Discharge Information About Adverse Drug Reactions Indicates Lower Self-Reported Adverse Drug Reactions and Fewer Concerns in Patients After Percutaneous Coronary Intervention.

AIM: There are discrepancies between the information patients desire about adverse drug reactions (ADRs) and the information they receive from healthcare providers; this is an impediment to shared decision-making. This study aimed to establish whether patients received information about ADRs resulting from prescribed pharmacotherapy, before hospital discharge, after percutaneous coronary intervention (PCI) and to determine whether receiving information about ADRs was associated with incidence of self-reported ADRs or concerns related to prescribed pharmacotherapy. METHODS: CONCARDPCI, a prospective multicentre cohort study including 3,417 consecutive patients after PCI, was conducted at seven high-volume referral PCI centres in two Nordic countries. Clinical data were collected from patients' medical records and national quality registries. Patient-reported outcome measures were registered 2 months (T1), 6 months (T2), and 12 months (T3) after discharge. Covariate-adjusted logistic regression yielded adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: At discharge, 38% of participants had been informed about potential ADRs. For these patients, the incidence of self-reported ADRs was significantly lower at T1 (aOR 0.61, 95% CI 0.50-0.74; p<0.001), T2 (aOR 0.60, 95% CI 0.49-0.74; p<0.001), and T3 (aOR 0.57, 95% CI 0.46-0.71; p<0.001). Those who were not informed reported higher levels of concern about prescribed pharmacotherapy at all measuring points (p<0.001 for all comparisons). Those living alone (aOR 0.73, 95% CI 0.57-0.92; p=0.008), who were female (aOR 0.57, 95% CI 0.44-0.72; p<0.001), and with three or more versus no comorbidities (aOR 0.61, 95% CI 0.44-0.84; p=0.002) were less likely to receive information. CONCLUSION: A substantial proportion of patients were not informed about potential ADRs from prescribed pharmacotherapy after PCI. Patients informed about ADRs had lower incidences of self-reported ADRs and fewer concerns about prescribed pharmacotherapy.

Self-perceived learning outcomes of virtual and in-person academic detailing among general practitioners in Norway.

Self-perceived learning outcomes of virtual academic detailing (AD) are poorly studied. We compared self-perceived learning outcomes of virtual and in-person AD among general practitioners (GPs). GPs from the Western region of Norway received a questionnaire before and after AD concerning rational pharmacotherapy of migraine in the autumn 2022. Five statements addressing specific knowledge and two statements addressing general knowledge and skills in pharmacotherapy of migraine were rated in both questionnaires. A 7-point Likert scale ranging from 1: Strongly disagree to 7: Strongly agree was applied to all the statements. Histograms that showed the difference in the mean composite scores before and after AD were used to compare learning outcomes of virtual and in-person AD. Positive self-perceived learning outcomes were observed among 80%-88% of the GPs. No significant differences between virtual and in-person AD were observed.

Breastfeeding women in need of information about antiemetics for nausea and vomiting during pregnancy: a review of inquiries to a medicines information service.

Introduction: The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during pregnancy (NVP) or hyperemesis gravidarum (HG). However, treatment guidelines for NVP or HG do not address the use of antiemetics in women who are breastfeeding while becoming pregnant again. Our objective was to characterize inquiries to describe the need for lactation risk information among women with NVP or HG and also to raise awareness of this topic. Method: We conducted a review of inquiries to the Norwegian web-based medicines information service, SafeMotherMedicine. Results: In total, 97 inquiries addressing the use of antiemetics for NVP or HG during breastfeeding were identified. The following medications were addressed in the inquiries (n = 97): meclizine (51%), metoclopramide (33%), promethazine (16%), ondansetron (9%), and others (6%). The breastfed child was older than 6 months and 1 year in 96% and 71% of the inquiries, respectively. There was a preponderance of general inquiries (unclear motivation/double checking) (64%); however, one-third of the inquiries were generated by restrictive information from sources such as product information. Conclusion: Based on our small review of spontaneous inquiries, there seems to be an information need about the use of antiemetics during lactation among women breastfeeding an older infant whilst suffering from NVP or HG. Addressing such use in guidelines for NVP and HG and/or other easily available information sources may be considered in order to balance out the restrictive information provided by the manufacturers. This could avoid potential unnecessary weaning of breastfeeding in an otherwise challenging situation.

Healthcare professionals' information need related to antiseizure medication use in breastfeeding patients with epilepsy. Retrospective analysis of enquiries to Norwegian medicines information and pharmacovigilance centers.

Background: Safety information of antiseizure medication (ASM) during breastfeeding is scarce and conflicting. We aimed to identify characteristic traits of safety concerns among healthcare professionals by reviewing enquiries to the Norwegian Regional Medicines Information and Pharmacovigilance Centres (RELIS). Method: Enquiries related to breastfeeding, epilepsy, and ASM identified by their ATC-numbers were retrieved from the RELIS database of question-and-answer pairs (QAPs) by combining indexed and Boolean database searches and manual inspection. 112 QAPs were analyzed retrospectively using descriptive statistics. Results: Hospital-employed physicians and nurses were puzzled by ambiguous or conflicting drug information advice and called for general information about the compatibility of an ASM with breastfeeding, mainly related to lamotrigine and levetiracetam. Other enquiries were related to co-medication with other drugs, mainly antidepressants. Half of the enquiries were posed after birth, 12 of these motivated by suspected adverse events in the infants. Conclusion: Healthcare professionals with acknowledged high competence in the topic were uncertain about the prevailing safety information of ASM during breastfeeding. The fear to harm the infant may lead to the decision not to recommend breastfeeding. Future information strategies should aim to reach these professions, and support their information need on this topic.

Nurses as adverse drug reaction reporting advocates.

Adverse drug reactions (ADRs) is a challenge in modern healthcare, particularly given the increasing complexity of drug therapy, an ageing population, rising multimorbidity, and a high patient turnover. The core activity of detecting potential ADRs over the last half century has been spontaneous reporting systems. A recent Norwegian regulation commits healthcare professionals other than physicians and dentists to report serious ADRs. In this discussion paper, we share our preliminary experience with a training programme using nurses as ADR advocates to stimulate ADR reporting among the clinical staff in a hospital department.

Identifying target areas of medicines information efforts to pregnant and breastfeeding women by reviewing questions to SafeMotherMedicine: A Norwegian web-based public medicines information service.

BACKGROUND: Online information about safety of medications during pregnancy and breastfeeding is shown to be conflicting, resulting in anxiety and abstaining from use. The aim of this study was to characterize questions to SafeMotherMedicine, a web-based medicines information service for pregnant and breastfeeding women, to identify target areas that could guide subsequent development of medicines information directed at pregnant and breastfeeding women. METHODS: The SafeMotherMedicine database contains all questions received through the web-based service and their corresponding answers. A retrospective database analysis of questions received from January 2016 to September 2018 was performed, using descriptive statistics. RESULTS: A total of 11 618 questions were received including 5 985 questions (51.5%) concerning pregnancy, 4 878 questions (42.0%) concerning breastfeeding, and 755 questions (6.5%) concerning both conditions. The medications in question represented all therapeutic groups with paracetamol (7.0%), ibuprofen (4.1%), cetirizine (3.3%), desloratadine (3.2%) and meclizine (2.8%) being the top five. The 20 medications most frequently asked about for either pregnancy, breastfeeding or both pregnancy and breastfeeding, constituted half of all questions and were used to identify target areas. These included both symptomatic relief of common complaints, such as pain, nausea, and rhinitis, as well as treatment of chronic conditions such as allergy, psychiatric disorders, and asthma. Analysis of a subset of questions showed that most of these questions were asked before use of medications in a current pregnancy (49%) or during breastfeeding (72%). The questions concerned use of medications in all stages of pregnancy and breastfeeding. For 81.6% of the questions concerning pregnancy, and for 84.2% of the questions concerning breastfeeding, information of no or low risk for the foetus or the breastfed infant was provided by SafeMotherMedicine. CONCLUSIONS: We found that target areas for medicines information directed at pregnant and breastfeeding women included both symptomatic relief of common complaints as well as treatment of chronic conditions. The questions concerned a wide range of medications and involved use in all stages of pregnancy and breastfeeding. Our findings indicate that developing medicines information addressing the identified target areas will meet the information need for a large proportion of this patient group.

A liposomal formulation of simvastatin and doxorubicin for improved cardioprotective and anti-cancer effect.

Anthracyclines such as doxorubicin (Dox) are the preferred chemotherapeutics for several cancers. However, Dox-induced cardiotoxicity limits its therapeutic potential. Liposomal encapsulation of Dox has been used for patients with risk to develop Dox induced cardiotoxicity but does not surpass the efficacy of the unencapsulated drug. Statins are widely used as cholesterol lowering drugs and have also demonstrated cardioprotective activity in cancer patients undergoing Dox therapy. We developed a liposome loaded with Dox and simvastatin (Sim) and investigated their effect on cardiomyocytes and zebrafish larvae. Furthermore, we investigated if the doses required for cardioprotection compromised the cytotoxicity of Dox in mammary and prostate cancer cells. Combination of Sim and Dox reduced ROS generation in cardiomyocytes, both given as free drugs, or co-encapsulated in liposomes. In contrast, Sim potentiated ROS-generation and cytotoxic activity of Dox towards cancer cells also when co-encapsulated in liposomes. In zebrafish larvae, Sim treatment reduced Dox-induced cardiac affection, and the liposomes did not induce any sign of Dox-induced cardiotoxicity. Our results show that liposomal co-encapsulation of Sim and Dox can be an efficient way of further reducing the risk of cardiotoxic events of liposomal Dox, while retaining, or even potentiating the anti-cancer effect of Dox.

Perceptions of generic medicines and medication adherence after percutaneous coronary intervention: a prospective multicentre cohort study.

OBJECTIVE: To determine patient perceptions of generic medicines 2 and 6 months after percutaneous coronary intervention (PCI), and to determine whether these perceptions moderate medication adherence. DESIGN: Prospective multicentre cohort study with repeated measures of perceptions of generic medicines and medication adherence. SETTING: The CONCARDPCI study conducted at seven large referral PCI centres in Norway and Denmark between June 2017 and May 2020. PARTICIPANTS: A total of 3417 adults (78% men), using both generic and brand name medicines, with a mean age of 66 years (SD 11) who underwent PCI were followed up 2 and 6 months after discharge from hospital. MAIN OUTCOME MEASURES: Perceptions of generic medicines were the main outcome. The secondary outcome was medication adherence. RESULTS: Perceptions of generic medicines were significantly more negative at 2 than at 6 months (1.10, 95% CI 0.41 to 1.79, p=0.002). Female sex (-4.21, 95% CI -6.75 to -1.71, p=0.001), older age (-0.12, 95% CI -0.23 to -0.02, p=0.020), lower education level (overall p<0.001), ethnicity (overall p=0.002), Norwegian nationality (10.27, 95% CI 8.19 to 12.40, p<0.001) and reduced self-reported health status (0.19, 95% CI 0.09 to 0.41, p=0.003) were significantly associated with negative perceptions of generic medicines. There was no evidence to suggest that perceptions of generic medicines moderate the association between sociodemographic and clinical variables and medication adherence (p≥0.077 for all covariates). Moreover, self-reported medication adherence was high, with 99% scoring at or above the Medication Adherence Report Scale midpoint at both time points. There were no substantial correlations between negative perceptions of generic medicines and medication non-adherence at 2 months (r=0.041, 95% CI 0.002 to 0.081, p=0.037) or 6 months (r=0.038, 95% CI -0.005 to 0.081, p=0.057). CONCLUSIONS: Mistrust and uncertainty about the safety and efficacy of generic medicines remains in a sizeable proportion of patients after PCI. This applies especially to those of lower socioeconomic status, older age, female sex, immigrants and those with poorer mental health. However, this study demonstrated a shift towards more positive perceptions of generic medicines in the longer term.

Serum or Plasma for Quantification of Direct Oral Anticoagulants?

BACKGROUND: Direct oral anticoagulants are increasingly replacing vitamin K antagonists for prevention of stroke in patients with atrial fibrillation, partly owing to the lack of a need for routine monitoring. Therapeutic drug monitoring may still be warranted under certain circumstances. It is generally assumed that serum and plasma can be interchangeably used for this purpose. The aim of this study was to investigate possible differences between the serum, citrate-plasma, and ethylenediaminetetraacetic acid (EDTA)-plasma concentrations of apixaban and rivaroxaban in a larger patient group and their relation to factor X measurements. METHODS: Plasma and serum samples were drawn during the same venipuncture from patients treated with apixaban or rivaroxaban. Drug levels were measured using ultrahigh-performance liquid chromatography combined with tandem mass spectrometry. Three sample matrices were obtained from 8 healthy volunteers for measurement of factor X antigen and activity. RESULTS: Mean concentrations of apixaban and rivaroxaban were 16.8% and 36.6% higher in serum than in citrate-plasma, respectively (both P < 0.001). The corresponding differences in serum versus EDTA-plasma were 4.5% for apixaban and 13.1% for rivaroxaban (both P < 0.001). Factor X antigen measurements in citrate-plasma, EDTA-plasma, serum with clot activator, and serum without additives yielded comparable results, and factor X activity was significantly higher in serum than in plasma. CONCLUSIONS: Apixaban and rivaroxaban concentrations were significantly higher in serum than in plasma. The difference was more pronounced with rivaroxaban and was larger between serum and citrate-plasma than between serum and EDTA-plasma. Higher factor X activity in serum may explain the observed concentration differences. The choice of matrix is, thus, important when interpreting therapeutic drug monitoring results and in research involving analyses of direct oral anticoagulants. The authors recommend citrate-plasma as the preferred matrix.

A Patient With Sepsis-Induced Multiorgan Failure and Increasing Serum Methadone Concentration: A Case Study.

ABSTRACT: The authors describe a patient with substance use disorder admitted to the hospital with septic shock and multiorgan failure, in whom the serum concentration of methadone kept increasing despite discontinuation of the drug. Therapeutic drug monitoring was performed to monitor the methadone serum concentration during treatment of the underlying diseases.

Ultrasound and Microbubbles Enhance Uptake of Doxorubicin in Murine Kidneys.

The use of ultrasound and microbubble-enhanced drug delivery, commonly referred to as sonoporation, has reached numerous clinical trials and has shown favourable results. Nevertheless, the microbubbles and acoustic path also pass through healthy tissues. To date, the majority of studies have focused on the impact to diseased tissues and rarely evaluated the impact on healthy and collateral tissue. The aim of this study was to test the effect and feasibility of low-intensity sonoporation on healthy kidneys in a mouse model. In our work here, we used a clinical diagnostic ultrasound system (GE Vivid E9) with a C1-5 ultrasound transducer combined with a software modification for 20-µs-long pulses to induce the ultrasound-guided drug delivery of doxorubicin (DOX) in mice kidneys in combination with SonoVue® and Sonazoid™ microbubbles. The acoustic output settings were within the commonly used diagnostic ranges. Sonoporation with SonoVue® resulted in a significant decrease in weight vs. DOX alone (p = 0.0004) in the first nine days, whilst all other comparisons were not significant. Ultrasound alone resulted in a 381% increase in DOX uptake vs. DOX alone (p = 0.0004), whilst SonoVue® (p = 0.0001) and Sonazoid™ (p < 0.0001) further increased the uptake nine days after treatment (419% and 493%, respectively). No long-standing damage was observed in the kidneys via histology. In future sonoporation and drug uptake studies, we therefore suggest including an "ultrasound alone" group to verify the actual contribution of the individual components of the procedure on the drug uptake and to perform collateral damage studies to ensure there is no negative impact of low-intensity sonoporation on healthy tissues.

Quetiapine, Misuse and Dependency: A Case-Series of Questions to a Norwegian Network of Drug Information Centers.

PURPOSE: The second-generation antipsychotic quetiapine has been associated with misuse and dependency. We aimed to review questions to the Norwegian network of drug information centers concerning this potential drug safety problem. METHODS: We conducted a Boolean search in the database of the Regional Medicines Information and Pharmacovigilance Centres in Norway (RELIS) combining the indexed categories "quetiapine" and "adverse drug reaction" with the text words "misuse" or "dependency". Question-answer pairs (Q/As) in the full-text, searchable RELIS database were defined as cases. Cases were analyzed for drug safety issues linked to use of quetiapine, including off-label use, polypharmacy and other patient risk factors. RESULTS: The search resulted in 54 cases. Forty-six cases (85%) were patient-related, and a majority came from physicians working in hospitals. Twenty-nine cases (54%) concerned patients with a history of addiction, 14 cases (26%) had polypharmacy, and off-label use of quetiapine for insomnia was identified in 14 of the cases (26%). Only three of the cases included a specific question about patient dependency of quetiapine, and these cases were all associated with insomnia. CONCLUSION: We conclude that our case series from the Norwegian network of drug information centres reflects that quetiapine frequently involves clinical narratives of a history of addiction, polypharmacy or insomnia (off-label use). However, the case series did not reveal new information about the drug's addictive potential.

Acute Myocardial Injury in a Patient with Attention Deficit Hyperactivity Disorder and History of Substance Abuse: A Multimodality Imaging Point of View.

Both cannabis and amphetamine are the most commonly used illegal substances worldwide and are associated with a number of adverse cardiovascular effects including transient coronary vasospasm. Here, we present the case of a 39-year-old male admitted to our institution with a 6-h history of severe chest pain and ST-segment elevation on the ECG. Coronary angiography on admission showed normal coronary arteries. The patient had a 14-year history of substance abuse, primarily amphetamine and cannabis, and was prescribed lisdexamfetamin (Aduvanz®) for attention deficit hyperactivity disorder (ADHD) for the past 2 years. A cardiac magnetic resonance (CMR) the following day showed widely distributed focal lesions of late gadolinium enhancement in mid- and sub-epicardial myocardium in the anterior, lateral and inferior walls, suggestive of chronic fibrotic lesions. There was no sign of acute myocardial edema. No viral cause was identified during a thorough investigation, including negative SARS-COV-2 and endomyocardial biopsy. Substance-abuse-induced coronary vasospasm leading to ST-segment elevation, myocardial damage with a rise and fall of cardiac TnT, as well as a slightly reduced left ventricular ejection fraction (48%) and regional wall motion abnormalities on echocardiography, was the most likely diagnosis.

Review of Clinical Questions Submitted to Norwegian Drug Information Centres Concerning Administration and Dosage to Older Patients of Relevance to Patient-Centric Care.

Patient-centric care entails optimising healthcare provision to patients based on their perspective and opinion. It involves appropriate treatment at a reasonable cost and a focus on patient characteristics in the decision-making process to make it more personally useful. The optimisation of medicines in the older population is a challenge due to physiological changes, comorbidity, and polypharmacy. Furthermore, patient-centric care is difficult to achieve due to the high proportion of patients with dementia and frailty. Decision support concerning the appropriateness of indication, formulation, dose, administration, co-prescribing, and length of treatment to older patients is frequently in demand. In the current study, we aimed to review clinical questions concerning administration and dosage to older patients of relevance to patient-centric care. We analysed questions concerning medicines to patients 65 years or older in the database of the network of Norwegian drug information centres from 2010 to 2020. The analysis included the distribution of drugs, diseases, and recurring topics among the questions. Through a Boolean search that combined the indexed categories of "older" and "administration and dosage", we retrieved 84 question-answer pairs. Questions about psychotropic and cardiovascular drugs in relation to therapy, adverse drug reactions, and pharmacokinetics dominated, and more than 60% of the questions came from physicians. Topics relevant to patient-centric pharmacotherapy were drug withdrawal (10 questions), drug formulation (8 questions), drug initiation (8 questions), and switching drugs (5 questions). One question concerned drug withdrawal and switching, and one question drug formulation and switching. Answers provided decision support regarding appropriate formulations of drugs to patients with dementia who chew capsules or tablets, the use of parenteral administration in patients who refuse to take oral formulations, and the pharmacokinetics of transdermal or rectal drug administration. The results highlight the importance of including pharmacological factors in the assessment of the acceptability and appropriateness of oral and parenteral medicine to older patients.