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.

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.

Osteoporosis is a Predictive Factor for Nephrolithiasis in an Adult Free-Living Caucasian Population From Southern Italy: A Longitudinal Retrospective Study Based on a General Practice Database.

Osteoporosis and nephrolithiasis are common multifactorial disorders with high incidence and prevalence in the adult population worldwide. Both are associated with high morbidity and mortality if not correctly diagnosed and accurately treated. Nephrolithiasis is considered a risk factor for reduced bone mineral density. Aim of this retrospective longitudinal study was to evaluate if osteoporosis is a predictive factor for the nephrolithiasis occurrence. Free-living subjects referring to "COMEGEN" general practitioners cooperative operating in Naples, Southern Italy. Twelve thousand seven hundred ninety-four Caucasian subjects (12,165 female) who performed bone mineral density by dual-energy X-ray absorptiometry and have a negative personal history for nephrolithiasis. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary osteoporosis were excluded from the study. In a mean lapse of time of 19.5 months, 516 subjects had an incident episode of nephrolithiasis. Subjects with osteoporosis had an increased risk of nephrolithiasis than subjects without osteoporosis (Hazard Ratio = 1.33, 95% Confidence Interval 1.01-1.74, p = 0.04). Free-living adult subjects over the age of 40 with idiopathic osteoporosis have an increased risk of incident nephrolithiasis, suggesting the advisability of appropriate investigation and treatment of the metabolic alterations predisposing to nephrolithiasis in patients with osteoporosis. The study protocol was approved by the ASL Napoli 1 Ethical Committee, protocol number 0018508/2018.

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.

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.

Efficacy of Food Supplement Based on Monacolins, γ-Oryzanol, and γ-Aminobutyric Acid in Mild Dyslipidemia: A Randomized, Double-Blind, Parallel-Armed, Placebo-Controlled Clinical Trial.

The risk of cardiovascular disease (CVD) is approximately doubled in subjects with hypercholesterolemia compared to those with normal blood cholesterol levels. Monacolin K (MK), the main active substance in rice fermented by the Monascus purpureus, acts on cholesterol metabolism. Rice also contains other bioactive compounds such as γ-oryzanol (OZ) and γ-aminobutyric acid (GABA). In a randomized, placebo-controlled, double-blind trial, the efficacy and tolerability of a food supplement (FS) based on an ingredient standardized to contain monacolins (4.5%), OZ, and GABA were evaluated in subjects with mild dyslipidemia. For the duration of the trial, enrolled subjects (n = 44, each group) received the FS or placebo and were instructed to use an isocaloric diet. Compared to the placebo group, after a 3 months of the FS, the mean low-density lipoprotein cholesterol and mean TC values were reduced by 19.3 and 8.3%, respectively, while the mean high-density lipoprotein cholesterol value increased by 29.3%. On average, the subjects shifted from very high to moderate CVD risk. Glucose metabolism and hepatic and renal parameters did not change after the treatment and no adverse events were reported. Guidelines to handle hypercholesterolemia with food supplements in specific clinical settings are needed to better manage mild dyslipidemia.

A six-year study in a real-world population reveals an increased incidence of dyslipidemia during COVID-19.

BACKGROUNDRecent studies conducted in individuals who survived COVID-19 suggest that SARS-CoV-2 infection is associated with an increased risk of dyslipidemia. However, it remains unclear whether this augmented risk is confirmed in the general population and how this phenomenon is affecting the overall burden of cardiometabolic diseases.METHODSTo address these aspects, we conducted a 6-year longitudinal study to examine the broader effects of COVID-19 on dyslipidemia incidence in a real-world population (228,266 individuals) residing in Naples in southern Italy. The pre-COVID-19 and COVID-19 groups were balanced for demographic and clinical factors using propensity score matching.RESULTSOur analysis spans a period of 3 years during the COVID-19 pandemic (2020-2022), comparing dyslipidemia incidence with pre-pandemic data (2017-2019), with a follow-up of at least 1,095 days corresponding to 21,349,215 person-years. During the COVID-19 period, we detected an increased risk of developing any dyslipidemia when compared with the pre-COVID-19 triennium (OR = 1.29; 95% CI, 1.19-1.39). Importantly, these estimates were adjusted for comorbidities by a multivariate analysis.CONCLUSIONSTaken together, our data reveal a notable rise in dyslipidemia incidence during the COVID-19 pandemic, suggesting the utility of establishing specialized clinical monitoring protocols for patients who survive COVID-19 to mitigate the risk of developing dyslipidemia.

Chronic Kidney Disease Eligible for SGLT2 Inhibitors Through the Integration of Italian Administrative and Primary Care Data.

Background. Patients with chronic kidney disease (CKD) can be successfully treated with sodium-glucose cotransporter-2 inhibitors (SGLT2-Is), regardless of diabetes. Fondazione Ricerca e Salute's (ReSD) administrative and Health Search's (HSD) primary care databases were combined in the Database Consortium ReS-HS to quantify and describe patients with CKD potentially eligible for SGLT2-Is and assess costs charged to the Italian National Health Service (SSN). Methods. Patients aged ≥18 with CKD and estimated glomerular filtration rate (eGFR) <60 ml/min in 2018, without dialysis and/or renal transplantation, were included. HSD was used to develop and validate algorithms for estimating eGFR, based on covariates, within the ReSD. Comorbidities, dispensed drugs, and direct healthcare costs were assessed. Results. In 2018, 66,297 (5.0% of HSD population) and 211,494 (4.4% of ReSD population) patients with CKD potentially eligible for SGLT2-Is were identified (females ≥58%). Prevalence increased with age with a peak at 75-84 years. Within HSD and ReSD cohorts, respectively: 31.0% and 41.5% had diabetes; in the observation periods, >82% and >96% received ≥1 pharmacological treatment, of which ≥50% and ≥25% received cardiovascular/blood agents and antidiabetics, respectively. From ReSD, mean per capita direct SSN cost was € 3,825 (CI 95%, € 3,655-€ 4,000): 50.1% due to hospitalizations, and 40.2% to pharmaceuticals (31.6% to cardiovascular drugs and 10.1% to antidiabetics). Conclusion. The Database Consortium ReS-HS methodology found 5% of adult SSN beneficiaries with CKD potentially eligible for SGLT2-Is bringing with them a high cardio-metabolic burden which increases the risk of CKD progression.

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.

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).

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.

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.

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.

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.

The role of the general practictioner in the management of urinary calculi.

BACKGROUND: The prevalence of kidney stones tends to increase worldwide due to dietary and climate changes. Disease management involves a high consumption of healthcare system resources which can be reduced with primary prevention measures and prophylaxis of recurrences. In this field, collaboration between general practitioners (GPs) and hospitals is crucial. METHODS: a panel composed of general practitioners and academic and hospital clinicians expert in the treatment of urinary stones met with the aim of identifying the activities that require the participation of the GP in the management process of the kidney stone patient. RESULTS: Collaboration between GP and hospital was found crucial in the treatment of renal colic and its infectious complications, expulsive treatment of ureteral stones, chemolysis of uric acid stones, long-term follow-up after active treatment of urinary stones, prevention of recurrence and primary prevention in the general population. CONCLUSIONS: The role of the GP is crucial in the management and prevention of urinary stones. Community hospitals which are normally led by GPs in liaison with consultants and other health professional can have a role in assisting multidisciplinary working as extended primary care.

Proton pump inhibitors prescribing following the introduction of generic drugs.

BACKGROUND: In many countries, the introduction of generic proton pump inhibitors (PPIs) onto the pharmaceutical market increased the phenomenon of therapeutic substitution in acid-related disorders (ARDs). AIM: To investigate the treatment of ARDs in an Italian primary care setting from 2005 to 2008 by verifying: (i) dynamics of PPI prescribing; (ii) predictors of PPI switching; and (iii) healthcare resource consumption costs. METHODS: This was a retrospective cohort study of 102 general practitioners (GPs) who managed an average of 150000 inhabitants in Naples. Multilevel logistic regression was used to assess the potential predictors of both PPI switching and termination. Primary care costs were expressed as the cost of ARD management per PPI user year. RESULTS: The percentage of PPI users with ARD increased from 5·5% (2005) to 7·0% (2008) (P<0·0001), especially for dyspepsia (from 9·5% to 13·7%; P<0·0001) and chronic treatments (from 23·4% to 29·4%; P<0·0001). PPI switching rose from 13·0% to 16·7% during the period observed (P<0·0001). Calendar years, long-term treatments and gastroesophageal reflux disease were positive predictors of PPI switching. Primary care costs relating to PPI switchers increased by 61·14€ compared with nonswitchers (P<0·0001). CONCLUSIONS: The introduction of generic PPIs onto the Italian market was associated with an increasing amount of PPI prescribing related to chronic treatments, unlicensed indications (e.g. dyspespsia) and therapeutic substitutions. Growing overall costs linked to the phenomenon of PPI switching was also found. Our data support the need to assess the effects of the introduction of generic drugs on both clinical outcomes and the cost management of ARDs.

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.

The value of the polypill in cardiovascular disease: an Italian multidisciplinary Delphi panel consensus.

The purpose of this work was to reach the consensus of a multidisciplinary and multistakeholder Italian panel on the value of polypill in cardiovascular disease, with respect to the clinical, technological, economic and organizational dimension. A three-step modified Delphi method was used to establish consensus. Eleven experts in the area of cardiology, pharmaceutical technology, general practice, hospital pharmacy, pharmacology, and health economics participated in the expert panel. To identify existing evidence concerning the value of polypill in the prevention of patients with cardiovascular disease, a systematic literature review was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement guidelines. In the first round, 22 statements were distributed to the panel. Panel members were asked to mark 'agree' or 'disagree' for each statement and provide any comments. The same voting method was again used for the second round. In the first round nine statements met consensus. In the second round, 10 statements reached consensus. Overall, consensus was reached for 19 statements representing five value polypill domains: clinical, technological, economic and organizational. During a final web meeting with all panel members consensus document open points were discussed. Panel members agreed to recognize polypill as effective in reducing cardiovascular events, blood pressure and lipids, cardiovascular risk and the weight of therapy, in therapeutic adherence improvement, in the absence of differences in bioavailability between drugs administered in fixed or free combinations and the better cost-effectiveness profile compared with standard care. This document represents a knowledge framework to inform decision makers of the value of polypill in cardiovascular prevention.