The interplay between excess weight and hyper-glycemia on NCDs in Italy: results from a cross-sectional study.

PURPOSE: To evaluate the prevalence of chronic comorbidities according to BMI classes and assess the interplay between excess body weight and blood glucose abnormalities in increasing the risk of major chronic diseases. METHODS: The study is based on data from the Health Search/IQVIA Health LPD Longitudinal Patient Database, an Italian general practice registry, with data obtained from electronic clinical records of 800 general practitioners throughout Italy. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2 and 3) and glucose metabolism status (normoglycemia-NGT; impaired fasting glucose-IFG; diabetes mellitus-DM). Comorbidities were identified through ICD-9 CM codes. RESULTS: Data relative to 991,917 adults were analyzed. The prevalence of overweight was 39.4%, while the prevalence of obesity was 11.1% (class 1: 7.9%, class 2: 2.3%, class 3: 0.9%). In the whole population, the prevalence of DM and IFG was 8.9% and 4.2%, respectively. Both overweight and obesity were associated with an increasing prevalence of glucose metabolism alterations and a large array of different chronic conditions, including cardio-cerebrovascular diseases, heart failure, chronic kidney disease, osteoarticular diseases, depression, sleep apnea, and neoplasms of the gastrointestinal tract. Within each BMI class, the presence of IFG, and to a greater extent DM, identified subgroups of individuals with a marked increase in the risk of concomitant chronic conditions. CONCLUSION: Addressing the double burden of excess weight and hyperglycemia represents an important challenge and a healthcare priority.

Effect of a multidisciplinary team approach in patients with diabetic foot ulcers on major adverse limb events (MALEs): systematic review and meta-analysis for the development of the Italian guidelines for the treatment of diabetic foot syndrome.

The treatment of patients with diabetic foot ulcers (DFUs) is extremely complex, requiring a comprehensive approach that involves a variety of different healthcare professionals. Several studies have shown that a multidisciplinary team (MDT) approach is useful to achieve good clinical outcomes, reducing major and minor amputation and increasing the chance of healing. Despite this, the multidisciplinary approach is not always a recognized treatment strategy. The aim of this meta-analysis was to assess the effects of an MDT approach on major adverse limb events, healing, time-to-heal, all-cause mortality, and other clinical outcomes in patients with active DFUs. The present meta-analysis was performed for the purpose of developing Italian guidelines for the treatment of diabetic foot with the support of the Italian Society of Diabetology (Società Italiana di Diabetologia, SID) and the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD). The study was performed using the Grading of Recommendations Assessment, Development, and Evaluation approach. All randomized clinical trials and observational studies, with a duration of at least 26 weeks, which compared the MDT approach with any other organizational strategy in the management of patients with DFUs were considered. Animal studies were excluded. A search of Medline and Embase databases was performed up until the May 1st, 2023. Patients managed by an MDT were reported to have better outcomes in terms of healing, minor and major amputation, and survival in comparison with those managed using other approaches. No data were found on quality of life, returning-to-walking, and emergency admission. Authors concluded that the MDT may be effective in improving outcomes in patients with DFUs.

Lifetime costs of overweight and obesity in Italy.

We use longitudinal electronic clinical data on a large representative sample of the Italian population to estimate the lifetime profile costs of different BMI classes - normal weight, overweight, and obese (I, II, and III) - in a primary care setting. Our research reveals that obese patients generate the highest cost differential throughout their lives compared to normal weight patients. Moreover, we show that overweight individuals spend less than those with normal weight, primarily due to reduced expenditures beginning in early middle age. Our estimates could serve as a vital benchmark for policymakers looking to prioritize public interventions that address the obesity pandemic while considering the increasing obesity rates projected by the OECD until 2030.

To retrieve values of albuminuria to define the size of CKD patients eligible to SGLT-2Is: An explorative analysis using a primary care database.

PURPOSE: To address missingness of albuminuria values, which establish the eligibility to SGLT-2Is for patients with CKD, using the multiple imputation (MI) method. METHODS: We selected patients aged 18 or older and diagnosed with CKD in a primary care database. Those with severe CKD and/or previously treated with SGLT-2Is were excluded. Then, we collected all available information on albuminuria within 90 days the measure of GFR. A value of albumin-creatinine ratio (ACR) ranging 200-5000 mg/g or otherwise was the response variable on which we ran MI. Using logistic regression, odds ratios (OR) and related 95% confidence intervals (CI) were estimated for each covariate toward the response variable for both full and imputed dataset. RESULTS: The determinants showed consistent estimates between the full and imputed datasets as demonstrated by the overlaps of the CIs and the similar point estimates. As expected, there were some exceptions, such as diabetes (OR of 1.2 vs. 0.5) and use of diabetic medications (OR of 1.0 vs. 2.1) and/or statins (OR of 1.1 vs. 1.8). CONCLUSIONS: Besides being a reminder for GPs to prescribe and register albuminuria in certain patients' categories, these determinants might be translated into an operational algorithm to input ACR values in administrative data sources. Scenarios for the reimbursement criteria regulating SGLT-2Is to treat CKD would be therefore simulated on more inferable estimates.

Development of the Italian clinical practice guidelines for the treatment of diabetic foot syndrome: design and methodological aspects.

AIMS: Diabetic foot syndrome (DFS) and its complications are a growing public health concern. The Italian Society of Diabetology (SID) and the Italian Association of Clinical Diabetologists (AMD), in collaboration with other scientific societies, will develop the first Italian guidelines for the treatment of DFS. METHODS: The creation of SID/AMD Guidelines is based on an extended work made by 19 panelists and 12 members of the Evidence Review Team. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology has been used to decide aims, reference population, and target health professionals. Clinical questions have been created using PICO (Patient, Intervention, Comparison, Outcome) conceptual framework. The definition of questions has been performed using a two-step web-based Delphi methodology, a structured technique aimed at obtaining by repeated rounds of questionnaires a consensus opinion from a panel of experts in areas wherein evidence is scarce or conflicting, and opinion is important. RESULTS: The mean age of panelists (26.3% women) was 53.7 ± 10.6 years. The panel proposed 34 questions. A consensus was immediately reached for all the proposed questions, 32 were approved and 2 were rejected. CONCLUSIONS: The areas covered by clinical questions included diagnosis of ischemia and infection, treatment of ischemic, neuropathic, and infected ulcers, prevention of foot ulceration, organization and education issues, and surgical management. The PICO presented in this paper are designed to provide indications for healthcare professionals in charge of diabetic foot treatment and prevention, primarily based on clinical needs of people with diabetic foot syndrome and considering the existing organization of health care.

Outpatient healthcare costs associated with overweight and obesity in Italy.

BACKGROUND: To evaluate outpatient healthcare expenditure associated with different levels of BMI and glucose metabolism alterations. METHODS: The study is based on a representative national sample of adults, with data obtained from electronic clinical records of 900 Italian general practitioners. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2, and 3) and glucose metabolism status (normoglycemia - NGT; impaired fasting glucose - IFG; diabetes mellitus - DM). Outpatient health expenditures include diagnostic tests, specialist visits, and drugs. RESULTS: Data relative to 991,917 adults were analyzed. Annual per capita expenditure rose from 252.2 Euro among individuals with normal weight to 752.9 Euro among those with class 3 obesity. The presence of obesity determined an excess cost, particularly among younger individuals. Within each BMI class, the presence of IFG or DM2 identified subgroups of individuals with substantially higher healthcare expenditures. CONCLUSIONS: Outpatient healthcare costs markedly increased with increasing BMI in all age categories, particularly among individuals below 65. Addressing the double burden of excess weight and hyperglycemia represents a significant challenge and a healthcare priority.

To predict the risk of chronic kidney disease (CKD) using Generalized Additive2 Models (GA2M).

OBJECTIVE: To train and test a model predicting chronic kidney disease (CKD) using the Generalized Additive2 Model (GA2M), and compare it with other models being obtained with traditional or machine learning approaches. MATERIALS: We adopted the Health Search Database (HSD) which is a representative longitudinal database containing electronic healthcare records of approximately 2 million adults. METHODS: We selected all patients aged 15 years or older being active in HSD between January 1, 2018 and December 31, 2020 with no prior diagnosis of CKD. The following models were trained and tested using 20 candidate determinants for incident CKD: logistic regression, Random Forest, Gradient Boosting Machines (GBMs), GAM, and GA2M. Their prediction performances were compared by calculating Area Under Curve (AUC) and Average Precision (AP). RESULTS: Comparing the predictive performances of the 7 models, the AUC and AP for GBM and GA2M showed the highest values which were equal to 88.9%, 88.8% and 21.8%, 21.1%, respectively. These 2 models outperformed the others including logistic regression. In contrast to GBMs, GA2M kept the interpretability of variable combinations, including interactions and nonlinearities assessment. DISCUSSION: Although GA2M is slightly less performant than light GBM, it is not "black-box" algorithm, so being simply interpretable using shape and heatmap functions. This evidence supports the fact machine learning techniques should be adopted in case of complex algorithms such as those predicting the risk of CKD. CONCLUSION: The GA2M was reliably performant in predicting CKD in primary care. A related decision support system might be therefore implemented.

To support the use of NT-proBNP to better detect heart failure in patients with type 2 diabetes.

PURPOSE: Heart failure (HF) is a chronic disease that causes approximately 300,000 and 250,000 deaths per year in Europe and United States, respectively. Type 2 Diabetes Mellitus (T2DM) is one the major risk factors of HF, and the investigation of NT-proBNP might support the early identification of HF in T2DM sufferers. Nevertheless, this parameter is poorly investigated. Thus, we aimed to demographically and clinically characterize diabetic patients which were prescribed with NT-proBNP in the primary care setting. METHODS: Using a primary care database, we formed a cohort of patients aged ≥18 years diagnosed with T2DM between 2002 and 2021. A multivariate Cox model was adopted to assess the determinants associated with the prescription of NT-proBNP. RESULTS: Among 167,961 T2DM patients, 7558 (4.5%, 95% CI: 4.4-4.6) were prescribed with NT-proBNP. Males and increasing age were expectedly associated with a higher propensity to be prescribed with NT-proBNP. In addition, a significant association was found for those suffering from obesity, ischemic cardiomyopathy, stroke, atrial fibrillation, hypertension, and with a Charlson Index of 2+. CONCLUSION: These determinants might contribute to investigate the NT-proBNP in T2DM sufferers. A decision support system to appropriately ease the prescription of NT-proBNP might be therefore implemented in primary care settings.

A methodology to assess the population size and estimate the needed resources for new licensed medications by combining clinical and administrative databases: The example of glycated haemoglobin in type 2 diabetes.

PURPOSE: To develop and validate a model to estimate glycated haemoglobin (HbA1c) values in patients with type 2 diabetes mellitus (T2DM) using a clinical data source, with the aim to apply this equation to administrative databases. METHODS: Using a primary care and administrative Italian databases, namely the Health Search database (HSD) and the ReS (Ricerca e Salute) database, we selected all patients aged 18 years or older on 31 December 2018 being diagnosed with T2DM and without prior prescription of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. We included patients prescribed with and adherent to metformin. HSD was used to develop and test (using 2019 data as well) the algorithm imputing HbA1c values ≥7% according to a series of covariates. The algorithm was gathered by combining beta-coefficients being estimated by logistic regression models using complete case (excluding missing values) and imputed (after multiple imputation) dataset. The final algorithm was applied to ReS database using the same covariates. RESULTS: The tested algorithms were able to explain 17%-18% variation in assessing HbA1c values. Good discrimination (70%) and calibration were obtained as well. The best algorithm (three) cut-offs, namely those providing correct classifications ranging 66%-70% was therefore calculated and applied to ReS database. By doing so, from 52 999 (27.9, 95% CI: 27.7%-28.1%) to 74 250 (40.1%, 95% CI: 38.9%-39.3%) patients were estimated with HbA1c ≥7%. CONCLUSION: Through this methodology, healthcare authorities should be able to quantify the population eligible to a new licensed medication, such as SGLT-2 inhibitors, and to simulate scenarios to assess reimbursement criteria according to precise estimates.

Early identification of chronic kidney disease: it is time to enhance patient and population-based informatics tools for general practitioners.

Chronic kidney disease (CKD) is a global public health issue that can lead to several complications such as, kidney failure, cerebro/cardiovascular disease, and death. There is a well-documented "awareness gap" among general practitioners (GPs) to recognize CKD. As shown by estimates stemming from the Health Search Database (HSD) of the Italian College of General Practitioners and Primary Care (SIMG), no substantial changes were observed in terms of the incident rate of CKD over the last 10 years. Namely, 10.3-9.5 per 1000 new cases of CKD were estimated in 2012 and 2021, respectively. Thus, strategies to reduce under-recognized cases are needed. Early identification of CKD might improve patient's quality of life and clinical outcomes. In this context, patient- and population-based informatic tools may support both opportunistic and systematic screening of patients at greater risk of CKD. As such, the new effective pharmacotherapies for CKD would be proficiently administered. To this aim, these two complimentary tools have been developed and will be further implemented by GPs. The effectiveness of these instruments in identifying the condition at an early stage and reducing the burden of CKD on the national health system needs to be verified according to the new regulations on medical device (MDR: (EU) 2017/745).

How many and who are patients with heart failure eligible to SGLT2 inhibitors? Responses from the combination of administrative healthcare and primary care databases.

BACKGROUND: Recent successful findings (i.e. DAPA-HF trial) in patients with heart failure (HF) with/without diabetes treated with sodium-glucose co-transporter inhibitors (SGLT2-I) have fostered real-world data analyses. Fondazione Ricerca e Salute's (ReSD) administrative and Health Search's (HSD) primary healthcare databases were combined in the ReS-HS DB Consortium, to identify and characterize HF-patients eligible to SGLT2-I, and assess their costs charged to the Italian National Health Service (INHS). METHODS AND RESULTS: Eligibility to SGLT2-I was HF diagnosis, age ≥ 18 years, reduced (≤40%) ejection fraction (HFrEF) and glomerular filtration rate (GFR) ≥30 ml/min. The HSD, including 13,313 HF-patients (1.5% of the total HSD population) was used to develop and test the algorithms for imputing HFrEF and GFR ≥ 30 ml/min, based on a set of covariates, to the ReSD, including 67,369 (1.5% of the total ReSD population). Subjects eligible to SGLT2-I were 2187 in HSD (61.1% of HFrEF); after the imputation, 15,145 in ReSD (58.8% of HFrEF). Prevalence of eligibility to SGLT2-I was higher in males then in females and increased with age; diabetic patients were 44.3% and 33.4% of HSD and ReSD populations eligible to SGLT2-I, respectively. Estimated from ReSD, the mean annual cost charged to the INHS per patient with HF eligible to SGLT2-I was €7122 (68% due to hospitalizations). CONCLUSIONS: Approximately 20% of patients with HF was eligible to SGLT2-I. Real-world data can identify, quantify and characterize patients eligible to SGLT2-Is and assess related costs for the health care system, thus providing useful information to Regulatory Decision makers.

Updating obesity management strategies: an audit of Italian specialists.

Obesity negatively affects physical and psychological health and increases health care costs. Although there is increasing interest in early diagnosis and timely intervention, there are several principles of care included in the current guidelines for clinical management of obesity that can potentially be updated and improved to address the "clinical inertia" and, consequently, to optimize the management of adult obesity. Using an online Delphi-based process, an Italian board of experts involved in the management of obesity discussed the usefulness of a pro-active approach to the care of patients with obesity, providing a consensus document with practical indications to identify risk factors for morbidity and death and raise awareness throughout the treatment continuum, including the early stages of the disease. In clinical practice, it seems inappropriate to delay an intervention that could avoid progression to a more severe level of obesity and/or prevent the onset of obesity-related comorbidities.Level of evidence Level V, report of expert committee.

Italian guidelines on management of persons with multimorbidity and polypharmacy.

Multimorbidity and polypharmacy are emerging health priorities and the care of persons with these conditions is complex and challenging. The aim of the present guidelines is to develop recommendations for the clinical management of persons with multimorbidity and/or polypharmacy and to provide evidence-based guidance to improve their quality of care. The recommendations have been produced in keeping with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Overall, 14 recommendations were issued, focusing on 4 thematic areas: (1.) General Principles; (2.) target population for an individualized approach to care; (3.) individualized care of patients with multimorbidity and/or polypharmacy; (4.) models of care. These recommendations support the provision of individualized care to persons with multimorbidity and/or polypharmacy as well as the prioritization of care through the identification of persons at increased risk of negative health outcomes. Given the limited available evidence, recommendations could not be issued for all the questions defined and, therefore, some aspects related to the complex care of patients with multimorbidity and/or polypharmacy could not be covered in these guidelines. This points to the need for more research in this field and evidence to improve the care of this population.

Predicting the risk of severe COVID-19 outcomes in primary care: development and validation of a vulnerability index for equitable allocation of effective vaccines.

BACKGROUND: General practitioners (GPs) need a valid, user-friendly tool to identify patients most vulnerable to COVID-19, especially in the hypothesis of a booster vaccine dose. The aim of this study was to develop and validate a GP-friendly prognostic index able to forecast severe COVID-19 outcomes in primary care. Indeed, no such prognostic score is as yet available in Italy. RESEARCH DESIGN AND METHODS: In this retrospective cohort study, a representative sample of 47,868 Italian adults were followed up for 129,000 person-months. The study outcome was COVID-19-related hospitalization and/or death. Candidate predictors were chosen on the basis of systematic evidence and current recommendations. The model was calibrated by using Cox regression. Both internal and external validations were performed. RESULTS: Age, sex and several clinical characteristics were significantly associated with severe outcomes. The final multivariable model explained 60% (95%CI 58-63%) of variance for COVID-19-related hospitalizations and/or deaths. The area under the receiver-operator curve (AUC) was 84% (95% CI: 83-85%). On applying the index to an external cohort, the AUC was 94% (95% CI: 93-95%). CONCLUSIONS: This index is a reliable prognostic tool that can help GPs to prioritize their patients for preventive and therapeutic interventions.

Phytosterols, Cholesterol Control, and Cardiovascular Disease.

The use of phytosterols (or plant sterols) for the control of plasma cholesterol concentrations has recently gained traction because their efficacy is acknowledged by scientific authorities and leading guidelines. Phytosterols, marketed as supplements or functional foods, are formally classified as food in the European Union, are freely available for purchase, and are frequently used without any health professional advice; therefore, they are often self-prescribed, either inappropriately or in situations in which no significant advantage can be obtained. For this reason, a panel of experts with diverse medical and scientific backgrounds was convened by NFI-Nutrition Foundation of Italy-to critically evaluate and summarize the literature available on the topic, with the goal of providing medical doctors and all health professionals useful information to actively govern the use of phytosterols in the context of plasma cholesterol control. Some practical indications to help professionals identify subjects who will most likely benefit from the use of these products, optimizing the therapeutic outcomes, are also provided. The panel concluded that the use of phytosterols as supplements or functional foods to control Low Density Lipoprotein (LDL) cholesterol levels should be preceded by the assessment of some relevant individual characteristics: cardiovascular risk, lipid profile, correct understanding of how to use these products, and willingness to pay for the treatment.

How to Treat COVID-19 Patients at Home in the Italian Context: An Expert Opinion.

The impact of the coronavirus disease (COVID-19), caused by the novel coronavirus SARS-CoV-2, continues to be widespread, with more than 100 million cases diagnosed in more than 220 countries since the virus was first identified in January 2020. Although patients with mild to moderate forms of COVID-19 could be efficiently managed at home, thus reducing the pressure on the healthcare system and minimizing socio-psychological impact on patients, no trial has been proposed, conducted, or even published on COVID-19 home therapy to date. These expert opinions provide indications on the therapeutical at home management of COVID-19 patients, based on the evidence from the literature and on current guidelines.