Impact of the early COVID-19 pandemic on adult mental health-related dispensed medications, hospitalizations and specialist outpatient visits in Norway and Sweden: Interrupted time series analysis.

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.

Socioeconomic factors associated with poor medication adherence in patients with type 2 diabetes.

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.

The environmental impact of pharmaceuticals in Italy: Integrating healthcare and eco-toxicological data to assess and potentially mitigate their diffusion to water supplies.

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.

Feasibility and validity of using healthcare databases to conduct cross-national comparative studies of opioid use, its determinants and consequences.

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.

Knowledge support for environmental information on pharmaceuticals: experiences among Swedish Drug and Therapeutics Committees.

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.

Oral anticoagulants in patients with atrial fibrillation at low stroke risk: a multicentre observational study.

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.

Non-persistence to antihypertensive drug therapy in Lithuania.

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.

Core concepts in pharmacoepidemiology: Measures of drug utilization based on individual-level drug dispensing data.

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.

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study.

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.

Persistence and adherence to non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation across five Western European countries.

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.

Survival of esophageal and gastric cancer patients with adjuvant and palliative chemotherapy-a retrospective analysis of a register-based patient cohort.

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.

Challenges facing drug utilization research in the Latin American region.

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.

Current antihypertensive drug therapy in 12,436 Swedish patients, 90 years and above, in relation to sex and comorbidity.

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.

Forecasting drug utilization and expenditure: ten years of experience in Stockholm.

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.

Drug-disease interactions in Swedish senior primary care patients were dominated by non-steroid anti-inflammatory drugs and hypertension - a population-based registry study.

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.

Sibship and dispensing patterns of asthma medication in young children-a population-based study.

PURPOSE: Our aim was to study the association between sibship and dispensing patterns of asthma medication in young children, focusing on incidence and persistence, and taking sibship status, asthma diagnoses, and siblings' medication into account. METHODS: A register-based cohort study including all children (n = 50 546) born in Stockholm, Sweden 2006 to 2007, followed up during 2006 to 2014. Exposure was sibling status; outcome was incidence of dispensed asthma medication and persistence over time. A Cox model was used to study the association between sibship and asthma medication. Persistence was defined using two different time windows (4 and 18 months) in a refill sequence model including siblings' and unrelated control children's medication. RESULTS: After 1 year of age, the adjusted hazard ratio of dispensed asthma medication was 0.85 (95% CI 0.80-0.90) among children with siblings compared with singletons. The estimated proportion of children with persistent controller medication was 7.2% (4-month model) and 64.5% (18-month model). When including the siblings' controller medication, the estimated proportion was 8.8% (4 months) and 7.8% for control children (relative risk (RR) 0.89, 95% CI 0.81-0.98). The persistence was lower for those with siblings compared with singletons (adj. RR 0.72, 95% CI 0.62-0.85 for 4 months) with similar estimates for older, younger, and full siblings and regardless of asthma diagnoses. CONCLUSIONS: Siblings have different dispensing patterns of asthma medications compared with singletons regardless of asthma diagnoses. After including the siblings' asthma medication and compared with control children, the proportion of children with persistent medication increased which may indicate that siblings share asthma medications.

Medication persistence to antihypertensive drug treatment - a cross-sectional study of attitudes towards hypertension and medication in persistent and non-persistent patients.

Purpose: To study the differences in attitudes towards hypertension and drug treatment between patients persistent and non-persistent to antihypertensive drug treatment. Materials and methods: Cross-sectional study on patients with hypertension treated at 25 primary healthcare centres in Stockholm, Sweden. Questionnaires were sent to the patients 3-12 months after initiation of antihypertensive drug treatment. Persistent medication users, defined as patients with less than 30 days without tablet supply between prescription refills, were compared with non-persistent users by scores from Likert scales: Brief-Illness Perception Questionnaire (Brief IPQ, 0-10) and Beliefs about Medicines Questionnaire (BMQ General, 4-20 and BMQ Specific, 5-25). Results: A total of 711 patients were included in the final analyses (mean age: 62 years; 50% women), of whom 609 (86%) were classified as persistent and 102 (14%) as non-persistent by analyses of their filled prescriptions. Likert scales from the Brief-IPQ showed (all p < 0.02) that persistent patients believed that hypertension was a chronic condition (median 6 vs. 4), that hypertension had less consequences on their life (median 2 vs. 3) and that they can prevent cardiovascular disease by taking antihypertensive treatment (median 7 vs. 5). Likert scales from the BMQ General showed (all p < 0.02) that persistent patients believed that there are potential benefits from taking the treatment (median 16 vs. 16), and they did not believe that the doctors put too much trust in drugs (median 12 vs. 13). Further, results from the BMQ Specific showed that they believed that the antihypertensive drugs are necessary for them in order to maintain or improve their own health (median 17 vs. 16). Conclusions: Primary healthcare providers should further emphasize the chronicity of hypertension diagnosis and the benefits of treatment, to improve the patients' medication persistence to antihypertensive treatment.

Improved Stroke Prevention in Atrial Fibrillation After the Introduction of Non-Vitamin K Antagonist Oral Anticoagulants.

Background and Purpose- The purpose of this study was to investigate the impact of improved antithrombotic treatment in atrial fibrillation after the introduction of non-vitamin K antagonist oral anticoagulants on the incidence of stroke and bleeding in a real-life total population, including both primary and secondary care. Methods- All resident and alive patients with a recorded diagnosis for atrial fibrillation during the preceding 5 years in the Stockholm County Healthcare database (Vårdanalysdatabasen) were followed for clinical outcomes during 2012 (n=41 008) and 2017 (n=49 510). Results- Pharmacy claims for oral anticoagulants increased from 51.6% to 73.8% (78.7% among those with CHA2DS2-VASc ≥2). Non-vitamin K antagonist oral anticoagulant claims increased from 0.4% to 34.4%. Ischemic stroke incidence rates decreased from 2.01 per 100 person-years in 2012 to 1.17 in 2017 (incidence rate ratio, 0.58; 95% CI, 0.52-0.65). The largest increases in oral anticoagulants use and decreases in ischemic strokes were seen in patients aged ≥80 years who had the highest risk of stroke and bleeding. The incidence rates for major bleeding (2.59) remained unchanged (incidence rate ratio, 1.00; 95% CI, 0.92-1.09) even in those with a high bleeding risk. Poisson regression showed that 10% of the absolute ischemic stroke reduction was associated with increased oral anticoagulants treatment, whereas 27% was related to a generally decreased risk for all stroke. Conclusions- Increased oral anticoagulants use contributed to a marked reduction of ischemic strokes without increasing bleeding rates between 2012 and 2017. The largest stroke reduction was seen in elderly patients with the highest risks for stroke and bleeding. These findings strongly support the adoption of current guideline recommendations for stroke prevention in atrial fibrillation in both primary and secondary care.

Association Between Proton Pump Inhibitor Use and Risk of Progression of Chronic Kidney Disease.

BACKGROUND & AIMS: Proton pump inhibitors (PPI) have been associated with acute kidney injury and recent studies suggest that they may be associated with the risk of chronic kidney disease (CKD). METHODS: We performed a retrospective analysis using the Stockholm creatinine measurements database, which contains information on diagnoses, dispensation claims, and laboratory test results for all citizens in the Stockholm region from 2007 through 2010. We identified new users of PPIs (n = 105,305) and new users of H2 blockers (H2B; n = 9578); data on renal outcomes were collected for a median 2.7 years. The primary outcome was progression CKD, defined as doubling of creatinine or decrease in estimated glomerular filtration rate of 30% or more. Secondary outcomes were end-stage renal disease and acute kidney injury. Complete collection of repeated PPI and H2B dispensations at pharmacies in Sweden allowed modeling the time-dependent risk associated with cumulative PPI exposure. RESULTS: Users of PPIs, compared with users of H2Bs, had an increased risk for doubled levels of creatinine (1985 events; adjusted hazard ratio [HR], 1.26; 95% CI, 1.05-1.51) and decrease in estimated glomerular filtration rate of 30% or more (11,045 events; 1.26; 95% CI, 1.16-1.36). PPI use also associated with development of end-stage renal disease (HR, 2.40; 95% CI, 0.76-7.58) and acute kidney injury (HR, 1.30; 95% CI, 1.00-1.69). There was a graded association between cumulative exposure to PPIs and risk of CKD progression. This was not the case for cumulative H2B use. CONCLUSIONS: Initiation of PPI therapy and cumulative PPI exposure is associate with increased risk of CKD progression in a large, North European healthcare system. Although consistent, the association was modest in magnitude, and cannot exclude residual confounding.

Stroke and bleeding with non-vitamin K antagonist oral anticoagulant or warfarin treatment in patients with non-valvular atrial fibrillation: a population-based cohort study.

Aims: Oral anticoagulants (OACs) effectively reduce the risk of stroke in atrial fibrillation (AF). Three non-vitamin K antagonist OACs (NOACs) are introduced in regular care based on promising results compared with warfarin in randomized trials. This study compares outcomes with NOAC vs. warfarin treatment in OAC naïve AF patients in routine care, including primary care, in a large region with decentralized anticoagulant treatment. Methods and results: Population-based cohort study. Individuals with non-valvular AF who initiated treatment with NOAC (n = 9279) or warfarin (n = 12 919) from 2012 to 2015 were identified in the Stockholm administrative health data register (population 2.2 million). Adjusted Cox regression analyses were performed to evaluate TIA/ischaemic or unspecified stroke/death, and severe bleeds (co-primary endpoints); and secondarily for components of the composites. NOAC patients were younger (72.9 vs. 74.1 years) and had lower CHA2DS2VASc scores (3.42 vs. 3.68) than warfarin patients. NOAC vs. warfarin treatment was associated with similar risks for TIA/ischaemic or unspecified stroke/death [hazard ratio (HR) 0.94; 0.85-1.05] and severe bleeds (HR 1.02; 0.88-1.19); lower risks of intracranial bleeds (HR 0.72; 0.53-0.97) or haemorrhagic stroke (HR 0.56; 0.34-0.93), but a higher risk for gastrointestinal bleeds (HR 1.28; 1.04-1.59). The advantages with NOAC treatment were most pronounced with standard dose in patients below 80 years, and with dose reduction in patients aged 80 and above. Conclusion: This population-based cohort study of routine care indicates similar or better effectiveness and safety with NOAC compared with warfarin treatment. NOACs were associated with fewer intracranial bleeds, but more gastrointestinal bleeds.