Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>95%), Cure Prevalence (women who will not die of cancer), and Already Cured (living longer than Time to Cure). In 2018, 0.4% (121,704) of Italian women were alive after corpus uteri cancer, 0.2% (52,551) after cervical, and 0.2% (52,153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (Cure Prevalence). Women with gynaecological cancers have a residual excess risk of death <5% after 5 years since diagnosis. The Cure Fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time To Cure was ≤10 years for women with gynaecological cancers aged <55 years. 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were Already Cured. These results will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

Cancer and Pregnancy: Estimates in Italy from Record-Linkage Procedures between Cancer Registries and the Hospital Discharge Database.

The aim of this study is to describe the frequency and trend of pregnancy-associated cancer (PAC) in Italy, an increasingly relevant phenomenon due to postponing age at childbirth. To this purpose, a population-based retrospective longitudinal study design based on cohorts of women aged 15-49 diagnosed with cancer and concomitant pregnancy is proposed. The study uses 19 population-based Cancer Registries, covering about 22% of Italy, and linked at an individual level with Hospital Discharge Records. A total of 2,861,437 pregnancies and 3559 PAC are identified from 74,165 women of the cohort with a rate of 1.24 PAC per 1000 pregnancies. The most frequent cancer site is breast (24.3%), followed by thyroid (23.9%) and melanoma (14.3%). The most frequent outcome is delivery (53.1%), followed by voluntary termination of pregnancy and spontaneous abortion (both 12.0%). The trend of PAC increased from 2003 to 2015, especially when the outcome is delivery, thus confirming a new attitude of clinicians to manage cancer throughout pregnancy. This represents the first attempt in Italy to describe PAC from Cancer Registries data; the methodology is applicable to other areas with the same data availability. Evidence from this study is addressed to clinicians for improving clinical management of women with PAC.

Complete prevalence and indicators of cancer cure: enhanced methods and validation in Italian population-based cancer registries.

Objectives: To describe the procedures to derive complete prevalence and several indicators of cancer cure from population-based cancer registries. Materials and methods: Cancer registry data (47% of the Italian population) were used to calculate limited duration prevalence for 62 cancer types by sex and registry. The incidence and survival models, needed to calculate the completeness index (R) and complete prevalence, were evaluated by likelihood ratio tests and by visual comparison. A sensitivity analysis was conducted to explore the effect on the complete prevalence of using different R indexes. Mixture cure models were used to estimate net survival (NS); life expectancy of fatal (LEF) cases; cure fraction (CF); time to cure (TTC); cure prevalence, prevalent patients who were not at risk of dying as a result of cancer; and already cured patients, those living longer than TTC at a specific point in time. CF was also compared with long-term NS since, for patients diagnosed after a certain age, CF (representing asymptotical values of NS) is reached far beyond the patient's life expectancy. Results: For the most frequent cancer types, the Weibull survival model stratified by sex and age showed a very good fit with observed survival. For men diagnosed with any cancer type at age 65-74 years, CF was 41%, while the NS was 49% until age 100 and 50% until age 90. In women, similar differences emerged for patients with any cancer type or with breast cancer. Among patients alive in 2018 with colorectal cancer at age 55-64 years, 48% were already cured (had reached their specific TTC), while the cure prevalence (lifelong probability to be cured from cancer) was 89%. Cure prevalence became 97.5% (2.5% will die because of their neoplasm) for patients alive >5 years after diagnosis. Conclusions: This study represents an addition to the current knowledge on the topic providing a detailed description of available indicators of prevalence and cancer cure, highlighting the links among them, and illustrating their interpretation. Indicators may be relevant for patients and clinical practice; they are unambiguously defined, measurable, and reproducible in different countries where population-based cancer registries are active.

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990-2015).

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990-2001 to 81.9% in 2009-2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70-79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003-2015 versus 1990-2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.

BACKGROUND: Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. METHODS: Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. RESULTS: The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. CONCLUSIONS: These results highlight the need to personalize follow-up strategies for AYA cancer survivors.

Psoriasis severity matters when dealing with all-cause mortality in psoriasis patients: a record linkage analysis in Northern Italy.

Psoriasis has been linked with several comorbidities and increased all-cause mortality compared with the general population. Data are still limited concerning mortality especially from Southern European countries. Between January 2012 and December 2018, we conducted a retrospective cohort study on psoriasis patients and population controls in Northern Italy. Through record linkage of health-care databases, psoriasis cases were identified, and their morbidity and mortality were compared with the general population. The Charlson index was used as an index of comorbidities. Standardized mortality ratios (SMR) were estimated for overall psoriasis cases and for patients with mild vs moderate-to-severe disease, separately. We identified 12,693 psoriasis patients (mean age: 60.8 ± 16.3 years). They had a significantly higher Charlson index compared with the general population (p < 0.001). In spite of the higher rate of comorbidities, age-specific SMR was not increased in the psoriasis population as a whole (1.04 (95% CI 0.89-1.20)) or in people with mild psoriasis. However, a 40% higher than the expected risk of all-cause mortality was documented in individuals with moderate-to-severe psoriasis (SMR: 1.41; 95% CI 1.12-1.75). Notably, an excess mortality in these patients occurred as early as age 40-49 years. The proportion of deaths from malignancies and cardiovascular diseases was remarkably high. Our results support the notion that psoriasis severity influences mortality and indicate that patients with psoriasis, especially those with severe disease, should receive appropriate screening and health education.

Magnitude and time-course of excess mortality during COVID-19 outbreak: population-based empirical evidence from highly impacted provinces in northern Italy.

BACKGROUND: The real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on overall mortality remains uncertain as surveillance reports have attributed a limited number of deaths to novel coronavirus disease 2019 (COVID-19) during the outbreak. The aim of this study was to assess the excess mortality during the COVID-19 outbreak in highly impacted areas of northern Italy. METHODS: We analysed data on deaths that occurred in the first 4 months of 2020 provided by the health protection agencies (HPAs) of Bergamo and Brescia (Lombardy), building a time-series of daily number of deaths and predicting the daily standardised mortality ratio (SMR) and cumulative number of excess deaths through a Poisson generalised additive model of the observed counts in 2020, using 2019 data as a reference. RESULTS: We estimated that there were 5740 (95% credible set (CS) 5552-5936) excess deaths in the HPA of Bergamo and 3703 (95% CS 3535-3877) in Brescia, corresponding to a 2.55-fold (95% CS 2.50-2.61) and 1.93 (95% CS 1.89-1.98) increase in the number of deaths. The excess death wave started a few days later in Brescia, but the daily estimated SMR peaked at the end of March in both HPAs, roughly 2 weeks after the introduction of lockdown measures, with significantly higher estimates in Bergamo (9.4, 95% CI 9.1-9.7). CONCLUSION: Excess mortality was significantly higher than that officially attributed to COVID-19, disclosing its hidden burden likely due to indirect effects on the health system. Time-series analyses highlighted the impact of lockdown restrictions, with a lower excess mortality in the HPA where there was a smaller delay between the epidemic outbreak and their enforcement.

Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

OBJECTIVE: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy. METHOD: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models. RESULTS: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945. CONCLUSIONS: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Adolescent and Young Adult Cancer Survivors: Design and Characteristics of the First Nationwide Population-Based Cohort in Italy.

Purpose: Adolescent and young adult (AYA, 15-39 years) cancer survivors (alive at least 5 years after cancer diagnosis) are less studied than younger and older cancer survivors and research on their late effects is limited. To facilitate research on long-term outcomes of AYA cancer survivors, we established, in Italy, a population-based AYA cancer survivors' cohort. This article describes the study design and main characteristics of this cohort. Methods: The cohort derives from population-based cancer registries (CRs). Each CR identified AYA cancer patients retrospectively. Treatment for first primary cancer and all health events from diagnosis to death can be traced through linkage with available health databases, such as hospital discharge records (HDRs), mortality files, and outpatient and pharmaceutical databases. Results: Thirty-four CRs participated to the cohort which overall includes 93,291 AYAs with cancer and 67,692 cancer survivors. First primary cancer distribution in AYA cancer survivors differs by sex and age groups because of the different cancer types diagnosed in AYAs. Almost 78% of AYA cancer survivors have HDRs and 14.8% also pharmaceutical and outpatient databases. Conclusion: This cohort will be used to study, for the first time in Italy, the pattern and excess risk of late effects in AYA cancer survivors. HDRs, outpatient and pharmaceutical databases will be used to define primary treatment to assess its impact on AYA cancer survivors' late effects. This cohort exploiting data sources already available at CRs, minimize the data collection effort and it will contribute to assess the feasibility of using administrative database to study cancer survivors' late effects.

Effects of aircraft noise on annoyance, sleep disorders, and blood pressure among adult residents near the Orio al Serio International Airport (BGY), Italy.

BACKGROUND: Aircraft noise may cause several non-auditory health effects, including annoyance, sleep disorders, hypertension, cardiovascular diseases, and impaired cognitive skills in children. OBJECTIVES: To perform a cross-sectional study among adult residents near the Orio al Serio International Airport (BGY), Italy to investigate the association between aircraft noise, annoyance, sleep disorders, blood pressure levels, and prevalence of hypertension. METHODS: Residential addresses of subjects aged 45-70 years were geocoded and classified in three groups according to noise levels: <60 (Reference), 60-65 (Zone A), and 65-75 dBA (Zone B). A sample of subjects was invited to undergo a personal interview and blood pressure measurements. Multiple linear and robust Poisson regression models were used to analyze quantitative and categorical variables, respectively. RESULTS: Between June and September 2013, we enrolled 400 subjects (166 in the Reference Zone, 164 in Zone A, and 70 in Zone B). Compared to the Reference Zone, we found elevated adjusted annoyance scores (day and night) in Zone A (+2.7) and Zone B (+4.0) (p<0.001) and about doubled proportions of severely annoyed subjects (p<0.001). Reported sleep disorders in the previous month were also more frequent in Zones A and B. Sleep disorders in general were 19.9% in the Reference Zone, 29.9% in Zone A, and 35.7% in Zone B (p<0.001). CONCLUSIONS: We found a strong association between aircraft noise levels, annoyance, and sleep disorders among adult residents near the Orio al Serio International Airport. We found no relationship with blood pressure levels and prevalence of hypertension.

Psychometric Properties of the Romanian Version of the Hospital Survey on Patient Safety Culture (HSOPS).

OBJECTIVE: To explore psychometrics of the Romanian version of the Hospital Survey on Patient Safety Culture (HSOPS) released by the US Agency for Healthcare Research and Quality in 2004. MATERIAL AND METHODS: The original US survey with 12 composites and 42 items was translated (back translation method), pre-tested on a few staff and then minimally adjusted. A qualitative cross-sectional study was carried out in units from six hospitals in four Romanian regions, based on the census of medical and non-medical staff (n. 969). Participants completed a paper-based self-administered questionnaire. The main outcome measures were: descriptive statistics, confirmatory factor analysis (CFA), internal reliability and intercorrelations among survey composites. RESULTS: Nurses accounted for 67% of respondents, and doctors for 23%. Most work units were surgery (24%) and medical specialties (22%). After individual-level CFA on half of the sample, Staffing and Overall perceptions of patient safety composites were dropped and Feedback & communication about error and Communication openness composite items were aggregated to a single Communication composite. Subsequent CFA on the second half of the sample indicated that the novel composite structure adequately fitted the data: comparative fit index=0.90; root mean square error of approximation=0.06; standardized root mean square residual=0.06. Internal consistency was .0.70 for most composites. Spearman intercorrelations among the patient safety composites at the individual level averaged 0.28. CONCLUSION: Psychometrics of the Romanian version of the HSOPS tested in Romania was acceptable for nine composites with 31 items. Integration of this survey with items more pertinent for Romania is suggested.

Survey on patient safety culture in the Republic of Moldova: a baseline study in three healthcare settings.

BACKGROUND AND AIMS: The Republic of Moldova is a small ex-soviet country in the Central Eastern European group of states, whose official language is Romanian. In countries with limited resources, quality improvement in healthcare and patient safety are very challenging. This study aims to identify which areas of the patient safety culture (PSC) need prompt intervention. METHODS: A cross-sectional study was conducted in three Moldovan healthcare settings, using the Romanian translation of the US Hospital Survey on Patient Safety Culture HSOPSC. Descriptive statistics were carried out, based on the responses from n. 929 staff. Percentages of positive responses (PPRs) by item (41 items) and composite (12 PSC areas) were computed. RESULTS: Most respondents were nurses (53%), followed by doctors (35%). The main work areas were: primary care (27%), medical specialties (20%), gynecology and obstetrics (16%), and general surgery (11%). The highest composite PPRs were for: teamwork within units (80%), feedback & communication about error, organizational learning-continuous improvement and supervisor/manager expectations & actions promoting patient safety (78%), and management support for patient safety (75%). The lowest composites were for: frequency of events reported (57%), non-punitive response to errors (53%), communication openness (51%) and staffing (37%). CONCLUSION: Our results suggest that staffing issues should be tackled to provide safe care. Staff avoid to openly report adverse events and/or discuss errors, likely because a poor understanding of the potential of these events for learning and because of fear of blame or punitive actions. Future research should check psychometrics of the Romanian version of the HSOPSC applied to Moldovan staff.

Experimenting the hospital survey on patient safety culture in prevention facilities in Italy: psychometric properties.

OBJECTIVE: The Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture (HSOPS) was designed to assess staff views on patient safety culture in hospital. This study examines psychometrics of the Italian translation of the HSOPS for use in territorial prevention facilities. DESIGN: After minimal adjustments and pre-test of the Italian version, a qualitative cross-sectional study was carried out. SETTING: Departments of Prevention (DPs) of four Local Health Authorities in Northern Italy. PARTICIPANTS: Census of medical and non-medical staff (n. 479). INTERVENTION: Web-based self-administered questionnaire. MAIN OUTCOME MEASURES: Descriptive statistics, internal reliability, Confirmatory Factor Analysis (CFA) and intercorrelations among survey composites. RESULTS: Initial CFA of the 12 patient safety culture composites and 42 items included in the original version of the questionnaire revealed that two dimensions (Staffing and Overall Perception of Patient Safety) and nine individual items did not perform well among Italian territorial Prevention staff. After dropping those composites and items, psychometric properties were acceptable (comparative fit index = 0.94; root mean square error of approximation = 0.04; standardized root mean square residual = 0.04). Internal consistency for each remaining composite met or exceeded the criterion 0.70. Intercorrelations were all statistically significant. CONCLUSIONS: Psychometric analyses provided overall support for 10 of the 12 initial patient safety culture composites and 33 of the 42 initial composite items. Although the original instrument was intended for US Hospitals, the Italian translation of the HSOPS adapted for use in territorial prevention facilities performed adequately in Italian DPs.

Indicators based on registers and administrative data for breast cancer: routine evaluation of oncologic care pathway can be implemented.

RATIONALE, AIMS AND OBJECTIVES: Assuring the best standards of care - in a sustainable way - in chronic diseases as breast cancer is nowadays an important challenge for any health system. The aim of this study was to present the methodology used to define a set of quality indicators, computable from administrative data for the pathway of care of breast cancer, and its application at a population level. METHOD: The cohort of 2007-2009 incident cases of breast cancer was identified through a network of six cancer registers in Northern Italy. Cases of sarcoma and lymphoma, patients with multiple primary cancers and those metastatic at diagnosis were excluded; 9614 women were retained for the analysis. For each indicator, the sub-cohort of women eligible for the diagnostic/therapeutic procedures was identified and calculations were performed through record linkage between the cohort and sources of health information. Data on potential available confounders or prognostic factors were also collected. RESULTS: For a few indicators, such as cyto-histological assessment before surgery (62%) and intensive follow-up (79%), deviation from recommendations was evident. Younger patients (≤50 years) more frequently needed a short term re-intervention, while older patients less frequently underwent reconstructive surgery and received palliative care. Several indicators had a great variability across hospitals. In some cases, this heterogeneity appeared to be related to the hospital size, with high-volume hospitals being more compliant to guidelines. CONCLUSION: It is possible to evaluate the quality of cancer care delivered in clinical practice in recent years, in order to implement interventions aimed to improve adherence to international standards of care.

[A set of indicators to monitor the adherence to the guidelines for the diagnosis and treatment of breast cancer]. / Indicatori per il monitoraggio dei percorsi diagnostico-terapeutici del tumore della mammella.

OBJECTIVES: to present a set of indicators developed from six Local Health Authorities of the Lombardy Region to monitor the diagnostic and therapeutic pathway of breast cancer patients, applied to 2007-2009 incident cases. DESIGN: retrospective cohort study. SETTING AND PARTICIPANTS: all subjects with primary breast cancer, incident in the period 2007-2009, and collected by cancer registries of Milano 1, Bergamo, Cremona, Milano, Milano 2 and Monza-Brianza (5,320,272 inhabitants) were included. MAIN OUTCOME MEASURES: through the use of combined current health databases (health registry, hospitalizations, outpatient, pharmaceutical prescription and specific database for anticancer drugs), for each incident case 34 different indicators have been developed to measure the appropriateness of the procedures provided for diagnosis, treatment (surgical and medical) and follow-up. For each indicator, we analyzed the relationship with age, stage, deprivation index, type of treatment, volume of the specific procedure of the hospital where primary surgery was performed. Estimates were adjusted using multilevel regression models. RESULTS: 12,988 incident cases, without metastatic diseases and other cancers, were included in the cohort: 62% were localized to the breast, 33% to the axillary lymph-nodes, 3% metastatic ab initio, and 2% with unknown stage. Deviations from the expected value of different magnitude depending on the type of indicator were observed: the most important differences were detected for the follow-up indicators. There was, in fact, an excess of several procedures in the first year of follow-up: 75% of the cases performed a dosage of a tumor marker, 67% an ecography or a CT scan or an MR, and 37% a bone scan. On the other hand, the access to neoadjuvant and adjuvant treatments in older women was far below the expected values. CONCLUSIONS: the study presents data derived from a large cohort of population cases; the set of indicators was validated by a board of oncologists. The use of indicators calculated by linking the cancer registries (that provide staging) and administrative databases allows the assessment of compliance to the guidelines for diagnosis and treatment of tumours. This experience shows that it is possible to develop a methodology, shared with clinicians, to define indicators that measure the distance between guidelines and current clinical practice in order to decrease variability, to limit inappropriateness, and to reduce unnecessary diagnostic tests for patients (and, consequently, hospitals organizational overload). In order to be sustainable and equitable, a health care system must be able to ensure implementation of protocols/procedures based exclusively on the best available scientific evidences.

Measurable urinary albumin predicts cardiovascular risk among normoalbuminuric patients with type 2 diabetes.

Micro- or macroalbuminuria is associated with increased cardiovascular risk factors among patients with type 2 diabetes, but whether albuminuria within the normal range predicts long-term cardiovascular risk is unknown. We evaluated the relationships between albuminuria and cardiovascular events in 1208 hypertensive, normoalbuminuric patients with type 2 diabetes from the BErgamo NEphrologic Diabetes Complication Trial (BENEDICT), all of whom received angiotensin-converting enzyme inhibitor (ACEI) therapy at the end of the trial and were followed for a median of 9.2 years. The main outcome was time to the first of fatal or nonfatal myocardial infarction; stroke; coronary, carotid, or peripheral artery revascularization; or hospitalization for heart failure. Overall, 189 (15.6%) of the patients experienced a main outcome event (2.14 events/100 patient-years); 24 events were fatal. Albuminuria independently predicted events (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.08). Second-degree polynomial multivariable analysis showed a continuous nonlinear relationship between albuminuria and events without thresholds. Considering the entire study population, even albuminuria at 1-2 µg/min was significantly associated with increased risk compared with albuminuria <1 µg/min (HR, 1.04; 95% CI, 1.02-1.07). This relationship was similar in the subgroup originally randomly assigned to non-ACEI therapy. Among those originally receiving ACEI therapy, however, the event rate was uniformly low and was not significantly associated with albuminuria. Taken together, among normoalbuminuric patients with type 2 diabetes, any degree of measurable albuminuria bears significant cardiovascular risk. The association with risk is continuous but is lost with early ACEI therapy.

Minimally invasive (encapsulated) follicular carcinoma of the thyroid gland is the low-risk counterpart of widely invasive follicular carcinoma but not of insular carcinoma.

Minimally invasive (encapsulated) follicular carcinoma (MIFC), widely invasive follicular carcinoma (WIFC), and insular carcinoma (IC) are three distinct types of thyroid carcinomas composed of follicular cells, IC representing the poorly differentiated counterpart. Our aim was to test whether there is a time-dependent relationship among these three entities, in particular whether MIFC is the low-risk form of the entire group. We used overall survival analysis and multiple correspondence analysis (MCA), the latter exploring the clinicopathological characteristics at onset (sex, age, TNM/pTNM classification). The study included 18 MIFCs, 29 WIFCs, and 27 ICs. On the basis of both overall survival and MCA, WIFC emerged as the high-risk counterpart of MIFC, occurring in older age, with a larger size, a widespread growth into the thyroid parenchyma, and presenting with distant metastases. In both types of follicular carcinoma distant metastases involved only lung and bone, and there was no tendency for local spread beyond the thyroid capsule or nodal metastases. By contrast, IC confirmed to be a distinct high-risk lesion, showing both follicular and papillary-related biological behavior characteristics.