Comparative analysis of diagnostic techniques for melanoma detection: a systematic review of diagnostic test accuracy studies and meta-analysis

Melanoma has the highest mortality rate among skin cancers, and early-diagnosis is essential to maximize survival rate. The current procedure for melanoma diagnosis is based on dermoscopy, i.e., a qualitative visual inspection of lesions with intrinsic limited diagnostic reliability and reproducibility. Other non-invasive diagnostic techniques may represent valuable solutions to retrieve additional objective information of a lesion. This review aims to compare the diagnostic performance of non-invasive techniques, alternative to dermoscopy, for melanoma detection in clinical settings. A systematic review of the available literature was performed using PubMed, Scopus and Google scholar databases (2010-September 2020). All human, in-vivo, non-invasive studies using techniques, alternative to dermoscopy, for melanoma diagnosis were included with no restriction on the recruited population. The reference standard was histology but dermoscopy was accepted only in case of benign lesions. Attributes of the analyzed studies were compared, and the quality was evaluated using CASP Checklist. For studies in which the investigated technique was implemented as a diagnostic tool (DTA studies), the QUADAS-2 tool was applied. For DTA studies that implemented a melanoma vs. other skin lesions classification task, a meta-analysis was performed reporting the SROC curves. Sixty-two references were included in the review, of which thirty-eight were analyzed using QUADAS-2. Study designs were: clinical trials (13), retrospective studies (10), prospective studies (8), pilot studies (10), multitiered study (1); the remain studies were proof of concept or had undefined study type. Studies were divided in categories based on the physical principle employed by each diagnostic technique. Twenty-nine out of thirty-eight DTA studies were included in the meta-analysis. Heterogeneity of studies' types, testing strategy, and diagnostic task limited the systematic comparison of the techniques. Based on the SROC curves, spectroscopy achieved the best performance in terms of sensitivity (93%, 95% CI 92.8-93.2%) and specificity (85.2%, 95%CI 84.9-85.5%), even though there was high concern regarding robustness of metrics. Reflectance-confocal-microscopy, instead, demonstrated higher robustness and a good diagnostic performance (sensitivity 88.2%, 80.3-93.1%; specificity 65.2%, 55-74.2%). Best practice recommendations were proposed to reduce bias in future DTA studies. Particular attention should be dedicated to widen the use of alternative techniques to conventional dermoscopy

Efficient embedded sleep wake classification for open-source actigraphy

This study presents a thorough analysis of sleep/wake detection algorithms for efficient on-device sleep tracking using wearable accelerometric devices. It develops a novel end-to-end algorithm using convolutional neural network applied to raw accelerometric signals recorded by an open-source wrist-worn actigraph. The aim of the study is to develop an automatic classifier that: (1) is highly generalizable to heterogenous subjects, (2) would not require manual features’ extraction, (3) is computationally lightweight, embeddable on a sleep tracking device, and (4) is suitable for a wide assortment of actigraphs. Hereby, authors analyze sleep parameters, such as total sleep time, waking after sleep onset and sleep efficiency, by comparing the outcomes of the proposed algorithm to the gold standard polysomnographic concurrent recordings. The relatively substantial agreement (Cohen’s kappa coefficient, median, equal to 0.78 ± 0.07) and the low-computational cost (2727 floating-point operations) make this solution suitable for an on-board sleep-detection approach

A framework for the evaluation of human machine interfaces of robot-assisted colonoscopy

The Human Machine Interface (HMI) of intraluminal robots has a crucial impact on the clinician's performance. It increases or decreases the difficulty of the tasks, and is connected to the users' physical and mental stress. Objective: This article presents a framework to compare and evaluate different HMIs for robotic colonoscopy, with the objective of identifying the optimal HMI that minimises the clinician's effort and maximises the clinical outcomes. Methods: The framework comprises a 1) a virtual simulator (clinically validated), 2) wearable sensors measuring the cognitive load, 3) a data collection unit of metrics correlated to the clinical performance, and 4) questionnaires exploring the users' impressions and perceived stress. The framework was tested with 42 clinicians investigating the optimal device for tele-operated control of robotic colonoscopes. Two control devices were selected and compared: a haptic serial-kinematic device and a standard videogame joypad. Results: The haptic device was preferred by the endoscopists, but the joypad enabled better clinical performance and reduced cognitive and physical load. Conclusion: The framework can be used to evaluate different aspects of a HMI, both hardware and software, and determine the optimal HMI that can reduce the burden on clinicians while improving the clinical outcome. Significance: The findings of this study, and of future studies performed with this framework, can inform the design and development of HMIs for intraluminal robots, leading to improved clinical performance, reduced physical and mental stress for clinicians, and ultimately better patient outcomes.Peer ReviewedPostprint (published version

Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Introduction Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked.This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register.MethodsThe Register collects, through a standardized Web-based Application, unique patients.Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated.ResultsThe Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients.The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were >= 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2).Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months.ConclusionsData from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Analisi accelerometrica della motilita del polso per la determinazione automatica degli stati di vigilanza

Introduzione: Recentemente lo studio del ruolo del sonno nella modulazione delle prestazioni motorie e sportive ha acquisito un sempre maggiore interesse. Numerose evidenze sperimentali hanno chiarito come gli atleti dormano in media di meno (6,5–6,7 h per notte) e abbiano una qualità di sonno significativamente ridotta, rispetto alla popolazione generale [1]–[5]. Esistono inoltre prove sperimentali dell’effetto negativo di vari fattori sul sonno dell’soggetto atleta, come l’organizzazione delle sedute di allenamento, i viaggi dovuti alle competizioni, il jet lag e l’ansia pre-gara [1], [5], [6]. Il complesso quadro disegnato dalle relazioni che intercorrono fra questi fattori e gli andamenti circadiani della prestazione hanno come risultato condizioni di restrizione o privazione di sonno che possono alterare i livelli di performance motoria. In un lavoro ormai classico è stato dimostrato come livelli relativamente moderati di privazione di sonno (17-19 h di veglia consecutive) riducano le prestazioni sportive a livelli paragonabili all’assunzione di moderate quantità di alcol (tasso alcolemico 0,05%) [7]. Ad oggi il gold-standard per lo studio del sonno è la polisonnografia (PSG), ovvero lo studio delle onde elettroencefalografiche durante stati prolungati di sonno e veglia, nonostante alcune limitazioni: essa infatti richiede attrezzature complesse, è costosa e relativamente invasiva. Viste queste caratteristiche, la PSG non si presta ad essere utilizzata per il monitoraggio longitudinale del sonno e in ambiti naturalistici come l’attività fisica. Al contrario l’actigrafia, una tecnica di misura e registrazione dell’attività motoria, fa uso di strumentazioni compatte e non invasive che possono raccogliere dati per periodi protratti di tempo. Oltre a questi vantaggi questa tecnica ha potuto beneficiare della generalizzata diminuzione del costo dei componenti elettronici (accelerometri in particolare) utilizzati in ogni actigrafo, con conseguente riduzione delle spese di utilizzo. L’obiettivo di questa tesi è stato quello di sviluppare un algoritmo basato su reti neurali artificiali, che sia in grado di analizzare automaticamente dati actigrafici ad alta risoluzione, con lo scopo di determinare in modo accurato i principali parametri di qualità e quantità del sonno. Il raggiungimento di questo obiettivo consente di ampliare e facilitare lo studio del sonno anche in ambiti non usuali o non adatti all’impiego della PSG. Il sistema da noi proposto è stato progettato per essere flessibile e modulare, caratteristiche che lo rendono adatto ad essere applicato in varie situazioni; è possibile, infatti, adattare l’algoritmo in modo da poter classificare vari parametri e analizzare altri stati, oltre al sonno, essendo sufficiente che l’attività motoria dell’individuo analizzato contenga le informazioni adeguate. Materiali e Metodi: in 30 soggetti sani (35,1±16,8 anni, 9 femmine) è stata registrata: 1) l’attività motoria del polso tramite un actigrafo ad alta risoluzione dotato di un accelerometro triassiale 2) l’attività poligrafica portatile (elettrica cerebrale, elettromiografica ed elettroculografica) per la determinazione degli stati di vigilanza. L’actigrafo utilizzato in questo studio è denominato Axivity AX3. Si tratta di un dispositivo open-source ad alte prestazioni. La frequenza di campionamento per AX3 è stata impostata a 100Hz, il fondoscala dell’accelerometro è stato settato a ±8g, e tutti i dati acquisiti sono stati codificati con risoluzione di 10bit. La PSG è stata eseguita secondo gli standard AASM [8]. Lo scoring del segnale EEG è stato effettuato a mano su epoche di 30s da un tecnico specializzato. L’intero pre-processing dei dati, così come la rete neurale artificiale sono stati sviluppati in ambiente MATLAB. Risultati: L’algoritmo di analisi proposto in questo studio ha raggiunto elevati livelli di concordanza (88,3±6,5%), specificità (87,3±8,6%) e sensibilità (88,9±7,4%) rispetto allo scoring sonno/veglia ottenuto tramite il gold-standard PSG, per epoche di una risoluzione di 60 secondi. La stima dei parametri di: quantità del sonno (TST, total sleep time) e qualità del sonno (SE%, efficienza del sonno e WASO, Waking After Sleep Onset) da parte dell’algoritmo di analisi automatica si è rivelata analoga rispetto alla PSG (differenza non significativa in test dei ranghi con segno di Wilcoxon). Attraverso il metodo di Bland-Altman sono stati calcolati i bias associati alle metriche TST, SE% e WASO, risultati rispettivamente: 3,8±32,7 minuti, -0,3±4,8% e 1,8±22,6 minuti. Conclusioni: Il metodo di analisi actigrafica proposto in questo studio ha raggiunto una elevata concordanza, specificità e sensibilità rispetto alla PSG nella determinazione dei principali parametri quantitativi e qualitativi del sonno. La registrazione longitudinale dell’attività motoria tramite actigrafia ad alta risoluzione rappresenta quindi una tecnica affidabile, utilizzabile per lo studio non invasivo del sonno. Questo metodo di indagine si rende particolarmente utile nei casi in cui non è possibile utilizzare la PSG, come negli studi protratti in ambito sportivo o nel contesto di studi in ambiente naturalistico. Referenze: [1] C. D. Mah, K. E. Mah, E. J. Kezirian, and W. C. Dement, “The effects of sleep extension on the athletic performance of collegiate basketball players.,” Sleep, vol. 34, no. 7, pp. 943–950, 2011. [2] I. Fietze, J. Strauch, M. Holzhausen, M. Glos, C. Theobald, H. Lehnkering, and T. Penzel, “Sleep Quality in Professional Ballet Dancers,” Chronobiol. Int., vol. 26, no. 6, pp. 1249–1262, 2009. [3] C. Hausswirth, J. Louis, A. Aubry, G. Bonnet, R. Duffield, and Y. Le Meur, “Evidence of disturbed sleep and increased illness in overreached endurance athletes,” Med. Sci. Sports Exerc., vol. 46, no. 5, pp. 1036–1045, 2014. [4] J. Leeder, M. Glaister, K. Pizzoferro, J. Dawson, and C. Pedlar, “Sleep duration and quality in elite athletes measured using wristwatch actigraphy,” J. Sports Sci., vol. 30, no. March 2014, pp. 541–545, 2012. [5] C. Sargent, M. Lastella, S. L. Halson, and G. D. Roach, “The impact of training schedules on the sleep and fatigue of elite athletes.,” Chronobiol. Int., vol. 31, no. 10, pp. 1160–8, 2014. [6] L. E. Juliff, S. L. Halson, and J. J. Peiffer, “Understanding sleep disturbance in athletes prior to important competitions,” J. Sci. Med. Sport, vol. 18, no. 1, pp. 13–18, 2015. [7] a M. Williamson and a M. Feyer, “Moderate sleep deprivation produces impairments in cognitive and motor performance equivalent to legally prescribed levels of alcohol intoxication.,” Occup. Environ. Med., vol. 57, no. 10, pp. 649–655, 2000. [8] C. Iber, “AASM - Manual for the Scoring ofSleep and Associted Events,” 2007. [Online]. Available: http://www.nswo.nl/userfiles/files/AASM - Manual for the Scoring ofSleep and Associted Events - 05-2007_2.pdf

Optimization of Experimental Infection of the Animal Model Galleria mellonella Linnaeus 1758 (Lepidoptera: Pyralidae) with the Gram-Positive Bacterium Micrococcus luteus

The aim of this work was to develop an experimental protocol for the infection of Galleria mellonella with Gram-positive bacteria. Some physiological characteristics of these insects are comparable to those of vertebrates, therefore allowing the replacement of mammals in the preclinical phases of drug development. G. mellonella Linnaeus 1758 (Lepidoptera: Pyralidae) is accepted as an alternative model for the study of infectious diseases. Since data on infection procedures with different bacterial strains are scarce and sometimes conflicting, also due to different and non-uniform protocols, we developed an experimental protocol that would allow for controlled and repeatable infections, using the Gram-positive bacterium GRAS (Generally Regarded As Safe) Micrococcus luteus. After analyzing the morphology and defining the growth rate of M. luteus, doses of between 101 and 106 CFU/larvae were administered to late-stage larvae. The survival rate of the larvae was monitored up to 7 days and the LD50 determined. The bacterial clearance capacity of the larvae after injection with 103 and 105 CFU/larvae was assessed by hemolymph bacterial load analysis. The results made it possible to define the growth curve of M. luteus correlated with the CFU count; based on the LD50 (103.8 CFU/larvae) calculated on the survival of G. mellonella, infections were carried out to evaluate the immune efficiency of the larvae in bacterial clearance. This protocol, standardized on G. mellonella larvae, could provide a functional tool to study the course of bacterial infections

35. Healthcare (Data Science in)

This Encyclopedia brings together jurists, computer scientists, and data analysts to map the emerging field of data science and law for the first time, uncovering the challenges, opportunities, and fault lines that arise as these groups are increasingly thrown together by expanding attempts to regulate and adapt to a data-driven world. It explains the concepts and tools at the crossroads of the many disciplines involved in data science and law, bridging scientific and applied domains. Entries span algorithmic fairness, consent, data protection, ethics, healthcare, machine learning, patents, surveillance, transparency and vulnerability.Peer ReviewedPreprin