Patient Safety and Surgery: the Experience of the Lombardy Region. A Project on External Evaluation of Best Practices Implementation.

Meta-analysis studies published over the past 20 years document that approximately 10 -14 % of hospitalised patients have an adverse event in Surgery and at least half of these adverse events are considered preventable using the current standards of care. In order to improve the safety of surgical patients and increasing adherence to current standard of care in surgery, including communication within the team and teamwork, in 2007 the WHO launched the campaign "Safe Surgery Saves Lives". The WHO has also built a checklist for safety in the operating room containing 19 item in support of the operating team. The Ministry of Health in 2009 has taken the instruments produced by WHO in the "Guide to Safety in the operating room: Recommendations and Checklist". Studies conducted in industrialized countries report a strong heterogeneity in compliance to the check list for the surgical safety, with a range of between 38% and 96%. The aim of this project was to adopt the methodology of the external "peer review" to improve quality and patient safety applied to the surgical process and assess the degree of implementation of good practice in the operating room, both in public and private structures. Between 2015 and 2018 we have carried out 16 external evaluation visits. These visits included a first plenary session followed by the inspection of the operating theaters identified and a second plenary session. Several factors emerged during the visits; these factors represent both the strengths and criticalities of the organizations. The creation of a team of experts, coordinated by the Lombardy Region with the role of leadership, using the "peer review" methodology, is the leverage to promote among operators the growth of awareness of the usefulness of the tools.

Multiple Medication Adherence and Related Outcomes in Community-Dwelling Older People on Chronic Polypharmacy: A Retrospective Cohort Study on Administrative Claims Data.

Poor medication adherence compromises treatment efficacy and adversely affects patients' clinical outcomes. This study aims to assess (1) multiple medication adherence to the most common drug classes chronically prescribed to older people, (2) the factors associated, and (3) the clinical outcomes. This retrospective cohort study included 122,655 community-dwelling patients aged 65-94 years old, newly exposed to chronic polypharmacy, and recorded in the Lombardy Region (northern Italy) administrative database from 2016 to 2018. Multiple medication adherence was assessed for drugs for diabetes, antithrombotics, antihypertensives, statins, and bisphosphonates, by calculating the daily polypharmacy possession ratio (DPPR). One-year mortality, nursing home, emergency department (ED), and hospital admission rates were calculated for 2019. The most prescribed drugs were antihypertensives (89.0%). The mean (std.dev) DPPR was 82.9% (15.6). Being female (OR = 0.85, 95%CI: 0.84-0.86), age ≥85 years (OR = 0.77, 95%CI: 0.76-0.79), and multimorbidity (≥4 diseases, OR = 0.88, 95%CI: 0.86-0.90) were associated with lower medication adherence. A higher DPPR was associated with clinical outcomes-in particular, improved survival (HR = 0.93 for 10/100-point increase, 95%CI: 0.92-0.94) and lower incidence in nursing home admissions (SDHR = 0.95, 95%CI: 0.93-0.97). Adherence to the most common chronic drugs co-prescribed to the older population was high. Better multiple medication adherence was associated with better clinical outcomes.

Is EuroSCORE II still a reliable predictor for cardiac surgery mortality in 2022? A retrospective study study.

OBJECTIVES: The European System for Cardiac Operation Risk Evaluation II (EuroSCORE II) is the most common tool used to evaluate the perioperative risk of mortality after cardiac surgery in Europe, and its use is currently recommended by the relevant guidelines. However, recently, its role has been questioned: Several papers have suggested that these algorithms may no longer be adequate for risk prediction due to an overestimation of adult cardiac surgical risk. Our goal was to validate the EuroSCORE II in the prediction of 30-day in-hospital mortality in patients undergoing open cardiac surgery in a high-volume hospital. METHODS: In this retrospective cohort study, we included all patients who underwent cardiac surgery from January 2016 to May 2022 within the departments of cardiac surgery of the Monzino Cardiology Centre in Milan, Italy. We evaluated the discrimination power of the EuroSCORE II by using the receiver operating characteristic curve and the corresponding area under the curve. We performed calibration plots to assess the concordance between the model's prediction and the observed outcomes. RESULTS: A total of 4,034 patients were included (mean age = 65.1 years; 68% males), of which 674 (16.7%) underwent isolated coronary artery bypass grafting. The EuroSCORE II showed a good discrimination power in predicting 30-day in-hospital mortality (area under the curve = 0.834). However, for interventions performed in an elective setting, very low values of the EuroSCORE II overestimated the observed mortality, whereas for interventions performed in an emergency setting, EuroSCORE II values above 10 extensively underestimated the observed mortality. CONCLUSIONS: Our study suggests that the EuroSCORE II seems not to be a reliable score in estimating the true risk of death, especially in high-risk patients.

Cost-effectiveness of the adherence with recommendations for clinical monitoring of patients with diabetes.

BACKGROUND AND AIMS: To validate a set of indicators for monitoring the quality of care of patients with diabetes in 'real-life' practice through its relationship with measurable clinical outcomes and healthcare costs. METHODS AND RESULTS: A population-based cohort study was carried out by including the 20,635 patients, residents in the Lombardy Region (Italy), who in the year 2012 were newly taken-in-care for diabetes. Adherence with clinical recommendations (i.e., controls for glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine) was recorded during the first year after the patient was taken-in-care, and categorized according whether he/she complied with none or almost none (0 or 1), just some (2) or all or almost all (3 or 4) the recommendations, respectively denoted as poor, intermediate and high adherence. Short- and long-term complications of diabetes, and healthcare cost incurred by the National Health Service, were assessed during follow-up. Compared with patients with poor adherence, those with intermediate and high adherence respectively showed (i) a delay in outcome occurrence of 13 days (95% CI, -2 to 27) and 23 days (9-38), and (ii) a lower healthcare cost of 54 € and 77 €. In average, a gain of 18 Euros and 15 Euros for each day free from diabetic complication by increasing adherence respectively from poor to intermediate and from poor to high were observed. CONCLUSION: Close control of patients with diabetes through regular clinical examinations must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes.

Use of preventive drugs during the last year of life in older adults with cancer or chronic progressive diseases.

PURPOSE: To evaluate the prescription of preventive medications with questionable usefulness in community dwelling elderly adults with cancer or chronic progressive diseases during the last year of life. METHODS: Through the utilization of the healthcare databases of the Lombardy region, Italy, we identified two retrospective cohorts of patients aged 65 years or more, who died in 2018 and had a diagnosis of either a solid cancer (N = 19 367) or a chronic progressive disease (N = 27 819). We estimated prescription of eight major classes of preventive drugs 1 year and 1 month before death; continuation or initiation of preventive drug use during the last month of life was also investigated. RESULTS: Over the last year of life, in both oncologic and non-oncologic patients, we observed a modest decrease in the prescription of blood glucose-lowering drugs, anti-hypertensives, lipid-modifying agents, and bisphosphonates, and a slight increase in the prescription of vitamins, minerals, antianemic drugs, and antithrombotic agents (among oncologic patients only). One month before death, the prescription of preventive drugs was still common, particularly for anti-hypertensives, antithrombotics, and antianemics, with more than 60% of patients continuing to be prescribed most preventive drugs and an over 10% starting a therapy with an antithrombotic, an antianemic, or a vitamin or mineral supplement. CONCLUSION: These findings support the need for an appropriate drug review and improvement in the quality of drug prescription for vulnerable populations at the end-of-life.

Medication adherence in community-dwelling older people exposed to chronic polypharmacy.

BACKGROUND: To evaluate medication adherence and associated factors of seven of the most common drug classes prescribed to community-dwelling older people. METHODS: This is a retrospective cohort study on medication adherence in community-dwelling older people (65-94 years old) on chronic polypharmacy and recorded from 2013 to 2015 in the administrative database of the Lombardy region (Northern Italy). Adherence was assessed for diabetic drugs, antithrombotic agents, drugs acting on the renin-angiotensin system, statins, bisphosphonates, antidepressants and drugs for obstructive airway diseases by calculating the medication possession ratio (MPR). Patients were then divided in fully (MPR ≥80%), partially (40%≤MPR<80%) and poorly adherent (10%

Influence of adherence with guideline-driven recommendations on survival in women operated for breast cancer: Real-life evidence from Italy.

BACKGROUND: A set of indicators to assess the quality of care for women operated for breast cancer was developed by an expert working group of the Italian Health Ministry in order to compare the Italian regions. A study to validate these indicators through their relationship with survival was carried out. METHODS: The 16,753 women who were residents in three Italian regions (Lombardy, Emilia-Romagna and Lazio) and hospitalized for breast cancer surgery during 2011 entered the cohort and were followed until 2016. Adherence to selected recommendations (i.e., surgery timeliness, medical therapy timeliness, appropriateness of complementary radiotherapy and mammographic follow-up) was assessed. Multivariable proportional hazards models were fitted to estimate hazard ratios for the association between adherence with recommendations and the risk of all-cause mortality. RESULTS: Adherence to recommendations was 53% for medical therapy timeliness, 73% for appropriateness of mammographic follow-up, 74% for surgery timeliness and 82% for appropriateness of complementary radiotherapy. Risk reductions of 26%, 62% and 56% were observed for adherence to recommendations on medical therapy timeliness, appropriateness of complementary radiotherapy and mammographic follow-up, respectively. There was no evidence that mortality was affected by surgery timeliness. CONCLUSIONS: Clinical benefits are expected from improvements in adherence to the considered recommendations. Close control of women operated for breast cancer through medical care timeliness and appropriateness of radiotherapy and mammographic monitoring must be considered the cornerstone of national guidance, national audits, and quality improvement incentive schemes.

Number of lung resections performed and long-term mortality rates of patients after lung cancer surgery: evidence from an Italian investigation.

OBJECTIVES: Although it has been postulated that patients might benefit from the centralization of high-volume specialized centres, conflicting results have been reported on the relationship between the number of lung resections performed and the long-term, all-cause mortality rates among patients who underwent surgery for lung cancer. A population-based observational study was performed to contribute to the ongoing debate. METHODS: The 2613 patients, all residents of the Lombardy region (Italy), who underwent lung resection for lung cancer from 2012 to 2014 were entered into the cohort and were followed until 2018. The hospitals were classified according to the annual number of pulmonary resections performed. Three categories of lung resection cases were identified: low (≤30), intermediate (31-95) and high (>95). The outcome of interest was all-cause death. A frailty model was used to estimate the death risk associated with the categories of numbers of lung resections performed, taking into account the multilevel structure of the data. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS: The 1-year and 5-year survival rates of cohort members were 90% and 63%. Patients operated on in high-volume centres were on average younger and more often women. Compared to patients operated on in a low-volume centre, the mortality risk exhibited a significant, progressive reduction as the numbers of lung resections performed increased to intermediate (-13%; 95% confidence interval +10% to -31%) and high (-26%; 0% to -45%). Sensitivity analyses revealed that the association was consistent. CONCLUSIONS: Further evidence that the volume of lung resection cases performed strongly affects the long-term survival of lung cancer patients has been supplied.

Peripheral arterial disease: Changes in clinical outcomes and therapeutic strategies in two cohorts, from 2002 to 2008 and from 2008 to 2014. A population-based study.

Background The aim of our study was to evaluate whether treatments for peripheral artery disease changed in two different cohorts identified in 2002 and 2008, and whether this had an impact on mortality and major clinical outcomes after six years of follow-up. Methods Using administrative health databases of the largest region in Northern Italy, we identified patients admitted to hospital for peripheral artery disease in 2002 and 2008. Both cohorts were followed for six years. All cause death, acute coronary syndrome, stroke and major amputations, cardiovascular prevention drugs and revascularization procedures were collected. Incidence of events was plotted using adjusted cumulative incidence function estimates. The risk, for each outcome, was compared between 2002-2008 and 2008-2014 using a multivariable Fine and Gray's semiparametric proportional subdistribution hazards model. Results In 2002 and 2008, 2885 and 2848 patients were identified. Adjusting for age, sex, Charlson comorbidity index and severity of peripheral artery disease we observed a significant reduction (in 2008 vs. 2002) in the risk of acute coronary syndrome (28%), stroke (27%) and major amputation (17%). No change was observed in the risk of death. The percentages of patients with peripheral artery revascularizations, during the hospital stay, increased: 43.8% in 2002 vs. 49.0% in 2008, p < 0.001. From 2002 to 2008 there was a significant absolute increase in the prescription of lipid-lowering drugs (+18%), antiplatelets (+7.2%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (+11.8%), p < 0.001. Conclusions In six years of follow-up we observed a reduction in risk of major cardiovascular events in 2008-2014 in comparison with the 2002-2008 cohort. Increasing use of revascularization interventions and cardiovascular prevention drugs could have contributed to the better prognosis.

Management, prognosis and predictors of unfavourable outcomes in patients newly hospitalized for transient ischemic attack: a real-world investigation from Italy.

BACKGROUND: Understanding the gap between evidence-based recommendations and real-world management is important to inform priority setting and health service planning. METHODS: The 7,776 residents in the Italian Lombardy Region who were newly hospitalized for transient ischemic attack (TIA) during 2008-2009 entered into the cohort and were followed until 2012. Exposure to medical care including selected drugs, diagnostic procedures and laboratory tests was recorded. A composite outcome was employed taking into account all-cause death and hospitalization for stroke and acute myocardial infarction. A multivariable proportional hazards model was fitted to estimate hazard ratio, and 95% confidence intervals (CI), for the exposure-outcome association. RESULTS: During the first year after discharge, 8.6, 49.7 and 48.5% of patients did not use any drugs, diagnostic procedures and laboratory tests respectively. Patients exposed to medical care had 59% reduced risk (95% CI, 50 to 66%) with respect to those who did not use any of these services. CONCLUSIONS: Although the Italian National Health System supplies universal coverage for healthcare, several TIA patients receive suboptimal care. Systematic improvements are necessary in order to improve patient outcomes.

Metformin, other antidiabetic drugs, and endometrial cancer risk: a nested case-control study within Italian healthcare utilization databases.

Metformin may reduce the risk of endometrial cancer whereas other drugs for the treatment of type 2 diabetes mellitus appear to increase it, although the evidence is still limited. We investigated this issue using data from a nested case-control study within the healthcare utilization databases of the Lombardy Region, Italy. This study included 376 diabetic women with endometrial cancer and 7485 diabetic controls matched for cases on age, date at cohort entry, and duration of follow-up. We used conditional logistic regression models to estimate the odds ratio (OR) of endometrial cancer in relation to use of antidiabetic drugs, adjusted for the Charlson's comorbidity index, selected medical conditions, prescription of selected drugs, and concomitant use of other antidiabetic drugs. At cohort entry, no significant associations were observed for metformin [OR=0.99, 95% confidence interval (CI) 0.80-1.23], sulfonylureas (OR=1.14, 95% CI 0.91-1.42), insulin (OR=0.72, 95% CI 0.34-1.56), and other antidiabetic drugs (OR=1.21, 95% CI 0.75-1.95). When we considered use during follow-up, a borderline significant excess risk was found for metformin (OR=1.30, 95% CI 1.00-1.70). However, this estimate decreased to 1.07 (95% CI 0.82-1.41) when taking into account BMI using a Monte Carlo sensitivity analysis. No significant associations were found for sulfonylureas (OR=1.16, 95% CI 0.91-1.47), thiazolidinediones (OR=0.77, 95% CI 0.48-1.24), repaglinide (OR=1.32, 95% CI 0.94-1.87), incretins (OR=1.21, 95% CI 0.63-2.32), and insulin (OR=1.19, 95% CI 0.82-1.71). Our data indicate that metformin, insulin, and other antidiabetic drugs did not meaningfully affect the risk of endometrial cancer.

Drug treatment and adherence of subjects <40 years with diagnosis of heterozygous familial hypercholesterolemia.

BACKGROUND AND AIMS: We aimed at describing the therapeutic approach in young adult patients diagnosed with heterozygous familial hypercholesterolemia (HeFH) and their adherence and persistence to treatment. METHODS: From regional administrative databases, individuals aged ≤40 years, who received exemption for HeFH between January 1, 2003 and December 31, 2011, and concomitantly started statin treatment, were identified. Within the first year of treatment, we evaluated therapeutic changes, adherence as MPR (medication possession ratio), persistence as continuous drug coverage without gaps ≥60 days, and influencing factors using log binomial models. RESULTS: Of 1404 patients, 42.4% were initially treated with a high-efficacy statin. 23.4% of patients showed at least one treatment change. Mean MPR was 68.7% (29.9), and patients showing continued statin use were 47.0%. Therapy modification was significantly associated with a past cardiovascular event (relative risk, RR [95% confidential interval] 2.28 [1.69-3.09]) and at least one lipid test (RR 1.82 [1.31-2.53]). MPR ≥80% was significantly associated with the first statin prescribed (atorvastatin RR 1.28 [1.09-1.51] and rosuvastatin RR 1.21 [1.01-1.44], vs. simvastatin), a past cardiovascular event (RR 1.33 [1.12-1.59]), at least one therapy change (RR 1.28 [1.15-1.43]), at least a lipid test (RR 1.26 [1.07-1.49]). A similar pattern was observed for persistence. CONCLUSIONS: This analysis of young adult HeFH patients showed that therapy change was quite frequent, and probably reflected adjustments according to individual response. Adherence and persistence were inadequate, even in this population at high cardiovascular risk, and they need to be improved through proper patient education and shared treatment decision-making approach.

Statin use and risk of cataract: A nested case-control study within a healthcare database.

BACKGROUND AND AIMS: We aimed to assess the association between exposure to statins and hospitalization for cataract. METHODS: A population-based, nested case-control study was performed on a cohort of 134,441 patients from Lombardy (Italy), newly treated with statins between 2005 and 2007. Cases were patients hospitalized for cataract or lens extraction surgery after initial statin prescription until December 31, 2012. For each case patient, up to 5 controls were randomly selected from the cohort and matched by gender, age at cohort entry, and date of index prescription. Logistic regression was used to model the outcome risk associated with low (proportion of days covered, PDC 25-49%), intermediate (PDC 50-74%), and high (PDC ≥ 75%) adherence compared with very-low adherence (PDC < 25%). RESULTS: 1334 case patients were matched to 6601 controls. Mean age (SD) of cases and controls was about 70 years (9 years) and 51% of them were men. There was a slight but continuous trend toward an increased risk of cataract as adherence to statin therapy increased in the adjusted risk models, with a significant odds ratio of 1.19 (95% CI 1.01-1.40%) for PDC 50-74% and 1.20 (95% CI 1.02-1.40) for PDC ≥ 75% vs. PDC < 25%, respectively. There was no statistical evidence that the effect of statins on cataract risk differed according to statin potency at starting therapy. CONCLUSIONS: Statin therapy was associated with a modestly increased risk of cataract surgery. Nevertheless, in view of the overwhelming benefit of statins for reduction of CV events, clinical practice for statins therapy does not need to change.

Hip Fracture Surgery and Survival in Centenarians.

BACKGROUND: Hip fracture (HF) is increasingly frequent with advancing age. Studies describing the HF incidence rate and survival after surgery in centenarians are scanty. To fill this gap, we performed a large population-based investigation on Lombardy centenarians (Italy). METHODS: Retrospective observational cohort study based on information from the Healthcare Utilization Database. Among the cohort of 7,830 residents that reached 100 years of age between 2004 and 2011, incidence rate of HF was calculated. Two hundred fifty-nine patients were discharged alive from a hospital after HF and surgical repair (HF cohort). For each HF cohort member, a control was randomly selected from the initial cohort to be matched for gender and date of birth, and who did not experience HF from the date of their hundredth birthday until the date of hospital discharge of the corresponding HF cohort member. The survival curves and the hazard functions of HF and control cohort were calculated within 2 years. RESULTS: Over a mean follow-up of 1.85 years, HF incidence rate was 23.1 per 1,000 centenarians per year. Survival probability was significantly lower in HF cohort than in control cohort (31.5 vs 48.1%, p < .001). Hazard functions showed an increased risk of death in HF cohort than in control cohort, especially in the 3 months after surgery. CONCLUSION: Survival analysis exhibited an excess mortality in the first 3 months among HF cohort members, but not beyond this period. Every effort to counteract HF is warranted, including prevention of falls and high quality of care, especially in the early postsurgical time.

The importance of monitoring adverse drug reactions in elderly patients: the results of a long-term pharmacovigilance programme.

OBJECTIVE: To recognise and prevent ADRs (including DDIs) in the elderly through a 4-year post-marketing active pharmacovigilance programme. The programme was designed to enhance high quality spontaneous reporting of ADRs in elderly patients by sampling the Italian population and was termed 'Pharmacovigilance in Geriatry (ViGer)'. METHODS: ADRs were collected for adults aged over 65 years of age treated in nursing homes, continuing care retirement communities and territorial health services in Lombardy. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analysed with respect to time, sex, category of ADR, seriousness, suspected medicines, notoriety. We analysed all the potential DDIs. RESULTS: We detected 1073 cases reports corresponding to 2110 ADRs. Vaccines, antibacterials for systemic use and antineoplastic agents were the pharmacotherapeutic subgroups most frequently involved. 18% of ADRs reports were classified as serious. In 752 reports patients were described as in polytherapy; in 55 patients (7.3%) the reported ADR were probably preventable because of DDIs involvement. CONCLUSION: The ViGer project demonstrated that active pos-marketing pharmacovigilance programmes are a valid strategy to increase awareness on geriatrics pharmacology, reduce underreporting and provide important information on previous unknown ADRs and DDIs, resulting in a therapy optimisation in clinical practice in the geriatric setting.

Serological screening for celiac disease in a northern Italian child and adolescent population after the onset of type 1 diabetes: a retrospective longitudinal study of a 7-year period.

AIM: To evaluate the temporal trend and extent of screening for celiac disease in an Italian pediatric population of incident type 1 diabetes in the period 2006-2011, providing information on adherence to guidelines in primary care. METHODS: Using the Lombardy region's administrative database, 1-17-year-old children and adolescents diagnosed with type 1 diabetes during the 2006-2011 period were identified. Among these patients, the number screened for celiac disease was calculated on the basis of specific antibodies. RESULTS: Of the 1563 children and adolescents receiving a diagnosis of type 1 diabetes during the observational period, 53% were tested for celiac disease compared with 12% of individuals without diabetes. The extent to which screening was performed increased two-fold from the 2006-2008 to the 2009-2011 period (P<0.0001). Among the screened population, 1.8 of the non-type 1 diabetes population and 9.4% of the new cases of type 1 diabetes received a diagnosis of celiac disease (90% after type1 diabetes diagnosis and 10% before). Being female and less than 4 years old were factors associated with an increased risk of receiving both diagnoses. CONCLUSION: In conclusion, to the best of our knowledge, this is the first report in which celiac disease screening is measured in a type 1 diabetes population from the time of diagnosis up to at least 12 months afterwards. The results provide evidence that, although the rate of screening increased over time, nearly half of children with type 1 diabetes were not screened after diagnosis during the observed period, suggesting scarce adherence to guidelines in primary care.

Changes in clinical outcomes for community-dwelling older people exposed to incident chronic polypharmacy: a comparison between 2001 and 2009.

PURPOSE: The purpose of this study is to explore the effect of incident chronic polypharmacy on 1-year hospitalization, institutionalization, and mortality among older people and to evaluate whether or not the effect differed according to index year (2001 or 2009), sex, and age. METHODS: Data were obtained from the administrative database of the Lombardy region (Northern Italy). We compared community-dwelling elderly people with an incident exposure to chronic polypharmacy (five or more drugs during 1 month for at least 6 months in 1 year) in either index year (2001 and 2009) with not exposed elderly people in the same years. Multivariable logistic (institutionalization) and Cox (hospitalization and death) were performed including year, sex, age classes, and number of drugs as covariates and their respective interaction terms by chronic polypharmacy. RESULTS: We analyzed 1,800,257 elderly subjects in 2001 and 1,567,575 in 2009, with a prevalence of chronic polypharmacy of 1.46% and 2.86%, respectively. Overall, 1-year hospitalization, institutionalization, and mortality rates were lower in 2009 than in 2001. Chronic polypharmacy was significantly associated with the outcomes in multivariable analyses: hazard or odds ratios 1.16 (95% confidence interval 1.14-1.17) for hospitalization, 1.21 (1.12-1.30) for institutionalization, and 1.11 (1.08-1.14) for death. There was no consistent effect modification by index year or sex, whereas chronic polypharmacy was no longer a risk factor for adverse outcomes among those older than 85 years (p < 0.0001 for interaction). CONCLUSIONS: Incident chronic polypharmacy remained an independent predictor of adverse outcomes among community-dwelling elderly people, despite a reduction over time of 1-year hospitalization, institutionalization, and mortality rates.

Insulin and other antidiabetic drugs and hepatocellular carcinoma risk: a nested case-control study based on Italian healthcare utilization databases.

PURPOSE: Insulin and other antidiabetic drugs may modulate hepatocellular carcinoma (HCC) risk in diabetics. METHODS: We have analyzed the role of various antidiabetic drugs on HCC in a nested case-control study using the healthcare utilization databases of the Lombardy Region in Italy. This included 190 diabetic subjects with a hospital discharge reporting a diagnosis of malignant HCC and 3772 diabetic control subjects matched to each case on sex, age, date at cohort entry, and duration of follow-up. RESULTS: Increased risks of HCC were found for use of insulin (odds ratio [OR] = 3.73, 95% confidence interval [CI] 2.52-5.51), sulfonylureas (OR = 1.39, 95%CI 0.98-1.99), and repaglinide (OR = 2.12, 95%CI 1.38-3.26), while a reduced risk was found for use of metformin (OR = 0.57, 95%CI 0.41-0.79). The risk of HCC increased with increasing duration of insulin use (OR = 2.52 for <1 year, 5.41 for 1-2 years, and 6.01 for ≥2 years; p for trend < 0.001), while no clear pattern with duration was observed for sulfonylureas, repaglinide, and metformin. CONCLUSION: Our study supports the evidence that patients with diabetes using metformin, and possibly other antidiabetic drugs that increase insulin sensibility, have a reduced risk of HCC, while those using insulin or drugs that increase circulating insulin, such as insulin secretagogues, have an increased risk. Whether these associations are causal, or influenced by different severity of diabetes and/or possible residual bias or misclassification, is still open to discussion.

The drug prescription network: a system-level view of drug co-prescription in community-dwelling elderly people.

Networks are well suited to display and analyze complex systems that consist of numerous and interlinked elements. This study aimed at: (1) generating a series of drug prescription networks (DPNs) displaying co-prescription in community-dwelling elderly people; (2) analyzing DPN structure and organization; and (3) comparing various DPNs to unveil possible differences in drug co-prescription patterns across time and space. Data were extracted from the administrative prescription database of the Lombardy Region in northern Italy in 2000 and 2010. DPNs were generated, in which each node represents a drug chemical subclass, whereas each edge linking two nodes represents the co-prescription of the corresponding drugs to the same patient. At a global level, the DPN was a very dense and highly clustered network, whereas at the local level it was organized into anatomically homogeneous modules. In addition, the DPN was assortative by class, because similar nodes (representing drugs with the same anatomic, therapeutic, and pharmacologic annotation) connected to each other more frequently than expected, indicating that similar drugs are often co-prescribed. Finally, temporal changes in the co-prescription of specific drug sub-groups (for instance, proton pump inhibitors) translated into topological changes of the DPN and its modules. In conclusion, complementing more traditional pharmaco-epidemiology methods, the DPN-based method allows appreciatiation (and representation) of general trends in the co-prescription of a specific drug (e.g., its emergence as a heavily co-prescribed hub) in comparison with other drugs.