Patients’ Satisfaction by SmileInTM Totems in Radiotherapy: A Two-Year Mono-Institutional Experience

Background: Patient’s satisfaction is recognized as an indicator to monitor quality in healthcare services. Patient-reported experience measures (PREMs) may contribute to create a benchmark of hospital performance by assessing quality and safety in cancer care. Methods: The areas of interest assessed were: patient-centric welcome perception (PCWP), punctuality, professionalism and comfort using the Lean Six Sigma (LSS) methodology. The RAMSI (Radioterapia Amica Mia SmileINTM (SI) My Friend RadiotherapySI), project provided for the placement of SI totems with four push buttons using HappyOrNot technology in a high-volume radiation oncology (RO) department. The SI technology was implemented in the RO department of the Fondazione Policlinico Universitario A. Gemelli IRCCS. SI totems were installed in different areas of the department. The SI Experience Index was collected, analyzed and compared. Weekly and monthly reports were created showing hourly, daily and overall trends. Results: From October 2017 to November 2019, a total of 42,755 votes were recorded: 8687, 10,431, 18,628 and 5009 feedback items were obtained for PCWP, professionalism, punctuality, and comfort, respectively. All areas obtained a SI-approved rate ≥ 8.0 Conclusions: The implementation of the RAMSI system proved to be doable according to the large amount of feedback items collected in a high-volume clinical department. The application of the LSS methodology led to specific corrective actions such as modification of the call-in-clinic system during operations planning. In order to provide healthcare optimization, a multicentric and multispecialty network should be defined in order to set up a benchmar

Retro-inverso peptide inhibitor nanoparticles as potent inhibitors of aggregation of the Alzheimer’s Aβ peptide

Aggregation of Amyloid-β peptide (Aβ) is a key event in the pathogenesis of Alzheimer’s disease (AD). We investigated the effects of nanoliposomes decorated with the retro-inverso peptide RI-OR2-TAT (Ac-rGffvlkGrrrrqrrkkrGy-NH2) on the aggregation and toxicity of Aβ. Remarkably low concentrations of these peptide inhibitor nanoparticles (PINPs) were required to inhibit the formation of Aβ oligomers and fibrils in vitro, with 50% inhibition occurring at a molar ratio of ~1:2000 of liposome-bound RI-OR2-TAT to Aβ. PINPs also bound to Aβ with high affinity (Kd = 13.2 - 50 nM), rescued SHSY-5Y cells from the toxic effect of pre-aggregated Aβ, crossed an in vitro blood-brain-barrier model (hCMEC/D3 cell monolayer), entered the brains of C57/BL6 mice, and protected against memory loss in APPSWE transgenic mice in a novel object recognition test. As the most potent aggregation inhibitor that we have tested so far, we propose to develop PINPs as a potential disease-modifying treatment for AD

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Evidence for Sub-Haplogroup H5 of Mitochondrial DNA as a Risk Factor for Late Onset Alzheimer's Disease

BACKGROUND: Alzheimer's Disease (AD) is the most common neurodegenerative disease and the leading cause of dementia among senile subjects. It has been proposed that AD can be caused by defects in mitochondrial oxidative phosphorylation. Given the fundamental contribution of the mitochondrial genome (mtDNA) for the respiratory chain, there have been a number of studies investigating the association between mtDNA inherited variants and multifactorial diseases, however no general consensus has been reached yet on the correlation between mtDNA haplogroups and AD. METHODOLOGY/PRINCIPAL FINDINGS: We applied for the first time a high resolution analysis (sequencing of displacement loop and restriction analysis of specific markers in the coding region of mtDNA) to investigate the possible association between mtDNA-inherited sequence variation and AD in 936 AD patients and 776 cognitively assessed normal controls from central and northern Italy. Among over 40 mtDNA sub-haplogroups analysed, we found that sub-haplogroup H5 is a risk factor for AD (OR=1.85, 95% CI:1.04-3.23) in particular for females (OR=2.19, 95% CI:1.06-4.51) and independently from the APOE genotype. Multivariate logistic regression revealed an interaction between H5 and age. When the whole sample is considered, the H5a subgroup of molecules, harboring the 4336 transition in the tRNAGln gene, already associated to AD in early studies, was about threefold more represented in AD patients than in controls (2.0% vs 0.8%; p=0.031), and it might account for the increased frequency of H5 in AD patients (4.2% vs 2.3%). The complete re-sequencing of the 56 mtDNAs belonging to H5 revealed that AD patients showed a trend towards a higher number (p=0.052) of sporadic mutations in tRNA and rRNA genes when compared with controls. CONCLUSIONS: Our results indicate that high resolution analysis of inherited mtDNA sequence variation can help in identifying both ancient polymorphisms defining sub-haplogroups and the accumulation of sporadic mutations associated with complex traits such as AD

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Effect of DYRK1A dose reduction on the transcriptome of the developing mouse cerebral cortex : implications in gliogenesis

Cerebral cortex is essential to exert the highest functions in mammals. Understanding the developmental processes that underlie the generation and functionality of cortical cell populations represents a mayor issue in neurobiology. DYRK1A is a dosage-sensitive gene involved in neurodevelopment with putative roles in corticogenesis. In the present study, we show that the transcriptome of the cerebral cortex of newborn mice lacking one functional copy of Dyrk1a (Dyrk1a+/-) is substantially altered and is mostly the consequence of a delayed developmental gene expression program. We also show that neural progenitors of Dyrk1a+/- mice have a reduced capability to self-renew and to differentiate into oligodendroglial cells in vitro. Moreover, we demonstrate that the epigenetic state of S100b and Gfap glial genes in the cortex of Dyrk1a+/- embryos is altered at specific promoter positions before the onset of gliogenesis, suggesting that Dyrk1a+/- neural progenitors may have an increased astrogliogenic and a decreased oligodendrogenic potential in vivo. In accordance, the number of S100b+ oligodendrocytes is reduced in the postnatal cortex of Dyrk1a+/- mutants whereas the number of Gfap+ astrocytes is increased in the adult. Finally, we show that the myelin thickness of Corpus Callosum axons and of axons of the optic and sciatic nerves is significantly decreased in adult Dyrk1a+/- mice, indicating a possible role of Dyrk1a in myelination. Altogether our results indicate that Dyrk1a dose reduction alters the differentiation potential of the embryonic cortical progenitors and suggest a new role of Dyrk1a in glial development and function.L’escorça cerebral és essencial per dur a terme les funcions més complexes en els mamífers. Entendre el procés de desenvolupament involucrat en la generació i el funcionament de les poblacions cel·lulars de l’escorça representa un dels principals camps d’investigació de la neurobiologia. DYRK1A és un gen sensible a dosis involucrat en el neurodesenvolupament i molt possiblement en la corticogènesis. En aquest estudi demostrem que la reducció de la dosi gènica de Dyrk1a en ratolí (Dyrk1a+/-) provoca una alteració substancial del transcriptoma de l’escorça cerebral neonatal que es principalment la conseqüencia de un retard en el l’expresió seqüencial dels gens durant el desenvolupament. També hem demostrat que els progenitors neuronals dels ratolins Dyrk1a+/- tenen una menor capacitat d’autorenovació i diferenciació en cèl·lules oligodendroglials in vitro. El estat epigenetic dels gens glials S100b i Gfap es troba alterat en l’escorça d’embrions a posicions especifiques del promotor abans de l’inici de la gliogènesis, suggerint que els progenitors neuronals de ratolins Dyrk1a+/- podrien tenir un potencial astrogliogènic incrementat i un potencial oligodendrogènic disminuït in vivo. En concordança, l’escorça de ratolins Dyrk1a+/- neonatals presenta un major número de progenitors oligodendroglials S100b+, mentres que el número d’astròcits Gfap+ es troba incrementat en ratolins Dyrk1a+/- adults. Finalment, hem demostrat que la vaina de mielina dels axons del cos callos i del nervi òptic i ciàtic es troba significativament reduïda en els ratolins Dyrk1a+/- adults, fet que indica una posible implicació de Dyrk1a en mielinització. En conjunt els nostres resultats indiquen que la baixada de dosi de Dyrk1a altera el potencial de diferenciació dels progenitors embrionaris de l'escorça i suggereix un nou paper de Dyrk1a en el desenvolupament i en la funcionalitat glial

Effect of Dyrk1a dose reduction on the transcriptome of the developing mouse cerebral cortex: implications in gliogenesis

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