Appropriateness of antiplatelet therapy for primary and secondary cardio- and cerebrovascular prevention in acutely hospitalized older people

Aims: Antiplatelet therapy is recommended for the secondary prevention of cardio- and cerebrovascular disease, but for primary prevention it is advised only in patients at very high risk. With this background, this study aims to assess the appropriateness of antiplatelet therapy in acutely hospitalized older people according to their risk profile. Methods: Data were obtained from the REPOSI register held in Italian and Spanish internal medicine and geriatric wards in 2012 and 2014. Hospitalized patients aged ≥65 assessable at discharge were selected. Appropriateness of the antiplatelet therapy was evaluated according to their primary or secondary cardiovascular prevention profiles. Results: Of 2535 enrolled patients, 2199 were assessable at discharge. Overall 959 (43.6%, 95% CI 41.5–45.7) were prescribed an antiplatelet drug, aspirin being the most frequently chosen. Among patients prescribed for primary prevention, just over half were inappropriately prescribed (52.1%), being mainly overprescribed (155/209 patients, 74.2%). On the other hand, there was also a high rate of inappropriate underprescription in the context of secondary prevention (222/726 patients, 30.6%, 95% CI 27.3–34.0%). Conclusions: This study carried out in acutely hospitalized older people shows a high degree of inappropriate prescription among patients prescribed with antiplatelets for primary prevention, mainly due to overprescription. Further, a large proportion of patients who had had overt cardio- or cerebrovascular disease were underprescribed, in spite of the established benefits of antiplatelet drugs in the context of secondary prevention

Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine

Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis1,2,3. However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma4,5. Moreover, lymphatic vessels collapse and become dysfunctional as melanomas progress6,7. Therefore, it is unclear whether (and how) lymphangiogenesis contributes to visceral metastasis. Soluble and vesicle-associated proteins secreted by tumours and/or their stroma have been proposed to condition pre-metastatic sites in patients with melanoma8,9,10,11,12,13,14. Still, the identities and prognostic value of lymphangiogenic mediators remain unclear2,14. Moreover, our understanding of lymphangiogenesis (in melanomas and other tumour types) is limited by the paucity of mouse models for live imaging of distal pre-metastatic niches15. Injectable lymphatic tracers have been developed7, but their limited diffusion precludes whole-body imaging at visceral sites16. Vascular endothelial growth factor receptor 3 (VEGFR3) is an attractive ‘lymphoreporter’17 because its expression is strongly downregulated in normal adult lymphatic endothelial cells, but is activated in pathological situations such as inflammation and cancer17,18. Here, we exploit this inducibility of VEGFR3 to engineer mouse melanoma models for whole-body imaging of metastasis generated by human cells, clinical biopsies or endogenously deregulated oncogenic pathways. This strategy revealed early induction of distal pre-metastatic niches uncoupled from lymphangiogenesis at primary lesions. Analyses of the melanoma secretome and validation in clinical specimens showed that the heparin-binding factor midkine is a systemic inducer of neo-lymphangiogenesis that defines patient prognosis. This role of midkine was linked to a paracrine activation of the mTOR pathway in lymphatic endothelial cells. These data support the use of VEGFR3 reporter mice as a ‘MetAlert’ discovery platform for drivers and inhibitors of metastasis.M.S.S. is funded by grants from the Spanish Ministry of Economy and Innovation (project SAF2014-56868-R), the Asociación Española Contra el Cáncer (AECC), the Worldwide Cancer Research, an Established Investigator Award from the Melanoma Research Alliance (MRA), and a L’Oréal Paris USA-MRA Team Science Award for Woman in Scientific Research. The CNIO Proteomics Unit belongs to ProteoRed, PRB2-ISCIII, supported by grant PT13/0001. N.I. and J.M. are funded by SAF2013-45504-R (MINECO). J.M. is also supported by Ramon y Cajal Programme (MINECO) RYC-2012-10651. J.L.R.-P and P.O.-R are funded by grants FIS 2014/1737, 11/02568 and FIS 2014/01784, 11/1759, respectively, from the Spanish Ministry of Health. F.M. is funded by the AMIT Project/CDTI/CENIT Programme (MICINN), S.O. by SAF2013-44866-R (MINECO), and J.J.B.-C. by an NCI K22CA196750 grant and the TCI Young Scientist Cancer Research Award JJR Fund (P30 CA196521). J.D.M. is the recipient of a postdoctoral fellowship from the ARC Foundation and E.R.-F. from Fundación Científica de la Asociación Española Contra el Cáncer. D.C.-W. is the recipient of a predoctoral fellowship from Fundación La Caixa, and M.C.-A. and X.C. are recipients of the Immutrain Marie Skłodowska-Curie ITN Grant.Peer reviewe

Antibiotic use and associated factors in a large sample of hospitalised older people.

OBJECTIVES: The aims of this study were to assess (i) the prevalence of antibiotic use, (ii) factors associated with their use and (iii) the association with in-hospital mortality in a large sample of hospitalised older people in Italy. METHODS: Data were obtained from the 2010-2017 REPOSI register held in more than 100 internal medicine and geriatric wards in Italy. Patients aged ≥65 years with at least one antibiotic prescription during their hospitalisation were selected. Multivariable logistic regression models were used to determine factors associated with antibiotic use. RESULTS: A total of 5442 older patients were included in the analysis, of whom 2786 (51.2%) were prescribed antibiotics during their hospitalisation. The most frequently prescribed antibiotic class was β- lactams, accounting for 50% of the total prescriptions. Poor physical independence, corticosteroid use and being hospitalised in Northern Italy were factors associated with a higher likelihood of being prescribed antibiotics. Antibiotic use was associated with an increased risk of in-hospital mortality (odds ratio=2.52, 95% confidence interval 1.82-3.48) also when accounting for factors associated with their use. CONCLUSION: Hospitalised older people are often prescribed antibiotics. Factors related to poor physical independence and corticosteroid use are associated with increased antibiotic use. Being prescribed antibiotics is also associated with an increased risk of in-hospital death. These results demand the implementation of specific stewardship programmes to improve the correct use of antibiotics in hospital settings and to reduce the risk of antimicrobial resistance

Prognostic value of degree and types of anaemia on clinical outcomes for hospitalised older patients

Study objective This study investigated in a large sample of in-patients the impact of mild-moderate-severe anaemia on clinical outcomes such as in-hospital mortality, re-admission, and death within three months after discharge. Methods A prospective multicentre observational study, involving older people admitted to 87 internal medicine and geriatric wards, was done in Italy between 2010 and 2012. The main clinical/laboratory data were obtained on admission and discharge. Based on haemoglobin (Hb), subjects were classified in three groups: group 1 with normal Hb, (reference group), group 2 with mildly reduced Hb (10.0–11.9 g/dL in women; 10.0–12.9 g/dL in men) and group 3 with moderately-severely reduced Hb (<10 g/dL in women and men). Results Patients (2678; mean age 79.2 ± 7.4 y) with anaemia (54.7%) were older, with greater functional impairment and more comorbidity. Multivariable analysis showed that mild but not moderate-severe anaemia was associated with a higher risk of hospital re-admission within three months (group 2: OR = 1.62; 95%CI 1.21–2.17). Anaemia failed to predict in-hospital mortality, while a higher risk of dying within three months was associated with the degree of Hb reduction on admission (group 2: OR = 1.82;95%CI 1.25–2.67; group 3: OR = 2.78;95%CI 1.82–4.26) and discharge (group 2: OR = 2.37;95%CI 1.48–3.93; group 3: OR = 3.70;95%CI 2.14–6.52). Normocytic and macrocytic, but not microcytic anaemia, were associated with adverse clinical outcomes. Conclusions Mild anaemia predicted hospital re-admission of older in-patients, while three-month mortality risk increased proportionally with anaemia severity. Type and severity of anaemia affected hospital re-admission and mortality, the worst prognosis being associated with normocytic and macrocytic anaemia

Risk factors for three-month mortality after discharge in a cohort of non-oncologic hospitalized elderly patients: Results from the REPOSI study

Background: Short-term prognosis, e.g. mortality at three months, has many important implications in planning the overall management of patients, particularly non-oncologic patients in order to avoid futile practices. The aims of this study were: i) to investigate the risk of three-month mortality after discharge from internal medicine and geriatric wards of non-oncologic patients with at least one of the following conditions: permanent bedridden status during the hospital stay; severely reduced kidney function; hypoalbuminemia; hospital admissions in the previous six months; severe dementia; ii) to establish the absolute risk difference of three-month mortality of bedridden compared to non-bedridden patients. Methods: This prospective cohort study was run in 102 Italian internal medicine and geriatric hospital wards. The sample included all patients with three-months follow-up data. Bedridden condition was defined as the inability to walk or stand upright during the whole hospital stay. The following parameters were also recorded: estimated GFR <= 29 mL/min/1.73 m(2); severe dementia; albuminemia << 2.5 g/dL; hospital admissions in the six months before the index admission. Results: Of 3915 patients eligible for the analysis, three-month follow-up were available for 2058, who were included in the study. Bedridden patients were 112 and the absolute risk difference of mortality at three months was 0.13 (CI 95% 0.08-0.19, p << 0.0001). Logistic regression analysis also adjusted for age, sex, number of drugs and comorbidity index found that bedridden condition (OR 2.10, CI 95% 1.12-3.94), severely reduced kidney function (OR 2.27, CI 95% 1.22-4.21), hospital admission in the previous six months (OR 1.96, CI 95% 1.22-3.14), severe dementia (with total or severe physical dependence) (OR 4.16, CI 95% 2.39-7.25) and hypoalbuminemia (OR 2.47, CI 95% 1.12-5.44) were significantly associated with higher risk of three-month mortality. Conclusions: Bedridden status, severely reduced kidney function, recent hospital admissions, severe dementia and hypoalbuminemia were associated with higher risk of three-month mortality in non-oncologic patients after discharge from internal medicine and geriatric hospital wards

Pattern of in-hospital changes in drug use in the older people from 2010 to 2016

Purpose: To assess the pattern of in-hospital changes in drug use in older patients from 2010 to 2016. Methods: People aged 65 years or more acutely hospitalized in those internal medicine and geriatric wards that did continuously participate to the REgistro POliterapie Società Italiana di Medicina Interna register from 2010 to 2016 were selected. Drugs use were categorized as 0 to 1 drug (very low drug use), 2 to 4 drugs (low drug use), 5 to 9 drugs (polypharmacy), and 10 or more drugs (excessive polypharmacy). To assess whether or not prevalence of patients in relation to drug use distribution changed overtime, adjusted prevalence ratios (PRs) was estimated with log-binomial regression models. Results: Among 2120 patients recruited in 27 wards continuously participating to data collection, 1882 were discharged alive and included in this analysis. The proportion of patients with very low drug use (0-1 drug) at hospital discharge increased overtime, from 2.7% in 2010 to 9.2% in 2016. Results from a log-logistic adjusted model confirmed the increasing PR of these very low drug users overtime (particularly in 2014 vs 2012, PR 1.83 95% CI 1.14-2.95). Moreover, from 2010 to 2016, there was an increasing number of patients who, on polypharmacy at hospital admission, abandoned it at hospital discharge, switching to the very low drug use group. Conclusion: This study shows that in internal medicine and geriatric wards continuously participating to the REgistro POliterapie Società Italiana di Medicina Interna register, the proportion of patients with a very low drug use at hospital discharge increased overtime, thus reducing the therapeutic burden in this at risk population