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.

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.

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.

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.

Persistence in Therapy With Risperidone and Aripiprazole in Pediatric Outpatients: A 2-Year Naturalistic Comparison.

OBJECTIVE: The practical effectiveness of second-generation antipsychotics in children and adolescents is an understudied issue. It is a crucial area of study, though, because such patients are often treated for long-lasting disorders. METHODS: We carried out a 24-month (March 2012-March 2014) observational study on an unselected population of pediatric outpatients treated with risperidone, aripiprazole, olanzapine, or quetiapine aiming to (1) describe drug use, (2) compare post hoc the discontinuation rates due to specific causes and dose adjustments by Kaplan-Meier analyses between drugs, and (3) analyze predictors influencing these outcomes by Cox multivariate models. RESULTS: Among 184 pediatric patients, 77% patients were prescribed risperidone, and 18% were prescribed aripiprazole. Olanzapine or quetiapine were scantly used; therefore, they were excluded from analyses. Risperidone was prevalent in younger, male patients with disruptive behavioral disorders; aripiprazole, in patients with tic disorders. Overall, discontinuations occurred mostly in the first 6 months, and, at 24 months, the discontinuation numbers were similar between users of risperidone and aripiprazole (41.5% vs 39.4%). In univariate analyses, dose reduction was higher for aripiprazole (P = .033). Multivariate analyses yielded the following predictors: for all-cause discontinuation, baseline severity (hazard ratio [HR] = 1.48, P = .001) and dose increase (HR = 3.55, P = .001); for patient-decided discontinuation, dose change (increase: HR = 6.43, P = .004; reduction: HR = 7.89, P = .049) and the presence of concomitant drugs (HR = 4.03, P = .034), while autistic patients discontinued less (HR = 0.23, P = .050); for clinician-decided discontinuation due to adverse drug reactions, baseline severity (HR = 1.96, P = .005) and dose increase (HR = 5.09, P = .016); for clinician-decided discontinuation due to inefficacy, baseline severity (HR = 2.88, P = .014) and the use of aripiprazole (HR = 5.55, P = .013); for dose increase, none; for dose reduction, the occurrence of adverse drug reactions (HR = 4.74, P = .046), while dose reduction was less probable in autistic patients (HR = 0.22, P = .042). CONCLUSIONS: The findings of this study show a similarity between the overall effectiveness of risperidone and aripiprazole in a real-life pediatric outpatient setting.

The Contribution of National Spontaneous Reporting Systems to Detect Signals of Torsadogenicity: Issues Emerging from the ARITMO Project.

INTRODUCTION: Spontaneous reporting systems (SRSs) are pivotal for signal detection, especially for rare events with a high drug-attributable component, such as torsade de pointes (TdP). Use of different national SRSs is rarely attempted because of inherent difficulties, but should be considered on the assumption that rare events are diluted in international databases. OBJECTIVE: The aim was to describe TdP-related events associated with antipsychotics, H1-antihistamines and anti-infectives in three national SRSs (in Italy, Germany and France) and highlight potential signals of torsadogenicity through a combined literature evaluation. METHODS: A common search strategy was applied to extract TdP-related events: (1) TdP, (2) QT interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. Signals of disproportionate reporting (SDRs) were calculated for TdP + QT interval abnormalities and defined by a lower limit of the 95 % confidence interval of the reporting odds ratio (ROR) >1. Among SDRs with at least three cases without concomitant pro-arrhythmic drugs, we defined potential new signal of torsadogenicity as drugs with no published evidence from (a) the crediblemeds(®) website ( http://www.crediblemeds.com , as of November 1st, 2014); (b) studies on the FDA Adverse Event Reporting System (FAERS); and (c) safety trials or pharmaco-epidemiological studies (as of December 16th, 2014). RESULTS: Overall, 3505 cases were retrieved (1372, 1468, and 801 for France, Germany and Italy, respectively). Antipsychotics were mainly recorded in Germany (792 cases), whereas antibiotics peaked at 515 and 491 (France and Italy, respectively). Forty-one drugs met criteria for SDRs in at least one single source, of which 31 were detected only from one single SRS: 18, ten and three (French, German and Italian SRS, respectively). By contrast, only five SDRs were detected in all national data sources (amisulpride, aripiprazole, haloperidol, olanzapine, risperidone). Overall, five potential new signals of torsadogenicity were identified: flupentixol, ganciclovir, levocetirizine, oxatomide and tiapride. CONCLUSIONS: We found differences across and within national SRSs in the reporting of drug-induced TdP, which finally resulted in five potential new signals of torsadogenicity. These findings warrant targeted pharmacovigilance studies to formally assess the existence of actual drug-event associations.

On the connection between autoimmunity, tic disorders and obsessive-compulsive disorders: a meta-analysis on anti-streptolysin O titres.

Anti-streptolysin O (ASO) titration is useful in the context of autoimmune pathologies, including specific cases of tic and obsessive-compulsive disorders occurring after streptococcal infections. There is currently a lack of consensus on the use of ASO titres; therefore we performed a meta-analysis to systematise available data and clarify the role of ASO titres in the context of neuropsychiatric disorders. A meta-analysis was performed on ASO titration in neuropsychiatric patients, including tic disorders and obsessive-compulsive disorders. Included studies reported numbers of positive subjects, depending on a chosen threshold, or detailed ASO titrations. Three hundred and twenty nine studies were identified, of which 13 were eligible for meta-analysis. Due to limited available data, only tic disorders were evaluated. The odds ratio of finding an abnormal ASO titre in patients was 3.22 (95% C.I. 1.51-6.88) as compared to healthy controls and 16.14 (95% C.I. 8.11-32.11) as compared to non-psychiatric patients. Studies using different thresholds were generally concordant. ASO titres were also compared quantitatively, finding an overall difference of the means of 70.50 U/ml (95% C.I. 25.21-115.80) in favour of patients with tic disorders. Based on current evidence, tic disorders are associated with a significant increase in ASO titres, evident both in a threshold-level perspective and on a quantitative level. These results encourage the systematisation of ASO titration in the context of tic disorders.