[Opioid use and misuse among patients at the emergency department]. / Opioïdgebruik en -misbruik onder patiënten op de SEH.

OBJECTIVE: To determine the prevalence of use and misuse of prescription opioids among patients at Dutch emergency departments (EDs). DESIGN: Cross-sectional multicenter study. METHOD: This study was performed at three EDs in the Nijmegen-Arnhem region. ED-patients of 18 years and older were screened for current opioid use. The Current Opioid Misuse Measure (COMM) questionnaire was used to assess opioid misuse. The presence of opioid use disorder was determined using DSM-5 based interviews. RESULTS: A total of 997 patients was screened for opioid use. The prevalence of opioid use was 15.0% (95%CI 12.9 -17.4). 22.6% (95%CI 14.6-32.4) scored positive for opioid misuse, 9.8% (95%CI 4.5-17.8) fulfilled DSM-5 criteria for opioid use disorder. CONCLUSION: Opioid use and misuse are relatively common among patients in Dutch EDs.

The prevalence of prescription opioid use and misuse among emergency department patients in The Netherlands.

RATIONALE: Prescription opioid use and misuse have increased rapidly in many Western countries in the past decade. Patients (mis)using opioids are at risk of presenting to the emergency department (ED) with opioid-related problems. European data concerning prescription opioid (mis)use among the ED population is lacking. AIMS AND OBJECTIVES: This study aims to determine prevalence of prescription opioid use, misuse, and opioid use disorder (OUD) among Dutch ED patients. Secondary objectives were to explore factors associated with prescription opioid misuse and the number of patients discharged with a new opioid prescription. METHODS: In a cross-sectional multicenter study at three hospitals in the Netherlands, adult ED patients were screened for current prescription opioid use. Opioid users filled out questionnaires regarding opioid (mis)use, and underwent a structured interview to assess OUD criteria. The primary outcomes were prevalence rates of (1) current prescription opioid use, (2) prescription opioid misuse (based on a Current Opioid Misuse Measure [COMM] score > 8), (3) OUD, based on DSM-5 criteria. Independent T-tests, Pearson χ2 and Fisher's Exact tests were used to analyse differences in characteristics between groups. RESULTS: A total of 997 patients were screened, of which 15% (n = 150) used prescription opioids. Out of 93 patients assessed, 22.6% (n = 21) showed signs of prescription opioid misuse, and 9.8% (n = 9, 95% CI: 4.5-17.8) fulfilled criteria for OUD. A medical history of psychiatric disorder was significantly more common in patients with prescription opioid misuse and OUD. CONCLUSION: This study shows that prescription opioid use is relatively common in ED patients in the Netherlands, compared to the overall population. Over one fifth of these patients shows signs of opioid misuse or OUD. Awareness among ED personnel about the high prevalence of prescription opioid (mis)use in their population is critical for signalling opioid-related problems.

Real-World Adverse Effects of Capecitabine Toxicity in an Elderly Population.

BACKGROUND: Few studies have assessed the safety and effectiveness of the numerous available chemotherapeutic therapies for geriatric oncology patients. Most safety studies are conducted in large trials, and there is some uncertainty surrounding whether the results would be the same in typical daily use. OBJECTIVE: This retrospective study aims to assess the adverse effects of real-world capecitabine use in elderly patients. METHODS: We reviewed the records of patients treated with capecitabine in an oncology department of a University Clinic in Nijmegen, The Netherlands. We scored adverse effects such as hand-foot syndrome and diarrhea, and dosage adjustments and the reasons for them. In total, 132 patients were included, 69 of whom were aged 70 years or below (mean age: 57 years), while 63 were aged older than 70 years (mean age: 74 years). RESULTS: Patients aged over 70 years experienced more serious adverse effects than younger patients. Grade 2 or 3 hand-foot syndrome toxicity was experienced by 20.2% of patients aged younger than 70 years and by 34.9% of patients older than 70 years (p = 0.059). Grade 2, 3, or 4 diarrhea was experienced by 17.4% of the patients aged younger than 70 years but by 31.7% of the patients aged older than 70 years (p = 0.044). Dosage was adjusted for 27/69 patients in the younger group and 52/63 patients in the older group (p = 0.001). CONCLUSION: The difference in observed adverse effects cannot be the sole explanation for the high incidence of observed dose adjustments. A prospective follow-up study of elderly patients using capecitabine outside clinical trials is needed to evaluate the optimum balance between adverse effects and efficacy.

Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: A randomized controlled trial.

OBJECTIVE: To study the efficacy and safety of low-dose oral tetrahydrocannabinol (THC) in the treatment of dementia-related neuropsychiatric symptoms (NPS). METHODS: This is a randomized, double-blind, placebo-controlled study. Patients with dementia and clinically relevant NPS were randomly assigned to receive THC 1.5 mg or matched placebo (1:1) 3 times daily for 3 weeks. Primary outcome was change in Neuropsychiatric Inventory (NPI), assessed at baseline and after 14 and 21 days. Analyses were based on intention-to-treat. RESULTS: Twenty-four patients received THC and 26 received placebo. NPS were reduced during both treatment conditions. The difference in reduction from baseline between THC and placebo was not significant (mean difference NPItotal: 3.2, 95% confidence interval [CI] -3.6 to 10.0), nor were changes in scores for agitation (Cohen-Mansfield Agitation Inventory 4.6, 95% CI -3.0 to 12.2), quality of life (Quality of Life-Alzheimer's Disease -0.5, 95% CI -2.6 to 1.6), or activities of daily living (Barthel Index 0.6, 95% CI -0.8 to 1.9). The number of patients experiencing mild or moderate adverse events was similar (THC, n = 16; placebo, n = 14, p = 0.36). No effects on vital signs, weight, or episodic memory were observed. CONCLUSIONS: Oral THC of 4.5 mg daily showed no benefit in NPS, but was well-tolerated, which adds valuable knowledge to the scarce evidence on THC in dementia. The benign adverse event profile of this dosage allows study of whether higher doses are efficacious and equally well-tolerated. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with dementia-related NPS, low-dose THC does not significantly reduce NPS at 21 days, though it is well-tolerated.

Neuropsychiatric adverse events of varenicline: a systematic review of published reports.

INTRODUCTION: Over the past years, the impact of varenicline in patients with mental illness has been debated as serious neuropsychiatric adverse events (AEs) have been reported with varenicline use. AIM: To identify and summarize published case reports of neuropsychiatric AEs ascribed to varenicline and to determine potential risk factors for these AEs. METHODS: A literature search of MEDLINE, the Cochrane Library, EMBASE, and PsychInfo database was conducted for case reports concerning the neuropsychiatric AEs of varenicline published in English from 2006 (approval year by the US Food and Drug Administration and the Dutch Medicines Evaluation Board) to January 1, 2012. RESULTS: We identified 25 published cases. In most reports, patients had been admitted to psychiatric hospitals with serious neuropsychiatric AEs due to varenicline. The average patient age was 46.4 years, and 56% were men; 68% of patients had a psychiatric history. The onset of symptoms started 2 days to 3 months after the initiation of varenicline. One report described completed suicide in a man with no psychiatric history. In most cases (84%), the neuropsychiatric symptoms resolved after the discontinuation of varenicline. Analysis of all reports using the Naranjo causality scale, a method for estimating the probability of adverse drug reactions, indicated probable causality in 76% of the cases and definite causality in 12% of cases. CONCLUSION: Varenicline is associated with an increased risk of serious neuropsychiatric AEs, especially in patients with a psychiatric illness. It is strongly recommended that varenicline be administered only to mentally stable patients and under close monitoring.

Targeting outpatient drug safety: recommendations of the Dutch HARM-Wrestling Task Force.

BACKGROUND: Two Dutch observational studies (HARM [Hospital Admissions Related to Medication] and IPCI [Integrated Primary Care Information]) have shown that approximately 5% of all unplanned hospital admissions are associated with adverse drug events (ADEs), of which 40-46% are potentially preventable. These studies prompted the initiation of a Dutch multidisciplinary task force, which was assigned to reduce the number of prescriber-related hospital admissions related to medications (HARMs) in a quick-win way. OBJECTIVE: The aim of the study was to identify the most relevant ADEs and to develop a limited number of recommendations for concrete interventions, which should be feasible and relatively easy to convert into computerized drug safety alerts. METHOD: To identify the major ADEs, crude data of HARM and IPCI were reanalysed and compared with different international studies, followed by structured literature searches for further characterization of the identified ADEs, their risk factors and potential risk-reduction strategies. Based on this information, the Task Force drew up general and drug-specific recommendations. As the recommendations of the Task Force are a mixture of evidence- and expert-based risk-reducing strategies, they have been graded in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. RESULTS: Seven pharmacologically predictable ADEs associated with ten drug classes were responsible for more than half of all potentially preventable hospital admissions in the IPCI and HARM studies, which was comparable to the results of international studies. Gastrointestinal and other bleedings were the most frequent ADE, followed by disturbances of diabetes mellitus control, electrolyte disturbances, fractures, renal insufficiency and heart failure. Nine general and 34 drug-specific recommendations were developed. CONCLUSIONS: As HARMs constitute a significant public health problem, the Task Force underlines the need to implement its recommendations as soon as possible. They do not replace existing guidelines, but reinforce, complement and fine-tune existing Dutch and international guidelines. Further research is still required to assess the cost consequences and cost effectiveness of some recommendations, and to monitor the implementation of the recommendations and their effect on the incidence of potentially preventable HARMs.

[Intentional paracetamol intoxication in children]. / Intentionele paracetamolintoxicatie bij kinderen.

As paracetamol is widely used and easily available acetaminophen auto-intoxication is frequently seen. In the majority of patients no complications will occur, but in a small group it may lead to liver damage and death. Children are less susceptible to complications than adults. Cornerstone of treatment is the antidote acetylcysteine, administration of which can be based on the Rumack-Matthew nomogram. This nomogram has only been validated in adults, but nevertheless is also used in children. Gastric lavage should not be implemented, active charcoal can be given to a conscious cooperative patient within 1 hour of ingestion of acetaminophen. A multidisciplinary approach to treatment is needed with the collaboration of an emergency physician, paediatrician or internist, pharmacist and also a child psychiatrist.

A composite screening tool for medication reviews of outpatients: general issues with specific examples.

Regular performance of medication reviews is prominent among methods that have been advocated to reduce the extent and seriousness of drug-related problems, such as adverse drug reactions, drug-disease interactions, drug-drug interactions, drug ineffectiveness and cost ineffectiveness. Several screening tools have been developed to guide practising healthcare professionals and researchers in reviewing the medication patterns of elderly patients; however, each of these tools has its own limitations. This review discusses a wide range of general prescription-, treatment- and patient-related issues that should be taken into account when reviewing medication patterns by implicit screening. These include generic and therapeutic substitution; potentially superfluous or inappropriate medications; potentially inappropriate dosages or duration of treatment; drug-disease and drug-drug interactions; under-treatment; making use of laboratory test results; patient adherence, experiences and habits; appropriate dosage forms and packaging. A broad selection of specific examples and references that can be used as a basis for explicit screening of medication patterns in outpatients is also offered.