Use and prescription appropriateness of drugs for peptic ulcer and gastrooesophageal reflux disease in hospitalized older people.

PURPOSE: The aims of this study were to assess the prevalence of use and prescription appropriateness of drugs for peptic ulcer and gastrooesophageal reflux disease (GERD) at hospital admission and discharge. METHODS: Patients aged 65 years or more hospitalized from 2010 to 2016 in 101 Italian internal medicine and geriatric wards in the context of the REPOSI register were scrutinized to assess if they were prescribed with drugs for peptic ulcer and GERD at hospital admission and discharge. Appropriateness of prescription was assessed considering the presence of specific conditions (i.e., history of peptic ulcer or gastrointestinal hemorrhages, advanced age, Helicobacter Pylori) or gastro-toxic drug combinations, according to the criteria provided by the reimbursement rules of the Agenzia Italiana del Farmaco (NOTA 1 and 48). RESULTS: Among 4715 enrolled patients, 3899 were discharged alive. At hospital discharge, 2412 (61.9%, 95%CI: 60.3-63.4%) patients were prescribed with drugs for peptic ulcer and GERD, a 12% of increase from hospital admission. Almost half of the patients (N = 1776, 45.6%, 95%CI: 44.0-47.1%) were inappropriately prescribed or not prescribed: among the drugs for peptic ulcer and GERD users, about 60% (1444/2412) were overprescribed, and among nonusers, 22% (332/1487) were underprescribed. Among patients newly prescribed at hospital discharge, 60% (392/668) were inappropriately prescribed. The appropriateness of drugs for peptic ulcer and GERD therapy decreased by 3% from hospital admission to discharge. CONCLUSIONS: Hospitalization missed the opportunity to improve the quality of prescription of this class of drug.

Drug prescriptions in nursing home residents: an Italian multicenter observational study.

PURPOSE: Pharmacoepidemiological studies aimed to distinguish drug use in nursing home (NH) residents with and without dementia could be useful to target specific interventions to improve prescribing. This multicenter retrospective study aimed (i) to describe drug therapy in a large sample of NH residents according to the diagnosis of dementia, and (ii) to record the most frequent potentially severe drug-drug interactions. METHODS: This study was conducted in a sample of Italian long-term care NHs. Drug prescription information, diseases, and socio-demographic characteristics of NH residents were collected at three different times during 2018. RESULTS: The mean number of drugs was significantly higher in NH residents without dementia than in those with (p = 0.05). Antipsychotics, laxatives, benzodiazepines, antiplatelets, and proton pump inhibitors (PPIs) were most commonly prescribed in patients with dementia, and PPIs, benzodiazepines, and laxatives in those without. The prevalence of patients with potentially severe drug-drug interactions was higher among those without dementia, 1216 (64.7%) and 518 (74.2%, p < 0.0001). There were significant differences between the mean numbers of drugs prescribed in individual NH after adjusting the analysis for age, sex, and mean Charlson index, the estimated mean number of drugs prescribed (± standard error) ranging from 5.1 (± 0.3) to 9.3 (± 0.3) in patients with dementia (p < 0.0001) and from 6.0 (± 0.7) to 10.9 (± 0.50) in those without dementia (p < 0.0001). Chronic use of psychotropic drugs was common in NH residents with and without dementia. CONCLUSIONS: The wide variability between NHs in drug prescriptions and potentially inappropriate prescribing suggests the need to recommend a standardized approach to medication review of psychotropic drugs, antiulcer, laxatives, and antiplatelets in this complex and vulnerable population.

Dispersion of elastic waves in a layer interacting with a Winkler foundation.

Dispersion of plane harmonic waves in an elastic layer interacting with a one- or two-sided Winkler foundation is analyzed. The long-wave low-frequency polynomial approximations of the full transcendental dispersion relations are derived for a relatively soft foundation. The validity of the conventional engineering formulation of a Kirchhoff plate resting on an elastic foundation is investigated. It is shown that this formulation has to be refined near the cutoff frequency of bending waves. The associated near cutoff expansion is obtained for both cases. A simple explicit formula demonstrating veering of bending and extensional waves is presented for a one-sided foundation.

Pattern of in-hospital changes in drug use in the older people from 2010 to 2016.

PURPOSE: To assess the pattern of in-hospital changes in drug use in older patients from 2010 to 2016. METHODS: People aged 65 years or more acutely hospitalized in those internal medicine and geriatric wards that did continuously participate to the REgistro POliterapie Società Italiana di Medicina Interna register from 2010 to 2016 were selected. Drugs use were categorized as 0 to 1 drug (very low drug use), 2 to 4 drugs (low drug use), 5 to 9 drugs (polypharmacy), and 10 or more drugs (excessive polypharmacy). To assess whether or not prevalence of patients in relation to drug use distribution changed overtime, adjusted prevalence ratios (PRs) was estimated with log-binomial regression models. RESULTS: Among 2120 patients recruited in 27 wards continuously participating to data collection, 1882 were discharged alive and included in this analysis. The proportion of patients with very low drug use (0-1 drug) at hospital discharge increased overtime, from 2.7% in 2010 to 9.2% in 2016. Results from a log-logistic adjusted model confirmed the increasing PR of these very low drug users overtime (particularly in 2014 vs 2012, PR 1.83 95% CI 1.14-2.95). Moreover, from 2010 to 2016, there was an increasing number of patients who, on polypharmacy at hospital admission, abandoned it at hospital discharge, switching to the very low drug use group. CONCLUSION: This study shows that in internal medicine and geriatric wards continuously participating to the REgistro POliterapie Società Italiana di Medicina Interna register, the proportion of patients with a very low drug use at hospital discharge increased overtime, thus reducing the therapeutic burden in this at risk population.

Neuregulin 1 signalling modulates mGluR1 function in mesencephalic dopaminergic neurons.

Neuregulin 1 (NRG1) is a trophic factor that has an essential role in the nervous system by modulating neurodevelopment, neurotransmission and synaptic plasticity. Despite the evidence that NRG1 and its receptors, ErbB tyrosine kinases, are expressed in mesencephalic dopaminergic nuclei and their functional alterations are reported in schizophrenia and Parkinson's disease, the role of NRG1/ErbB signalling in dopaminergic neurons remains unclear. Here we found that NRG1 selectively increases the metabotropic glutamate receptor 1 (mGluR1)-activated currents by inducing synthesis and trafficking to membrane of functional receptors and stimulates phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway, which is required for mGluR1 function. Notably, an endogenous NRG1/ErbB tone is necessary to maintain mGluR1 function, by preserving its surface membrane expression in dopaminergic neurons. Consequently, it enables striatal mGluR1-induced dopamine outflow in in vivo conditions. Our results identify a novel role of NRG1 in the dopaminergic neurons, whose functional alteration might contribute to devastating diseases, such as schizophrenia and Parkinson's disease.

Long-term prognosis of epilepsy, prognostic patterns and drug resistance: a population-based study.

BACKGROUND AND PURPOSE: Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). METHODS: People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. RESULTS: In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. CONCLUSION: The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs.

Inappropriate prescription of allopurinol and febuxostat and risk of adverse events in the elderly: results from the REPOSI registry.

PURPOSE: To investigate the prevalence of xanthine oxidase (XO) inhibitors prescription at admission and discharge in elderly hospital in-patients, to analyze the appropriateness of their use in relation to evidence-based indications, to evaluate the predictors of inappropriate prescription at discharge and the association with adverse events 3 months after hospital discharge. METHODS: This cross-sectional study, based upon a prospective registry, was held in 95 Italian internal medicine and geriatric hospital wards. The sample included 4035 patients aged 65 years or older at admission and 3502 at discharge. The prescription of XO inhibitors was considered appropriate in patients with diagnosis of gout, gout nephropathy, uric acid nephrolithiasis, tophi, and chemotherapy-induced hyperuricemia. In order to evaluate the predictors of inappropriate prescription of XO inhibitors, we compared the characteristics of patients considered inappropriately treated with those appropriately not treated. RESULTS: Among the 4035 patients eligible for the analysis, 467 (11.6 %) were treated with allopurinol or febuxostat at hospital admission and 461 (13.2 %) among 3502 patients discharged. At admission, 39 (8.6 %) of patients receiving XO inhibitors and 43 (9.4 %) at discharge were appropriately treated. Among those inappropriately treated, hyperuricemia, polytherapy, chronic renal failure, diabetes, obesity, ischemic cardiomyopathy, heart failure, and cardiac dysrhythmias were associated with greater prescription of XO inhibitors. Prescription of XO inhibitors was associated with a higher risk of adverse clinical events in univariate and multivariate analysis. CONCLUSIONS: Prevalence of inappropriate prescription of XO inhibitors remained almost the same at admission and discharge. Inappropriate use of these drugs is principally related to treatment of asymptomatic hyperuricemia and various cardiovascular diseases.

Elevated risk of death and major cardiovascular events in subjects with newly diagnosed diabetes: findings from an administrative database.

AIMS: To investigate the incidence of major cardiovascular complications and mortality in the first years of follow-up in patients with newly diagnosed diabetes. METHODS AND RESULTS: We examined incidence rates of hospitalization for cardiovascular reasons and death among new patients with diabetes using the administrative health database of the nine million inhabitants of Lombardy followed from 2002 to 2007. Age and sex-adjusted rates were calculated and hazard ratios (HR) were estimated with a matched population without diabetes of the same sex, age (± 1 year) and general practitioner. There were 158,426 patients with newly diagnosed diabetes and 314,115 subjects without diabetes. Mean follow-up was 33.0 months (SD ± 17.5). 9.7% of patients with diabetes were hospitalized for cardiovascular events vs. 5.4% of subjects without diabetes; mortality rate was higher in patients with diabetes (7.7% vs. 4.4%). The estimated probability of hospitalization during the follow up was higher in patients with diabetes than in subjects without for coronary heart disease (HR 1.4, 95% CI 1.3-1.4), cerebrovascular disease (HR 1.3.95% CI 1.2-1.3), heart failure (HR 1.4, 95% CI 1.3-1.4) as was mortality (HR 1.4, 95% CI 1.4-1.4). Younger patients with diabetes had a risk of death or hospital admission for cardio-cerebrovascular events similar to subjects without diabetes ten years older. CONCLUSIONS: The elevated morbidity and mortality risks were clear since the onset of diabetes and rose over time. These data highlight the importance of prompt and comprehensive patients care in addition to anti-diabetic therapy in patients with newly diagnosed diabetes.

Prevalence of potentially inappropriate medications and risk of adverse clinical outcome in a cohort of hospitalized elderly patients: results from the REPOSI Study.

WHAT IS KNOWN AND OBJECTIVE: Inappropriate prescribing is highly prevalent for older people and has become a global healthcare concern because of its association with negative health outcomes including ADEs, hospitalization and resource utilization. Beers' criteria are widely utilized for evaluating the appropriateness of medications, and an up-to-date version has recently been published. To assess the prevalence of patients exposed to PIMs at hospital discharge according to the 2003 and 2012 versions of Beers' criteria and to evaluate the risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up. METHODS: This cross-sectional study was held in 66 Italian internal medicine and geriatric wards. The sample included 1380 inpatients aged 65 years or older. Prescriptions of PIM were analysed at hospital discharge. We considered all patients with complete 3-month follow-up. RESULTS AND DISCUSSION: The prevalence of patients receiving at least one PIM was 20·1% and 23·5% according to the 2003 and 2012 versions of the Beers' criteria, respectively. The 2012 Beers' criteria identified more patients with at least one PIM than the 2003 version, although a high percentage of those patients (72·2%) were also identified by the criteria updated in 2003. The main difference in the prevalence of patients receiving a PIM according to the two versions of Beers' criteria involved prescriptions of benzodiazepines for insomnia or agitation, chronic use of non-benzodiazepine hypnotics, prescription of antipsychotics in people with dementia and oral iron at dosage higher than 325 mg/day. Prescription of PIMs was not associated with a higher risk of adverse clinical events, re-hospitalization and all-cause mortality at 3-month follow-up in both univariate and multivariate analysis, after adjusting for age, sex and CIRS comorbidity index. WHAT IS NEW AND CONCLUSIONS: This study found no significant effect of inappropriate drug use according to Beers' criteria on health outcomes among older adults 3 month after discharge. Even though these criteria have been suggested as helpful in promoting appropriate prescribing, reducing drug-related adverse events and associated healthcare costs, to date there is no clear evidence that their application can achieve objective and quantifiable improvements in clinical outcomes. A possible explanation is that both versions of the Beers' criteria have several recognized limitations, one of the main ones being the restricted availability of some drugs in Europe or their limited prescription in everyday clinical practice.

E-learning to improve the drug prescribing in the hospitalized elderly patients: the ELICADHE feasibility pilot study.

BACKGROUND: E-learning is an efficient and cost-effective educational method. AIMS: This study aimed at evaluating the feasibility of an educational e-learning intervention, focused on teaching geriatric pharmacology and notions of comprehensive geriatric assessment, to improve drug prescribing to hospitalized elderly patients. METHODS: Eight geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control. Clinicians of the two groups had to complete a specific per group e-learning program in 30 days. Then, ten patients (aged ≥75 years) had to be consecutively enrolled collecting clinical data at hospital admission, discharge, and 3 months later. The quality of prescription was evaluated comparing the prevalence of potentially inappropriate medications through Beer's criteria and of potential drug-drug interactions through a specific computerized database. RESULTS: The study feasibility was confirmed by the high percentage (90 %) of clinicians who completed the e-learning program, the recruitment, and follow-up of all planned patients. The intervention was well accepted by all participating clinicians who judged positively (a mean score of >3 points on a scale of 5 points: 0 = useless; 5 = most useful) the specific contents, the methodology applied, the clinical relevance and utility of e-learning contents and tools for the evaluation of the appropriateness of drug prescribing. CONCLUSIONS: The pilot study met all the requested goals. The main study is currently ongoing and is planned to finish on July 2015.

Emerging role of mitochondria dysfunction in the onset of neurodegenerative diseases.

Mitochondria play a pivotal role in a number of biochemical processes in the neuron including energy metabolism and ATP production, intracellular Ca2+ homeostasis and cell signalling which are all implicated in the regulation of neuronal excitability. For this reason, it is not surprising that alterations in mitochondrial function have emerged as a hallmark of aging and various age-related neurodegenerative diseases in which a progressive functional decline of mitochondria has been described. The evidence that mitochondria are concentrated in synapses, together with the observation that synaptic dysfunction identifies an early forerunner of a later neurodegeneration, strongly suggests that significant alterations to synaptic mitochondrial localization, number, morphology, or function can be detrimental to synaptic transmission and might characterize the early stages of many neurological diseases. Thus, the characterization of both molecular players and pathway involved in mitochondria dysfunction will provide new chances to identify pharmacological target for new mitochondria-based drugs aimed at interrupting or slowing down pathological processes and/or ameliorating symptoms of neurological disorders. In this review we provide a current view on the role of mitochondria for neuronal function and how mitochondrial functions impinge on neurological diseases.

Comparison of disease clusters in two elderly populations hospitalized in 2008 and 2010.

BACKGROUND: As chronicity represents one of the major challenges in the healthcare of aging populations, the understanding of how chronic diseases distribute and co-occur in this part of the population is needed. OBJECTIVES: The aims of this study were to evaluate and compare patterns of diseases identified with cluster analysis in two samples of hospitalized elderly. METHODS: Data were obtained from the multicenter 'Registry Politerapie SIMI (REPOSI)' that included people aged 65 or older hospitalized in internal medicine and geriatric wards in Italy during 2008 and 2010. The study sample from the first wave included 1,411 subjects enrolled in 38 hospitals wards, whereas the second wave included 1,380 subjects in 66 wards located in different regions of Italy. To analyze patterns of multimorbidity, a cluster analysis was performed including the same diseases (19 chronic conditions with a prevalence >5%) collected at hospital discharge during the two waves of the registry. RESULTS: Eight clusters of diseases were identified in the first wave of the REPOSI registry and six in the second wave. Several diseases were included in similar clusters in the two waves, such as malignancy and liver cirrhosis; anemia, gastric and intestinal diseases; diabetes and coronary heart disease; chronic obstructive pulmonary disease and prostate hypertrophy. CONCLUSION: These findings strengthened the idea of an association other than by chance of diseases in the elderly population.

Evaluation of the prevalence of dental agenesis through the use of orthopantomography in a sample of subjects residing in Lombardy and Piedmont regions.

AIM: Dental agenesis is one of the most frequent dental anomalies, with a prevalence varying from 1.6% to 36.5%, depending on the populations studied. The patient's age at diagnosis, sex, and ethnic differences are considered possible influenting factors that can explain such a wide range of prevalence. The objective of the study was to define the frequency of dental agenesis in a sample of subjects living in Piedmont and Lombardy regions of Italy. MATERIALS: X-rays, already taken for other diagnostic purposes, were collected. Orthopantomographies belonging to subjects born after 1995 and aged between 7.9 and 16.9 years were selected. It was assessed the presence of each tooth, except for third molars since they are frequently absent due to their variability. If a tooth was missing and the patient had additional radiographs, the other radiographs were evaluated to confirm the diagnosis or to rule out a delayed calcification or the presence of a malposition tooth. Results: Orthopantomographies were collected from 1,020 subjects and 98 of them presented agenesis, with a prevalence of 5% for females and 4.61% for males. The most affected teeth were 35 and 45, followed by 12 and 22. The lower arch was more frequently involved by agenesis: there were 107 teeth absent in the mandibular arch and 83 in the maxillary arch.

Prevalence, incidence and mortality of diagnosed diabetes: evidence from an Italian population-based study.

AIMS: To describe trends in diagnosed diabetes prevalence, incidence and mortality from 2000 to 2007 in the most heavily populated Italian region. METHODS: We examined the prevalence and incidence rates of Type 1 and Type 2 diabetes and yearly mortality rates among individuals with diabetes from 2000 to 2007 using an administrative health database of prescription, disease-specific exemption and hospitalization records of more than 9 million inhabitants of Lombardy. Age- and sex-specific rates were calculated and temporal trends for subjects aged ≥ 30 years were analysed. RESULTS: The crude point diabetes prevalence rose from 3.0% in 2000 to 4.2% in 2007, a 40% increase. The incidence remained stable during the study period with a rate of 4/1000 per year. Overall mortality declined from 43.2/1000 in 2001 to 40.3/1000 in 2007 (6.7% decrease) at a rate slightly higher than that of the general population (4.8% decrease). Our projection in subjects aged ≥ 30 years indicates that the prevalence will rise continuously over the next years, reaching 11.1% in 2030. CONCLUSIONS: The prevalence of diabetes increased substantially between 2000 and 2007, mainly because there are more patients with a new diagnosis each year than those who die. The increase observed by 2007 almost reached the World Health Organization prediction for 2030. Our analyses suggest that the increase will continue over the next few decades. These data are important for defining the burden of diabetes in the near future, to help in planning health services and ensure proper allocation of resources.

Prevalence and characteristics of antidepressant drug prescriptions in older Italian patients.

BACKGROUND: During last few decades, the proportion of elderly persons prescribed with antidepressants for the treatment of depression and anxiety has increased. The aim of this study was to evaluate prevalence of antidepressant prescription and related factors in elderly in-patients, as well as the consistency between prescription of antidepressants and specific diagnoses requiring these medications. METHODS: Thirty-four internal medicine and four geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI study during 2008. In all, 1,155 in-patients, 65 years or older, were enrolled. Prevalence of the use of antidepressants was calculated at both admission and discharge. Logistic regression was used to evaluate the association between patients' characteristics (age, gender, Charlson Index, number of drugs, specific diseases, other psychotropic medications) and the prescription of antidepressants. RESULTS: The number of patients treated with antidepressant medication at hospital admission was 115 (9.9%) and at discharge 119 (10.3%). In a multivariate analysis, a higher number of drugs (OR = 1.2; 95% CI = 1.1-1.3), use of anxiolytic drugs (OR = 2.1; 95% CI = 1.2-3.6 and OR = 3.8; 95% CI = 2.1-6.8), and a diagnosis of dementia (OR = 6.1; 95% CI = 3.1-11.8 and OR = 5.8; 95% CI = 3.3-10.3, respectively, at admission and discharge) were independently associated with antidepressant prescription. A specific diagnosis requiring the use of antidepressants was present only in 66 (57.4%) patients at admission and 76 (66.1%) at discharge. CONCLUSIONS: Antidepressants are commonly prescribed in geriatric patients, especially in those receiving multiple drugs, other psychotropic drugs, and those affected by dementia. There is an inconsistency between the prescription of antidepressants and a specific diagnosis that the hospitalization only slightly improves.

Relation between drug therapy-based comorbidity indices, Charlson's comorbidity index, polypharmacy and mortality in three samples of older adults.

BACKGROUND: Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available. AIMS: This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy. METHODS: Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE). RESULTS: Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings. CONCLUSION: On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.

Abatement of thermal noise due to internal damping in 2D oscillators with rapidly rotating test masses.

Mechanical oscillators can be sensitive to very small forces. Low frequency effects are up-converted to higher frequency by rotating the oscillator. We show that for 2-dimensional oscillators rotating at frequency much higher than the signal the thermal noise force due to internal losses and competing with it is abated as the square root of the rotation frequency. We also show that rotation at frequency much higher than the natural one is possible if the oscillator has 2 degrees of freedom, and describe how this property applies also to torsion balances. In addition, in the 2D oscillator the signal is up-converted above resonance without being attenuated as in the 1D case, thus relaxing requirements on the read out. This work indicates that proof masses weakly coupled in 2D and rapidly rotating can play a major role in very small force physics experiments.

Differences in outpatient antibiotic prescription in Italy's Lombardy region.

OBJECTIVES: We assessed the antibiotic patterns of use and geographical distribution of prevalence and consumption by age in 15 Local Health Units (LHUs) of Italy's Lombardy region. METHODS: A retrospective analysis of reimbursement data for the community-dwelling population in 2005 was performed. Prescriptions reimbursed by the National Health System and consumption as defined daily doses (DDD) per 1,000 inhabitants per day (DID) were analyzed. A logistic regression was performed to evaluate the association between antibiotic drug prescription and age, gender, and LHU of residence of the population. RESULTS: During 2005, a total of 3,120,851 people (34% of the population) received at least one antibiotic drug prescription. The highest prescription prevalence was observed in the 0-17 and 80 or more years age ranges (41.6 and 41.9%, respectively). Large differences were found in the prevalence rates between different LHUs (ranging from 28.7% in Milan to 39.4% in Brescia) and in DID (ranging from 12.6 DID in Sondrio to 18.9 DID in Brescia). The age and residence of the population were the main determinants of drug exposure. In particular, patients aged <18 years (odds ratio [OR] = 1.73; 95% confidence interval [CI] 1.73, 1.74), aged 65 years or older (OR = 1.64; 95% CI 1.63, 1.65), and those that live in Brescia (OR = 1.66; 95% CI 1.65, 1.66) had a statistically significant higher risk of antibiotic drug exposure. CONCLUSIONS: The observed intra-regional differences underline the need for a careful monitoring with the aim to reduce antibiotic resistance and improve the rational use of drugs.