Morten Rix Hansen

Comparison of the Five Danish Regions Regarding Demographic Characteristics, Healthcare Utilization, and Medication Use—A Descriptive Cross-Sectional Study

Background While Denmark is well known for its plethora of registers. Many studies are conducted on research databases that only cover parts of Denmark, and regional differences could potentially threaten these studies’ external validity. The aim of this study was to assess sociodemographic and health related homogeneity of the five Danish regions. Methods We obtained descriptive data for the five Danish regions, using publicly available data sources: Statbank Denmark, the Danish Ministry of Economic Affairs, and Medstat.dk. These data sources comprise aggregate data from four different nationwide registers: The Danish National Patient Register, The Danish Civil Registration System, The Danish Register of Medicinal Product Statistics, and The Danish National Health Service Register for Primary Care. We compared the Danish regions regarding demographic and socioeconomic characteristics, health care utilization, and use of medication. For each characteristic, one-year prevalence was obtained and analyses were performed for 2013 and 2008 to account for possible change over time. Results In 2013, 5,602,628 persons were living in Denmark. The mean age was 40.7 years in the entire Danish population and ranged between 39.6 to 42.4 years in the five regions (coefficient of variation between regions [CV] = 0.028). The proportion of women in Denmark was 50.4% (CV = 0.009). The proportion of residents with low education level was 28.7% (CV = 0.051). The annual number of GP contacts was 7.1 (range: 6.7–7.4, CV = 0.040), and 114 per 1,000 residents were admitted to the hospital (range: 101–131, CV = 0.107). The annual number of persons redeeming a prescription of any medication was 723 per 1,000 residents (range: 718–743, CV = 0.016). Analyses for 2008 showed comparable levels of homogeneity as for 2013. Conclusions We found substantial homogeneity between all of the five Danish regions with regard to sociodemographic and health related characteristics. Epidemiologic studies conducted on regional subsets of Danish citizens have a high degree of generalizability.

Effect of an In-Hospital Multifaceted Clinical Pharmacist Intervention on the Risk of Readmission: A Randomized Clinical Trial

Importance Hospital readmissions are common among patients receiving multiple medications, with considerable costs to the patients and society. Objective To determine whether a multifaceted pharmacist intervention based on medication review, patient interview, and follow-up can reduce the number of readmissions and emergency department (ED) visits. Design, Setting, and Participants This randomized clinical multicenter study (Odense Pharmacist Trial Investigating Medication Interventions at Sector Transfer [OPTIMIST]) enrolled patients from September 1, 2013, through April 23, 2015, with a follow-up of 6 months completed on October 31, 2015. Consecutive medical patients in an acute admission ward who were 18 years or older and who used 5 or more medications were invited to participate. Of 1873 patients invited to participate, 1499 (80.0%) accepted. The medication review and patient interview were conducted in the hospital and followed up in collaboration with primary care. Analysis was based on intention to treat. Interventions The patients were randomized into 3 groups receiving usual care (no intervention), a basic intervention (medication review), and an extended intervention (medication review, 3 motivational interviews, and follow-up with the primary care physician, pharmacy, and nursing home). Main Outcomes and Measures The prespecified primary outcomes were readmission within 30 or 180 days and ED visits within 180 days. The primary composite end point was readmission or an ED visit within 180 days. Secondary outcomes were drug-related readmissions within 30 and 180 days after inclusion, and all-cause mortality and drug-related mortality. Results A total of 1467 patients (679 men [46.3%] and 788 women [53.7%]; median age, 72 years; interquartile range, 63-80 years) were part of the primary analysis, including 498 randomized to usual care, 493 randomized to the basic intervention, and 476 randomized to the extended intervention. The extended intervention had a significant effect on the numbers of patients who were readmitted within 30 days (hazard ratio [HR], 0.62; 95% CI, 0.46-0.84) or within 180 days (HR, 0.75; 95% CI, 0.62-0.90) after inclusion and on the number of patients who experienced the primary composite end point (HR, 0.77; 95% CI, 0.64-0.93). The study showed a nonsignificant reduction in drug-related readmissions within 30 days (HR, 0.65; 95% CI, 0.39-1.09) and within 180 days (HR, 0.80; 95% CI, 0.59-1.08) after inclusion and in deaths (HR, 0.83; 95% CI, 0.22-3.11). The number needed to treat to achieve the primary composite outcome for the extended intervention (vs usual care) was 12. Conclusions and Relevance A multifaceted clinical pharmacist intervention may reduce the number of ED visits and hospital readmissions. Trial Registration clinicaltrials.gov Identifier: NCT03079375

The potential drug–drug interaction between proton pump inhibitors and warfarin

Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug–drug interaction is sparsely investigated in a clinical setting. The aim was to assess whether initiation of PPI treatment among users of warfarin leads to increased INR values.

SearCh for humourIstic and Extravagant acroNyms and Thoroughly Inappropriate names For Important Clinical trials (SCIENTIFIC): qualitative and quantitative systematic study

Objectives To describe the development of acronym use across five major medical specialties and to evaluate the technical and aesthetic quality of the acronyms. Design Acronyms obtained through a literature search of Pubmed.gov followed by a standardised assessment of acronym quality (BEAUTY and CHEATING criteria). Participants Randomised controlled trials within psychiatry, rheumatology, pulmonary medicine, endocrinology, and cardiology published between 2000 and 2012. Main outcome measures Prevalence proportion of acronyms and composite quality score for acronyms over time. Results 14 965 publications were identified, of which 18.3% (n=2737) contained an acronym in the title. Acronym use was more common among cardiological studies than among the other four medical specialties (40% v 8-15% in 2012, P<0.001). Except for within cardiology, the prevalence of acronyms increased over time, with the average prevalence proportion among the remaining four specialties increasing from 4.0% to 12.4% from 2000 to 2012 (P<0.001). The median combined acronym quality score decreased significantly over the study period (P<0.001), from a median 9.25 in 2000 to 5.50 in 2012. Conclusion From 2000 to 2012 the prevalence of acronyms in trial reports increased, coinciding with a substantial decrease in the technical and aesthetic quality of the acronyms. Strict enforcement of current guidelines on acronym construction by journal editors is necessary to ensure the proper use of acronyms in the future.

The Stop-Only-While-Shocking algorithm reduces hands-off time by 17% during cardiopulmonary resuscitation - a simulation study.

Introduction Reducing hands-off time during cardiopulmonary resuscitation (CPR) is believed to increase survival after cardiac arrests because of the sustaining of organ perfusion. The aim of our study was to investigate whether charging the defibrillator before rhythm analyses and shock delivery significantly reduced hands-off time compared with the European Resuscitation Council (ERC) 2010 CPR guideline algorithm in full-scale cardiac arrest scenarios. Methods The study was designed as a full-scale cardiac arrest simulation study including administration of drugs. Participants were randomized into using the Stop-Only-While-Shocking (SOWS) algorithm or the ERC2010 algorithm. In SOWS, chest compressions were only interrupted for a post-charging rhythm analysis and immediate shock delivery. A Resusci Anne HLR-D manikin and a LIFEPACK 20 defibrillator were used. The manikin recorded time and chest compressions. Results Sample size was calculated with an &agr; of 0.05 and 80% power showed that we should test four scenarios with each algorithm. Twenty-nine physicians participated in 11 scenarios. Hands-off time was significantly reduced 17% using the SOWS algorithm compared with ERC2010 [22.1% (SD 2.3) hands-off time vs. 26.6% (SD 4.8); P<0.05]. Conclusion In full-scale cardiac arrest simulations, a minor change consisting of charging the defibrillator before rhythm check reduces hands-off time by 17% compared with ERC2010 guidelines.

Using the “proportion of patients covered” and the Kaplan-Meier survival analysis to describe treatment persistence

Standard Kaplan‐Meier (KM) survival analysis is often used to study treatment persistence estimating the proportion of patients who have not yet experienced a treatment break by a given day after treatment initiation. This method only allows patients to be studied until their first treatment break. The “proportion of patients covered” (PPC) method is another approach to study treatment persistence. It measures the proportion of live patients currently covered by treatment. We aimed to describe the PPC method, show how the KM survival analysis and the PPC method can describe treatment persistence, and discuss the interpretation/application of the methods.

Cost-consequence analysis evaluating multifaceted clinical pharmacist intervention targeting patient transitions of care from hospital to primary care

Drug‐related problems are a common complication in the transition from hospital to primary care and are associated with morbidity and increased health care costs. In this study, we evaluated the cost and consequences of a comprehensive pharmaceutical intervention compared with usual care, comprised of a medication review and patient interview before discharge and follow‐up for polypharmacy patients.

Use of beta-blockers and risk of serious upper gastrointestinal bleeding: a population-based case-control study:

Background: Some studies indicate a reduced risk of serious upper gastrointestinal bleeding (UGIB) for users of beta-blockers, but the association remains to be confirmed in larger studies and characterized with respect to differences among beta-blockers. We aimed to assess whether beta-blocker use decreases the risk of UGIB. Methods: We conducted a register-based, population-based case-control study in Denmark. We identified cases with a first validated discharge diagnosis of UGIB during the period 1995–2006. Controls were selected by risk-set sampling in a ratio of 10:1. We estimated crude and adjusted odds ratios (ORs) of the association between current beta-blocker use and the risk of UGIB by using conditional logistic regression and further stratified by selective and non-selective beta-blockers, respectively. Results: We identified 3571 UGIB cases and 35,582 controls. Use of beta-blockers was not found to be associated with a decreased risk of UGIB (adjusted OR 1.10; 95% CI: 1.00–1.21). The association remained neutral after stratification by selective and non-selective beta-blockers, and by single beta-blocker substances. Similarly, we found no association between current beta-blocker use and the risk of UGIB within different subgroups. Conclusions: We found no association between beta-blocker use and UGIB.

Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting: Analysis of Age, Sex and Dose Concentration Relationships

Venlafaxine is a commonly used antidepressant agent. We aimed to provide detailed information on the associations between venlafaxine dose and concentrations of venlafaxine, by patient age and sex. From a therapeutic drug monitoring (TDM) database located at Odense University Hospital, Denmark, we identified all adults for whom the treating physician had requested clinical advice on the TDM result for venlafaxine between 2002 and 2012. We identified 1077 TDM samples of venlafaxine from 334 males and 743 females (median age 45 years), and the median daily dose was 225 mg. Median plasma concentration of venlafaxine and o‐desmethylvenlafaxine (ODV) was 306 nmol/L and 861 nmol/L, respectively. The median dose‐corrected serum level for venlafaxine was 1.49 nmol/L/mg., while the dose‐corrected serum level of men and women were 1.21 nmol/L/mg and 1.60 nmol/L/mg, respectively. The dose‐corrected sum of venlafaxine and ODV was 8.91 nmol/L/mg (IQR 6.56–12.26) versus 5.52 nmol/L/mg (IQR 4.16–7.52) for patients above 64 years and below the age of 65 years, respectively. Dose‐corrected plasma concentrations of venlafaxine and ODV are increased to a clinically significant degree in patients above the age of 64, and initiation of venlafaxine therapy in the elderly should be made cautiously and supported by drug measurements.

Modelling of endpoint postponement for all-cause mortality in statin trials

Background: Sudden discontinuation of some antihypertensive agents such as beta-blockers and centrally acting antihypertensive agents are associated with increased risk of acute coronary events. Objectives: The aim of this study was to assess the association between discontinuation of different antihypertensive agents and the risk of acute myocardial infarction (AMI). Methods: A nested case control study was performed in a cohort of antihypertensive drug users from the Utrecht Cardiovascular Pharmacogenetics (UCP) database. Within this cohort, patients who were hospitalized for first AMI were considered cases. Cases were matched (1 up to 4) to controls at the same AMI date (index date). Antihypertensive users were defined as current users if the index date fell within prescribed duration or as stoppers if this date fell outside the prescribed duration. According to recency of stopping, stoppers were divided into recent stoppers (≤90 days), intermediate-term stoppers (91-180 days), and longterm stoppers (>180 days). The study included only antihypertensive users who were specifically current users or stoppers of one antihypertensive agent. Logistic regression analysis was used to assess the association between the discontinuation of antihypertensive agents and the risk of AMI and to control for confounding. Results: We included 1245 cases and 4994 controls in our analysis. The risk of AMI was significantly increased with all stoppers of beta-blockers (adjusted OR: 1.54, 95%CI (1.25-1.90)), calcium channel blockers (CCBs) (adjusted OR: 2.25, 95%CI (1.53- 3.30)), and diuretics (adjusted OR: 1.76, 95%CI (1.24-2.48)) compared with current users. Moreover, the risk of AMI was significantly increased for longterm stoppers (beta-blockers, CCBs, angiotensinconverting enzyme inhibitors, and diuretics) and intermediate- term stoppers (beta-blockers and CCBs) versus current users. There was no difference in AMI risk between recent stoppers of antihypertensive agents versus current users. Conclusions: Discontinuation of antihypertensive agents increases the risk of AMI after more than 90 days of stopping. Adherence to antihypertensive agents plays an important role in reducing the risk of AMI in patients with hypertension.Background: It has been reported that patients with type 1 diabetes (T1DM) have a decreased lung function. Studies on the association of T1DM and asthma in children show controversial results. Objectives: The aim of this study was to quantify asthma medication use in children and adolescents with and without (reference cohort) T1DM 5 years before and after the onset of diabetes. Methods: A population-based cohort study was conducted in the Dutch PHARMO Record Linkage System. All children (1. Modelling of Endpoint Postponement for All-Cause Mortality in Statin Trials Morten Rix Hansen, Anton Pottegård, Asbjørn Hróbjartsson, Per Damkier, René D Christensen, Kasper Søltoft Larsen, Malene EL Kristensen, Palle M Christensen, Jesper Hallas. Clinical Pharmacology, University of Southern Denmark, Odense, Denmark; Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark; The Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark; Research Unit for General Practice, University of Southern Denmark, Odense, Denmark. Background: The average postponement of the outcome event has been proposed as a novel method to present the magnitude of effect for preventive medications. This measure has been shown to have better agreement with patient preferences than conventional outcomemeasures, including the “number needed to treat” (NNT), possibly because it is more intuitively understood. For some interventions, it may also provide a better theoretical frame for how benefit is distributed among participants than the NNT measure. The aim of this study was to present a novel method for modelling endpoint postponement (EP) from trial data and compare it with the usual approach of measuring the area between survival curves. We also present a formalized meta-analysis of modelled EP for all-cause mortality in statin trials. Methods: We identified 17 placebo-controlled statin trials that fulfilled our inclusion criteria. Eleven of these presented Kaplan–Meier curves for all-cause mortality. Average EP was calculated as the area between Kaplan–Meier curves by counting pixels on magnified prints for these 11 trials. The modelled EP was computed for all trials on the basis of (1) hazard ratio, relative risk or odds ratio; (2) the cumulative event rate in the untreated group; and (3) the trial’s running time. The underlying assumption was that the mortality was reasonably stable within the trials’ running time. The modelled EP was subjected to a meta-analysis, using inverse variance weighting in a random effect model. Results: EPswere generally small for estimates based on pixel-counting, 10 and 27days for trials both primary and secondary intervention that typically ran over 1.9– 6.1years. The modelled EPs varied between 2 and 34days. The difference between modeled EP and EP based on pixel-counting was between 8 and 12days. The results of the meta-analyses will be presented at the meeting. Conclusions: Based on these trial data, statin treatment results in a surprisingly small gain in average survival. Our modelled EP estimates agreed reasonably with EPs based on pixel-counting. The modeled EP is amenable to meta-analyses and may be a useful approach to presenting the benefit of preventive treatment. 2. Permanent User Bias in Case–Crossover Studies in Pharmacoepidemiology Jesper Hallas, Shirley V. Wang, Joshua J. Gagne, Sebastian Schneeweiss, Anton Pottegård. Clinical Pharmacology, University of Southern Denmark, Odense C, Denmark; Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA. Background: In pharmacoepidemiology, the case– crossover design is based on cases that have contrasting drug exposure at the time of an event and at a reference time in the past. If the drug in question should be taken permanently, only certain exposure patterns will occur. These patients cannot be unexposed at the event time and exposed at the reference time, while the opposite pattern can occur if the drug was initiated recently. The resulting odds ratio (OR) would thus be biased upward. As many drugs have a subpopulation of permanent users, this bias might pervade many case–crossover analyses of drug effects. Objectives: The aims of this study were to demonstrate this “permanent user bias” and to evaluate whether it can be remedied by including a control group (case–time–control design). Methods: Using nationwide Danish data resources, we conducted case–crossover and case–time–control analyses for combinations of three exposures that are