) did reveal outcome benefit. Conclusions Among non-specialist therapeutic strategies available to general critical care units, low tidal volumes and prone position ventilation for greater than 12 hours improve mortality in ARDS.

Biliary tract cancer is an uncommon cancer in developed countries. In localized stages, surgery is the cornerstone of treatment with curative purpose. Conversely in advanced stages, chemotherapy with platinum-gemcitabine combination is the standard of care. Biliary tract cancers are a biologically heterogeneous group of malignancies, which perhaps explains the failure of targeted therapies in unselected patient populations to demonstrate benefit in advanced disease, although there are promises in selected populations (e.g. PD1/PD-L1 positive, BRAFV600E-mutated or IDH1-mutant). In view of the limited benefit of second line therapies in metastatic biliary tract cancer, various targeted agents have been tested in progressive disease. Furthermore, several ongoing trials are using next-generation sequencing of multiple genes to identify molecular abnormalities in the tumors of patients with refractory cancers that may potentially be used in pretreated disease (e.g. FGFR or IDH genes). Immunotherapy with immune checkpoint inhibitors may be interesting for patients whose tumors have programmed cell death 1 ligand 1 (PD-L1) overexpression. Ongoing and future trials will further advance our knowledge toward the optimal treatment strategy for the management of biliary tract cancer in its different stages, starting from metastatic and then reaching early stages of disease. We here provided an overview of these novel treatment strategies for advanced biliary tract cancers not amenable of curative treatment modalities.

Introduction: The continuous increase of antimicrobial resistance (AMR) requires antimicrobial stewardship programs (ASPs) to optimize antimicrobial use, including selection, dose, duration, and way of administration. Methods and Results: An “Antimicrobial Stewardship Team” (AST) was established at “F. Miulli” Hospital of Bari. The AST is a multidisciplinary group formed by a pharmacist, an infectious disease specialist, a microbiologist, an anesthetist and a hygienist. The AST has started a clinical path of professional interactions and optimization of antimicrobial use. The AST was focused on surgical antibiotic prophylaxis, planning events/meetings with 13 wards of “F. Miulli” hospital and writing 13 operating guidelines. The AST was focused on antimicrobial therapies too. On this occasion, the AST did not organize events or meetings but was focused on professional interactions with clinicians to optimize the antimicrobial use in the treatment of multi-drug resistant (MDR) pathogens. A reduction of antimicrobial use (defined daily dose, DDD) and pharmaceutical expenditure was reached in surgical wards during 2017-2018, while, in the same period, an increase of antimicrobial use (DDD) and pharmaceutical expenditure was observed in non-surgical wards. Conclusions: The “Antimicrobial Stewardship Team” programs are essential to monitor the hospital economic resources and to support the purchase of the innovative antimicrobial therapies to treat multi-drug resistant pathogens.

Background Type 2 diabetes, a highly prevalent chronic disease, is associated with increasing frailty and functional decline in older people. We aimed to evaluate the effectiveness of a multimodal intervention on functional performance in frail and pre‐frail participants aged ≥70 years with type 2 diabetes mellitus. Methods The MID‐Frail study was a cluster‐randomized multicenter clinical trial conducted in 74 trial sites across seven European countries. The trial recruited 964 participants who were aged >70 years [mean age in intervention group, 78.4 (SD 5.6) years, 49.2% male and 77.6 (SD 5.29) years, 52.4% male in usual care group], with type diabetes mellitus and determined to be frail or pre‐frail using Fried's frailty phenotype. Participants were allocated by trial site to follow either usual care (UCG) or intervention procedures (IG). Intervention group participants received a multimodal intervention composed of (i) an individualized and progressive resistance exercise programme for 16 weeks; (ii) a structured diabetes and nutritional educational programme over seven sessions; and (iii) Investigator‐linked training to ensure optimal diabetes care. Short Physical Performance Battery (SPPB) scores were used to assess change in functional performance at 12 months between the groups. An analysis of the cost‐effectiveness of the intervention was undertaken using the incremental cost‐effectiveness ratio (ICER). Secondary outcomes included mortality, hospitalization, institutionalization, quality of life, burden on caregivers, the frequency and severity of hypoglycaemia episodes, and the cost‐effectiveness of the intervention. Results After 12 months, IG participants had mean SPPB scores 0.85 points higher than those in the UCG (95% CI, 0.44 to 1.26, P

Background: Childhood obesity is related to a wide spectrum of cardiovascular and metabolic comorbidities. Objectives: (1) To identify precocious, preclinical, cardiovascular sonographic modifications, in a cohort of overweight (OW) and obese (OB) children and adolescents compared to lean controls; (2) to investigate the association between clinical and metabolic variables and cardiovascular sonographic parameters; (3) to evaluate their relation with two different phenotypes of obesity: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). Materials and Methods: Fifty-nine OW and OB children and adolescents (9.8 ± 2.9 years) and 20 matched lean controls underwent anthropometric, biochemical, echocardiography assessment, and sonographic evaluation of carotid artery and ascending aorta (AA). OW and OB subjects were divided in MHO and MUO, according to the Camhi et al. definition. Results: OW and OB children showed significantly higher left ventricular (LV) dimensions and mass, carotid artery intima-media thickness (CIMT), carotid stiffness [β-index, pulse wave velocity (PWV)], significantly lower mitral peak early (E) and late (A) velocity ratio (E/A ratio), and significantly impaired global longitudinal strain (GLS) compared to controls. BMI SD and HOMA-IR were positively significantly related to LV dimensions, LA volume and epicardial adipose tissue (EAT), and negative to E/A ratio. Waist circumference (WC) was positively correlated to LV dimensions, LA volume, CIMT, PWV, AA diameter, and EAT. Furthermore, WC was a strong predictor of LV dimensions, LA volume and strain, AA stiffness and diameter; BMI SD was significantly associated with EAT, LVM index, and E/A ratio; HOMA-IR and triglycerides were significant predictors of GLS. MUO patients showed higher BMI SD (p = 0.02), WC (p = 0.001), WHtR (p = 0.001), HOMA-IR (p = 0.004), triglycerides (p = 0.01), SBP (p = 0.001), as well as LV dimensions, EAT (p = 0.03), CIMT (p = 0.01), AA diameter (p = 0.02), β-index (p = 0.03) and PWV (p = 0.002), AA stiffness (p = 0.006), and significantly impaired GLS (p = 0.042) compared to MHO. Conclusions: Severity of overweight, abdominal obesity, insulin resistance, and MUO phenotype negatively affect cardiovascular remodeling and subclinical myocardial dysfunction in OW and OB children. MUO phenotype is likely to increase the risk of developing cardiometabolic complications since the pediatric age. Distinction between MHO and MUO phenotypes might be useful in planning a personalized follow-up approach in obese children.

The intensive care unit (ICU) is among the more important settings in which echocardiography plays a pivotal role. The ease of use, speed of execution, and completeness of information on heart anatomy and function that echocardiography is able to provide makes this tool the perfect diagnostic technique in patients for whom exhaustive information must be quickly obtained by physicians who sometimes lack specific skills in cardiovascular imaging. However, the clinical entities encountered by ICU clinicians are often difficult to distinguish and patient symptoms may not be obvious. This brief review describes three common clinical scenarios that benefit from echocardiography in the ICU, based on symptoms frequently claimed by patients admitted to the ICU. For each symptom we describe the most likely clinical possibilities, underlining the fundamental role that echocardiography plays in the differential diagnosis, and the echocardiographic elements most relevant to obtain the correct diagnosis and to guide treatment.

Purpose To confirm GLS diagnostic sensitivity as parameter for the evaluation of LV systolic function in women with breast cancer who underwent chemotherapy including anthracyclines and to identify a pattern of decreased 2D speckle tracking regional longitudinal strain through the analysis of polar maps obtained with AFI technology. Methods We enrolled 60 female patients (age with 56.5±12 years) with breast cancer before the beginning of chemotherapy. The study protocol included clinical examination, ECG with QTc calculation, lab test (BNP and troponin I) and echocardiography with TDI and speckle tracking analysis (STI), that were performed before the beginning of the chemotherapy (basal) and after 3, 6 and 12 months. Echocardiography evaluation included the following parameters: LV end-diastolic and end-systolic volumes, LV ejection fraction (EF), average TDI S' at the mitral annulus, Global Longitudinal Strain (GLS), regional longitudinal strain, E/A ratio, E/E' ratio and sPAP. For each patient we analyzed the bull's eye maps before the beginning of the therapy (basal value) and when GLS showed the lowest values during the FU (FU value), to identify the pattern of regional longitudinal strain alterations. We compared basal and FU strain values for each of the 17 LV segments and the difference between them (delta) was calculated according to the formula [(FU LS –basal LS, (%)]. Results During the FU, systolic blood pressure, systolic pulse pressure and BNP values increased from the basal assessment to the 3 and 6 months FU. Similarly, a progressive worsening of GLS values has been observed (basal −20.4±2.6%, 3 months FU −18.2±2.5%, 6 months FU −17.7±2.9, 12 months FU −17.6±3, p value Conclusion GLS is able to identify LV systolic dysfunction that EF is not able to detect. However, since that it describes the global function of LV, GLS could result as normal (18–20%) when strain impairment of some LV segments is counterbalanced by the compensatory strain increase of other segments, determining an misdiagnosis of myocardial damage. Regional strain and particularly the Δ-strain, seem to suggest that anthracyclines induce a damage more evident in the apical cap and in the apical segment of the interventricular septum and this pattern could be typical in these patients. Thus, polar maps analysis could be provide additional information about cardiac damage in this population.

Background Myocardial work (MW) is a parameter of myocardial function which takes into account deformation as well as afterload. LV pressure-strain loops (PSLs) are a novel and reliable tool for the non-invasive assessment of MW. Purpose To evaluate MW indices in ischemic heart disease and their changes according to ejection fraction (EF) and type of myocardial infarction (MI) namely no-ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI). Methods A total of 61 patients (mean age: 64.4±12 years) since at least 30 days from acute STEMI or NSTEMI treated with primary PTCA and 31 healthy subjects (controls) were enrolled. Patients with MI were divided into three groups according to the EF-based heart failure (HF) classification: a) group 1, HF preserved EF (HFpEF, EF >50%); 2) group 2, HF mid-range EF (HFmrEF, EF 40–49%); 3) group 3, HF reduced EF (HFrEF, EF Results As shown in Table 1, GWE was significantly reduced in HFmrEF and HFrEF group (p=0.001) compared to both the controls and HFpEF group, while GWW was significantly higher (p Conclusions The non-invasive MW indices show a good correlation with traditional 2D parameters of myocardial systolic function in patients with ischemic heart disease. In addition, STEMI patients have lower constructive work than those with previous NSTEMI.

Background and Purpose— The aim of this article was to analyze the likelihood of receiving informal care after a stroke and to study the burden and risk of burnout of primary caregivers in Spain. Methods— The CONOCES study is an epidemiological, observational, prospective, multicenter study of patients diagnosed with stroke and admitted to a Stroke Unit in the Spanish healthcare system. At 3 and 12 months post-event, we estimated the time spent caring for the patient and the burden borne by primary caregivers. Several multivariate models were applied to estimate the likelihood of receiving informal caregiving, the burden, and the likelihood of caregivers being at a high risk of burnout. Results— Eighty percent of those still alive at 3 and 12 months poststroke were receiving informal care. More than 40% of those receiving care needed a secondary caregiver at 3 months poststroke. The likelihood of receiving informal care was associated with stroke severity and the individual’s health-related quality of life. When informal care was provided, both the burden borne by caregivers and the likelihood of caregivers being at a high risk of burnout was associated with (1) caregiving hours; (2) the patient’s health-related quality of life; (3) the severity of the stroke measured at discharge; (4) the patient having atrial fibrillation; and (5) the degree of dependence. Conclusions— This study reveals the heavy burden borne by the caregivers of stroke survivors. Our analysis also identifies explanatory and predictive variables for the likelihood of receiving informal care, caregiver burden, and high risk of burnout.

Aims: Echocardiography is the main technique for the diagnosis of endocarditis in patients with Staphylococcus aureus bacteremia (SAB), but a consensus about performing transthoracic echocardiography or transesophageal echocardiography (TEE) as first-line tests is currently lacking. Recently, a new scoring system has been proposed by Palraj et al. to guide the use of TEE in this population. Our aim was to validate this scoring system or modify it, if necessary. Methods and results: Data from SAB patients admitted from 2012 to 2014 were collected. We tested the Palraj scores to stratify patients’ risk for endocarditis. Moreover, we analyzed our population to identify any other possible clinical predictors of endocarditis not included in the score. Endocarditis was diagnosed in 38 of 205 patients (18.5%). Palraj’s score was effective in the detection of patients at high risk of endocarditis. In addition, we identified the presence of cardiac devices, prolonged bacteremia and intravenous drug abuse (IVDA) as elements strongly correlated with endocarditis. Two scoring systems (Day-1 and Day-5) were derived including IVDA as a variable. Using a Day-1 cut-off value ≥5 and a Day-5 cut-off value ≥2, the ‘modified Palraj’s score’ showed sensitivities of 42.1% and 97.0% and specificities of 88.6% and 32.0% for Day-1 and Day-5 scores, respectively. Conclusion: We modify and expand upon an effective scoring system to identify SAB patients at high risk for endocarditis in order to guide use of TEE. The inclusion of IVDA in the criteria for the calculation of the scores improves its effectiveness.

In recent years, the role of left ventricular ejection fraction (EF) as the gold standard parameter for the evaluation of systolic function has been questioned, and many efforts have been concentrated in the clinical validation of new noninvasive tools for the study of myocardial contractility. Improvement in the accuracy of speckle-tracking echocardiography has resulted in a large amount of research showing the ability of two-dimensional strain to overcome EF limitations in the majority of primary and secondary heart diseases. Currently, global longitudinal strain (GLS) is considered the most accurate and sensitive parameter for the assessment of early left ventricular dysfunction. This review summarizes the advantages that this measurement can provide in several clinical settings. Moreover, the important cautions that should be considered in making the choice to use GLS also are addressed. Finally, a special focus on bull’s-eye polar maps for the assessment of regional changes of longitudinal function and the usefulness of these maps in the differential diagnosis of several diseases is provided.

A correction to this paper has been published: https://doi.org/10.1007/s10198-021-01323-y

Aims. The Assessment of left ventricular (LV) function remains a clinical challenge especially in patients with preserved LV ejection fraction (EF) and valvular heart diseases (VHD). Mechanical dispersion is supposed to be a strong predictor of events and, to be related to the extent of fibrosis. Regional cardiac work is a new validated and very promising approach to quantify LV-function. We investigated the differences in mechanical dispersions and global LV work (totW) and wasted work fraction (WWF) in normal subjects and in patients with severe primary mitral regurgitation (MR) and severe aortic stenosis (AS). Methods and Results A complete transthoracic echocardiography was performed in 21 normal subject, 97 patients with severe valvulopathy (47 AS, 50 MR) and preserved LV EF. Segmental strain analysis was performed in all patients and the dispersion of regional LV strain curves was computed automatically considering peaks and integrals. The LV-pressure was estimated non-invasively using a standard waveform fitted to valvular events and scaled to systolic blood pressure. Using pressure-strain loops, regional cardiac work indices were computed. LVEF was 66±12 in controls, 65±9 in MR and 65±4% in AS (p=0.125). Global longitudinal strain was -23±2.7 in controls, -24±2.9 in MR and -18±3.2% in AS (p < 0.001). The mechanical dispersion was 38±7.9 in controls, 36±11 in MR, and much higher in the hypertrophied LV of the AS: 60±19ms (p < 0.001). Cardiac work was 2200±260 in controls, 2100±270 in MR, and much lower in AS: 1700±280 mmHg.% (p < 0.001). The wasted work fraction (WWF) was even more describing how different the LV systolic function is in the 3 groups (figure1). Conclusion Longitudinal strain data are robusted and new indices might be calculated based on them. These seem especially promising for a more pathophysiological driven analyzing of LV-functions. Abstract P697 Figure. Abstract P697 Figure.

Background The main objective of this study was to analyse how the inclusion (exclusion) of social costs can alter the results and conclusions of economic evaluations in the field of Alzheimer’s disease interventions. Methods We designed a systematic review that included economic evaluations in Alzheimer’s disease. The search strategy was launched in 2000 and ran until November 2018. The inclusion criteria were: being an original study published in a scientific journal, being an economic evaluation of any intervention related to Alzheimer’s disease, including social costs (informal care costs and/or productivity losses), being written in English, using QALYs as an outcome for the incremental cost–utility analysis, and separating the results according to the perspective applied. Results It was finally included 27 studies and 55 economic evaluations. Around 11% of economic evaluations changed their main conclusions. More precisely, three of them concluded that the new intervention became cost-effective when the societal perspective was considered, whereas when using just the health care payer perspective, the new intervention did not result in a cost–utility ratio below the threshold considered. Nevertheless, the inclusion of social cost can also influence the results, as 37% of the economic evaluations included became the dominant strategy after including social costs when they were already cost-effective in the health care perspective. Conclusions Social costs can substantially modify the results of the economic evaluations. Therefore, taking into account social costs in diseases such as Alzheimer’s can be a key element in making decisions about public financing and pricing of health interventions.

SUMMARYThe prompt availability of reliable epidemiological information on emerging pandemics is crucial for public health policy-makers. Early in 2013, a possible new H1N1 epidemic notified by an intensive care unit (ICU) to GiViTI, the Italian ICU network, prompted the re-activation of the real-time monitoring system developed during the 2009–2010 pandemic. Based on data from 216 ICUs, we were able to detect and monitor an outbreak of severe H1N1 infection, and to compare the situation with previous years. The timely and correct assessment of the severity of an epidemic can be obtained by investigating ICU admissions, especially when historical comparisons can be made.

Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis) methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector) or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry). Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients. © 2015 by the authors; licensee MDPI, Basel, Switzerland., This work was support in part by Consejería de Salud y Bienestar Social (Junta de Andalucía) Grant (PI05142012), RETICEF (RD06/0013/1014-RD12/0043/0014) and Fondo de Investigación Sanitaria (Instituto Carlos III) Grants (PI12/02141) with co-financing from FEDER (Fondo Europeo de Desarrollo Regional). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

This review will discuss the most frequent sources of cardiac embolism and the role of echocardiography in these different clinical settings, and, in addition, provide suggestions about the choice between transthoracic (TTE) and transesophageal echocardiography (TEE). Stroke is the third leading cause of death in industrial countries, and 15–40% of all ischemic strokes are due to cardioembolism. TTE and TEE are cornerstones in the detection of cardioembolic sources and provide fundamental information about the embolic risk and most suitable treatment of these patients, improving long-term outcomes. Echocardiography is a widely available, inexpensive, and safe diagnostic tool that is almost free from contraindication, and these elements allow the common use of this technique in almost all the patients with ischemic stroke. The most common cardioembolic sources include left atrial appendage thrombosis during atrial fibrillation; vegetations in infective endocarditis; cardiac masses including left ventricular thrombosis, cardiac tumors, etc.; atherosclerotic plaques; and passageways within the heart serving as conduits for paradoxical embolization, e.g., patent foramen ovale.

The evaluation by cardiovascular imaging of chemotherapy patients became a central topic in the last several years. The use of drugs for the treatment of cancers increased, and new molecules and protocols were developed to improve outcomes in these patients. Although, these novel approaches also produced a progressive increase in side effects, particularly myocardial dysfunction. Imaging of the heart was highly accurate in the early diagnosis of cancer therapeutics related-cardiac dysfunction. Echocardiography is the first-line method to assess ventricular function alterations, and it is required to satisfy the need for an early, easy and accurate diagnosis to stratify the risk of heart failure and manage treatments. A careful monitoring of cardiac function during the course of therapy should prevent the onset of severe heart impairment. This review provides an overview of the most important findings of the role of echocardiography in the management of chemotherapy-treated patients to create a clear and complete description of the efficacy of conventional measurements, the importance of comprehensive heart evaluations, the additional role of new echocardiographic techniques, the utility of integrated studies using other imaging tools and the positions of the most important international societies on this topic.

Early detection of anticancer drug-induced cardiotoxicity (CTX) has been evaluated by most international scientific cardiology and oncology societies. High expectations have been placed on the use of specific biomarkers. In recent years, conventional biomarkers and molecules of more recent interest have been tested and compared in the context of anticancer drug-related CTX. Encouraging results were obtained from studies on molecules of myocardial damage, such as troponin and markers of myocardial wall stress, including circulating natriuretic peptides, as well as from the assessment of the products of inflammation or circulating levels of free radicals. However, clear guidelines on their sensitivity, specificity, and accuracy are not yet available, and many challenges, such as the optimal time of assessing, optimal schedule for evaluation, optimal cut-off point for positivity with the highest level of specificity, and optimal comparability of different assays for the measurements, remain unresolved. Given the importance of having a reliable and accurate tool for monitoring anticancer drug-induced CTX, this review will focus on the available data on the most effective and widely used biomarkers and the studies that are currently underway that aim to identify the effectiveness of new approaches in this therapeutic setting.

Background/objectivesTo analyze mortality, costs, residents and personnel characteristics, in six long-term care facilities (LTCF) during the outbreak of COVID-19 in Spain.DesignEpidemiological study.SettingSix open LTCFs in Albacete (Spain).Participants198 residents and 190 workers from LTCF A were included, between 2020 March 6 and April 5. Epidemiological data were also collected from six LTCFs of Albacete for the same period of time, including 1,084 residents.MeasurementsBaseline demographic, clinical, functional, cognitive and nutritional variables were collected. 1-month and 3-month mortality was determined, excess mortality was calculated, and costs associated with the pandemics were analyzed.ResultsThe pooled mortality rate for the first month and first three months of the outbreak were 15.3% and 28.0%, and the pooled excess mortality for these periods were 564% and 315% respectively. In facility A, the percentage of probable COVID-19 infected residents were 33.6%. Probable infected patients were older, frail, and with a worse functional situation than those without COVID-19. The most common symptoms were fever, cough and dyspnea. 25 residents were transferred to the emergency department, 21 were hospitalized, and 54 were moved to the facility medical unit. Mortality was higher upon male older residents, with worse functionality, and higher comorbidity. During the first month of the outbreak, 65 (24.6%) workers leaved, mainly with COVID-19 symptoms, and 69 new workers were contracted. The mean number of days of leave was 19.2. Costs associated with the COVID-19 in facility A were estimated at € 276,281/month, mostly caused by resident hospitalizations, leaves of workers, staff replacement, and interventions of healthcare professionals.ConclusionThe COVID-19 pandemic posed residents at high mortality risk, mainly in those older, frail and with worse functional status. Personal and economic costs were high.

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0–5·5) with an incidence of respiratory critical events of 3·1% (2·9–3·3). Cardiovascular instability occurred in 1·9% (1·7–2·1), with an immediate poor outcome in 5·4% (3·7–7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86–0·90; p

BACKGROUND: In spite of its high prevalence and its clinical relevance, the economic impact of malnutrition has not been sufficiently explored.OBJECTIVE: To study whether malnutrition predicts total hospital healthcare costs and costs related to specialist visits, emergency department visits and hospitalization in older adults.METHODS: Concurrent cohort study in Albacete City, Spain. The study sample included 827 subjects aged 70 and over from the FRADEA Study. Mini Nutritional Assessment®-Short Form (MNA®-SF) was recorded at baseline. Use of hospital resources (hospital admissions, emergency visits, and specialist visits), and hospital healthcare costs were recorded at follow-up. Generalized linear models (GLM) adjusted for age, sex, comorbidity, polypharmacy, and disability in basic activities of daily living were used to estimate the impact of nutritional factors on total healthcare costs per person/year (€ base year 2013) as well as specialist visit costs, emergency department visit costs and hospitalization costs.RESULTS: The average cost associated with the use of health resources was 1922€/year. Subjects with MNA®-SF between 0 and 7 had an average total health cost of 3492€/year, 2744€/year in those with MNA®-SF between 8 and 11, and 1542€/year in those with MNA®-SF between 12 and 14. Of the total health cost, 67.2% was associated with hospital admission costs. Adjusted healthcare costs were 714€/year greater in subjects with malnutrition or nutritional risk. Subjects with malnutrition or nutritional risk presented an increased adjusted risk of hospitalization (OR1.72, 95% CI 1.22-2.43).CONCLUSIONS: Malnutrition assessed by MNA®-SF is a prognostic factor of high healthcare cost and use of resources in older adults.

Aims Bicuspid aortic valve (BAV) is associated with aortic wall alterations. We aimed to detect any correlation between aortic elasticity and genetic and biomolecular patterns of elastin. Methods and results Forty-nine BAV patients (mean age: 38 ± 17.05) were prospectively enrolled. A blood sample was drawn for analysis of a single nucleotide polymorphism of elastin gene (ELN rs2071307) responsible for misfolding of elastin, and for the amount of elastin soluble fragments (ESF) in the plasma. Aortic dimensions and elastic properties were determined by echocardiography, aortic stiffness (AS) by M-mode analysis, and longitudinal strain (LS) of the ascending aorta (AA) by speckle-tracking echocardiography; values of aortic strain were compared with 45 age-matched subjects (mean age: 33 ± 9.67) with tricuspid aortic valve (TAV). BAV patients had greater aortic dimensions [Valsalva sinus (P = 0.004), sinotubular junction (P = 0.013), AA (P

[Background] The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood. [Objectives] This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort. [Methods] The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry. [Results] At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc. [Conclusions] DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations., This work was supported by grants from the following institutions: Instituto de Salud Carlos III (ISCIII) (PI14/ 0967, PI15/01551, AC16/0014), CIBERCV (CB16/11/00403), Progreso and Salud Foundation (Junta de Andalucia) (PI-0011/201), Ministry of Economy, Industry and Competitiveness (IJCI-2016-29393), Mutual Medical (Research Award 2017), ERA-CVD Joint Transnational Call 2016 (Genprovic), British Heart Foundation (SP/10/10/28431), Wellcome Trust (107469/Z/15/), NIHR Royal Brompton Cardiovascular Biomedical Research Unit, NIHR Imperial Biomedical Research Center, Health Innovation Challenge Fund award from the Wellcome Trust and Department of Health, U.K. (HICF-R6-373), Danish Heart Foundation (16-R107-A6617), University of Southern Denmark, the Region of Southern Denmark, Odense University Hospital, German Competence Network Heart Failure, (TP9, FKZ 01GI0205), DETECTIN-HF project (ERA-CVD framework), and PROMEX Charitable Foundation. UCL Hospitals NIHR Biomedical Research Center and Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2015-12 eDETECT and CVON2014-40 DOSIS. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Grants from ISCIII and the Spanish Ministry of Economy and Competitiveness are supported by the Plan Estatal de IþDþI 2013-2016 – European Regional Development Fund (FEDER) “A way of making Europe.” The Hospital Universitario Puerta de Hierro Majadahonda, Hôpital PitiéSalpêtrière, and Saint Bartholomews’ Hospital are members of the European Reference Network for rare, low-prevalence, and complex diseases of the heart (ERN GUARD-Heart). Drs. Ochoa, Cicerchia, and Salazar-Mendiguchia are employees of Health In Code.

Objective and design: The late stages of carotid atherosclerosis are responsible for increased local stiffness, suggesting the need for a therapeutic target that affect either plaque composition and arterial stiffness. There is a lack of data on the role of the local arterial stiffness, assessed by radio-frequency based system and its relationship with the molecular profile of plaques. Subjects: In this study we enrolled 18 consecutive patients undergoing carotid endoarterectomy, with homogeneus or heterogeneous plaques, as established by Doppler-ultrasound and local pulse-wave velocity was assessed before surgery. Methods: In carotid plaque specimens, we evaluated inflammasome (NLRP3), Receptor Activator of Nuclear Factor κB (RANK) and its natural ligand (RANK-L), Osteoprotegerin (OPG), and other inflammatory and apoptotic molecules by Western Blotting and qPCR analysis. In addition, lipid peroxidation of arterial specimens was assessed by TBARS assay. Results: In heterogeneus plaques we observed increased OPG expression (p=0.04), positively correlated with lipid peroxidation values (r=0.511, p=0.03); increased levels of RANK (p=0.02), and other inflammatory and apoptotic molecules. RANK-L protein was augmented in homogeneus plaques (p=0.01) and correlated to s-index (r=0.514, p=0.03) and PWV (r=0.525, p=0.03) values. Conclusions: Our data provide evidence that increased local PWV and s-index might identify plaque evolution towards calcification.

Lamin A/C gene (LMNA)-related familial dilated cardiomyopathy (fDCM) is an aggressive heart disease that often leads to transplantation and sudden death. The aim of our study was to evaluate the circulating microRNA (miRNA) profiles of patients with LMNA pathogenic mutations. The study population (N = 75) included (i) patients with pathogenic LMNA mutations responsible for fDCM (LMNAMUT), (ii) age- and sex-matched LMNA wild-type controls (LMNAWT control), and (iii) LMNA wild-type idiopathic DCM (iDCM) patients (LMNAWT iDCM). Detailed clinical information was obtained from each participant. A panel of 179 plasma miRNAs was evaluated using RT-qPCR. An initial screening study was performed in LMNAMUT carriers and age-matched LMNAWT controls (N = 16). Forty-four miRNAs were specifically deregulated in LMNAMUT carriers. Ten miRNA candidates were selected for subsequent validation after coexpression analyses and filtered for expression levels and statistical significance. Among the candidates, let-7a-5p, miR-142-3p, miR-145-5p and miR-454-3p levels were significantly increased in LMNAMUT carriers compared to LMNAWT controls and iDCM patients (P, This work was supported by the Fundación Pública Andaluza Progreso y Salud para la Financiación de la I+i Biomédica y en Ciencias de las Salud en Andalucia (PI-0011/2014) and a grant in the framework of the Integrated Territorial Initiative (ITI)2014-2020 for the province of Cádiz by the Ministry of Health and the European Regional Developement Fund (ERDF) PI0048-2017 (project co-finantiated 80% by funds from the ERDF operational program of Andalusia 2014-2020) (ITI 0048-2017). This work was also supported by FIS PI14/01729 from the Instituto Salud Carlos III, co-financed by the European Fund for Regional Development (E.F.R.D.), Fundació Marató TV3 (201521 10), and Fundació BLa Caixa.^ CIBER Cardiovascular (CB16/11/00403) is an Instituto de Salud Carlos III Project. DdG-C was a recipient of a Juan de la Cierva-Incorporación grant from the Ministerio de Economía y Competitividad (IJCI-2016-29393).

Takotsubo cardiomyopathy (TTS), also known as left ventricular apical ballooning syndrome, is an acute, usually reversible heart failure syndrome that most often affects postmenopausal women experiencing an emotionally stressful event. It is characterized by sudden left ventricular dysfunction and wall motion abnormalities involving the apical and mid segments. TTS has been increasingly recognized in recent years, and more and more information about the pathophysiology, diagnosis, and treatment of these patients has been reported. However, much is still unknown. TTS has a wide variety of clinical subtypes and has been described in several clinical contexts. Moreover, TTS simulates ST-segment elevation myocardial infarction and acute myocarditis, and it can be difficult to obtain a certain diagnosis. As a result, clinical decisions are challenging, and many patients currently receive an inappropriate management strategy. The aim of this review is to critically analyze the evidence about this disease reported in the literature, with particular focus on the pathophysiological processes, the diagnostic elements that can help the clinician differentiate it from other diseases, and the best management of these patients.

The aim of this paper was to arrive at an approximation of the value of non-professional (informal) care provided to disabled people living within a household in Spain.We used the Survey on Disabilities, Autonomy and Dependency carried out in 2008 to obtain information about disabled individuals and their informal caregivers. We computed the total number of informal caregiving hours provided by main caregivers in Spain in 2008. The monetary value of informal care time was obtained using three different approaches: the proxy good method, the opportunity cost method and the contingent valuation method.Total hours of informal care provided in 2008 were estimated at 4193 million and the monetary value ranged from EUR23,064 to EUR50,158 million depending on the method used. The value of informal care was estimated at figures equivalent to 1.73-4.90 % of the gross domestic product for that year.Informal care represents a very high social cost regardless of the estimation method considered. A holistic approach to care of dependent people should take into account the role and needs of informal caregivers, promote their social recognition and lead to policies that enhance efficient use of formal and informal resources.

Fundamentos: El impacto económico que causan las enfermedades va mucho más allá del gasto sanitario, transmitiéndose a la sociedad a través de diferentes dimensiones. El principal objetivo de este estudio fue estimar la evolución de las pérdidas de productividad laboral causadas por muertes prematuras en España durante el periodo 2005-2009. Métodos: Se emplearon varias fuentes estadísticas (Registro de defunciones según la causa de muerte, Encuesta de Población Activa y Encuesta de Estructura Salarial) para desarrollar un modelo de simulación basado en el enfoque de capital humano que permitió estimar las pérdidas laborales ocasionadas por muertes prematuras para el periodo analizado. Adicionalmente, se llevaron a cabo dos escenarios alternativos en los que se analizó la influencia de la evolución epidemiológica en los resultados obtenidos. Resultados: El modelo de simulación mostró una caída de las pérdidas laborales asociadas a muertes prematuras que fue desde 8.935 millones de euros en 2005 a 8.073 millones de euros en 2009. El análisis de las causas reducidas de muerte señaló que nueve causas de enfermedad (accidentes de tráfico, tumor maligno de tráquea, suicidios, infarto agudo de miocardio, SIDA, cirrosis, tumor de mama, enfermedades cerebrovasculares y cáncer de colon) supusieron el 35,6% del total de Años Potenciales de Vida Laboral Perdidos y 36,6% del total de pérdida estimada. Las pérdidas estimadas representaron el 0,98%, 0,85% y 0,77% del Producto Interior Bruto de 2005, 2007 y 2009, respectivamente. Conclusiones: Las pérdidas laborales ocasionadas por muertes prematuras en España disminuyeron sustancialmente en el periodo analizado. Esta reducción se debió fundamentalmente a la favorable evolución epidemiológica de la mortalidad prematura. Background: The economic impact caused by diseases goes far beyond health care costs and, therefore it is transferred to the society through different dimensions. The aim of this study was to estimate the productivity losses due to premature deaths caused by diseases occurred in Spain during the period 2005-2009. Methods: We used data from several sources (Death Registry, Labour Force Survey and Wage Structure Survey) to develop a simulation model based on the human-capital approach that allowed us to estimate the labour productivity losses caused by premature deaths in the period analysed. Additionally, we also carried out two alternative scenarios in which we analysed how epidemiologic data influenced our results. Results: Our model showed the estimated loss of productivity due to premature death fell from 8,935 billion euros in 2005 to 8,073 billion euros in 2009. Nine diseases (traffic accidents, malignant tumour of the trachea, suicides, acute myocardial infarction, AIDS, cirrhosis, breast tumour, cerebrovascular disease and colon cancer) accounted for 35.6% of the total Years of Potential Productive Life Lost and 36.5% of the estimated productivity losses. The estimated losses represented 0.98%, 0.85% and 0.77% of Gross Domestic Product in 2005, 2007 and 2009, respectively. Conclusions: The labour productivity losses caused by premature deaths decreased substantially in the period analysed. This reduction was mainly due to the epidemiological evolution of premature mortality.

Background: Alzheimer’s disease constitutes one of the leading causes of burden of disease, and it is the third leading disease in terms of economic and social costs. Objective: To analyze the burden and problems borne by informal caregivers of patients who suffer from Alzheimer’s disease in Spain. Data and Methods: We used the Survey on Disabilities, Autonomy and Dependency to obtain information on the characteristics of disabled people with Alzheimer’s disease and the individuals who provide them with personal care. Additionally, statistical multivariate analyses using probit models were performed to analyze the burden placed on caregivers in terms of health, professional, and leisure/social aspects. Results: 46% of informal caregivers suffered from health-related problems as a result of providing care, 90% had leisure-related problems, and 75% of caregivers under 65 years old admitted to suffering from problems related to their professional lives. The probability of a problem arising for an informal caregiver was positively associated with the degree of dependency of the person cared for. In the case of caring for a greatly dependent person, the probability of suffering from health-related problems was 22% higher, the probability of professional problems was 18% higher, and there was a 10% greater probability of suffering from leisure-related problems compared to non-dependents. Conclusions: The results show a part of the large hidden cost for society in terms of problems related to the burden lessened by the caregivers. This information should be a useful tool for designing policies focused toward supporting caregivers and improving their welfare.

Background The aim of this study was to determine the economic burden and health-related quality of life (HRQOL) of patients with Spinal Muscular Atrophy (SMA) and their caregivers in Spain. Methods This was a cross-sectional and retrospective study of patients diagnosed with SMA in Spain. We adopted a bottom up, prevalence approach design to study patients with SMA. The patient’s caregivers completed an anonymous questionnaire regarding their socio-demographic characteristics, use of healthcare services and non-healthcare services. Costs were estimated from a societal perspective (including healthcare costs and non-healthcare costs), and health-related quality of life (HRQOL) was assessed using the EQ-5D questionnaire. The main caregivers also answered a questionnaire on their characteristics and on their HRQOL. Results A total of 81 caregivers of patients with different subtypes of SMA completed the questionnaire. Based on the reference unitary prices for 2014, the average annual costs per patient were € 33,721. Direct healthcare costs were € 10,882 (representing around 32.3% of the total cost) and the direct non-healthcare costs were € 22,839 (67.7% of the total cost). The mean EQ-5D social tariff score for patients was 0.16, and the mean score of the EQ-5D visual analogue scale was 54. The mean EQ-5D social tariff score for caregivers was 0.49 and their mean score on the EQ-5D visual analogue scale was 69. Conclusion The results highlight the burden that SMA has in terms of costs and decreased HRQOL, not only for patients but also for their caregivers. In particular, the substantial social/economic burden is mostly attributable to the high direct non-healthcare costs.

Despite the already well-known role the right side of the heart plays in many diseases, right ventricular (RV) function has only recently been carefully considered. Echocardiography is the first-line diagnostic technique for the assessment of the right ventricle and right atrium, whereas cardiac magnetic resonance is considered the gold standard but is limited by cost and availability. According to the current guidelines, systolic RV function should be assessed by several conventional measurements, but the efficacy of these parameters as diagnostic and prognostic tools has been questioned by many authors. The development in recent years of myocardial deformation imaging techniques and their application to the right heart chambers has allowed deeper evaluation of the importance of RV function in the pathophysiology of a large number of cardiovascular conditions, but the real value of this new tool has not been completely clarified. The aim of this review is to provide a wide and careful analysis of findings available in the literature about the assessment of RV systolic function by strain measurements, comparing them with conventional parameters and evaluating their role in several clinical settings.

> ‘ Estragon : What do we do now? Vladimir : Wait for Godot.’1 In the last decades, several authors focused their efforts on the evaluation of atrial function. It is now well known that atria play a key role in the physiological equilibrium of the heart. Indeed, atria are not mere conduits that allow blood to pass from the big vessels to the ventricles. In each cardiac cycle, atria, and particularly the left atrium (LA), act as reservoirs, receiving pulmonary venous return during left ventricular (LV) systole; as a conduit, transferring blood to the LV during early diastole; and as a pump, actively pushing blood to the LV in late diastole, providing in each of these phases 40%, 35%, and 25% of atrial contribution to stroke volume, respectively2 ( Figure 1 ). Interestingly, LA contributions became more important in the first stages of heart failure and its changes allow the LV to keep a precarious equilibrium until the increased LV filling pressure overcomes it, leading to the onset of symptoms. Consequently, LA function became a relevant predictor of prognosis in several clinical settings, including heart failure with preserved ejection fraction (HFpEF),3 coronary artery disease,4 and heart valve diseases,5 etc. Several echocardiographic parameters have been developed to evaluate atrial function, such as the peak A wave velocity of transmitral flow in late diastole obtained by pulsed wave Doppler and its velocity time integral (VTI), the A’ velocity using Doppler tissue imaging, LA …