[The mortality rate for homicide among women in Italy: a historical and geographical analysis as a contribution to the study of femicide]. / La mortalità per omicidio tra le donne in Italia: un'analisi storico-geografica come contributo allo studio del femminicidio.

As 70% of the killings of women takes place in the context of relational dynamics and in 80% of the cases the perpetrator is a man, we can presume that femicide constitutes much of the homicide mortality among women. Epidemiological surveillance of the killings of women can, therefore, provide indicators on the trends and geographical distribution of femicide and, indirectly, of the more general phenomenon of harassment and violence against women. The analysis of 40 years of mortality shows only a slight decrease of the murders of women nationwide. This suggests that the factors that underline this phenomenon are deeply rooted in the relationship between men and women. The decrease has taken place mainly in the South and Islands and the percentage SMRs point to a reversal of the relationship between geographic areas: thus, at the end of the observation period the North-West assumes a greater weight than the South and Islands. So we cannot exclude that part of the decrease in murders of women can be attributed to the overall decrease in homicides related to criminal activity, most pronounced in the South and Islands.

Information provided by Italian breast cancer screening programmes: a comparison between 2001 and 2014.

Debate on efficacy, benefits, and risks of breast cancer screening continues to rage, and scientific controversy surrounding overdiagnosis, false positives/false negatives, raises questions about communication to women attending screening programmes. The study compares information provided by invitation letters and leaflets of Italian breast screening programmes in 2001 (N=47) and 2014 (N=80). At both times, nearly all programmes provided adequate practical information and details about screening objectives and test procedures. Information regarding epidemiology/figures was scarce or absent in 2001, while in 2014 a number of programmes began to inform women about screening risks (false negative and positive results and overdiagnosis, 65%, 16%, and 21% respectively) although actual figures were rarely supplied. Despite this small improvement, Italian programmes are still far from giving balanced information. Further efforts should be addressed to providing accurate and transparent information, enabling women to make an informed choice.

Problems, solutions, and perspectives in the evaluation of interval cancers in Italian mammography screening programmes: a position paper from the Italian group for mammography screening (GISMa).

In this position paper, a self-convened team of experts from the Italian Group for Mammography Screening (Gruppo italiano screening mammografico, GISMa) pointed out the problems that increasingly hamper the feasibility and validity of the estimate of the proportional incidence of interval breast cancer (IBC) in Italy, suggested potential solutions and an agenda for research, and proposed that the question of the sensitivity of mammography be viewed in a larger perspective, with a greater attention to radiological review activities and breast radiology quality assurance programmes. The main problems are as follows: the coverage of cancer registration is incomplete; the robustness of using the pre-screening incidence rates as underlying rates decreases with time since the start of screening; the intermediate mammograms performed for early detection purposes may cause an overrepresentation of IBCs; the classification of many borderline screening histories is prone to subjectivity; and, finally, the composition of cohorts of women with negative screening results is uncertain, because several mammography reports are neither clearly negative nor clearly positive, and because of the limitations and instability of the electronic mammography records. Several possibilities can be considered to cope with these issues: standard methods for using the hospital discharge records in the identification of IBCs should be established; for the calculation of regional estimates of the underlying incidence, a suitable mathematical model should be identified; the definition of IBC according to the 2008 GISMa guidelines needs to be updated, especially with respect to in situ cancers and to invasive cancers with borderline screening histories; a closer adherence to standard screening protocols, with a simplified patient management, would make it easier to objectively identify IBCs; alternative methods for estimating the sensitivity of mammography should be taken into consideration; and, finally, analysis could be restricted to the absolute incidence rate of IBC, which would make comparison of the risk between neighbouring populations possible. Epidemiologists must extend their attention to the prevention of the risk of IBC and the implementation of breast radiology quality assurance practices. Epidemiologists and radiologists can share common objectives: it is necessary to promote the idea that the availability of a registry-based series of IBCs is not a prerequisite for their radiological review; radiological review of breast cancers greater than 20mm in size detected at second and subsequent screens, that are potential substitutes for IBCs, needs radiological and epidemiological validation studies; the advent of digital mammography brings about the possibility to create libraries of mammograms accessible online, which enables the conduct of large studies of the diagnostic variability of radiologists; and, finally, epidemiologists and radiologists have the responsibility to monitor the effects that a loss of cumulative professional experience in screening centres, due to the imminent retirement of a substantial proportion of healthcare workforce, could cause on their performance.

Tixagevimab/Cilgavimab as pre-exposure prophylaxis against SARS-CoV-2 in patients with hematological malignancies.

The approved combination of Tixagevimab/Cilgavimab has been shown to decrease the rate of symptomatic SARS-CoV-2 infection in patients at increased risk of inadequate response to vaccination. However, Tixagevimab/Cilgavimab was tested in a few studies that included patients with hematological malignancies, even if this population has shown an increased risk of unfavorable outcomes following infection (with high rates of hospitalization, intensive care unit admission, and mortality) and poor significant immunization following vaccines. We performed a real-life prospective cohort study to evaluate the rate of SARS-CoV-2 infection following pre-exposure prophylaxis with Tixagevimab/Cilgavimab in anti-spike seronegative patients compared to a cohort of seropositive patients who were observed or received a fourth vaccine dose. We recruited 103 patients with a mean age of 67 years: 35 (34%) received Tixagevimab/Cilgavimab and were followed from March 17, 2022, until November 15, 2022. After a median follow-up of 4.24 months, the 3-month cumulative incidence of infection was 20% versus 12% in the Tixagevimab/Cilgavimab and observation/vaccine groups respectively (HR 1.57; 95% CI: 0.65-3.56; p = 0.34). In this study, we report our experience with Tixagevimab/Cilgavimab and a tailored approach to SARS-CoV-2 infection prevention in patients with hematological malignancies during the SARS-CoV-2 omicron surge.

[Meaningful words? Cancer screening communication in Italy]. / Parole diversamente abili.

Over the last ten years, Italian work groups of communication within The National Centre for Screening Monitoring have been working on various aspects of communication in screening: quality surveys, information materials, guidelines, websites, and training. This has been done taking into account that good quality information must be clear, accessible, up to date, evidence based, clear about its limitations and capable of indicating further sources of information. Whenever possible, information has been developed in collaboration with the target groups: citizens but also health professionals. However, if good quality information must be clear about benefits and harms, the communication of quantitative information is particularly complex in cancer screening. Moreover, receiving more information on risks and benefits does not seem to modify participation. In addition, more balanced information does not entail that a person will include it in the decision process.Throughout several focus groups, citizens have made it clear that the information received from the programmes was only a part of the decisional process in which other elements were just as, if not more, important: trust in doctors, family and friends, perception of health authority efficiency, personal experiences, inconsistencies in information or public disagreements with other credible sources. Such elements can be seen as an opportunity to strengthen partnerships with professional and advocacy groups and to cooperate more efficiently with media and specialists from different fields.

[Immigration from countries with a strong migratory pressure and participation in cervical cancer screening program in the Local Health Unit 2, Umbria Region. Impact on the probability of high-grade lesions and cervical cancer]. / Provenienza da Paesi a forte pressione migratoria e partecipazione allo screening citologico nell'AUSL2 dell'Umbria. Impatto sulla probabilità di presentare lesioni di alto grado e tumori del collo dell'utero.

OBJECTIVE: to measure the risk of having serious lesions and cervical cancer for immigrant women, by evaluating the impact of their lack of participation in the previous rounds. DESIGN: retrospective study. SOURCE OF DATA: archive of the screening programme of Local Health Unit 2, Umbria. People subjected to the study: those adhering to the last round (2008- 2010) and belonging to an age group potentially capable of participating in all the previous rounds (1999-2007). MAIN OUTCOME MEASURES: positivity to Pap test; lesions that require colposcopy (AGCH,AGCUS,ASCH, HSIL); tumours (squamous cell carcinomas and adenocarcinomas). RESULTS: 1.7% of the women were positive to the Pap test, 0.7% presented lesions with the immediate need for colposcopy, and 0.039% were diagnosed with cancer. The percentage of women who resulted either positive to the Pap test, or presenting lesions requiring colposcopy or with cancer, is significantly higher among those who come from poor countries. Furthermore, participation in previous rounds has proven to be protective with reference to the above-mentioned markers. CONCLUSION: the independent weight of several risk factors has emerged and consequently the need to promote with particular commitment the participation in screening of women coming from poor countries.

[Hospital admission in terminally ill cancer patients: a survey in the Umbrian Local Health Unit 2]. / Il ricovero ospedaliero nei pazienti oncologici in fase terminale: un'analisi nell'AUSL 2 dell'Umbria.

OBJECTIVE: describing, using administrative data, the extent and modalities of hospitalization in terminally ill cancer patients, residing in Local Health Unit (LHU) 2 of Umbria Region, Italy. DESIGN: retrospective cohort study based on current administrative data: Nominative Registry of Causes of Death (ReNCaM) and Hospital Discharge Records (HDR). SETTING AND PARTICIPANTS: residents in LHU 2 dead of cancer (ICD9-CM categories: 140-239) in 2004-2006 (N=3,122). MAIN OUTCOME MEASURES: percentage of patients hospitalized within thirty days before death, percentage of those admitted to hospital within 2 days before death, percentage of patients discharged once dead, percentage of those discharged alive on the day of death. We used a multivariate logistic analysis model to assess the role played by the variables on the available indicators. RESULTS: percentage of patients hospitalized within thirty days before death was 56.5% (N=1,764) percentage of those admitted to hospital within 2 days before death was 9.0% (N=281) percentage of those discharged alive on the day of death was 24.4% (N=763); percentage of discharged alive on the day of death was 6,1% (N=190). The age group 40-59 years and any residence other than the District of Assisi (the first with a palliative care network), are factors associated with increased hospitalization in the terminally ill.

[Interval cancers as indicators of performance in screening programmes]. / I carcinomi di intervallo quali indicatori di performance di un programma di screening.

GISMa analyses the interval cancer (IS) topic providing guidelines and reference standards in addition to CE recommendations. IC identification is based on Cancer Registries (CR), if existing, or on hospital discharge records, in alternative. The optimal measure of IC frequency (inversely correlated with sensitivity) is the IC proportional incidence (observed IC/carcinomas expected in absence of screening). Other formulas (IC/IC + screen detected cancers; IC rate per 1000 negative screens) look less reliable. IC stage at diagnosis (if available through CR) must be compared with screen detected cancer and cancer detected in non-attenders. Review of mammograms preceding the IC (coded as screening error, minimal signs, or occult) should be done mainly with a blind procedure (IC mixed with negative controls), as this procedure is more representative of the original scenario and more respectful of radiologist's rights.

[Process indicators and standards for the evaluation of breast cancer screening programmes]. / Indicatori e standard per la valutazione di processo dei programmi di screening del cancro della mammella.

In order to obtain the maximum benefit from breast cancer screening it is essential for every programme to reach high levels of sensitivity and specificity. This can only be achieved if skill and a comprehensive quality assurance system is applied to the entire process, involving each individual part of the programme. Monitoring of outcomes and continuous evaluation of the entire screening process are key operational objectives for a successful population screening programme. The aim of this document, born in the framework of the Italian Group for Mammography Screening (GISMa), is to propose a unique methodology for collecting and reporting screening data using commonly agreed terminology, definitions and classifications. The indicators considered are those referred to the entire screening process and its sequelae, such as organizational, logistic and performance indicators. The indicators are provided under form of a synthetic and easy to use card. Every card is structured in short sections: definition, aim of the indicator, the data necessary to build it, the summarizing formula, possible problems of interpretation, the acceptable and desirable standards (derived both from the experience of national and European breast cancer screening programmes).

Cervical cancer screening in immigrant women in Italy: a survey on participation, cytology and histology results.

Cervical cancer screening programmes in Italy actively invite all 25-64-year-old resident women for the Pap test every 3 years irrespective of their citizenship. Immigrant women come from countries where screening is absent or poorly implemented and the prevalence of human papillomavirus is often high. These women therefore have significant risk factors for cervical cancer. The Italian Group for Cervical Cancer Screening promoted a survey of all the screening programmes on the participation and the positivity and detection rates in Italian and foreign women in 2009-2011. Aggregated data for participation, cytology results, compliance with colposcopy and histology results were collected, distinguishing between women born in Italy and abroad. All comparisons were age adjusted. Forty-eight programmes out of 120 participated in the immigrant survey, with 3 147 428 invited and 1 427 412 screened Italian women and 516 291 invited and 205 948 screened foreign women. Foreign women had a slightly lower participation rate compared with Italians (39.9 vs. 45.4%), whereas compliance with colposcopy was similar (90%). Foreigners showed a higher risk of pathological findings than Italians: cytology positivity [relative risk (RR)=1.25, 95% confidence interval (CI) 1.24-1.27] and detection rate for cervical intraepithelial neoplasia grade 2 (CIN2) (RR=1.39, 95% CI 1.31-1.47), CIN3 (RR=2.07, 95% CI 1.96-2.18) and cancer (RR=2.68, 95% CI 2.24-3.22). The ratio between cancer and CIN was higher in immigrants (0.06 vs. 0.04, P<0.01). Foreign women had a higher risk of cervical precancer and cancer. Because of their high risk and because opportunistic screening does not cover this often disadvantaged group, achieving high participation in screening programmes for foreigners is critical to further reducing the cervical cancer burden in Italy.

Might the M184V substitution in HIV-1 RT confer clinical benefit?

The M184V substitution in HIV-1 RT develops rapidly following initiation of therapy with 3TC and confers high-level phenotypic resistance to this drug both in vitro and in vivo. Interestingly, the presence of M184V is also associated with alteration of several mechanisms relating to RT function that include decreased RT processivity, reduced nucleotide-dependent primer unblocking, increased fidelity, hypersensitization to other NRTIs, impaired viral fitness, and delayed appearance of mutations in RT that are responsible for resistance to thymidine analogues (i.e. thymidine-associated mutations or TAMs). Collectively, these factors might explain the residual antiviral effect and clinical benefit observed with continued use of 3TC in combination therapy regimens following the emergence of M184V. Indeed, the results of numerous controlled as well as observational clinical studies are suggestive of improved therapeutic outcome associated with continued usage of 3TC and maintenance of the M184V mutation. However, several of these trials did not possess adequate statistical power to resolve whether or not continued use of 3TC provided actual benefit, nor were they specifically designed to test the M184V benefit hypothesis in prospective fashion. There is a need for randomized clinical trials of this type in order to validate the potential benefit of maintenance of M184V and whether continued use of 3TC is the only means of attaining this objective.

[HIV drug resistance and optimization of antiviral treatment in resource-poor countries]. / Résistance du VIH aux antirétroviraux: conséquences pour les pays à faibles revenus.

HIV drug resistance has been associated with treatment failure in Western countries but the lessons learned can be useful in optimization of highly active antiretroviral treatment (HAART) in resource-poor settings. There is a need to improve access to HAART in such regions, but appropriate strategies must be rapidly implemented, such as adapted programs to facilitate adherence to therapy, rational use of genotypic drug resistance monitoring in specific situations, and use of alternative treatment regimens. The implications of HIV genetic diversity must also be considered in management of drug resistance.

Breast screening: axillary lymph node status of interval cancers by interval year.

The aim of this study was to determine whether the excess risk of axillary lymph node metastases (N+) differs between interval breast cancers arising shortly after a negative mammography and those presenting later. In a registry-based series of pT1a-pT3 breast carcinoma patients aged 50-74 years from the Italian screening programmes, the odds ratio (OR) for interval cancers (n=791) versus the screen-detected (SD) cancers (n=1211) having N+ was modelled using forward stepwise logistic regression analysis. The interscreening interval was divided into 1-12, 13-18, and 19-24 months. The prevalence of N+ was 28% among SD cancers. With a prevalence of 38%, 42%, and 44%, the adjusted (demographics and N staging technique) OR of N+ for cancers diagnosed between 1-12, 13-18, and 19-24 months of interval was 1.41 (95% confidence interval 1.06-1.87), 1.74 (1.31-2.31), and 1.91 (1.43-2.54), respectively. Histologic type, tumour grade, and tumour size were entered in turn into the model. Histologic type had modest effects. With adjustment for tumour grade, the ORs decreased to 1.23 (0.92-1.65), 1.58 (1.18-2.12), and 1.73 (1.29-2.32). Adjusting for tumour size decreased the ORs to 0.95 (0.70-1.29), 1.34 (0.99-1.81), and 1.37 (1.01-1.85). The strength of confounding by tumour size suggested that the excess risk of N+ for first-year interval cancers reflected only their higher chronological age, whereas the increased aggressiveness of second-year interval cancers was partly accounted for by intrinsic biological attributes.