Efficacy and Tolerability of a Scutellaria lateriflora L. and Cistus × incanus L.-Based Chewing Gum on the Symptoms of Gingivitis: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Preclinical studies have shown that the combination of Cistus × incanus L. and Scutellaria lateriflora L. extracts exerts beneficial effects on oral health against gingivitis. Thus, this study aimed to assess the tolerability of a chewing gum and its efficacy on gingivitis in a double-blind, placebo-controlled clinical trial. Enrolled subjects (n = 60, 18-70 years) were randomized to receive two chewing gums or a placebo daily for 3 months. At baseline (t0) and monthly (t1, t2, and t3) timepoints, the Quantitative Gingival Bleeding Index (QGBI), the Modified Gingival Index (MGI), and the Oral Health 15 items (OH-15)] were employed to assess potential improvements in gingivitis. Pain was self-quantified via the Visual Analogue Scale (VAS), and the Clinical Global Impression Scale for Severity of illness (CGI-S) helped in evaluating the oral general conditions. This study is listed on the ISRCTN registry. At t3, the QGBI, MGI, OH-15, VAS, and CGI-S values decreased in the treated but not in the placebo group (ß = 0.6 ± 0.1, t176 = 3.680, p < 0.001; ß = 0.87 ± 0.21, t115 = 4.263, p < 0.001; ß = 5.3 ± 2.5, t172 = 2.086, p = 0.038; ß = 3.16 ± 0.51, t88 = 6.253, p < 0.001; and ß = 1.09 ± 0.32, t83 = 3.419, p < 0.001, respectively). A significant improvement in gingival health occurred after a 3-month intervention with the chewing gums containing S. lateriflora and C. incanus extracts.

Incidence of new-onset hypertension before, during, and after the COVID-19 pandemic: a 7-year longitudinal cohort study in a large population.

BACKGROUND: While the augmented incidence of diabetes after COVID-19 has been widely confirmed, controversial results are available on the risk of developing hypertension during the COVID-19 pandemic. METHODS: We designed a longitudinal cohort study to analyze a closed cohort followed up over a 7-year period, i.e., 3 years before and 3 years during the COVID-19 pandemic, and during 2023, when the pandemic was declared to be over. We analyzed medical records of more than 200,000 adults obtained from a cooperative of primary physicians from January 1, 2017, to December 31, 2023. The main outcome was the new diagnosis of hypertension. RESULTS: We evaluated 202,163 individuals in the pre-pandemic years and 190,743 in the pandemic years, totaling 206,857 when including 2023 data. The incidence rate of new hypertension was 2.11 (95% C.I. 2.08-2.15) per 100 person-years in the years 2017-2019, increasing to 5.20 (95% C.I. 5.14-5.26) in the period 2020-2022 (RR = 2.46), and to 6.76 (95% C.I. 6.64-6.88) in 2023. The marked difference in trends between the first and the two successive observation periods was substantiated by the fitted regression lines of two Poisson models conducted on the monthly log-incidence of hypertension. CONCLUSIONS: We detected a significant increase in new-onset hypertension during the COVID-19 pandemic, which at the end of the observation period affected ~ 20% of the studied cohort, a percentage higher than the diagnosis of COVID-19 infection within the same time frame. This observation suggests that increased attention to hypertension screening should not be limited to individuals who are aware of having contracted the infection but should be extended to the entire population.

Persistent increase of cardiovascular and cerebrovascular events in COVID-19 patients: a 3-year population-based analysis.

AIMS: We evaluated the incidence and relative risk of major post-acute cardiovascular consequences of SARS-CoV-2 infection in a large real-world population from a primary care database in a region at moderate cardiovascular risk followed up in the period 2020-22. METHODS AND RESULTS: This is a retrospective cohort analysis using data from a cooperative of general practitioners in Italy. Individuals aged >18 affected by COVID-19 starting from January 2020 have been followed up for 3 years. Anonymized data from 228 266 patients in the period 2020-22 were considered for statistical analysis and included 31 764 subjects with a diagnosis of COVID-19. An equal group of subjects recorded in the same database in the period 2017-19 was used as propensity score-matched comparison as an unquestionable COVID-19-free population. Out of the 228 266 individuals included in the COMEGEN database during 2020-22, 31 764 (13.9%) were ascertained positive with SARS-CoV-2 infection by a molecular test reported to general practitioners. The proportion of individuals with a new diagnosis of major adverse cardiovascular and cerebrovascular events was higher in the 2020-22 COVID-19 group than in the 2017-19 COMEGEN propensity score-matched comparator, with an odds ratio of 1.73 (95% confidence interval: 1.53-1.94; P < 0.001). All major adverse cardiovascular and cerebrovascular events considered showed a significantly higher risk in COVID-19 individuals. Incidence calculated for each 6-month period after the diagnosis of COVID-19 in our population was the highest in the first year (1.39% and 1.45%, respectively), although it remained significantly higher than in the COVID-19-free patients throughout the 3 years. CONCLUSION: The increase of cardiovascular risk associated with COVID-19 might be extended for years and not limited to the acute phase of the infection. This should promote the planning of longer follow-up for COVID-19 patients to prevent and promptly manage the potential occurrence of major adverse cardiovascular and cerebrovascular events.

In Vitro Assessment of Cortisol Release Inhibition, Bioaccessibility and Bioavailability of a Chemically Characterized Scutellaria lateriflora L. Hydroethanolic Extract.

Excess cortisol release is associated with numerous health concerns, including psychiatric issues (i.e., anxiety, insomnia, and depression) and nonpsychiatric issues (i.e., osteoporosis). The aim of this study was to assess the in vitro inhibition of cortisol release, bioaccessibility, and bioavailability exerted by a chemically characterized Scutellaria lateriflora L. extract (SLE). The treatment of H295R cells with SLE at increasing, noncytotoxic, concentrations (5-30 ng/mL) showed significant inhibition of cortisol release ranging from 58 to 91%. The in vitro simulated gastric, duodenal, and gastroduodenal digestions, induced statistically significant reductions (p < 0.0001) in the bioactive polyphenolic compounds that most represented SLE. Bioavailability studies on duodenal digested SLE, using Caco-2 cells grown on transwell inserts and a parallel artificial membrane permeability assay, indicated oroxylin A glucuronide and oroxylin A were the only bioactive compounds able to cross the Caco-2 cell membrane and the artificial lipid membrane, respectively. The results suggest possible applications of SLE as a food supplement ingredient against cortisol-mediated stress response and the use of gastroresistant oral dosage forms to partially prevent the degradation of SLE bioactive compounds. In vivo studies and clinical trials remain necessary to draw a conclusion on the efficacy and tolerability of this plant extract.

The Emerging Role of Prediabetes and Its Management: Focus on L-Arginine and a Survey in Clinical Practice.

The worldwide impressive growth of metabolic disorders observed in the last decades, especially type 2 diabetes mellitus and obesity, has generated great interest in the potential benefits of early identification and management of patients at risk. In this view, prediabetes represents a high-risk condition for the development of type 2 diabetes mellitus and cardiovascular diseases, and an ideal target to intercept patients before they develop type 2 diabetes gaining a prominent role even in international guidelines. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of about 50% relative risk reduction. Accumulating data also show potential benefits from pharmacotherapy. In this context, the only available data pertain to metformin as a pharmaceutical drug and vitamin D and L-arginine as nutraceuticals. L-arginine appears to be a very interesting tool in the clinical management of patients with pre-diabetes. In this review we summarize the current knowledge on the role of L-arginine in prediabetes as a potentially useful preventive strategy against the progression to type 2 diabetes, with a particular focus on the underlying molecular mechanisms and the past and ongoing trials. In this article we also report the interesting data about the perception of the prediabetic condition and its therapeutic management in the clinical practice in Italy. An early identification and a prompt management of people with prediabetes appears to be of paramount importance to prevent the progression to diabetes and avoid its cardiovascular consequences.

Incidence of type 2 diabetes before and during the COVID-19 pandemic in Naples, Italy: a longitudinal cohort study.

Background: The association of COVID-19 with the development of new-onset diabetes has been recently investigated by several groups, yielding controversial results. Population studies currently available in the literature are mostly focused on type 1 diabetes (T1D), comparing patients with a SARS-CoV-2 positive test to individuals without COVID-19, especially in paediatric populations. In this study, we sought to determine the incidence of type 2 diabetes (T2D) before and during the COVID-19 pandemic. Methods: In this longitudinal cohort study, we analysed a cohort followed up over a 6-year period using an Interrupted Time Series approach, i.e. 3-years before and 3-years during the COVID-19 pandemic. We analysed data obtained from >200,000 adults in Naples (Italy) from January 1st 2017 to December 31st 2022. In this manner, we had the opportunity to compare the incidence of newly diagnosed T2D before (2017-2019) and during (2020-2022) the COVID-19 pandemic. The key inclusion criteria were age >18-year-old and data availability for the period of observation; patients with a diagnosis of diabetes obtained before 2017 were excluded. The main outcome of the study was the new diagnosis of T2D, as defined by the International Classification of Diseases 10 (ICD-X), including prescription of antidiabetic therapies for more than 30 days. Findings: A total of 234,956 subjects were followed-up for at least 3-years before or 3-years during the COVID-19 pandemic and were included in the study; among these, 216,498 were analysed in the pre-pandemic years and 216,422 in the pandemic years. The incidence rate of T2D was 4.85 (95% CI, 4.68-5.02) per 1000 person-years in the period 2017-2019, vs 12.21 (95% CI, 11.94-12.48) per 1000 person-years in 2020-2022, with an increase of about twice and a half. Moreover, the doubling time of the number of new diagnoses of T2D estimated by unadjusted Poisson model was 97.12 (95% CI, 40.51-153.75) months in the prepandemic period vs 23.13 (95% CI, 16.02-41.59) months during the COVID-19 pandemic. Interestingly, these findings were also confirmed when examining patients with prediabetes. Interpretation: Our data from this 6-year study on more than 200,000 adult participants indicate that the incidence of T2D was significantly higher during the pandemic compared to the pre-COVID-19 phase. As a consequence, the epidemiology of the disease may change in terms of rates of outcomes as well as public health costs. COVID-19 survivors, especially patients with prediabetes, may require specific clinical programs to prevent T2D. Funding: The US National Institutes of Health (NIH: NIDDK, NHLBI, NCATS), Diabetes Action Research and Education Foundation, Weill-Caulier and Hirschl Trusts.

Efficacy of digestive enzyme supplementation in functional dyspepsia: A monocentric, randomized, double-blind, placebo-controlled, clinical trial.

Functional dyspepsia is a form of dyspepsia lacking in clear causes following clinical assessment. Dyspepsia is characterized by episodic or persistent abdominal pain or discomfort of the upper gastrointestinal (GI) tract. Its onset has been linked with a deficiency or dysfunction of digestive enzymes. Thus, consumption of digestive multi-enzymatic preparations may be effectively used for the reduction of symptoms. The aim of this study is to assess the effectiveness and tolerability of the supplementation of a normal diet with a multi-enzyme blend obtained from fungal fermentation, in a randomized, placebo-controlled, double-blind, clinical trial. Enrolled subjects (n = 120, male: 63, female: 57), aged 18-59 years, were randomized (allocation ratio 1:1) to receive either 2 capsules per day of the food supplement (containing 200 mg of the multi-enzyme blend/capsule) or placebo, for 2 months. The primary outcome of the study (i.e., improvements in quality of life) was evaluated by the Nepean Dyspepsia Index-SF (NDI-SF) questionnaire, while the secondary outcomes (i.e., severity of pain and the quality of sleep) were assessed through the Visual Analogue Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) questionnaire. The results showed an improvement in NDI-SF1, NDI-SF2-5, VAS, and PSQI scores in subjects treated with the multi-enzyme blend, indicating an improvement in quality of life and of sleep, and a decreased severity of pain, following the supplementation with digestive enzymes, without side effects. In conclusion, treatment with digestive enzymes was found to be effective in the reduction of functional dyspepsia symptoms and in the improvement of sleep quality, and is well-tolerated.

Combination of Chemically Characterized Pomegranate Extract and Hydrophilic Vitamins against Prolonged Fatigue: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Prolonged fatigue is associated with non-pathological causes and lacks an established therapeutic approach. The current study is aimed at assessing the efficacy of a new food supplement (Improve™) based on a chemically characterized pomegranate extract and hydro-soluble vitamins (B complex and C). UHPLC-HRMS analysis of pomegranate extract showed the presence of 59 compounds, with gallotannins and ellagitannins being the most abundant phytochemicals. For the clinical study, 58 subjects were randomized into two groups, 1 and 2 (n = 29, each), which received either the food supplement or placebo. The effects of the food supplement against fatigue were assessed via validated questionnaires, recorded at time intervals t0 (at baseline), t1 (after 28 days), t2 (56 days), and t3 (after follow-up) in combination with the analysis of biochemical markers at t0 and t2. Fatigue severity scale (FSS) questionnaire scores were significantly decreased at the t2 and t3 time intervals in subjects treated with the food supplements, while the effect of the food supplement on a 12-Item Short Form Survey (SF-12) was not considerable. Moreover, the food supplement did not significantly affect biochemical parameters associated with fatigue and stress conditions. This study shows that the food supplement tested reduces prolonged fatigue following two months of supplementation in healthy subjects with mild prolonged fatigue.

In Vitro Antimicrobial and Antibiofilm Properties and Bioaccessibility after Oral Digestion of Chemically Characterized Extracts Obtained from Cistus × incanus L., Scutellaria lateriflora L., and Their Combination.

Periodontal diseases are oral inflammatory diseases ranging from gingivitis to chronic periodontitis. Porphyromonas gingivalis is one of the major pathogens responsible for severe and chronic periodontitis. Plant extracts with antimicrobial activity could be considered possible alternatives to chlorhexidine, an antiseptic substance used in oral hygiene thatcan cause bacteria resistance. Here, two commercial extracts obtained from Cistus × incanus L. and Scutellaria lateriflora L. were chemically characterized usingUltra-High-Performance Liquid Chromatography (UHPLC) coupled with a Q-Exactive Hybrid Quadrupole Orbitrap Mass Spectrometer. The extracts were studied for their bioaccessibility after simulated in vitro oral digestion, their antimicrobial activity against P. gingivalis, their protective effects against cellular invasion by P. gingivalis, and their antibiofilm activity. The extracts were found to contain very complex mixtures of polyphenols, which were quite stable after in vitro simulated oral digestion and demonstrated mild, dose-dependent inhibitory activity against P. gingivalis growth. This activity increased with the combination of the two extracts. Moreover, the combination of the extracts induced a reduction in P. gingivalis HaCaT invasiveness, and the reduction in biofilm came to around 80%. In conclusion, a combination of C. incanus and S. lateriflora showed promising effects useful in the treatment of gingivitis.

Postprandial Glycemic and Insulinemic Response by a Brewer's Spent Grain Extract-Based Food Supplement in Subjects with Slightly Impaired Glucose Tolerance: A Monocentric, Randomized, Cross-Over, Double-Blind, Placebo-Controlled Clinical Trial.

Dietary fiber exerts beneficial effects on human health reducing the risk factors of metabolic related diseases such as hyperglycemia, insulin resistance, and hypercholesterolemia. The aim of this study is to demonstrate the efficacy of a food supplement based on brewer's spent grain (BSG) extract in the reduction of postprandial glycemia and insulinemia in normoglycemic subjects. BSG was chemically characterized, revealing the presence of resistant starch (14.64 g/100 g), arabinoxylans (7.50 g/100 g), ß-glucans (1.92 g/100 g) and other soluble fibers (6.43 g/100 g), and bioaccessible ferulic acid (91.3 mg/100 g). For the clinical study, 40 normoglycemic subjects were randomized into two groups, 1 and 2 (n = 20), for a cross-over clinical design and received either BSG extract-based food supplement or placebo. Postprandial blood glucose values were significantly lower than corresponding values in the placebo group after 90 and 120 min, while at the baseline and in the first 60 min, the two glycemic curves overlapped substantially. This improved clinical outcome was corroborated by significant reductions in postprandial insulinemia. None of the subjects reported adverse effects. This study showed that the tested BSG extract-based food supplement improves glucose metabolism and insulinemic response in normoglycemic subjects with at most a mild insulin resistance.

Safety and efficacy of alpha-lipoic acid oral supplementation in the reduction of pain with unknown etiology: A monocentric, randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Extensive evidence suggests that alpha-lipoic acid (ALA) is effective in diabetic neuropathy pain management. However, little is known on its safety and efficacy in reducing idiopathic pain in normoglycemic subjects. The aim of this study was to evaluate ALA food supplement safety and efficacy in the reduction of different forms of idiopathic pain. METHODS: Two-hundred and ten normoglycemic adults suffering from idiopathic pain (i.e. 57 subjects with primitive neuropathic pain, 141 subjects with arthralgia with unknown etiology, and 12 subjects with idiopathic myalgia) were randomized to receive placebo, 400 mg/day, or 800 mg/day of ALA. Participants underwent two visits (at baseline = t0, and after 2 months = t1) in which two validated questionaries for pain (numerical rating scale [NRS] and visual analogue scale [VAS]) were collected; fasting blood glucose assessment, adverse effects, and renal and hepatic toxicity were also monitored. RESULTS: At t1, none of subjects treated with ALA reported a decreased glycemia or adverse effects. The treated subjects showed a significant reduction in NRS (p < 0.001) while the placebo group did not show any NRS reduction (p = 0.86). Similar results were also obtained for VAS. Statistical analysis aimed at detecting possible differences in NRS and VAS scores among treatment groups based on the source of pain did not reveal any significant effect. CONCLUSIONS: Since the management of idiopathic pain is challenging for physicians, the use of ALA food supplements could be a feasible option, based on its safety and efficacy compared to commonly-used analgesic drugs.

Fixed Versus Free Combinations Of Antihypertensive Drugs: Analyses Of Real-World Data Of Persistence With Therapy In Italy.

PURPOSE: To analyse the pattern of use and cost of antihypertensive drugs in new users in an Italian population, and explore the patient/treatment factors associated with the risk of therapy discontinuation. PATIENTS AND METHODS: In this retrospective study, information was collected from a population-based electronic primary-care database. Persistence with medication use 1 year from therapy initiation was evaluated for each user using the gap method. Each new user was classified according to his/her pattern of use as: "continuer", "discontinuer" "switching" or "add-on". A Cox regression model was used to analyse the factors influencing therapy discontinuation. Primary-care costs comprised specialists' visits, diagnostic procedures and pharmacologic therapies. RESULTS: Among 14,999 subjects included in persistence analyses, 55.1% of cases initially started on monotherapy were classified as discontinuers vs 36.5% of cases taking combination therapy (42.3% vs 32.7%, respectively, for free and fixed combinations, P < 0.01). Old age, high cardiovascular risk and being in receipt of fixed-combination therapy were associated with greater persistence. Overall, the primary-care cost/person/year of hypertension management was ~€95.3 (IQR, 144.9). The monotherapy cost was €88 per patient (IQR, 132.9), and that for combination therapy was €151±148.3. The median cost/patient with a fixed combination was lower than that for a free combination (€98.4 (IQR, 155.3) and €154.9 (IQR, 182.6), respectively). CONCLUSION: The initial type of therapy prescribed influences persistence. Prescribing fixed combinations might be a good choice as initial therapy.

Further Effort is Needed to Improve Management of Chronic Pain in Primary Care. Results from the Arkys Project.

Treatment of chronic pain is challenging. The Arkys project was initiated in Italy to assist general practitioners (GPs) in the management of chronic pain. The main objective of this study was to determine the usefulness of Arkys for selecting new therapeutic strategies. An online interactive questionnaire for assessing pain and guiding therapeutic decisions was made available to GPs participating to Arkys. The GPs were invited to complete the questionnaire for each patient who presented moderate-severe chronic pain, and to decide on a new analgesic treatment based on the information provided by the questionnaire. Two hundred and forty four GPs participated with a total of 3035 patients. Patients (mean age 68.9 years) had mostly chronic non-cancer pain (87.7%). In 42.3%, pain had neuropathic components. Only 53.6% of patients were in treatment with analgesics (strong opioids, 38.9%; NSAIDs, 32.6%; weak opioids, 25.6%; anti-epileptics, 17.3%; paracetamol, 14.9%). Use of the questionnaire resulted in the prescription of analgesics to all patients and in increased prescription of strong opioids (69.7%). NSAID prescription decreased (12.8%), while anti-epileptics use remained stable. These findings show that current management of chronic pain in primary care is far from optimal and that efforts are needed to educate GPs and improve guideline implementation.

Demographic and comorbidity profile of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia in a real-life clinical setting: Are 5-alpha-reductase inhibitor consumers different?

PURPOSE: We aimed to describe, in a daily clinical practice setting, the demographic and comorbidity profile of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS), to compare the characteristics of patients receiving 5-alpha-reductase inhibitors (5-ARIs) with those not receiving them and to investigate predictors of 5-ARI prescription. METHODS: We performed a retrospective observational study using data retrieved from a general practitioners database. Male patients with diagnosis of BPH-LUTS were included. The following demographic and clinical data were available and extracted: age, comorbidities, BPH-LUTS medical therapy, drugs for comorbidities. A subgroup analysis was performed according to the use of 5-ARIs. Factors associated with 5-ARI prescription were assessed with uni- and multivariate analyses. RESULTS: A total of 7,103 patients were identified. Most patients (71.7%) were aged ≥65 years. Hypertension was present in 64.9% of patients; it was the most prevalent comorbidity followed by diabetes mellitus, hypercholesterolemia, coronary artery disease and other dyslipidemias. Overall, 38.22% of patients were treated with 5-ARIs. Mean age of patients taking 5-ARIs was significantly higher. The prevalence of hypertension and the use of antihypertensive drugs were significantly higher among patients receiving 5-ARIs. Older age was an independent predictor of 5-ARI prescription. CONCLUSIONS: In a daily clinical practice setting, patients with BPH-LUTS receiving 5-ARIs are significantly older and have significantly higher prevalence of hypertension if compared with patients with BPH-LUTS not receiving 5-ARIs. Older age is an independent predictor of 5-ARI prescription.

Urolithiasis in Italy: an epidemiological study.

OBJECTIVES: Worldwide the urolithiasis is the third most frequent urological disease affecting both males and females. In literature there are not recent Italian epidemiological data about stone disease. The objective of this study is the evaluation of current epidemiology of urolithiasis in Italy using the Health Search/CSD Longitudinal Patient Database (HS) database. MATERIAL AND METHODS: An observational, descriptive, retrospective trial was conducted. Inclusion criteria were: family physician- assisted Italian living population member of HS database within 31 December 2012, both genders, age over 17 years, at least two years of clinical history recorded from the beginning the trial. Data were collected by HS database and elaborated by its software Millewin®. RESULTS: In Italy prevalence of urolithiasis in 2012 was 4.14%, it was higher in males than in females (4.53% versus 3.78%) with a positive relation with increasing age. The highest prevalence rate of urolithiasis was reported in the region Campania (6.08%). The general incidence was 2.23 * 1000, with the highest incidence in the region Sicilia (3.15 * 1000). Incidence was higher in group age 65-74 years (3.18 * 1000). CONCLUSIONS: In Italy the incidence and prevalence of urolithiasis is increasing with particular distribution in relation to gender, age and regional position.

Determinants of alanine aminotransferase levels in a large population from Southern Italy: relationship between alanine aminotransferase and age.

BACKGROUND: Determinants of alanine aminotransferase levels have never been investigated in real-life settings. The relationship between alanine aminotransferase and age remains controversial. We evaluated epidemiological, anthropometric, and metabolic factors associated with alanine aminotransferase, focusing on the relationship between alanine aminotransferase and age. METHODS: A 5-year retrospective analysis was performed on data recorded by 120 general practitioners from Naples (Italy), caring for 170,000 subjects. Exclusion criteria were age <18 years, diagnosis of chronic liver disease, positive markers for viral hepatitis, alcohol abuse, and alanine aminotransferase >100UI/L. RESULTS: 44,232 subjects were enrolled (42.7% males, mean age 56±18 years). Alanine aminotransferase showed independent direct associations with body mass index, glycaemia, cholesterol, and triglycerides (p<0.001), and inverse associations with high-density lipoprotein cholesterol (p<0.001) and creatinine (p<0.01). The relationship between alanine aminotransferase and age was better expressed by polynomial regression (r=0.18, p<0.001), creating an inverted parabola. Mean alanine aminotransferase increased until the third decade in males and the fifth in females, with a subsequent progressive decrease in both genders. The inverse association between alanine aminotransferase and age in older subjects was independent from metabolic factors. CONCLUSIONS: This real-life setting study, supports the concept that dysmetabolism is a strong determinant of liver injury. Based on our data, a reduction of the standard upper limit of normal alanine aminotransferase should be considered for older subjects.

Diagnosis and management of atrial fibrillation by primary care physicians in Italy : a retrospective, observational analysis.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a heavy burden of morbidity and mortality, mainly due to an increased risk of cerebrovascular events and cardiac failure. Oral anticoagulant (OAC) treatment prevents stroke and systemic thromboembolism in patients with AF and its use is strongly recommended in guidelines. However, its use in this patient group remains limited. Primary care physicians (PCPs) have an important role to play in this context. OBJECTIVE: The primary objective was to estimate prevalence and epidemiological features of AF in the primary care setting, focusing on ischaemic and bleeding risk assessment. A secondary objective was to examine the PCPs' level of adherence to the guidelines for the prevention of thromboembolic risk in these patients. METHODS: This retrospective, observational study was based on data entered by 128 PCPs into the Health Search (HS) Thales database, identifying patients with a diagnosis of AF at the time of the analysis. RESULTS: Out of 167,056 patients analysed, 2,173 (1.3 %) were diagnosed with AF, with 86 % at high risk for ischaemic stroke, according to CHA(2)DS(2)-VASc (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65-74 years, sex category [female]) stratification. After the diagnosis of AF, 84 % of patients were prescribed OAC treatment. However, at 2 years' follow-up, only 29.6 % were still being treated with OACs. CONCLUSION: The prevalence of AF in this analysis was consistent with previously reported Italian national epidemiological data. Adherence to the European Society of Cardiology AF guidelines by PCPs was low, despite the high levels of stroke risk. At the end of the observation period less than one-third of patients were still on OAC therapy. Awareness of the benefits of OACs in stroke prevention in AF patients needs to be improved.