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INTRODUZIONE Il consumo eccessivo e talvolta inappropriato di farmaci antibiotici rappresenta una delle principali cause di sviluppo di resistenza batterica; ciò accade principalmente nella popolazione pediatrica. Numerosi studi riportano differenze tra i Paesi del Nord e Sud Europa in ambito di terapia antibiotica. Scopo del progetto di ricerca è confrontare le modalità prescrittive di farmaci antibiotici nei bambini di età compresa fra 0 e 5 anni, in Emilia Romagna e in Norvegia. METODI I dati sono stati ottenuti dalla bancadati regionale dell’Assistenza Farmaceutica Territoriale (AFT) per l’Emilia Romagna e dal Norwegian Prescription Database (NORPD) per la Norvegia. E’ stata condotta un’analisi descrittiva dei dati italiani in cinque differenti gruppi di età: 0-12 mesi, 13-24 mesi, 25-36 mesi, 37-48 mesi e 49-60 mesi. I risultati sono stati quindi messi a confronto con i dati norvegesi. RISULTATI In Emilia Romagna si osserva un uso maggiore di antibiotici (prevalenza variabile dal 68% al 59% nel periodo in studio), mentre in Norvegia il 29% circa dei bambini ha ricevuto almeno una prescrizione di antibiotici. In tutti i gruppi di età, i bambini italiani hanno ricevuto un numero di prescrizioni per anno maggiore rispetto a quelli norvegesi. Importanti differenze emergono anche in relazione alla tipologia di farmaci prescritti: amoxicillina, da sola e in combinazione ad acido clavulanico sono i principi attivi più prescritti in Emilia Romagna contro la fenossimetilpenicillina in Norvegia. CONCLUSIONI I risultati dello studio mostrano differenze nell’utilizzo di terapie antibiotiche nei bambini in Emilia Romagna e Norvegia. In particolare, è emerso un utilizzo eccessivo di antibiotici nella popolazione pediatrica italiana considerata e un approccio terapeutico spesso non coerente con quanto riportato dalle linee guida e dalle raccomandazioni nazionali e internazionali. Il confronto con una realtà più virtuosa pone le basi per una riflessione sulle strategie di migl, INTRODUCTION Population level exposure to antibiotics is associated with antibiotic resistance, and frequent antibiotic prescribing to children is accepted as an indicator for sub-optimal prescribing to outpatients. There are a number of European studies investigating antibiotic prescribing to children and adolescents that report large variations between countries in choice of therapy and periodic prevalence of prescribing. Aim of this study is to analyse and compare the pattern of antibiotic prescription and use in children 0-5 years in Norway and in Italy (Emilia-Romagna Region). METHODS A retrospective observational study was conducted; data on antibiotic prescribing were obtained from the Norwegian Prescription Database (NorPD) and from Emilia-Romagna Health Authority Database (AFT). All outpatients between 0 and 5 years, with a dispensed prescription on antibiotics (Anatomical Therapeutic Chemical, ATC code J01) were included and a descriptive analysis was made to compare patients, prescriptions of antibiotics and prescribers characteristics among the following 5 age groups: 0-12 months, 13-24 months, 25-36 months, 37-48 months, 49-60 months. RESULTS In Emilia Romagna a greater use of antibiotics was registered (prevalence ranging from 68% to 59% in the study period), while in Norway about 29% of children received at least one prescription of antibiotics. Important differences also emerged in relation to the type of drugs prescribed: amoxicillin, alone and in combination with clavulanic acid, was the most used in Emilia Romagna against phenoxymethylpenicillin in Norway. CONCLUSION The results of the study showed differences in the use of antibiotic therapies in children in Emilia Romagna and Norway. In particular, excessive use of antibiotics has emerged in the Italian pediatric population; this therapeutic approach was often not consistent with national and international guidelines and recommendations. The comparison with a more virtuous reality leads to a ref

INTRODUZIONE Il consumo eccessivo e talvolta inappropriato di farmaci antibiotici rappresenta una delle principali cause di sviluppo di resistenza batterica; ciò accade principalmente nella popolazione pediatrica. Numerosi studi riportano differenze tra i Paesi del Nord e Sud Europa in ambito di terapia antibiotica. Scopo del progetto di ricerca è confrontare le modalità prescrittive di farmaci antibiotici nei bambini di età compresa fra 0 e 5 anni, in Emilia Romagna e in Norvegia. METODI I dati sono stati ottenuti dalla bancadati regionale dell’Assistenza Farmaceutica Territoriale (AFT) per l’Emilia Romagna e dal Norwegian Prescription Database (NORPD) per la Norvegia. E’ stata condotta un’analisi descrittiva dei dati italiani in cinque differenti gruppi di età: 0-12 mesi, 13-24 mesi, 25-36 mesi, 37-48 mesi e 49-60 mesi. I risultati sono stati quindi messi a confronto con i dati norvegesi. RISULTATI In Emilia Romagna si osserva un uso maggiore di antibiotici (prevalenza variabile dal 68% al 59% nel periodo in studio), mentre in Norvegia il 29% circa dei bambini ha ricevuto almeno una prescrizione di antibiotici. In tutti i gruppi di età, i bambini italiani hanno ricevuto un numero di prescrizioni per anno maggiore rispetto a quelli norvegesi. Importanti differenze emergono anche in relazione alla tipologia di farmaci prescritti: amoxicillina, da sola e in combinazione ad acido clavulanico sono i principi attivi più prescritti in Emilia Romagna contro la fenossimetilpenicillina in Norvegia. CONCLUSIONI I risultati dello studio mostrano differenze nell’utilizzo di terapie antibiotiche nei bambini in Emilia Romagna e Norvegia. In particolare, è emerso un utilizzo eccessivo di antibiotici nella popolazione pediatrica italiana considerata e un approccio terapeutico spesso non coerente con quanto riportato dalle linee guida e dalle raccomandazioni nazionali e internazionali. Il confronto con una realtà più virtuosa pone le basi per una riflessione sulle strategie di migl, INTRODUCTION Population level exposure to antibiotics is associated with antibiotic resistance, and frequent antibiotic prescribing to children is accepted as an indicator for sub-optimal prescribing to outpatients. There are a number of European studies investigating antibiotic prescribing to children and adolescents that report large variations between countries in choice of therapy and periodic prevalence of prescribing. Aim of this study is to analyse and compare the pattern of antibiotic prescription and use in children 0-5 years in Norway and in Italy (Emilia-Romagna Region). METHODS A retrospective observational study was conducted; data on antibiotic prescribing were obtained from the Norwegian Prescription Database (NorPD) and from Emilia-Romagna Health Authority Database (AFT). All outpatients between 0 and 5 years, with a dispensed prescription on antibiotics (Anatomical Therapeutic Chemical, ATC code J01) were included and a descriptive analysis was made to compare patients, prescriptions of antibiotics and prescribers characteristics among the following 5 age groups: 0-12 months, 13-24 months, 25-36 months, 37-48 months, 49-60 months. RESULTS In Emilia Romagna a greater use of antibiotics was registered (prevalence ranging from 68% to 59% in the study period), while in Norway about 29% of children received at least one prescription of antibiotics. Important differences also emerged in relation to the type of drugs prescribed: amoxicillin, alone and in combination with clavulanic acid, was the most used in Emilia Romagna against phenoxymethylpenicillin in Norway. CONCLUSION The results of the study showed differences in the use of antibiotic therapies in children in Emilia Romagna and Norway. In particular, excessive use of antibiotics has emerged in the Italian pediatric population; this therapeutic approach was often not consistent with national and international guidelines and recommendations. The comparison with a more virtuous reality leads to a ref

There is evidence that the use oral bisphosphonates can lead to osteronecrosis of the jaws (ONJ). Although the occurrence of ONJ appears rare among oral bisphosphonates (BPs) users, it is important to know that it exists and can be opportunely minimized. The purpose of this study is to evaluate the association between BPs prescribed for the secondary prevention of osteoporotic fractures and the occurrence of ONJ. An Italian record linkage claims database with a target population of around 18 million individuals (6 million over 55 years of age) constituted the data source. We conducted a nested case-control study within a cohort of individuals aged 55+ years old, who were discharged from hospitals with a primary diagnosis of incident osteoporotic fracture. The date related to the discharge diagnosis of ONJ was the index date. Conditional logistic regression for matched data was fitted to estimate the odds ratio (OR) along with 95 % confidence intervals (95 % CI) for the likely association between use of BPs and the risk of ONJ. Any one of the 61 ascertained cases of ONJ (incidence rate, 36.6 per 100,000 person-years) was matched to 20 controls for a total of 1120 controls. When the exposure to BPs was modeled according to recency (i.e., exposure time window prior to the index date) of use, the adjusted OR (95 % CI) for current users was 2.8 (1.3-5.9) against never users. The cumulative use of BPs has shown to increase the incidence of ONJ among patients with primary osteoporotic fractures, although not statistically significant risk has been observed. Although the risk of BP-related ONJ appears low in non-oncological indications, it is important to be aware that it exists and to know how it may be predicted and possibly minimized.

Background: Fluoroquinolones are widely used both in primary care and in hospital settings. Since the last comparison performed in Italy on the safety profiles of different fluoroquinolones, a new molecule, prulifloxacin, has been Introduced into the market and several warnings concerning this class of drugs have been released. The aim of this study was to reassess the safety profiles of fluoroquinolones using the database of the Italian Interregional Group of Pharmacovigilance (IGP) and the administrative data of fluoroquinolone prescriptions Methods: All adverse drug reactions (ADRs) reported in four Italian regions (Lombardy, Veneto. Emilia Romagna and Tuscany) were retrieved from the IGP database Consumption data (defined daily dose [DDD]/1000 inhabitants/day) were used as denominators. Both single reports and all ADRs (classified by System Organ Classes and MedDRA (R) Preferred Term [PT]) due to fluoroquinolones were considered as numerators of each analysis, comparing two periods (2005 vs 2006) All fluoroquinolones with at least ten reports per year were included in the analysis Results: On the basis of 272 reports (532 single ADRs or PTs), patients did not show any statistically significant differences between 2005 and 2006 in terms of sex, age and number of concurrent medications After adjustment for drug consumption, moxifloxacin showed the highest reporting rate (84 6 reports/DDD/1000 inhabitants/day; 15 4 serious reports/DDD/1000 inhabitants/day) followed by prulifloxacin (72 2; 22 2 serious) and levofloxacin (55.3, 30 6 serious) in 2005 An increment of ADR/report rates was observed over the 2 years for all fluoroquinolones except prulifloxacin, which had the lowest ADR reporting rate in 2006 (25.0; 125 serious) In 2006, the rate of serious ADRs associated with prulifloxacin was lower than with ciprofloxacin, while in 2005 serious events were almost equal for both compounds (55 6 vs 47 6 serious ADRs/DDD/1000 inhabitants/day) Ciprofloxacin showed the high

Background: Antihypertensives (AHs) are the main drug class both for prevalence of use and costs in Western Countries. Continuity of use is an important factor influencing the success of these therapies, but low adherence by patients has been frequently observed. Objectives: To identify potential predictors of continuity of drug use and of blood pressure target values achievement. Methods: Data on drug prescriptions, clinical events, diagnoses, hospital admissions and causes of death on 600,000 Italian subjects (400 GPs) were collected from the Health Search Database. Patients with a diagnosis of hypertension before 2004 were selected and their 2004–05 data were analysed. Patients who received an amount of AHs consistent with daily use were defined continuous. Results: Overall, 63,260 hypertensive patients were selected. Females were 59% and the average age was 66. Sixty-two percent had hypertension diagnosis in the last 5 years, 16% were diabetics, 8% had cerebrovascular accidents; 60% had no smoking history. During 2005, 6% withdrew their treatment (especially in case of recent diagnosis) and 35% did not take drugs continuously, more frequently in case of diuretics and -blockers, recent diagnosis, absence of diabetes and of previous ictus/TIA. Among continuous patients, 51% achieved a good control of hypertension without dose or drug changes, 23% changed drugs (especially among diabetic patients and those with previous ictus/TIA), 24% changed doses (more frequently in case of Ca channel blockers and ACE inhibitors) and 2% of subjects resulted continuous for drugs and doses without achieving target pressure values. Conclusions: In 2005, only 1/3 of patients receiving AHs were continuous and had well controlled blood pressure. Older diagnosis of hypertension, concomitant diabetes and use of specific drugs (Ca channel blockers, ACE inhibitors or angiotensin antagonists) positively influenced continuity of use of AHs.

Summary: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year.Introduction: Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure.Methods: We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95 % confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91–180), past (181–364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out.Results: In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95 % CI = 1.46–2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95 % CI, 1.59–2.43).Conclusion: In our nested case-control study, current users of BP are associated

Obiettivo Analisi di consumi e costi degli antibiotici sistemici negli ospedali dell’Emilia-Romagna dal 2004 al 2011, con attenzione alla variabilità interaziendale e al significato, in termini di resistenza batterica, dell’aumento di alcuni gruppi terapeutici; Sottoanalisi nei reparti pediatrici, individuando i gruppi terapeutici critici, e valutazione delle reazioni avverse pediatriche da antibiotici segnalate, per il periodo in esame. Metodi I dati di consumo e spesa degli antibiotici sistemici per il periodo 2004-2011 sono stati ottenuti dal database regionale AFO e le giornate di degenza per ogni reparto dal database regionale di dimissione ospedaliera SDO. Le segnalazioni di sospette reazioni avverse da antibiotici tra gennaio 2004 e dicembre 2011 sono state estratte dal database nazionale VigiSegn. Risultati Negli otto anni, il consumo di antibiotici negli ospedali dell’Emilia-Romagna è aumentato del 27% e la spesa del 3%. Il consumo è apparso nettamente superiore nei reparti chirurgici che medici. La prima classe per consumo e spesa sono le penicilline/inibitori delle beta lattamasi. Nei reparti pediatrici, sono stati utilizzati 65 principi attivi diversi e amoxicillina/acido clavulanico è stato il più usato (26% del totale del 2011). Tra gli antibiotici critici, le cefalosporine di terza generazione sono state le più consumate in tutti i reparti pediatrici nel 2011. Tra le molecole il cui uso ospedaliero è vincolato, spiccano il linezolid e la teicoplanina che, comunque, hanno inciso più di tutte nella spesa del 2011 (18% e 15%, rispettivamente). Per la farmacovigilanza, i bambini (3-13 anni) sono stati coinvolti in 23 casi, mentre gli infanti (≤2 anni) solo in 4. L’associazione amoxicillina/acido clavulanico è stata più frequentemente segnalata (n=7), e soltanto 2 casi erano gravi. Conclusioni I risultati mostrano un quadro critico sul massiccio uso delle cefalosporine di terza generazione e sull’incremento del linezolid, da approfondire se per inappropria, Aim To assess antibiotic consumption and expenditure in all hospitals of Emilia-Romagna from 2004 to 2011, highlighting on variability and meaning, in terms of bacterial resistance, of the rise in some therapeutic groups; To analyze antibiotic use among the pediatric wards, identifying the critical therapeutic groups, and evaluation of antibiotic-associated adverse reactions in pediatric inpatients, in the period considered. Methods Consumption and expenditure data of antibacterial for systemic use in the period 2004-2011 were obtained from the regional database (AFO) and the number of bed-days was available for the single wards from the regional hospital discharge database (SDO). Adverse reaction reports associated to antibiotics and recorded between January 2004 and December 2011 have been extracted from the national database VigiSegn. Results In the eight years analyzed, the overall antibiotic consumption increased by 27% and expenditure by 3% in all hospitals of Emilia-Romagna. Antibiotic consumption appeared markedly higher in the wards of surgical wards than medical ones. Penicillins/beta-lactamase inhibitors ranked first in consumption and expenditure. Sixty-five different antibiotics were used among the pediatric wards and amoxicillin/clavulanic acid was the most used (26% of the total in 2011). Among the critical antibiotics identified, the third-generation cephalosporins were the most used in all pediatric wards in 2011. Among the antibiotics with a defined limited use, the data highlighted that linezolid and teicoplanin affected most of all expenditure in 2011 (18% and 15%, respectively). About pharmacovigilance data, children (3-13 years) were involved in 23 cases, whereas infants (≤2 years) just in 4. Amoxicillin/clavulanic acid was the antibiotic most frequently reported (n = 7), and 2 cases of them were serious. Conclusions Results show a critical picture on the marked use of third-generation cephalosporins and on increase of linezolid consumption, be

Obiettivo Analisi di consumi e costi degli antibiotici sistemici negli ospedali dell’Emilia-Romagna dal 2004 al 2011, con attenzione alla variabilità interaziendale e al significato, in termini di resistenza batterica, dell’aumento di alcuni gruppi terapeutici; Sottoanalisi nei reparti pediatrici, individuando i gruppi terapeutici critici, e valutazione delle reazioni avverse pediatriche da antibiotici segnalate, per il periodo in esame. Metodi I dati di consumo e spesa degli antibiotici sistemici per il periodo 2004-2011 sono stati ottenuti dal database regionale AFO e le giornate di degenza per ogni reparto dal database regionale di dimissione ospedaliera SDO. Le segnalazioni di sospette reazioni avverse da antibiotici tra gennaio 2004 e dicembre 2011 sono state estratte dal database nazionale VigiSegn. Risultati Negli otto anni, il consumo di antibiotici negli ospedali dell’Emilia-Romagna è aumentato del 27% e la spesa del 3%. Il consumo è apparso nettamente superiore nei reparti chirurgici che medici. La prima classe per consumo e spesa sono le penicilline/inibitori delle beta lattamasi. Nei reparti pediatrici, sono stati utilizzati 65 principi attivi diversi e amoxicillina/acido clavulanico è stato il più usato (26% del totale del 2011). Tra gli antibiotici critici, le cefalosporine di terza generazione sono state le più consumate in tutti i reparti pediatrici nel 2011. Tra le molecole il cui uso ospedaliero è vincolato, spiccano il linezolid e la teicoplanina che, comunque, hanno inciso più di tutte nella spesa del 2011 (18% e 15%, rispettivamente). Per la farmacovigilanza, i bambini (3-13 anni) sono stati coinvolti in 23 casi, mentre gli infanti (≤2 anni) solo in 4. L’associazione amoxicillina/acido clavulanico è stata più frequentemente segnalata (n=7), e soltanto 2 casi erano gravi. Conclusioni I risultati mostrano un quadro critico sul massiccio uso delle cefalosporine di terza generazione e sull’incremento del linezolid, da approfondire se per inappropria, Aim To assess antibiotic consumption and expenditure in all hospitals of Emilia-Romagna from 2004 to 2011, highlighting on variability and meaning, in terms of bacterial resistance, of the rise in some therapeutic groups; To analyze antibiotic use among the pediatric wards, identifying the critical therapeutic groups, and evaluation of antibiotic-associated adverse reactions in pediatric inpatients, in the period considered. Methods Consumption and expenditure data of antibacterial for systemic use in the period 2004-2011 were obtained from the regional database (AFO) and the number of bed-days was available for the single wards from the regional hospital discharge database (SDO). Adverse reaction reports associated to antibiotics and recorded between January 2004 and December 2011 have been extracted from the national database VigiSegn. Results In the eight years analyzed, the overall antibiotic consumption increased by 27% and expenditure by 3% in all hospitals of Emilia-Romagna. Antibiotic consumption appeared markedly higher in the wards of surgical wards than medical ones. Penicillins/beta-lactamase inhibitors ranked first in consumption and expenditure. Sixty-five different antibiotics were used among the pediatric wards and amoxicillin/clavulanic acid was the most used (26% of the total in 2011). Among the critical antibiotics identified, the third-generation cephalosporins were the most used in all pediatric wards in 2011. Among the antibiotics with a defined limited use, the data highlighted that linezolid and teicoplanin affected most of all expenditure in 2011 (18% and 15%, respectively). About pharmacovigilance data, children (3-13 years) were involved in 23 cases, whereas infants (≤2 years) just in 4. Amoxicillin/clavulanic acid was the antibiotic most frequently reported (n = 7), and 2 cases of them were serious. Conclusions Results show a critical picture on the marked use of third-generation cephalosporins and on increase of linezolid consumption, be

A Summary Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. Introduction Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. Methods We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95 % confidence intervals (CI). The BP exposure was classified into current (< 90 days prior to ID), recent (91-180), past (181-364), and distant past (>= 365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out. Results In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95 % CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95 % CI, 1.59-2.43). Conclusion In our nested case-control study, current users of BP are

Summary: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year.Introduction: Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure.Methods: We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95 % confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91–180), past (181–364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out.Results: In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95 % CI = 1.46–2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95 % CI, 1.59–2.43).Conclusion: In our nested case-control study, current users of BP are associated

Background: Data on the effect of oral bisphosphonates (BPs) on risk of upper gastrointestinal complications (UGIC) are conflicting. We conducted a large population-based study from a network of Italian healthcare utilization databases aimed to assess the UGIC risk associated with use of BPs in the setting of secondary prevention of osteoporotic fractures.Methods: A nested case-control study was carried out within a cohort of 68,970 patients aged 45 years or older, who have been hospitalized for osteoporotic fracture from 2003 until 2005. Cases were the 804 patients who experienced hospitalization for UGIC until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current and past use of BPs (i.e. for drug dispensation within 30 days and over 31 days prior the outcome onset, respectively) after adjusting for several covariates.Results: Compared with patients who did not use BPs, current and past users had OR (and 95% confidence interval) of 0.86 (0.60 to 1.22) and 1.07 (0.80 to 1.44) respectively. There was no difference in the ORs estimated according with BPs type (alendronate or risedronate) and regimen (daily or weekly), nor with co-therapies and comorbidities.Conclusions: Further evidence that BPs dispensed for secondary prevention of osteoporotic fractures are not associated with increased risk of severe gastrointestinal complications is supplied from this study. Further research is required to clarify the role BPs and other drugs of co-medication in inducing UGIC.

Purpose: Different strategies applicable to control for confounding by indication in observational studies were compared in a large population-based study regarding the effect of bisphosphonates (BPs) for secondary prevention of fractures. Methods: The cohort was drawn from healthcare utilization databases of 13 Italian territorial units. Patients aged 55years or more who were hospitalized for fracture during 2003-2005 entered into the cohort. A nested case-control design was used to compare BPs use in cohort members who did (cases) and who did not experience (controls) a new fracture until 2007 (outcome). Three designs were employed: conventional-matching (D1), propensity score-matching (D2), and user-only (D3) designs. They differed for (i) cohort composition, restricted to patients who received BPs straight after cohort entry (D3); (ii) using propensity score for case-control matching (D2); and (iii) compared groups of BPs users versus no users (D1 and D2) and long-term versus short-term users (D3). Results: Bisphosphonate users had odds ratios (95% confidence interval) of 1.20 (1.01 to 1.44) and 0.95 (0.74 to 1.24) by applying D1 and D2 designs, respectively. Statistical evidence that long-term BPs use protects the outcome onset with respect to short-term use was observed for user-only design (D3) being the corresponding odds ratio (95% confidence interval) 0.64 (0.44 to 0.93). Conclusions: User-only design yielded closer results to those seen in RCTs. This approach is one possible strategy to account for confounding by indication. © 2014 John Wiley & Sons, Ltd.

Purpose: Osteoporosis is a chronic disease of the bone, whose incidence increases progressively with aging. The main consequences of osteoporosis are fragility fractures, which have considerable medical, social, and economic implications. Adequate treatment of osteoporosis must be considered as a compelling public health intervention. Bisphosphonates (BPs) represent the most significant advance in this field in the past decade, and they are widely used in the treatment of osteoporosis. However, evidence for their effectiveness is limited to secondary prevention, whereas their effect in primary prevention is uncertain and needs further investigation. Methods: Using administrative data collected in the "Biphosphonates Efficacy-Safety Tradeoff" (BEST) study, a nested case-control study was conducted by including 56,058 participants, aged 55 years who were started on oral BPs from 2003 to 2005. Cases were the 1,710 participants who were hospitalized for osteoporotic fractures until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio of fracture associated with categories of treatment duration. Results: Compared with participants assuming BPs for less than 1 year, those who remained on therapy for at least 2 years had a 21 % (95 % confidence interval (CI) 7 to 33 %) fracture risk reduction. Conclusion: This study provides evidence that BPs, dispensed for primary prevention of osteoporotic fractures, are associated with a reduced risk of osteoporotic fractures after at least 2 years of treatment. © 2014 Springer-Verlag.

Background: Data on the effect of oral bisphosphonates (BPs) on risk of upper gastrointestinal complications (UGIC) are conflicting. We conducted a large population-based study from a network of Italian healthcare utilization databases aimed to assess the UGIC risk associated with use of BPs in the setting of secondary prevention of osteoporotic fractures. Methods: A nested case-control study was carried out within a cohort of 68,970 patients aged 45 years or older, who have been hospitalized for osteoporotic fracture from 2003 until 2005. Cases were the 804 patients who experienced hospitalization for UGIC until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current and past use of BPs (i.e. for drug dispensation within 30 days and over 31 days prior the outcome onset, respectively) after adjusting for several covariates. Results: Compared with patients who did not use BPs, current and past users had OR (and 95% confidence interval) of 0.86 (0.60 to 1.22) and 1.07 (0.80 to 1.44) respectively. There was no difference in the ORs estimated according with BPs type (alendronate or risedronate) and regimen (daily or weekly), nor with co-therapies and comorbidities. Conclusions: Further evidence that BPs dispensed for secondary prevention of osteoporotic fractures are not associated with increased risk of severe gastrointestinal complications is supplied from this study. Further research is required to clarify the role BPs and other drugs of co-medication in inducing UGIC.

Background: Data on the effect of oral bisphosphonates (BPs) on risk of upper gastrointestinal complications (UGIC) are conflicting. We conducted a large population-based study from a network of Italian healthcare utilization databases aimed to assess the UGIC risk associated with use of BPs in the setting of secondary prevention of osteoporotic fractures.Methods: A nested case-control study was carried out within a cohort of 68,970 patients aged 45 years or older, who have been hospitalized for osteoporotic fracture from 2003 until 2005. Cases were the 804 patients who experienced hospitalization for UGIC until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current and past use of BPs (i.e. for drug dispensation within 30 days and over 31 days prior the outcome onset, respectively) after adjusting for several covariates.Results: Compared with patients who did not use BPs, current and past users had OR (and 95% confidence interval) of 0.86 (0.60 to 1.22) and 1.07 (0.80 to 1.44) respectively. There was no difference in the ORs estimated according with BPs type (alendronate or risedronate) and regimen (daily or weekly), nor with co-therapies and comorbidities.Conclusions: Further evidence that BPs dispensed for secondary prevention of osteoporotic fractures are not associated with increased risk of severe gastrointestinal complications is supplied from this study. Further research is required to clarify the role BPs and other drugs of co-medication in inducing UGIC.

There is evidence that the use oral bisphosphonates can lead to osteronecrosis of the jaws (ONJ). Although the occurrence of ONJ appears rare among oral bisphosphonates (BPs) users, it is important to know that it exists and can be opportunely minimized. The purpose of this study is to evaluate the association between BPs prescribed for the secondary prevention of osteoporotic fractures and the occurrence of ONJ. An Italian record linkage claims database with a target population of around 18 million individuals (6 million over 55 years of age) constituted the data source. We conducted a nested case-control study within a cohort of individuals aged 55+ years old, who were discharged from hospitals with a primary diagnosis of incident osteoporotic fracture. The date related to the discharge diagnosis of ONJ was the index date. Conditional logistic regression for matched data was fitted to estimate the odds Any one of the 61 ascertained cases of ONJ (incidence rate, 36.6 per 100,000 person-years) was matched to 20 controls for a total of 1120 controls. When the exposure to BPs was modeled according to recency (i.e., exposure time window prior to the index date) of use, the adjusted OR (95 % CI) for current users was 2.8 (1.3-5.9) against never users. The cumulative use of BPs has shown to increase the incidence of ONJ among patients with primary osteoporotic fractures, although not statistically si Although the risk of BP-related ONJ appears low in non-oncological indications, it is important to be aware that it exists and to know how it may be predicted and possibly minimized.

BACKGROUND: Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed. AIM: To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases. METHODS: A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty. RESULTS: The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations. CONCLUSIONS: No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use

Introduction: Clinical trials indicate that oral BP reduce the incidence of osteoporotic fractures up to 60%. Although the safety of BP appears similar to placebo, adverse reaction reports have suggested an association between BP use and ONJ. On this concern, no epidemiological study including ‘validated’ cases of ONJ has been still conducted. Methods: A case-control study was nested into a cohort of 65,220 fractured osteoporotic patients. An Adjudication Committee selected codes plausibly related to ‘true’ cases of ONJ according to two levels of contiguity: level I ‘possibly contiguous with ONJ’ (e.g. 730.08 ‘multiple bone infections, site unspecified’), level II ‘probably contiguous with ONJ’ (e.g. 526.4 ‘jaw inflammation’). Up to 20 controls were matched to each case according to gender, age (±3 years), month and year of the cohort entry. Odds Ratio [OR; 95% Confidence Intervals (CIs)] of being exposed to BPs among cases vs. controls were estimated through conditional logistic regression model. Multivariable analysis includes use of steroids, proton pump inhibitors and diabetes as confounders. Results: Among (43 level I, 61 level II) 104 cases of ONJ the odds of being exposed to BPs was not different from controls (OR = 1.1; 95% CI: 0.6–1.1). When the analysis was restricted to level II cases, OR was 2.8 (95% CI, 1.3–5.9) higher among current users (last prescription within 1 year before the case’s date) of BP than never users. Conclusions: These findings seem to suggest an association between use of oral BP and ONJ. Further analyses on definitively validated cases are needed.

In questa tesi vogliamo studiare le proprietà macroscopiche di sistemi stocastici di particelle, ossia il comportamento di sistemi di SDEs quando si considera un numero grande di particelle. Qui siamo più che altro interessati a usare tali sistemi per modellare fenomeni, quindi qui li con un fine prettamente pratico. Il problema principale che ci si presenta è di trovare un modo di approssimare la distribuzione del sistema, dal momento che nella maggior parte dei casi tale essa non è esplicita. Il fatto chiave che vogliamo mostrare è che ci sono due modi per approssimare tale distribuzione: attraverso il limite macroscopico o attraverso PDEs. Infine si vuole vedere tali concetti in azione per calibrare ai prezzi di mercato i modelli a volatilità locale stocastica.

Il presente lavoro di tesi si inserisce in un progetto di ricerca focalizzato sullo sviluppo di nuove tecnologie per la sostituzione delle imbottiture schiumate classiche per fondelli da ciclista con lo scopo di ottenere una produzione personalizzata e, parallelamente, avere una riduzione o eliminazione degli scarti di materiale. Con questo obiettivo sono state messe a punto alcune metodiche specifiche di caratterizzazione dinamico meccanica (DMA) per ottenere dei dati rappresentativi delle principali caratteristiche richieste nelle condizioni d’uso delle imbottiture, e sono state utilizzate per confrontare le proprietà dei nuovi materiali studiati con quelle delle schiume attualmente in uso. I materiali sono stati, inoltre, caratterizzati tramite spettroscopia infrarossa a riflettanza totale attenuata (FTIR-ATR) e analisi calorimetrica differenziale a scansione (DSC).

In questa tesi vogliamo studiare le proprietà macroscopiche di sistemi stocastici di particelle, ossia il comportamento di sistemi di SDEs quando si considera un numero grande di particelle. Qui siamo più che altro interessati a usare tali sistemi per modellare fenomeni, quindi qui li con un fine prettamente pratico. Il problema principale che ci si presenta è di trovare un modo di approssimare la distribuzione del sistema, dal momento che nella maggior parte dei casi tale essa non è esplicita. Il fatto chiave che vogliamo mostrare è che ci sono due modi per approssimare tale distribuzione: attraverso il limite macroscopico o attraverso PDEs. Infine si vuole vedere tali concetti in azione per calibrare ai prezzi di mercato i modelli a volatilità locale stocastica.

Il presente lavoro di tesi si inserisce in un progetto di ricerca focalizzato sullo sviluppo di nuove tecnologie per la sostituzione delle imbottiture schiumate classiche per fondelli da ciclista con lo scopo di ottenere una produzione personalizzata e, parallelamente, avere una riduzione o eliminazione degli scarti di materiale. Con questo obiettivo sono state messe a punto alcune metodiche specifiche di caratterizzazione dinamico meccanica (DMA) per ottenere dei dati rappresentativi delle principali caratteristiche richieste nelle condizioni d’uso delle imbottiture, e sono state utilizzate per confrontare le proprietà dei nuovi materiali studiati con quelle delle schiume attualmente in uso. I materiali sono stati, inoltre, caratterizzati tramite spettroscopia infrarossa a riflettanza totale attenuata (FTIR-ATR) e analisi calorimetrica differenziale a scansione (DSC).