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Doping and compositional tuning of Cs(2)AInCl(6) (A = Ag, Na) double perovskite nanocrystals (PNCs) is considered a promising strategy toward the development of light-emitting sources for applications in solution-processed optoelectronic devices. Oleic acid and oleylamine are by far the most often used surface capping ligands for PNCs. However, the undesirable desorption of these ligands due to proton-exchange reaction during isolation and purification processing results in colloidal and structural instabilities. Thus, the improvement of colloidal and optical stability of PNCs represents one of the greatest challenges in the field. Here, we report a trioctylphosphine-mediated synthesis and purification method toward Sb-alloyed Cs2NaInCl6 PNCs with excellent stability and optical features. Nuclear magnetic resonance spectroscopy enabled one to explain the role of trioctylphosphine and to reveal the reaction mechanism during crystal nucleation and growth. Under the optimized reaction conditions, in situ-generated trioctylphosphonium chloride and benzoyl trioctylphosphonium chloride serve as highly reactive halide sources, while benzoyl trioctylphosphonium and oleylammonium cations together with the oleate anion serve as surface capping ligands, which are bound strongly to the PNC surface. The tightly bound ionic pair of oleylammonium oleate and benzoyl trioctylphosphonium chloride/oleate ligands allows one to obtain monodispersed bright-blue-emitting PNCs with high photoluminescence quantum yields exceeding 50% at an optimum Sb content (0.5%), which also exhibit long-term colloidal stability. The approach based on dual cationic ligand passivation of double PNCs opens the doors for applications in other systems with a potential to achieve higher stability along with superior optical properties. Web of Science 13 40 47859 47845

In Italy, the cohorts of women who were offered Human papillomavirus (HPV) vaccination in 2007/08 will reach the age (25years) for cervical cancer (CC) screening from 2017. The simultaneous shift from cytology-based screening to HPV test-based screening gives the opportunity for unprecedented reorganisation of CC prevention. The ONS (National Screening Monitoring Centre) Directive and the GISCi (Italian Group for Cervical Screening) identified the consensus conference as the most suitable method for addressing this topic. A summary of consensus recommendations is reported here. The main objective was to define the best screening methods in girls vaccinated against HPV and the knowledge required for defining evidence-based screening strategies. A Jury made recommendations about questions and proposals formulated by a panel of experts representative of Italian scientific societies involved in CC prevention and based on systematic reviews of literature and evidence. The Jury considered changing the screening protocols for girls vaccinated in their twelfth year as appropriate. Tailored screening protocols based on vaccination status could be replaced by "one size fits all" protocols only when a herd immunity effect has been reached. Vaccinated women should start screening at age 30, instead of 25, with HPV test. Furthermore, there is a strong rationale for applying longer intervals for re-screening HPV negative women than the currently recommended 5years, but research is needed to determine the optimal screening time points. For non-vaccinated women and for women vaccinated in their fifteenth year or later, the current protocol should be kept.

Chronicity is the real challenge for public healthcare systems especially in relation to multi-morbidity. The growing demand for multidisciplinary care could be addressed by implementing integrated programs in the primary care field and facilitating other specific care only as necessary. Some models of long-term management have been suggested since the 2000s. The objective here is to propose the Individual Profile of Pathology (IPP) model as the preliminary step for identifying groups of population which shares health and social needs and for optimizing the management of chronicity, referring to the Kaiser Permanente Pyramid paradigm. The IPP model is able to inform a data feedback system for improving performances at the patient's individual level and for addressing and evaluating health policies. The stratification of needs comes out of the IPP algorithm. It works on patient information databases based on the logic of disease as a process that evolves over time and interacts with many factors unique to that patient. Individual patients' data used in this work refers to 138,859 subjects from a large area in Italy and concerns hospitalization, outpatient drug prescriptions, access to the emergency room and outpatient prescriptions for visits, laboratory/imaging tests, and medications. The IPP model allows to identify for each subject a complexity level, taking into account the weight of groups of pathologies, both in terms of absorption of resources and the level of severity. Costs and healthcare performances have been analyzed taking into account the complexity levels. The IPP model can be an efficient methodology for (a) improving performances at the patient's individual level (b) allowing standardized comparison among different geographical areas (c) supporting large population-focused surveillance programs and (d) providing knowledge to identify and fill the gaps in public health policies. Currently, the IPP algorithm is limited by data availability, restricted to the administrative databases processing, but the theoretical model is able to include more data dimensions providing the potential to identify homogeneous groups of subjects with a higher level of precision.

Women who were previously treated for breast cancer (BC) are an important particular subgroup of women at intermediate BC risk. Their breast follow-up should be planned taking in consideration a 1.0-1.5 % annual rate of loco-regional recurrences and new ipsilateral or contralateral BCs during 15-20 years, and be based on a regional/district invitation system. This activity should be carried out by a Department of Radiology integrating screening and diagnostics in the context of a Breast Unit. We recommend the adoption of protocols dedicated to women previously treated for BC, with a clear definition of responsibilities, methods for invitation, site(s) of visits, methods for clinical and radiological evaluation, follow-up duration, role and function of family doctors and specialists. These women will be invited to get a mammogram in dedicated sessions starting from the year after the end of treatment. The planned follow-up duration will be at least 10 years and will be defined on the basis of patient's age and preferences, taking into consideration organizational matters. Special agreements can be defined in the case of women who have their follow-up planned at other qualified centers. Dedicated screening sessions should include: evaluation of familial/personal history (if previously not done) for identifying high-risk conditions which could indicate a different screening strategy; immediate evaluation of mammograms by one or, when possible, two breast radiologists with possible addition of supplemental mammographic views, digital breast tomosynthesis, clinical breast examination, breast ultrasound; and prompt planning of possible further workup. Results of these screening sessions should be set apart from those of general female population screening and presented in dedicated reports. The following research issues are suggested: further risk stratification and effectiveness of follow-up protocols differentiated also for BC pathologic subtype and molecular classification, and evaluation of different models of survivorship care, also in terms of cost-effectiveness.

Objective To assess the impact of ambient temperature on faecal immunochemical test (FIT) performance in the colorectal cancer screening programme of Emilia-Romagna (Italy). Methods A population-based retrospective cohort study on data from 2005 to 2011. Positive rate, detection rate, and positive predictive value rate for cancers and adenomas, and incidence rate of interval cancers after negative tests were analysed using Poisson regression models. In addition to ambient temperature, gender, age, screening history, and Local Health Unit were also considered. Results In 1,521,819 tests analysed, the probability of a positive result decreased linearly with increasing temperature. Point estimates and 95% Confidence Intervals were estimated for six temperature classes (Conclusions Ambient temperatures can affect screening performance. Continued monitoring is needed to verify the effect of introducing FIT tubes with a new buffer, which should guarantee a higher stability of haemoglobin.

Screening mammogram reading volume (SMRV) and total (screening and clinical) mammogram reading volume (TMRV) per year are strongly associated with the radiologist’s diagnostic performance in breast cancer screening. The current article reports the prevalence and correlates of a SMRV and a TMRV ≥5000 among Italian breast screening radiologists. A questionnaire survey was carried out in 2013–2014 by the Italian Group for Mammography Screening (GISMa). The questionnaire included items of information for radiologist’s experience-related characteristics and for facility-level factors supposedly associated with SMRV and TMRV. Multivariate analysis was performed using backward stepwise multiple logistic regression models. Data for 235 radiologists from 51 local screening programmes were received. Of the 222 radiologists who were eligible, 133 (59.9 %) reported a SMRV ≥5000 and 163 (73.4 %) a TMRV ≥5000. Multivariate factors positively associated with both characteristics included: the number of years of experience reading mammograms; the percentage of total working time dedicated to breast imaging and breast care; the participation in diagnostic assessment; and the availability of digital tomosynthesis at facility. Full-time dedication to breast imaging and breast care was associated with the highest odds ratio for a SMRV and a TMRV ≥5000, i.e. 11.80 and 46.74, respectively, versus a percentage of time ≤50 %. An early (

Objectives To assess detection rate and predictive factors of sessile serrated polyps (SSPs) in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). Design Data from a case series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected, including the age-standardised and sex-standardised adenoma detection rate (ADR) of the individual endoscopists. The SSP detection rate (SSP-DR) was assessed for the study population. To identify SSP-predictive factors, multilevel analyses were performed according to patient/centre/endoscopist characteristics. Results We analysed 72 021 colonoscopies, of which 1295 presented with at least one SSP (SSP-DR 1.8%; 95% CI 1.7% to 1.9%). At the per-patient level, SSP-DR was associated with males (OR 1.35; 95% CI 1.17 to 1.54) and caecal intubation (OR 3.75; 95% CI 2.22 to 6.34), but not with the FIT round. The presence of at least one advanced adenoma was more frequent among subjects with SSPs than those without (OR 2.08; 95% CI 1.86 to 2.33). At the per-endoscopist level, SSP-DR was associated with ADR (third vs first ADR quartile: OR 1.55; 95% CI 1.03 to 2.35; fourth vs first quartile: OR 1.89; 95% CI 1.24 to 2.90). Conclusion The low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes.

Colorectal cancer screening programmes in Italy invite 50-69-year-old residents for a faecal immunochemical test every two years, regardless of their citizenship.The 2013 National Survey on Italian colorectal cancer screening programmes compared immigrants born in low- or middle-income countries with subjects who were born in Italy, by collecting aggregated data on compliance, faecal immunochemical test results, compliance with colonoscopy, detected lesions and stage at diagnosis separately for Italians and immigrants.Overall, 85 screening programmes invited 3,292,451 subjects, of whom 192,629 had been born abroad (5.9%). Compliance with invitation was lower in immigrants (34.3% vs. 51.3% in Italians), with p0.001. Compliance was higher in females, regardless of the country of birth, in the youngest age group of immigrants but in the oldest of Italians. Immigrants showed a borderline excess of standardised faecal immunochemical test positivity rate at first screening (5.4% vs. 5.1% in Italians, p=0.05) and a significant excess at repeat screenings (4.8% vs. 4.4%, p=0.002). The detection rates for carcinoma and advanced adenomas were lower in immigrants than in Italians at first screening (respectively 1.34‰ vs. 1.62‰ and 8.41‰ vs. 9.25‰) - although the differences were not statistically significant - but not at repeat screening (respectively 1.06‰ vs. 0.98‰ and 6.90‰ vs. 6.79‰).Migrants showed a lower compliance with screening than Italians. The prevalence of neoplasia was lower at first screening and similar to the Italians' at repeat screenings.

Objectives To assess the appropriateness of recommendations for endoscopic surveillance in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). Design 74 Italian CRC screening programmes provided aggregated data on the recommendations given after FIT-positive colonoscopies in 2011 and 2013. Index colonoscopies were divided into negative/no adenoma and low- risk, intermediate-risk and high-risk adenomas. Postcolonoscopy recommendations included a return to screening (FIT after 2 years or 5 years), an endoscopic surveillance after 6 months or after 1 year, 3 years or 5 years, surgery or other. We assessed the deviation from the postcolonoscopy recommendations of the European Guidelines in 2011 and 2013 and the correlation between overuse of endoscopic surveillance in 2011 and the process indicators associated with the endoscopic workload in 2013. Results 49 704 postcolonoscopy recommendations were analysed. High-risk, intermediate-risk and low-risk adenomas, and no adenomas were reported in 5.9%, 19.3%, 15.3% and 51.5% of the cases, respectively. Endoscopic surveillance was inappropriately recommended in 67.4% and 7%, respectively, of cases with low-risk and no adenoma. Overall, 37% of all endoscopic surveillance recommendations were inappropriate (6696/17 860). Overuse of endoscopic surveillance was positively correlated with the extension of invitations (correlation coefficient (cc) 0.29; p value 0.03) and with compliance with post-FIT+ colonoscopy (cc 0.25; p value 0.05), while it was negatively correlated with total colonoscopy waiting times longer than 60 days (cc −0.26; p value 0.05). Conclusions In organised screening programmes, a high rate of inappropriate recommendations for patients with low risk or no adenomas occurs, affecting the demand for endoscopic surveillance by a third.

Most invasive cervical cancers in industrialized countries are due to the lack of Pap test coverage, very few are due to screening failures. This study aimed at quantifying the proportion of invasive cancers occurring in nonscreened or underscreened women and that in women with a previous negative screening, that is, screening failure, during the first two screening rounds (1996-2002) and in the following rounds (2003-2008) in the Emilia-Romagna region. All cases of invasive cancers registered in the regional cancer registry between 1996 and 2008 were classified according to screening history through a record linkage with the screening programme registry. The incidence significantly decreased from 11.6/100 000 to 8.7/100 000; this decrease is due to a reduction in squamous cell cancers (annual percentage change -6.2; confidence interval: -7.8, -4.6) and advanced cancers (annual percentage change -6.6; confidence interval: -8.8, -4.3), whereas adenocarcinomas and microinvasive cancers were essentially stable. The proportion of cancers among women not yet invited and among nonresponders decreased over the two periods, from 45.5 to 33.3%. In contrast, the proportion of women with a previous negative Pap test less than 5 years and 5 years or more before cancer incidence increased from 5.7 to 13.3% and from 0.3 to 5.5%, respectively. Although nonattendance of the screening programme remains the main barrier to cervical cancer control, the introduction of a more sensitive test, such as the human papillomavirus DNA test, could significantly reduce the burden of disease.

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.

Aims: The objective of the study is to determine the demographics and the in-hospital outcome of diabetic and non-diabetic patients treated with percutaneous coronary interventions (PCI) in Europe, to report the type of equipment and technology used for PCI procedures in diabetics and to clarify whether the treatment of diabetic patients complies with current European Society of Cardiology (ESC) guidelines. Methods and results: A total of 14,458 patients treated with PCI were enrolled from 29 member countries of the ESC between June 2005 and January 2006. Data were collected on patient characteristics and treatment, using new Cardiology Audit and Registration Data standards. In total, 3,603 patients (24.9%) were diabetic. Diabetics were older, more often female and had a higher body mass index than non-diabetics. Diabetics had higher rates of hypercholesterolaemia and hypertension, while current smokers were more frequent in the non-diabetics. Diabetics also had significantly higher rates of previous cardiovascular events. Clopidogrel was administered only in 48.1% of diabetic patients before PCI, while IIb/IIIa inhibitors were 22.9% during PCI. At discharge, there was a major adjustment of treatment with increases in the use of Beta-blocker (80.4%), angiotensin converting enzyme inhibitor (ACEI, 71.3%) and statins (89.8%) compared with on admission (Beta-blocker 60.9%, ACEI 55.0%, statin 63.1%). Inhospital mortality was higher in diabetics (1.8% vs 1.2%) although the in-hospital MACCE rate was not significantly different (3.6% vs 3.0%, p=0.09). Conclusions: Diabetic patients treated with PCI were older with more comorbidity. According to ESC guideline, the under-usage of clopidogrel, GP IIb/IIIa inhibitors should be improved. PCI is now taken as a good opportunity to adjust the use of appropriate medication. © Europa Edition. All rights reserved.

Background The objective of this study was to evaluate if mammography screening attendance is associated with a reduction in late-stage breast cancer incidence. Methods The cohort included over 400,000 Italian women who were first invited to participate in regional screening programmes during the 1990s and were followed for breast cancer incidence for 13 years. We obtained individual data on their exposure to screening and correlated this with total and stage-specific breast cancer incidence. Socio-economic status and pre-screening incidence data were used to assess the presence of self-selection bias. Results Overall, screening attendance was associated with a 10% excess risk of in situ and invasive breast cancer (IRR = 1.10; 95% confidence interval (CI): 1.06–1.14), which dropped to 5% for invasive cancers only (IRR = 1.05; 95% CI: 1.01–1.09). There were significant reductions among attenders for specific cancer stages; we observed a 39% reduction for T2 or larger (IRR = 0.61; 95% CI: 0.57–0.66), 19% for node positives (IRR = 0.81; 95% CI: 0.76–0.86) and 28% for stage II and higher (IRR = 0.72; 95% CI: 0.68–0.76). Our data suggest that the presence of self-selection bias is limited and, overall, invited women experienced a 17% reduction of advanced cancers compared with pre-screening rates. Conclusions Comparing attenders' and non-attenders' stage-specific breast cancer incidence, we have estimated that screening attendance is associated with a reduction of nearly 30% for stages II+.

This position paper, issued by ICBR/SIRM and GISMa, summarizes the evidence on DBT and provides recommendations for its use. In the screening setting, DBT in adjunct to digital mammography (DM) increased detection rate by 0.5-2.7‰ and decreased false positives by 0.8-3.6% compared to DM alone in observational and double-testing experimental studies. The reduction in recall rate could be less prominent in those screening programs which already have low recall rates with DM. The increase in radiation exposure associated with DM/DBT protocols has been solved by the introduction of synthetic mammograms (sDM) reconstructed from DBT datasets. Thus, whenever possible, sDM/DBT should be preferred to DM/DBT. However, before introducing DBT as a routine screening tool for average-risk women, we should wait for the results of randomized controlled trials and for a statistically significant and clinically relevant reduction in the interval cancer rate, hopefully associated with a reduction in the advanced cancer rate. Otherwise, a potential for overdiagnosis and overtreatment cannot be excluded. Studies exploring this issue are ongoing. Screening of women at intermediate risk should follow the same recommendations, with particular protocols for women with previous BC history. In high-risk women, if mammography is performed as an adjunct to MRI or in the case of MRI contraindications, sDM/DBT protocols are suggested. Evidence exists in favor of DBT usage in women with clinical symptoms/signs and asymptomatic women with screen-detected findings recalled for work-up. The possibility to perform needle biopsy or localization under DBT guidance should be offered when DBT-only findings need characterization or surgery.

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.

BACKGROUND: Maintaining continence is among the functions of the pelvic floor muscles (PFM) and their dysfunction can cause urinary incontinence (UI), which is a common occurrence during pregnancy and the puerperal period. Pelvic floor muscle training (PFMT), therefore, is important during pregnancy, although most women perform the muscle contractions unsatisfactorily. OBJECTIVES: This study is an exploratory analysis of the results of three electromyographic (EMG) activity biofeedback sessions in pregnant women. METHODS: The study sample included 19 nulliparous women with low risk pregnancies. The participants performed three sessions of EMG biofeedback consisting of slow and fast contractions. The average value of the normalized amplitudes of surface electromyography was used to evaluate the results. The linear regression model with mixed effects was used for statistical analysis, with the EMG data normalized by maximum voluntary contraction (MVC). RESULTS: A steady increase in EMG amplitude was observed during each contraction and by the end of the biofeedback sessions, although this difference was only significant when comparing the first tonic contraction of each session (p=0.03). CONCLUSIONS: The results indicate that three sessions of training with biofeedback improved PFM EMG activity during the second trimester in women with low-risk pregnancies. The effectiveness of this protocol should be further investigated in randomized controlled trials. CONTEXTUALIZAÇÃO: Dentre as funções dos músculos do assoalho pélvico (MAPs), pode-se citar a manutenção da continência, sendo que sua disfunção pode causar a incontinência urinária (IU), muito frequente no período gestacional e no puerpério. Diante disso, se faz importante o treinamento dos músculos do assoalho pélvico (TMAP) durante o período gestacional, entretanto grande parte das mulheres realiza a contração dessa musculatura de maneira insatisfatória. OBJETIVOS: Realizar uma análise exploratória dos resultados de três sessões de biofeedback na atividade eletromiográfica em mulheres gestantes. MÉTODOS: Este estudo incluiu 19 gestantes nulíparas com gravidez de baixo risco. Foram realizadas três sessões de biofeedback eletromiográfico compostas por contrações lentas e rápidas, utilizando-se como método de avaliação dos resultados as médias das amplitudes normalizadas da eletromiografia (EMG) de superfície. Para a análise estatística, utilizou-se o modelo de regressão linear com efeitos mistos, sendo que os dados da EMG foram normalizados pela contração voluntária máxima (CVM). RESULTADOS: Após as sessões de biofeedback, constatou-se um aumento crescente na amplitude eletromiográfica a cada contração realizada e a cada sessão, entretanto essa diferença só foi estatisticamente significante para a comparação entre a primeira contração tônica de cada sessão (p=0.03). CONCLUSÕES: Os resultados obtidos indicam que três sessões de treinamento com biofeedback melhoraram a atividade eletromiográfica dos MAPs em gestantes de baixo risco no segundo trimestre. A efetividade do protocolo necessita ser futuramente investigada em estudo randomizado controlado.

Background Acute myocardial infarction (AMI; ICD9-CM 410*) is a leading cause of morbidity and mortality all over the world, and its community surveillance is essential to monitor variation in the occurrence of the disease. Between the late 1990s and the early 2000s more sensitive and specific biomarkers of myocardial necrosis (ie, troponins) were introduced and new diagnostic criteria, emphasising the role of biomarkers, have been developed for clinical and epidemiological purposes. Methods Tosc-AMI is a population-based registry based on the record linkage between hospital and mortality databases; it provides trends of coronary events in Tuscany, Italy. Two random samples of patients admitted to hospital in 2003 were validated according to the American Heart Association (AHA; 2003) and the Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) (1983) criteria. Sample 1 (380 cases) was represented by patients admitted to hospital for AMI and sample 2 (380 cases) for other coronary diagnosis. Results Tosc-AMI attack rates increased from the period 1997 to 2005 (men: +17%; women: +30%) and then they decreased in the following 2 years (men: −8%; women: −13%). The rise of AMI hospital admissions was due to cases with ICD9-CM code 410.7 (largely representing non-ST elevation MI). According to the AHA criteria, 94.6% events of sample 1 and 29.8% events of sample 2 fulfilled the most extensive criteria for definite, probable or possible AMI. As expected, the more updated AHA definition identified as definite AMI an additional 33.3% when compared to the MONICA criteria (86.0% vs 52.7%). Conclusions The study suggests an influence of the new diagnostic criteria on the rising AMI trend observed in the early 2000s, an increase of less severe cases and a decreasing trend of forms with a more extended myocardial damage.

The destruction of the surfactants, sodium dodecylbenzene sulfonate (DBS) and dodecyl pyridinium chloride (DPC), using an advanced oxidation process is described. The use of zero valent iron (ZVI) and hydrogen peroxide at pH = 2.5 (the advanced Fenton process), with and without, the application of 20 kHz ultrasound leads to extensive mineralisation of both materials as determined by total organic carbon (TOC) measurements. For DBS, merely stirring with ZVI and H2O2 at 20°C leads to a 51% decrease in TOC, but using 20 kHz ultrasound at 40°C, maintaining the pH at 2.5 throughout and adding extra amounts of ZVI and H2O2 during the degradation, then the extent of mineralisation of DBS is substantially increased to 93%. A similar result is seen for DPC where virtually no degradation occurs at 20°C, but if extra amounts of both ZVI and hydrogen peroxide are introduced during the reaction at 40°C and the pH is maintained at 2.5, then an 87% mineralisation of DPC is obtained. The slow latent remediation of both surfactants and the mechanism of degradation are also discussed.

Summary Background Human papillomavirus (HPV) testing is known to be more sensitive, but less specific than cytology for detecting cervical intraepithelial neoplasia (CIN). We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing. Methods Between March, 2004, and December, 2004, in two separate recruitment phases, women aged 25–60 years were randomly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology (first phase) or alone (second phase). Randomisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres. During phase one, women who were HPV-positive and aged 35–60 years were referred to colposcopy, whereas women aged 25–34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive. During phase two, women in the HPV group were referred for colposcopy if the HPV test was positive. Two rounds of screening occurred in each phase, and all women had cytology testing only at the second round. The primary endpoint was the detection of grade 2 and 3 CIN, and of invasive cervical cancers during the first and second screening rounds. Analysis was done by intention to screen. This trial is registered, number ISRCTN81678807. Findings In total for both phases, 47 001 women were randomly assigned to the cytology group and 47 369 to HPV testing. 33 851 women from the cytology group and 32 998 from the HPV-testing group had a second round of screening. We also retrieved the histological diagnoses from screening done elsewhere. The detection of invasive cervical cancers was similar for the two groups in the first round of screening (nine in the cytology group vs seven in the HPV group, p=0·62); no cases were detected in the HPV group during round two, compared with nine in the cytology group (p=0·004). Overall, in the two rounds of screening, 18 invasive cancers were detected in the cytology group versus seven in the HPV group (p=0·028). Among women aged 35–60 years, at round one the relative detection (HPV vs cytology) was 2·00 (95% CI 1·44–2·77) for CIN2, 2·08 (1·47–2·95) for CIN3, and 2·03 (1·60–2·57) for CIN2 and 3 together. At round two the relative detection was 0·54 (0·23–1·28) for CIN2, 0·48 (0·21–1·11) for CIN3, and 0·51 (0·28–0·93) for CIN2 and 3 together. Among women aged 25–34 years, there was significant heterogeneity between phases in the relative detection of CIN3. At round one the relative detection was 0·93 (0·52–1·64) in phase one and 3·91 (2·02–7·57) in phase two. At round two the relative detection was 1·34 (0·46–3·84) in phase one and 0·20 (0·04–0·93) in phase two. Pooling both phases, the detection ratio of CIN2 for women aged 25–34 years was 4·09 (2·24–7·48) at round one and 0·64 (0·23–1·27) at round two. Interpretation HPV-based screening is more effective than cytology in preventing invasive cervical cancer, by detecting persistent high-grade lesions earlier and providing a longer low-risk period. However, in younger women, HPV screening leads to over-diagnosis of regressive CIN2. Funding European Union, Italian Ministry of Health, Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia-Romagna, and Public Health Agency of Lazio.

The pericarp and seeds from fruits of Garcinia brasiliensis were subjected to extraction with hexane and ethanol. The pericarp hexane extract (PHE) and seed ethanol extract (SEE) were purified by silica gel column chromatography, which permitted isolation of the prenylated benzophenones 7-epiclusianone (1) and guttiferone-A (2), respectively. The antimicrobial activity of PHE, SEE, and compounds 1 and 2 were evaluated against Candida albicans, Staphylococcus aureus, Escherichia coli, and Bacillus cereus cultures. The minimum inhibitory concentration and minimum bactericidal concentration were established. The substances presented activity against S. aureus and B. cereus as follows: PHE, 4.0 microg/mL and 2.4 microg/mL; SEE, 10.0 microg/mL and 12.6 microg/mL; 7-epiclusianone, 1.2 microg/mL and 0.6 microg/mL; and guttiferone-A, 2.4 microg/mL and 2.4 microg/mL, respectively. The direct relationship between the lipophilic character of the structure and activity in Gram-positive bacteria was specifically observed. Therefore these extracts and prenylated benzophenones represent an interesting topic for further studies and open possibilities for an alternative control of diseases associated with Gram-positive bacteria.

• Growing difficulties in calculating the proportional incidence of interval breast cancers are emerging in screening programmes.

BRCA1/2 mutation status is of paramount importance to identify families at risk of Hereditary Breast and Ovarian Cancer (HBOC). Most HBOC and BRCA1/2 mutation studies have focused on highly selected sub-populations, and few data are available for large population cohorts. For this reason, as part of a regional cancer prevention strategy in North-Central Italy, we set up a population-based screening programme to identify all resident HBOC families, and to determine their BRCA1/2 mutation status. To date, 44 different BRCA1/2 variants have been identified in 55 HBOC families. Of the seven newly reported mutations, only BRCA1 Q284X is clearly deleterious. The analysis of clinical disease characteristics in relation to age of disease onset and family history showed a difference between BRCA1/2 wild type and mutation carrier families. Interestingly, BRCA1/2 mutations were significantly more common in women who developed breast canceror=40 years of age than in BRCA1/2 wild type women (50% vs. 29%, respectively, P = 0.005). The family history selection criteria most likely to indicate the presence of deleterious BRCA1/2 mutations are breast canceror=35 years (P = 0.012), two first-degree relatives with breast canceror=50 years (P = 0.022), and male breast cancer (P = 0.047). The penetrance of BRCA1/2 alterations in our cohort seems to be aligned with other published results. However, new data interpretations have emerged in relation to the clinical criteria and the presence of deleterious mutations. This information shows that a correct and accurate clinical selection could avoid unnecessary molecular tests and could better address genetic analysis and clinical management.

Purpose Both health interview surveys (HISs) and health examination surveys (HESs) are used to describe the health status of populations. In Italy, to determine the feasibility of conducting a national-level HES, a pilot HES was conducted in the city of Florence among participants of a previous national-level HIS. The aim of the present analysis was to compare the results of the two surveys. Methods The study population consisted of the 343 Florence residents 35 to 74 years of age who participated in both surveys (sample drawn with probabilistic criteria). We compared the self-reported HIS data to the HES health measurements for diabetes, hypertension, osteoporosis, smoking, height, weight, and body mass index. For categorical variables, contingency tables were used, calculating symmetric and asymmetric indices. For the continuous variables, Student's t test for matched samples was used. Results The prevalence of the most important pathologic conditions and risk factors determined with HES measurements was significantly higher than that based on self-reported HIS data. Conclusions The results stress that individuals have poor knowledge of their own health; therefore health measurements need to be taken.

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.

We enrolled all 2162 in situ and 21 148 invasive cases of breast cancer in 17 areas of Italy, diagnosed in 1997–2001. Rates of early cancer increased by 13.7% in the screening age group (50–69 years), and breast conserving surgery by 24.6%. Advanced cancer rates decreased by 19.4%, and mastectomy rates by 24.2%. Service screening did not increase mastectomy rates in the study population.

Background: Human papillomavirus (HPV)–based screening needs triage. In most randomized controlled trials (RCTs) on HPV testing with cytological triage, cytology interpretation has been blind to HPV status. Methods: Women age 25 to 60 years enrolled in the New Technology in Cervical Cancer (NTCC) RCT comparing HPV testing with cytology were referred to colposcopy if HPV positive and, if no cervical intraepithelial neoplasia (CIN) was detected, followed up until HPV negativity. Cytological slides taken at the first colposcopy were retrieved and independently interpreted by an external laboratory, which was only aware of patients’ HPV positivity. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were computed for histologically proven CIN2+ with HPV status–informed cytology for women with a determination of atypical squamous cells of undetermined significance (ASCUS) or more severe. All statistical tests were two-sided. Results: Among HPV-positive women, informed cytology had cross-sectional sensitivity, specificity, PPV and 1-NPV for CIN2+ of 85.6% (95% confidence interval [CI] = 76.6 to 92.1), 65.9% (95% CI = 63.1 to 68.6), 16.2% (95% CI = 13.0 to 19.8), and 1.7 (95% CI = 0.9 to 2.8), respectively. Cytology was also associated with subsequent risk of newly diagnosed CIN2+ and CIN3+. The cross-sectional relative sensitivity for CIN2+ vs blind cytology obtained by referring to colposcopy and following up only HPV positive women who had HPV status–informed cytology greater than or equal to ASCUS was 1.58 (95% CI = 1.22 to 2.01), while the corresponding relative referral to colposcopy was 0.95 (95% CI = 0.86 to 1.04). Conclusions: Cytology informed of HPV positivity is more sensitive than blind cytology and could allow longer intervals before retesting HPV-positive, cytology-negative women.

The Tuscany Region was the first Italian Region to initiate a program for the prevention of hip fractures in over 65 year old. The T.A.R.Ge.T. project "Appropriate treatment of geriatric re-fractures in Tuscany" (Trattamento Appropriato delle Rifratture Geriatriche in Toscana), which is still on-going, includes a preliminary phase (2009-2010) for baseline analysis and education of the participating centers and a 4-year-prospective phase (2011-2014). The monitoring system is performed horizontally analyzing 5 different flows: SDO (Performance Hospitalization), SPF (Pharmaceutical Distribution Dataset), FED (Direct Distribution Dataset), SAA (Registry of Patients), SPA (Specialized Outpatient) flows. In this review will be shown some of the most important results of analyzes of the retrospective phase. Between 2006 and 2011 only 26% of hip fractured patients has being treated with anti-osteoporotic drugs. The percentage of treatment increases 10% after the second fracture. Until 2011 there wasn't in Tuscany a prevention program of bone fragility; patients were treated with specific treatment only in severe cases: this phenomenon implies that mortality and re-fracture are higher on treated patients than in patients who did not have any kind of treatment. The treated patients are the most severe and therefore they have a higher risk of death and re-fracture.

A new method for altered enamel surface remineralization has been proposed. To this aim carbonate-hydroxyapatite nanocrystals which mimic for composition, structure, nanodimensions, and morphology dentine apatite crystals and resemble closely natural apatite chemical-physical properties have been used. The results underline the differences induced by the use of fluoride ions and hydroxyapatite nanocrystals in contrasting the mechanical abrasions and acid attacks to which tooth enamel is exposed. Fluoride ions generate a surface modification of the natural enamel apatite crystals increasing their crystallinity degree and relative mechanical and acid resistance. On the other hand, the remineralization produced by carbonate-hydroxyapatite consists in a deposition of a new apatitic mineral into the eroded enamel surface scratches. A new biomimetic mineral coating, which progressively fills and shadows surface scratches, covers and safeguards the enamel structure by contrasting the acid and bacteria attacks.

To assess variation in the main colonoscopy quality indicators in organised colorectal cancer (CRC) screening programmes based on faecal immunochemical test (FIT).Data from a case-series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected. The adenoma detection rate (ADR) and caecal intubation rate (CIR) were assessed for the whole population and the individual endoscopists. To explore variation in the quality indicators, multilevel analyses were performed according to patient/centre/endoscopist characteristics.We analysed 75 569 (mean age: 61.3 years; men: 57%) colonoscopies for positive FIT performed by 479 endoscopists in 79 centres. ADR ranged from 13.5% to 75% among endoscopists (mean: 44.8%). ADR was associated with gastroenterology specialty (OR: 0.87 for others, 95% CI 0.76 to 0.96) and, at the endoscopy centre level, with the routine use of sedation (OR: 0.80 if occasional (33%); 95% CI 0.64 to 1.00) and availability of screening-dedicated sessions (OR: 1.35; 95% CI 1.11 to 1.66). CIR ranged between 58.8% and 100% (mean: 93.1%). Independent predictors of CIR at the endoscopist level were the yearly number of screening colonoscopies performed (OR: 1.51 for endoscopists with600 colonoscopies; 95% CI 1.11 to 2.04) and, at the endoscopy centre level, screening-dedicated sessions (OR: 2.18; 95% CI 1.24 to 3.83) and higher rates of sedation (OR: 0.47 if occasional; 95% CI 0.24 to 0.92).The quality of colonoscopy was affected by patient-related, endoscopist-related and centre-related characteristics. Policies addressing organisational issues should improve the quality of colonoscopy in our programme and similar programmes.

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

Objectives: To evaluate the relation between the exposure to specific pesticides in agricultural work and the risk of multiple myeloma (MM).

Objectives To assess whether maternal blood pressure (BP) and heart rate (HR) change significantly in response to pelvic floor muscle training during pregnancy. Design Longitudinal exploratory study with repeated measurements. Sample Twenty-seven nulliparous healthy women of mean age 23.3 years (range 18–36) and mean body mass index 23.4 (range 23.1–29.5). Methods Individual supervised pelvic floor muscle training from gestational week 20 till 36 with assessment of BP and HR at gestational weeks 20, 24, 28, 32 and 36. Main outcome measures Systolic and diastolic BP was measured before and after each training session and HR was monitored during each session. Results Pelvic floor muscle training did not change BP. 77% (n = 21) of participants exceeded 70% of estimated maximum HR during at least one session. The time for exceeding 70% of estimated maximum HR was between 2.2 and 3.2 % of the total exercise session. Increases in BP and HR from gestational weeks 20 till 36 were within normal limits for pregnant women. Conclusions Pelvic floor muscle training in nulliparous sedentary pregnant women does not increase BP. It significantly increases HR during the exercise sessions, but only for a limited period of time and with no negative long-term effect on BP or HR.

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.

Background Although among women a decreasing prevalence of human papillomavirus (HPV) infection with increasing age has been consistently observed in high-resource countries, different age profiles have been reported elsewhere. Methods We compared the age profile of high-risk (HR)-HPV prevalence in nine different areas of Northern and Central Italy by studying the women recruited in the intervention arm of the New Technologies in Cervical Cancer study and tested by Hybrid Capture 2. Differences in the age-distribution of HPV infection were investigated in each centre by the joinpoint approach in a logistic model. 46,900 women aged 25 to 60 years were included in the analysis. Results The HR-HPV age-standardised (on Italian population) prevalence ranged from 5.7% (Trento) to 10.3% (Ravenna). HR-HPV prevalence decreased as a logistic function of increasing age in 6 of 9 centres (Trento, Verona, Florence, Bologna, Imola, and Viterbo). The effect of age on HR-HPV prevalence slopes did not differ significantly among these 6 centres, whereas significant heterogeneity in intercepts (p

Aims In 1990, The Bethesda System (TBS) was introduced into spontaneous cervical screening practice in Ravenna, Italy. Negative/benign reports with the recommendation for early repeat smears (RERS) due to some limitation in sample adequacy were considered no longer acceptable. A monitoring program for the rate of unsatisfactory smears (UNS) was implemented. The aim of the present study was to evaluate the effects of such changes in the screening procedure. Methods The frequency of UNS in 1990 was compared with that of UNS+RERS in 1988 (assumed as a baseline year) by the calculation of the standardized rate ratio with the 95% confidence interval (CI). The trend in the standardized rate of UNS from 1990 to 1994 was evaluated by the calculation of the average annual variation with the 95% CI. Results The immediate effect of TBS (1990:1988 comparison) was a significant increase in the rate of UNS attributable to scant cellularity, poor fixation and thick areas (rate ratio, 2.35; 95% CI, 2.18 to 2.53) and to the absence of endocervical component (1.45; 95% CI, 1.30 to 1.60). The rate of UNS attributable to the presence of cytolysis, inflammation, blood and foreign material decreased by about 6 times (0.16; 95% CI, 0.13 to 0.19). The midterm effect of TBS (trend from 1990 to 1994) was a decrease in the total rate of UNS by an average of 2.3% per year. The downward trend was significant for smears showing scant cellularity, poor fixation and thick areas (-1.5% per year) and the absence of endocervical component (-0.7% per year). UNS attributable to the presence of cytolysis, inflammation, blood and foreign material stabilized. Conclusions TBS led to a substantial change in the type of information provided by the cytology report (Immediate effect). The monitoring program according to TBS led to a reduction in UNS attributable to sample taker (midterm effect).

Background: In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model. Methods: Data from district screening centres were used to evaluate the process of identification and selection of eligible FDRs (residence in the Emilia-Romagna Region, age 40–75 years, no recent colonoscopy) of screen-detected CRC patients and the detected prevalence of disease. The probability for an FDR to undergo colonoscopy and to be diagnosed with CRC and advanced adenoma was estimated using the Kaplan–Meier method. The sex- and age-standardised ratio of detected prevalence to that expected based on results from a colonoscopy screening study of the Italian general population was estimated. Results: Between 2005 and 2011, 9319 FDRs of 2437 screen-detected CRC patients (3.8 per patient) were identified and contacted. Their likelihood of being eligible for, and accepting, colonoscopy was 0.11 (95% confidence interval: 0.11–0.12). Among the 926 subjects undergoing colonoscopy, the prevalence of previous negative screening FOBT was 63%. Eleven CRCs (1.2%) and 100 advanced adenomas (10.8%) were detected. The standardised ratio of detected prevalence to that expected was 0.91 (95% confidence interval: 0.19–2.66) for CRC and 1.48 (1.04–2.05) for advanced adenoma. Conclusions: The procedure of selection of FDRs was extremely ineffective. Due to previous negative screening tests, the prevalence of disease was less than expected. A population-based FOBT screening programme is a highly unsuitable setting for the provision of surveillance to FDRs of CRC patients.

This study of seven healthy young subjects was designed both to establish whether endothelin-1 (ET-1) is involved in the homeostasis of blood volume and to clarify the relationship between plasma and urinary ET-1. Acute volume expansion (+17%) caused increases in venous blood pressure (+4.4 mmHg) and the plasma concentration of ET-1 (+129%) and a decrease (-99%) in the urinary excretion of ET-1. Volume depletion (-8.5%) provoked an increase in the plasma concentration of ET-1 without altering the urinary excretion of ET-1. Passive elevation of an arm resulting in a local decrease of venous blood pressure (-17 mmHg) elicited an increase of the local formation of ET-1, with a 10-fold increase in the venous-arterial gradient compared with the opposite arm, which lay at the level of the heart. The increased local formation of ET-1 was blunted by volume expansion. The results indicate that 1) plasma ET-1 and urinary ET-1 represent two different endothelin-generating systems, both of which are involved in the regulation of blood volume, and 2) plasma ET-1 appears to be an important mechanism for the long-lasting adaptations of venous wall tension to changes in blood volume.

Summary Background Immunostaining for p16-INK4A (henceforth p16) is a sensitive and specific method for detection of high-grade cervical intraepithelial neoplasia (CIN) in women infected with human papillomavirus (HPV), but longitudinal data have not been obtained. We investigated the relation between p16 status and risk of CIN during 3 years of follow-up. Methods Women aged 25–60 years were enrolled between June 10, 2003, and Dec 31, 2004, in a multicentre randomised trial comparing HPV testing with cytology. HPV-positive women were referred for colposcopy and, in seven of nine centres, were tested for p16 overexpression by immunostaining. If no CIN was detected, these women were followed up at yearly intervals until clearance of HPV infection. The primary endpoint was histologically confirmed CIN of grade 2 or worse (CIN of grade 2 [CIN2], CIN of grade 3 [CIN3], or invasive cervical cancer) at recruitment or during follow-up. We calculated the absolute and relative risks by p16 status at recruitment. We also calculated the longitudinal sensitivity of p16 testing. Additionally, we assessed the relative sensitivity of an alternative strategy (referral to colposcopy and follow-up of only HPV-positive, p16-positive women) versus conventional cytology in two age groups. Percentages were weighted by the inverse of the tested fraction. The trial in which this study is nested is registered, number ISRCTN81678807. Findings Of 1042 HPV-positive women who were tested for p16 with no CIN detected during the first round of screening, 944 (91%) had further HPV tests. 793 (84%) of these 944 were followed up until detection of CIN2 or worse, HPV infection clearance, or for at least 3 years. CIN2 or worse was detected during follow-up in more p16-positive women (31 of 365, 8·8% [95% CI 5·8–11·8]) than in p16-negative women (17 of 579, 3·7% [1·9–5·4]; relative risk [RR] 2·61 [95% CI 1·49–4·59]). RR was higher in women aged 35–60 years at recruitment (3·37 [1·39–8·15]) than in those aged 25–34 years (2·15 [1·00–4·61]), but age was not a significant modifier. CIN3 or worse was detected during follow-up in more p16-positive women (16 of 365, 4·4% [2·3–6·6]) than in p16-negative women (six of 579, 1·3% [0·2–2·3]; RR 3·90 [95% CI 1·57–9·68]). Longitudinal sensitivity of p16 testing for detection of CIN3 or worse during follow-up at all ages was 77·8% (95% CI 63·9–91·6). The relative sensitivity of the alternative strategy compared with conventional cytology was 2·08 (1·13–3·56) in women aged 35–60 years and 2·86 (1·28–5·36) in those aged 25–34 years. HPV-positive, p16-negative women aged 35–60 years had a higher cumulative risk of CIN3 or worse during recruitment or follow-up (2·0%, 95% CI 0·3–3·7) than did HPV-negative women (0·01%, 0–0·04) or those who were cytologically normal (0·04%, 0·02–0·09) at recruitment. Interpretation p16 overexpression is a marker for CIN2 or worse or for development of CIN2 or worse within 3 years in HPV-positive women, especially those aged 35–60 years. HPV-positive, p16-positive women need immediate colposcopy and, if the assessment is negative, annual follow-up. Immediate colposcopy can be avoided in HPV-positive, p16-negative women, who can be safely managed with repeat screening after 2–3 year intervals. Funding European Union; Italian Ministry of Health; Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia Romagna; and Public Health Agency of Lazio Region.

Aims and Background In the field of breast cancer control, obtaining population-based data on spontaneous mammography (MG) screening should be a priority. This study focuses on the breast cancer incidence and stage distribution in relation to MG use in Ravenna (Italy), 1987-88. Methods We estimated the MG rates, expected (E) incidence based on mortality data, observed (O) incidence, predicted excess incidence based on MG rates, observed excess incidence, and stage distribution according to the MG history. Results The highest MG rate (37%) was found among residents aged 40-44 but none of these had a T1a-bN0 breast cancer diagnosed nor was the predicted excess incidence demonstrated. Between 45 and 64 years, 80% of self-selected screenees had repeat (“incidence”) MG and the O:E incidence ratio was 1.32 (95% Cl 1.09-1.58). The observed excess incidence was 3.8-fold (95% Cl 2.56-5.16) greater than that predicted. Advanced (T2+ and/or N1+) cases accounted for 42% of patients diagnosed within 3 years of their last MG, for 55% of those diagnosed more than 3 years after their last MG, and for 70% of those with no previous MG. Above age 70, a significant worsening of stage at diagnosis was associated with a clear-cut drop in the proportion of breast cancer patients with previous self-referral for MG. Conclusions The results indicate that self-selection and its implications are major features of spontaneous screening practice.

Background Although poorly described in the literature, the practice of early (short-interval) rescreen after a negative screening mammogram is controversial due to its financial and psychological burden and because it is of no proven benefit. Methods The present study targeted an Italian 2-yearly screening programme (Emilia-Romagna Region, 1997-2002). An electronic dataset of 647,876 eligible negative mammography records from 376,257 women aged 50-69 years was record-linked with the regional breast cancer registry. The statistical analysis addressed the following research questions: (1) the prevalence of recommendation for early ( Results RES was used in eight out of 13 screening centres, where it was found in 4171 out of 313,320 negative reports (average rate 1.33%; range 0.05%-4.33%). Reports with RES were more likely for women aged 50-59 years versus older women (odds ratio (OR) 1.33; 95% CI 1.25-1.42), for the first versus subsequent screening rounds (OR 1.91; 95% CI 1.79-2.04) and with a centre-specific recall rate below the average of 6.2% (OR 1.41; 95% CI 1.32-1.50). RES predicted a 3.51-fold (95% CI 0.94-9.29) greater proportional incidence of first-year interval cancers, a 1.90-fold (95% CI 1.62-2.22) greater recall rate at the next screen, a 1.72-fold (95% CI 1.01-2.74) greater detection rate of cancer at the next screen and a non-significantly decreased risk of late disease stage (OR 0.59; 95% CI 0.23-1.53). Conclusion The prevalence of RES was in line with the maximum standard level established by the Italian national guidelines. RES identified a subset of women with greater incidence of interval cancers and greater prevalence of cancers detected at the next screen.

Computer-aided diagnosis (CAD) has been extensively reported to increase sensitivity by about 10% when added to a single reading while increasing recall rate by 12%, and its current use can be safely recommended in clinical practice. CAD has been suggested as a possible alternative to conventional double reading in screening. Uncontrolled comparison is consistent and suggests that CAD is comparable to double reading in incremental cancer detection rate (CAD +10.6%, double reading +9.1%) and possibly better in recall rate (CAD +12.5%, double reading +28.8%). However, controlled studies comparing single reading + CAD to conventional double reading are not consistent and on average suggest a lower cancer detection rate (−5.1%) and a lower recall rate (−9.8%) for CAD. Scientific evidence is not sufficient for a safe recommendation of single reading + CAD as a current alternative to conventional double reading.

Photocatalytic activity of both commercial and homemade samples was tested for the degradation of toluene in the gas phase by using two different irradiation sources, UV and solar. The role played by humidity in affecting the final toluene degradation was discussed. Catalyst deactivation (due to the high toluene level, 1000 ppm) and subsequent regeneration, by washing with water, were analyzed. Highest degradations and corresponding kinetic constants were achieved in the case of the anatase/brookite composite samples, while the commercial ones (including P25 Degussa) showed lower efficiency. Various adsorbed aromatic species (benzoic acid, the major surface product hydroquinone, benzylic alcohol, benzaldehyde, and cresols) obtained by washing the exhaust catalysts were analyzed by HPLC. Parallel results were achieved by Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. The presence of different photodegradation surface species for the various photocatalysts suggests the occurrence of different reaction pathways, depending on the fine physicochemical features of the specific TiO2 adopted in the reaction.

To assess the adequacy of a routine screening to identify cervical intraepithelial neoplasia 2 or worse (CIN2+) in women over 50 years of age, a retrospective cohort was set in six Italian organised population-based screening programmes. In all, 287 330 women (1 714 550 person-years of observation, 1110 cases) screened at age 25–64, with at least two cytological screening tests, the first negative, were followed from their first negative smear until a biopsy proven CIN2+ lesion or their last negative smear. For women aged 25–49 and 50–64 years, crude and age-standardised detection rate (DR), cumulative risk (CR), adjusted hazard risk for number of previous negative screens, probability of false-positive CIN2+ after two or more smear tests were calculated. Detection rate is significantly lower over 50 years of age. Multivariable analysis shows a significant protective effect from four screening episodes (DR=0.70, 95% CI: 0.51–0.97); the effect of age ⩾50 is 0.29 (95% CI: 0.24–0.35). The CR of CIN2+ is at least eightfold higher in women

ObjectivesTo estimate the total proportional incidence of interval breast cancers in a two-yearly mammography screening programme, and to perform subgroup analyses by woman's age, screening centre-specific recall rate and screening round.MethodsUsing unconverted electronic datasets from the 13 screening centres in the Emilia-Romagna Region of northern Italy (540,450 women aged 50-69 years), a database of 919,538 mammography records was created. Of these, 655,175 eligible single-mammography records (1997-2002) from 379,318 women were record-linked with the regional Breast Cancer Registry. In the two-year inter-screening interval, a total of 1,022,694.3 woman-years at risk were accumulated, with 695 interval cancers observed and 2428.3 expected. The observed number of interval cancers was divided by the expected number to obtain the proportional incidence.ResultsThe total proportional incidence of first- and second-year interval cancers was 0.18 (95% CI 0.15-0.20) and 0.43 (0.39-0.47), respectively. woman's age was inversely associated with proportional incidence in both interval years, with a cut-off point at age 60. A screening centre-specific recall rate greater than the regional average of 5% was associated with a proportional incidence of 0.14 (0.11-0.17) versus 0.20 (0.17-0.24) in the first interval year, and of 0.36 (0.31-0.41) versus 0.50 (0.44-0.56) in the second. The proportional incidence remained unchanged between the first and subsequent screening rounds.ConclusionsThe results were in line with the previous Italian data and with the recommended European standards. The inverse effect of woman's age and of recall rate was expected.

Background In the first recruitment phase of a randomized trial of cervical cancer screening methods (New Technologies for Cervical Cancer Screening [NTCC] study), we compared screening with conventional cytology with screening by human papillomavirus (HPV) testing in combination with liquid-based cytology. HPV-positive women were directly referred to colposcopy if aged 35 or older; if younger, they were retested after 1 year. Methods In the second recruitment phase of NTCC, we randomly assigned women to conventional cytology (n = 24 661) with referral to colposcopy if cytology indicated atypical squamous cells of undetermined significance or more severe abnormality or to testing for high-risk HPV DNA alone by Hybrid Capture 2 (n = 24 535) with referral to colposcopy if the test was positive at a concentration of HPV DNA 1 pg/mL or greater. For the main endpoint of the study, histologic detection of cervical intraepithelial neoplasia of grade 2 or more (CIN2+), we calculated and compared sensitivity and positive predictive value (PPV) of the two screening methods using HPV DNA cutoffs of 1 pg/mL and 2 pg/mL. All statistical tests were two-sided. Results For women aged 35 – 60 years, the relative sensitivity of HPV testing for detection of CIN2+ at a cutoff of 1 pg/mL vs conventional cytology was 1.92 (95% CI = 1.28 to 2.87) and the relative PPV was 0.80 (95% CI = 0.55 to 1.18). At a cutoff of 2 pg/mL HPV DNA, the relative sensitivity was 1.81 (95% CI = 1.20 to 2.72) and the relative PPV was 0.99 (95% CI = 0.67 to 1.46). In this age group, there was no evidence of heterogeneity between study phases. Among women aged 25 – 34 years, the relative sensitivity for detection of CIN2+ of HPV testing at a cutoff of 1 pg/mL vs cytology was 3.50 (95% CI = 2.11 to 5.82), statistically significantly larger ( P = .019) than that observed in phase 1 at this age (1.58; 95% CI = 1.03 to 2.44). Conclusions For women aged 35 – 60 years, HPV testing with a cutoff of 2 pg/mL achieves a substantial gain in sensitivity over cytology with only a small reduction in PPV. Among women aged 25 – 34 years, the large relative sensitivity of HPV testing compared with conventional cytology and the difference between relative sensitivity during phases 1 and 2 suggests that there is frequent regression of CIN2+ that are detected by direct referral of younger HPV-positive women to colposcopy. Thus, triage test or repeat testing is needed if HPV is to be used for primary testing in this context. J Natl Cancer Inst 2008;100: 492 – 501