The laboratory promotes and coordinates projects aimed at the study and monitoring of the appropriateness of use of drugs and services in the elderly population, particularly in frail older adults with multiple chronic diseases and polypharmacy.
The main topics of the clinical and epidemiological research activities are focused on:
- the evaluation of adherence to medications
- the use inappropriate of drugs
- drug interactions
- iatrogenic risk and pharmacovigilance.
In the field of public health, the laboratory activities are aimed to develop studies on the assessment of quality of care and on the protection of rights in mental health.
Medication Adherence in elderly patients
The issue of medication adherence concerns patients in all age group, but the elderly are the population at highest risk. The data available in the literature indicate a prevalence of medication adherence ranging from 38% to 57%, with an average of less than 45% for most chronic therapies. Non-adherence can limit the effectiveness of pharmacological treatments and produce several other negative consequences. Currently, the laboratory coordinates several projects aimed to assess the problem in different care settings and to promote interventions involving general practitioners, clinicians, other healthcare professionals and patients themselves with the purpose to improve adherence to therapies.
The availability of computerized system and administrative database for the management and care of community-dwelling and in-hospital patients represents an opportunity for developing and implementing new strategies in the field of the evaluation, monitoring and improvement of the appropriateness of drug prescription and the continuity of care. In collaboration with the Health Directorate of Lombardy Region, several Local Health Units and hospitals, a collaborative study (EPIFARM-Elderly Project) has been set up with the aim to evaluate, in some critical prescribing fields, the effectiveness of multidisciplinary integrated interventions and educational actions in improving the prescribing practice and to implement the utilisation of generic drugs. In this framework, drug utilization studies aimed to investigate the overall drug prescription rate, the prescribing pattern of chronic therapies and polypharmacy in relation to gender and different age groups of community-dwelling elderly people have been set up.
REPOSI Register: an Italian Register of hospitalized elderly patient focusing on multimorbidity and polypharmacy
As a consequence of population aging we have witnessed in internal medicine hospital wards a progressive shift from a population of in-patients relatively young and mainly affected by a single ailment to one of older and older and more and more complex patients with multiple chronic diseases. They are also treated as out-patients by many different specialists with poor integration and handled with multiple concomitant medications. Polypharmacy (defined as the chronic intake of five or more drugs) is associated with increased risks of drug-drug interactions and related adverse effects, prescription and intake errors, poor adherence, re-hospitalization and mortality. With this background, the Italian Society of Internal Medicine chose to start in 2008 a prospective register called REPOSI in internal medicine and geriatric hospital wards. The country wide register is an ongoing observatory on multimorbidity and polypharmacy in the oldest old, with the goal to improve prescription appropriateness and thus avoid potentially inappropriate medications. The register, that accrued so far 7,000 older patients throughout a 10 year period, involved more than 100 internal medicine and geriatrics wards and more than 300 clinicians. The Register is ongoing and still recruiting patients. Starting from 2020, the data from the REPOSI Register will be made available to AIFA (The Italian Agency on Medicines) for inclusion in the OsMED Report for the use of drugs in the hospital setting.
Frail older adults: assessment of diagnostic and therapeutic pathways
Through the use of administrative databases by record-linkage and network analysis models applicable to big-data, different studies are underway to assess the complexity of care and care pathways in frail elderly. Furthermore, with national and international public bodies and family associations, we are involved in projects for the evaluation of the organization of mental health services, strategies to address frailty (FOCUS Project, http://focus-aha.eu/home) and on quality of life in different care settings and in particular in Healthcare Residences (RSA). Finally, in a sample of 27,468 people derived from the SHARE database, progression towards pre-frailty or frailty in two years was observed in 21% and reversion in 18% of the individuals. Although high social isolation and high loneliness were not common, average social isolation was reported by almost two thirds and of loneliness by one fourth of the population and increased the risk of progression into prefrailty and frailty. Attention should be given also to average loneliness and social isolation, which professionals and patients themselves often consider normal or acceptable, and should be actively addressed even in the absence of other health conditions.
Participation of patients in the choice and goals of care
The active role of patients in identifying the goals and priority of care in chronic diseases and multimorbidity was promoted in the Esmeralda study, which proposed and evaluated the acceptability of the intervention of a care facilitator for people discharged from the hospital and with complex needs and which used an approach characterized by personalization, support in self-management and identification of patient preferences. A meta-analysis on 10 studies that tested the effectiveness of goal-oriented care did not show superiority of this approach over usual care on quality of life, patient satisfaction or hospitalizations. However, the heterogeneity of the studies and their unsatisfactory quality in general suggest that the effects of the goal-oriented approach must be studied with more adequate methods.
Appropriate drug prescribing at the end of life
The aim of pharmacotherapy in people at end-of-life should be symptom control, more than prolonging life. Drugs for disease prevention should therefore be discouraged, but this is not the usual practice. The prevalence of unnecessary preventive drugs at the end of life is not sufficiently investigated, although some studies suggest it is common. Since 2017, a collaborative project with the Casa Vidas Hospice in Milan is underway with the objective of assessing the prescriptive appropriateness and risk of potential drug interactions in the last week of the life of patients admitted to hospices. The results will allow start educational interventions targeted to medical and health personnel to promote shared actions between professionals for the assessment of appropriate prescribing, iatrogenic risk and deprescribing in terminally ill patients.
Appropriateness in drug prescriptions, deprescribing and expenditure control in the health system
The use of technology in diagnostic and prescription processes, together with the widening use of technologic tools either in in-patient and out-patient settings, provide new possibilities to assess and monitor appropriateness in prescribing and to rationalize drug prescription. The collaboration with the Health Directorate of the Lombardy Region and several Local Health Trusts (ASL Toscana Centro and ASL Toscana Nord-Ovest) and hospitals (Policlinico of Milan) has enabled us to start several projects, like EPIFARM, in order to promote interventions and strategies aimed to improve appropriateness in drug prescription, deprescribing, reporting of adverse reactions to drugs, and care continuity between hospital and community agencies, avoiding waste and rationalising expenditure. Italian internists, geriatricians and general practitioners reported many system-level barriers to deprescribing as well as some doubts about its necessity. Strategies to address the barriers to deprescribing include regular medication review and enhancing collaboration with colleagues and patients.
Quality assessement of mental health services
The QUADIM project, funded by the 2016 call of the Centre for Disease Control of the Italian Ministry of Health, assesses the severity and complexity of the cases in charge to the mental health services of nine Departments of Mental Health. It also investigates how to develop a financing system based on clusters of illness severity. Thirteen thousands users of mental health services were described through the Mental Health Clustering Tool by 450 professionals ad hoc trained. Such tool allows clustering users according to complexity, care needs and resources likely necessary for an effective treatment. The use of data from regional psychiatry information systems for the prospective evaluation of the effectiveness of interventions provided in public and affiliated mental health services requires a methodological approach called Within-patient self-controlled case series (SCCS) that uses each case as a comparison of himself and thus allows to eliminate the confusion due to the heterogeneity between the subjects. The application of this method of analysis confirmed on a sample of 12,054 new cases representative of the population of four Italian regions that hospitalizations are almost halved when patients receive integrated treatment compared to when they do not receive any treatment. The consequences of the lockdown of mental health services due to the COVID-19 epidemic were investigated in a sample of 1046 operators from different regions, especially in Northern Italy. A good ability to adapt to the new working conditions has emerged. The most appreciated changes were the introduction of communication technologies and the ability to more carefully identify interventions and objectives for each patient. The people who seemed to suffer the most from the lockdown were those who lived alone, while those who seemed least affected were those with psychotic disorders.
Proton Pump Inhibitors (PPI): a study to promote appropriate prescribing in primary care
In Italy nearly 3.5 million of people (21% of the population) were treated with PPIs in 2015. This prevalence increased with advancing age. Despite the extensive literature regarding PPI adverse events, their inappropriate prescription rate is still increasing. The rapid increase in PPIs prescriptions, outside their licensed indications as established by the Italian Medicines Agency reimbursement criteria, especially in older people, represents a concern either in terms of patient safety and resource waste for the National Health System (NHS). With this background, we designed a low-cost intervention addressing General Practitioners, accompanied by the distribution of informative leaflets helping patient compliance. The aim of the LAPTOP-PPI study is to promote a cluster-randomized controlled trial in order to assess its effectiveness in improving the appropriate prescription of PPIs.
Efficacy and safety of antidepressants in the elderly
Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues must not be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action, that may have a promising tolerability profile in the elderly. This pragmatic, multicentre, open-label, parallel-group, superiority randomised trial is funded by the Italian Medicines Agency and aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression, with rate of participants withdrawing from treatment due to adverse events after six months as primary outcome. Thirteen Italian Community Psychiatric Services consecutively enrol elderly participants suffering from an episode of major depression over a period of 12 months.
Side-effects of psychiatric drugs
Although the European Medicines Agency has issued a warning about the effects in the sexual sphere of SSRI and SNRI antidepressants that arise or persist long after the drug has been discontinued (Post-SSRI Sexual Dysfunction, PSSD), not all manufacturers have updated warnings accordingly and doctors' familiarity with the problem appears to be very poor. The prevalence of the disorder is reported by some authors as very high, but due to the difficulty in distinguishing it from other sexual dysfunctions associated with SSRIs and SNRIs, a specific prevalence estimate is not available. In collaboration with Dutch, British and Canadian research groups and with organized users groups active on this issue, a survey on physicians' attitudes and awareness of the problem and an epidemiological study for a correct estimate of the prevalence of PSSD among people taking or having taken SSRIs and SNRIs are being planned.
Assessment of efficacy and implementation of psychologic intervention
Psychological interventions have a recognized efficacy in the treatment of depression and other mental disorders, not only common. The effectiveness between intervention models is comparable and it is necessary to identify the areas in which the models can best express their effectiveness. In a meta-analysis released for the Cochrane Collaboration, couples therapy showed comparable efficacy to individual therapy in treating depression in both couples with relationship problems and those without, but was superior in improving the well-being of the couple in presence. of relationship difficulties. The results show that couples therapy may be more suitable than individual therapy in couples with relationship distress, but they suggest that the mechanism by which depression improves is not by improving relationships in the couple. Psychological interventions for insomnia have been shown to be as effective as benzodiazepines, probably with an effect that lasts longer, but their use in clinical practice is markedly lower than that of benzodiazepines. A study is being implemented in all mental health services of the Autonomous Province of Trento which evaluates the application of specific psychological skills for the treatment of insomnia and the interruption of benzodiazepines in order to identify and overcome obstacles to implementation. psychological interventions and reduce drug use.
Aging, multimorbidity and polypharmacy in patients with haemophilia (PWH)
In the last few decades, Western societies have experienced a relevant improvement in life expectancy. As a consequence, several cohorts of patients who had previously a short life expectancy have witnessed significantly progress in management and thus their life expectancy at birth has much improved. This is true also for patients with haemophilia PWH, especially those with severe and moderate forms of the disease. A direct consequence of the improvement in the clinical and therapeutic management of PWH is that PWH have currently reached a life expectancy similar to that of males in the general population. A national Italian registry of congenital coagulopathies run by the Italian Association of Hemophilia Centers (AICE) includes simple demographic and hematologic data, but the social, functional, mood, cognitive and pharmacological data so critically important for the optimal management of older PWH are not included. The aim of this project is to provide tools for the assessment of patients with multimorbidities, and problems related to functional, mood, cognitive status and health-related quality of life in PWH affected with severe or moderate haemophilia A and B included in the AICE Register.
PHARMAGOOD-BIOSIMILARS: intervention to promote the appropriate use of biosimilars
This project aims to provide specific competences to Regions, Healthcare Authorities and other structures of the Italian National Health Service to promote appropriate use of biosimilars and avoid waste related to inappropriate use of these drugs. We aim to build activities and interventions in agreement and shared with healthcare professionals of the Regional Health Service to promote the rational prescriptions of the biologicals and biosimilars and to monitor their benefit-risk profile in clinical practice.
Educational and information activities
The laboratory regularly carries out training and education activities on the topics of prescription appropriateness, adherence to therapies, pharmacovigilance and mental health services aimed at clinicians, general practitioners, pharmacists, health and social workers and citizens. The Laboratory coordinates with the University of Milan a Master's Degree in Clinical Research Methodology and with Italian Society of Internal medicine (SIMI) the SIMI WINTER SCHOOL, an intensive course for medical specialists on the management of the frail hospitalised older patient. Furthermore, the laboratory developed and regularly update INTERCheck-WEB® (https://clinicalweb.marionegri.it/intercheckweb/) a computerized support system for physicians and health professionals, to optimize the pharmacological prescription, which has been used in many studies and in several hospitals, long-term care and primary care services of the Italian NHS. Finally, a Drug Information Service is available through a call center for questions on the appropriate and safe use of drugs in older adults.
International Consensus on Cardiopulmonary Resuscitation.