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Non-steroidal anti-inflammatory drugs (NSAIDs) are largely used for controlling various pain conditions and are widely available in community pharmacies, with and without prescription. Despite their effectiveness, NSAIDs can pose significant risks due to potential side effects and drug interactions, particularly in polypharmacy and comorbidity contexts and for vulnerable users. This study investigated whether and how NSAIDs deprescribing can be conducted at the community pharmacy level by assessing pharmacists' confidence, attitudes, and potential barriers and facilitators. Additionally, we aimed to identify any deprescribing guidelines that pharmacists could use. A literature search and a cross-sectional digital questionnaire targeting community pharmacists in Norway were conducted. Results showed that study participants (N = 73) feel confident in identifying needs for deprescribing NSAIDs but barriers such as time constraints, lack of financial compensation, and communication challenges were noted. Participants reported positive attitudes toward deprescribing but highlighted a need for better guidelines and training. This study highlights a gap in specific guidelines for deprescribing NSAIDs and a potential for enhancing pharmacists' roles in the deprescribing process, for example, through training and improved financial incentives. Further research is encouraged to develop concrete strategies for an effective implementation where community pharmacists can be involved in the deprescribing of NSAIDs.

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Dementia is a major public health concern due to its increasing prevalence, substantial caregiver burden, and high financial costs. Currently, the anti-dementia drugs aim only at a symptomatic effect. The subject of prescribing these drugs in advanced stages is a matter of considerable debate, with different countries making distinct recommendations. In this review article, we analyzed the evidence regarding cognitive and functional outcomes, adverse events, health-related costs, and caregiver burden in patients with advanced Alzheimer disease (AD) and mixed dementia. We included 35 studies. Most studies are heterogeneous, focus exclusively on AD, and show small benefits in terms of cognitive and functional scales. The overall evidence seems to suggest a benefit in introducing or maintaining anti-dementia drugs in patients with advanced dementia, but clinical meaningfulness is difficult to ascertain. The issue of costs and caregiver burden is significantly underexplored in this field but also seems to favor treatment continuation, despite a reduced overall effect. The decision of introducing or withdrawing anti-dementia drugs in advanced stages of dementia should be individualized. Future studies with homogeneous designs and outcomes are warranted.

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The global increase of aging with the related increase of multiple noncommunicable diseases is inevitably accompanied by the associated issue of multimorbidity and polypharmacy. The latter is not without peculiar consequences on health, because it has been shown to be associated with drug-related adverse events, mainly due to poor prescription appropriateness and drug-drug interactions. To contribute to tackle this gigantic problem, a registry of drug dispensation in hospitalized older patient has been initiated in Italy in 2008. Through the last 15 years, data on nearly 11,000 older people have been accrued during their hospital stay in internal medicine and geriatric wards. This review article summarizes the main findings obtained, and how these data contribute to tackle the issue of appropriateness of drug prescription and the need of deprescribing in hospitalized older people affected by the most common noncommunicable diseases.

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This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with deprescribing intervention trials (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with medication cessation trials (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with deprescribing intervention trials. Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of medication cessation trials, a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.

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Behavioural treatments are recommended first-line for insomnia, but long-term benzodiazepine receptor agonist (BZRA) use remains common and engaging patients in a deprescribing consultation is challenging. Few deprescribing interventions directly target patients. Prescribers' support of patient-targeted interventions may facilitate their uptake. Recently assessed in the Your Answers When Needing Sleep in New Brunswick (YAWNS NB) study, Sleepwell (mysleepwell.ca) was developed as a direct-to-patient behaviour change intervention promoting BZRA deprescribing and non-pharmacological insomnia management. BZRA prescribers of YAWNS NB participants were invited to complete an online survey assessing the acceptability of Sleepwell as a direct-to-patient intervention. The survey was developed using the seven construct components of the theoretical framework of acceptability (TFA) framework. Respondents (40/250, 17.2%) indicated high acceptability, with positive responses per TFA construct averaging 32.3/40 (80.7%). Perceived as an ethical, credible, and useful tool, Sleepwell also promoted prescriber-patient BZRA deprescribing engagements (11/19, 58%). Prescribers were accepting of Sleepwell and supported its application as a direct-to-patient intervention.

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BACKGROUND: In March 2020, the outbreak caused by the SARS-CoV-2 virus was declared a pandemic, resulting in numerous fatalities worldwide. To effectively combat the virus, it would be beneficial to involve professionals who specialize in symptom control for advanced illnesses, working closely with other specialties throughout the illness process. This approach can help manage a range of symptoms, from mild to severe and potentially life-threatening. No studies have been conducted in Portugal to analyse the intervention of Palliative Medicine at the end of life of Covid-19 patients and how it differs from other specialties. This knowledge could help determine the importance of including it in the care of people with advanced Covid-19. OBJECTIVES: The objective of this study is to examine potential differences in the care provided to patients with Covid-19 during their Last Hours and Days of Life (LHDOL) between those who received care from Palliative Medicine doctors and those who did not. METHODS: This is a retrospective cohort study spanning three months (Dec 2020 to Feb 2021), the duration of the Support Unit especially created to deal with Covid-19 patients. The database included clinical files from 181 patients admitted to the Support Unit, 27 of which died from Covid-19. RESULTS: Statistically significant differences were identified in the care provided. Specifically, fewer drugs were administered at the time of death, including drugs for dyspnoea, pain and agitation, suspension of futile devices and use of palliative sedation to control refractory symptoms. CONCLUSIONS: End-of-life care and symptomatic control differ when there's regular follow-up by Palliative Medicine, which may translate less symptomatic suffering and promote a dignified and humane end of life.

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OBJECTIVES: To describe the extent, characteristics, and knowledge gaps regarding explicit decision criteria for deprescribing drugs with anticholinergic or sedative properties (Ach/Sed) in older adults. DESIGN: Scoping review. SETTING AND PARTICIPANTS: Original studies, clinical trial protocols, grey literature, and Summaries of Product Characteristics. METHODS: Searches targeting explicit decision criteria for deprescribing Ach/Sed were performed across MEDLINE, EMBASE, CINAHL, and Web of Science, including trial registries (clinicaltrials.gov, ICTRP, EU-CTR, ANZCTR) for pertinent articles, study protocols. Additionally, to encompass non-traditional or 'grey literature' sources, Google searches and relevant agency websites were explored, alongside the summary of product characteristics for Ach/Sed. RESULTS: The initial literature search identified 8,192 unique data sources. After review, 188 original articles or books, 79 internet sources, and 127 SmPCs were included. Examining these sources for explicit criteria for 154 Ach/Sed, overall, 1,271 explicit criteria guidance for identifying clinical scenarios warranting deprescription of Ach/Sed across 145/154 Ach/Sed were identified. These criteria were identified mainly from qualitative research and Summaries of Product Characteristics. Additionally, 455 criteria-based recommendations suggesting approaches for tapering implementation across 76/154 Ach/Sed were identified, mostly from sources classified as expert opinions. Significant heterogeneity was found across the approaches for tapering Ach/Sed. CONCLUSIONS: This scoping review provides a comprehensive overview of the literature providing guidance for clinical scenarios where Ach/Sed should be deprescribed and highlights the existing knowledge gaps regarding comprehensive guidance on tapering these drugs which warranties future research and development.

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INTRODUCTION: Glucagon-like peptide 1 receptor agonists (GLP-1) elicit substantial reductions in glycemia and body weight in people with type 2 diabetes (T2D) and obesity, but existing data suggest the therapy must be continued indefinitely to maintain clinical improvements. Given the high cost and poor real-world persistence of GLP-1, an effective therapy that enables deprescription with sustained clinical improvements would be beneficial. Thus, the purpose of this real-world study was to assess the effect of GLP-1 deprescription on glycemia and body weight following co-therapy with carbohydrate restricted nutrition therapy (CRNT) supported via telemedicine in a continuous remote care model. METHODS: A retrospective, propensity score matched cohort study among patients with T2D at a telemedicine clinic was conducted. Patients in whom GLP-1 were deprescribed (DeRx; n = 154) were matched 1:1 with patients in whom GLP-1 were continued (Rx). HbA1c and body weight at enrollment in clinic (pre-CRNT), at date of deprescription or index date (derx/ID), and at 6 and 12 months (m) post-derx/ID were utilized in this study. RESULTS: No regression in weight was observed following deprescription with > 70% maintaining ≥ 5% weight loss 12 m post-derx/ID. HbA1c rose 6 m and 12 m post-derx/ID in both DeRx and Rx cohorts, but most patients maintained HbA1c < 6.5%. HbA1c and body weight measured 6 m and 12 m following derx/ID did not significantly differ between cohorts and were improved at derx/ID and at follow-up intervals compared to pre-CRNT. CONCLUSION: These results demonstrate the potential for an alternate therapy, such as CRNT supported via telemedicine, to enable maintenance of weight loss and glycemia below therapeutic targets following discontinuation of GLP-1 therapy.

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OBJECTIVES: Overtreatment with glucose-lowering treatment (GLT) is frequent and a source of high morbidity and mortality in older adults with type 2 diabetes mellitus (T2DM). This study aimed to identify and synthesize barriers and enablers for deprescribing GLT in older adults (≥65 years) with T2DM. DESIGN: Systematic review of qualitative and mixed-methods studies. SETTING AND PARTICIPANTS: Older adults with T2DM, any participants [patients, health care providers (HCPs), caregivers], any settings. METHODS: Two researchers (and a referred third researcher at all stages) independently screened original articles reporting qualitative and mixed-methods studies exploring barriers and enablers for deprescribing GLT in older adults published during 2010-2023, identified from MEDLINE, Embase, CINAHL, and gray literature. Quality of the included studies was assessed with the Mixed-Methods Appraisal Tool. Verbatim statements on barriers and enablers were extracted, and determinants of behaviors were identified with the Theoretical Domains Framework (TDF) version 2, and related intervention functions (targets for future interventions) were proposed according to the Behavior Change Wheel (BCW). RESULTS: We identified only 4 studies from 2 countries (United States and the Netherlands), all recently published (2019-2023), that primarily reported barriers to GLT deprescribing from interviews or focus groups of patients or HCPs practicing outpatient medicine. Knowledge, fear, poor communication, inertia, and trust with HCPs were the main determinants of behaviors that influenced deprescribing, and education, training, persuasion and environmental restructuring were the main intervention functions for proposing future interventions. Studies did not cover financial aspects, physician characteristics, or caregiver and family viewpoints. CONCLUSIONS AND IMPLICATIONS: The use of a behavioral theory and a validated implementation framework provided a comprehensive approach to identifying barriers and enablers for deprescribing GLT in older adults (≥65 years) with T2DM. The behavioral determinants identified may be useful in tailoring interventions to improve the implementation of GLT deprescribing in older adults in ambulatory settings.

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AIM: To investigate the prevalence and indications of benzodiazepines (BZD) usage among patients admitted to an acute geriatric unit and assess changes in prescriptions. METHODS: BZD indications were documented reviewing clinical records, with appropriateness assessed based on the STOPP-START criteria. Changes in BZD prescriptions were recorded at discharge and 3 months later. RESULTS: Among the 366 patients included (mean age: 92.8 years, 68% females), 91 (24.9%) were on BZD upon admission, being inappropriate in 93.4%. At discharge, BZD discontinuation was observed in 40.7% and dose reduction initiated in 57.4%. Among patients discharged without prescriptions, 10.8% resumed their use at 3 months. Of those discharged with BZD tapering, 74.1% were still on them 3 months later. CONCLUSIONS: The majority of patients employing BZD lacked a medical indication. Admission to a geriatric ward resulted in successful discontinuation or dose reduction for most patients but was not maintained in the outpatient setting.

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ABSTRACT Background: Proton pump inhibitors (PPIs) are widely prescribed worldwide, often resulting in their overuse. Consequently, it is essential to identify the likely causes of this overuse to facilitate their appropriate prescription. Objective: This study aims to assess physician prescribing patterns, their knowledge of PPIs, and factors affecting their knowledge. Methods: An online survey was conducted among Latin American and Spanish physicians, collecting the following data: professional information, patterns of PPI usage, familiarity with published evidence, and the management approach in three hypothetical case-scenarios. Participant knowledge was categorized as sufficient or insufficient based on the results of the case scenarios. Subsequently, subgroup analysis was performed based on physician training level, years in practice, specialty, and time since the last PPI literature review. Results: A total of 371 physicians participated in the survey. Thirty-eight percent frequently prescribe PPIs, primarily for prophylactic purposes (57.9%). Eighty percent were unfamiliar with PPI deprescribing strategies, and 54.4% rarely reviewed the ongoing indication of patients taking a PPI. Sixty-four percent demonstrated sufficient knowledge in the case-scenarios. A significant association was observed between specialty type (medical vs surgical: 69.4% vs 46.8%, P<0.001), the timing of the PPI indication literature review (<5 years vs >5 years: 71.4% vs 58.7%, P=0.010), and sufficient knowledge. Conclusion: While most participants prescribed PPIs regularly and for prophylaxis purposes, the majority were unfamiliar with deprescribing strategies and rarely reviewed ongoing indications. Sufficient knowledge is correlated with recent literature reviews and medical specialty affiliation.

RESUMO Contexto: Os inibidores da bomba de prótons (IBPs) são amplamente prescritos em todo o mundo, muitas vezes resultando em seu uso excessivo. Consequentemente, é essencial identificar as prováveis causas desse uso excessivo para facilitar sua prescrição adequada. Objetivo: Este estudo tem como objetivo avaliar o padrão de prescrição dos médicos, seu conhecimento sobre IBPs e fatores que afetam seu conhecimento. Métodos: Uma pesquisa on-line foi conduzida entre médicos latino-americanos e espanhóis, coletando os seguintes dados: informações profissionais, padrões de uso de IBP, familiaridade com evidências publicadas e abordagem de manejo em três casos-cenários hipotéticos. O conhecimento dos participantes foi categorizado em suficiente ou insuficiente com base nos resultados dos cenários de caso. Posteriormente, a análise de subgrupos foi realizada com base no nível de formação do médico, anos de prática, especialidade e tempo desde a última revisão da literatura dos IBPs. Resultados: Um total de 371 médicos participaram da pesquisa. Trinta e oito por cento prescrevem frequentemente IBP, principalmente para fins profiláticos (57,9%). Oitenta por cento não estavam familiarizados com as estratégias de prescrição de IBP, e 54,4% raramente revisaram a indicação contínua de pacientes em uso de IBP. Sessenta e quatro por cento demonstraram conhecimento suficiente nos cenários-caso. Observou-se associação significativa entre o tipo de especialidade (médica vs cirúrgica: 69,4% vs 46,8%, P<0,001), o momento da revisão da literatura de indicação do IBP (<5 anos vs >5 anos: 71,4% vs 58,7%, P=0,010) e conhecimento suficiente. Conclusão: Embora a maioria dos participantes prescrevesse IBPs regularmente e para fins de profilaxia, no entanto, não estava familiarizada com estratégias de prescrição e raramente revisava as indicações em andamento. O conhecimento suficiente está correlacionado com revisões recentes da literatura e afiliação à especialidade médica.

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INTRODUCTION: Drug-drug interactions (DDIs) represent an important clinical problem, particularly in older patients, due to polytherapy, comorbidity, and physiological changes in pharmacodynamic and pharmacokinetic pathways. In this study, we investigated the association between drugs prescribed after discharge from the hospital or clinic and the risk of DDIs with drugs used daily by each patient. METHODS: We performed an observational, retrospective, multicenter study on the medical records of outpatients referred to general practitioners. DDIs were measured using the drug interaction probability scale. Potential drug interactions were evaluated by clinical pharmacologists (physicians) and neurologists. Collected data were analyzed using the Statistical Package for the Social Sciences. RESULTS: During the study, we evaluated 1772 medical records. We recorded the development of DDIs in 10.3% of patients; 11.6% of these patients required hospitalization. Logistic regression showed an association among DDIs, sex, and the number of drugs used (p = 0.023). CONCLUSIONS: This observational real-life study shows that the risk of DDIs is common in older patients. Physicians must pay more attention after hospital discharge, evaluating the treatment to reduce the risk of DDIs.

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Mistakes in the medication process are frequent and a common cause of morbidity and mortality. Medication reconciliation (MRec) and medication review (MRev) are the processes of creating the most accurate medication list and adapting it to optimize the effectiveness of medicines and minimize adverse effects. This is crucial in all stages of medical care, especially at discharge. The present study aims to evaluate and describe the process of MRec and MRev, with a focus on deprescribing, that we conduct at the Hospital at Home. We performed a retrospective cohort study including adult patients admitted at our Hospital at Home from 1 November 2022 to 30 April 2023. MRec and MRev were applied during hospitalization, according to patients' characteristics and clinical evolution, and then communicated to patients upon discharge. Our study involved 125 patients, with an average age of 67.6±18.0 years, and half of them had polypharmacy. We discovered discrepancies in 43.2% of patient's medication and did deprescribing in one-third of them. In the deprescribing group, patients were significantly older (mean age, 76.1 versus 66.4 years; p=0.044). It is imperative to create mechanisms to identify patients at a greater risk of adverse drug events and to minimize the burden of care and harms associated with treatments. The Hospital at Home could be an opportunity, although further research is essential.

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Background: The increasing utilization of proton pump inhibitors (PPIs) in patients without clear medical indications has raised concerns regarding potential risks, highlighting the importance of deprescription. However, comparative analyses of withdrawal strategies (abrupt vs gradual) in this context remain scarce or of low quality. Aim: This study aimed to evaluate the success rate of deprescribing PPIs in hospitalized patients without a documented indication and compare the proportion of treatment restarts based on withdrawal strategy. Method: An uncontrolled, open-label prospective observational study was conducted on patients receiving PPI treatment during hospital admission between May 2017 and July 2018. Deprescription was recommended for patients without a clear indication. Follow-up continued until discharge, with monitoring for rebound symptoms. The percentage of restarts based on the withdrawal strategy was compared using the chi-square test. Results: A total of 402 patients were reviewed, among whom 27% lacked a medical indication (mean age > 60 years, polymedicated), while 70% were prescribed PPIs electronically. Deprescription was performed in 49% of patients, with 64% undergoing abrupt withdrawal. Rebound symptoms led to treatment restart in 15% of cases. However, the chi-square test revealed no significant differences in restart proportions between the abrupt and gradual withdrawal groups (P = 0.365). Conclusion: Deprescribing PPIs is deemed safe, particularly for polymedicated geriatric patients, as it leads to a low percentage of restarts regardless of the chosen withdrawal strategy. However, the high percentage of PPI prescription without a clear indication underlines the need for periodic reassessment to avoid unnecessary risks and overuse.

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BACKGROUND: Consolidated and reliable evidence regarding the effectiveness of pharmacist interventions for deprescribing benzodiazepines in older outpatients is lacking. AIM: This study evaluated and summarized the impact of pharmacist interventions on benzodiazepine deprescribing among older outpatients. METHOD: A literature search was conducted until August 2022 in PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials databases. The review included randomized controlled trials that assessed the impact of pharmacist interventions on deprescribing benzodiazepine in older outpatients. Two independent investigators conducted the study selection, data extraction, and risk of bias assessment. Meta-analyses were conducted using random-effect models in the RStudio software. RESULTS: A total of 893 records were identified. Five studies, including 3,879 patients, met the inclusion criteria and were included in the systematic review. All five studies used health education as an intervention strategy, and three also conducted medication reviews. There was no evidence of the pharmacist's authority to modify prescriptions during benzodiazepine deprescribing. One study was classified as having a low risk of bias, whereas the other had some concerns or a high risk of bias. Three studies were included in the meta-analysis and a significant impact of pharmacist interventions on benzodiazepines deprescribing rates in older outpatients was observed (RR = 2.75 [95%CI 1.29; 5.89]; p = 0.04; I2 = 69%; low certainty of evidence). CONCLUSION: Pharmacists may contribute to deprescribing benzodiazepines in older outpatients. Further studies are needed to increase the reliability of these findings. PROSPERO registration number: CRD42022358563.

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BACKGROUND: According to § 27 and § 87 1b of the German Social Code, Book V, general outpatient palliative care (GOPC) aims to promote, maintain, and improve the quality of life and self-determination of seriously ill people. It should enable them to live in dignity until death in their preferred environment. Instead of a curative approach GOPC treatment focuses on the multiprofessional objective of alleviating symptoms and suffering on a case-by-case basis using medication or other measures, as well as the management of an individual treatment plan. The aim of this study was therefore to investigate to what extent medication differs from 12 months prior GOPC treatment within 12 months following GOPC treatment. METHODS: A retrospective database cross sectional study based on the IQVIA Disease Analyzer (DA) was performed, including adult patients with cancer diagnosis and at least one documentation of palliative support between January 1st, 2018 and December 31st, 2021, in 805 general practices (GP). RESULTS: The results of this study show, that in the context of general general outpatient palliative care, there is a significant increase in the prescription of opioids (18.3% vs. 37.7%), sedatives (7.8% vs. 16.2%) and antiemetics (5.3% vs. 9.7%), as well as a significant reduction in other medications such as statins (21.4% vs. 11.5%), proton pump inhibitors (PPI) (41.2% vs. 35.3%), or antihypertensives (57.5% vs. 46.6%). CONCLUSIONS: Our results support the role of GOPC as an important element in improving pharmacological symptom control and deprescription to improve quality of life of patients at the end of their life.

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Polypharmacy is the simultaneous use of multiple medicines, usually more than five. Polypharmacy is highly prevalent among older individuals and is associated with several adverse health outcomes, including frailty. The role of polypharmacy in nutritional status seems to be crucial: although a clear association between polypharmacy and malnutrition has been widely reported in older people, the magnitude of the effect of increased number of drugs in combination with their type on the risk for malnutrition remains to be largely explored. Therefore, this review aims to discuss the association between polypharmacy and malnutrition in older people and to provide suggestions for its management. Polypharmacy is prevalent among malnourished frail patients, and the relative contribution of comorbidities and polypharmacy to malnutrition is difficult to be determined. Several mechanisms by which commonly used medications have the potential to affect nutritional status have been identified and described. Deprescribing (i.e., a systematic process of identification and discontinuation of drugs or a reduction of drug regimens) could be an essential step for minimizing the effects of polypharmacy on malnutrition. In this regard, the literature suggests that in older patients taking several medications, the best method to solve this problem is the comprehensive geriatric assessment, based on a holistic approach, including drug review, to find potential unnecessary and inappropriate medications. Nutritional and deprescribing interventions must be tailored to patient needs and to the local context to overcome barriers when applied in different settings.

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BACKGROUND AND OBJECTIVE: There are barriers to deprescription that hinder its implementation in clinical practice. The objective of this study was to analyse the main barriers and limitations of the deprescription process perceived by physicians who care for multipathological patients. MATERIALS AND METHODS: The "deprescription questionnaire of elderly patients" was adapted to an online format and sent to physicians in geriatrics. Question 1 is a reference to establish agreement or disagreement with this practice. The influence of different aspects of deprescription was analysed via the demographic characteristics of the clinicians and perceptions of the various barriers (questions 2-9) by means of bivariate analysis. Based on the latter, a multivariate model was carried out to demonstrate the relationship between barriers and the degree of deprescription agreement among respondents. RESULTS: Of the 72 respondents, 72.2% were in favour of deprescribing. Regarding the analyses, the demographic characteristics did not influence rankings. The deprescription of preventive drugs and consensus with patients were associated with a positive attitude towards deprescribing, while withdrawing drugs prescribed by other professionals, time constraints and patient reluctance emerged as possible barriers. The only factor independently associated with deprescribing was lack of time. CONCLUSIONS: Time was found to be the main barrier to deprescription. Training, the creation of multidisciplinary teams and integrated health systems are key facilitators.

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Introduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential impact of CYP2D6 phenotypes and sex on the clinical and safety outcomes during an opioid use disorder (OUD) tapering process. Methods: A prospective observational study was conducted on CNCP ambulatory OUD patients (cases, n = 138) who underwent a 6-month opioid dose reduction and discontinuation. Pain intensity, relief and quality of life (Visual analogue scale, VAS 0-100 mm), global activity (GAF, 0-100 scores), morphine equivalent daily dose (MEDD), analgesic drugs adverse events (AEs) and opioid withdrawal syndrome (OWS, 0-96 scores) were recorded at basal and final visits. Sex differences and CYP2D6 phenotypes (poor (PM), extensive (EM) and ultrarapid (UM) metabolizers based on CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, *41, 2D6*5, 2D6 × N, 2D6*4 × 2 gene variants) were analyzed. Results: Although CYP2D6-UM consumed three-times less basal MEDD [40 (20-123) mg/day, p = 0.04], they showed the highest number of AEs [7 (6-11), p = 0.02] and opioid withdrawal symptoms (46 ± 10 scores, p = 0.01) after deprescription. This was inversely correlated with their quality of life (r = -0.604, p < 0.001). Sex-differences were evidenced with a tendency to a lower analgesic tolerability in females and lower quality of life in men. Discussion: These data support the potential benefits of CYP2D6-guided opioid deprescription, in patients with CNCP when OUD is detected. Further studies are required to understand a sex/gender interaction.