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Background: Poor medication adherence is a well-recognized problem, and behavior change techniques (BCTs) have shown promise in improving patient adherence to prescribed drug treatment. Through the utilization of medication adherence technologies (MATech), these BCT interventions could be delivered effectively in a person-centered way. MATech can be defined as systems, services or physical devices (hardware), with a digital component, used to support patients in their drug utilization. However, there is a lack of knowledge regarding their availability and to what extent they apply evidence-based BCTs., Purpose: This study aimed to identify and describe MATech with BCT interventions available in the Swedish language., Methods: A cross-sectional survey study was conducted in 2023. After identifying potential MATech developers by contacting umbrella organizations in the private sector, public agencies and regions, and conducting an app search, a survey was distributed to 381 potential MATech developers. Included MATech were in Swedish, used by patients, incorporated a BCT intervention, and had survey response from the developer. The survey was based on the BCT taxonomy and the framework of attributes from the COST ENABLE project, and included questions regarding BCT features. Following correspondence with 189 potential developers, 32 with products of interest responded to the survey, and 21 MATech were identified (12 standalone software and nine hardware solutions)., Results: Among the 21 MATech identified, nine were hardware and ten were specifically designed for a particular disease or medication. The majority of technologies incorporated BCTs of reminding the patient to take the medication (81%), information about the treatment (71%) and providing feedback on the monitoring of medication adherence or clinical outcomes (76%)., Conclusion: Swedish-language MATech employing BCTs are available, encompassing both hardware and software solutions. There is a need to enhance the visibility of these technologies, enabling patients to discover and utilize the support they provide., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ekenberg et al.)

Objectives: Antihypertensives reduce the risk of myocardial infarction and stroke. Restrictions during the COVID-19 pandemic limited access to healthcare, which may have had a negative impact on drug prescribing. This study aimed to assess the effect of the COVID-19 pandemic on the initiation of antihypertensive drugs., Design: Interrupted time series study using a segmented linear regression model., Setting: Swedish population assessed through linked national healthcare registers., Participants: 720 300 new users of antihypertensives., Intervention: March 2020, COVID-19 pandemic onset., Main Outcomes Measures: The change in the initiation of antihypertensives expressed as monthly cumulative incidence, stratified by age and sex. Data on dispensed prescriptions of diuretics, beta-blockers, calcium channel blockers, ACE inhibitors (ACEi) and angiotensin receptor blockers were extracted from the Swedish Prescribed Drug Register, from March 2018 to November 2021. Initiation (new use) was defined as having no previous dispensations before March 2019. Monthly cumulative incidence in March 2019-November 2021 was calculated as the number of patients initiating each drug class in each month divided by the population., Results: The start of the pandemic was associated with an immediate drop in the initiation of any antihypertensive, but no sustained effects were observed, as the incidence continued to increase in the postinterruption period by +0.02% each month in both sexes. The immediate drop was statistically significant for ACEi in both sexes and all antihypertensive classes except diuretics in patients >65 years. А significant postintervention trend change was observed for initiation of diuretics (+0.013% overall), driven mainly by a significant increase in patients >65 years. Similar findings were also observed for diuretics in females (+0.02%) and ACEi (+0.03%) in patients >65 years., Conclusions: The pandemic had an immediate negative short-term effect, but we found no major long-term negative influence of the COVID-19 pandemic on initiation of any type of antihypertensive drugs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Age is a major risk factor for atherosclerotic cardiovascular disease (CVD) and death, but there has been a debate about benefit-risk of statin treatment in the elderly with limited evidence on benefits for primary prevention, while there is strong evidence for its use in secondary prevention., Aim: The aim of this study was to provide an overview of statin utilization in primary and secondary prevention for patients 75-84 years and ≥ 85 years in the Swedish capital Region Stockholm in 2019., Methods: This is a cross-sectional study based on the regional healthcare database VAL containing all diagnoses and dispensed prescription drugs for all 174,950 inhabitants ≥ 75 years old in the Stockholm Region. Prevalence and incidence were analyzed by sex, age, cardiovascular risk, substance, and the intensity of treatment., Results: A total of 35% of all individuals above the age of 75 in the region were treated with statins in 2019. The overall incidence in this age group was 31 patients per 1000 inhabitants. Men, individuals 75-84 compared to ≥ 85 years of age, and those with higher cardiovascular risk were treated to a greater extent. Simvastatin was used primarily by prevalent users and atorvastatin by incident users. The majority was treated with moderate-intensity dosages and fewer women received high intensity treatment., Conclusions: Statins are widely prescribed in the elderly. Physicians seem to consider individual cardiovascular risk when deciding to initiate statin treatment for elderly patients, but here may still be some undertreatment among high-risk patients (especially women and elderly 85 + years) and some overtreatment among patients with low-risk for CVD., (© 2024. The Author(s).)

Background and Aims: While the rationale for coronavirus disease 2019 (COVID-19) vaccination is to reduce complications and overall mortality, some cardiovascular complications from the vaccine itself have been demonstrated. Myocarditis and pericarditis are recognized as rare acute adverse events after mRNA vaccines in young males, while evidence regarding other cardiovascular events remains limited and inconsistent. This study assessed the risks of several cardiovascular and cerebrovascular events in a Swedish nationwide register-based cohort., Methods: Post-vaccination risk of myocarditis/pericarditis, dysrhythmias, heart failure, myocardial infarction, and cerebrovascular events (transient ischaemic attack and stroke) in several risk windows after each vaccine dose were assessed among all Swedish adults (n = 8 070 674). Hazard ratios (HRs) with 95% confidence intervals (95% CIs) compared with unvaccinated were estimated from Cox regression models adjusted for potential confounders., Results: For most studied outcomes, decreased risks of cardiovascular events post-vaccination were observed, especially after dose three (HRs for dose three ranging from .69 to .81), while replicating the increased risk of myocarditis and pericarditis 1-2 weeks after COVID-19 mRNA vaccination. Slightly increased risks, similar across vaccines, were observed for extrasystoles [HR 1.17 (95% CI 1.06-1.28) for dose one and HR 1.22 (95% CI 1.10-1.36) for dose two, stronger in elderly and males] but not for arrhythmias and for transient ischaemic attack [HR 1.13 (95% CI 1.05-1.23), mainly in elderly] but not for stroke., Conclusions: Risk of myopericarditis (mRNA vaccines only), extrasystoles, and transient ischaemic attack was transiently increased after COVID-19 vaccination, but full vaccination substantially reduced the risk of several more severe COVID-19-associated cardiovascular outcomes, underscoring the protective benefits of complete vaccination., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cardiovascular diseases are the main causes of death, and statins can reduce the risk of major vascular events. Lithuania is among the European countries with the highest cardiovascular mortality despite a rapidly increasing use of statins. Previous reviews have shown the problem of poor patient adherence, but there are limited studies from Eastern European countries. The aim of this study was to evaluate treatment persistence in new users of statins in Lithuania and to investigate factors associated with persistence. Dispensed prescriptions from patients aged >18 years old initiated on statins in 2018-2019 were included, and data were obtained from a national health insurance fund. Persistence was assessed by the proportion of patients who still had statins dispensed 1 year after the first dispensing. Factors associated with persistence were assessed using logistic regression. A total of 104 726 patients (41.3% men) were initiated on statin treatment. Only 41% of them continued statin use 1 year after initiation. Factors associated with higher persistence rate were older age, higher dose of statin, use of other medicines and use of statins as secondary prevention. Low persistence to statin therapy needs to be recognized by healthcare workers, pharmacists and policy makers to address this problem., (© 2024 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Aims: Norway and Sweden had different early pandemic responses that may have impacted mental health management. The aim was to assess the impact of the early COVID-19 pandemic on mental health-related care., Methods: We used national registries in Norway and Sweden (1 January 2018-31 December 2020) to define 2 cohorts: (i) general adult population; and (ii) mental health adult population. Interrupted times series regression analyses evaluated step and slope changes compared to prepandemic levels for monthly rates of medications (antidepressants, antipsychotics, anxiolytics, hypnotics/sedatives, lithium, opioid analgesics, psychostimulants), hospitalizations (for anxiety, bipolar, depressive/mood, eating and schizophrenia/delusional disorders) and specialist outpatient visits., Results: In Norway, immediate reductions occurred in the general population for medications (-12% antidepressants to -7% hypnotics/sedatives) except for antipsychotics; and hospitalizations (-33% anxiety disorders to -17% bipolar disorders). Increasing slope change occurred for all medications except psychostimulants (+1.1%/month hypnotics/sedatives to +1.7%/month antidepressants); and hospitalization for anxiety disorders (+5.5%/month), depressive/mood disorders (+1.7%/month) and schizophrenia/delusional disorders (+2%/month). In Sweden, immediate reductions occurred for antidepressants (-7%) and opioids (-10%) and depressive/mood disorder hospitalizations (-11%) only with increasing slope change in psychostimulant prescribing of (0.9%/month). In contrast to Norway, increasing slope changes occurred in specialist outpatient visits for depressive/mood disorders, eating disorders and schizophrenia/delusional disorders (+1.5, +1.9 and +2.3%/month, respectively). Similar changes occurred in the pre-existing mental health cohorts., Conclusion: Differences in early COVID-19 policy response may have contributed to differences in adult mental healthcare provision in Norway and Sweden., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aims: To compare statin utilization and ischemic heart disease (IHD) mortality trends in Lithuania and Sweden and to assess correlations between the total utilization of statins and IHD mortality., Methods: An ecological study assessing time trends in statin utilization (DDDs per 1000 inhabitants per day; DDD/TID) and IHD mortality in Lithuania and Sweden between 2000 and 2020. Statin utilization data in Lithuania were wholesale trade data, and Swedish data were drugs dispensed at pharmacies. IHD mortality data were extracted from national databases as rates per 100 000 inhabitants. Associations between statin utilization and IHD mortality in Lithuania and Sweden were examined using Spearman's rank and Pearson's correlation coefficients, respectively., Results: Statin utilization increased from 16.8 to 135.8 DDD/TID in Sweden and from 0.2 to 61.8 DDD/TID in Lithuania between 2000 and 2020. Medium intensity was the most common statin dosage in Lithuania, while Sweden used more high intensity than moderate-intensity statins from 2017. IHD mortality in Lithuania remained high between 2000 and 2020 (from 359.1 to 508.8 deaths per 100 000 population), while it decreased markedly in Sweden (from 226.87 to 88.7 deaths per 100 000 population). IHD mortality and statin utilization were inversely correlated in Sweden (r = -0.993, P < 0.001), while a positive correlation was found in Lithuania (rs = 0.871, P < 0.001)., Conclusion: Despite the growing statin utilization in both countries, Lithuania recorded a slight increase in IHD mortality rates unlike the situation in Sweden. This indicates room for improvement in the management of modifiable cardiovascular risk factors in Lithuania including how statins are prescribed and used in clinical practice., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)

Purpose: This study aims to determine initiation and persistence for patients with type 2 diabetes receiving their first prescription of an antidiabetic agent and the associations with socioeconomic factors., Methods: A cohort study including 8515 patients with type 2 diabetes who were prescribed their first antidiabetic medication between 2012 and 2019 in Uppsala, Sweden, was followed during 2 years. Medical records were linked to national registers on dispensed drugs and socioeconomic data. Adherence was assessed based on patients' medication claims within 30 days of prescription (initiation) and continued claims after 24 months (persistence). Multivariable logistic regression was used to determine the associations with the socioeconomic factors age, sex, living status, country of birth, education, occupation, and income., Results: Within 30 days, 92.4% of the patients claimed their first prescription, and 64.0% were still being dispensed the initially prescribed medication after 24 months. Unemployed patients had lower initiation rates, and women had lower persistence rates. Factors associated with both low initiation and persistence were low income, young or old age, birth outside Europe, and being prescribed other diabetes drugs than metformin monotherapy., Conclusion: Socioeconomic factors have different impact on the initiation of a new medication and the persistence to treatment in type 2 diabetes. It is important to acknowledge these differences to develop appropriate interventions to improve medication nonadherence., (© 2023. The Author(s).)

Purpose: Few studies explored what patients initiated on blood pressure medication in primary care think about their disease and their medications. The aim of this study was to gain an understanding of hypertensive patients' views on and experiences of hypertension and the use of antihypertensive medications., Methods: A qualitative study based on open-ended questions from a survey on medication adherence, which captured treated hypertensive patients' perspective on their condition and treatment. Data were collected for 219 patients on antihypertensive medication, ≥ 30 years old, who consulted 25 primary health care centers in Stockholm, Sweden, during 2016. Thematic analysis with both inductive and deductive approach was applied., Results: We identified 21 codes from the data and grouped them under the World Health Organization's five dimensions of adherence: condition-, therapy-, health care team and system-, patient-, and socioeconomic-related factors. The analyses revealed that many patients with hypertension have limited knowledge of their disease, are afraid of drug side effects and experience various issues in primary health care that may negatively impact adherence, including short doctor appointments, prescribing without communication and room for improvement in individualization of therapy and a person-centered approach., Conclusion: Many patients with hypertension have limited understanding of their hypertension and fear of adverse events from their antihypertensive medications. There is also room for improvement in how the patients are managed in primary health care. Interventions should focus on these issues to promote a better blood pressure target achievement., Competing Interests: TK reports research grants to Karolinska Institutet from Medtronic and ReCor Medical; all outside the submitted work. The other authors report no conflicts of interest., (© 2023 Malkon et al.)

Aims: To develop a disease risk score for COVID-19-related hospitalization and mortality in Sweden and externally validate it in Norway., Method: We employed linked data from the national health registries of Sweden and Norway to conduct our study. We focused on individuals in Sweden with confirmed SARS-CoV-2 infection through RT-PCR testing up to August 2022 as our study cohort. Within this group, we identified hospitalized cases as those who were admitted to the hospital within 14 days of testing positive for SARS-CoV-2 and matched them with five controls from the same cohort who were not hospitalized due to SARS-CoV-2. Additionally, we identified individuals who died within 30 days after being hospitalized for COVID-19. To develop our disease risk scores, we considered various factors, including demographics, infectious, somatic, and mental health conditions, recorded diagnoses, and pharmacological treatments. We also conducted age-specific analyses and assessed model performance through 5-fold cross-validation. Finally, we performed external validation using data from the Norwegian population with COVID-19 up to December 2021., Results: During the study period, a total of 124,560 individuals in Sweden were hospitalized, and 15,877 individuals died within 30 days following COVID-19 hospitalization. Disease risk scores for both hospitalization and mortality demonstrated predictive capabilities with ROC-AUC values of 0.70 and 0.72, respectively, across the entire study period. Notably, these scores exhibited a positive correlation with the likelihood of hospitalization or death. In the external validation using data from the Norwegian COVID-19 population (consisting of 53,744 individuals), the disease risk score predicted hospitalization with an AUC of 0.47 and death with an AUC of 0.74., Conclusion: The disease risk score showed moderately good performance to predict COVID-19-related mortality but performed poorly in predicting hospitalization when externally validated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Shakibfar, Zhao, Li, Nordeng, Lupattelli, Pavlovic, Sandve, Nyberg, Wettermark, Hajiebrahimi, Andersen and Sessa.)

Purpose: Database heterogeneity can impact effect estimates. Harmonisation provided by common protocols and common data models (CDMs) can increase the validity of pharmacoepidemiologic research. In a case study measuring the changes in the safety and effectiveness of stroke prevention therapy after the introduction of direct oral anticoagulants (DOACs), we performed an international comparison., Methods: Using data from Stockholm, Denmark, Scotland and Norway, harmonised with a common protocol and CDM, two calendar-based cohorts were created: 2012 and 2017. Patients with a diagnosis code of atrial fibrillation 5 years preceding the 1-year cohort window were included. DOAC, vitamin K antagonist and aspirin treatment were assessed in the 6 months prior to the start of each year while strokes and bleeds were assessed during the year. A Poisson regression generated incidence rate ratios (IRRs) to compare outcomes from 2017 to 2012 adjusted for changes in individual-level baseline characteristics., Results: In 280 359 patients in the 2012 cohort and 356 779 in the 2017 cohort, treatment with OACs increased on average from 45% to 65%, while treatment with aspirin decreased from 30% to 10%. In all countries except Scotland, there were decreases in the risk of stroke and no changes in bleeding risk, after adjustment for changes in baseline characteristics. In Scotland, major bleeding (IRR 1.09, 95% confidence interval [CI] [1.00; 1.18]) and intracranial haemorrhage (IRR 1.31, 95% CI [1.13; 1.52]) increased from 2012 to 2017., Conclusions: Stroke prevention therapy improved from 2012 to 2017 with a corresponding reduction in stroke risk without increasing the risk of bleeding in all countries, except Scotland. The heterogeneity that remains after methodological harmonisation can be informative of the underlying population and database., (© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: A cross-national comparative (CNC) study about opioid utilization would allow the identification of strategies to improve pain management and mitigate risk. However, little is known about the accessibility and validity of information in healthcare databases internationally. This study aimed to identify the feasibility of using healthcare databases to conduct a CNC study of opioid utilization and its associated consequences., Methods: A cross-sectional survey was launched in March 2018, including experts interested in CNC studies comparing opioid utilization by purposeful sampling. An electronic survey was used to collect database characteristics, medicine information, and linkage information of each aggregate-level dataset (AD) and individual patient-level dataset (IPD)., Results: Overall, participants from 21 geographical regions reported 18 ADs and 19 IPDs. Information on dispensed medications is available from 17 ADs and 17 IPDs. Of the 16 ADs that include primary care settings, only 9 ADs can obtain information from secondary care settings. Fourteen IPDs included patients' characteristics or could be retrieved from linkage databases. Although most ADs are publicly accessible (n = 13), only five IPDs can be accessed without extra cost., Conclusion: Most ADs could be used to report opioid utilization in a primary care setting. IPDs with linkage databases should be applied to identify potential determinants, clinical outcomes, and policy impact. Data access restrictions and governance policies across jurisdictions can be challenging for timely analysis and require further collaboration., (© 2023 John Wiley & Sons Ltd.)

Background: Pharmaceuticals treat and prevent diseases but can pose a risk to organisms, predominantly in aquatic environments. The use of pharmaceuticals is predicted to increase due to, among other factors, a growing and aging population and climate change. Therefore, it is important to develop mitigation strategies to prevent pharmaceutical residues from entering the environment. In Sweden, two public pharmaceutical web-based knowledge supports provide information on the environmental impact of pharmaceuticals., Objective: To explore stakeholder perspectives, use and future opportunities related to two webbased knowledge supports publicizing environmental information on pharmaceuticals., Methods: Stakeholders identified for their experience with the knowledge supports, pharmaceutical policy, and stakeholder collaboration were recruited using purposive and snowball sampling for semi-structured interviews. Interviews were conducted in person or via video calls. Respondents included twenty-one representatives from the pharmaceutical industry, regional and national authorities, academia, and an independent research institute. Interview transcripts were analyzed using content analysis., Results: Respondents valued having environmental information on pharmaceuticals publicly accessible on two well-known pharmaceutical knowledge supports. The knowledge supports have been used in Sweden and internationally. Perceived differences were recognized between the impact and perspectives of the two knowledge supports with a general preference for the Janusinfo knowledge support. The preference was especially identified regarding transparency and the use of the information in clinical practice. Barriers to impact were a lack of resources and decision-making criteria. Respondents believed that the impact and value of the knowledge supports could be improved with more authority involvement., Conclusion: Public knowledge support providing environmental information on pharmaceuticals has been valuable across sectors, especially, among Drug and Therapeutics Committees. We believe the results from this study could be useful for other countries interested in implementing a similar system., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Pharmaceuticals can reach the environment at all stages of their lifecycle and accumulate in the ecosystem, potentially reaching toxic levels for animals and plants. In recent years, efforts have been made to map and control this hazard. Assessing country-specific environmental risks could drive regulatory actions towards eco-friendlier drug utilization and disposal practices. By starting from a list of 25 environmentally hazardous pharmaceuticals developed by Region Stockholm, we integrated eco-toxicological and 2019-2021 Italian drug utilization data to estimate the environmental impact of pharmaceuticals in Italy. We calculated the risk as the ratio between the predicted environmental concentration (PEC) and the predicted no-effect concentration (PNEC). We found a high risk for levonorgestrel, ciprofloxacin, amoxicillin, azithromycin, venlafaxine, sertraline and diclofenac and a moderate risk for ethinyloestradiol, oestradiol and clarithromycin. This analysis can be periodically performed to identify the pharmaceuticals with the highest risk for the environment and ascertain if containment measures should be implemented., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Two publicly available Swedish knowledge support systems, "Pharmaceuticals and Environment" on Janusinfo.se and Fass.se, provide environmental information on pharmaceuticals. Janusinfo is provided by the public healthcare system in Stockholm and Fass is provided by the pharmaceutical industry. The objectives of this study were to investigate the experiences among Swedish Drug and Therapeutics Committees (DTCs) with using the databases, retrieve development proposals for these, and investigate the DTCs' challenges with working with pharmaceuticals in the environment., Methods: A cross-sectional survey with 21 questions, both closed and open-ended, was distributed electronically in March 2022 to Sweden's 21 DTCs. Descriptive statistics and inductive categorization were used for the analysis., Results: A total of 132 respondents from 18 regions filled out the survey. The average regional response rate was 42%. The DTCs used the knowledge supports to consider environmental aspects of pharmaceuticals in their formularies and in education. Respondents were more familiar with Janusinfo compared to Fass but appreciated the availability of both. The DTCs especially valued the concrete proposals for certain active pharmaceutical ingredients on Janusinfo. Respondents requested that all medicinal products have environmental information on Fass. Challenges included lack of data, lack of transparency from the pharmaceutical industry and difficulties considering the environmental aspect of pharmaceuticals in their healthcare practice. Respondents wanted more knowledge, clear messages, and legislation to support their work to reduce the negative environmental impact of pharmaceuticals., Conclusions: This study demonstrates that knowledge supports for environmental information on pharmaceuticals are valuable for the DTCs in Sweden, but the respondents experienced challenges in their work in this field. The study can provide insights to those in other countries interested in considering environmental aspects in their formulary decision-making., (© 2023. The Author(s).)

Medication adherence is a key precondition of the effectiveness of evidence-based therapies. However, in real-life settings, non-adherence to medication is still very common. This leads to profound health and economic consequences at both individual and public health levels. The problem of non-adherence has been extensively studied in the last 50 years. Unfortunately, with more than 130,000 scientific papers published on that subject so far, we are still far from finding an ultimate solution. This is, at least partly, due to fragmented and poor-quality research that has been conducted in this field sometimes. To overcome this deadlock, there is a need to stimulate the adoption of best practices in medication adherence-related research in a systematic way. Therefore, herein we propose the establishment of dedicated medication adherence research Centres of Excellence (CoEs). These Centres could not only conduct research but could also create a profound societal impact, directly serving the needs of patients, healthcare providers, systems and economies. Additionally, they could play a role as local advocates for good practices and education. In this paper, we propose some practical steps that might be taken in order to establish such CoEs. We describe two success stories, i.e., Dutch and Polish Medication Adherence Research CoEs. The COST Action "European Network to Advance Best practices & technoLogy on medication adherencE" (ENABLE) aims to develop a detailed definition of the Medication Adherence Research CoE in the form of a list of minimal requirements regarding their objectives, structure and activities. We hope that it will help to create a critical mass and catalyse the setup of regional and national Medication Adherence Research CoEs in the near future. This, in turn, may not only increase the quality of the research but also raise the awareness of non-adherence and promote the adoption of the best medication adherence-enhancing interventions.

The clinical support system Electronic Expert Support (EES) is available at all pharmacies in Sweden to examine electronic prescriptions when dispensing to prevent drug-related problems (DRPs). DRPs are common, and result in patient suffering and substantial costs for society. The aim of this research was to study the use of EES for the pediatric population (ages 0-12 years), by describing what types of alerts are generated for potential DRPs, how they are handled, and how the use of EES has changed over time. Data on the number and categories of EES analyses, alerts, and resolved alerts were provided by the Swedish eHealth Agency. The study shows that the use of EES has increased. The most common type of alert for a potential DRP among pediatric patients was regarding high doses in children (30.3% of all alerts generated). The most common type of alert for a potential DRP that was resolved among pediatrics was therapy duplication (4.6% of the alerts were resolved). The most common reason for closing an alert was dialogue with patient for verification of the treatment (66.3% of all closed alerts). Knowledge of which type of alerts are the most common may contribute to increased prescriber awareness of important potential DRPs.

Background: Multimorbidity of mental and physical disorders may be common. Our objectives were to estimate the prevalence of mental disorders and determine physical-mental multimorbidity relationships adjusted for sex and age within a primary care population in Region Stockholm, Sweden., Methods: From 2.4 million Region Stockholm inhabitants, we included adult patients with ≥ 1 primary care consultation from 2013 through 2017. We clustered 40 physical diagnoses into 9 categories and grouped mental disorders into mild-moderate (i.e., depression, anxiety, stress disorder, sleep disturbance) or severe (i.e., bipolar disorder, schizophrenia)., Results: Of 1 105 065 patients, mean age was 49 years, 56% were females, and nearly one-third had a mental disorder (97% mild-moderate). Adjusted odds ratios (AOR) for mild-moderate and severe mental disorders were highest in patients with alcohol abuse (AOR=3.7, 95% CI 3.6-3.8; AOR=7.2, 95% CI 6.7-7.6, respectively) vs. those with no abuse. Higher odds for either level of mental comorbidity occurred in patients with chronic heart failure (CHF), cerebrovascular disease, Transient ischemic attack (TIA), Chronic obstructive pulmonary disease (COPD), Gastroesophageal reflux disease- irritable bowel syndrome (GERD-IBS), chronic pain, dementia, nicotine dependence, and Parkinson's disease. For mild-moderate mental disorders, AOR in males was highest (1.45) at age 28 and was below 1.0 after age 46; AOR in females was highest (1.30) at age 38 and was below 1.0 after age 38. For severe mental disorders, AOR was below 1.0 after age 58 in males and after age 62 in females., Conclusion: Physical-mental multimorbidity was common in primary care patients in Sweden, with the highest odds occurring in those who were female, younger, and/or had an alcohol abuse disorder., Competing Interests: Conflict of Interest Statement The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We estimated real-world vaccine effectiveness (VE) against COVID-19 infection, hospitalization, ICU admission, and death up to 13 months after vaccination. VE before and after the emergence of Omicron was investigated., Methods: We used registered data from the entire Swedish population above age 12 ( n = 9,153,456). Cox regression with time-varying exposure was used to estimate weekly/monthly VE against COVID-19 outcomes from 27 December 2020 to 31 January 2022. The analyses were stratified by age, sex, and vaccine type (BNT162b2, mRNA-1273, and AZD1222)., Results: Two vaccine doses offered good long-lasting protection against infection before Omicron (VE were above 85% for all time intervals) but limited protection against Omicron infection (dropped to 43% by week four and no protection by week 14). For severe COVID-19 outcomes, higher VE was observed during the entire follow-up period. Among individuals above age 65, the mRNA vaccines showed better VE against infection than AZD1222 but similar high VE against hospitalization., Conclusions: Our findings provide strong evidence for long-term maintained protection against severe COVID-19 by the basic two-dose schedule, supporting more efforts to encourage unvaccinated persons to get the basic two doses, and encourage vaccinated persons to get a booster to ensure better population-level protection.

Objective: To describe consumption of antidepressants in Brazil through dispensing data from pharmacy retail outlets, in between 2011 and 2017, and explore the relationship between consumption patterns and changing economic context during this period., Methods: A time-series analysis of dispensing data from pharmacy retail outlets was carried out considering 10 commonly used antidepressants. DDDs/1000 inhabitants/year for each drug were calculated for each quarter. Ttime-series graphs were constructed to analyze the volumes of drugs purchasedRelationship between economic context and consumption was assessed using the following indicators: annual percent change in Gross Domestic Product (GDP), public debt (% of GDP), and annual net savings (in billions of Brazilian reais - BRL)., Results: Overall consumption of antidepressants increased over the study period despite a sharp fall of -3.55% in annual percent change in GDP, negative net annual savings of -53.568 BRL, and an increase in public debt exceeding 32% of the GDP during the economic crisis of 2015., Conclusion: Consumption of antidepressants from pharmacy retail outlets increased even within a context of economic crisis, which may be a reflection of the disease burden in Brazil. Health budget cuts due to the economic crisis may be directing users to out-of-pocket expenses, deepening social inequalities.

Due to the Russian invasion, which started on 24 February 2022, the Ukrainian healthcare system is facing multiple challenges. A great number of healthcare facilities have been destroyed, while availability of other ones is often limited due to a lack of qualified medical staff. Certain services, e.g. cancer therapies, have been seriously disrupted. Moreover, millions of Ukrainians with chronic conditions are also suffering as due to war-related problems with execution of their long-term therapies. Availability of drugs is particularly limited in the occupied regions. According to the national statistics, as of 18 August 2022, about 505 pharmacies were damaged in Eastern Ukraine and 47 completely ruined. Moreover, the invaders have been blocking humanitarian aid provided to these territories by the Ukrainian government or other countries. Fortunately, in the areas controlled by the Government of Ukraine, the acute shortage of medicines, observed at the beginning of the war, has already been eliminated. Nevertheless, not all drugs are now fully available, even in the areas where no military attacks occur. The economic availability of drugs is also profoundly influenced by the significant increase in the cost of medications and the fall in average salaries. The Government of Ukraine is trying to minimise the impact of these war-related challenges by adopting a new legislation. This includes, among others, simplification of procedures for licensing, quality control and import of medicinal products to Ukraine. Other measures involve securing displaced people with the option of benefiting from local healthcare facilities, broadening the scope of the ePrescription system, authorizing primary care doctors to issue prescriptions to refugees, increasing the number of drugs reimbursed for long-term therapies, etc. These solutions, however, cannot balance all the harmful consequences the war in Ukraine brings in terms of maintenance of long-term therapies. Therefore, in order to minimise this negative impact, Ukraine still needs urgent international support in this area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khanyk, Hromovyk, Levytska, Agh, Wettermark and Kardas.)

Aims: There is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (one non-sex-related CHA2DS2-VASc point) should be treated with an oral anticoagulant., Methods and Results: We conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischaemic stroke was 0.70 per 100 person-years and the rate for a bleed was also 0.70 per 100 person-years. Comparing NOAC with no treatment, the stroke rate was lower [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.56-0.94], and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54-1.30). Comparing VKA with no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59-1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88-2.14). Comparing NOAC with VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70-1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 95% CI 0.42-0.94)., Conclusion: These observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomized controlled trial., Competing Interests: Conflict of interest: J.J.K. is currently employed by Daiichi-Sankyo, but not during the conduct of this study, and reports personal fees from Boehringer Ingelheim, outside the submitted work; A.P. reports grants from Alcon, grants from Almirall, grants from Astellas, grants from Astra-Zeneca, grants from Boehringer Ingelheim, grants from Novo Nordisk, grants from Servier, grants from LEO Pharma, outside the submitted work; Ø.K. reports participation in imposed Post-Authorization Safety Studies on an antidiabetic and an anti-psoriasis drug. The studies are funded by Leo Pharma and Novo Nordisk, with funds paid to the institution where he is employed (no personal fees) and with no relation to the work reported in this paper; L.J.K. was supported by the Research Council of Norway as part of the International Pregnancy Drug Safety Studies (InPreSS, Project No. 273366) during the conduct of the study. All other authors have nothing to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Background: Drug utilization studies are essential to facilitate rational drug use in the society., Aim: In this review, we provide an overview of drug utilization measures that can be used with individual-level drug dispensing data, referencing additional reading on the individual analysis. This is intended to serve as a primer for those new to drug utilization research and a shortlist from which researchers can identify useful analytical approaches when designing their drug utilization study., Results and Discussion: We provide an overview of: (1) basic measures of drug utilization which are used to describe changes in drug use over time or compare drug use in different populations; (2) treatment adherence measures with specific focus on persistence and implementation; (3) how to measure drug combinations which is useful when assessing drug-drug interactions, concomitant treatment, and polypharmacy; (4) prescribing quality indicators and measures to assess variations in drug use which are useful tools to assess appropriate use of drugs; (5) proxies of prescription drug misuse and skewness in drug use; and (6) considerations when describing the characteristics of drug users or prescribers., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe., Methods: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years., Results: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from -39.4% in Romagna to -14.2% in Scotland) and nasal preparations (from -34.4% in Lithuania to -5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia., Conclusions: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas., (© 2022 John Wiley & Sons Ltd.)

Purpose: Poor persistence to antihypertensive therapy is an important cause of treatment failure. Investigating persistence is especially important in countries with a high cardiovascular mortality, like Lithuania. The aim of this study was to describe the antihypertensive treatment at initiation, to determine the percentage of patients not being persistent with antihypertensive treatment after 1 year and to explore factors associated with non-persistence., Methods: In this cohort study, data on dispensed prescription medicines from the Lithuanian National Health Insurance Fund (NHIF) were used. All adult patients with a diagnosis of hypertension having first antihypertensive dispensed in 2018 were included. Descriptive statistics was used to determine the number of patients started with monotherapy and combination therapy. Treatment choice by Anatomical Therapeutic Chemical (ATC) and number of active pharmaceutical ingredient (API) was described. Non-persistence was assessed using the anniversary method. Multivariate logistic regression was used to explore factors associated with non-persistence., Results: A total of 72,088 patients were included into the study, 56% started on monotherapy treatment, with 49% being dispensed an angiotensin converting enzyme inhibitor, and 44% started on combination therapy. Overall, 57% of patients were non-persistent after 1 year. Patients' gender and prescriber qualification showed no association with non-persistence. Younger patients, patients from rural area, patients started with monotherapy, and patients with no medication change had higher odds to become non-persistent., Conclusions: The majority of patients were initiated with treatment following hypertension management guidelines, but it is of concern that over half of the patients were non-persistent to antihypertensive therapy in the first year., (© 2022. The Author(s).)

Purpose: Hypertension is an important risk factor for severe outcomes in patients with COVID-19, and antihypertensive drugs may have a protective effect. However, the pandemic may have negatively impacted health care services for chronic diseases. The aim of this study was to assess initiations of antihypertensive medicines in patients infected by COVID-19., Methods: A cohort study including all Swedish residents 20-80 years old with a COVID-19 positive test compared with an unexposed group without COVID-19 matched for age, sex, and index date (date of confirmed COVID-19). Data were collected within SCIFI-PEARL, a study including linked data on COVID tests, hospital diagnoses, dispensed prescriptions, and socioeconomic data from Swedish national registers. Initiations of different antihypertensive drugs were studied from March 2020 until October 2020. Associations between COVID-19 and initiation of antihypertensives were assessed by a multivariable Cox proportional hazards model., Results: A total of 224 582 patients (exposed and unexposed) were included. After adjusting for cardiovascular comorbidities and education level, ACEi was the most commonly initiated antihypertensive agent to patients with COVID-19. Hazard ratio and 95% confidence interval for initiation of drug therapy was 1.83 [1.53-2.19] for ACEi, followed by beta-blockers 1.74 [1.55-1.95], calcium channel blockers 1.61 [1.41-1.83], angiotensin receptor blockers 1.61 [1.40-1.86], and diuretics 1.53 [1.32-1.77]., Conclusion: All antihypertensive medicines were initiated more frequently in COVID-19 patients. This can either be associated with hypertension caused by the COVID-19 infection, more frequent diagnosis of hypertension among people with COVID-19 since they consult health care, or residual confounding factors not adjusted for in the study., (© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

The impact of statins on COVID-19 remains unclear. This study aims to investigate whether statin exposure assessed both in the population and in well-defined cohorts of COVID-19 patients may affect the risk and severity of COVID-19 using nationwide Swedish population-based register data. A population ≥ 40 years was selected by age/sex-stratified random sampling from the Swedish population on 1 Jan 2020. COVID-19 outcomes were identified from the SmiNet database, the National Patient Register and/or Cause-of-Death Register and linked with the National Prescribed Drug Register and sociodemographic registers. Statin exposure was defined as any statin prescriptions in the year before index date. In Cox regressions, confounding was addressed using propensity score ATT (Average Treatment effect in the Treated) weighting. Of 572,695 individuals in the overall cohort, 22.3% had prior statin treatment. After ATT weighting, protective effects were observed among statin user for hospitalization and COVID-19 death in the overall cohort and onset cohort. In the hospitalized cohort, statin use was only associated with lower risk for death (HR = 0.86, 95% CI 0.79-0.95), but not ICU admission. Statin-treated individuals appear to have lower COVID-19 mortality than nonusers, whether assessed in the general population, from COVID-19 onset or from hospitalization., (© 2022. The Author(s).)

Background: Rising expenditure for new cancer medicines is accelerating concerns that their costs will become unsustainable for universal healthcare access. Moreover, early market access of new oncology medicines lacking appropriate clinical evaluation generates uncertainty over their cost-effectiveness and increases expenditure for unknown health gain. Patient-level data can complement clinical trials and generate better evidence on the effectiveness, safety and outcomes of these new medicines in routine care. This can support policy decisions including funding. Consequently, there is a need for improving datasets for establishing real-world outcomes of newly launched oncology medicines. Aim: To outline the types of available datasets for collecting patient-level data for oncology among different European countries. Additionally, to highlight concerns regarding the use and availability of such data from a health authority perspective as well as possibilities for cross-national collaboration to improve data collection and inform decision-making. Methods: A mixed methods approach was undertaken through a cross-sectional questionnaire followed-up by a focus group discussion. Participants were selected by purposive sampling to represent stakeholders across different European countries and healthcare settings. Descriptive statistics were used to analyze quantifiable questions, whilst content analysis was employed for open-ended questions. Results: 25 respondents across 18 European countries provided their insights on the types of datasets collecting oncology data, including hospital records, cancer, prescription and medicine registers. The most available is expenditure data whilst data concerning effectiveness, safety and outcomes is less available, and there are concerns with data validity. A major constraint to data collection is the lack of comprehensive registries and limited data on effectiveness, safety and outcomes of new medicines. Data ownership limits data accessibility as well as possibilities for linkage, and data collection is time-consuming, necessitating dedicated staff and better systems to facilitate the process. Cross-national collaboration is challenging but the engagement of multiple stakeholders is a key step to reach common goals through research. Conclusion: This study acts as a starting point for future research on patient-level databases for oncology across Europe. Future recommendations will require continued engagement in research, building on current initiatives and involving multiple stakeholders to establish guidelines and commitments for transparency and data sharing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pisana, Wettermark, Kurdi, Tubic, Pontes, Zara, Van Ganse, Petrova, Mardare, Fürst, Roig-Izquierdo, Melien, Bonanno, Banzi, Marković-Peković, Mitkova and Godman.)

Objective: To evaluate if proton pump inhibitor (PPI) treatment reduces the risk of upper gastrointestinal bleeding (UGIB) in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs)., Design: We used a common protocol, common data model approach to conduct a cohort study including patients with AF initiated on a NOAC in Stockholm, Denmark and the Netherlands from April 2011 until July 2018. The outcome of interest was a UGIB diagnosed in a secondary care inpatient setting. We used an inverse probability weighted (IPW) Poisson regression to calculate incidence rate ratios (IRRs), contrasting PPI use to no PPI use periods., Results: In 164 290 NOAC users with AF, providing 272 570 years of follow-up and 39 938 years of PPI exposure, 806 patients suffered a UGIB. After IPW, PPI use was associated with lower UGIB rates (IRR: 0.75; 95% CI: 0.59 to 0.95). On an absolute scale, the protective effect was modest, and was found to be largest in high-risk patients, classified as age 75-84 years (number needed to treat for 1 year (NNTY): 787), age ≥85 years (NNTY: 667), HAS-BLED score ≥3 (NNTY: 378) or on concomitant antiplatelet therapy (NNTY: 373)., Conclusion: Concomitant treatment with a PPI in NOAC-treated patients with AF is associated with a reduced risk of severe UGIB. This indicates that PPI cotreatment can be considered, in particular among the elderly patients, patients with a HAS-BLED score ≥3, and/or in patients on concomitant antiplatelet therapy., Competing Interests: Competing interests: JK reports personal fees from Boehringer Ingelheim, outside the submitted work. AP reports grants from Alcon, grants from Almirall, grants from Astellas, grants from AstraZeneca, grants from Boehringer Ingelheim, grants from Novo Nordisk, grants from Servier, grants from LEO Pharma, outside the submitted work. JH reports grants from AstraZeneca, outside the submitted work. RH and LS report other fees from University of Utrecht, during the conduct of the study., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the frequency of use, sources of information, and selection criteria of Greek residents regarding over-the-counter (OTC) drugs, as well as their opinion about their dispensing in nonpharmacy settings., Methods: This was a survey study in which an anonymous cross-sectional questionnaire was used to assess the knowledge, habits, and attitudes about OTC drugs. Data were collected from March 2017 to July 2017 in Thessaloniki, the second largest city in Greece. Logistic regression was used to investigate significant factors that affect the participants' behavior., Results: A total of 782 participants completed the questionnaire. The population had a mean (SD) age of 46 (17) years and 55.1% were females. About one-third (32.5%) of the participants used nonsteroidal anti-inflammatory drugs more than once per week. OTC drugs acting on the gastrointestinal tract were used to a lower extent (13.2%). The majority (84%) of the respondents consult a healthcare professional about the information on OTC drugs. Furthermore, when not sure about which OTC drug to use, 510 participants (65.6%) valued their physician's advice, whereas 480 participants (60.2%) valued their pharmacist's advice. Most participants (61.2%) were negatively inclined toward the purchase of OTC drugs in nonpharmacy settings, with younger participants being more receptive to out-of-pharmacy OTC drug purchase than older ones (odds ratio 2.20; 95% confidence interval 1.37-3.54)., Conclusions: Healthcare professionals play an important role in providing people information on their selection of OTC drugs. This could be the main reason why participants prefer to buy OTC drugs from community pharmacies rather than retail shops., (Copyright © 2021 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Depression is a common, recurrent disorder. There is a need for readily available treatments with few negative side effects, that demands little resources and that are effective both in the short- and long term. Our aim was to investigate the long-term effectiveness of two different interventions; physical exercise and internet-based cognitive behavioural therapy (internet-CBT), compared to usual care in patients with mild to moderate depression in a Swedish primary care setting. We performed a register-based 3-year follow-up study of participants in the randomized controlled trial REGASSA (n = 940) using healthcare utilization and dispensed medicines as outcomes. We found no difference between the three groups regarding proportion of participants consulting healthcare due to mental illness or pain during follow-up. Regarding number of consultations, there was no difference between the groups, except for consultations related to pain. For this outcome both treatment arms had significantly fewer consultations compared to usual care, during year 2-3, the risk ratio (RR) for physical exercise and internet-CBT was 0.64 (95% CI = 0.43-0.95) and 0.61 (95% CI = 0.41-0.90), respectively. A significantly lower proportion of patients in both treatment arms were dispensed hypnotics and sedatives year 2-3 compared to the usual care arm, RR for both physical exercise and internet-CBT was 0.72 (95% CI = 0.53-0.98). No other differences between the groups were found. In conclusion, considering long-term effects, both physical exercise and internet-CBT, being resource-efficient treatments, could be considered as appropriate additions for patients with mild to moderate depression in primary care settings. Trial registration: The original RCT was registered with the German Clinical Trial Register (DRKS study ID: DRKS00008745)., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Åsa Ringqvist declares: Lectures on chronic pain for medical professions arranged and paid for by Sanofi. No recommendations on medication is provided during or following lectures. All other authors declare no conflicts of interest., (© 2021 The Authors.)

Aims: To assess persistence and adherence to non-vitamin K antagonist oral anticoagulant (NOAC) treatment in patients with atrial fibrillation (AF) in five Western European healthcare settings., Methods and Results: We conducted a multi-country observational cohort study, including 559 445 AF patients initiating NOAC therapy from Stockholm (Sweden), Denmark, Scotland, Norway, and Germany between 2011 and 2018. Patients were followed from their first prescription until they switched to a vitamin K antagonist, emigrated, died, or the end of follow-up. We measured persistence and adherence over time and defined adequate adherence as medication possession rate ≥90% among persistent patients only., Results: Overall, persistence declined to 82% after 1 year and to 63% after 5 years. When including restarters of NOAC treatment, 85% of the patients were treated with NOACs after 5 years. The proportion of patients with adequate adherence remained above 80% throughout follow-up. Persistence and adherence were similar between countries and was higher in patients starting treatment in later years. Both first year persistence and adherence were lower with dabigatran (persistence: 77%, adherence: 65%) compared with apixaban (86% and 75%) and rivaroxaban (83% and 75%) and were statistically lower after adjusting for patient characteristics. Adherence and persistence with dabigatran remained lower throughout follow-up., Conclusion: Persistence and adherence were high among NOAC users in five Western European healthcare settings and increased in later years. Dabigatran use was associated with slightly lower persistence and adherence compared with apixaban and rivaroxaban., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3-5 in routine care., Methods: We studied cohorts of adults with confirmed CKD G3-5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden ( N  = 57 880) and Geisinger, PA, USA ( N  = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression., Results: During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80-0.90] in SCREAM and OR 0.80 [95% CI 0.72-0.89] in Geisinger}., Conclusions: One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients' CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Medication non-adherence is associated with almost 200,000 deaths annually and €80-125 billion in the European Union. Novel technological advances (smart pill bottles, digital inhalers and spacers, electronic pill blisters, e-injection pens, e-Health applications, big data) could help managing non-adherence. Healthcare professionals seem however inadequately informed about non-adherence, availability of technological solutions in daily practice is limited, and collaborative efforts to push forward their implementation are scarce. The European Network to Advance Best practices and technoLogy on medication adherencE (ENABLE, COST Action 19132) aims to 1) raise awareness of adherence enhancing solutions, 2) foster knowledge on medication adherence, 3) accelerate clinical application of novel technologies and 4) work collaboratively towards economically viable policy, and implementation of adherence enhancing technology across healthcare systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 van Boven, Tsiligianni, Potočnjak, Mihajlović, Dima, Nabergoj Makovec, Ágh, Kardas, Ghiciuc, Petrova, Bitterman, Kamberi, Culig, Wettermark and European Network to Advance Best Practices and Technology on Medication AdherencE (ENABLE).)

Background: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology . Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel., Results: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups., Conclusions: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed., Competing Interests: The authors have no relevant conflicts of interest to declare. However, a number of the coauthors work for health authorities or are advisers to them., (Copyright © 2021 Brian Godman et al.)

Evidence-based recommendations for choice of antiepileptic drug (AED) in post-stroke epilepsy (PSE) are lacking. The aim of this study was to describe the use and persistence of AEDs when initiating treatment in men and women with PSE. An observational study based on individual-level patient data from a regional healthcare register in Stockholm, Sweden, was conducted. Adults (≥18 years) with a stroke diagnosis 2012-2016, a dispensed prescription of any AED within two years after the stroke, and with an epilepsy-related diagnosis were identified. Multinomial logistic regression and logistic regression were used to identify factors associated with choice of AED and discontinuation within 90 days, respectively. Of 9652 men and 9844 women with a stroke diagnosis, 287 men and 273 women had PSE and were dispensed AED. More than 60% of both men and women with PSE were treated with levetiracetam. Carbamazepine was the second most common drug followed by lamotrigine and valproic acid. There were significant differences in AED choice depending on for instance sex, age and renal impairment. Levetiracetam had the highest persistence in both men and women. Choice of AED, oral anticoagulant use and percutaneous endoscopic gastrostomy (PEG) showed an association with the persistence to therapy. We conclude that in both men and women with PSE, levetiracetam was the most used AED for initiation of treatment and also had the highest persistence., (© 2021 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background: In response to the Covid-19 pandemic, we designed and initiated a nationwide linked multi-register, regularly updated, observational study for timely response to urgent scientific questions., Aim: To describe the SCIFI-PEARL (Swedish Covid-19 Investigation for Future Insights - a Population Epidemiology Approach using Register Linkage) linked database encompassing essentially all known diagnosed Swedish Covid-19 patients plus a large general population comparison cohort and outline its utility in the current and future phases of the pandemic., Methods: Individuals with Covid-19 from the entire country are identified on a regularly updated basis, from different sources: all individuals from SmiNet, the national database of notifiable diseases, with positive SARS-CoV-2 polymerase chain reaction (PCR) test results; patients identified in the healthcare system by condition (ICD-10) or procedure codes in the National Patient Register or Cause-of-Death Register; patients identified through several disease-specific national quality registers (NQRs); and in two regions additionally patients identified in primary care. A comparison population was obtained by stratified random sampling from Swedish national population registers. Data from all these registers plus the National Prescribed Drug Register, the Cancer Register, national sociodemographic registers, some additional NQRs, the National Vaccination Register, and further data sources, are then linked to all study subjects (Covid-19 cases and population cohort). New cases in the study population and all data for all subjects are updated every few months, as required., Conclusion and Utility: The SCIFI-PEARL study cohort captures Swedish residents with Covid-19 on an ongoing basis, includes a representative general population comparison cohort, and links to a broad range of national and regional healthcare data for a comprehensive longitudinal view of the Covid-19 pandemic. By combining high-quality national registers with short time delay and continuous repeated linkage and updating, the project brings timely and internationally relevant data for epidemiological research on SARS-CoV-2. Our efforts provide an example and important learnings for similar efforts internationally in the future., Competing Interests: Dr. Nyberg reports prior employment at AstraZeneca until 2019, and ownership of some AstraZeneca shares. Dr. Vanfleteren reports grants and personal fees from AstraZeneca, personal fees from Novartis, GSK, Chiesi, Menarini, Pulmonx, Resmed, Boehringer, Verona Pharma, AGA Linde outside the submitted work. Dr. Sundström reports ownership in companies providing services to Itrim, Amgen, Janssen, Novo Nordisk, Eli Lilly, Boehringer, Bayer, Pfizer and AstraZeneca, outside the submitted work. Dr. Gisslén reports personal fees from Gilead, personal fees from GSK/ViiV, personal fees from MSD, other from Gilead, other from GSK/ViiV, personal fees from Biogen, personal fees from Novocure, personal fees from Amgen, personal fees from Novo Nordisk, outside the submitted work. Dr. Lindh, Dr. Santosa, Dr. Franzén, Dr. Wettermark, Dr Björck and Dr. Hammar have nothing to disclose., (© 2021 Nyberg et al.)

Maintaining healthcare for noncommunicable diseases (NCDs) is particularly important during the COVID-19 pandemic; however, diversion of resources to acute care, and physical distancing restrictions markedly affected management of NCDs. We aimed to assess the medication management practices in place for NCDs during the second wave of the COVID-19 pandemic across European countries. In December 2020, the European Network to Advance Best practices & technoLogy on medication adherencE (ENABLE) conducted a cross-sectional, web-based survey in 38 European and one non-European countries. Besides descriptive statistics of responses, nonparametric tests and generalized linear models were used to evaluate the impact on available NCD services of the number of COVID-19 cases and deaths per 100,000 inhabitants, and gross domestic product (GDP) per capita. Fifty-three collaborators from 39 countries completed the survey. In 35 (90%) countries face-to-face primary-care, and out-patient consultations were reduced during the COVID-19 pandemic. The mean ± SD number of available forms of teleconsultation services in the public healthcare system was 3 ± 1.3. Electronic prescriptions were available in 36 (92%) countries. Online ordering and home delivery of prescription medication (avoiding pharmacy visits) were available in 18 (46%) and 26 (67%) countries, respectively. In 20 (51%) countries our respondents were unaware of any national guidelines regarding maintaining medication availability for NCDs, nor advice for patients on how to ensure access to medication and adherence during the pandemic. Our results point to an urgent need for a paradigm shift in NCD-related healthcare services to assure the maintenance of chronic pharmacological treatments during COVID-19 outbreaks, as well as possible future disasters., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ágh, van Boven, Wettermark, Menditto, Pinnock, Tsiligianni, Petrova, Potočnjak, Kamberi and Kardas.)

Competing Interests: Dr. Tsiligianni reports personal fees from Honoraria for educational activities, speaking engagements, advisory boards from Boehringer Ingelheim, Astra Zeneca, GSK, Novartis and grants from GSK Hellas and Elpen, outside the submitted work. Other authors declare no competing interests. The views expressed in this paper are those of the authors alone and do not represent the policies or views of the affiliated institutions.

Aims: Studies on adherence and persistence with non-vitamin K oral anticoagulant (NOAC) treatment have relied on data from the early years of NOAC availability. We aimed to study long-term adherence and persistence with NOACs and their association with stroke risk., Methods and Results: From the Stockholm Healthcare database, we included 21 028 atrial fibrillation patients claiming a first NOAC prescription from July 2011 until October 2018, with more than 1000 patients having more than 5 years of follow-up (median: 2.0, interquartile range: 1.0-3.2). Persistence rates, defined as continuing to claim NOAC prescriptions within a 90-day gap, decreased to 70% at the end of follow-up. However, 85% of the patients were treated at the end of the study due to reinitiations. Adherence, calculated as medication possession rate (MPR) in 3 and 6-month intervals among persistent users, remained stable at 90%, with 75% of patients having an MPR >95% throughout the study period. Using a case-control design, we calculated associations of persistence and adherence with stroke risk, adjusting for potential confounders. The outcome was a composite of ischaemic or unspecified stroke and transient ischaemic attack. Non-persistence and poor adherence were both associated with increased stroke risk [non-persistence adjusted odds ratio (aOR): 2.05; 95% confidence interval (CI): 1.49-2.82, 1% reduction MPR aOR: 1.03; CI: 1.01-1.05]. There was no association between non-persistence or poor adherence and the falsification endpoints; fractions and respiratory infections, indicating no 'healthy-adherer' effect., Conclusion: Persistence rates decreased slowly over time, but persistent patients had high adherence rates. Both non-persistence and poor adherence were associated with an increased stroke risk., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Psoriasis is an immune-mediated chronic inflammatory disease having a significant negative health impact. Psoriasis has societal impact; loss of productivity has been estimated at approximately 10% and it may influence the patient's financial status. Relationships between quality of life, disease severity, and cost of care need exploration. Understanding the disease burden is important for health policy and research allocation. Few studies address the research gaps in socioeconomics, comorbidity, and medication use., Objective: Observing differences in education, income, employment status, marital status, health care consumption, and drug utilization between patients with psoriasis and matched controls., Methods: Cohort study following socioeconomics and health care consumption for all psoriasis patients from the Swedish patient register. All individuals with a first diagnosis of psoriasis in outpatient or inpatient care from 2002 to 2013 were followed until death, emigration, or end of the study., Results: Overall, 109,803 patients were included (mean age 51.2 years, 53% women) and matched with 1.08 million controls. The levels of education and income were similar, but the proportion employed was significantly lower for patients with psoriasis. There was a tendency for fewer patients with psoriasis to be married., Limitations: Generalizability, lack of primary care diagnoses, and lack of early treatments (available from 2005)., Conclusion: Understanding of the socioeconomic impact of psoriasis is extended by showing reductions in employment., Competing Interests: Dr Linder and Dr Hägg are employees of the Centre for Pharmacoepidemiology, Karolinska Institutet, which receives grants from several entities (pharmaceutical companies, regulatory authorities, and contract research organizations) for performance of drug safety and drug utilization studies. Dr Wettermark is employed by the health region but has an affiliation with the Centre for Pharmacoepidemiology as associate professor. Dr Wennerström is an employee of Janssen and the Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. Dr Villacorta is an employee of Janssen. Dr Häbel has nothing to disclose., (© 2021 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Purpose: The International Society of Pharmacoepidemiology (ISPE) in collaboration with the Latin America Drug Utilization Research Group (LatAm DURG), the Medicines Utilization Research in Africa (MURIA) group, and the Uppsala Monitoring Center, is leading an initiative to understand challenges to drug utilization research (DUR) in the Latin American (LatAm) and African regions with the goal of communicating results and proposing solutions to these challenges in four scientific publications. The purpose of this first manuscript is to identify the main challenges associated with DUR in the LatAm region., Methods: Drug utilization (DU) researchers in the LatAm region voluntarily participated in multiple discussions, contributed with local data and reviewed successive drafts and the final manuscript. Additionally, we carried out a literature review to identify the most relevant publications related to DU studies from the LatAm region., Results: Multiple challenges were identified in the LatAm region for DUR including socioeconomic inequality, access to medical care, complexity of the healthcare system, limited investment in research and development, limited institutional and organization resources, language barriers, limited health education and literacy. Further, there is limited use of local DUR data by decision makers particularly in the identification of emerging health needs coming from social and demographic transitions., Conclusions: The LatAm region faces challenges to DUR which are inherent in the healthcare and political systems, and potential solutions should target changes to the system., (© 2020 John Wiley & Sons Ltd.)

Objective: Drug-disease interactions (DDSIs) are present when a drug prescribed for one disease worsens a concomitant disease. The prevalence of DDSIs in older patients in primary care is largely unknown, as well as to what extent physicians individualize drug prescribing in relation to concomitant diseases. We therefore analysed the prevalence of DDSIs in older patients in primary care and explored to what extent physicians take possible DDSIs into account when prescribing. Design and Setting: Cross-sectional population-based register study in primary care in Region Stockholm, Sweden. Thirty-one DDSIs derived from Irish STOPP-START-Criteria were assessed. We derived data from a regional administrative healthcare database including information on all healthcare consultations and dispensed prescription drugs in the region. Data on demography, diagnoses, drug dispensations and healthcare consumption were extracted. Drugs were assessed during 2016., Subjects: A total of 336,295 patients aged ≥65 registered with one of the 206 primary care practices in Region Stockholm., Main Outcome Measures: Prevalence and prevalence differences for DDSIs., Results: In 10.8% of older patients, at least one DDSI was observed. Non-steroidal anti-inflammatory drugs (NSAIDs) were implicated in more than 75% of cases. The most common DDSI was NSAID/hypertension (8.1%), followed by NSAID/cardiovascular disease and loop diuretics/urinary incontinence (both 0.7%). The use of NSAIDs among patients with heart failure or impaired renal function was 15% lower than among patients without these diseases., Conclusion: DDSIs were present in every tenth older patient in primary care. Patients with cardiovascular disease receive NSAIDs to a lower extent, possibly indicating physician awareness of DDSI. Key points Evidence on the prevalence of drug-disease interactions in older patients in primary care is sparse despite their potential to cause harm. In this study, we found that every 10th older patient attending primary care had at least one drug-disease interaction. Interactions with NSAIDs were far more common than interactions with other drugs. The use of NSAIDs among patients with heart failure or impaired renal function was 15% lower than among patients without these diseases.

Purpose: The survival of esophageal and gastric cancer patients treated with chemotherapy is rarely assessed outside of clinical trials. Therefore, we compared the effectiveness of various curative or palliative chemotherapy regimens on the survival of esophageal and gastric cancer patients in a "real world" clinical setting., Methods: We identified a cohort of 966 incident esophageal and gastric cancer patients in Stockholm/Gotland County (a low-risk Western population) during 2008-2013. Patients who received chemotherapy with curative intention (n = 279) and palliative intention (n = 182) were analyzed separately. Using Cox proportional hazards regression models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and adjusted for the potential confounding factors: age, sex, TNM stage, radiotherapy, comorbidity, marital status, education, income, and country of birth., Results: In esophageal cancer patients with curative treatment intention, we observed a higher hazard for death among patients who received carboplatin-fluorouracil compared to patients who received cisplatin-fluorouracil, corresponding to a HR of 2.18 (95% CI 1.09-4.37). Conversely, in patients with cancer in the gastroesophageal junction who had a curative treatment intention at diagnosis, we observed a reduced hazard for death among those who received fluorouracil-oxaliplatin, compared to patients who received cisplatin-fluorouracil (HR 0.28; 95% CI 0.08-0.96)., Conclusion: Among patients with esophageal cancer who received treatment with curative intention, cisplatin-fluorouracil was associated with better survival compared to carboplatin-fluorouracil, while patients with gastroesophageal junction cancer who were treated with cisplatin-fluorouracil had worse survival compared to fluorouracil-oxaliplatin.

Purpose: To describe current antihypertensive treatment in very old hypertensive patients according to sex and comorbidity. Materials and methods: We used the Stockholm regional healthcare data warehouse (Vårdanalysdatabasen) providing information on all healthcare consultations, diagnoses, hospitalizations, dispensed prescription drugs, sex and age in 2.1 million people living in the greater Stockholm region, Sweden. This cross-sectional analysis identified 12,436 individuals with a diagnosis of hypertension, who were 90 years or older. Results: Mean age was 92.6 ± 2.6 years, 75% were women; and 34% of women and 24% of men had no diagnoses of concomitant diabetes or cardiovascular disease. The number of dispensed drug classes was similar (2.1 ± 1.4) in women and in men. Women more often used angiotensin receptor blockers and beta-blockers, while men more frequently used ACE inhibitors and calcium channel blockers (all p  < .05). Compared to men, women with concomitant diabetes or heart failure used less ACE inhibitors or angiotensin receptor blockers (52 vs. 60% and 49 vs. 55%, respectively; all p  < .01and adjusted for age and comorbidity), which is contrary to current recommendations. Conclusion: Our findings suggest that antihypertensive treatment is common also in very old patients. Given the rapidly ageing population and circumstantial evidence in favour of maintaining well-tolerated antihypertensive therapy in very old patients, prospective well-designed outcome studies are warranted.

Background: Operating under constrained budgets, payers and providers globally face challenges in enabling appropriate and sustainable access to new medicines. Among payer initiatives aiming to improve preparedness of healthcare systems for the introduction of new medicines, drug utilization and expenditure forecasting has played an increasingly important role. This study aims to describe the forecasting model used in Region Stockholm and to evaluate the accuracy of the forecasts produced over the past decade., Methods: In this repeated cross-sectional study, we compared the predicted pharmaceutical expenditure with actual expenditure during the entire available follow-up period (2007-2018) both for overall drug utilization and for individual therapeutic groups. All analyses were based on pharmaceutical expenditure data that include medicines used in hospitals and dispensed prescription medicines for all residents of the region., Results: According to the forecasts, the total pharmaceutical expenditure was estimated to increase between 2 and 8% annually. Our analyses showed that the accuracy of these forecasts varied over the years with a mean absolute error of 1.9 percentage points. Forecasts for the same year were more accurate than forecasts for the next year. The accuracy of forecasts also differed across the therapeutic areas. Factors influencing the accuracy of forecasting included the timing of the introduction of both new medicines and generics, the rate of uptake of new medicines, and sudden changes in reimbursement policies., Conclusions: Based on the analyses of all forecasting reports produced since the model was established in Stockholm in the late 2000s, we demonstrated that it is feasible to forecast pharmaceutical expenditure with a reasonable accuracy. A number of factors influencing the accuracy of forecasting were also identified. If forecasting is used to provide data for decisions on budget allocation and agreements between payers and providers, we advise to update the forecast as close as possible prior to the decision date.

We aimed to quantify the effects of antidepressant (AD) use in oral anticoagulant (OAC)-treated patients with atrial fibrillation (AF). Using the Stockholm Healthcare database, we analyzed AF patients initiated with an OAC. Outcomes were severe bleeds and strokes and were analyzed using Cox models. We included 17,210 patients claiming warfarin and 13,385 claiming a non-vitamin K OAC. The number of patients that claimed an AD during follow-up was 4,303. Concomitant OAC and AD use was associated with increased rates of severe bleeds (4.7 vs. 2.7 per 100 person-years) compared with OAC treatment alone (adjusted hazard ratio (aHR) 1.42, confidence interval (CI): 1.12-1.80), but not significantly associated with increased stroke rates (3.5 vs. 2.1 per 100 person-years, aHR 1.23, CI: 0.93-1.62). No significant differences in risks were observed between different OAC classes or different AD classes. In conclusion, concomitant use of an OAC and an AD is associated with an increased bleeding risk., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)