Cardiovascular risk profiles and 20-year mortality in older people: gender differences in the Pro.V.A. study.

The age- and gender-related cardio-metabolic changes may limit the applicability of guidelines for the prevention of cardiovascular diseases (CVD) in older people. We investigated the association of cardiovascular risk profile with 20-year all-cause and CVD-mortality in older adults, focusing on age- and gender-specific differences. This prospective study involved 2895 community-dwelling individuals aged ≥65 years who participated in the Pro.V.A study. The sum of achieved target levels (smoking, diet, physical activity, body weight, blood pressure, lipids, and diabetes) recommended by the European Society of Cardiology 2016 guidelines was assessed in each participant. From this sum, cardiovascular risk profile was categorised as very high (0-2), high (3), medium (4), low (5), and very low (6-7 target levels achieved). All-cause and CV mortality data over 20 years were obtained from health registers. At Cox regression, lower cardiovascular risk profile was associated with reduced 20-year all-cause mortality in both genders, with stronger results for women (HR = 0.42 [95%CI:0.25-0.69] and HR = 0.61 [95%CI:0.42-0.89] for very low vs. very high cardiovascular risk profile in women and men, respectively). This trend was more marked for CVD mortality. Lower cardiovascular risk profile was associated with reduced all-cause and CVD mortality only in men < 75 years, while the associations persisted in the oldest old women. A lower cardiovascular risk profile, as defined by current guidelines, may reduce all-cause and CVD mortality in older people, with stronger and longer benefits in women. These findings suggest that personalised and life-course approaches considering gender and age differences may improve the delivery of preventive actions in older people. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10433-021-00620-y.

Non-compliance with colonoscopy after a positive faecal immunochemical test doubles the risk of dying from colorectal cancer.

BACKGROUND: The risk of colorectal cancer (CRC) among subjects with a positive faecal immunochemical test (FIT) who do not undergo a colonoscopy is unknown. We estimated whether non-compliance with colonoscopy after a positive FIT is associated with increased CRC incidence and mortality. METHODS: The FIT-based CRC screening programme in the Veneto region (Italy) invited persons aged 50 to 69 years with a positive FIT (>20 µg Hb/g faeces) for diagnostic colonoscopy at an endoscopic referral centre. In this retrospective cohort study, we compared the 10-year cumulative CRC incidence and mortality among FIT positives who completed a diagnostic colonoscopy within the programme (compliers) and those who did not (non-compliers), using the Kaplan-Meier estimator and Cox-Aalen models. RESULTS: Some 88 013 patients who were FIT positive complied with colonoscopy (males: 56.1%; aged 50-59 years: 49.1%) while 23 410 did not (males: 54.6%; aged 50-59 years: 44.9%).The 10-year cumulative incidence of CRC was 44.7 per 1000 (95% CI, 43.1 to 46.3) among colonoscopy compliers and 54.3 per 1000 (95% CI, 49.9 to 58.7) in non-compliers, while the cumulative mortality for CRC was 6.8 per 1000 (95% CI, 5.9 to 7.6) and 16.0 per 1000 (95% CI, 13.1 to 18.9), respectively. The risk of dying of CRC among non-compliers was 103% higher than among compliers (adjusted HR, 2.03; 95% CI, 1.68 to 2.44). CONCLUSION: The excess risk of CRC death among those not completing colonoscopy after a positive faecal occult blood test should prompt screening programmes to adopt effective interventions to increase compliance in this high-risk population.

A direct method for the identification of patterns of care using administrative databases: the case of breast cancer.

OBJECTIVES: To identify and provide lists of procedures and drugs related to diagnosis and treatment of breast cancer. These lists can be used for the estimation of the cost of illness. METHODS: The method consists of identifying lists of procedures/interventions/drugs related to the tumour of interest, drawn by a panel of expert clinicians and oncologists on the basis of clinical guidelines and current practice. The lists are applied to data referring to breast cancer female patients, collected by population-based Cancer Registries and linked at individual level with information on health care treatments. A comparison with lists obtained via the matched control method is implemented. RESULTS: The distribution of administered procedures and drug prescriptions is coherent with the patient clinical pathway: surgery is the main cause of hospitalization in the first year since diagnosis, diagnostic and monitoring interventions are more frequent in the following years (recurrences detection), and at end-of-life (palliative care). Most outpatient services are due to diagnosis and monitoring, one third of services in the first year since diagnosis is radiotherapy and chemotherapy. Drugs prescribed to patients and sold in pharmacy include hormonal drugs as first course treatment and analgesics as palliative care. CONCLUSIONS: This direct method represents a valid alternative to the matched control method in describing patterns of care and costs related to the entire disease pathway. It is particularly suitable in case of cancer sites with complex patterns of care, such as breast cancer. The lists of codes developed here are based on international classification systems and can be easily applicable to other countries.

The Economic Impact of Rectal Cancer: A Population-Based Study in Italy

Costs of cancer care are increasing worldwide, and sustainability of cancer burden is critical. In this study, the economic impact of rectal cancer on the Italian healthcare system, measured as public healthcare expenditure related to investigation and treatment of rectal cancer patients is estimated. A cross-sectional cohort of 9358 rectal cancer patients is linked, on an individual basis, to claims associated to rectal cancer diagnosis and treatments. Costs refer mainly to years 2010-2011 and are estimated by phase of care, as healthcare needs vary along the care pathway: diagnostic procedures are mainly provided in the first year, surveillance procedures are addressed to chronically ill patients, and end-of-life procedures are given in the terminal status. Clinical approaches and corresponding costs are specific by cancer type and vary by phase of care, stage at diagnosis, and age. Surgery is undertaken by the great majority of patients. Thus, hospitalization is the main cost driver. The evidence produced can be used to improve planning and allocation of healthcare resources. In particular, early diagnosis of rectal cancer is a gain in healthcare budget. Policies raising spreading of and adherence to screening plans, above all when addressed to people living in Southern Italy, should be strongly encouraged.

Interval colorectal cancers after negative faecal immunochemical test in a 13-year screening programme.

OBJECTIVE: To assess faecal immunochemical test sensitivity for cancer in a very large population-based cohort followed up for six rounds with biennial faecal immunochemical test repetition. METHODS: This study is based on interval colorectal cancers diagnosed in a cohort of subjects aged 50-69 undergoing repeated faecal immunochemical test screening (six rounds) from 2002 to 2015. Test sensitivity was calculated using both the Proportional Interval Cancer Rate and the Interval Cancer Proportion method. RESULTS: Among 441,647 faecal immunochemical tests (123,347 individuals), 150 interval colorectal cancers were detected after a negative faecal immunochemical test. Interval colorectal cancer incidence rate was 1.87 per 10,000 person-years (95%CI: 1.60-2.20), and it was higher during the second interval year (rate ratio: 1.78; 95%CI: 1.28-2.47), for proximal locations (rate ratio: 3.00; 95%CI: 1.92-4.68), and among 60-71 year old subjects (rate ratio: 2.37; 95%CI: 1.61-3.50). The Proportional Interval Cancer Rate was 13.1%, with an overall faecal immunochemical test sensitivity of 86.9% (95%CI: 84.7-89.0). Sensitivity was lowest at the first round (81.5%; 95%CI: 75.6-86.2), and increased to 91.9% (95%CI: 83.9-96.5) for subsequent rounds. Applying the Interval Cancer Proportion method, sensitivity was 83.9% (95%CI: 81.3-86.2), and it was highest at the first round (89.0%; 95%CI: 85.7-91.6), ranging between 73% and 83.1% at subsequent rounds. CONCLUSIONS: A faecal immunochemical test sensitivity for cancer higher than 80% resulted in a low incidence of interval colorectal cancers, representing an accurate estimate of one of the major limits of screening programmes. Due to intrinsic biases, the Proportional Interval Cancer Rate and the Interval Cancer Proportion methods generated different trends in faecal immunochemical test sensitivity by screening round.

Colonoscopy later than 270 days in a fecal immunochemical test-based population screening program is associated with higher prevalence of colorectal cancer.

BACKGROUND : Colorectal cancer (CRC) screening programs based on fecal immunochemical testing (FIT) generate substantial pressure on colonoscopy capacity in Europe. Thus, a relevant proportion of FIT-positive patients undergo colonoscopy after the recommended 30-day interval, which may be associated with an excess CRC risk. METHODS : In a cohort of 50-69-year-old patients undergoing biennial rounds of FIT (OC-Hemodia latex agglutination test; cutoff 20 µg hemoglobin/g feces) between 2004 and 2017, we assessed the outcome at colonoscopy (low/high risk adenoma/CRC/advanced stage CRC) among FIT-positive patients, according to different time intervals. The association of each outcome with waiting time, and demographic and clinical factors, was analyzed through multivariable analysis. RESULTS : 123 138/154 213 FIT-positive patients (79.8 %) underwent post-FIT colonoscopy. Time to colonoscopy was ≤ 30 days, 31-180 days, and ≥ 181 days in 50 406 (40.9 %), 71 724 (58.3 %), and 1008 (0.8 %) patients, respectively. At colonoscopy, CRC, high risk adenoma, and low risk adenoma were diagnosed in 4813 (3.9 %), 30 500 (24.8 %), and 22 986 (18.7 %) patients, respectively. An increased CRC prevalence at colonoscopy was observed for a time to colonoscopy of ≥ 270 days (odds ratio [OR] 1.75, 95 % confidence interval [CI] 1.15-2.67), whereas it was stable for waiting times of < 180 days. The proportion of advanced CRC also increased after 270 days (OR 2.79, 95 %CI 1.03-7.57). No increase for low or high risk adenomas according to time to colonoscopy was observed. CONCLUSION : In a European FIT-based screening program, post-FIT colonoscopy after 9 months was associated with an increased risk of CRC and CRC progression.

Patterns of care and cost profiles of women with breast cancer in Italy: EPICOST study based on real world data.

OBJECTIVES: To estimate total direct health care costs associated to diagnosis and treatment of women with breast cancer in Italy, and to investigate their distribution by service type according to the disease pathway and patient characteristics. METHODS: Data on patients provided by population-based Cancer Registries are linked at individual level with data on health-care services and corresponding claims from administrative databases. A combination of cross-sectional approach and a threephase of care decomposition model with initial, continuing and final phases-of-care defined according to time occurred since diagnosis and disease outcome is adopted. Direct estimation of cancer-related costs is obtained. RESULTS: Study cohort included 49,272 patients, 15.2% were in the initial phase absorbing 42% of resources, 79.7% in the continuing phase absorbing 44% of resources and 5.1% in the final phase absorbing 14% of resources. Hospitalization was the most important cost driver, accounting for over 55% of the total costs. CONCLUSIONS: This paper represents the first attempt in Italy to estimate the economic burden of cancer at population level taking into account the entire disease pathway and using multiple current health care databases. The evidence produced by the study can be used to better plan resources allocation. The model proposed is replicable to countries with individual health care information on services and claims.

Management and 5-year outcome of patients with coronary artery disease in different periods of stent technology.

BACKGROUND: The availability of bare metal stents (BMS) followed by drug-eluting stents of first- (DES1) and second-generation (DES2) progressively increased the rate of the percutaneous revascularizations [percutaneous coronary intervention (PCI)] with unknown impact on the long-term outcome of real-world patients with established coronary artery disease. We sought to investigate treatments applied in patients with coronary artery disease in BMS, DES1 and DES2 eras and their 5-year outcome. METHODS: A total of 3099 consecutive patients with at least one coronary stenosis more than 50% observed in 2002 (BMS era), 2005 (DES1 era) and 2011(DES2 era) were enrolled at 13 hospitals in Veneto region, Italy. RESULTS: Moving from BMS to DES1 and DES2 eras patients became significantly older, had more comorbidities and received more frequently statins, betablockers, renin-angiotensin modulators and antiplatelets (P < 0.0001 for all). The PCI/conservative therapy ratio increased from 1.9 to 2.2 and 2.3, the PCI/coronary artery by-pass surgery ratio from 3.6 to 4.0 and 5.1. The crude 5-year survival was 84.9, 83.4 and 81.4% (P = 0.20) and survival free of myocardial infarction, stroke or further revascularizations was 62.1, 60.2 and 60.1% (P = 0.68), with cardiovascular mortality accounting for 60.9, 55.6 and 43.4% of deaths. At multivariable analysis cardiovascular mortality was significantly lower in patients enrolled in 2011 vs. 2002 (hazard ratio = 0.712, 95% confidence interval 0.508-0.998, P = 0.048). CONCLUSION: From BMS to DES1 and DES2 eras progressive worsening of patients characteristics, improvement of medical treatment standards and increase in PCI/conservative therapy and PCI/coronary artery by-pass surgery ratios were observed. Five-year outcomes remained similar in the three cohorts, but in the DES2 era cardiovascular mortality was reduced.

Association between acute histopathological changes of rectal walls and late radiation proctitis following radiotherapy for prostate cancer.

PURPOSE: The impact of acute histopathological changes (HC) of the rectum on development of late clinical proctitis (LCP) after external radiotherapy (RT) for prostate cancer is poorly explored and was the primary end point of this prospective study. METHODS: In 70 patients, 15 HC of early rectal biopsies after RT were identified, whereby RT was conventional 2D RT in 41 cases and conformational 3D RT in 29. Associations of HC in anterior and posterior rectal walls (ARW, PRW) with LCP, acute endoscopic (AEP) and acute clinical proctitis (ACP) were statistically evaluated considering as explicative variables the patient general characteristics and the HC. RESULTS: The mean patients' follow-up was 123.5 months (24-209). The median prostatic dose was 72 Gy (2 Gy/fraction). For the 41 and 29 patients the ARW and PRW doses were 64 and 49 Gy vs. 63 and 50 Gy, respectively. The incidence of LCP ≥ grade 2 at 10 years was 12.9%. The univariate (p = 0.02) and Kaplan-Meyer methods (p = 0.007) showed that the gland (or crypts) loss in the ARW was significantly associated with LCP. AEP and ACP occurred in 14.3 and 55.7% of cases. At multivariate level AEP significantly correlated with hemorrhoids (p = 0.014) and neutrophilia in ARW (p = 0.042). CONCLUSIONS: Early after RT, substantial gland loss in ARW is predictive of LCP. To reduce this complication with conventional fractionation, we suggest keeping the mean dose to ARW ≤48-52 Gy.

Effectiveness of a community care management program for multimorbid elderly patients with heart failure in the Veneto Region.

BACKGROUND: The rapidly growing population of elderly subjects with multimorbidity is at risk of receiving fragmented and uncoordinated care, and have frequent hospitalizations and emergency room (ER) visits. AIMS: The study aims to describe the impact of a care management program (CMP) developed in the Veneto region (Northeastern Italy) for patients affected by chronic heart failure (CHF) and multimorbidity. METHODS: The CMP was provided to 330 patients > 65 years suffering from CHF and multimorbidity. They were compared to a propensity score matched reference group who received usual care. The intervention was provided by care manager nurses and General Practitioners working in the community. The quality of care from the patients' perspective was assessed by means of the Patient Assessment of Chronic Illness Care (PACIC). The effectiveness of the CMP has been evaluated comparing time changes in hospital admissions in the medical area and ER visits between the intervention and the reference group. RESULTS: The median PACIC overall score was 4 out of 5. The intervention group showed a reduction over time by 39% in hospitalization rates and by 33% in ER visits. The recourse to hospital care and ER did not change in the reference group. DISCUSSION: The current results indicate that a CMP can reduce Emergency Room visits and hospital admissions for elderly patients with CHF and multimorbidity. CONCLUSIONS: The CMP by emphasizing prevention, self-management, continuity and coordination of care, is beneficial among older community-dwelling multimorbid persons as compared to usual care.

Colorectal cancer screening: The surgery rates they are a-changing. A nationwide study on surgical resections in Italy.

BACKGROUND: Growing evidence suggests that colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) reduces CRC incidence and surgical resection rates. AIMS: To compare trends in surgery for proximal and distal CRC among Italian regions at different stages of screening implementation. METHODS: From the National Hospital Discharge Database we selected hospitalizations with CRC resection of residents aged 50-74 years during 2002-2014, and computed surgery rates for the 8 most populous Italian regions with/without a screening program. RESULTS: In regions with screening, implemented around 2006-2007, the annual percent change (APC) of distal CRC resection was +1.7 (95% confidence interval -1.0, 4.4) during 2002-2007 and -9.1 (-10.6, -7.7) during 2007-2014. No significant change was observed in regions without screening. The APC for proximal colon resection in regions with screening was +5.8 (2.5, 9.0) during 2002-2007 and -4.1 (-5.8, -2.4) during 2007-2014, while in regions without screening surgical rates increased through the whole study period. Compared to 2002, in 2014 distal CRC resection rates were greatly reduced in regions with screening, reaching values similar to proximal CRC resection. CONCLUSION: Following the implementation of screening programs surgery rates steeply decreased, confirming the deep impact of FIT-based screening on the burden of CRC.

Divergent Long-Term Detection Rates of Proximal and Distal Advanced Neoplasia in Fecal Immunochemical Test Screening Programs: A Retrospective Cohort Study.

Background: Short-term studies have reported that the fecal immunochemical test (FIT) is less accurate in detecting proximal than distal colorectal neoplasia. Objective: To assess the long-term detection rates for advanced adenoma and colorectal cancer (CRC), according to anatomical location. Design: Retrospective study. Setting: Population-based, organized screening program in the Veneto region of Italy. Participants: Persons aged 50 to 69 years who completed 6 rounds of FIT screening. Measurements: At each screening round, the detection rates for advanced adenoma and cancer, as well as the proportional interval cancer rate (PICR), were calculated by anatomical location (proximal colon, distal colon, or rectum). Results: Between 2002 and 2014, a total of 123 347 participants had 441 647 FITs. The numbers of advanced adenomas and cancer cases detected, respectively, were 1704 and 200 in the proximal colon, 3703 and 324 in the distal colon, and 1220 and 209 in the rectum. Although the detection rate for proximal colon cancer declined only from the first to the second screening round (0.63 to 0.36 per 1000 screenees), the rate for both distal colon and rectal cancer steadily decreased across 6 rounds (distal colon, 1.65 in the first round to 0.17 in the sixth; rectum, 0.82 in the first round to 0.17 in the sixth). Similar trends were found for advanced adenoma (proximal colon, 5.32 in the first round to 4.22 in the sixth; distal colon, 15.2 in the first round to 5.02 in the sixth). Overall, 150 cases of interval cancer were diagnosed. The PICR was higher in the proximal colon (25.2% [95% CI, 19.9% to 31.5%]) than the distal colon (6.0% [CI, 3.9% to 8.9%]) or rectum (9.9% [CI, 6.9% to 13.7%]). Limitations: Participants with irregular attendance were censored. Those who had a false-positive result on a previous FIT but negative colonoscopy results were included in subsequent rounds. Conclusion: This FIT-based, multiple-round, long-term screening program had a negligible reduction in detection rates for neoplastic lesions in the proximal versus the distal colon after the first round. This was related to a higher PICR in the proximal colon and suboptimal efficacy in preventing the age-related proximal shifting of CRC. Primary Funding Source: None.

Impact of breast cancer screening in a population with high spontaneous coverage with mammography.

OBJECTIVE: The impact of organized screening programs on breast cancer (BC) mortality is unclear in an era of high spontaneous referral of women to mammography. The aim of this study was to analyze if the introduction of mammographic screening programs reduced BC mortality in the Veneto region, Italy, despite already widespread spontaneous access to mammography. METHODS: In Veneto, screening was introduced in different years between 1999 and 2009 across 21 local health units (LHUs), inviting asymptomatic women aged 50-69 years to undergo mammography biennially. We compared BC mortality for the 1995-2014 period of women aged 40-49 and 50-74 years who were resident in LHUs where screening programs started in 2003 (early LHUs) with women resident in LHUs where screening was introduced later (late LHUs). Poisson regression models were applied to incidence-based mortality (IBM), including only deaths from BC arising within the screening period. RESULTS: In the prescreening period and until 2010, BC mortality rates in early and late LHUs were similar in both age groups. In the last study period (2010-2014), we observed a 10% decrease in overall BC mortality in early compared to late LHU, limited to women aged 50-74 years. IBM was reduced by 8% (95% CI 1%-16%) in the overall study period and by 16% (6%-25%) in 2010-2014. CONCLUSIONS: In the Veneto region, screening programs were associated with a significant impact on BC-specific mortality; such effect appeared at least 8 years after screening implementation.

Long-term performance of colorectal cancerscreening programmes based on the faecal immunochemical test.

BACKGROUND: The long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear. METHODS: In a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20 µg haemoglobin/g faeces), we examined: (1) the FIT positivity rate, the CRC and advanced adenoma detection rate and the FIT's positive predictive value (PPV) for advanced neoplasia, at each round of screening and (2) the cumulative CRC and advanced adenoma detection rate after five rounds of FIT. RESULTS: Over 12 years (2002-2014), 123 347 individuals were administered the FIT up to six times, and 781 CRCs and 4713 advanced adenomas were diagnosed. The CRC and advanced adenoma detection rates declined substantially from the first to the third (rate ratio (RR) 0.25, 95% CI 0.20 to 0.32) and second (RR 0.51, 95% CI 0.47 to 0.56) rounds, respectively, and then remained stable. The PPV for advanced neoplasia dropped by 18% in the second round (RR 0.82, 95% CI 0.77 to 0.89), with no further reduction thereafter due to a concomitant decline in the FIT positivity rate (RR first to sixth rounds: 0.56, 95% CI 0.53 to 0.60).The cumulative CRC and advanced adenoma detection rates over five consecutive rounds were 8.5‰ (95% CI 7.8 to 9.2), and 58.9‰ (95% CI 56.9 to 61.0), respectively. CONCLUSIONS: Repeated FIT significantly reduces the burden of colorectal disease while facilitating an efficient use of colonoscopy resources. The cumulative detection rate after five rounds of FIT is similar to primary screening with colonoscopy, supporting the need to account for the cumulative sensitivity of repeated FITs when evaluating the test's efficacy.

Excess mortality in 2015: a time series and cause-of-death analysis in Northern Italy.

AIMS: To investigate the excess mortality registered in the Veneto Region (Northern Italy) in 2015. METHODS: A Seasonal Autoregressive Integrated Moving Average Model was applied to predict overall mortality expected in 2014-2015 based on that observed in 2000-2013. The annual percent change in age-standardized rates (APC) was estimated for specific causes of death in 2007-2015. RESULTS: Compared to 2014, the number of deaths and the overall age-standardized mortality increased in 2015 by 7.8 and 4.5%, respectively. When accounting for time trends, the observed mortality was lower than expected in 2014 (-4.5%) and slightly higher in 2015 (+1.1%). In 2015, mortality increased especially for causes with an already rising trend: neurologic/psychiatric (APC = 1.2; 95% Confidence Interval 0.3-2.0%) and infectious diseases (APC = 5.9; 3.6-8.2%). CONCLUSIONS: Short-term changes and long-term trends in mortality must be interpreted within the frame of a rapid growth in the population of elderly subjects affected by multiple comorbidities.

Contemporary burden of excess cardiovascular mortality on Monday. A retrospective study in the Veneto region of Italy.

BACKGROUND: An increased risk for adverse cardiovascular events on Monday has been consistently reported in the literature. It remains to be assessed if a Monday peak in cardiovascular deaths can still be detected within the contemporary context of decreasing mortality rates from circulatory diseases in developed countries. METHODS: Mortality records were extracted from January 2000 to December 2013 in the Veneto region (Italy). The Monday excess in mortality from cerebrovascular diseases, ischemic heart diseases, and other circulatory diseases was investigated in subjects aged 35-74years by means of Poisson regression models adjusted by age, gender, time trend and seasonality. RESULTS: Among 41,024 deaths from circulatory diseases registered in the study population, mortality rates on Monday were increased by 13% (CI 9-17%) with respect to Sunday and by 6% (CI 4-9%) with respect to the overall daily mean. The Monday peak could be detected in both genders and in all the analyzed disease categories, and was more pronounced in younger age classes and in more recent years. CONCLUSIONS: The persistency of the Monday effect on cardiovascular mortality is confirmed by recent large population-based data. Further research is warranted to investigate causal mechanisms.