The influence of bias in randomized controlled trials on rehabilitation intervention effect estimates: what we have learned from meta-epidemiological studies

This study aimed to synthesize evidence from studies that addressed the influence of bias domains in randomized controlled trials on rehabilitation intervention effect estimates and discuss how these findings can maximize the trustworthiness of an RCT in rehabilitation. We screened studies about the influence of bias on rehabilitation intervention effect estimates published until June 2023. The characteristics and results of the included studies were categorized based on methodological characteristics and summarized narratively. We included seven studies with data on 227,806 RCT participants. Our findings showed that rehabilitation intervention effect estimates are likely exaggerated in trials with inadequate/unclear sequence generation and allocation concealment when using continuous outcomes. The influence of blinding was inconsistent and different from the rest of medical science, as meta-epidemiological studies showed overestimation, underestimation, or neutral associations for different types of blinding on rehabilitation treatment effect estimates. Still, it showed a more consistent pattern when looking at patient-reported outcomes. The impact of attrition bias and intention to treat has been analyzed only in two studies with inconsistent results. The risk of reporting bias seems to be associated with overestimation of treatment effects. Bias domains can influence rehabilitation treatment effects in different directions. The evidence is mixed and inconclusive due to the poor methodological quality of RCTs and the limited number and quality of studies looking at the influence of bias and treatment effects in rehabilitation. Further studies about the influence of bias in RCTs on rehabilitation intervention effect estimates are needed

In vitro and in vivo efficacy, toxicity, bio-distribution and resistance selection of a novel antibacterial drug candidate

A synthetic antimicrobial peptide was identified as a possible candidate for the development of a new antibacterial drug. The peptide, SET-M33L, showed a MIC90 below 1.5 μM and 3 μM for Pseudomonas aeruginosa and Klebsiella pneumoniae, respectively. In in vivo models of P. aeruginosa infections, the peptide and its pegylated form (SET-M33L-PEG) enabled a survival percentage of 60-80% in sepsis and lung infections when injected twice i.v. at 5 mg/Kg, and completely healed skin infections when administered topically. Plasma clearance showed different kinetics for SET-M33L and SET-M33L-PEG, the latter having greater persistence two hours after injection. Bio-distribution in organs did not show significant differences in uptake of the two peptides. Unlike colistin, SET-M33L did not select resistant mutants in bacterial cultures and also proved non genotoxic and to have much lower in vivo toxicity than antimicrobial peptides already used in clinical practice. The characterizations reported here are part of a preclinical development plan that should bring the molecule to clinical trial in the next few years

Diagnosis of Imported Dengue and Zika Virus Infections in Italy from November 2015 to November 2022: Laboratory Surveillance Data from a National Reference Laboratory

Dengue (DENV) and Zika (ZIKV) viruses are mosquito-borne human pathogens. In Italy, the presence of the competent vector Aedes albopictus increases the risk of autochthonous transmission, and a national plan for arboviruses prevention, surveillance, and response (PNA 2020–2025) is in place. The results of laboratory diagnosis of both viruses by the National Reference Laboratory for arboviruses (NRLA) from November 2015 to November 2022 are presented. Samples from 655 suspected cases were tested by both molecular and serological assays. Virus and antibody kinetics, cross-reactivity, and diagnostic performance of IgM ELISA systems were analysed. Of 524 cases tested for DENV, 146 were classified as confirmed, 7 as probable, while 371 were excluded. Of 619 cases tested for ZIKV, 44 were classified as confirmed, while 492 were excluded. All cases were imported. Overall, 75.3% (110/146) of DENV and 50% (22/44) of ZIKV cases were confirmed through direct virus detection methods. High percentages of cross reactivity were observed between the two viruses. The median lag time from symptoms onset to sample collection was 7 days for both DENV molecular (range 0–20) and NS1 ELISA (range 0–48) tests, with high percentages of positivity also after 7 days (39% and 67%, respectively). For ZIKV, the median lag time was 5 days (range 0–22), with 16% positivity after 7 days. Diagnostic performance was assessed with negative predictive values ranging from 92% to 95% for the anti-DENV systems, and of 97% for the ZIKV one. Lower positive predictive values were seen in the tested population (DENV: 55% to 91%, ZIKV: 50%). DENV and ZIKV diagnosis by molecular test is the gold standard, but sample collection time is a limitation. Serological tests, including Plaque Reduction Neutralization Test, are thus necessary. Co-circulation and cross-reactivity between the two viruses increase diagnostic difficulty. Continuous evaluation of diagnostic strategies is essential to improve laboratory testing

Progetto S.In.A.T.Ra - S.orveglianza In.quinamento Atmosferico Territorio di Ra.venna

Un’area urbana rappresenta un ambiente particolarmente delicato per la presenza di elevate concentrazioni di attività antropiche inquinanti e per la contemporanea significativa densità di popolazione residente. Le criticità legate all’inquinamento atmosferico per l’intero bacino padano e, di conseguenza, anche per la città di Ravenna sono dovute alle concentrazioni di NO2 e di particolato PM10, come dimostrano i risultati del monitoraggio della qualità dell'aria e come ripreso da documenti istituzionali (es. PAIR2020). In questo contesto, è stato avviato il progetto Sinatra con l’obiettivo generale di valutare gli effetti sulla salute della popolazione derivanti dall'esposizione agli inquinanti atmosferici emessi dal traffico autoveicolare, dal riscaldamento domestico, dalle industrie e dal porto nonché quello di fornire metodologie e strumenti operativi per l'eventuale implementazione di un sistema di sorveglianza in materia di inquinamento e salute. Lo studio è focalizzato su un dominio definito dell'area urbana del Comune di Ravenna considerando la popolazione ivi residente. Il progetto prevede una “ricostruzione storica” degli impatti, in termini emissivi ed immissivi, prodotti dalle principali sorgenti di inquinamento che insistono sull’area studio: traffico veicolare, riscaldamento domestico, industria, porto. Verranno inoltre valutati gli effetti dell'esposizione agli inquinanti indagati sullo stato della salute della popolazione residente attraverso uno studio di coorte storica. Il presente contributo intende fornire una descrizione delle attività condotte nell’ambito della “ricostruzione storica” degli impatti. In particolare, attraverso la valutazione storica delle sorgenti emissive presenti e dei relativi contributi emissivi, sono state elaborate e ricostruite le concentrazioni medie mensili ed annuali degli inquinanti considerati per il periodo 2004-2013 attraverso la simulazione della dispersione degli inquinanti mediante l’impiego del modello ADMS-Urban. Questa attività ha permesso di valutare la diversa distribuzione sul territorio degli inquinanti atmosferici per effetto della diversificazione delle sorgenti presenti, del relativo contributo emissivo e delle caratteristiche meteorologiche. Tali risultati costituiscono una delle informazioni necessarie alla successiva valutazione dell’esposizione della popolazione residente

CALPUFF e ADMS-URBAN: due modelli a confronto per la trattazione di sorgenti puntuali

L’affidabilità dei modelli di dispersione degli inquinanti in atmosfera è un elemento fondamentale nella scelta degli strumenti da utilizzare per le valutazioni ambientali. L’obiettivo del presente studio è quello di confrontare i risultati di due modelli numerici (CALPUFF e ADMS-URBAN) applicati nell’area urbana di Ravenna. Gli inquinanti considerati sono il PM 10 e gli NO 2 . I risultati mostrano che CALPUFF simula valori di concentrazione superiori rispetto ad ADMS-URBAN, in particolare in prossimità delle sorgenti emissive ed in condizioni di calma di vento. I risultati sono stati validati mediante analisi statistica (media aritmetica, Bias, FB, COR, FA2, NMSE, IOA) e diagnostica. Le analisi suggeriscono che la diversa risposta dei due modelli sia principalmente influenzata dalla diversa influenza che la velocità del vento ha nella trattazione matematica del modello

Spatial surrogates for the disaggregation of emission inventories inside the urban area

Air pollution resulting from sources located inside and nearby the urban context represents a significant problem in urban areas. Emission inventories offer comprehensive information on emission sources and fluxes and they are important tools to manage air quality. The main purpose of inventories is to provide an estimate of the pressure exerted on an area; clearly data accuracy is strongly related to their spatial resolution. This work describes a top-down approach to disaggregate a municipal emission inventory from an higher scale down to a lower one (100x100 m cells). The proposed methodology aims to develop a tool able to detail information on pressures impacting on a high density population area. The case study is the urban area of Ravenna (North-Eastern Italy). The methodology focuses on the main urban emission sources in the air: domestic heating and vehicular traffic. In order to develop a methodology applicable also with low information availability, different surrogate variables allowing the disaggregation were identified starting from the easiness of data retrieval. The selected variables are: resident population and volume of buildings (for domestic heating), type and length of roads (for vehicular traffic). The methodology is based on the following assumptions: 1) strong correlation between the emission of a given activity and the surrogate variable; 2) the correlation does not lose its significance down-sizing from higher to lower scale. The results obtained using the surrogate variables have been verified by the ones obtained by using the following data: fuel consumption for each household and emission flows for each road. The comparison has confirmed that the selected surrogate variables allow to obtain satisfactory results, in particular for domestic heating. The traffic has more uncertainty situations, particularly for the shorter secondary roads. The results of this work will then be use to evaluate the urban area air quality

Studio di una metodologia per l’individuazione spazio/temporale del monitoraggio di fonti emissive

La qualità dell'aria e gli effetti causati dall'esposizione di recettori sensibili agli inquinanti atmosferici rappresentano un problema di fondamentale rilievo. In particolare, risulta di interesse comune il tema del controllo e del monitoraggio delle emissioni in atmosfera, soprattutto delle sorgenti presenti in aree urbane ed industriali, spesso in stretta connessione tra loro. L'obiettivo del presente studio consiste nello sviluppo di una metodologia innovativa rivolta alla progettazione delle campagne di monitoraggio della qualità dell'aria attraverso l'impiego di mezzi mobili. L'approccio proposto integra l'utilizzo di variabili proxy per la disaggregazione a livello locale degli inventari di emissione, i risultati di modelli matematici di dispersione degli inquinanti in atmosfera, l'impiego di funzioni di danno specifiche per i diversi recettori sensibili all'esposizione alle sostanze inquinanti ed algoritmi di allocazione per la scelta dei punti di monitoraggio

Development and evaluation of emission disaggregation models for the spatial distribution of non-industrial combustion atmospheric pollutants

The aim of the present work is to define top-down approaches to allocate atmospheric emissions from non-industrial combustion plants (residential, institutional and commercial sectors) to a detailed grid system of 100 7 100 m2. The conceptual model adopted permits the use of suitable proxy variables for the scaling down of atmospheric emissions from a provincial to a local scale. \u2018Resident population\u2019, \u2018building volume\u2019 and a statistical combination of both have been used as proxy variables for realizing three emission disaggregation models. The choice of the proxy variables was influenced by both data availability and relevance. The results of the emission disaggregation models have been compared with emission values resulting from a bottom-up approach starting from local data. The selected case study was located in the Emilia-Romagna Region (NE Italy), and NOx was the reference pollutant