Assessing short-term risk of ischemic stroke in relation to all prescribed medications

We examined the short-term risk of stroke associated with drugs prescribed in Norway or Sweden in a comprehensive, hypothesis-free manner using comprehensive nation-wide data. We identified 27,680 and 92,561 cases with a first ischemic stroke via the patient- and the cause-of-death registers in Norway (2004–2014) and Sweden (2005–2014), respectively, and linked these data to prescription databases. A case-crossover design was used that compares the drugs dispensed within 1 to 14 days before the date of ischemic stroke occurrence with those dispensed 29 to 42 days before the index event. A Bolasso approach, a version of the Lasso regression algorithm, was used to select drugs that acutely either increase or decrease the apparent risk of ischemic stroke. Application of the Bolasso regression algorithm selected 19 drugs which were associated with increased risk for ischemic stroke and 11 drugs with decreased risk in both countries. Morphine in combination with antispasmodics was associated with a particularly high risk of stroke (odds ratio 7.09, 95% confidence intervals 4.81–10.47). Several potentially intriguing associations, both within and across pharmacological classes, merit further investigation in focused, follow-up studies.

100Identification of a latitude gradient in the prevalence of Primary Biliary Cholangitis in Australia

Background Primary biliary cholangitis (PBC) is an autoimmune destructive condition of the gall bladder, with environmental factors like sun exposure implicated in its aetiology, similar to multiple sclerosis. PBC prevalence varies significantly and appears to have a positive latitudinal gradient. To determine whether there was a latitudinal gradient of PBC prevalence in Australia using two methods of prevalence estimation: private pathology anti-mitochondrial antibody (AMA) results, the primary diagnostic test for PBC, and ursodeoxycholic acid (UDCA) prescriptions, the sole pharmacological treatment for PBC. Methods We investigated the latitudinal variation in PBC prevalence across the states and territories of Australia (latitudinal range 18.0° to 42.7°S) using pathology-based (private pathology AMA results search (three of the major private pathology companies in Australia which cover 77% of all private pathology testing) and PBC-specific prescription databases (prescriptions for UDCA). Results Pathology-based PBC prevalence was significantly increased with latitude, such that the postcodes in the highest quintile of latitude (encompassing the south coastal areas of the Australian mainland and insular Tasmania (latitude range -37.75 to -42.72)) had 1.83-times higher frequencies than those in the lowest quintile (encompassing tropical and southern Queensland (latitude range -18.02 to -27.59). Analogous results were seen for state-based UDCA prescriptions, being 2.31-times higher in Tasmania than Queensland. Conclusions We have found for the first time that the prevalence of PBC significantly varies with latitude in Australia. While the most immediate mediating factors underlying this association would be ultraviolet radiation and vitamin D levels, studies to substantiate this mechanism are needed. Key messages In line with some other autoimmune conditions, PBC shows a significant positive latitudinal gradient, with nearly 2-times higher prevalence in the southernmost state than the northernmost.

Comparison of Two Different Analgesic Prescription Strategies and Healthcare Systems: Slovenia vs. the Netherlands

Background: Prescribing practice of pain medication is changing in the Netherlands; opioids are used more often instead of nonsteroidal anti-inflammatory drugs (NSAIDs), therefore we aimed to compare the use of pain medication with Slovenia which has stringent prescribing rules for strong opioids.Methods: We conducted a cohort study into national prescription databases of the Netherlands and Slovenia covering pharmacy claims between January 1, 2013 and December 31, 2019. In the analysis about 17 million Dutch and 2 million Slovenian residents were included.Findings: The use of opioids and NSAIDs was higher in Slovenia than in the Netherlands. More frequent use of opioids in Slovenia could be almost entirely explained by weak opioids (about 6% of the population), whereas they were prescribed 50% less frequently in the Netherlands. The opioid use has increased by about 20% in the Netherlands (4.85 and 6.00% of the population in 2013 and 2018, respectively), and the majority of this increase could be explained by strong opioids (4.05% in 2018), specifically, by oxycodone whose use increased by more than 2-fold between 2013 and 2019. In comparison, oxycodone was seldomly used in Slovenia (about 0.3% of the population received a prescription in a year).Interpretation: When medication use is controlled by stringent prescribing rules, like for strong opioids in Slovenia, the use is lower as compared to when such rules do not exist.

Viewpoint: do antipsychotics protect against early death? A critical view

In the past 15 years, researchers utilizing prescription databases to assess medication usage have concluded that antipsychotics reduce mortality in patients diagnosed with schizophrenia and other psychotic disorders. These findings stand in contrast to studies in non-psychiatric patients that have found that antipsychotics, because of their adverse effects on physical health, increase the risk of early death. A critical review of the evidence reveals that the worry remains. There is reason to conclude that antipsychotics contribute to the ‘mortality gap’ between the seriously mentally ill and the general population and that the database studies are plagued with methodological and reporting issues. Most importantly, the database studies tell of mortality rates within a drug-centered paradigm of care, which confounds any comparison of mortality risks when patients are on or off antipsychotics.

M199. COPY NUMBER VARIANCE (CNV) ANALYSIS TO DETERMINE OPTIMAL ANTIPSYCHOTIC DOSAGE IN SCHIZOPHRENIA: A PILOT STUDY

Background The relationship between genetic polymorphisms of antipsychotic drug-metabolizing agents and drug response has been thoroughly investigated and analyzed. However, from a pharmacokinetic standpoint, few studies have explored the relationship between Copy number variants (CNV) and antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosage and CNV in schizophrenia (SCZ) patients. Methods The current dosage of antipsychotic medications was collected from 263 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent(CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5–8 BeadChip Kit. Results The CNV analysis did not show that CNVs are associated with dosage variation for CPZe, PM %, and DDD. Discussion In this pilot sample, we investigated for the first time CNVs and standardized antipsychotic dosage. The relationship between CNV and optimal antipsychotic dosage has far reaching clinical implications. Further analysis is required that utilitze large prescription databases to build on the results presented in this pilot study.

Opioid prescribing habits differ between Denmark, Sweden and Norway – and they change over time

Background and aims The medical use of opioids in different countries is often subject to public concern and debate, frequently based on rough figures from prescription databases made for registration of consumption. However, public access to some of these databases allow for further exploration of the prescription data, which can be processed to increase knowledge and insight into national opioid prescribing-behavior. Denmark, Sweden and Norway are considered closely related with regard to health care and culture. So, this study aims to provide a more detailed picture of opioid prescribing and its changes in the three Scandinavian countries during 2006–2014, using public assessable prescription data. Methods Data on dispensed opioid prescriptions (ATC; N02A, and R05DA04) were downloaded from each country’s prescription-databases. The amounts of dispensed opioids were used as proxy for consumption or use of opioids. Potential differences between dispensed prescriptions and actual use cannot be drawn from these databases. Consumption-data were converted from defined daily doses (DDDs) to mg oral morphine equivalents (omeqs). Changes in the choice of opioid-types, consumption and number of users were presented using descriptive statistics and compared. Results Opioid users: during the whole period, Norway had the highest, and Denmark the lowest, number of opioid users/1,000 inhabitants. From 2006 to 2014 the numbers of users/1,000 inhabitants changed from 98 to 105 in Norway, from 66 to 75 in Denmark, and from 79 to 78 in Sweden. Opioid consumption/1,000 inhabitants: The results depended much on the unit of measurement. The differences between the countries in consumption/1,000 inhabitants were small when DDDs was used as unit, while using mg omeqs significant differences between the countries appeared. Denmark had a much higher consumption of omeqs per 1,000 inhabitants compared to Sweden and Norway. Opioid consumption/user: during the whole period, Norway had the lowest, and Denmark the highest consumption/user. In 2006, the annual average consumption/user was 1979, 3615, 6025 mg omeq/user in Norway, Sweden and Denmark, respectively. In 2014 the corresponding consumption was 2426, 3473, 6361 mg omeq/user. The preferred choices of opioid-types changed during the period in all three countries. The balance between use of weak or strong opioids showed more prominent changes in Norway and Sweden compared to Denmark. Conclusions This study has shown how public assessable opioid prescription data can provide insight in the doctors’ prescribing behavior, and how it might change over time. The amounts of dispensed opioids, opioid prescribing habits and changes were compared between the countries, and significant differences appeared. Within each country, the overall picture of opioid consumption appeared rather stable. Implications Studies like this can contribute to qualify the ongoing debates of use of opioids in different nations and to monitor effects of initiatives taken by health-care authorities and health-care policy-makers.

Opioid usage in Denmark, Norway and Sweden - 2006-2014 and regulatory factors in the society that might influence it

AimsTo relate changes in the number of opioid users in Denmark, Norway and Sweden during 2006-2014 to changes in national regulatory and economic incentive factors.MethodsThe material consists of data drawn from the national prescription databases in Denmark, Norway and Sweden. Data on the number of opioid users per 1000 inhabitants were collected for all ages, both sexes and for the period 2006-2014. Concomitant changes in regulatory or economic incentives were identified and related to the drug statistics.ResultsFor all opioids in the period 2006-2014 Denmark had the lowest number ofusers but the largest increase in users. Norway had the highest number of users but a lower increase. The number of users in Sweden was very stable showing no change in number of users.The number of morphine users in Denmark increased from 2009 to 2014. The number of users of oxycodone decreased from 2010 to 2014. The Danish health authorities recommended using morphine as first drug of choice in 2010 and warned about potential drug dependency of oxycodone in 2011.In Sweden the number of users of oxycodone increased over the period with the largest increase from 2012 to 2013. The number af tramadol users decreased from 2011. Prior to these changes tramadol was declared to be classified as an addictive drug 2011.ConclusionsChanges in the countries’ opioid use appeared in the public prescription-databases in a timely manner after introduction of national recommendations not to use oxycodone and prefer morphine as first choice, or classify tramadol as an addictive drug. National drug statistics show the end-result of the doctors’ prescribing behavior and the population’s use of opioids. Thorough investigation of prescription-data can help to detect and explain the interplay between culture, society and medical reasons for prescribing opioids.

Changes in opioid prescribing behaviour in Denmark, Sweden and Norway - 2006-2014

Aims A country’s use of opioids is frequently debated in the public, usually based on rough figures from prescription databases made for consumption registration purposes. However, these databases hold much more detailed information that can be processed to increase knowledge and insight into nationally opioid prescribing-behaviour. This study aims to provide a more detailed picture of opioid prescribing and its changes in Denmark, Sweden and Norway during 2006-2014. Methods Data on opioid-use (ATC; N02A) were downloaded from each country’s publically assessable prescription-databases. Consumption-data were converted from defined daily doses (DDDs) to mg oral morphine equivalents (omeqs). Changes in choice of opioid-types, use and number of users were presented using descriptive statistics and compared. Results Opioid users: During the whole period, Norway had the highest, and Denmark the lowest, number of opioid users/1000 inhabitants. In 2006, Norway, Sweden and Denmark had 98, 79, 66 users/1000 inhabitants. In 2014 the numbers were 105, 78, 75 users/1000 inhabitants, respectively. Opioid use/user: During the whole period, Norway had the lowest, and Denmark the highest use/user. In 2006, the mean use/user was 1979, 3615, 6025 mg omeq/user in Norway, Sweden and Denmark respectively. In 2014 the corresponding use was 2426,3473,6361 mg omeq/user. The preferred choices of opioid-types changed during the period for all three countries. The balance between use of weak or strong opioids showed more prominent changes for Norway and Sweden compared to Denmark. Conclusions Three nations, closely related in culture and geo graphically, showed significant differences and changes in opioid prescribing behaviour. This knowledge can easily be overlooked using the traditional way of presenting opioid consumption statistics. More detailed and clinically relevant presentation can increase the knowledge of doctors’ opioid prescribing behaviour, that can be related to changes in the society or health care system, like demography, legislation and guidelines from authorities.