Marketing of healthcare services in Denmark: the concept of misleading advertising.

As severe ill and incurable patients can be easy victims of misleading advertising activities for dangerous and non-effective healthcare treatments, the marketing of healthcare services are in many jurisdictions legislations tightly regulated. This article reviews the Danish regulation on marketing of healthcare services to identify which types of advertising activities that are legal. As the legislation only allows healthcare authorities to control the marketing and not the content and quality of the marketed healthcare services, their ability to intervene in serious cases of misleading advertising is limited. Misleading advertising are statements with the purpose to exaggerate or underestimate the effects and risks of healthcare services or to prevent patients from seeking conventional medical treatments. From a public health perspective, there is a need for a common EU legislation for regulation of the marketing of healthcare services as the increasing use of information technologies makes it possible for the providers to access consumers and patients directly across countries and legal systems.

Effect of a medicines management model on medication-related readmissions in older patients admitted to a medical acute admission unit-A randomized controlled trial.

RATIONALE, AIMS, AND OBJECTIVES: Medication-related problems are frequent and can lead to serious adverse events resulting in increased morbidity, mortality, and costs. Medication use in frail older patients is even more complex. The aim of this study was to investigate the effect of a pharmacist-led medicines management model among older patients at admission, during inpatient stay and at discharge on medication-related readmissions. METHOD: A randomized controlled trial conducted at the acute admission unit in a Danish hospital with acutely admitted medical patients, randomized to either a control group or one of two intervention groups. The intervention consisted of pharmacist-led medication review and patient interview upon admission (intervention ED) or pharmacist-led medication review and patient interview upon admission, medication review during inpatient stay, and medication report and patient counselling at discharge (intervention STAY). RESULTS: In total, 600 patients were included. The pharmacist identified 920 medication-related problems with 57% of the recommendations accepted by the physician. After 30 days, 25 patients had a medication-related readmission, with no statistical significant difference between the groups on either primary or secondary outcomes. CONCLUSIONS: This study showed that a clinical pharmacist can be used to identify and solve medication-related problems, but this study did not find any effect on the selected outcomes. The frequency of medication-related readmissions was low, leaving little room for improvement. Future research should consider other study designs or outcome measures.

Off-label and unlicensed prescribing in Europe: implications for patients' informed consent and liability.

This article reviews the implications of off-label (OL) and unlicensed (UL) medicine use with respect to the legal duty to inform patients and the liability for failure to provide the patient with adequate information on benefits and risks. Informed consent is a legal prerequisite to any medical treatment and requires the physician to inform the patient about benefits and risks important for the patient's decision. Since OL/UL medicine use is common in all fields of medical practice, physicians must be aware of the stricter requirements for information of the patient. The UK High Supreme Court ruled in the case Montgomery v. Lanarkshire Health Board that physicians' information duty is not limited to the level of information that the physician finds important, but to what the patient deems important. In general, violations of the rule of informed consent does not constitute a physical injury, and patients can only claim compensation for damages, if adequate disclosure had been given, and its likely, that patients would have either rejected or opted for an alternative treatment.

Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood. The psychostimulant methylphenidate is the most frequently used medication to treat it. Several studies have investigated the benefits of methylphenidate, showing possible favourable effects on ADHD symptoms, but the true magnitude of the effect is unknown. Concerning adverse events associated with the treatment, our systematic review of randomised clinical trials (RCTs) demonstrated no increase in serious adverse events, but a high proportion of participants suffered a range of non-serious adverse events. OBJECTIVES: To assess the adverse events associated with methylphenidate treatment for children and adolescents with ADHD in non-randomised studies. SEARCH METHODS: In January 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 12 other databases and two trials registers. We also checked reference lists and contacted authors and pharmaceutical companies to identify additional studies. SELECTION CRITERIA: We included non-randomised study designs. These comprised comparative and non-comparative cohort studies, patient-control studies, patient reports/series and cross-sectional studies of methylphenidate administered at any dosage or formulation. We also included methylphenidate groups from RCTs assessing methylphenidate versus other interventions for ADHD as well as data from follow-up periods in RCTs. Participants had to have an ADHD diagnosis (from the 3rd to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders or the 9th or 10th edition of theInternational Classification of Diseases, with or without comorbid diagnoses. We required that at least 75% of participants had a normal intellectual capacity (intelligence quotient of more than 70 points) and were aged below 20 years. We excluded studies that used another ADHD drug as a co-intervention. DATA COLLECTION AND ANALYSIS: Fourteen review authors selected studies independently. Two review authors assessed risk of bias independently using the ROBINS-I tool for assessing risk of bias in non-randomised studies of interventions. All review authors extracted data. We defined serious adverse events according to the International Committee of Harmonization as any lethal, life-threatening or life-changing event. We considered all other adverse events to be non-serious adverse events and conducted meta-analyses of data from comparative studies. We calculated meta-analytic estimates of prevalence from non-comparative cohorts studies and synthesised data from patient reports/series qualitatively. We investigated heterogeneity by conducting subgroup analyses, and we also conducted sensitivity analyses. MAIN RESULTS: We included a total of 260 studies: 7 comparative cohort studies, 6 of which compared 968 patients who were exposed to methylphenidate to 166 controls, and 1 which assessed 1224 patients that were exposed or not exposed to methylphenidate during different time periods; 4 patient-control studies (53,192 exposed to methylphenidate and 19,906 controls); 177 non-comparative cohort studies (2,207,751 participants); 2 cross-sectional studies (96 participants) and 70 patient reports/series (206 participants). Participants' ages ranged from 3 years to 20 years. Risk of bias in the included comparative studies ranged from moderate to critical, with most studies showing critical risk of bias. We evaluated all non-comparative studies at critical risk of bias. The GRADE quality rating of the evidence was very low.Primary outcomesIn the comparative studies, methylphenidate increased the risk ratio (RR) of serious adverse events (RR 1.36, 95% confidence interval (CI) 1.17 to 1.57; 2 studies, 72,005 participants); any psychotic disorder (RR 1.36, 95% CI 1.17 to 1.57; 1 study, 71,771 participants); and arrhythmia (RR 1.61, 95% CI 1.48 to 1.74; 1 study, 1224 participants) compared to no intervention.In the non-comparative cohort studies, the proportion of participants on methylphenidate experiencing any serious adverse event was 1.20% (95% CI 0.70% to 2.00%; 50 studies, 162,422 participants). Withdrawal from methylphenidate due to any serious adverse events occurred in 1.20% (95% CI 0.60% to 2.30%; 7 studies, 1173 participants) and adverse events of unknown severity led to withdrawal in 7.30% of participants (95% CI 5.30% to 10.0%; 22 studies, 3708 participants).Secondary outcomesIn the comparative studies, methylphenidate, compared to no intervention, increased the RR of insomnia and sleep problems (RR 2.58, 95% CI 1.24 to 5.34; 3 studies, 425 participants) and decreased appetite (RR 15.06, 95% CI 2.12 to 106.83; 1 study, 335 participants).With non-comparative cohort studies, the proportion of participants on methylphenidate with any non-serious adverse events was 51.2% (95% CI 41.2% to 61.1%; 49 studies, 13,978 participants). These included difficulty falling asleep, 17.9% (95% CI 14.7% to 21.6%; 82 studies, 11,507 participants); headache, 14.4% (95% CI 11.3% to 18.3%; 90 studies, 13,469 participants); abdominal pain, 10.7% (95% CI 8.60% to 13.3%; 79 studies, 11,750 participants); and decreased appetite, 31.1% (95% CI 26.5% to 36.2%; 84 studies, 11,594 participants). Withdrawal of methylphenidate due to non-serious adverse events occurred in 6.20% (95% CI 4.80% to 7.90%; 37 studies, 7142 participants), and 16.2% were withdrawn for unknown reasons (95% CI 13.0% to 19.9%; 57 studies, 8340 participants). AUTHORS' CONCLUSIONS: Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children and adolescents, which often lead to withdrawal of methylphenidate. Our certainty in the evidence is very low, and accordingly, it is not possible to accurately estimate the actual risk of adverse events. It might be higher than reported here.Given the possible association between methylphenidate and the adverse events identified, it may be important to identify people who are most susceptible to adverse events. To do this we must undertake large-scale, high-quality RCTs, along with studies aimed at identifying responders and non-responders.

Off-Label Prescribing of Antipsychotics in a Danish Child and Adolescent Mental Health Center: A Register-Based Study.

OBJECTIVE: We analyzed prescribing patterns of antipsychotics for children and adolescent affiliated with a Danish Child and Adolescent Mental Health Center) with respect to age, sex, medicine, diagnoses, off-label status, and time. METHODS: We included all patients below 19 years of age prescribed antipsychotics during 2007-2008 and as of November 1, 2014. Prescription data included all antipsychotic prescriptions and prescriptions of concomitant psychotropic medications. We defined an antipsychotic user as a patient receiving at least one prescription during the study period, irrespective of any previous history of antipsychotic use. We defined off-label prescribing as prescriptions outside the licensed age group and approved indication. FINDINGS: We analyzed 404 antipsychotic prescriptions that were located for 150 patients. The patients were between 7 and 18 years of age. Two-thirds of the prescriptions were for girls and two-thirds of prescriptions for olanzapine and quetiapine. Totally, 92% of all prescribed antipsychotics were used off-label. For typical antipsychotics, this share was 96% and for atypical antipsychotics 90%. As of November 1, 2014, the total share of off-label antipsychotic prescriptions was 96%, and 63% of these were for medications prescribed outside the approved age group, and 26% for nonlicensed indication(s). CONCLUSION: This study demonstrated a high level of off-label prescribing over time with respect to age and indication. The prescribing patterns underpin the need for further economic incentives for pharmaceutical companies to register pediatric indications, particular for off-patent products.

Dipeptidyl Peptidase-4 Inhibitor Induced Angioedema - An Overlooked Adverse Drug Reaction?

INTRODUCTION: Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzymeinhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl peptidase-4 inhibitors (gliptins) and angioedema. Dipeptidyl peptidase-4 inhibitors are antidiabetic drugs used to improve glycaemic control. They, as a class effect, inadvertently affect the degradation of the vasoactive kinins bradykinin and substance P, both of which can cause angioedema due to vasodilatation and increase in vascular permeability in the capillaries. OBJECTIVE: To assess the risk and pathomechanism of angioedema due to inhibition of dipeptidyl peptidase- 4 inhibitors when used as monotherapy and in combination with angiotensin converting enzymeinhibitors. METHOD: PubMed, Embase, the Cochrane Library, PubMed Central, Web of Science, Google Scholar and clinicaltrials.gov were searched using different combinations of keywords "angioedema", "dipeptidyl peptidase 4", "dipeptidyl peptidase 4 inhibitors", "gliptins", "bradykinin", "substance P" and "angiotensin converting enzyme-inhibitors". Original research papers were preferably used as references and their bibliographies were used to further the search for original research results. RESULTS: Both angiotensin converting enzyme and dipeptidyl peptidase-4 are major enzymes in the degradation pathway of bradykinin and substance P, and when inhibited pharmacologically - especially at the same time - the theoretical risk of angioedema is increased due to accumulation of vasoactive kinins. CONCLUSION: Treatment with dipeptidyl peptidase-4 inhibitors must be carefully considered and monitored especially during concurrent treatment with angiotensin converting enzyme-inhibitors or when treating patients with a known predisposition to angioedema.

A multi-national comparison of antipsychotic drug use in children and adolescents, 2005-2012.

Over the last decades, an increase in antipsychotic (AP) prescribing and a shift from first-generation antipsychotics (FGA) to second-generation antipsychotics (SGA) among youth have been reported. However, most AP prescriptions for youth are off-label, and there are worrying long-term safety data in youth. The objective of this study was to assess multinational trends in AP use among children and adolescents. A repeated cross-sectional design was applied to cohorts from varied sources from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006-2012. The annual prevalence of AP use was assessed, stratified by age group, sex and subclass (FGA/SGA). The prevalence of AP use increased from 0.78 to 1.03% in the Netherlands' data, from 0.26 to 0.48% in the Danish cohort, from 0.23 to 0.32% in the German cohort, and from 0.1 to 0.14% in the UK cohort. In the US cohort, AP use decreased from 0.94 to 0.79%. In the US cohort, nearly all ATP dispensings were for SGA, while among the European cohorts the proportion of SGA dispensings grew to nearly 75% of all AP dispensings. With the exception of the Netherlands, AP use prevalence was highest in 15-19 year-olds. So, from 2005/6 to 2012, AP use prevalence increased in all youth cohorts from European countries and decreased in the US cohort. SGA were favoured in all countries' cohorts.

Long-term patterns of adherence to medication therapy among patients with type 2 diabetes mellitus in Denmark: The importance of initiation.

AIMS: Poor adherence to medication therapy among type 2 diabetes patients is a clinical challenge. We aimed to determine which factors are associated with the three phases of long-term adherence to medication: initiation, implementation and discontinuation in a register-based study. METHODS: Adherence to six medicine groups (metformin, sulfonylureas, acetylsalicylic acid, thiazide diuretics, renin angiotensin system inhibitors, and statins) were analysed among 5,232 patients with type 2 diabetes at a tertiary referral hospital during 1998-2009. Rate-ratios of initiation of treatment, recurrent gaps in supply of medication, and discontinuation of treatment were analysed using Poisson regression. RESULTS: Poor initiation rather than poor implementation or discontinuation was the main contributor to medication nonadherence. Polypharmacy was a risk factor for slower initiation of treatment for all six medicine groups (rate ratio ranging 0.79 95%CI [0.72-0.87] to 0.89 95%CI [0.82-0.96] per already prescribed medicine), but once patients were in treatment, polypharmacy was not associated with recurrence of gaps in supply of medication, and polypharmacy was associated with lower risk of discontinuation (rate ratio ranging 0.93 95%CI [0.86-1.00] to 0.96 95%CI [0.93-0.99] per prescribed medicine). Other identified risk factors for slow initiation, poor implementation, and discontinuation were diabetes duration, younger age, and Turkish/Pakistani origin. DISCUSSION: This study showed that a risk factor does not necessarily have the same association with all three elements of adherence (initiation, implementation and discontinuation), and that efforts supporting patients introduced to more complex drug combinations should be prioritized.

International trends in antipsychotic use: A study in 16 countries, 2005-2014.

The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.

Specific Genes Associated with Adverse Events of Methylphenidate Use in the Pediatric Population: A Systematic Literature Review.

The aim of this study was to review empirical studies examining associations between candidate genes and adverse events (AEs) from methylphenidate (MPH) use in children and adolescents. The PubMed, EMBASE, CINAHL, and Web of Science databases were searched from their inception until March 2017. We included empirically based articles on pharmacogenetic studies in 0-17-year-old patients that investigated associations between specific candidate genes, their polymorphisms, and reported AEs. We extracted information about study design, setting, type of AE reporter, studied genes and their polymorphisms, age and gender, administered doses, method of genotyping, outcome measures, and main findings. A total of nine articles reporting information about four double-blind, placebo-controlled, cross-over studies and five open-label cohort studies were eligible for inclusion. Studies were published from 2006 onward and included a total of 998 patients (3-17-year-olds) diagnosed with attention-deficit hyperactivity disorder (ADHD). Studies predominantly involved males and lasted from 1 to 12 weeks. Studies used polymerase chain reaction and single nucleotide polymorphism genotyping methodology. Reported AEs were significantly associated with the following genes: appetite reduction (CES1*G); buccal-lingual movements (T1065G); diastolic blood pressure (ADRA2A Mspl C/C-GC); emotionality (DAT1*9/9); irritability (SNAP25 T1065G); picking (DRD4*7/DRD4*4); social withdrawal (DRD4*7/DRD4*4); somatic complaints (DAT1*10/10); tics (5-HTTLRP*S/L*L/L; SNAP25 T1065G); sadness (CES1*rsl12443580); and vegetative symptoms (5-HTTLPR). In conclusion, only few MPH pediatric pharmacogenetic studies were located, and large between-study heterogeneity was found. Studies were of naturalistic design and of short duration. They included small patient samples, poorly standardized treatment regimens, and limited outcome assessments. In the future, more pharmacogenomic studies in ADHD are needed, preferably using randomized, controlled study designs and of longer duration (more than 6 months).

Trends in ADHD medication use in children and adolescents in five western countries, 2005-2012.

Over the last two decades, the use of ADHD medication in US youth has markedly increased. However, less is known about ADHD medication use among European children and adolescents. A repeated cross-sectional design was applied to national or regional data extracts from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006-2012. The prevalence of ADHD medication use was assessed, stratified by age and sex. Furthermore, the most commonly prescribed ADHD medications were assessed. ADHD medication use prevalence increased from 1.8% to 3.9% in the Netherlands cohort (relative increase: +111.9%), from 3.3% to 3.7% in the US cohort (+10.7%), from 1.3% to 2.2% in the German cohort (+62.4%), from 0.4% to 1.5% in the Danish cohort (+302.7%), and from 0.3% to 0.5% in the UK cohort (+56.6%). ADHD medication use was highest in 10-14-year olds, peaking in the Netherlands (7.1%) and the US (8.8%). Methylphenidate use predominated in Europe, whereas in the US amphetamines were nearly as common as methylphenidate. Although there was a substantially greater use of ADHD medications in the US cohort, there was a relatively greater increase in ADHD medication use in youth in the four European countries. ADHD medication use patterns in the US differed markedly from those in western European countries.

Pain monitoring and medication assessment in elderly nursing home residents with dementia.

OBJECTIVE: To monitor pain intensity, pain symptoms, and medication use in elderly with dementia. METHODS: Nursing home residents above 65 years of age, diagnosed with dementia, and showing pain symptoms were included in the study. The patients' mental status was monitored through a mini-mental state examination score and observations of pain symptoms using Part 1 of the Mobilization-Observation-Behaviour-Intensity-Dementia-2 (MOBID-2) pain scale. Community pharmacists reviewed the patients' medication use, and the prescriptions were compared with guidelines for treatment of geriatric patients. Alterations to the patients' medicine use were forwarded to the general practitioners. FINDINGS: Sixty-one nursing home residents diagnosed with dementia were identified, 15 of these fulfilled the inclusion criteria, and 12 agreed to participate in the study. The mean age was 87 years of age (range: 77-96), and 42% of the residents were males. The patients' overall pain intensity was 83% for observations on the numeric pain rating scale (NRS) >0 and 67% for NRS ≥3. Most painful were the situations in which the residents were to mobilize their legs, turn around to both sides of the bed, and when sitting on the bed. The medication reviews identified a total of 95 individual prescriptions, and 33% of these were for nervous system medications, followed by medicines for the treatment of alimentary tract and metabolism disorders (31% of total). Eleven prescriptions for pain medicine were identified; the majority of these were for paracetamol and opioids. Seventeen proposals to patients' medication use were suggested, but the general practitioners accepted only 6% of these. CONCLUSION: This study indicates that the MOBID-2 pain scale in combination with medication reviews can be used as a tool for optimization of patients' medication use. However, we recommend the conduction of a larger-scale study in multiple settings, to validate our results and the generalizability of the findings.

Cutaneous Porphyrias: Causes, Symptoms, Treatments and the Danish Incidence 1989-2013.

Porphyrias are rare diseases caused by altered haem synthesis leading to the accumulation of different haem intermediates. Neurovisceral attacks may occur in acute porphyrias, while photosensitivity is the presenting symptom in cutaneous porphyrias. We present here an overview of symptoms and a flowchart for the diagnosis of cutaneous porphyrias, with recommendations for monitoring and an update of treatment options. From the Danish Porphyria Register, we present the incidences and approximate prevalences of cutaneous porphyrias within the last 25 years. A total of 650 patients with porphyria cutanea tarda were identified, 73 with erythropoietic protoporphyria, 9 with variegate porphyria, 4 with hereditary coproporphyria and one with congenital erythropoietic porphyria. The total incidence of all porphyrias was ~0.52/100,000 per year.

Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005-2012.

Following the FDA black box warning in 2004, substantial reductions in antidepressant (ATD) use were observed within 2 years in children and adolescents in several countries. However, whether these reductions were sustained is not known. The objective of this study was to assess more recent trends in ATD use in youth (0-19 years) for the calendar years 2005/6-2012 using data extracted from regional or national databases of Denmark, Germany, the Netherlands, the United Kingdom (UK), and the United States (US). In a repeated cross-sectional design, the annual prevalence of ATD use was calculated and stratified by age, sex, and according to subclass and specific drug. Across the years, the prevalence of ATD use increased from 1.3% to 1.6% in the US data (+26.1%); 0.7% to 1.1% in the UK data (+54.4%); 0.6% to 1.0% in Denmark data (+60.5%); 0.5% to 0.6% in the Netherlands data (+17.6%); and 0.3% to 0.5% in Germany data (+49.2%). The relative growth was greatest for 15-19 year olds in Denmark, Germany and UK cohorts, and for 10-14 year olds in Netherlands and US cohorts. While SSRIs were the most commonly used ATDs, particularly in Denmark (81.8% of all ATDs), Germany and the UK still displayed notable proportions of tricyclic antidepressant use (23.0% and 19.5%, respectively). Despite the sudden decline in ATD use in the wake of government warnings, this trend did not persist, and by contrast, in recent years, ATD use in children and adolescents has increased substantially in youth cohorts from five Western countries.

Switch in Therapy from Methylphenidate to Atomoxetine in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: An Analysis of Patient Records.

OBJECTIVE: The purpose of this study was to investigate therapy switching from methylphenidate (MPH) to atomoxetine (ATX) in a clinical sample of Danish children and adolescents with attention-deficit/hyperactivity disorder (ADHD); specifically, to determine the duration of MPH treatment before switching to ATX, and the reasons leading to a switch in therapy. METHODS: We included 55 patients with ADHD who switched from first-line MPH to second-line ATX during January 01, 2012 and May 15, 2014. Patient and treatment characteristics along with clinical reasons for switching therapy were extracted from individual patients' records. RESULTS: Mean duration of MPH treatment until switch to ATX was 11.2 months (range = 0.3-28.5 months); 36% of the patients switched within the first 6 months, 56% within the first year, and 76% within 1.5 years of initiating MPH; 24% continued MPH treatment for up to 2.5 years prior to switching. Most common reasons for switching were "adverse events" (AEs) (78%), "wish for more optimal day coverage" (24%), and "lack of efficacy" (16%). Other reasons for switching included "patient/parental request" (13%) and "noncompliance" (2%). Most common AEs leading to switch were psychiatric disorders (insomnia, aggression, tic, depression, anxiety) and decreased appetite. CONCLUSIONS: Our findings highlight the importance of continuous evaluation of the need for prescription switch to ATX in children and adolescents treated with MPH, taking into consideration various factors including potential AEs, non-optimal day coverage, lack of efficacy, patient/parental preferences, and noncompliance. These factors should be considered, not only at the initial stage of MPH treatment but throughout the whole treatment course.

Medication histories by pharmacy technicians and physicians in an emergency department.

BACKGROUND: Medication histories (MHs) obtained at the time of patients' admission to hospital are often incomplete, and lack of information about patients' actual medicine use can potentially lead to prescribing failures and serious adverse events. Uses of clinical pharmacists in obtaining MHs are beneficial, but due to limited economic resources clinical pharmacists cannot be present in every hospital ward, and therefore pharmacy technicians (PTs) could probably be trained in obtaining MHs. OBJECTIVE: To compare discrepancies in MHs obtained by physicians and PTs in an emergency department. Second to evaluate, whether PTs could assist and/or replace physicians in obtaining MHs. METHODS: The study was conducted in the emergency department at Svendborg Hospital, Denmark and patients treated with a minimum of three prescribed medicines were included. On patients' admission to hospital, physicians recorded the primary MHs, and within 48 h the secondary MHs were made by PTs. All MHs were conducted using standard guidelines. A clinical pharmacist reviewed the MHs, and based on these reviews, a final medication list was defined, and the MHs were compared to this. The discrepancies were registered with respect to type and therapeutic group (medicines). RESULTS: A total of 113 patients were included in this study, and data for 106 patients were analysed. On average, three discrepancies were detected for each patient in the primary MHs, and less than one discrepancy per patient in the secondary MHs. A total of 1075 prescriptions were registered, and for the physicians, 287 discrepancies (27 % of total prescriptions) were found, and for PTs the number was 28 (2 % of total prescriptions). The commonly detected discrepancy was "drug missing in the electronic patient record". The largest number of discrepancies was found for nervous system medications (ATC group N), medicines from ATC group A (alimentary tract and metabolism) and respiratory medicine (ATC group R). CONCLUSION: Fewer discrepancies in the MHs obtained by PTs than physicians were detected compared to standard medicine lists made by an experienced clinical pharmacist.

Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines.

OBJECTIVE: Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: "Combinations of oral blood-glucose lowering medicines" (A10BD), "dipeptidyl peptidase-4 (DDP-4) inhibitors" (A10BH), and "other blood glucose lowering medicines" (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment. METHODS: For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness and labeling status. FINDINGS: A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with "other blood glucose lowering medications," the remaining 2 (13%) with "DDP-4 inhibitors." CONCLUSION: Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about potentially serious and unlabeled ADRs.