Appropriateness of prescription of oral anticoagulant therapy in acutely hospitalized older people with atrial fibrillation. Secondary analysis of the SIM-AF cluster randomized clinical trial.

AIMS: To assess the appropriateness of oral anticoagulant (OAC) prescription and its associated factors in acutely hospitalized elderly patients. METHODS: Data were obtained from the prospective phase of SIM-AF (SIMulation-based technologies to improve the appropriate use of oral anticoagulants in hospitalized elderly patients with Atrial Fibrillation) randomized controlled trial, aimed to test whether an educational intervention improved OAC prescription, compared to current clinical practice, in internal medicine wards. In this secondary analysis, appropriateness of OAC prescription was assessed at hospital admission and discharge. RESULTS: For 246 patients, no significant differences were found between arms (odds ratio 1.38, 95% confidence interval [CI] 0.84-2.28) in terms of appropriateness of OAC prescription. Globally, 92 patients (37.4%, 95% CI = 31.6-43.6%) were inappropriately prescribed or not prescribed at hospital discharge. Among 51 patients inappropriately prescribed, 82% showed errors on dosage, being mainly under-dosed (n = 29, 56.9%), and among 41 inappropriately not prescribed, 98% were taking an antiplatelet drug. Factors independently associated with a lower probability of appropriateness at discharge were those related to a higher risk of bleeding (older age, higher levels of aspartate aminotransferase, history of falls, alcohol consumption) and antiplatelet prescription at admission. The prescription of OACs at admission was the strongest predictor of appropriateness at discharge (odds ratio = 7.43, 95% CI = 4.04-13.73). CONCLUSIONS: A high proportion of hospitalized older patients with AF remains inappropriately prescribed or nonprescribed with OACs. The management of these patients at hospital admission is the strongest predictor of prescription appropriateness at discharge.

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation.

AIMS: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. METHODS: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in those who were and were not prescribed OACs at hospital discharge. Multivariable logistic regression was used to establish factors independently associated with the appropriateness of OAC prescription. RESULTS: A total of 328 patients were included in the retrospective phase of the study. Of these, almost 44% (N = 143) were inappropriately prescribed OACs, being mainly underprescribed or prescribed an inappropriate antithrombotic drug (N = 88). Among the patients prescribed OACs (N = 221), errors in the prescribed doses were the most frequent cause of inappropriate use (N = 55). Factors associated with a higher degree of patient frailty were inversely associated with the appropriateness of OAC prescription. CONCLUSIONS: In hospitalized older patients with AF, there is still a high prevalence of inappropriate OAC prescribing. Characteristics usually related to frailty are associated with the inappropriate prescribing. These findings point to the need for targeted interventions designed for internists and geriatricians, aimed at improving the appropriate prescribing of OACs in this complex and high-risk population.

The combination of pharmacogenetic and pharmacokinetic analyses to optimize clomipramine dosing in major depression: a case report.

WHAT IS KNOWN AND OBJECTIVE: Polymorphisms in cytochrome P450 2D6 and 2C19 can lead to interindividual differences in drug plasma concentrations, affecting clomipramine efficacy. Pharmacokinetic and pharmacogenetic analyses may improve drug therapy. CASE SUMMARY: We report the case of a depressed woman requiring higher doses than standard of clomipramine. Identification of low plasma drug levels led to extensive pharmacogenetic analyses of all genes and major functional polymorphisms reported to affect clomipramine metabolism. WHAT IS NEW AND CONCLUSION: Therapeutic drug monitoring and pharmacogenetic analyses may be useful in the investigation and optimization of clomipramine in standard-dose non-responders.

Paediatric drug use with focus on off-label prescriptions in Lombardy and implications for therapeutic approaches.

The persistent lack of information on the paediatric use of most medicinal products is a major hindrance towards an optimal treatment of paediatric patients. Several studies have documented the high prevalence of off-label use in paediatric population. No comprehensive studies, however, exist that analyse in full all prescriptions for all dispensed drugs, especially in view of the recent intervention by the European Medicine Agency to tackle this issue. We have assessed the drug prescription pattern in the paediatric outpatient population of Lombardy, which has a reliable record of such prescriptions focusing on off-label drug use. We analysed all dispensed outpatient prescriptions to children aged 0-18 years and the proportion of off-label drug use in 2011, using data from the regional administrative prescriptions database. A total of 4,027,119 prescriptions were dispensed, of which 133,619 (3.3 %) were off-label. The anatomical therapeutic chemical classes most involved in off-label prescriptions were antibiotics for systemic use (33,629), alimentary tract and metabolism (31,739) and respiratory tract (31,458). The highest rate (8 %) of off-label drug prescriptions was observed in the age range 0-1. The study revealed also an inappropriate prescription pattern for fluoroquinolones and drugs targeting the cardiovascular and musculoskeletal systems. We identified inappropriate prescriptions for specific drug classes, highlighting the need of increasing pharmacological studies in the paediatric patients and specific critical drugs/drug classes in which such studies are particularly urgent. Depending on the region, inappropriate paediatric drug prescriptions may affect different drug classes, indicating the need of tailoring specific programmes of information.

Pharmacist-driven medication recognition/ reconciliation in older medical patients.

BACKGROUND: In older medical patients polypharmacy is often associated with poor prescription appropriateness and harmful drug-drug interactions. An effort that jointly involved hospital pharmacists and clinicians attending multimorbid older patients acutely admitted to medical wards was implemented for medication recognition and reconciliation aided by the use of a computerized support system. METHODS: Six internal medicine wards enrolled consecutively 90 acutely admitted multimorbid patients aged 75 years or more taking 5 or more different drugs. Two hospital pharmacists carried out the recognition of medications taken at hospital ward admission, and interacted with the clinicians in a process of drug reconciliation, using also the computerized support system to evaluate drug related problems, prescription inappropriateness or drug-drug interactions. The process was repeated at hospital discharge. RESULTS: Among a total number of 911 drugs prescribed to 90 older medical patients at ward admission, the pharmacists identified during their recognition/reconciliation 455 drug-related problems, mainly due to prescription of medications inappropriate for older multimorbid patients and clinically harmful drug-drug interactions. When these drug-related problems were identified by the pharmacist, the attending clinicians accepted and implemented the suggestions for changes for approximately two thirds of the discrepancies, thereby leading to deprescribing the implicated drugs or at least to their closer monitoring. CONCLUSIONS: This interventional prospective study based upon the integrated expertise of hospital pharmacists and clinicians confirms that drug-related problems are frequent in multimorbid older patients acutely admitted to hospital medical wards, and demonstrates afresh the feasibility and mutual acceptance of a trajectory of recognition/reconciliation based upon an integrated collaboration between hospital pharmacists and ward clinicians in the process of medication optimization.

Simulation-Based Education for Physicians to Increase Oral Anticoagulants in Hospitalized Elderly Patients with Atrial Fibrillation.

PURPOSE: This study was intended to determine whether a simulation-based education addressed to physicians was able to increase the proportion of hospitalized elderly with atrial fibrillation prescribed with oral anticoagulants (OACs) compared with the usual practice. METHODS: We conducted a cluster randomized trial (from April 2015 to September 2018) on 32 Italian internal medicine and geriatric wards randomized 1:1 to intervention or control arms. The physicians of wards randomized to intervention received a computer-based e-learning tool with clinical scenarios (Dr Sim), and those of wards randomized to control received no formal educational intervention. The primary outcome was the OAC prescription rate at hospital discharge in the intervention and control arms. RESULTS: Of 452 patients scrutinized, 247 were included in the analysis. Of them, 186 (75.3%) were prescribed with OACs at hospital discharge. No difference was found between the intervention and control arms in the post-intervention phase (odds ratio, 1.46; 95% confidence interval [CI], 0.81-2.64). The differences from the pre- to post-intervention phases in the proportions of patients prescribed with OACs (15.1%; 95% CI, 0%-31.5%) and with direct oral anticoagulants (DOACs) (20%; 95% CI, 0%-39.8%) increased more in the intervention than in the control arm. CONCLUSIONS: This simulation-based course did not succeed in increasing the rate of elderly patients prescribed with OACs at hospital discharge compared with the usual practice. Notwithstanding, over time there was a greater increase in the intervention than in the control arm in the proportion of patients prescribed with OACs and DOACs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03188211.

Adverse drug events related to mood and emotion in paediatric patients treated for ADHD: A meta-analysis.

BACKGROUND: ADHD is frequently comorbid with anxiety and mood disorders, which may increase the severity of inattention and hyperactivity symptoms. Emotional symptoms (anxiety, irritability, mood lability) also affect patients without comorbidity or emerge as adverse drug events. The influence of ADHD drugs on emotional symptoms demands investigation to improve therapies. METHODS: Systematic review of trials reporting adverse events in patients pharmacologically treated for ADHD. Meta-analysis of the occurrence of irritability, anxiety, apathy, reduced talk, sadness, crying, emotional lability, biting nails, staring, perseveration, euphoria. Meta-regression analysis. RESULTS: Forty-five trials were meta-analysed. The most frequently reported outcomes were irritability, anxiety, sadness, and apathy. Methylphenidates, especially immediate-release formulations, were most studied; amphetamines were half as studied and were predominantly mixed amphetamine salts. Reports on atomoxetine were scant. Meta-analysis showed that methylphenidates reduced the risk of irritability, anxiety, euphoria, whereas they worsened the risk of apathy and reduced talk; amphetamines worsened the risk of emotional lability. Factors influencing risks were study year and design, patients' sex and age, drug dose and release formulation. LIMITATIONS: Possible discrepancy between adverse events as indicated in clinical trials and as summarised herein. Confounding due to the aggregation of drugs into groups; uninvestigated sources of bias; incomplete lists of adverse events; lack of observations on self-injury. CONCLUSIONS: Methylphenidates appeared safer than amphetamines, although younger patients and females may incur higher risks, especially with high-dose, immediate-release methylphenidates. Only atomoxetine holds a black-box warning, but amphetamines and methylphenidates also did not show a safe profile regarding mood and emotional symptoms.