Prognostic significance of pathological sub-classification of pT3 rectal cancer.

PURPOSE: Patients with pT3 rectal cancer represent a heterogeneous prognostic group. A more accurate histological sub-classification of pT status has been suggested as an improvement of the TNM staging system. The aim of the study was to evaluate the prognostic implication of a histopathologic sub-classification of pT3 rectal cancer. METHODS: In this retrospective single-center study, pT3 rectal cancer patients who underwent surgery from January 2000 to December 2018 were evaluated. The maximum depth of tumor invasion beyond the muscularis propria was recorded. A ROC curve identified the best prognostic cutoff value to classify patients in two prognostic groups. Survival curves were estimated by the Kaplan-Meier method, and univariate and multivariate analyses with the Cox regression model were used to find independent factors influencing survival. RESULTS: Overall, 203 patients were included. Four millimeters was identified as the best cutoff value: 82 patients showed a depth of invasion < 4 mm (group A) and 121 ≥ 4 mm (group B). Both the estimated 5-year OS and DFS were statistically better in group A than in group B (OS: 83.9% vs 62.2%, p < 0.01; DFS: 78.3% vs 40.6%, p < 0.01). The depth of tumor invasion was an independent risk factor for OS (HR 2.25, 95% CI 1.26-3.99, p = 0.006) and DFS (HR 2.30, 95% CI 1.40-3.78, p = 0.001). CONCLUSION: Our findings suggest that a sub-classification of pT3 rectal cancer, based on the depth of tumor invasion, should be considered to be introduced in the TNM staging system.

[Impact of COVID-19 on the immigrant population in the Veneto Region (Northern Italy), by geographical area of origin]. / Impatto del COVID-19 nella popolazione immigrata in Veneto, per area geografica di provenienza.

OBJECTIVES: to examine the differences in SARS-CoV-2 infection and hospitalization rates among migrant populations in Veneto Region (Northern Italy), according to the geographic area of origin. SETTING AND PARTICIPANTS: all residents in Veneto Region aged <65 years were included in the analyses. All subjects infected by SARS-CoV-2 and hospitalized for COVID-19 were identified by means of the regional biosurveillance system. MAIN OUTCOME MEASURES: age- and gender-specific infection and hospitalization rates were stratified by geographic area of origin and were estimated using the number of incident cases over the resident population in Veneto on 01.01.2021. Incidence rate ratios (IRR) for infection and hospitalization rates were estimated using a Poisson model, adjusted for age and gender, among migrants compared to Italians. RESULTS: compared to Italians, SARS-CoV-2 infection rates were significantly higher among migrants from Central and South America and Central and South Asia, lower among those from North Africa and High-Income Countries (HIC), and were approximately halved for those coming from Other Asian Countries (mainly represented by China). Hospitalization rates were significantly higher for all migrant populations when compared to Italians, with the exception of those coming from HIC. Neither age nor gender seemed to modify the association of the geographic area of origin with SARS-CoV-2 infection and hospitalization rates. IRR for SARS-CoV-2 infection of migrants compared to Italians showed how migrants from Other Asian Countries had the lowest infection rates (-53%), followed by people from HIC (-25%), North Africa (-21%), and Eastern Europe (-10%). Higher infection rates were present for Central and South America and Central and South Asia (+17% and +10, respectively). Hospitalization rates were especially high among migrants from Central and South Asia, Africa, and Central and South America, ranging from 1.84 to 3.14 times those observed for Italians. CONCLUSIONS: a significant heterogeneity in SARS-CoV-2 infection and hospitalization rates of migrant populations from different geographic areas of origin were observed. The significantly lower incidence rate ratio for infections, compared to that observed for hospitalizations, is suggestive of a possible under-diagnosis of SARS-CoV-2 infection among migrant populations. Public health efforts should be targeted at increasing support among migrants to contrast the spread of the pandemic by potentiating vaccination campaigns, contact tracing, and COVID-19 diagnostic tests.

Access to SARS-CoV-2 diagnostic tests: are there barriers for the immigrants in Italy?

OBJECTIVES: to describe the epidemiology of SARS-CoV-2 infection in relation with the use of nasal swabs in the immigrant population in Italy, using data from the COVID-19 national surveillance system and to verify if a difference is present comparing natives and immigrant. DESIGN: descriptive study based on longitudinal health-administrative data. SETTING AND PARTICIPANTS: general population of six Italian Regions (Piedmont, Lombardy, Veneto, Emilia-Romagna, Tuscany, Lazio) covering about 55% of the resident population and 72% of foreigners' population. MAIN OUTCOME MEASURES: regional rates of access to at least a nasal swab, separately by country of origin. RESULTS: across all the periods, a lower rate in the foreigners' group was observed, with the only exception of the period May-June 2021. Considering separately High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs), a higher proportion of nasal swabs performed in people coming from HDC with respect to HMPCs and natives was noticed. This observation is consistent in males and females. CONCLUSIONS: during the first wave of the pandemic, Italians have had a higher proportion of nasal swabs compared to migrants across all Regions. This difference disappeared in the following periods, probably due to a major availability of diagnostic tests.

[SARS-CoV-2 epidemic among Italians e resident immigrant population: differential incidence from an interregional multicentre study]. / L'epidemia di SARS-CoV-2 nella popolazione italiana e straniera: differenze di incidenza che emergono da uno studio multicentrico interregionale.

OBJECTIVES: to describe differences in the incidence of SARS-CoV-2 infections between Italians and foreigners residing in seven Italian Regions during the different phases of the pandemic and by gender. DESIGN: retrospective observational study. SETTING AND PARTICIPANTS: all confirmed SARS-CoV-2 infections from 02.02. 2020 to 16.07.2021 in the seven Regions under study were included. Italian resident population calculated by the National Institute of Statistics as of 01.01.2020 was used to calculate the rates. The considered period is divided into 5 sub-periods (phases). MAIN OUTCOME MEASURES: number of confirmed SARS-CoV-2 infections in the five phases of the pandemic and crude rates by citizenship (Italian vs foreign). Distribution of infections by age group and by week. Crude and age-adjusted incidence rates ratios (IRR) were calculated, by Region, gender, and phase of the pandemic. RESULTS: an epidemic curve delay was observed in foreigners in the first phase of the epidemic, in particular in the northern Regions, the most affected in that phase. The first phase of the epidemic was characterized by a greater proportion of cases occurred in people aged over 60 years than the other phases, both in Italians and in foreigners. The incidence among foreigners is higher during the summer of 2020 (intermediate period: June-September 2020) and during the last period (May-July 2021) in all Regions. The overall figure shows a lower incidence among foreigners than Italians, except for males in Tuscany. CONCLUSIONS: the lower incidence rates among foreigners should be interpreted with caution as the available data suggest that it is at least partly attributable to less access to diagnostic tests. Regional differences found in the study deserve further research together with the effect of gender and country of origin.

[Mortality and impact of COVID-19 by citizenship in seven Italian Regions from the beginning of the pandemic to mid-July 2021]. / Mortalità per COVID-19 nella popolazione immigrata in sette Regioni italiane da inizio pandemia a metà luglio 2021.

OBJECTIVES: to quantify the variability of COVID-19 mortality from the beginning of the pandemic to mid-July 2021, in relation to the immigrant status and by Region and period. DESIGN: observational incidence study. SETTING AND PARTICIPANTS: the study population consists of the residents at the beginning of 2020 in seven Regions (Piedmont, Lombardy, Veneto, Emilia-Romagna, Tuscany, Lazio, Sicily) aged <=74 years. MAIN OUTCOME MEASURES: absolute frequency of deaths occurred in subjects who tested positive for SARS-CoV-2, crude and standardized rates (standard: Italian population at the beginning of 2020), and mortality rates ratios (obtained using Poisson models), by immigrant status and stratified by gender, Region of residence, and period. The study period was divided into 5 subperiods: 22.02.2020-25.05.2020, 26.05.2020-02.10.2020, 03.10.2020-26.02.2021, 27.02.2021-16.07.2021. RESULTS: the study includes more than one half of the Italian population and most of the immigrants residing in the country, who are younger than Italians and experienced fewer COVID-19 deaths. Deaths among those who tested positive varied greatly between Regions and periods; standardized rates showed considerable increases over time among immigrants. In terms of rate ratios, there were excesses among immigrant males in the third period (MRR: 1.46; 95%CI 1.30-1.65) and in the fourth period (MRR: 1.55; 95%CI 1, 34-1.81). Among immigrant females, there is an indication of lower risk in the third period (MRR: 0.79; 95%CI 0.65-0.97) and of greater risk in the fourth period (MRR: 1. 46; 95%CI 1.21-1.77). Finally, the effect is modified by the Region of residence, both in the third and in the fourth period for males and only in the fourth period for females. CONCLUSIONS: the risk of premature mortality due to COVID-19 is linked to immigrant status and with an intensity that varies by gender, Region, and period. More accessible tools for prevention, diagnosis and early healthcare can support immigrant communities in managing the risk factors linked to the spread of infections and, in particular, counteract their evolution into more severe disease outcomes.

Impact of laparoscopic approach on the short-term outcomes of elderly patients with colorectal cancer: a nationwide Italian experience.

INTRODUCTION: The laparoscopic approach is increasingly adopted in colorectal cancer surgery; however, its role in elderly patients is controversial. We sought to examine the relationship between age and short-term outcomes following laparoscopic surgery for colorectal cancer (CRC). METHODS: Data of patients 65 + years old who underwent laparoscopic surgery for CRC between 2002 and 2014 were retrieved from the administrative National Italian Hospital Discharge Dataset. Patients were divided into three age categories (65-74, 75-84, and 85 +). The impact of age on length of stay, 30-day readmission, in-hospital mortality, and postoperative complications was evaluated. RESULTS: During the study period, 47,704 patients underwent laparoscopic surgery for CRC. The median postoperative length of stay was 9 days, and 30-day readmission and in-hospital mortality were 4.4% and 0.9%, respectively. Age was found to be an independent risk factor of prolonged length of stay and increased in-hospital mortality. With respect to patients in 65-74 years age category, patients aged 75-84 years and those aged 85 + years had a higher risk of complications (OR 1.43, 95% CI 1.36-1.50, and OR 2.00, 95% CI 1.83-2.17, respectively). However, no statistically significant association was found between age and anastomotic leakage or surgical site infection (p = 0.29, and p = 0.58, respectively). CONCLUSIONS: In patients with CRC who underwent laparoscopic surgery, age was found to be an independent risk factor for prolonged length of stay, in-hospital mortality, and global postoperative complications. These findings should be considered when planning laparoscopic surgery in elderly patients.

Intensity of integrated cancer palliative care plans and end-of-life acute medical hospitalisation among cancer patient in Northern Italy.

A high hospital utilisation at the end of life (EOL) is an indicator of suboptimal quality of health care. We evaluated the impact of the intensity of different Integrated Cancer Palliative Care (ICPC) plans on EOL acute medical hospitalisation among cancer decedents. Decedents of cancer aged 18-84 years, who were residents in two Italian regions, were investigated through integrated administrative data. Outcomes considered were prolonged hospital stay for medical reasons, 2+ hospitalisations during the last month of life and hospital death. The ICPC plans instituted 90 to 31 days before death represented the main exposure of interest. Other variables considered were gender, age class at death, marital status, recent hospitalisation and primary cancer site. Among 6,698 patients included in ICPC plans, 44.3% presented at least one critical outcome indicator; among these, 76.5% died in hospital, 60.3% had a prolonged (12+ days) medical hospitalisation, 19.1% had 2+ hospitalisations at the EOL. These outcomes showed a strong dose-response effect with the intensity of the ICPC plans, which is already evident at levels of moderate intensity. A well-ICPC approach can be very effective-beginning at low levels of intensity of care-in reducing the percentage of patients spending many days or dying in hospital.

Impact of fecal immunochemical test-based screening programs on proximal and distal colorectal cancer surgery rates: A natural multiple-baseline experiment.

BACKGROUND: Colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) were found to reduce overall CRC surgery rates, but to the authors' knowledge data by subsite are lacking. The objective of the current study was to assess the impact of FIT-based screening on proximal and distal CRC surgical resection rates. METHODS: The Veneto region in Italy can be subdivided into 3 areas with staggered introduction of FIT-based screening programs: early (2002-2004), intermediate (2005-2007), and late (2008-2009) areas. Time series of proximal and distal CRC surgery were investigated in the 3 populations between 2001 and 2012 by Joinpoint regression analysis and segmented Poisson regression models. RESULTS: The impact of screening was similar in the study populations. Rates of distal CRC surgical resection were stable before screening, increased at the time of screening implementation (rate ratio [RR], 1.25; 95% confidence interval [95% CI], 1.14-1.37), and thereafter declined by 10% annually (RR, 0.90; 95% CI, 0.88-0.92). Rates of proximal CRC surgical resection increased by 4% annually before screening (RR, 1.04; 95% CI, 1.03-1.05) but, after a peak at the time of screening initiation, the trend was reversed. The percentage represented by proximal CRC surgery rose from 28% in 2001 to 41% in 2012. CONCLUSIONS: In this natural multiple-baseline experiment, consistent findings across each time series demonstrated that FIT-based screening programs have an impact both on proximal and distal CRC surgery rates. However, underlying preexisting epidemiological trends are leading to a rapidly increasing percentage of proximal CRC.

Mortality from chronic liver diseases in diabetes.

OBJECTIVES: Mortality from chronic liver diseases (CLDs) is increased in diabetes, but little is known about the etiology. The aim of this study was to assess mortality rates from CLD by etiology in known diabetic subjects living in the Veneto Region, Northern Italy. METHODS: A total of 167,621 diabetic subjects, aged 30-89 years (54.6% men), were identified in the year 2007 and their vital status was assessed between 2008 and 2010. Standardized mortality ratios (SMR) with 95% confidence intervals (CIs) were computed with regional mortality rates as reference. The underlying cause of death and all comordidities reported on the certificate were scrutinized in order to identify CLD deaths and their main etiologies. The latter were grouped into the following three categories: (i) virus-related, (ii) alcohol-related, and (iii) non-virus, non-alcohol-related (mainly represented by nonalcoholic fatty liver disease, NAFLD). RESULTS: Analyses were based upon 473,374 person-years of follow-up and 17,134 deaths. We observed an increased risk of dying from CLD in diabetic subjects with an SMR of 2.47 (95% CI=2.19-2.78) in men and 2.70 (2.24-3.23) in women. SMRs were 2.17 (1.90-2.47), 2.25 (1.98-2.54), and 2.86 (2.65-3.08) for virus-related, alcohol-related, and non-virus, non-alcohol-related CLD, respectively. CONCLUSIONS: Diabetic patients have a twofold to threefold higher risk of dying of CLD, mainly associated with a non-virus and non-alcohol-related etiology, which is largely attributable to NAFLD. An early diagnosis and treatment of NAFLD, if any, may have a beneficial clinical impact on the survival of diabetic patients.

Access to SARS-CoV-2 vaccination in immigrants in Italy, by geographical area of origin.

OBJECTIVE: Immigrants are commonly considered disadvantaged and at high risk of not receiving appropriate care, including vaccination. This study aimed to evaluate the access to SARS-CoV-2 vaccination in immigrants, by geographical area of origin, compared with Italian citizens. We also evaluated sex differences in vaccine's coverage by geographical area of origin. METHODS: We performed a retrospective observational study in four Italian regions, including all resident subjects aged 5-69 years, and undergoing first dose SARS-CoV-2 vaccination in the period 28th December 2020- 3rd April 2022. We estimated cumulative coverage percentages, by age class and geographical area. To compare first-dose vaccine coverage by geographical area of origin, we estimated, through a Poisson analysis, Vaccine Coverage Ratios (VCR) with 95 % confidence intervals (95 %CI), adjusting for age and sex. RESULTS: We included 16,294,785 Italian citizens and 2,534,351 immigrants aged 5-69 years and resident in the four regions considered. Regarding the geographical area of origin, 40.7 % of immigrants came from Eastern Europe, 13.5 % from North Africa and 13.1 % from Western Asia. A great variability in the first dose vaccine coverage emerged. We documented substantial heterogeneity in the first-dose vaccine coverage within immigrant's population, expressed with Italy as a reference, ranging from 0,768 (95 %CI: 0,766-0,769) in Eastern Europe countries to 1,013 (95 %CI: 1,009 - 1,018) in Eastern Asia. The chance of being vaccinated was found higher in males compared with females for African countries (VCR 1.07, 95 %CI 1.06-1.08) and Western Asian countries (VCR 1.08, 95 %CI 1.07-1.09). CONCLUSION: We observed substantial heterogeneity in first-dose SARS-CoV-2 vaccination coverage in immigrants, suggesting a different propensity to vaccines according to the geographical area of origin. These data can help define appropriate and tailored strategies in order to improve vaccine coverage in some specific immigrant groups at the local health district level.

Lower urinary tract symptoms in patients with inflammatory bowel diseases: A cross-sectional observational study.

BACKGROUND: Inflammatory Bowel Diseases (IBD), Crohn's Disease (CD), and Ulcerative Colitis (UC) may have extraintestinal manifestations, including disorders of the urinary tract. The prevalence of lower urinary tract symptoms (LUTS) in IBD patients remains unclear. AIMS: Assess the prevalence of LUTS in patients with CD or UC, evaluate the variables implicated in any difference in LUTS prevalence between CD or UC, and assess any relationship between disease activity and LUTS METHODS: LUTS were evaluated in 301 IBD patients through standardised questionnaires: Bristol Female Lower Urinary Tract Symptoms (BFLUTS), NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), and International Prostate Symptom Score (IPSS). IBD activity was determined through the Crohn's Disease Activity Index (CDAI), Partial Mayo Score (PMS), and Total Mayo Score (TMS). RESULTS: BFLUTS total score for females was 6 (3-11). Patients with a higher age at diagnosis had worse filling symptoms (p = 0.049) and a worse quality of life (p = 0.005). In males, 67.1% had mild, 28.5% moderate, and 4.4% severe IPSS symptom grades. The overall NIHCPSI prevalence of chronic prostatitis-like symptoms was 26.8%. The questionnaires revealed some significant differences in the subgroups analysed. CONCLUSION: LUTS should be evaluated in IBD patients by urologic-validated questionnaires for prompt diagnosis and early treatment.

Estimating Overall and Cause-Specific Excess Mortality during the COVID-19 Pandemic: Methodological Approaches Compared.

During the COVID-19 pandemic, excess mortality has been reported worldwide, but its magnitude has varied depending on methodological differences that hinder between-study comparability. Our aim was to estimate variability attributable to different methods, focusing on specific causes of death with different pre-pandemic trends. Monthly mortality figures observed in 2020 in the Veneto Region (Italy) were compared with those forecasted using: (1) 2018-2019 monthly average number of deaths; (2) 2015-2019 monthly average age-standardized mortality rates; (3) Seasonal Autoregressive Integrated Moving Average (SARIMA) models; (4) Generalized Estimating Equations (GEE) models. We analyzed deaths due to all-causes, circulatory diseases, cancer, and neurologic/mental disorders. Excess all-cause mortality estimates in 2020 across the four approaches were: +17.2% (2018-2019 average number of deaths), +9.5% (five-year average age-standardized rates), +15.2% (SARIMA), and +15.7% (GEE). For circulatory diseases (strong pre-pandemic decreasing trend), estimates were +7.1%, -4.4%, +8.4%, and +7.2%, respectively. Cancer mortality showed no relevant variations (ranging from -1.6% to -0.1%), except for the simple comparison of age-standardized mortality rates (-5.5%). The neurologic/mental disorders (with a pre-pandemic growing trend) estimated excess corresponded to +4.0%/+5.1% based on the first two approaches, while no major change could be detected based on the SARIMA and GEE models (-1.3%/+0.3%). The magnitude of excess mortality varied largely based on the methods applied to forecast mortality figures. The comparison with average age-standardized mortality rates in the previous five years diverged from the other approaches due to the lack of control over pre-existing trends. Differences across other methods were more limited, with GEE models probably representing the most versatile option.

Quality of bowel preparation in patients with inflammatory bowel disease undergoing colonoscopy: What factors to consider?

An adequate bowel preparation in patients with inflammatory bowel disease (IBD) is a prerequisite for successful colonoscopy for screening, diagnosis, and surveillance. Several bowel preparation formulations are available, both high- and low-volume based on polyethylene glycol. Generally, low-volume formulations are also based on several compounds such as magnesium citrate preparations with sodium picosulphate, oral sulphate solution, and oral sodium phosphate-based solutions. Targeted studies on the quality of bowel preparation prior to colonoscopy in the IBD population are still required, with current evidence from existing studies being inconclusive. New frontiers are also moving towards the use of alternatives to anterograde ones, using preparations based on retrograde colonic lavage.

Gender Related Differences in Gastrointestinal Bleeding With Oral Anticoagulation in Atrial Fibrillation.

Background: DOACs are characterized by a higher incidence of gastrointestinal bleeding and this may be different among males and females. Female patients were underrepresented in the DOAC pivotal trials. We aimed to assess real-world differences in gastrointestinal bleeding with oral anticoagulants (DOACs and VKAs) among males and females with atrial fibrillation. Methods: We performed a population-based retrospective analysis on linked administrative claims. Atrial fibrillation patients of 65 years and above were considered. Bleeding risk factors were assessed through HASBED and previous history of gastrointestinal disease. A time-to-event analysis compared gastrointestinal bleeding between males and females. Results: The overall cohort consisted of 15338 (55% female) DOAC and 44542 (50% female) VKA users. Most of the patients showed HASBED ≥2. Incidence rate of GI bleeding was higher in females as compared to males among DOAC users (0.90% vs 0.59%), and significant gender difference in GI bleeding was found, after adjustment, in the Cox regression analysis (HR 1.48, 95%CI 1.02-2.16). In the VKA group, no significant difference among genders was found in the time-to-event analysis. Conclusions: Our data suggest that female patients treated with DOACs have a higher risk of GI bleeding versus male patients; this difference is not observed in VKA patients.

Congestive heart failure and comorbidity as determinants of colorectal cancer perioperative outcomes.

There has been an increase in surgical interventions in frailer elderly with concomitant chronic diseases. The purpose of this paper was to evaluate the impact of aging and comorbidities on outcomes in patients who underwent surgery for the treatment of colorectal cancer (CRC) in Veneto Region (Northeastern Italy). This is a retrospective cohort study in patients ≥ 40 years who underwent elective or urgent CRC surgical resection between January 2013 and December 2015. Independent variables included: age, sex, and comorbidities. We analyzed variables associated with the surgical procedure, such as stoma creation, hospitalization during the year before the index surgery, the surgical approach used, the American Society of Anesthesiologists (ASA) score, and the Charlson Comorbidity Index score. Eight thousand four hundred and forty-seven patients with CRC underwent surgical resection. Patient age affected both pre- and post-resection LOS as well as the overall survival (OS); however, it did not affect the 30-day readmission and reoperation rates. Multivariate analysis showed that age represented a risk factor for longer preoperative and postoperative LOS as well as for 30-day and 365-day mortality, but it was not associated with an increased risk of 30-day reoperation and 30-day readmission. Chronic Heart Failure increased the 30-day mortality risk by four times, the preoperative LOS by 51%, and the postoperative LOS by 33%. Chronic renal failure was associated with a 74% higher 30-day readmission rate. Advanced age and comorbidities require a careful preoperative evaluation and appropriate perioperative management to improve surgical outcomes in older patients undergoing elective or urgent CRC resection.

Reduction in all-cause mortality in COVID-19 patients on chronic oral anticoagulation: A population-based propensity score matched study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) global pandemic has strikingly high mortality rate with hypercoagulability state being part of the imputed mechanisms. We aimed to compare the rates of in hospital mortality in propensity score matched cohorts of COVID-19 patients in chronic anticoagulation versus those that were not. METHODS: In this population-based study in the Veneto Region, we retrospectively reviewed all patients aged 65 years or older, with a laboratory-confirmed COVID-19 diagnosis. We compared, after propensity score matching, those who received chronic anticoagulation for atrial fibrillation with those who did not. RESULTS: Overall, 4697 COVID-19 patients fulfilled inclusion criteria, and the propensity score matching yielded 559 patients per arm. All-cause mortality rate ratio was significantly higher among non-anticoagulated patients (32.2% vs 26.5%, p = 0.036). On time to event analysis, all-cause mortality was found lower among anticoagulated patients, although the estimate was not statistically significant. (HR 0.81, 95%CI 0.65-1.01, p = 0.054). CONCLUSION: Among elderly patients with COVID-19, those on chronic oral anticoagulant treatment for atrial fibrillation seem to be at lower risk of all-cause mortality compared to their propensity score matched non-anticoagulated counterpart. This finding needs to be confirmed in further studies.

Death rates and causes in anticoagulated atrial fibrillation patients: a population-based study.

AIMS: To compare mortality between anticoagulated atrial fibrillation patients and general population and among anticoagulation specific categories [direct oral anticoagulants (DOACs) vs. vitamin K antagonists(VKA)]. METHODS: This was a population-based study including all residents in the Veneto Region aged 18 years or older. Administrative claims from July 2013 to September 2017 were used to identify anticoagulation-naïve atrial fibrillation patients. Propensity score matching was employed to compare patients on new and old anticoagulants. RESULTS: Overall, 17 225 patients on direct anticoagulants were 1 : 1 matched to patients on VKA (49% males, median age 77 years). Mortality was higher with respect to the general population by 22 and 39% among patients on direct anticoagulants and VKA, respectively. Mortality from intracranial hemorrhage in the direct anticoagulant group was similar to that in the general population [standardized mortality ratio: 1.06, 95% confidence intervals (CI) 0.76-1.48], whereas it almost doubled in VKA group (1.92, 95% CI 1.49-2.46). When directly compared with the VKA cohort, the risk of death from intracranial hemorrhage halved with DOACs (hazard ratio 0.56, 95% CI 0.37-0.84). CONCLUSION: The mortality rate of anticoagulated atrial fibrillation patients is increased with respect to the general population, particularly among patients treated with VKAs. The mortality rate for intracranial bleeding with DOACs is similar to that observed in the general population.

Tracing day-zero and forecasting the COVID-19 outbreak in Lombardy, Italy: A compartmental modelling and numerical optimization approach.

INTRODUCTION: Italy became the second epicenter of the novel coronavirus disease 2019 (COVID-19) pandemic after China, surpassing by far China's death toll. The disease swept through Lombardy, which remained in lockdown for about two months, starting from the 8th of March. As of that day, the isolation measures taken in Lombardy were extended to the entire country. Here, assuming that effectively there was one case "zero" that introduced the virus to the region, we provide estimates for: (a) the day-zero of the outbreak in Lombardy, Italy; (b) the actual number of asymptomatic infected cases in the total population until March 8; (c) the basic (R0)and the effective reproduction number (Re) based on the estimation of the actual number of infected cases. To demonstrate the efficiency of the model and approach, we also provide a tentative forecast two months ahead of time, i.e. until May 4, the date on which relaxation of the measures commenced, on the basis of the COVID-19 Community Mobility Reports released by Google on March 29. METHODS: To deal with the uncertainty in the number of the actual asymptomatic infected cases in the total population Volpert et al. (2020), we address a modified compartmental Susceptible/ Exposed/ Infectious Asymptomatic/ Infected Symptomatic/ Recovered/ Dead (SEIIRD) model with two compartments of infectious persons: one modelling the cases in the population that are asymptomatic or experience very mild symptoms and another modelling the infected cases with mild to severe symptoms. The parameters of the model corresponding to the recovery period, the time from the onset of symptoms to death and the time from exposure to the time that an individual starts to be infectious, have been set as reported from clinical studies on COVID-19. For the estimation of the day-zero of the outbreak in Lombardy, as well as of the "effective" per-day transmission rate for which no clinical data are available, we have used the proposed SEIIRD simulator to fit the numbers of new daily cases from February 21 to the 8th of March. This was accomplished by solving a mixed-integer optimization problem. Based on the computed parameters, we also provide an estimation of the basic reproduction number R0 and the evolution of the effective reproduction number Re. To examine the efficiency of the model and approach, we ran the simulator to "forecast" the epidemic two months ahead of time, i.e. from March 8 to May 4. For this purpose, we considered the reduction in mobility in Lombardy as released on March 29 by Google COVID-19 Community Mobility Reports, and the effects of social distancing and of the very strict measures taken by the government on March 20 and March 21, 2020. RESULTS: Based on the proposed methodological procedure, we estimated that the expected day-zero was January 14 (min-max rage: January 5 to January 23, interquartile range: January 11 to January 18). The actual cumulative number of asymptomatic infected cases in the total population in Lombardy on March 8 was of the order of 15 times the confirmed cumulative number of infected cases, while the expected value of the basic reproduction number R0 was found to be 4.53 (min-max range: 4.40- 4.65). On May 4, the date on which relaxation of the measures commenced the effective reproduction number was found to be 0.987 (interquartiles: 0.857, 1.133). The model approximated adequately two months ahead of time the evolution of reported cases of infected until May 4, the day on which the phase I of the relaxation of measures was implemented over all of Italy. Furthermore the model predicted that until May 4, around 20% of the population in Lombardy has recovered (interquartile range: ∼10% to ∼30%).

Real-world persistence with direct oral anticoagulants (DOACs) in naïve patients with non-valvular atrial fibrillation.

BACKGROUND: Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications. METHODS: We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy, including any therapeutic switching among DOACs. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression. RESULTS: Naïve patients initiating direct oral anticoagulants for stroke prevention in NVAF identified in a 4.25-year period are 17,920. After one year, the persistence to the DOACs is 72.9%. Approximately 9.8% of the discontinuations are due to switch to vitamin k antagonists (VKAs). On multivariate analysis, factors negatively affecting persistence were female gender, age <65 years, renal disease and history of bleeding. On the other hand, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction. CONCLUSION: In this study of real world data, one out four naive patients stopped treatment with DOACs within 12 months. Some characteristics may identify patients with poor persistence.

Topographic and Biomechanical Changes after Application of Corneal Cross-Linking in Recurrent Keratoconus.

Background: Recurrent keratoconus (RKC) develops as a progressive thinning of the peripheral and the inferior cornea after keratoplasty, in both graft and host, causing secondary astigmatism, refractive instability, and reduced visual acuity. We evaluated the effectiveness of corneal cross-linking (CXL) in patients diagnosed with RKC. Methods: Accelerated-CXL via the epi-off technique was performed in15 patients (18 eyes) diagnosed with RKC. Topographic and biomechanical changes were assessed at 12 months. Results: Differences in maximum keratometry, thinnest corneal thickness, and biomechanical parameters (deformation amplituderatio, inverse concave radius, applanation 1 velocity, and applanation 2 velocity, stiffness A1) versus baseline were statistically significant (p < 0.05).Best corrected visual acuity was improved in 13 eyes and unchanged in 4;manifest refractive spherical equivalent was reduced in 13 eyes, increased in 3,and unchanged in 1 eye; topographic astigmatism was reduced in 9 eyes, remained stable in 1 eye, and increased in 7 eyes. Conclusions: Improved topographic and biomechanic indexes at 1 year after CXL suggest it's potential as first-line therapy for RKC, as it is for KC.