Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Gender differences of ADRs related to psychotropic drug: a survey from Italy, France and Spain

Background: It is well recognized that being female appears to be a risk factor for developing ADRs. A number of studies clearly suggest that ADRs are 50% to 75% more likely in women than in men. It has also been suggested that there is a female preponderance in the number of ADRs experienced with nervous system agents. Results from the European Study of the Epidemiology of Mental disorders (ESEMED) conducted in 2001-2003, highlight that the use of psychotropic drugs was more prevalent among women than men. Anxiolytics, sedatives and hypnotics were more often used, followed by antidepressants and antipsychotics. A female propensity to experience of drug adverse effects may result from “gender” related differences in drug exposure as well as “sex” related differences in drug pharmacokinetics and pharmacodynamics. Nonetheless, the reasons for this increased risk in female patients are not entirely clear, notably whether adverse drug reactions among women reflect an inappropriate use of psychotropic medications. Objective: The aim of this study is to analyze the difference between women and men of psychotropic drugs ADRs reported in the regional pharmacovigilance centre of Midi-Pyrénées (France), Veneto (Italy) and Castilla-Leon (Spain) using spontaneously reported reactions. Specifically the spontaneous reports of ADRs studied regarded antipsychotics, anxiolytics, hypnotics, antidepressant and stimulants that were reported between 2007 and 2009. Methods: Within the French, Italian and Spanish Pharmacovigilance System databases, the case/non-case method was used to measure the association with the exposure of psychotropic medications of interest and gender. Cases were the reports corresponding to the ADRs related at least to one type of psychotropic drugs of interest and the non-cases are all reports of ADRs other than that being studied. The association was estimated by calculating a reporting odds ratio (ROR) with its 95% confidence interval (CI). Results: A total of 967 patients were included in the study, 592 (61%) were female and 375 (39%) were male (p< 0,001). Mean age of the study population was 51 years (range 08-97 years). The association between the use of psychotropic medications of interest and gender was statistically significant for women taking antidepressants (ROR crude =1.67; 95% CI 1,35-2,06; ROR stratified for seriousness =1,71; 95% CI 1,39-2,11; ROR stratified for age = 1,53; 95% CI 1,24- 1,90; ROR stratified for age and seriousness =1.54; 95% CI 1,25-1,90) [all p < 0,001]. Analyzing all reports of ADRs reported, the most involved drugs were risperidone (14 % of the total N05A drugs), alprazolam (14 % of the total N05B drugs), zolpidem (32% of the total N05C drugs), paroxetine (16 % of the total N06A drugs) and methylphenidate (39% of the total N06B drugs), while the most associated with sex, in particular with female sex, were lithium carbonate (p<0.05) and prazepam (p<0.05), and with male sex were clozapine (p<0.05) and sertraline (p<0.05). The most frequent type of ADRs reported in all women reports were classified as “Central & peripherical nervous system disorders” (24%) and “Psychiatric disorders” (18%), while in all men reports were “Body as a whole - general disorders” (14%) and “Resistance mechanism disorders” (13%). Conclusions: The present study which investigated the role of gender in ADRs reported to a regional French, Italian and Spain Pharmacovigilance centres indicates that female sex is a risk factor for the development of ADRs related to psychotropic drugs especially to antidepressants. Further research should be performed to investigate the sex-specific drug safety of psychtropic use, taking into account potential risk factors, not only in relation to pharmacogenetics, pharmacokinetics and pharmacodynamics, but also in psychological, social, economic, political and cultural aspects.Introduzione. È ormai ampiamente riconosciuto come le differenze tra donne e uomini possano influire sulla risposta al trattamento farmacologico e sulla sicurezza dell’impiego dei farmaci nelle due diverse popolazioni. Il genere femminile sembra essere un fattore di rischio per la manifestazione delle reazioni avverse ai farmaci (ADR): le donne hanno una probabilità del 50-75% superiore rispetto agli uomini di manifestare un’ ADR. I farmaci psicotropi rappresentano una delle classi maggiormente coinvolte nella manifestazione degli eventi avversi. Dai risultati di uno studio europeo ESEMED (Epidemiologia dei Disturbi Mentali) emerge come Francia, Italia e Spagna rappresentino i paesi in cui sono state rilevate le più alte percentuali di utilizzo di farmaci psicotropi. Gli ansiolitici, i sedativi e gli ipnotici sono stati rilevati in questo studio come gli psicofarmaci più frequentemente utilizzati, seguiti dagli antidepressivi ed ansiolitici. La propensione delle donne alla segnalazione, nonché le differenze delle donne rispetto agli uomini nella farmacocinetica e farmacodinamica, l’età, il numero dei farmaci prescritti alle donne possono chiaramente influenzare l’entità della segnalazione. Nonostante queste evidenze, le ragioni di questo aumento del rischio in pazienti di sesso femminile non sono del tutto chiare, in particolare se le reazioni avverse al farmaco tra le donne riflettono un uso improprio dei farmaci psicotropi. Obiettivi. Lo scopo principale dello studio è stato quello di indagare le differenze tra la popolazione maschile e quella femminile riguardo alla comparsa di ADRs da farmaci psicotropi, rilevate nel centro di farmacovigilanza della regione del Midi- Pyrénées (Francia), del Veneto (Italia) e della Castilla y Leòn (Spagna), utilizzando dati provenienti dalla segnalazione spontanea. Nello specifico, sono stati rilevati tutti i report di segnalazione delle ADRs relative alle seguenti classi di psicofarmaci: antipsicotici, ansiolitici, ipnotici, antidepressivi e stimolanti; riportate tra il 1 gennaio 2007 e il 31 dicembre 2009. Metodo. Le ADRs sono state classificate secondo il sesso, la gravità, la tipologia della reazione, l’esito, i farmaci sospetti ed i farmaci concomitanti assunti. La distribuzione per sesso è stata analizzata con il metodo caso-non caso (report associati alle 5 categorie di psicofarmaci in studio e report associati a tutti gli altri farmaci) calcolando il reporting odds ratio (ROR) crudo e aggiustato su tutte le variabili, e considerando un intervallo di confidenza del 95% (IC 95%). Risultati. Un totale di 967 pazienti sono stati inclusi nello studio, 592 (61%) era di sesso femminile e 375 (39%) era di sesso maschile (p <0,001). L'età media della popolazione in studio era di 51 anni (range 08-97 anni). L'associazione tra l'uso di farmaci psicotropi di interesse e il genere è stata rilevata statisticamente significativa per le donne che assumevano antidepressivi (ROR grezzo = 1,67, IC 95% 1,35-2,06; ROR stratificato per gravità = 1,71, IC 95% 1,39-2,11; ROR stratificato per età = 1,53, IC 95% 1,24-1,90; ROR stratificato per età e gravità = 1.54, IC 95% 1,25-1,90) [tutte le p <0.001]. Dall’analisi di tutti i report di ADRs segnalati, i farmaci maggiormente coinvolti sono stati: il risperidone (il 14% di tutti i farmaci appartenenti alla classe ATC N05A), l’ alprazolam (il 14% degli N05B), il zolpidem (il 32% degli N05C), la paroxetina (il 16% degli N06A) e il metilfenidato (il 39% degli N06B). I farmaci, invece, maggiormente associati al sesso, in particolare al sesso femminile, sono stati il carbonato di litio (p <0,05) e il prazepam (p <0,05), e al sesso maschile sono stati la clozapina (p <0,05) e la sertralina (p <0,05). La tipologia di ADR più frequentemente riportata dalle donne riguardava " disturbi del sistema nervoso centrale" (24%) e "disturbi psichiatrici" (18%), mentre negli uomini "disturbi generali "(14%) e" disturbi nei meccanismi di resistenza "(13%). Conclusioni. Dal presente studio è possibile osservare come il sesso femminile rappresenti un fattore di rischio per lo sviluppo di reazioni avverse correlate a farmaci psicotropi, soprattutto in riferimento agli antidepressivi. Ulteriori ricerche dovrebbero essere effettuate per valutare la sicurezza dell’uso di farmaci psicotropi in funzione del sesso, tenendo conto dei potenziali fattori di rischio, non solo relativi alla farmacogenetica, farmacocinetica e farmacodinamica, ma anche ad aspetti psicologici, sociali, economici, politici e culturali

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Stressful life events and social health factors in women using anxiolytics and antidepressants: An Italian observational study in community pharmacies

BACKGROUND: In Italy, as in all of Europe, women differ from men in that they are somewhat more sensitive to the depressogenic effects of stressful life events related to their social networks and emotional sphere. Women are more likely than men to have experienced poverty, gender discrimination, and physical and sexual abuse. OBJECTIVE: The purpose of this study was to expand the knowledge about the occurrence of stressful life events in women exposed and not exposed to anxiolytics and antidepressants in a community pharmacy setting. METHODS: Women attending 100 community pharmacies in the Italian Veneto region were surveyed by pharmacists with regard to a number of general features of their current pharmacologic treatment. Women independently completed a written self-assessment questionnaire that focused on stressful life events. Unconditional logistic regression analysis was performed to investigate the association between anxiolytics and antidepressants use and potential factors, including stressful life events. RESULTS: The study population comprised 11,357 women. One or more stressful life events occurred in 90% of the women treated with anxiolytics and/or antidepressants (users [n = 3848]) and in 74% of the women not treated with these drugs (nonusers [n = 7509]) (odds ratio = 3.19; 95% CI, 2.83-3.60). On average, the life events occurred during the previous 6 months and the women considered the influence of these events on their well-being to be severe. After the unconditional logistic regression analysis, the association between anxiolytics and/or antidepressants use remained positive for most of the stressful life events studied as well as for other factors: separation/divorce, living alone or with others (family or friends), unemployment, whether currently being seen by a psychologist/psychiatrist, and treatment with drugs for the alimentary tract and metabolism, cardiovascular system, or nervous system. CONCLUSIONS: A significant association between stressful life events and anxiolytics and/or antidepressants use was observed. Further efforts are needed to increase our knowledge of the use of anxiolytics or antidepressants in relation to the occurrence of life events

Numerical and experimental investigations on new jar designs for high efficiency planetary ball milling

The internal shape of planetary ball mill jars was modified to increase the efficiency of the milling process. Four new jar designs are presented, where obstacles on the surface of a traditional cylindrical jar modify the ratio of normal-to-tangential transferred mechanical action, thus improving the comminution of the mill charge and reducing the process time. Multibody dynamics simulations, validated by operando video recordings of the process, were employed to investigate modified ball motion regimes promoting the increase of the number of high-energy impacts. Moreover, experimental grinding of calcium fluoride powder was performed to assess the effect of milling time and jar-to-plate velocity ratio, through the evaluation of size and microstrain of the end product deduced from X-ray diffraction line profile analysis