Early Detection Screening of Cognitive Decline in Patients Over 60 Years: ELDERCARE Study.

Background: Dementia is the fourth leading cause of death in people >  65 years old in western countries. Objective: This cross-sectional assisted survey aimed to evaluate a multidisciplinary team approach of specialists of the Associazione Geriatri Extraospedalieri a favore di Anziani Svantaggiati and pharmacists to facilitate progress in the early identification and management of cognitive decline in patients >  60 years. Methods: A multidisciplinary team conducted this cross-sectional assisted survey. Patients (>60 years) with independent and/or assisted walking, subjective memory impairment, mild cognitive impairment or mild Alzheimer's disease (AD) who regularly attended pharmacies underwent the survey. An internal medical examination, a cardiovascular visit, and a short neuropsychological evaluation were conducted for each patient. Demographic, anamnestic, and clinical data were collected anonymously. Results: 279 eligible patients underwent the screening phase. 44% were overweight, 23% obese and 29% hypertensive. 62% of cases showed alterations of supra-aortic trunk with different percentages of stenosis. The neuropsychological evaluation highlighted that 67% of cases were normal according to age and education level, while 18% were in a state condition of cognitive frailty. Mild/moderate cognitive decline, or probably AD, was identified in 14% of cases. Conclusions: A multidisciplinary collaboration between pharmacists and specialist medical doctors is essential in early identification of prodromal symptoms of cognitive impairment and AD. The Prompt detection of the condition in this group of patients allowed the specialists to recommend in-depth diagnostic tests and follow-up procedures to slow the course of the disease. This would give time to carry out adequate caregiver training.

Changes in antiepileptic drug prescriptions over a decade in childbearing women in Lombardy region, Italy.

AIMS: To describe the antiepileptic drug (AED) prescription pattern in pregnant women and women of childbearing age in the 2010-2019 period in the Lombardy region, Italy. METHODS: The Lombardy region administrative healthcare databases (2010-2019) were analysed. AEDs were classified as drugs belonging to the N03A subgroup of the Anatomical Therapeutic Chemical Classification System. Women aged 15-49 years were considered as being of childbearing age, while exposure during pregnancy was estimated taking into account the 12 months before delivery (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes in the diagnosis record from 650 to 659). RESULTS: During 2019, 16 605 women of childbearing age (prevalence: 14.8‰) received at least 1 AED prescription. Pregabalin was the most widely used antiepileptic in women of childbearing age (22.3%), followed by valproic acid (20.0%). In 2010, the prevalence of valproic acid prescription to women of childbearing age was 30.2%; in 2019 this was 20.0%. In pregnant women, this prevalence was 24.9% in 2010 and 14.1% in 2019. Starting from 2017, levetiracetam and lamotrigine were the most commonly drugs prescribed to pregnant women. CONCLUSION: Despite the decrease in valproic acid prescription over time, this drug is still among the most used AEDs, in particular in women of childbearing age. Educational interventions for healthcare professionals and women are needed in order to reduce the risk of unplanned pregnancy.

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

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

Treatments in neurogenic bowel dysfunctions: evidence reviews and clinical recommendations in adults.

INTRODUCTION: Neurogenic bowel dysfunction (NBD) is an impairment of defecation control due to any nervous system lesion negatively affecting physical health status and quality of life. We aimed at systematically assessing all available evidence on NBD treatment in adults and providing clinical management guidance and recommendations. EVIDENCE ACQUISITION: PICOs and questions (N.=7) were identified by an expert panel. We searched for and retrieved evidence from the PUBMED and EMBASE databases, limited to the English language and the Western countries context, related to any type of setting and published from 2009 to 2019. Health effects, patient values, preferences and resource use were assessed. Of all, only RCTs, observational studies and systematic reviews on adult population (≥18 years) were analyzed. The study was conducted according to PRISMA guidelines and Cochrane recommendations. The effect size, if possible, was calculated for the interpretation of the outcomes, and evidence was assessed through the GRADE method. EVIDENCE SYNTHESIS: Thirty-one studies were included in our qualitative synthesis. Evidence is generally scarce. Most of the outcomes are narratively described and therefore defined by imprecision. Besides, most of the included studies are affected by risk of bias. Digital stimulation was found to be effective in short term follow-up. The pharmacological treatment choice, combined or alone, needs to be balanced case by case considering clinical history, setting of use and bowel management protocol. According to only one RCT supporting evidence mainly in persons affected by spinal cord injury (SCI), trans-anal irrigation (TAI) improves QoL and patient independency with a significant reduction of time spent for defecation and daily bowel program. History of urinary infections predicts the choice of using TAI. Patient-reported efficacy of colostomy alone or in combination with other surgeries appears evident in terms of patient's satisfaction and QoL over time. Nonetheless, perioperative and late complications can occur and may result in reduced acceptability over time. CONCLUSIONS: Evidence is somehow weak and mainly reported in SCI. The systematic use of assistive interventions does not reduce the need of conservative or invasive approaches. Studies are needed on the role of bowel management in protecting patients from complications secondary to NBD in long term follow-ups.

Fixed Versus Free Combinations Of Antihypertensive Drugs: Analyses Of Real-World Data Of Persistence With Therapy In Italy.

PURPOSE: To analyse the pattern of use and cost of antihypertensive drugs in new users in an Italian population, and explore the patient/treatment factors associated with the risk of therapy discontinuation. PATIENTS AND METHODS: In this retrospective study, information was collected from a population-based electronic primary-care database. Persistence with medication use 1 year from therapy initiation was evaluated for each user using the gap method. Each new user was classified according to his/her pattern of use as: "continuer", "discontinuer" "switching" or "add-on". A Cox regression model was used to analyse the factors influencing therapy discontinuation. Primary-care costs comprised specialists' visits, diagnostic procedures and pharmacologic therapies. RESULTS: Among 14,999 subjects included in persistence analyses, 55.1% of cases initially started on monotherapy were classified as discontinuers vs 36.5% of cases taking combination therapy (42.3% vs 32.7%, respectively, for free and fixed combinations, P < 0.01). Old age, high cardiovascular risk and being in receipt of fixed-combination therapy were associated with greater persistence. Overall, the primary-care cost/person/year of hypertension management was ~€95.3 (IQR, 144.9). The monotherapy cost was €88 per patient (IQR, 132.9), and that for combination therapy was €151±148.3. The median cost/patient with a fixed combination was lower than that for a free combination (€98.4 (IQR, 155.3) and €154.9 (IQR, 182.6), respectively). CONCLUSION: The initial type of therapy prescribed influences persistence. Prescribing fixed combinations might be a good choice as initial therapy.

The evidence-based choice for antipsychotics in children and adolescents should be guaranteed.

PURPOSE: Drug use in the pediatric population still often features off-label prescriptions, particularly for psychotropic drugs. We reviewed the registration status, scientific evidence, and recommendations from the guidelines for antipsychotics used for psychiatric disorders in children. METHODS: Antipsychotic drugs marketed in Italy, the United Kingdom (UK) and United States (US) were identified with the ATC Classification System. The licensing status and Summary of Product Characteristics (SPC) were taken from the national formularies. We analyzed reviews and guidelines on antipsychotics use in children and adolescents in the MEDLINE, EMBASE, and PsycINFO databases. RESULTS: Out of 67 drugs, 19 were marketed with a pediatric license in at least one country: three in all the selected countries, and only paliperidone with the same indications. Haloperidol was the only antipsychotic authorized for autism in Italy and the UK, and as well as risperidone and aripiprazole in the US. Aripiprazole and paliperidone were licensed in all three countries for schizophrenia. Aripiprazole was licensed for bipolar disorders in all three countries. Haloperidol was licensed for Tourette syndrome in Italy and the UK, and pimozide and aripiprazole in the US. We retrieved 21 pertinent reviews and 13 guidelines for the management of neuropsychiatric disorders in pediatrics. There was a complete overlap between the authorized therapeutic indications and the available scientific evidence for autism in the US, for conduct disorders and bipolar disorders in the UK, and for Tourette syndrome and tics in the UK and Italy. CONCLUSIONS: These results highlight the different regulatory processes that deny to many children and adolescents the most appropriate and rational antipsychotic therapy.

Perinatal outcome and healthcare resource utilization in the first year of life after antiepileptic exposure during pregnancy.

Healthcare administrative databases of Italy's Lombardy Region were analyzed with the aim to assess perinatal outcomes and healthcare resource utilization during the first year of life in infants exposed to antiepileptic drugs (AEDs) during pregnancy. Drug prescriptions dispensed in the 12 months before delivery to women, who delivered between 2005 and 2011, were analyzed. Neonates were classified as cases if exposed to AEDs, and each case was randomly matched to seven controls. No significant differences were observed in the risk of congenital malformations between 526 cases and 3682 controls except for valproic acid (odds ratio (OR): 2.29; 95% confidence interval (CI): 1.24-4.22) where cases were more likely to be small for gestational age (χ2 = 7.66; p = 0.006). Cases also had a higher probability than controls of needing at least one specialist visit in a child neuropsychiatry outpatient service (OR: 1.74; 95% CI: 1.22-2.49).

Differences in drug use between men and women: an Italian cross sectional study.

BACKGROUND: Drugs are the most important treatment option for most diseases, and the majority of medical consultations result in a prescription. Women and men receive different drug prescriptions and differ in therapeutic response to pharmacological therapy. This disparity is due to biological factors (sex differences) or/and behavior, lifestyle and life experience (gender differences). Sex differences in drug use have been demonstrated in several therapeutic areas; however, there is a lack of overviews on sex and gender differences of drug use in an entire population. METHODS: We conducted a descriptive cross - sectional drug use study, involving the entire Italian population in 2012, aimed at showing and analyzing differences between men and women as regards their exposure to drugs. The data source was IMS LifeLink Treatment DynamicsTMLRx Database and it included all prescribed drugs reimbursed by the Italian National Healthcare System in 2012 and covered 90% of the entire Italian population. The information about the prescriptions was stratified by men and women and age. Drug consumption was expressed as DDD/ 1000 ab die. Exposure to drug prescriptions was expressed as period prevalence (the proportion of the population dispensed ≥1 prescription in 2012 per 1000 inhabitants). Differences of prevalence between men and women were expressed as crude and age adjusted risk ratios with 95% CI. RESULTS: Our findings suggested that the largest differences in drug prescriptions regarded drugs affecting bone structure and mineralization (RR 15.9), calcium (RR 8.6) and thyroid therapy (RR 5.4), dispensed more to women than men. Otherwise ACE inhibitors were more commonly used in men. CONCLUSIONS: This is the first study exploring difference in drug use between men and women and carried out on the entire Italian population. Our findings showed substantial differences between men and women in term of prevalence of drug prescriptions. Some differences in drug use may be explained by sex differences (variations in disease prevalence and severity, pathophysiology, or by other biological differences), other differences need further investigation to explain the apparent lack of a rational medical explanation for some findings. The findings may subsequently be used to plan future studies to address differences suggesting inequity in treatment approaches.

Antiepileptic drug use in Italian children over a decade.

PURPOSE: The aim of the study was to evaluate prescription profiles of antiepileptic drugs (AEDs) and to assess hospitalizations and specialist visits in pediatric patients with epilepsy. METHODS: The data sources were administrative health databases of Italy's Lombardy Region, which collect prescriptions for drugs, diagnostic tests, specialist visits, and hospital discharge forms. All patients aged 0-16 years with at least seven AED (group N03A of the International Anatomical Therapeutic Chemical Classification) prescriptions over two consecutive years between 2003 and 2010 were identified and classified as prevalent or incident cases (no prescriptions in two previous years). The first prescription to incident cases was analyzed. For each incident case, drug prescriptions, specialist visits, diagnostic tests, and hospitalizations in the 24 months following the first (index) prescription were monitored. RESULTS: A total of 6527 incident cases (5.4/10,000 person-years, 95% CI 5.4-5.5) were identified. Valproic acid and carbamazepine were the most prescribed drugs (65.9 and 15.0%, respectively). The use of newer AEDs increased over time. In the 24-month observation period, 74% of incident cases continued the treatment with the index AED. The percentage of cases who changed therapy was higher in preschoolers (34%) and decreased with age. In all, 21% of incident cases were hospitalized for epilepsy and 86% had a specialist visit in the 24 months after the first AED prescription. CONCLUSIONS: In conclusion, older AEDs, particularly valproic acid, remained the first therapeutic approach to pediatric epilepsy in Italy. For three quarters of cases, the initial AED treatment was likely effective and well tolerated.

The Citicholinage Study: Citicoline Plus Cholinesterase Inhibitors in Aged Patients Affected with Alzheimer's Disease Study.

BACKGROUND: Citicoline can have beneficial effects both in degenerative and in vascular cognitive decline in a variety of ways (apoptosis inhibition, neuroplasticity potentiation, phospholipid, and acetylcholine (ACh) synthesis). Acetylcholinesterase inhibitors (AChEIs) have been used for treatment of Alzheimer's disease (AD). When co-administered with cholinergic precursors, they are able to increase the intrasynaptic levels of ACh more than when the single drugs given alone. OBJECTIVE: The aim of the present study was to show the effectiveness of oral citicoline plus AChEIs in patients affected with AD. METHODS: This was a retrospective multi-centric case-control study, involving seven Centers for Cognitive Impairment and Dementia in Italy, on 448 consecutive patients aged 65 years old or older affected with AD. 197 patients were treated with an AChEI while 251 were treated with an AchEI + citicoline 1000 mg/day given orally. Cognitive functions were assessed by MMSE, daily life functions by ADL and IADL, behavioral symptoms by NPI, comorbidities by CIRS, and mood by GDS-short form. Tests were administered at baseline (T0), after 3 (T1), and 9 months (T2). The primary outcomes were effects of combined administration versus AChEIs given alone on cognitive functions assessed by MMSE. The secondary outcomes were possible side effects or adverse events of combination therapy versus AChEIs alone. RESULTS: Patients treated with citicoline plus an AChEI showed a statistically significant increase in MMSE between T0 and T1 (16.88±3.38 versus 17.62±3.64; p = 0.000) and between T1 and T2 (17.62±3.64 versus 17.89±3.54; p = 0.000). CONCLUSION: The present study encourages the role of combined administration in disease management by slowing disease progression.

Doctors commitment and long-term effectiveness for cost containment policies: lesson learned from biosimilar drugs.

BACKGROUND: Agency is a pervasive feature of the health care market, with doctors acting as agents for both patients and the health care system. In a context of scarce resources, doctors are required to take opportunity cost into account when prescribing treatments, while cost containment policies cannot overlook their active role in determining health care resource allocation. This paper addresses this issue, investigating the effects of cost containment measures in the market of biosimilar drugs that represent a viable and cost-saving strategy for the reduction of health care expenditure. The analysis focuses on a particular region in Italy, where several timely policies to incentivize biosimilar prescribing were launched. METHODS: Drugs were identified by the anatomical therapeutic chemical classification system. Information about biosimilar drugs and their originator biological products was extracted from the IMS Health regional database. Drug consumption was expressed in terms of counting units, while expenditure was evaluated in Euro (€). The market penetration of biosimilars was analyzed by year and quarterly. RESULTS: In the Campania region of Italy, the effects of cost containment policies, launched between 2009 and 2013, showed the prescription of biosimilars strongly increasing in 2010 until prescribing levels reached and exceeded the market share of the reference biological products in 2012. After a slight reduction, a plateau was observed at the beginning of 2013. At the same time, the use of the originator products had been decreasing until the first quarter of 2011. However, after a 1-year plateau, this trend was reversed, with a new increase in the consumption of the originators observed. CONCLUSION: Results show that the cost containment policies, applied to cut health expenditure "to cure and not to care", did not produce the cultural change necessary to make these policies effective in the long run. Therefore, top-down policies for cost containment are not successful; rather, a bottom-up approach based on consensus among professionals should become the preferred option.

Prescription Patterns of Antidiabetic Treatment in the Elderly. Results from Southern Italy.

The treatment of diabetes in the elderly is a major challenge both in terms of clinical management and of public health. Evidence about prescribing patterns in the elderly diabetic population is limited. The aim was to describe trends in antidiabetic drug (AD) utilization patterns in the elderly in Southern Italy with a focus on drugs for cardiovascular prevention and pharmaceutical costs. The data used for this study were obtained from pharmacy records of Caserta Local Health Authority, a province in Southern Italy with 1 million of inhabitants, comprising urban and rural areas. Subjects above 65 years who received at least one dispensing of antidiabetic between January 2010 and December 2014 were selected. Prevalence and incidence rates (%) of AD use were calculated for each calendar year and stratified by class therapy and age group. Sub-analyses by cardiovascular co-medication therapy and pharmaceutical cost analysis were performed. The prevalence rate decreases from 22.0% in 2010 to 17.5% in 2014 (p<0.001). Proportion of subjects treated with monotherapy increases over the study period (33.9% in 2010; 38.6% in 2014; p<0.001). In particular, increases the proportion of users of metformin (18.2% in 2010; 23.7% in 2014; p<0.001), while the proportion of users of sulfonylureas dropped (11.0% in 2010; 7.2% in 2014; p< 0.001). About 90% of elderly diabetic patients are treated with drugs for cardiovascular prevention. The per/patient/yearly drug costs were 2,349 ∈: 28.5% for AD therapy and 71.5% for other treatments. Trend in drug utilization patterns showed a tendency towards treatment recommendations in older adults.

[Evaluation of therapeutical appropriateness in psychiatric treatment of schizophrenia, by integrating computer data records with clinical audit results]. / Valutazione dell'appropriatezza prescrittiva in psichiatria: un progetto di clinical audit nella ASL di Caserta.

AIM: The aim is to evaluate prescriptive patterns of atypical antipsychotic drugs for the treatment of schizophrenia in the LHU Caserta in 2011-2013, and to indicate potentially inappropriate therapy; to plan or schedule corrective/preventive activities to support the continuous improvement of health services. METHODS: Retrospective cohort study, based on integration of health records and clinical audit. The study was performed in the following steps: data retrieval and analysis; comparison of data with international literature; editing of the Diagnostic-Therapeutic Path. The analysis was performed by using the administrative database of drug prescriptions and treatment plans in the SANIARP portal, a web platform available to specialist facilities and private and public pharmacies of LHU Caserta. The subject of our analysis was to gain information about the diagnosis and treatment of users of atypical antipsychotics in the LHU of Caserta in the years 2011-2013. RESULTS: We identified 2,768 patients with at least one prescription of atypical antipsychotics and diagnosis coded in the study period. Schizophrenia is the most frequent diagnosis (31.1%) and the most common drug in use is olanzapine (29.1%). About 70% of schizophrenics were on monotherapy with no change in drug, 23.6% were under polytherapy and 7.9% made a switch. DISCUSSION AND CONCLUSION: Our findings were a starting point for editing Diagnostic and Therapeutic Paths aimed at raising the awareness of the scientific community about the appropriateness of diagnosis and treatment in schizophrenia. Pharmacological treatment of schizophrenia should be focused on improving the overall quality of life aimed at remission and possible recovery, although difficult.

Retrospective study on the benefits of combined Memantine and cholinEsterase inhibitor treatMent in AGEd Patients affected with Alzheimer's Disease: the MEMAGE study.

BACKGROUND: Combined therapy of memantine and acetylcholinesterase inhibitors (AChEIs) in patients with Alzheimer's disease (AD) may be associated with higher benefits than either monotherapy. OBJECTIVE: This retrospective multicentric study conducted in seven Italian Ambulatory Centers for Dementia assessed the efficacy and safety of memantine 20 mg/day administered for 6 months in addition to an AChEI in AD patients with worsened cognitive functions and behavioral disorders. METHODS: A total number of 240 patients (61.7% of women, 38.3% men, mean age 77.9 ± 7.32 years old) who had started treatment with the combination therapy were recruited. At baseline (T0), Month 3 (T1), and Month 6 (T2), cognitive functions were assessed by Mini-Mental State Examination (MMSE), functional dependence by activities of daily living (ADL) and instrumental ADL, behavioral disturbances by the Neuropsychiatric Inventory (NPI), and comorbidities by Cumulative Illness Rating Scale. Adverse events were reported during the study. RESULTS: MMSE total score significantly increased at Month 6 (p = 0.029 versus month 3) and IADL total score significantly decreased from baseline to endpoint (p = 0.033). There were no significant changes from baseline in mean ADL, despite significant improvements in NPI total score. The mean MMSE total score significantly increased with the combination donepezil + memantine compared to rivastigmine + memantine. The adverse events profile was in line with the expected range of the drugs studied and concomitant therapies. Overall, 17 patients discontinued treatment in the observation time. CONCLUSION: Combined treatment with memantine and AChEIs was effective in patients with AD, particularly in slowing cognitive impairment and preventing the onset of agitation and aggression in elderly AD patients.

Retrospective and observational study to assess the efficacy of citicoline in elderly patients suffering from stupor related to complex geriatric syndrome.

A significant percentage of elderly subjects (50%-80%) suffering from sub-acute ischemic cerebrovascular disease, with or without moderate or severe cognitive memory decline and with or without associated behavioral and psychological symptoms, shows a complex syndrome. This syndrome is related to the progressive impairment of health conditions and/or stressing events (ie, hospitalization), characterized by confusion and/or stupor, which are consequently difficult to manage and require a great deal of care. Geriatric patients often suffer from multiple chronic illnesses, may take numerous medications daily, exhibit clinical instability, and may experience worsening of medical conditions following cerebral ischemic events and thus have an increased risk of disability and mortality. There are several studies in literature which demonstrate the efficacy of citicoline, thanks to its neuroprotective function, for the recovery and in postischemic cerebral rehabilitation. It has been shown that, even soon after an ischemic stroke, administration of oral citicoline (500-4000 mg/day) improves the general conditions evaluated with the Rankin scale and the National Institute of Health Stroke Scale 12. In particular, it has been shown that the CDP-choline improves the cognitive and mental performance in Alzheimer's dementia and vascular dementia. We have evaluated the administration of citicoline in geriatric patients following a protocol of intravenous study on improvement of individual performances.