Determinants of survival in patients with chronic heart failure: a population-based study in Reggio Emilia, Italy.

AIMS: We aim to monitor and improve the quality of the heart failure (HF) integrated assistance model defined by national and regional guidelines and implemented in the province of Reggio Emilia, Italy. Specific aims of the audit were to estimate the prevalence of HF, describe the characteristics of patients with HF and the rate of patients enrolled in the integrated care treated in primary care, and identify socioeconomic and geographic determinants of the 4-year survival of these patients. METHODS AND RESULTS: Retrospective analysis of a cohort of prevalent cases of HF, diagnosed before 31 December 2015 in Reggio Emilia, Italy, alive on 1 January 2016, and residing at the time of diagnosis on the provincial territory. Age and sex-adjusted prevalence of HF by area of residence were calculated according to the standard European population 2013. Patients were followed until death or 31 December 2019, whatever came first. The outcome measure of the study was four-year case fatality. Cox proportional hazards models, adjusted for age, sex, and duration of disease were used to determine the association between socio-geographic factors and death. The 4-year case-fatality rate was 36.7%, and it was the highest in the mountains (50.8%) compared with hills (34.6%), lowland (35.4%) and city (37.7%). The prevalence of HF was the lowest in the mountain [149.9, 95% confidence interval (CI) 112.1-187.7] and the highest in the lowland (340.8, 95% CI 308.7-372.9) and city (308, 95% CI 276.0-321.2). Patients living in the mountains had a lower deprivation index, and fewer hospitalizations prior to official diagnosis, although these characteristics were not statistically significant determinants of HF death in multivariate analysis. Behavioural (smoking and obesity) and socio-geographic characteristics (educational level, deprivation index and area of residence) were not significantly associated with mortality in both univariable and multivariable analysis; however, patients who live in mountains (hazard ratio 1.10, 95% CI 0.73-1.66) or hills (hazard ratio 1.11, 95% CI 0.90-1.37) had a slightly higher risk of death than those living in the city. Only 197 (12.1%) of patients in the cohort were enrolled in the integrated care pathway over the course of 4 years. CONCLUSIONS: Although clinical determinants outweigh the geographic and behavioural disparities in the survival of patients with CHF treated in primary care, effective prevention strategies are needed to address environmental and socio-geographic inequalities in access to primary care and to hasten equitable linkage to integrated care.

Diabetes and COVID-19 testing, positivity, and mortality: A population-wide study in Northern Italy.

AIMS: To assess if patients with type 2 diabetes mellitus (DM2) are: a) at excess risk of undergoing testing, contracting, and dying from SARS-CoV-2 infection compared to the general population; b) whether cardiovascular diseases (CAVDs) contribute to COVID-19-related death; and c) what is the effect of DM2 duration and control on COVID-19-related death. METHODS: This population-based study involved all 449,440 adult residents of the Reggio Emilia province, Italy. DM2 patients were divided in groups by COVID testing, presence of CAVDs and COVID death. Several mediation analyses were performed. RESULTS: Patients with DM2 had an increased likelihood of being tested (Odds ratio, OR 1.27 95 %CI 1.23-1.30), testing positive (OR 1.21 95 %CI 1.16-1.26) and dying from COVID-19 (OR 1.75 95 %CI 1.54-2.00). COVID-19-related death was almost three times higher among obese vs non-obese patients with DM2 (OR 4.3 vs 1.6, respectively). For COVID-19 death, CAVDs mediated a) just 5.1 % of the total effect of DM2, b) 40 % of the effect of DM2 duration, and c) did not mediate the effect of glycemic control. CONCLUSIONS: For COVID-19-related deaths in DM2 patients, the effect is mostly direct, obesity amplifies it, DM2 control and duration are important predictors, while CAVDs only slightly mediates it.

Impact of Insulin Therapies on Cancer Incidence in Type 1 and Type 2 Diabetes: A Population-Based Cohort Study in Reggio Emilia, Italy.

OBJECTIVE: To assess the effect of insulin on cancer incidence in type 1 (T1DM) and type 2 diabetes (T2DM). METHODS: The cohort included all 401,172 resident population aged 20-84 in December 2009 and still alive on December 2011, classified for DM status. Drug exposure was assessed for 2009-2011 and follow up was conducted from 2012 to 2016 through the cancer registry. Incidence rate ratios (IRRs) were computed for all sites and for the most frequent cancer sites. RESULTS: among residents, 21,190 people had diabetes, 2282 of whom were taking insulin; 1689 cancers occurred, 180 among insulin users. The risk for all site was slightly higher in people with T2DM compared to people without DM (IRR 1.21, 95% CI 1.14-1.27), with no excess for T1DM (IRR 0.73, 95% CI 0.45-1.19). The excess in T2DM remained when comparing with diet-only treatment. In T2DM, excess incidence was observed for liver and pancreas and for NETs: 1.76 (95% CI 1.44-2.17) and 1.37 (95% CI 0.99-1.73), respectively. For bladder, there was an excess both in T1DM (IRR 3.00, 95% CI 1.12, 8.02) and in T2DM (IRR1.27, 95% CI 1.07-1.50). CONCLUSIONS: Insulin was associated with a 20% increase in cancer incidence. The risk was higher for liver, pancreatic, bladder and neuroendocrine tumours.

Correction: Determinants of inappropriate setting allocation in the care of patients with type 2 diabetes: A population-based study in Reggio Emilia province.

[This corrects the article DOI: 10.1371/journal.pone.0219965.].

Determinants of inappropriate setting allocation in the care of patients with type 2 diabetes: A population-based study in Reggio Emilia province.

The study aims to describe the distribution of patients with type 2 diabetes (T2D) by care plan and to highlight determinants of underuse and overuse of integrated care (IC). This cross-sectional study included all T2D patients resident in Reggio Emilia on 31/12/2015 based on the population-based diabetes registry. Eligibility for IC requires good glycaemic control, no rapid insulin, no kidney failure and no diabetes complications. We calculated the proportion of IC underuse and overuse and adjusted prevalence estimate using multivariate logistic regression. Determinants were age, sex, citizenship, district of residence and time since diagnosis. Of 29,776 patients, 15,364 (51.6%) were in diabetes clinic plan, 9851 (33.1%) in IC plan and 4561 (15.3%) not in any care plan (i.e., in Other group). There were 10,906 (36.6%) patients eligible for IC, of whom 1000 in Other group. When we adjusted for all covariates and restricted the analysis to patients included in care plans, the proportion of those eligible for IC plan but cared for in diabetes clinic plan (i.e. underuse of IC) was 28% (n = 3028/9906; 95%CI 27-29). Similarly, the proportion of those not eligible for IC but cared for in IC plan (i.e. overuse of IC) was 11% (n = 1720/11,896; 95%CI 10-11).The main determinant of both IC underuse and overuse was the district of residence. Foreign status was associated with underuse (37%; 95%CI 33-43), while old age (≥80 years) with both underuse (36%; 95%CI 0.33-0.38) and overuse (23%; 95%CI 22-25). The criterion for suspension of IC plan most frequently found was renal failure, followed by hospitalization for diabetes-related complications. Patients are more often allocated to more specialized settings than not. Healthcare provider-related factors are the main determinants of inappropriate setting allocation.

Compliance with Tuberculosis Screening in Irregular Immigrants.

Tuberculosis (TB) is a serious public health problem in many regions of the world, especially in the poorest areas. For this reason, screening for active and latent forms must be considered when dealing with high-risk groups such as irregular immigrants in Western countries. We conducted a retrospective cohort study by recruiting subjects aged ≥15 years who underwent a tuberculin skin test at a dedicated National Health Service Centre in a northern Italian province between 1 January 2012 and 31 December 2013. These participants were followed up until 31 December 2016. We aimed at evaluating an experimental protocol for active and latent tuberculosis screening, focusing on patient compliance, feasibility, and capability to detect clinical forms of the disease. We enrolled 368 irregular immigrants, i.e., immigrants not having a valid residence permit and who were therefore not entitled to choose a general practitioner. In total, 90.22% of these completed all the steps for the screening of active TB, while 87.33% also undertook screening for the latent form of the disease. Homelessness, self-reported prostitution, female sex, and employment status adversely affected compliance. Chronic alcohol consumption was associated with increased risk of no beginning or interruption of the procedures. All of the five patients with active TB successfully completed the treatment. Overall, adherence to the screening program was high compared to other studies in immigrants, possibly owing to organizational factors such as the availability of cultural mediators, the network between the different health services, the presence of dedicated nursing staff and a free-of-charge service. In addition, selected vulnerable subgroups should be targeted using tailored screening and follow-up programs.

Effect of different glucose-lowering therapies on cancer incidence in type 2 diabetes: An observational population-based study.

AIM: To assess the effect of metformin on cancer incidence in type 2 diabetes (T2DM), considering possible interactions with other glucose-lowering drugs and diabetes duration. METHODS: Study cohort included diabetes patients aged 20-84 on December 2009, still alive and resident in Reggio Emilia province as of December 2011. Drug exposure was assessed for 2009-2011; subjects taking metformin continuously, with or without other hypoglycaemic drugs, were compared to subjects on diet-only therapy. The cohort was followed up from 2012 to 2014 through the cancer registry. Age- and sex-adjusted incidence rate ratios (IRRs) were computed using Poisson regression models for all sites, lung, breast, liver, colorectal, prostate and pancreatic cancer. RESULTS: The cohort includes 17,026 people with T2DM, 7460 taking metformin. 887 cancers occurred during follow-up, 348 among metformin users. Cancer risk was similar in T2DM patients using metformin and those on diet-only. The risk for prostate (IRR = 0.65; 95%CI:0.36; 1.17), liver (IRR = 0.82; 95%CI:0.36; 1.85) and breast (IRR = 0.77; 95%CI:0.43; 1.40) cancers only was slightly reduced; for lung (IRR = 1.52; 95%CI:0.92; 2.50), pancreas (IRR = 1.51; 95%CI:0.59:3.89) and colon-rectum (IRR = 1.71; 95%CI:0.94; 3.08) the risk was slightly increased. CONCLUSIONS: There is no evidence of antitumor effect of metformin. A possible decrease only for breast, liver and prostate cancer, is compatible with random fluctuations.

Effectiveness of integrated care model for type 2 diabetes: A population-based study in Reggio Emilia (Italy).

AIMS: To compare the effectiveness of integrated care with that of the diabetes clinic care model in terms of mortality and hospitalisation of type 2 diabetes patients with low risk of complications. METHODS: Out of 27234 people with type 2 diabetes residing in the province of Reggio Emilia on 31/12/2011, 3071 were included in this cohort study as eligible for integrated care (i.e., low risk of complications) and cared for with the same care model for at least two years. These patients were followed up from 2012 to 2016, for all-cause and diabetes-related mortality and hospital admissions. We performed a Poisson regression model, using the proportion of eligible patients included in the integrated care model for each general practitioner as an instrumental variable. RESULTS: 1700 patients were cared for by integrated care and 1371 by diabetes clinics. Mortality rate ratios were 0.83 (95%CI 0.60-1.13) and 0.95 (95%CI 0.54-1.70) for all-cause and cardiovascular mortality, respectively, and incidence rate ratios were 0.90 (95%CI 0.76-1.06) and 0.91 (95%CI 0.69-1.20) for all-cause and cardiovascular disease hospitalisation, respectively. CONCLUSION: For low risk patients with type 2 diabetes, the integrated care model involving both general practitioner and diabetes clinic professionals showed similar mortality and hospitalisation as a model with higher use of specialized care in an exclusively diabetes clinic setting.

Diabetes and risk of cancer incidence: results from a population-based cohort study in northern Italy.

BACKGROUND: Aim of this study was to compare cancer incidence in populations with and without diabetes by cancer site. Furthermore, we aimed at comparing excess risk of cancer according to diabetes type, diabetes duration and treatment, the latter as regards Type 2 diabetes. METHODS: By use of the Reggio Emilia diabetes registry we classified the resident population aged 20-84 at December 31st 2009 into two groups: with and without diabetes. By linking with the cancer registry we calculated the 2010-2013 cancer incidence in both groups. The incidence rate ratios (IRR) by cancer site, type of diabetes, diabetes duration, and as concerns Type 2 diabetes, by treatment regimen were computed using Poisson regression model and non-diabetic group as reference. RESULTS: The cohort included 383,799 subjects without diabetes and 23,358 with diabetes. During follow-up, we identified 1464 cancer cases in subjects with diabetes and 9858 in the remaining population. Overall cancer incidence was higher in subjects with diabetes than in those without diabetes (IRR = 1.22, 95%CI 1.15-1.29), with similar results focusing on subjects with at least 2-year diabetes duration. Cancer sites driving overall increased risk were liver, pancreas, Colon rectum, and bladder in both sexes, corpus uteri for females. There was also suggestion of an increased risk for kidney cancer in females and a decreased risk for prostate cancer. Excess risk was found in patients with Type 2 diabetes, more marked among insulin users, especially with combined therapy. We observed an increasing risk for diabetes duration up to 10 years from diagnosis (IRR = 1.44, 95%CI 1.29-1.61) and a subsequent decrease to moderate-higher risk (IRR = 1.15, 95%CI 1.04-1.30). CONCLUSIONS: Our study indicates that the strength of association depends on specific cancer site. Insulin, monotherapy or combined therapy, per se or as an indication of poor blood glucose control, in addition to diabetes duration, may play a role in the association of diabetes and cancer.

Sex Differences in the Effect of Type 2 Diabetes on Major Cardiovascular Diseases: Results from a Population-Based Study in Italy.

The aim of the study is to assess sex difference in association between type 2 diabetes and incidence of major cardiovascular events, that is, myocardial infarction, stroke, and heart failure, using information retrieved by diabetes register. The inhabitants of Reggio Emilia (Italy) aged 30-84 were followed during 2012-2014. Incidence rate ratios and 95% confidence intervals were calculated using multivariate Poisson model. The age- and sex-specific event rates were graphed. Subjects with type 2 diabetes had an excess risk compared to their counterparts without diabetes for all the three major cardiovascular events. The excess risk is similar in women and men for stroke (1.8 times) and heart failure (2.7 times), while for myocardial infarction, the excess risk in women is greater than the one observed in men (IRR 2.58, 95% CI 2.22-3.00 and IRR 1.78, 95% CI 1.60-2.00, resp.; P of interaction < 0.0001). Women had always a lesser risk than men, but in case of myocardial infarction, the women with type 2 diabetes lost part of advantage gained by women free of diabetes (IRR 0.61, 95% CI 0.53-0.72 and IRR 0.36, 95% CI 0.33-0.39, resp.). In women with type 2 diabetes, the risk of major cardiovascular events is anticipated by 20-30 years, while in men it is by 15-20.

Diagnostic values of glycated haemoglobin and diagnosis of diabetes: Results of a cross-sectional survey among general practitioners in the province of Reggio Emilia, Italy.

AIMS: The aim of this study was to investigate whether subjects included in the diabetes register solely because their HbA1c was over the diagnostic threshold received a diagnosis of diabetes from their general practitioner (GP). METHODS: The study included all registered cases in 2009-2010 aged 18 or over that were identified only by the laboratory database because they had one or more HbA1c over the 6.5% threshold and for whom we did not find any information in the search of full electronic clinical records. Multilevel logistic regression was used to examine the influence of GP and patient characteristics. RESULTS: There were 228 participating GPs (76.3% of those invited) and 832 assessed subjects (68.8% of study population). There was a strong clustering among the GPs (residual intraclass correlation = 0.52, 95% CI 0.40-0.64). About one in two (55.5%) subjects with two or more HbA1c > =6.5% has been diagnosed as diabetic and the percentage declined - unless zeroing - in case the abnormal value was only one (28.3%). The likelihood of being labelled 'no diabetes' was greater in subjects aged less than 65 or over 74 with respect to the reference age group (OR 1.89, 95% CI 1.13-3.15; OR 1.55 95% CI 0.94-2.53). The same likelihood consistently decreased when HbA1c test was accompanied by abnormal fasting plasma glucose (FPG) assay (OR 0.20, 95% CI 0.12-0.32). CONCLUSIONS: A permanent exchange of information between the diabetes register and GPs should be maintained to improve the care of patients and the awareness of criteria for diabetes diagnosis among GPs.

Sex differences in cardiovascular mortality in diabetics and nondiabetic subjects: a population-based study (Italy).

The objective of this study is to assess the impact of diabetes on cardiovascular mortality, focusing on sex differences. The inhabitants of Reggio Emilia province on December 31, 2009, aged 20-84 were followed up for three years for mortality. The exposure was determined using Reggio Emilia diabetes register. The age-adjusted death rates were estimated as well as the incidence rate ratios using Poisson regression model. Interaction terms for diabetes and sex were tested by the Wald test. People with diabetes had an excess of mortality, compared with nondiabetic subjects (all cause: IRR = 1.68; 95%CI 1.60-1.78; CVD: IRR = 1.61; 95%CI 1.47-1.76; AMI: IRR = 1.59; 95%CI 1.27-1.99; renal causes: IRR = 1.71; 95%CI 1.22-2.38). The impact of diabetes is greater in females than males for all causes (P = 0.0321) and for CVD, IMA, and renal causes. Further studies are needed to investigate whether the difference in cardiovascular risk profile or in the quality of care delivered justifies the higher excess of mortality in females with diabetes compared to males.

Building a population-based diabetes register: an Italian experience.

AIMS: To describe the methodology used to set up the Reggio Emilia (northern Italy) Diabetes Register. The prevalence estimates on December 31st, 2009 are also provided. METHODS: The Diabetes Register covers all residents in the Reggio Emilia province. The register was created by deterministic linkage of six routinely collected data sources through a definite algorithm able to ascertain cases and to distinguish type of diabetes and model of care: Hospital Discharge, Drug Dispensation, Biochemistry Laboratory, Disease-specific Exemption, Diabetes Outpatient Clinics, and Mortality databases. Using these data, we estimated crude prevalence on December 31st, 2009 by sex, age groups, and type of diabetes. RESULTS: There were 25,425 ascertained prevalent cases on December 31st, 2009. Drug Dispensation and Exemption databases made the greatest contribution to prevalence. Analyzing overlapping sources, more than 80% of cases were reported by at least two sources. Crude prevalence was 4.8% and 5.9% for the whole population and for people aged 18 years and over, respectively. Males accounted for 53.6%. Type 1 diabetes accounted for 3.8% of cases, while people with Type 2 diabetes were the overriding majority (91.2%), and Diabetes Outpatient Clinics treated 75.4% of people with Type 2 diabetes. CONCLUSION: The Register is able to quantify the burden of disease, the first step in planning, implementing, and monitoring appropriate interventions. All data sources contributed to completeness and/or accuracy of the Register. Although all cases are identified by deterministic record linkage, manual revision and General Practitioner involvement are still necessary when information is insufficient or conflicting.

[Tuberculosis risk assessment in Italian healthcare centres]. / La valutazione del rischio tubercolosi nelle strutture sanitarie.

BACKGROUND: Tuberculosis transmission is a significant hazard in healthcare settings. METHODS: Risk factors suggested by CDC guidelines in 1994, which were adopted by the Italian Ministry of Health, were assessed in 29 centres via questionnaires in 2005. RESULTS: Few centers were equipped with negative pressure, respiratory isolation rooms. Half of the centres had high or ongoing risk. CONCLUSIONS: The hazard is underestimated mostly because of a high number of initially undiagnosed TB patients.

[The effect of a strategy to improve adherence of irregular non UE citizens to tuberculosis screening in a clinic of Reggio Emilia]. / L'effetto di una strategia per migliorare la compliance degli immigrati 'irregolari' allo screening per la tubercolosi in un ambulatorio di Reggio Emilia.

UNLABELLED: Latent tubercolar infection in irregular non EU-citizens in Italy is an important issue of public health. Aim of this paper is to describe the effects of a new organization of the Centre for the health of foreign families of Reggio Emilia. METHOD: A dedicated nurse, responsible of patients' screening and follow-up, in strict collaboration with a cultural interpreter were made available. Patients adherence to the screening was measured. RESULTS: On 177 eligible patients, 12 (6.7%) refused the Mantoux text. Over the 165 screened patients, 147 (89%) returned to the clinic after 3-4 days. Only 16 (10.8%) needed a phone reminder. Adherence to the screening improved remarkably compared to the previous year (89% vs 68%). CONCLUSIONS: A dedicated nurse and the improvement of communication may contribute to improve patients compliance.