Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register.

INTRODUCTION: Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked. This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register. METHODS: The Register collects, through a standardized Web-based Application, unique patients. Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated. RESULTS: The Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients. The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were ≥ 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2). Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months. CONCLUSIONS: Data from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications.

Cancer Incidence and Mortality According to Pre-Existing Heart Failure in a Community-Based Cohort.

Background: Studies assessing whether heart failure (HF) is associated with cancer and cancer-related mortality have yielded conflicting results. Objectives: This study assessed cancer incidence and mortality according to pre-existing HF in a community-based cohort. Methods: Among individuals ≥50 years of age from the Puglia region in Italy with administrative health data from 2002 to 2018, no cancer within 3 years before the baseline evaluation, and ≥5-year follow-up, the study matched 104,020 subjects with HF at baseline with 104,020 control subjects according to age, sex, drug-derived complexity index, Charlson comorbidity index, and follow-up duration. Cancer incidence and mortality were defined based on International Classification of Diseases-Ninth Revision codes in hospitalization records or death certificates. Results: The incidence rate of cancer in HF patients and control subjects was 21.36 (95% CI: 20.98-21.74) and 12.42 (95% CI: 12.14-12.72) per 1000 person-years, respectively, with the HR being 1.76 (95% CI: 1.71-1.81). Cancer mortality was also higher in HF patients than control subjects (HR: 4.11; 95% CI: 3.86-4.38), especially in those <70 years of age (HR: 7.54; 95% CI: 6.33-8.98 vs HR: 3.80; 95% CI: 3.44-4.19 for 70-79 years of age; and HR: 3.10; 95% CI: 2.81-3.43 for ≥80 years of age). The association between HF and cancer mortality was confirmed in a competing risk analysis (subdistribution HR: 3.48; 95% CI: 3.27-3.72). The HF-related excess risk applied to the majority of cancer types. Among HF patients, prescription of high-dose loop diuretic was associated with higher cancer incidence (HR: 1.11; 95% CI: 1.03-1.21) and mortality (HR: 1.35; 95% CI: 1.19-1.53). Conclusions: HF is associated with an increased risk of cancer and cancer-related mortality, which may be heightened in decompensated states.

Insulin treatment in patients with diabetes mellitus and heart failure in the era of new antidiabetic medications.

BACKGROUND: Coexistent heart failure (HF) and diabetes mellitus (DM) are associated with marked morbidity and mortality. Optimizing treatment strategies can reduce the number and severity of events. Insulin is frequently used in these patients, but its benefit/risk ratio is still not clear, particularly since new antidiabetic drugs that reduce major adverse cardiac events (MACEs) and renal failure have recently come into use. Our aim is to compare the clinical effects of insulin in a real-world setting of first-time users, with sodium-glucose cotransporter-2 inhibitor (SGLT-2i), glucagon-like peptide-1 receptor agonist (GLP-1RA) and the other antihyperglycemic agents (other-AHAs). METHODS: We used the administrative databases of two Italian regions, during the years 2010-2018. Outcomes in whole and propensity-matched cohorts were examined using Cox models. A meta-analysis was also conducted combining the data from both regions. RESULTS: We identified 34 376 individuals ≥50 years old with DM and HF; 42.0% were aged >80 years and 46.7% were women. SGLT-2i and GLP-1RA significantly reduced MACE compared with insulin and particularly death from any cause (SGLT-2i, hazard ratio (95% CI) 0.29 (0.23 to 0.36); GLP-1RA, 0.482 (0.51 to 0.42)) and first hospitalization for HF (0.57 (0.40 to 0.81) and 0.67 (0.59 to 0.76)). CONCLUSIONS: In patients with DM and HF, SGLT-2i and GLP-1RA significantly reduced MACE compared with insulin, and particularly any cause of death and first hospitalization for HF. These groups of medications had high safety profiles compared with other-AHAs and particularly with insulin. The inadequate optimization of HF and DM cotreatment in the insulin cohort is noteworthy.

Stratification of the risk of developing severe or lethal Covid-19 using a new score from a large Italian population: a population-based cohort study.

OBJECTIVES: To develop a population-based risk stratification model (COVID-19 Vulnerability Score) for predicting severe/fatal clinical manifestations of SARS-CoV-2 infection, using the multiple source information provided by the healthcare utilisation databases of the Italian National Health Service. DESIGN: Retrospective observational cohort study. SETTING: Population-based study using the healthcare utilisation database from five Italian regions. PARTICIPANTS: Beneficiaries of the National Health Service, aged 18-79 years, who had the residentship in the five participating regions. Residents in a nursing home were not included. The model was built from the 7 655 502 residents of Lombardy region. MAIN OUTCOME MEASURE: The score included gender, age and 29 conditions/diseases selected from a list of 61 conditions which independently predicted the primary outcome, that is, severe (intensive care unit admission) or fatal manifestation of COVID-19 experienced during the first epidemic wave (until June 2020). The score performance was validated by applying the model to several validation sets, that is, Lombardy population (second epidemic wave), and the other four Italian regions (entire 2020) for a total of about 15.4 million individuals and 7031 outcomes. Predictive performance was assessed by discrimination (areas under the receiver operating characteristic curve) and calibration (plot of observed vs predicted outcomes). RESULTS: We observed a clear positive trend towards increasing outcome incidence as the score increased. The areas under the receiver operating characteristic curve of the COVID-19 Vulnerability Score ranged from 0.85 to 0.88, which compared favourably with the areas of generic scores such as the Charlson Comorbidity Score (0.60). A remarkable performance of the score on the calibration of observed and predicted outcome probability was also observed. CONCLUSIONS: A score based on data used for public health management accurately predicted the occurrence of severe/fatal manifestations of COVID-19. Use of this score may help health decision-makers to more accurately identify high-risk citizens who need early preventive or treatment interventions.

Lower risk of death and cardiovascular events in patients with diabetes initiating glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors: A real-world study in two Italian cohorts.

AIM: To examine the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with other antihyperglycaemic agents (AHAs) in large and unselected populations of the Lombardy and Apulia regions in Italy. MATERIALS AND METHODS: An observational cohort study of first-time users of GLP-1RAs, SGLT2 inhibitors or other AHAs was conducted from 2010 to 2018. Death and cardiovascular (CV) events were evaluated using conditional Cox models in propensity-score-matched populations. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each region and in a meta-analysis for pooled risks. RESULTS: After propensity-score matching, the Lombardy cohort included 18 716 and 11 683 patients and the Apulia cohort 9772 and 6046 patients for the GLP-1RA and SGLT2 inhibitor groups, respectively. Use of GLP-1RAs was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischaemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy), peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia), and lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared with other AHAs, SGLT2 inhibitor use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy; HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy; HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1RAs (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency. CONCLUSION: Our findings from real-world practice confirm the favourable effect of GLP-1RAs and SGLT2 inhibitors on death and CV outcomes across both regions consistently. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond those with CV disease.

Cardiovascular mortality and morbidity burden in successive and age pre-stratified case-control cohorts of breast cancer women. A population-based study.

AIMS: To assess the existence, components and clinical relevance of cardiac causes of death and cardiovascular (CV) hospitalizations in a population-wide database of patients with breast cancer (BC). METHODS AND RESULTS: A population-wide database of the Puglia Region, Italy was analyzed, with a prospective comparative design. Three successive closely matched case/control cohorts representing current care in the period 2007-2014 were also stratified according to age to focus specifically on the potential interaction of treatment-related cardiac toxicity and the expected different baseline CV risk profiles. RESULTS: At 3-year follow-up, in the successive cohorts the incidence of BC-related (7.7, 7.0, 6.5%) and cardiac causes of death, specifically attributed to heart failure (HF, 1.3, 0.5, 0.5%), decreased. Significant mortality hazard ratio (HR) for HF was found in the total population (1.47, 95% CI 1.14-1.90), in particular in the 2007-2009 cohort (1.71, 95% CI 1.19-2.46) and in the 50-69 age group (7.96, 95% CI 2.81-22.55). Results at 5 years confirm the mortality findings, and a significant HR for hospitalizations for HF, non-atrial arrhythmias and ischemic heart disease in the younger than 50 subpopulation pointed to a late expression of toxicity in the youngest BC population. CONCLUSIONS: The incidence of CV causes of death 3 and 5 years after BC diagnosis was very low, even if an excess in risk of death for HF as compared with the control cohort was observed. While younger patients seems to tolerate BC and BC therapy better in the short term, HF mortality and morbidity resulted significantly increased at 5-year follow-up. As the risk for hospitalization for CV reasons increased at 5-year follow-up in particular in women aged less than 50 years, CV monitoring in this subgroup of patients seems mandatory.

The Drug Derived Complexity Index (DDCI) Predicts Mortality, Unplanned Hospitalization and Hospital Readmissions at the Population Level.

OBJECTIVE: to develop and validate the Drug Derived Complexity Index (DDCI), a predictive model derived from drug prescriptions able to stratify the general population according to the risk of death, unplanned hospital admission, and readmission, and to compare the new predictive index with the Charlson Comorbidity Index (CCI). DESIGN: Population-based cohort study, using a record-linkage analysis of prescription databases, hospital discharge records, and the civil registry. The predictive model was developed based on prescription patterns indicative of chronic diseases, using a random sample of 50% of the population. Multivariate Cox proportional hazards regression was used to assess weights of different prescription patterns and drug classes. The predictive properties of the DDCI were confirmed in the validation cohort, represented by the other half of the population. The performance of DDCI was compared to the CCI in terms of calibration, discrimination and reclassification. SETTING: 6 local health authorities with 2.0 million citizens aged 40 years or above. RESULTS: One year and overall mortality rates, unplanned hospitalization rates and hospital readmission rates progressively increased with increasing DDCI score. In the overall population, the model including age, gender and DDCI showed a high performance. DDCI predicted 1-year mortality, overall mortality and unplanned hospitalization with an accuracy of 0.851, 0.835, and 0.584, respectively. If compared to CCI, DDCI showed discrimination and reclassification properties very similar to the CCI, and improved prediction when used in combination with the CCI. CONCLUSIONS AND RELEVANCE: DDCI is a reliable prognostic index, able to stratify the entire population into homogeneous risk groups. DDCI can represent an useful tool for risk-adjustment, policy planning, and the identification of patients needing a focused approach in everyday practice.

The long-term effects of stillbirth on women with and without gestational diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: The aim of this study was to estimate the incidence of type 2 diabetes (primary objective) and hospitalisation for cardiovascular events (secondary objective) in women with previous gestational diabetes mellitus (GDM) and in those with normal glucose tolerance (NGT) in pregnancy, and to evaluate the role of stillbirth in differentiating the risks. METHODS: This was a population-based cohort study using administrative data and involving 12 local health authorities. Women with GDM (n = 3,851) during the index period from 2002 to 2010 were propensity matched with women with NGT (n = 11,553). Information was collected on type 2 diabetes development and hospitalisation for cardiovascular events. RESULTS: During a median follow-up of 5.4 years, the incidence rate per 1,000 person-years of type 2 diabetes was 2.1 (95% CI 1.8, 2.5) in women without GDM and 54.0 (95% CI 50.2, 58.0) among women with GDM and pregnancy at term (incidence rate ratio [IRR] 26.9; 95% CI 22.1, 32.7 compared with NGT and pregnancy at term). A history of stillbirth increased the risk of type 2 diabetes development by about twofold, irrespective of GDM status. No significant interaction between stillbirth and GDM on type 2 diabetes risk was found. GDM was associated with a significantly higher risk of cardiovascular events compared with NGT (IRR 2.4; 95% CI 1.5, 3.8). CONCLUSIONS/INTERPRETATION: Pregnancy complicated by GDM and ending in stillbirth represents an important contributory factor in determining type 2 diabetes development. Women with GDM are at a high risk of future cardiovascular events. Women with pregnancy complicated by GDM and stillbirth deserve careful follow-up.

Exploratory analysis on the use of statins with or without n-3 PUFA and major events in patients discharged for acute myocardial infarction: an observational retrospective study.

BACKGROUND: Combined treatment (CT) with statins and polyunsaturated fatty acids (n-3 PUFA) resulted in a reduction of death and major cardiovascular events when administered after a myocardial infarction (MI). However, recent data suggests that CT may be ineffective because patients are currently treated aggressively and the risk may not be further decreased. We aimed to study the prevalence and the results on major outcomes with CT among patients discharged with a MI in Italy. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective cohort study that used linked hospital discharge, prescription databases and vital statistics containing information on 14,704 patients who were discharged for MI between 1/2003 and 12/2003 in 117 hospitals in Italy. All analyses were time-dependent and adjusted for major confounders. Sensibility and paired matched analysis were conducted to further verify main results. A total of 11,532 (78.4%) filled a prescription for a statin. Of these, 4302 (37.3%) were on CT. There were 45,528 patients/years of follow-up. As compared with statins alone, CT was associated with an adjusted higher survival rate (HR = 0.59 [0.52-0.66], p<0.001), survival free of atrial fibrillation (HR = 0.78 [0.71-0.86], p<0.001) and survival free of new heart failure development (HR = 0.81 [0.74-0.88], p<0.001), but not with re-infarction (HR = 0.94 [0.86-1.02], p<0.127). Clinically this means that between 2 to 3 fewer events for each 100 patients/year were obtained in the group under CT. CONCLUSIONS/SIGNIFICANCE: Among a representative sample of patients discharged with MI in Italy, we observed clinically significant synergism between the effects of statins and n-3 PUFA for most cardiovascular outcomes, including all cause mortality.

Previous prescription of ß-blockers is associated with reduced mortality among patients hospitalized in intensive care units for sepsis.

OBJECTIVES: Results from basic science and narrative reviews suggest a potential role of ß-blockers in patients with sepsis. Although the hypothesis is physiologically appealing, it could be seen as clinically counterintuitive. We sought to assess whether patients previously prescribed chronic ß-blocker therapy had a different mortality rate than those who did not receive treatment. SETTING: Record linkage of administrative databases of Italian patients hospitalized for sepsis during years 2003-2008 were identified and followed up for all-cause mortality at 28 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 9,465 patients aged≥40 yrs who were hospitalized in critical care units for sepsis. Of these, 1,061 patients were on chronic prescription with ß-blockers and 8404 were not previously treated. Despite a higher risk profile, patients previously prescribed with ß-blockers had lower mortality at 28 days (188/1061 [17.7%]) than those previously untreated (1857/8404 [22.1%]) (odds ratio 0.78; 95% confidence interval 0.66-0.93; p=.005 for unadjusted analysis, and odds ratio 0.81; 95% confidence interval 0.68-0.97; p=.025 for adjusted analyses). Sensitivity and pair-matched results confirm the primary findings. CONCLUSIONS: As far as we are aware, this pharmacoepidemiologic assessment is the largest to examine the potential association of previous ß-blocker prescription and mortality in patients with sepsis. Chronic prescription of ß-blockers may confer a survival advantage to patients who subsequently develop sepsis with organ dysfunction and who are admitted to an intensive care unit. Prospective randomized clinical trials should formally test this hypothesis.

Association of aspirin use with major bleeding in patients with and without diabetes.

CONTEXT: The benefit of aspirin for the primary prevention of cardiovascular events is relatively small for individuals with and without diabetes. This benefit could easily be offset by the risk of hemorrhage. OBJECTIVE: To determine the incidence of major gastrointestinal and intracranial bleeding episodes in individuals with and without diabetes taking aspirin. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study, using administrative data from 4.1 million citizens in 12 local health authorities in Puglia, Italy. Individuals with new prescriptions for low-dose aspirin (≤300 mg) were identified during the index period from January 1, 2003, to December 31, 2008, and were propensity-matched on a 1-to-1 basis with individuals who did not take aspirin during this period. MAIN OUTCOME MEASURES: Hospitalizations for major gastrointestinal bleeding or cerebral hemorrhage occurring after the initiation of antiplatelet therapy. RESULTS: There were 186,425 individuals being treated with low-dose aspirin and 186,425 matched controls without aspirin use. During a median follow-up of 5.7 years, the overall incidence rate of hemorrhagic events was 5.58 (95% CI, 5.39-5.77) per 1000 person-years for aspirin users and 3.60 (95% CI, 3.48-3.72) per 1000 person-years for those without aspirin use (incidence rate ratio [IRR], 1.55; 95% CI, 1.48-1.63). The use of aspirin was associated with a greater risk of major bleeding in most of the subgroups investigated but not in individuals with diabetes (IRR, 1.09; 95% CI, 0.97-1.22). Irrespective of aspirin use, diabetes was independently associated with an increased risk of major bleeding episodes (IRR, 1.36; 95% CI, 1.28-1.44). CONCLUSIONS: In a population-based cohort, aspirin use was significantly associated with an increased risk of major gastrointestinal or cerebral bleeding episodes. Patients with diabetes had a high rate of bleeding that was not independently associated with aspirin use.

Hospital discharge database as a tool to monitor incidence, survival and burden of cancer in adolescents and young adults.

AIMS AND BACKGROUND: Cancer in young patients (15-39 years) is unique for the distribution of types, therapeutic options and clinical evolution. Administrative databases represent well-documented tools in epidemiology, and in oncology they are very important in those realities without cancer registries. Our study aimed to analyze the occurrence, outcomes and burden of cancer in young patients through the analysis of hospital discharge records. METHODS: Hospital discharge databases and civil registries were analyzed through record linkage technique. Annual incidence rate (AIR), standardized incidence rate (SR), overall survival, hospitalization rate, and mean number of hospitalizations were evaluated. RESULTS: Among 2,330,459 young adults, 1846 new cancer patients had been hospitalized in the analyzed period. The SR was 69.3/100,000/year: 1051, 56.9%, were females (AIR 91.0 and SR 76.0) and 795, 43.1%, were males (AIR 67.6 and SR 62.5). Hematological disease was more frequent in males than females (25.5% vs 14.7%, P <0.0001), whereas solid tumors were more frequent among females (85.3% vs 74.5, P <0.0001). The distribution by diagnostic group showed that among females breast cancer was the most frequent (n = 272, SR 17.2), whereas among males genitourinary tract cancer (n = 245, SR 19.2), especially testicular cancer (n = 187, SR 15.1), was the most frequent. Metastatic disease at diagnosis was already present in 198 patients with a solid cancer (13.3%), whereas 213 (11.5%) developed metastasis in the following years. At 12 months from the diagnosis, 87 of 1488 patients with solid cancers and 35 of 358 patients with hematologic disease failed: overall survival was 94% and 90%, respectively. Patients with a new diagnosis of cancer had produced 6663 hospitalizations, 4640 (69.6%) of which were due to solid tumors, 3992 (59.9%) produced by patients over 29 years old, and 3606 (54.1%) by females. The percentage of day hospital admissions increased proportionally with patient age: 25.7% of all hospitalizations among older adolescents (15-20 years) and 32.9% among young adults of 34-39 years. CONCLUSIONS: Administrative data have clear advantages in terms of availability and large numbers. Comparison of our results with the literature showed that a health care delivery database can provide useful information for clinical-epidemiologic evaluations in oncology as well as for the analysis of health services utilization.

Temporal trends of the gaps in post-myocardial infarction secondary prevention strategies of co-morbid and elderly populations vs. younger counterparts: an analysis of three successive cohorts between 2003 and 2008.

Aims Epidemiological studies reported two contrasting trends: on one hand, a significant improvement in the use of evidence-based treatments of patients discharged with a myocardial infarction (MI). On the other hand, the increasing number of elderly and co-morbid patients who are usually less treated. The aim of this study is to examine whether improvements in the treatment of MI are homogeneously distributed throughout all subgroups of patients. Methods and results Based on record linkage of administrative registers, 21 423 patients discharged with MI in three different periods (2003, 2005, and 2007), were identified and followed up for major clinical events up to 1 year. Using as a reference temporal category those patients discharged in 2003 (odds ratios, 95% confidence intervals) and as a demographic category male patients aged ≤75 years (1.00), the study identified: in-hospital mortality significantly decreased in all periods and in all groups of patients; out-of-hospital mortality decreased only in younger patients and not in older patients; prescription of evidence-based treatments increased in all periods for all patients; however, the magnitude of improvement was mostly concentrated in younger patients. Conclusion Although there was a mean improvement in the treatment and outcome of patients discharged from an MI, most of these benefits were strongly concentrated in younger, healthier patients. Old and co-morbid populations-although representing a substantial proportion of the burden of disease-received significant less attention and barely improved their survival.

Unexpected autoptic finding in a sudden death: gossypiboma.

Gossypiboma, i.e. a retained surgical sponge, is a serious and rare complication in surgical practice, most commonly occurring in abdominal procedures. Migration of retained surgical sponge is an unusual sequelae, particularly if occurring in tracheo-bronchial tree. Herein, we report a 35-year-old man who had had a retained surgical sponge forgotten during a radical thyroidectomy, and subsequently a trans-luminal migration of the gossypiboma which went through the trachea causing a sudden death of the patient. All the operators of the surgical team should keep in mind this terrible complication to avoid unpleasant consequences to patient and themselves.

Antidepressants and cardiovascular outcomes in patients without known cardiovascular risk.

PURPOSE: To identify a cohort of subjects without treatment for any cardiovascular risk and analyze the potential causative role of treatment for depression on the development of major cardiovascular outcomes during 2 years of follow-up. METHODS: We carried out a record-linkage analysis of hospital discharge records, prescription databases and vital statistics for all consecutive patients aged 30 years or older in one Italian region during a 4-year period. Depression was defined in terms of exposure to at least three prescriptions of antidepressant drugs within 1 year. Patients had no history of treatment with cardiovascular or antidiabetic agents and had not been hospitalized with a diagnosis of any cardiovascular condition in the preceding year. Follow-up was extended up to 2 years or to time to occurrence of major outcomes defined as either all-cause mortality, hospitalization for any cardiovascular cause or chronic exposure to cardiovascular drugs (antihypertensive, statins, antidiabetics). The results are expressed hazard ratios (HRs) and 95% confidence intervals (CIs) within age categories (30-49, 50-59, > or = 60 years). RESULTS: A total of 105,573 persons without treated cardiovascular risk at baseline were identified, among whom 1,129 (1.1%) had been chronically exposed to antidepressant treatment. Treated depression determined an increased risk of all cause-mortality (HR 1.88, 95% CI 1.33-2.66, p < 0.001) and of subsequent treatment with antidiabetic agents (HR 0.89, 95% CI 1.34-2.66, p < 0.001), statins (HR 1.87, 95% CI 1.53-2.29, p < 0.001) and antihypertensive drugs (HR 1.25, 95% CI 1.07-1.47, p = 0.006). CONCLUSION: Among the general population without treated cardiovascular risk, pharmacologic treatment for depression was associated with an increase in all-cause mortality and major cardiovascular outcomes.

Depression worsens outcomes in elderly patients with heart failure: an analysis of 48,117 patients in a community setting.

AIMS: To assess the relationship between depression and clinical outcomes among elderly patients with heart failure (HF) in a community setting. METHODS AND RESULTS: To identify patients with HF and depression we used record linkage analysis of hospital discharge records, prescription databases and vital statistics. All consecutive patients aged>or=60 years in 6 Local Health Authorities in Italy were included. HF was defined as either: 1) hospital discharge with HF diagnosis (ICD-9: 428) and/or 2) chronic treatment for HF identified as concomitant (within 45 days) prescription of any combination of ACE inhibitors, digoxin, furosemide, bisoprolol, carvedilol, spironolactone, ARB-blockers. Depression was identified from exposure to psychotropic drugs before HF diagnosis. Cox proportional hazards models adjusted for major confounders were used. To adjust for potential residual known confounders, a propensity score analysis was performed. Sensitivity and subgroup analysis were used to demonstrate the consistency or robustness of the results. 48,117 patients with HF were identified. Of these, 3328 (6.9%) were treated for depression. Among patients with HF, those with depression were significantly older, and more likely to be women with a previous stroke. Depression significantly worsened major outcomes including all cause mortality [HR (95%CI); 1.20 (1.08-1.33)] and the composite of stroke/TIA/AMI [1.23 (1.13-1.34)]. Patients with depression had no increased risk of rehospitalisation for HF. Propensity scores and subgroup analysis confirmed these findings. CONCLUSION: Among elderly patients with HF, depression was independently associated with poor clinical outcomes mostly due to an increase in vascular events.

Omega-3 fatty acid supplementation reduces one-year risk of atrial fibrillation in patients hospitalized with myocardial infarction.

PURPOSE: Current strategies for avoiding atrial fibrillation (AF) are of limited value. We aim to assess the relationship between omega-3 fatty acids (n-3 PUFA) and AF occurrence in post-myocardial infarction (MI) patients. METHODS: A population study, linking hospital discharge records, prescription databases, and vital statistics, was conducted and included all consecutive patients with MI (ICD-9: 410) in six Italian local health authorities over a 3-year period. A propensity score (PS)-based, 5-to-1, greedy 1:1 matching algorithm was used to check consistency of results. Sensitivity analysis was performed to assess the robustness of findings. RESULTS: N-3 PUFA reduced the relative risk of the hospitalization for AF [hazard ratio (HR) 0.19, 95% CI 0.07-0.51] and was associated with a further and complementary reduction in all-cause mortality (HR 0.15, 95% CI 0.05-0.46). PS-based matched analysis and sensitivity analysis confirmed the main results. CONCLUSION: n-3 PUFA reduced both all-cause mortality and incidence of 1-year AF in patients hospitalized with MI.

The prognostic influence of chronic obstructive pulmonary disease in patients hospitalised for chronic heart failure.

AIMS: To investigate the prevalence and the prognostic impact of chronic obstructive pulmonary disease (COPD), in patients hospitalised with chronic heart failure (CHF). METHODS AND RESULTS: In an observational study based on longitudinal information from administrative registers, 1020 patients aged >or=60 years, who were chronically treated for and hospitalised with CHF were identified and followed-up for major events up to 1 year. Median age was 80 years, half of the patients were female and 241 patients (23.6%) had concomitant COPD. There were no differences in the prevalence of cardiovascular and non-cardiovascular comorbidities between CHF patients with or without COPD. However, COPD patients were more often male (60.6% vs. 46.3%), more frequently treated with diuretics (95.9% vs. 91.5%) but less often exposed to beta-blockers (16.2% vs. 22.0%). Significantly higher adjusted in-hospital (HR 1.50 [95%CI 1.00-2.26]) and out-of-hospital (1.42 [1.09-1.86]) mortality rates were found in CHF patients with concomitant COPD. A higher occurrence of non-fatal AMI/stroke/rehospitalisation for CHF (1.26 [1.01-1.58]) as well as hospitalisation for CHF (1.35 [1.00-1.82]) was associated with COPD. CONCLUSIONS: COPD is a frequent concomitant disease in patients with heart failure and it is an independent short-term prognostic indicator of mortality and cardiovascular comorbidity in patients who have been admitted to hospital for heart failure.

Antithrombotic treatment is strongly underused despite reducing overall mortality among high-risk elderly patients hospitalized with atrial fibrillation.

AIMS: To assess the use of antithrombotic treatment (ATT) after hospitalization with atrial fibrillation (AF) and the attributable effectiveness of ATT during follow-up. METHODS AND RESULTS: On the basis of record linkage of administrative registers, 1812 patients discharged with AF were identified and followed-up for major clinical events up to 1 year. Mean age was 79 years. After hospitalization, 56% of the patients received ATT: 29% anticoagulants, 22% antiplatelets (APs), and 5% both agents. Among patients without comorbidities, 63.0% were exposed to ATT. Several factors significantly influence the use of antithrombotic agents, including increasing age [odds ratio (OR) 0.93 (95% confidence interval (CI), 0.92-0.95)], chronic obstructive pulmonary disease [0.77 (0.59-1.00)], malignancy [0.57 (0.39-0.82)], and previous use of ATT [4.56 (3.67-5.67)]. A significantly lower mortality was observed in patients exposed to ATT [hazard ratio (HR) 0.36 (95% CI, 0.28-0.47)], both to anticoagulants [0.23 (0.15-0.35)] and to APs [0.66 (0.50-0.86)]. ATT was associated with the reduction of thrombo-embolic events [0.52 (0.25-1.07)]. Major bleeding did not contribute to increased morbidity. Subgroups analysis, propensity score (PS), and sensitivity analysis confirmed these results. CONCLUSION: Our data demonstrated that ATT was underused, also in patients without comorbidities. Exposure to ATT is associated with improved survival among elderly high-risk community patients hospitalized with AF.

[Administrative data as source for epidemiological research: clinical pathways of diabetic patients]. / I database amministrativi come fonti di ricerca epidemiologica: il percorso clinico-assistenziale del diabete mellito.

UNLABELLED: Objectives 1. To assess if record linkage of two different databases could improve the quality and understand the epidemiology of diabetes and its complications. 2. To analyse how hospitalization relates to the natural history of the disease and to its pharmaceutical management. 3. To document how pharmacoepidemiology could be a challenging tool for clinicians. 4. To identify critical areas where improvement of care would be specifically important. METHODS: Data came from two large databases, the drugs prescription and the hospital discharge forms of the Local Health Unit of Rovigo, Italy, collected through 2000. A casecontrol design was adopted to compare two cohorts identified by prescription of antidiabetic vs any other drugs and the linkage to their hospitalizations over the index period. The study was focused on people > or = 50 year in order to concentrate the attention on NIDDM. A population of 5.603 patients were identified as diabetic and 63.155 were the controls. The prevalence of diabetes was 3.6% in the general population and 8.1% in 50 year and older. The hospitalizations analysis revealed differences between cases and controls in term of longer duration of stay (10.1 vs 8.4 days), higher in-hospital mortality (5.5% vs 5%) and higher presence of cardiovascular complications. Of the 2.922 hospitalizations registered for diabetics, 43% did not report the specific ICD-9-CM code for diabetic disease (250.x). Record linkage of these administrative databases offers new opportunities to improve the comprehension of the natural history of diabetic disease. The identification of diabetic patients from prescription data allows a more reliable picture of the hospitalization than the simple analyses of hospital discharge forms. Up to 43% of hospitalizations in the diabetic cohort did not report the specific diabetic disease diagnosis, compared to the 25% reported in a previous observation where linkage was not applied. The lack of this code registration during hospitalization can reflect a scant perception of the importance of diabetes as the major determinant of complications and could open a discussion table with other clinicians, general practitioners and health care professionals.