Rifaximin Use, Adherence and Persistence in Patients with Hepatic Encephalopathy: A Real-World Study in the South of Italy.

Real-world data on the therapeutic management of hepatic encephalopathy (HE) patients are limited. The aim of this study was to evaluate the HE medications prescribed in an Italian cohort of HE patients post-discharge and to assess the real-world rifaximin adherence and persistence over 1 year. An observation retrospective study was conducted using data retrieved from outpatient pharmaceutical databases and hospital discharge records of the Campania region. For all subjects hospitalized for HE during 2019 (cohort 1), the HE medications prescribed within 60 days after discharge were evaluated. Adherence (proportion of days covered, PDC) and persistence were estimated for rifaximin 550 mg incident users over 1 year (cohort 2). Patients with PDC ≥80% were considered adherents. Persistence was defined as the period of time from the first rifaximin prescription to the date of discontinuation. Discontinuation was assessed using the permissible gap method. In cohort 1, 544 patients were identified; 58.5% received rifaximin while 15.6% only received non-absorbable disaccharides and 25.9% did not receive any HE medications. In cohort 2, 650 users were selected; only 54.5% were adherents and 35% were persistent users at 1 year. This real-world study highlights that quality improvement in therapeutic management is needed to potentially improve the outcomes of HE patients.

[Real-world analysis of the use of rifaximin 200 mg in the Campania Region.] / Analisi real world sull'utilizzo di rifaximina 200 mg nella Regione Campania.

INTRODUCTION: Since its approval in Italy in 1987, rifaximin has been licensed in over 30 countries for the treatment of a wide range gastrointestinal diseases. The aim of the study was to analyze the real world use of rifaximin 200 mg in the Campania region. METHODS: An observation retrospective study was conducted analysing the prescriptions of rifaximin received by the subjects ≥18 years old resident in the Campania Region. For each user the first rifaximin prescription in 2019 was defined as index date. All the prescriptions during the 12 months following the index date were analyzed. The subjects were categorized according to the number of packages/year received (1-4, 5-12, 13-24, >24). RESULTS: 231,207 subjects received at least one package/year of rifaximin 200 mg with a prevalence of use of 4.9% and a total annual expenditure of 9.2 million euros. The 73.9% of users received 1-4 packages/year, 16.4% between 5-12 packages/year and 7.7% between 13-24 packages/year. The 2.0% of the users received more than 24 packages/year with an incidence on total expenditure equal to 14.8% (5% is due to those who received more than 40 packages/year). DISCUSSION: About two thirds of rifaximin users received no more than three packages, presumably for the treatment of the infectious gastroenteritis or diarrheal syndromes, while 24% received 5-24 packages/year probably for the relapsing chronic intestinal pathologies. The 15% of the expenditure and consumption is related to subjects receiving more than 24 packages/year, probably due to the treatment of chronic liver diseases. CONCLUSIONS: The use of rifaximin 200 mg should be further investigated in different recurrent chronic diseases, especially to verify which schemes and dosages are used in real life compared to those tested in clinical trials.

Hepatitis C Virus Micro-Elimination Plan in Southern Italy: The "HCV ICEberg" Project.

This study evaluates the feasibility of a local action program for HCV micro-elimination in highly endemic areas. Retrospective analysis: administrative and laboratory data (Local Health Unit, southern Italy) were integrated to quantize the anti-HCV-positive subjects not RNA tested and untreated HCV-infected subjects (2018-2022). Prospective analysis: all subjects admitted to a division of the LHU largest hospital (2021-2022) were tested for HCV, with linkage of active-infected patients to care. Overall, 49287 subjects were HCV-Ab tested: 1071 (2.2%) resulted positive without information for an HCV RNA test and 230 (0.5%) had an active infection not yet cured. Among 856 admitted subjects, 54 (6.3%) were HCV-Ab+ and 27 (3.0%) HCV RNA+. Of HCV-infected patients, 22.2% had advanced liver disease, highlighting the need for earlier diagnosis; 27.7% were unaware of HCV infection; and 20.4% were previously aware but never referred to a clinical center. Of these, 26% died and 74% received treatment. Our study emphasizes the value of an active HCV hospital case-finding program to enhance diagnosis in patients with several comorbidities and to easily link them to care. Our data strongly suggest extending this program to all hospital wards/access as a standard of care, particularly in highly endemic areas, to help HCV disease control and take steps in achieving the elimination goals.

Exploring Contemporary Data on Lipid-Lowering Therapy Prescribing in Patients Following Discharge for Atherosclerotic Cardiovascular Disease in the South of Italy.

Current international guidelines strongly recommend the use of high-intensity lipid-lowering therapy (LLT) after hospitalization for atherosclerotic cardiovascular disease (ASCVD) events. With this study, our aim was to evaluate LLT prescribing in a large Italian cohort of patients after discharge for an ASCVD event, exploring factors associated with a lower likelihood of receiving any LLT and high-intensity LLT. Individuals aged 18 years and older discharged for an ASCVD event in 2019-2020 were identified using hospital discharge abstracts from two local health units of the Campania region. LLT treatment patterns were analyzed in the 6 months after the index event. Logistic regression models were developed for estimating patient predictors of any LLT prescription and to compare high-intensity and low-to-moderate-intensity LLT. Results: A total of 8705 subjects were identified. In the 6 months post-discharge, 56.7% of patients were prescribed LLT and, of those, 48.7% were high-intensity LLT. Female sex, older age, and stroke/TIA or PAD conditions were associated with a higher likelihood of not receiving high-intensity LLT. Similar predictors were found for LLT prescriptions. LLT utilization and the specific use of high-intensity LLT remain low in patients with ASCVD, suggesting a substantial unmet need among these patients in the contemporary real-world setting.

Predictors of Opioid Prescribing for Non-Malignant Low Back Pain in an Italian Primary Care Setting.

This study explores which patient characteristics could affect the likelihood of starting low back pain (LBP) treatment with opioid analgesics vs. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in an Italian primary care setting. Through the computerized medical records of 65 General Practitioners, non-malignant LBP subjects who received the first pain intensity measurement and an NSAID or opioid prescription, during 2015-2016, were identified. Patients with an opioid prescription 1-year before the first pain intensity measurement were excluded. A multivariable logistic regression model was used to determine predictive factors of opioid prescribing. Results were reported as Odds Ratios (ORs) with a 95% confidence interval (CI), with p < 0.05 indicating statistical significance. A total of 505 individuals with LBP were included: of those, 72.7% received an NSAID prescription and 27.3% an opioid one (64% of subjects started with strong opioid). Compared to patients receiving an NSAID, those with opioid prescriptions were younger, reported the highest pain intensity (moderate pain OR = 2.42; 95% CI 1.48-3.96 and severe pain OR = 2.01; 95% CI 1.04-3.88) and were more likely to have asthma (OR 3.95; 95% CI 1.99-7.84). Despite clinical guidelines, a large proportion of LBP patients started with strong opioid therapy. Asthma, younger age and pain intensity were predictors of opioid prescribing when compared to NSAIDs for LBP treatment.

Cardiovascular Outcomes and Mortality Associated With Discontinuing Statins in Older Patients Receiving Polypharmacy.

Importance: Polypharmacy is a major health concern among older adults. While deprescribing may reduce inappropriate medicine use, its effect on clinical end points remains uncertain. Objective: To assess the clinical implications of discontinuing the use of statins while maintaining other drugs in a cohort of older patients receiving polypharmacy. Design, Setting, and Participants: This retrospective, population-based cohort study included the 29 047 residents in the Italian Lombardy region aged 65 years or older who were receiving uninterrupted treatment with statins, blood pressure-lowering, antidiabetic, and antiplatelet agents from October 1, 2013, until January 31, 2015, with follow-up through June 30, 2018. Data were collected using the health care utilization database of Lombardy region in Italy. Data analysis was conducted from March to November 2020. Exposures: Cohort members were followed up to identify those who discontinued statins. Among this group, those who maintained other therapies during the first 6 months after statin discontinuation were 1:1 propensity score matched with patients who discontinued neither statins nor other drugs. Main Outcome and Measures: The pairs of patients discontinuing and maintaining statins were followed up from the initial discontinuation until June 30, 2018, to estimate the hazard ratios (HRs) and 95% CIs for fatal and nonfatal outcomes associated with statin discontinuation. Results: The full cohort inclued 29 047 patients exposed to polypharmacy (mean [SD] age, 76.5 [6.5] years; 18 257 [62.9%] men). Of them, 5819 (20.0%) discontinued statins while maintaining other medications, and 4010 (68.9%) of them were matched with a comparator. In the discontinuing group, the mean (SD) age was 76.5 (6.4) years, 2405 (60.0%) were men, and 506 (12.6%) had Multisource Comorbidity Scores of 4 or 5. In the maintaining group, the mean (SD) age was 76.1 (6.3) years, 2474 (61.7%) were men, and 482 (12.0%) had multisource comorbidity scores of 4 or 5. Compared with the maintaining group, patients in the discontinuing group had increased risk of hospital admissions for heart failure (HR, 1.24; 95% CI, 1.07-1.43) and any cardiovascular outcome (HR, 1.14; 95% CI, 1.03-1.26), deaths from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.05-1.19). Conclusions and Relevance: In this study of patients receiving polypharmacy, discontinuing statins while maintaining other drug therapies was associated with an increase in the long-term risk of fatal and nonfatal cardiovascular outcomes.

Evolution in Real-World Therapeutic Strategies for HIV Treatment: A Retrospective Study in Southern Italy, 2014-2020.

Changes in HIV treatment guidelines over the last two decades reflect the evolving challenges in this field. Our study examined treatment change patterns throughout a 7-year period in a large Italian cohort of HIV patients as well as the reasons and direction of changes. Treatment-naïve and -experienced HIV patients managed by Cotugno Hospital of Naples between 2014 and 2020 were analyzed. During the period, the proportion of single-tablet regimen treatment sharply increased for the naïve and experienced patients. Regimens containing integrase strand transfer inhibitors rapidly replaced those containing protease inhibitor and non-nucleoside reverse transcriptase inhibitors. The use of the tenofovir alafenamide fumarate/emtricitabine backbone increased rapidly after its introduction in the Italian pharmaceutical market, making up 63.7 and 54.9% of all treatments in naïve and experienced patients, respectively, in 2020. The main reason for treatment changes was optimization and/or simplification (90.6% in 2018; 85.3% in 2019; 95.5 in 2020) followed by adverse effects and virological failure. Our real-world analysis revealed that the majority of treatment-naïve and treatment-experienced patients received antiretroviral drugs listed as preferred/recommended in current recommendations. Regimen optimization and/or simplification is a leading cause of treatment modification, while virologic failure or adverse effects are less likely reasons for modification in the current treatment landscape.

Influence of statin-potency on the risk of kidney disease - A nationwide cohort study using laboratory data.

PURPOSE: To estimate the risk of kidney disease in high-potency statin users compared to those treated with low-potency statins without history of kidney disease at statin initiation, linking the Swedish national healthcare registers and laboratory data. METHODS: Incident users of statins, ≥40 years of age, with estimated Glomerular Filtration Rate (eGFR) >60 ml/min/1.73 m2 and no diagnosis of kidney disease at treatment initiation were identified between 2006 and 2007 and then followed for 2-years. The outcome was the incidence of kidney disease identified by the presence of the diagnostic code in the healthcare registers or eGFR <60 ml/min/1.73 m2 . We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjusted and propensity score (PS)-matched Cox proportional hazards models. RESULTS: A total of 27 385 patients were identified, 25.2% of which treated with a high-potency statin. During the follow-up, 68 (0.25%) patients were identified with a diagnosis of kidney disease from the registers. The number increased to 2498 (9.1%) when the criteria of eGFR <60 ml/min/1.73 m2 was added. The adjusted HR of kidney disease in high-potency statin users was 1.14 (95%CI 1.03-1.25) compared to low-potency users; the result was unchanged after the PS approach. CONCLUSIONS: Adding information from laboratory data to those from the national health registers, a slightly increased risk for kidney disease was found in high-potency statin users without pre-existing kidney disease at treatment initiation compared to those treated with low-potency statins.

Screening, Linkage to Care and Treatment of Hepatitis C Infection in Primary Care Setting in the South of Italy.

Hepatitis C virus (HCV) infection remains a pressing public health issue. Our aim is to assess the linkage to care of patients with HCV diagnosis and to support the proactive case-finding of new HCV-infected patients in an Italian primary care setting. This was a retrospective cohort study of 44 general practitioners (GPs) who managed 63,955 inhabitants in the Campania region. Adults with already known HCV diagnosis or those with HCV high-risk profile at June 2019 were identified and reviewed by GPs to identify newly diagnosed of HCV and to assess the linkage to care and treatment for the HCV patients. Overall, 698 HCV patients were identified, 596 with already known HCV diagnosis and 102 identified by testing the high-risk group (2614 subjects). The 38.8% were already treated with direct-acting antivirals, 18.9% were referred to the specialist center and 42.3% were not sent to specialist care for treatment. Similar proportions were found for patients with an already known HCV diagnosis and those newly diagnosed. Given that the HCV infection is often silent, case-finding needs to be proactive and based on risk information. Our findings suggested that there needs to be greater outreach, awareness and education among GPs in order to enhance HCV testing, linkage to care and treatment.

[Therapeutic management of low back pain in general practice.] / La gestione terapeutica del dolore lombalgico in medicina generale.

INTRODUCTION: Low back pain is one of the most frequent causes of consultation of the General Practitioner (GP). The purpose of the present study is to analyze the therapeutic management of low back pain, in relation to pain intensity, in the primary care setting and to assess its impact on the patient's quality of life. METHODS: From the computerized medical records of 65 GPs, all working in the Salerno province (South of Italy), data concerning non-cancer subjects affected by low back or sciatica pain, over 18 years, who consulted the GP in the period between February 1, 2015 and January 31, 2016, were extracted. Pain intensity and quality of life were reported using the 0-10 numeric rating scale (NRS) and the EQ-5D instruments, respectively. RESULTS: A total of 2555 subjects were identified: 28.7% reported mild pain (NRS 0-3), 55.6% moderate pain (NRS 4-6) and 15.7% severe pain (NRS 7-10). Only 35% of patients received a prescription for pain therapy (24.5% in mild pain; 34.1% in moderate pain and 57.1% in severe pain); non-steroidal anti-inflammatory drugs in monotherapy were the most prescribed therapeutic category regardless of pain intensity (61.1% in mild pain, 65.1% in moderate pain and 57.6% in severe pain, p=0.099), followed by strong opioids (17.2%, 15.3% and 24.5%, p=0.011). Overall, mean value for EQ-5D utility was 0.44 (0.61 in mild pain, 0.47 in moderate pain, 0.22 in severe pain). CONCLUSIONS: The results of this study highlight that low back pain is a highly debilitating condition, probably still under-treated or inadequately treated by the GP.

The inpatient hospital burden of comorbidities in HCV-infected patients: A population-based study in two Italian regions with high HCV endemicity (The BaCH study).

BACKGROUND & AIMS: Hepatitis C (HCV) is associated with several extrahepatic manifestations, and estimates of the hospitalization burden related to these comorbidities are still limited. The aim of this study is to quantify the hospitalization risk associated with comorbidities in an Italian cohort of HCV-infected patients and to assess which of these comorbidities are associated with high hospitalization resource utilization. METHODS: Individuals aged 18 years and older with HCV-infection were identified in the Abruzzo's and Campania's hospital discharge abstracts during 2011-2014 with 1-year follow-up. Cardio-and cerebrovascular disease, diabetes and renal disease were grouped as HCV-related comorbidities. Negative binomial models were used to compare the hospitalization risk in patients with and without each comorbidity. Logistic regression model was used to identify the characteristics of being in the top 20% of patients with the highest hospitalization costs (high-cost patients). RESULTS: 15,985 patients were included; 19.9% had a liver complication and 48.6% had one or more HCV-related comorbidities. During follow-up, 36.0% of patients underwent at least one hospitalization. Liver complications and the presence of two or more HCV-related comorbidities were the major predictors of hospitalization and highest inpatient costs. Among those, patients with cardiovascular disease had the highest risk of hospitalization (Incidence Rate Ratios = 1.42;95%CI:1.33-1.51) and the highest likelihood of becoming high-cost patients (Odd Ratio = 1.37;95%CI:1.20-1.57). CONCLUSION: Beyond advanced liver disease, HCV-related comorbidities (especially cardiovascular disease) are the strongest predictors of high hospitalization rates and costs. Our findings highlight the potential benefit that early identification and treatment of HCV might have on the reduction of hospitalization costs driven by extrahepatic conditions.

Increasing trend in admission rates and costs for acute diverticulitis during 2005-2015: real-life data from the Abruzzo Region.

BACKGROUND: Scarce data are available on the epidemiological trend of diverticulitis and its financial burden in Italy. The aim of this work was to explore a potential variation in the rate and costs of hospital admissions for uncomplicated and complicated diverticulitis over the last decade. METHODS: We selected all hospitalizations for diverticulitis of residents in the Abruzzo Region, Italy between 2005 and 2015. Age-standardized hospitalization rates (HRs) per 100,000 inhabitants for overall, uncomplicated and complicated diverticulitis were calculated. A linear model on the log of the age-standardized rates was used to calculate annual percentage changes (APC). Costs were derived from the official DRG tariff. RESULTS: From 2005 to 2015, the HR for acute diverticulitis increased from 38.9 to 45.2 per 100,000 inhabitants (APC + 1.9%). The HR for complicated diverticulitis increased from 5.9 to 13.3 (APC + 7.6%), whereas it remained stable for uncomplicated diverticulitis. The mean hospital cost was 1.8-times higher for complicated diverticulitis compared with that for uncomplicated disease and 3.5-times higher for patients with a surgery stay compared with that for patients with a medical stay. CONCLUSION: During the last decade, in the Abruzzo Region, the HRs for diverticulitis and their costs increased significantly, mainly due to disease complications. Further studies are needed to explore strategies to prevent complications and to realise cost-saving policies.

Impact of comorbidity on the risk and cost of hospitalization in HIV-infected patients: real-world data from Abruzzo Region.

BACKGROUND: Due to the success of antiretroviral therapy, human immunodeficiency virus (HIV) infection has been transformed into a lifelong condition. In Italy, little is known about the impact of comorbidities (CMs) on the risk of hospitalization and related costs for people who live with HIV (PWLHIV). The objective of the study was to quantify the risk of hospitalization and costs associated with CMs in an Italian cohort of PWLHIV. METHODS: The study population included subjects aged ≥18 years with HIV infection, identified in the Abruzzo's hospital discharge database among files stored from 2004 until 2013 and then followed up until December 2015. Patients' CMs (Charlson Comorbidity Index [CCI)] were extracted from International Classification of Diseases, Ninth Revision, Clinical Modification codes in the hospital discharge abstracts. Poisson regression was used to compare the incidence rate of hospital admissions in patients with and without each CM class. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were adjusted for age, sex and the other CMs. A generalized linear model under gamma distribution was used to estimate adjusted mean hospital costs. Costs were derived from official Italian Diagnosis-related group (DRG) based reimbursements. RESULTS: Among 1,026 HIV patients identified (mean age 47 years), 30% had at least one CM and 14.5% underwent hospital admission during the follow-up period. The risk of acute hospitalization significantly increased among patients with hepatitis C virus (HCV) coinfection (adjusted IRR 1.98; 95% CI: 1.59-2.47), renal (adjusted IRR 2.27; 95% CI: 1.45-3.56), liver (adjusted IRR 2.21; 1.57-3.13) and chronic pulmonary CMs (adjusted IRR 2.31; 1.63-3.32). Adjusted mean hospital costs were €2,494 in patients without CMs and €4,422 and €9,734 in those with CCI=1 or CCI ≥2, respectively. CONCLUSION: The presence of renal, liver and chronic pulmonary CMs, as well as HCV coinfection doubled the risk of hospitalization in the PWLHIV cohort. A CCI ≥2 is associated with a fourfold increase in hospitalization costs. Our study provides new evidence that CMs in PWLHIV increase the risk of hospitalization and local health service facilities.

[Choice of antithrombotic therapy in patients with Non Valvular Atrial Fibrillation in real life]. / Scelta della terapia antitrombotica in pazienti con fibrillazione atriale non valvolare nella reale pratica clinica.

INTRODUCTION: Non-valvular atrial fibrillation (NVAF) is the most common cardiac arrhythmia and it is associated with a 5-fold increase in risk of ischemic stroke. Although clinical guidelines recommend antithrombotic therapy for stroke prevention in patients at moderate or high risk for stroke, little is known on the extent to which the increase of the risks influence the choice of the therapy. AIM: The aim of the study was to assess the level of adherence to the guidelines for the prevention of thromboembolic risk in patients with NVAF. METHODS: A population-based cohort study was conducted using administrative data from a local health authority in the Campania Region (~1,000,000 inhabitants). NVAF was defined as one or more claims for atrial fibrillation between July, 2013 and June, 2014 where none of the claims were associated with cardioversion or cardiac ablation during the identification period and there was no evidence of valve-related diagnoses or procedures. The cohort was classified according to the first drug dispensing during 6 months from the discharge date for atrial fibrillation. Patients were categorized in low ischemic stroke risk (LR, score = 0), moderate-risk (MR, score = 1), high-risk (HR, score≥2) according to the CHA2DS2-VASc score. Multivariable logistic regression was used to evaluate the associations between ischemic stroke risk with the choice of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) therapy. RESULTS: A total of 1963 patients were identified: 4.9% LR, 7.6% MR and 87.5% HR patients. Overall, 36.4% of patients were not treated (LR: 56.7%, MR: 55.0%, HR: 33.7%patients). The Vitamin K antagonists were prescribed to 17% of the patients (LR: 10.3%, MR: 12,1%, HR: 17,8%), NOAC to 12,7% (LR: 10,3%, MR: 8,1%, HR: 13,2%), low-dose aspirin to 17.5% (LR: 13,4%, MR: 15,4%, HR: 17,9%), other antiplatelet to 12,3% (LR: 7,2%, MR: 6,0%, HR: 13,2%). The ischemic stroke was not significantly associated with the choice of anticoagulant drug. CONCLUSIONS: High proportion of NVAF patients with CHA2DS2-VASc score of 2 or greater not received oral anticoagulant as recommended. In contrast with recent guidelines, aspirin was commonly prescribed even in HR patients. The stroke risk stratification did not influence the choice of anticoagulant drug.

Lower rate of cardiovascular complications in patients on bolus insulin analogues: a retrospective population-based cohort study.

BACKGROUND: Few studies are available evaluating the impact of rapid-acting insulin analogues on long-term diabetes outcomes. Our aim was to compare the use of rapid-acting insulin analogues versus human regular insulin in relation to the occurrence of diabetic complications in a cohort of diabetic patients through the analysis of administrative databases. METHODS: A population-based cohort study was conducted using administrative data from four local health authorities in the Abruzzo Region (900,000 inhabitants). Diabetic patients free of macrovascular disease at baseline and treated either with human regular insulin or rapid-acting insulin analogues were followed for a maximum of 3 years. The incidence of diabetic complications was ascertained by hospital discharge claims. Hazard ratios (HRs) and 95% CIs of any diabetic complication and macrovascular, microvascular and metabolic complications were estimated separately using Cox proportional hazard models adjusted for patients' characteristics and anti-diabetic drug use. Propensity score matching was also used to adjust for significant difference in the baseline characteristics between the two treatment groups. RESULTS: A total of 2,286 patients were included: 914 receiving human regular insulin and 1,372 rapid-acting insulin analogues. During the follow-up, 286 (31.3%) incident events occurred in the human regular insulin group and 235 (17.1%) in the rapid-acting insulin analogue group. After propensity score-based matched-pair analyses, rapid-acting insulin analogues users had a HR of 0.73 (0.58-0.92) for any diabetes-related complication and HRs of 0.73 (0.55-0.93) and 0.55 (0.32-0.96) for macrovascular and metabolic complications respectively, as compared with human regular insulin users. No difference between the two groups was found for microvascular complications. CONCLUSIONS: Our findings suggest that the use of rapid-acting insulin analogues is associated with a lower risk of cardiovascular and metabolic complications compared with human regular insulin use.

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.

Pharmaco-economic consequences of losartan therapy in patients undergoing diabetic end stage renal disease in EU and USA.

Diabetic nephropathy is the most frequent cause of end stage renal disease (ESRD). As ESRD incidence increases continuously, more resources are needed for treatment. The objective was to evaluate the economic impact of losartan added to the standard care administered to diabetic subjects with ESRD. The analysis has involved more than 500 million inhabitants. Standard methods have been used in order to conduct an economic evaluation comparing the economic outcomes deriving from the administration of losartan added to standard care versus standard care alone in patients with type 2 diabetes mellitus (DM) and nephropathy over 3.4 years. The study was hence conducted from the perspective of the third-party payer. The clinical outcome data were based on the results from the Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial. Direct medical costs are referred to the purchase costs of losartan and to the costs of hospitalization. The costs were discounted back at an annual rate of 3%. Also sensitivity analysis was performed. The RENAAL study showed that losartan confers strong renal protection in patients with DM and nephropathy. Losartan results into cost saving in all countries considered: 3,602.98€/Italy, 4,531.35€/France, 3,019.66€/Germany, 3,949.50€/Switzer-land, and 3,855.50€/US per patient. Results are not sensitive to both clinical and economic variables. In addition to the medical benefits, this analysis demonstrates the economic relevance of the treatment with losartan in DM patients affected by nephropathy.

Notification of undesirable effects of cosmetics and toiletries.

An undesirable effect (UE) of a cosmetic product is a harmful reaction attributable to its normal or reasonably foreseeable use. However, the knowledge of UEs, at the population level, is limited by the absence of formal and reliable cosmetovigilance systems, which nevertheless are characterized by underreporting. To test the feasibility of the collection of UEs in our territory we have carried out a pilot project aimed to assess either the notification procedures or the validation/evaluation of the collected forms in our territory. As reporting categories, we have chosen dermatologists and community pharmacists who were asked to notify UEs to cosmetics through a reporting form we have set up. During the period July 2006-December 2007, we have registered 76 reporting forms. Dermatologists who have sent 47 reporting forms represented the main reporting category, followed by community pharmacists (15 reports), other health professionals (9 reports) and consumers (5 reports). Several drawbacks, mainly represented by the incompleteness and inaccuracy of the filled in forms, affected the validation process. Thus, on receipt, we could validate only 34 forms and only after a careful check with each single reporter, we could include in the study other 36 forms. The validation of the collected reports has stressed the importance of a well-structured reporting form, an easy access to notification procedures as well as education and training programme. The evaluation of the validated forms has revealed the need of a controlled term vocabulary for the classification of the observed events and diagnosis, especially with regard to cutaneous reactions that represented almost the totality of the reported events (95.7%). Among the events (n=45) reported by dermatologists, 22 were diagnosed as allergic contact dermatitis (ACD) and 18 as irritant contact dermatitis (ICD). Facial care products (19.7%), followed by body care products (16.9%), perfumes (12.7%) and eye care products (11.3%) were the cosmetics mainly suspected to be responsible for the observed events. Correspondingly, face (n=37), including periorbital and perioral area, forehead, ocular mucous membrane and lips, followed by entire body (n=9) were the body sites reported as more involved. In conclusions, our experience allowed us to identify the main pitfalls of the system we have experienced. These are setting/formulation of the reporting form, notification step, description of the event and diagnosis. A careful settlement of these aspects could substantially contribute to the establishment of an efficient reporting system, although the bias due to underreporting is difficult to eliminate.

Inhibitory effects of peroxisome poliferator-activated receptor gamma on thyroid carcinoma cell growth.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor involved in such cellular processes as adipogenesis, inflammation, atherosclerosis, cell cycle control, apoptosis, and carcinogenesis. PPAR gamma gene mutations have been found in 4 of 55 sporadic colon cancers, and a chimeric PAX8-PPAR gamma 1 gene frequently generates a chromosomal translocation in thyroid follicular carcinomas, implicating PPAR gamma in tumor suppression. We investigated whether PPAR gamma is involved in the growth regulation of normal and tumor thyroid cells. We found no mutations in PPAR gamma exons 3 and 5 in human thyroid carcinoma cell lines and tissues. Moreover, 1 cell line (NPA) of 6 analyzed did not express PPAR gamma. Treatment of NPA with PPAR gamma agonists did not induce any inhibitory effect. Conversely, PPAR gamma agonists and PPAR gamma overexpression led to a drastic reduction of the cell growth rate in PPAR gamma-expressing thyroid carcinoma cells. Restoration of PPAR gamma expression in NPA cells induced cell growth inhibition; PPAR gamma agonists induced further inhibition. Growth inhibition induced by PPAR gamma agonists or by PPAR gamma gene overexpression in thyroid carcinoma cells was associated with increased p27 protein levels and apoptotic cell death. Should these data be confirmed, PPAR gamma could be a novel target for innovative therapy of thyroid carcinoma, particularly anaplastic carcinomas, which represent one of the most aggressive tumors in mankind and are unresponsive to conventional therapy.