The Smart Aging Platform for Assessing Early Phases of Cognitive Impairment in Patients With Neurodegenerative Diseases.

Background: Smart Aging is a serious game (SG) platform that generates a 3D virtual reality environment in which users perform a set of screening tasks designed to allow evaluation of global cognition. Each task replicates activities of daily living performed in a familiar environment. The main goal of the present study was to ascertain whether Smart Aging could differentiate between different types and levels of cognitive impairment in patients with neurodegenerative disease. Methods: Ninety-one subjects (mean age = 70.29 ± 7.70 years)-healthy older adults (HCs, n = 23), patients with single-domain amnesic mild cognitive impairment (aMCI, n = 23), patients with single-domain executive Parkinson's disease MCI (PD-MCI, n = 20), and patients with mild Alzheimer's disease (mild AD, n = 25)-were enrolled in the study. All participants underwent cognitive evaluations performed using both traditional neuropsychological assessment tools, including the Mini-Mental State Examination (MMSE), Montreal Overall Cognitive Assessment (MoCA), and the Smart Aging platform. We analyzed global scores on Smart Aging indices (i.e., accuracy, time, distance) as well as the Smart Aging total score, looking for differences between the four groups. Results: The findings revealed significant between-group differences in all the Smart Aging indices: accuracy (p < 0.001), time (p < 0.001), distance (p < 0.001), and total Smart Aging score (p < 0.001). The HCs outperformed the mild AD, aMCI, and PD-MCI patients in terms of accuracy, time, distance, and Smart Aging total score. In addition, the mild AD group was outperformed both by the HCs and by the aMCI and PD-MCI patients on accuracy and distance. No significant differences were found between aMCI and PD-MCI patients. Finally, the Smart Aging scores significantly correlated with the results of the neuropsychological assessments used. Conclusion: These findings, although preliminary due to the small sample size, suggest the validity of Smart Aging as a screening tool for the detection of cognitive impairment in patients with neurodegenerative diseases.

Smart Aging Platform for Evaluating Cognitive Functions in Aging: A Comparison with the MoCA in a Normal Population.

Background: Smart Aging is a Serious games (SGs) platform in a 3D virtual environment in which users perform a set of screening tests that address various cognitive skills. The tests are structured as 5 tasks of activities of daily life in a familiar environment. The main goal of the present study is to compare a cognitive evaluation made with Smart Aging with those of a classic standardized screening test, the Montreal Cognitive Assessment (MoCA). Methods: One thousand one-hundred thirty-one healthy adults aged between 50 and 80 (M = 64.3 ± 8.3) were enrolled in the study. They received a cognitive evaluation with the MoCA and the Smart Aging platform. Participants were grouped according to their MoCA global and specific cognitive domain (i.e., memory, executive functions, working memory, visual spatial elaboration, language, and orientation) scores and we explored differences among these groups in the Smart Aging indices. Results: One thousand eighty-six older adults (M = 64.0 ± 8.0) successfully completed the study and were stratified according to their MoCA score: Group 1 with MoCA < 27 (n = 360); Group 2 with 27 ≥ MoCA < 29 (n = 453); and Group 3 with MoCA ≥ 29 (n = 273). MoCA groups significantly differed in most of the Smart Aging indices considered, in particular as concerns accuracy (ps < 0.001) and time (ps < 0.001) for completing most of the platform tasks. Group 1 was outperformed by the other two Groups and was slower than them in these tasks, which were those supposed to assess memory and executive functions. In addition, significant differences across groups also emerged when considering the single cognitive domains of the MoCA and the corresponding performances in each Smart Aging task. In particular, this platform seems to be a good proxy for assessing memory, executive functions, working memory, and visual spatial processes. Conclusion: These findings demonstrate the validity of Smart Aging for assessing cognitive functions in normal aging. Future studies will validate this platform also in the clinical aging populations.

Interpretation of colposcopy in population-based cervical screening services in north-eastern Italy: an online interregional agreement study.

OBJECTIVE: An innovative web-based colposcopy quality assurance programme was implemented in population-based cervical screening services in three north-eastern Italian administrative regions with different colposcopists' training background. In this study, the levels of intra- and interregional intercolposcopist diagnostic agreement were evaluated. STUDY DESIGN: Of the 158 registered colposcopists, 125 accessed the website of the programme, logged-in, viewed a posted set of 50 digital colpophotographs selected by an expert steering committee, and classified them for the colposcopic impression, the visibility of the squamocolumnar junction, and the need for biopsy. Anonymous data were downloaded and analysed using the crude, or observed, proportion of agreement and the kappa coefficient. RESULTS: There were 113 eligible colposcopists. Overall, crude agreement on the colposcopic impression, the visibility of the squamocolumnar junction, and the need for biopsy was 0.72, 0.72, and 0.87, with kappa values of 0.60, 0.36, and 0.69, respectively. The homologous kappa values were 0.61, 0.41, and 0.69 in one region, 0.57, 0.36, and 0.69 in another, and 0.66, 0.38, and 0.74 in the third. Total intra- and interregional agreement were nearly identical, with kappa values of 0.59 and 0.60 for the colposcopic impression, 0.38 and 0.35 for the visibility of the squamocolumnar junction, and 0.69 and 0.69 for the need for biopsy. The width of 95% confidence intervals around the above kappa values was ≤0.01. CONCLUSIONS: The levels of agreement varied between moderate and substantial both within and between regions. Regional differences in training background had minor effects. The interpretation of colposcopy is potentially well-reproducible.

Accuracy of Colposcopically Directed Biopsy: Results from an Online Quality Assurance Programme for Colposcopy in a Population-Based Cervical Screening Setting in Italy.

PURPOSE: To report the accuracy of colposcopically directed biopsy in an internet-based colposcopy quality assurance programme in northern Italy. METHODS: A web application was made accessible on the website of the regional Administration. Fifty-nine colposcopists out of the registered 65 logged in, viewed a posted set of 50 digital colpophotographs, classified them for colposcopic impression and need for biopsy, and indicated the most appropriate site for biopsy with a left-button mouse click on the image. RESULTS: Total biopsy failure rate, comprising both nonbiopsy and incorrect selection of biopsy site, was 0.20 in CIN1, 0.11 in CIN2, 0.09 in CIN3, and 0.02 in carcinoma. Errors in the selection of biopsy site were stable between 0.08 and 0.09 in the three grades of CIN while decreasing to 0.01 in carcinoma. In multivariate analysis, the risk of incorrect selection of biopsy site was 1.97 for CIN2, 2.52 for CIN3, and 0.29 for carcinoma versus CIN1. CONCLUSIONS: Although total biopsy failure rate decreased regularly with increasing severity of histological diagnosis, the rate of incorrect selection of biopsy site was stable up to CIN3. In multivariate analysis, CIN2 and CIN3 had an independently increased risk of incorrect selection of biopsy site.

A fully integrated wireless system for intracranial direct cortical stimulation, real-time electrocorticography data transmission, and smart cage for wireless battery recharge.

Wireless transmission of cortical signals is an essential step to improve the safety of epilepsy procedures requiring seizure focus localization and to provide chronic recording of brain activity for Brain Computer Interface (BCI) applications. Our group developed a fully implantable and externally rechargeable device, able to provide wireless electrocorticographic (ECoG) recording and cortical stimulation (CS). The first prototype of a wireless multi-channel very low power ECoG system was custom-designed to be implanted on non-human primates. The device, named ECOGIW-16E, is housed in a compact hermetically sealed Polyether ether ketone (PEEK) enclosure, allowing seamless battery recharge. ECOGIW-16E is recharged in a wireless fashion using a special cage designed to facilitate the recharge process in monkeys and developed in accordance with guidelines for accommodation of animals by Council of Europe (ETS123). The inductively recharging cage is made up of nylon and provides a thoroughly novel experimental setting on freely moving animals. The combination of wireless cable-free ECoG and external seamless battery recharge solves the problems and shortcomings caused by the presence of cables leaving the skull, providing a safer and easier way to monitor patients and to perform ECoG recording on primates. Data transmission exploits the newly available Medical Implant Communication Service band (MICS): 402-405 MHz. ECOGIW-16E was implanted over the left sensorimotor cortex of a macaca fascicularis to assess the feasibility of wireless ECoG monitoring and brain mapping through CS. With this device, we were able to record the everyday life ECoG signal from a monkey and to deliver focal brain stimulation with movement elicitation.

An online quality assurance program for colposcopy in a population-based cervical screening setting in Italy: results on colposcopic impression.

OBJECTIVE: To report the results of an Internet-based colposcopy quality assurance program from a population-based cervical screening service in a large region of northern Italy. METHODS: In 2010 to 2011, a Web application was made accessible on the Web site of the regional administration. Fifty-nine colposcopists of the registered 65 participated. They logged-in, viewed a posted set of 50 high-quality digital colpophotographs selected by an expert committee, and rated them for colposcopic impression using a 4-tier classification (Negative; abnormal, grade 1 [G1]; abnormal, grade 2 [G2]; suspected invasive cancer [Cancer]) derived from the International Federation for Cervical Pathology and Colposcopy 2002 classification. kappa (κ) coefficients for intercolposcopist agreement and colposcopist-committee agreement were calculated. RESULTS: Colposcopist-committee agreement was greater than intercolposcopist agreement (overall κ 0.69 vs 0.60, p<.001). The κ values for colposcopist-committee agreement were 0.83 on Negative, 0.53 on G1, 0.66 on G2, and 0.80 on Cancer (all p values for pairwise comparisons<.001, except for Negative vs Cancer [p=.078]). There was no systematic tendency for colposcopists to underestimate or overestimate the colposcopic findings (2-tailed sign test, p=.13). Overall colposcopist-committee agreement was greater among patients 35 years or older (p<.001) and for colposcopists with previous quality assurance experiences (p<.01). Only 0.2% of Negative impressions were formulated for a cervical intraepithelial neoplasia grade 2 or worse. As a parallel finding, the impression of Cancer predicted cervical intraepithelial neoplasia grade 2 or less in 0.5% of cases. The histologic substrates of G1 were dispersed over a large spectrum. CONCLUSIONS: The reproducibility of colposcopic impression, when classified by trained colposcopists examining high-quality images, is higher than is generally thought.

Rationale and development of an on-line quality assurance programme for colposcopy in a population-based cervical screening setting in Italy.

BACKGROUND: Colposcopy, the key step in the management of women with abnormal Pap smear results, is a visual technique prone to observer variation, which implies the need for prolonged apprenticeship, continuous training, and quality assurance (QA) measures. Colposcopy QA programmes vary in level of responsibility of organizing subjects, geographic coverage, scope, model, and type of actions. The programmes addressing the clinical standards of colposcopy (quality of examination and appropriateness of clinical decisions) are more limited in space and less sustainable over time than those focused on the provision of the service (resources, accessibility, etc.). This article reports on the protocol of a QA programme targeting the clinical quality of colposcopy in a population-based cervical screening service in an administrative region of northern Italy. METHODS/DESIGN: After a situation analysis of local colposcopy audit practices and previous QA initiatives, a permanent web-based QA programme was developed. The design places more emphasis on providing education and feedback to participants than on testing them. The technical core is a log-in web application accessible on the website of the regional Administration. The primary objectives are to provide (1) a practical opportunity for retraining of screening colposcopists, and (2) a platform for them to interact with colposcopists from other settings and regions through exchange and discussion of digital colposcopic images. The retraining function is based on repeated QA sessions in which the registered colposcopists log-in, classify a posted set of colpophotographs, and receive on line a set of personal feedback data. Each session ends with a plenary seminar featuring the presentation of overall results and an interactive review of the test set of colpophotographs. This is meant to be a forum for an open exchange of views that may lead to more knowledge and more diagnostic homogeneity. The protocol includes the criteria for selection of colpophotographs and the rationale for colposcopic gold standards. DISCUSSION: This programme is an ongoing initiative open to further developments, in particular in the area of basic training. It uses the infrastructure of the internet to give a novel solution to technical problems affecting colposcopy QA in population-based screening services.

Follow-up of screening patients conservatively treated for cervical intraepithelial neoplasia grade 2-3.

OBJECTIVES: To evaluate the frequency and correlates of non-adherence to follow-up among patients conservatively treated for CIN2-3. STUDY DESIGN: Study population comprised 1560 patients aged 25-64 years from a screening programme in northern Italy. The regional standard protocol was used as a reference. Multinomial logistic regression analysis was used to estimate the odds ratio probability of a patient being lost to follow-up (no check-ups within 27 months of treatment) or incompletely followed-up (1-3 negative check-ups) versus having 4 negative check-ups. RESULTS: Three hundred twenty-six patients (21%) were lost to follow-up, 678 (43%) were incompletely followed-up, 352 (23%) presented for 4 negative check-ups and 204 (13%) were diagnosed with persistent disease. The probability of no or incomplete follow-up was greater for patients who lived in the urban district, who were treated in private settings (versus screening centres), who exhibited a visibile squamocolumnar junction on pre-treatment colposcopy, who were treated with cold knife excision and local destructive therapy (versus loop diathermy excision), and whose surgical specimens had positive excision margins. CONCLUSIONS: Adherence to the reference protocol was poor. Factors involved in follow-up failures require greater clinical attention.

Putting E-government to work in healthcare environment: a multiregional project funded by the Italian Innovation & Technology Ministry.

In 2002, the Italian Ministry of Innovation promoted a national bid for e-government projects. Specifically it allocated a budget of 120 M euro. One of the four project approved in healthcare sector was the "Information, Care ("Assistenza" in Italian) and healthcare Education by the Web" (IAEW), with a global budget of 2580 k euro, partially financed by Ministry with a quota of 830 k euro. The project involves 12 medical structures (both national excellences centers and local regional hospitals) located in two different Region of North Italy, dealing with two different healthcare regional systems (Lombardia and Emilia-Romagna), with potentially 3 millions of users.

Factors predicting human papillomavirus clearance in cervical intraepithelial neoplasia lesions treated by conization.

OBJECTIVE: The objective was to identify the factors, if any, that may predict long-term results of CIN treatment and HPV clearance/persistence after locally excisional therapy. METHODS: A series of 252 women with CIN lesions treated by conization were subjected to sequential HPV detection by repeated PCR during the prospective posttreatment follow-up. Factors predicting viral clearance during the follow-up (10.26 months) were elaborated using univariate and multivariate statistical techniques applied on epidemiological, clinical and biological data of the lesions. RESULTS: Sensitivity of the PAP test in detecting high-grade lesions was 93.9%, and specificity 27.3%. Odds ratio for having CIN 3/Stage IA1 squamous cervical cancer in the cone with HSIL PAP test was 5.69; 77.8 and 22.2% residual disease were found among PCR-positive and -negative cases, respectively. HPV DNA was negative in 74/252 (29.8%) samples at the first PCR. Multivariate logistic regression analysis showed that HPV 16 was an independent explanatory factor for high-grade CIN (P = 0.0001). HPV clearance increased to 63.5% at completion of the follow-up, corresponding to the monthly clearance rate of 5.27%. In Kaplan-Meier analysis, the highly significant (P = 0.0001) predictors of HPV clearance/persistence were age, lesion grade in the biopsy, lesion grade in the cone, volume of the cone, length of active sexual life, and involvement of endocervical margin (P = 0.0013). In chi-square tests, high-risk HPV type (P = 0.001) was such a predictor. In multivariate (Cox) model, the significant independent predictors of HPV clearance were involved endocervical margin (P = 0.001), lesion grade in the cone (P = 0.004), high-grade lesion in the colposcopic biopsy (P = 0.023), age (P = 0.029), and HSIL in PAP smear (P = 0.029). CONCLUSIONS: These data suggest that posttreatment follow-up should include both the PAP test and HPV detection techniques for early detection of any patients at increased risk for disease recurrence and progression, because of persistent oncogenic HPV types.

Independent determinants of inaccuracy of colposcopically directed punch biopsy of the cervix.

OBJECTIVE: The goal of this study was to determine the clinical factors independently associated with inaccuracy of colposcopically directed punch biopsy in defining extent and severity of epithelial lesions of the cervix. METHODS: The study was conducted in a colposcopy clinic devoted to the management of patients with abnormal Pap smear and/or histology diagnosis of cervical intraepithelial neoplasia (CIN) on punch biopsy or endocervical curettage. Seven hundred and thirty-nine patients (median age, 33 years; range, 18-83 years) referred with a punch biopsy diagnosis of CIN2-3 and treated with electrosurgical conization were evaluated. Cone histology diagnosis was assumed to supply the correct diagnosis. Two types of deviation of biopsy diagnosis were considered: (1). unconfirmed high-grade CIN diagnosis, defined as a cone diagnosis of CIN1 and reactive/reparative changes, and (2). nondiagnosis of carcinoma, defined as a cone diagnosis of microinvasive and invasive squamous carcinoma. Multinomial logistic regression analysis was used to assess the determinants of the probability of each type of deviation. RESULTS: The probability of unconfirmed high-grade CIN diagnosis (n = 190, 25.7%) was inversely related to number of quadrants involved, severity of referral Pap smear, and grade of biopsy. The probability of nondiagnosis of carcinoma (n = 43, 5.8%) was positively related to patient age, invisibility of the squamocolumnar junction, number of quadrants involved, and cone width. Endo-ectocervical location, cone depth, and time period had no effect whatsoever. CONCLUSIONS: The study confirmed previous observations regarding the positive association of patient age and invisibility of squamocolumnar junction with the probability of nondiagnosis of carcinoma. The concomitant positive effects of number of quadrants involved and cone width were suggested to mirror the effect of circumferential development and, respectively, surface area of CIN. Severity of referral Pap smear and grade of biopsy were shown to be inversely related to the probability of a cone diagnosis of CIN1 and benign changes.

Disease persistence in patients with cervical intraepithelial neoplasia undergoing electrosurgical conization.

OBJECTIVE: Cone margin status has been reported to be the most important predictor of residual disease in patients with cervical intraepithelial neoplasia (CIN) undergoing electrosurgical excisional treatment. The primary aim of this study of patients treated with electrosurgical conization was to evaluate the association of cone margin status and other clinical and pathologic factors with the probability of residual disease. METHODS: The study population comprised 699 patients with at least one follow-up visit within 12 months of conization. Residual disease was defined as a histology diagnosis of CIN within 3 years of conization. Multivariate associations were evaluated with multiple logistic regression analysis. RESULTS: Attendance to follow-up was 97% for the second visit and 34% for the third visit. Residual disease was detected in a total of 38 patients (5.4%). The detection rate was 3.3% at the first visit, 2.1% at the second visit, and 0.4% at the third visit. An increased probability of residual disease was associated with a referral Pap smear reported as high-grade squamous intraepithelial neoplasia and carcinoma (odds ratio, 2.9; reference category, low-grade squamous intraepithelial neoplasia). A decreased probability was associated with a squamocolumnar junction entirely visible at the first follow-up visit (odds ratio, 0.2; reference category, squamocolumnar junction not visible). Patient age, time period, lesion size, lesion site, grade of CIN, cone width, cone depth, and margin status had no influence. CONCLUSIONS: The determinants of residual disease in this study differed from those generally reported so far. Factors associated with effectiveness of electrosurgical treatment of CIN need further research.

Does microcolposcopy protect patients with CIN and unsatisfactory colposcopy from the risk of incomplete excision of disease at the time of conization?

OBJECTIVE: To evaluate the effectiveness of microcolposcopy in preventing incomplete electrosurgical excision at the endocervical cone margin in patients with CIN and unsatisfactory colposcopy. MATERIALS AND METHODS: Four-hundred and twenty-one patients were studied. Complete excision of disease at the endocervical margin was evaluated using multiple logistic regression analysis. RESULTS: One-hundred and eighty-three patients underwent microcolposcopy. In 160 patients, the cone depth exceeded the endocervical extension of the squamocolumnar junction as predicted by microcolposcopy. In 23 patients, the opposite was observed. Microcolposcopy was not performed in 238 patients. For the three groups, the frequency of endocervical cone margin involvement was 22%, 22%, and 13%, respectively. Multiple logistic regression analysis showed that patients with a cone depth exceeding the endocervical margin of the squamocolumnar junction as predicted by microcolposcopy had no reduction in the risk of incomplete conization. CONCLUSION: The use of microcolposcopy awaits validation for assessment of the transformation zone to predict negative conization margins.