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.

Economic and epidemiological impact of dengue illness over 16 years from a public health system perspective in Brazil to inform future health policies including the adoption of a dengue vaccine.

INTRODUCTION: Dengue is a serious global health problem endemic in Brazil. Consequently, our aim was to measure the costs and disease burden of symptomatic dengue infections in Brazil from the perspective of the Brazilian Public Health System (SUS) between 2000 and 2015, using Brazilian public health system databases. Specific age group incidence estimates were used to calculate the disability-adjusted life years (DALYs) to gain a better understanding of the disease burden. Areas covered: SUS spent almost USD159 million and USD10 million to treat dengue and severe dengue, respectively, between 2000 and 2015. This is principally hospitalization costs, with the majority of patients self-treated at home with minor symptoms. The average notification rate for dengue was 273 per 100,000 inhabitants and three per 100,000 for severe dengue, with annual DALYs estimates ranging between 72.35 and 6,824.45 during the 16 years. Expert commentary: The epidemiological and morbidity burden associated with dengue is substantial in Brazil, with costs affected by the fact that most patients self-treat at home with these costs not included in SUS. The Brazilian government urgently needs to proactively evaluate the real costs and clinical benefits of any potential dengue vaccination program by the National Immunization Program to guide future decision-making.

Use of text-mining methods to improve efficiency in the calculation of drug exposure to support pharmacoepidemiology studies.

Background: Efficient generation of structured dose instructions that enable researchers to calculate drug exposure is central to pharmacoepidemiology studies. Our aim was to design and test an algorithm to codify dose instructions, applied to the NHS Scotland Prescribing Information System (PIS) that records about 100 million prescriptions per annum. Methods: A natural language processing (NLP) algorithm was developed that enabled free-text dose instructions to be represented by three attributes - quantity, frequency and qualifier - specified by three, three and two variables, respectively. A sample of 15 593 distinct dose instructions was used to test, validate and refine the algorithm. The final algorithm used a zero-assumption approach and was then applied to the full dataset. Results: The initial algorithm generated structured output for 13 152 (84.34%) of the 15 593 sample dose instructions, and reviewers identified 767 (5.83%) incorrect translations, giving an accuracy of 94.17%. Following subsequent refinement of the algorithm rules, application to the full dataset of 458 227 687 prescriptions (99.67% had dose instructions represented by 4 964 083 distinct instructions) generated a structured output for 92.3% of dose instruction texts. This varied by therapeutic area (from 86.7% for the central nervous system to 96.8% for the cardiovascular system). Conclusions: We created an NLP algorithm, operational at scale, to produce structured output that gives data users maximum flexibility to formulate, test and apply their own assumptions according to the medicines under investigation. Text mining approaches can provide a solution to the safe and efficient management and provisioning of large volumes of data generated through our health systems.

Risk factors for resistance and MDR in community urine isolates: population-level analysis using the NHS Scotland Infection Intelligence Platform.

BACKGROUND: Urinary tract infections (UTIs) are common. Antibiotic treatment is usually empirical, with the risk of under-treatment of resistant infections. OBJECTIVES: To characterize risk factors for antibiotic-resistant community urine isolates using routine record-linked health data. METHODS: Within the NHS Scotland Infection Intelligence Platform, national surveillance patient-level data on community urine isolates (January 2012-June 2015) were linked to hospital activity and community prescribing data. Associations between age, gender, comorbidity, care home residence, previous hospitalizations, antibiotic exposure and resistant (any antibiotic) or MDR (≥1 antibiotic from ≥3 categories) urinary isolates were quantified using multivariable logistic regression. RESULTS: Of 40984 isolates, 28% were susceptible, 45% were resistant and 27% were MDR. Exposure to ≥ 4 different antibiotics in the prior 6 months increased MDR risk (OR 6.81, 95% CI 5.73-8.11). MDR was associated with ≥29 DDD cumulative exposure, in the prior 6 months, for any antibiotic (OR 6.54, 95% CI 5.88-7.27), nitrofurantoin (OR 8.56, 95% CI 6.56-11.18) and trimethoprim (OR 14.61, 95% CI 10.53-20.27). Associations persisted for 10-12 months for nitrofurantoin (OR 2.31, 95% CI 1.93-2.76) and trimethoprim (OR 1.81, 95% CI 1.57-2.09). Increasing age, comorbidity, previous hospitalization and care home residence were independently associated with MDR. For resistant isolates the factors were the same, but with weaker associations. CONCLUSIONS: To our knowledge, we have demonstrated, using national capability at scale, the risk of MDR in community urine isolates for the first time and quantified the cumulative and sustained impact of antibiotic exposure. These data will inform the development of decision support tools for UTI treatment.

The Assessment for Disinvestment of Intramuscular Interferon Beta for Relapsing-Remitting Multiple Sclerosis in Brazil.

In Brazil, inclusion and exclusion of health technologies within the Unified Health System (SUS) is the responsibility of the National Committee for Health Technology Incorporation (CONITEC). A recent Cochrane systematic review demonstrated that intramuscular interferon beta 1a (IFN-ß-1a-IM) was inferior to the other beta interferons (IFN-ßs) for multiple sclerosis (MS). As a result, CONITEC commissioned an analysis to review possible disinvestment within SUS. The objective of this paper is to describe the disinvestment process for IFN-ß-1a-IM in Brazil. The first assessment comprised a literature review and mixed treatment comparison meta-analysis. The outcome of interest was the proportion of relapse-free patients in 2 years. This analysis confirmed the inferiority of IFN-ß-1a-IM. Following this, CONITEC recommended disinvestment, with the decision sent for public consultation. More than 3000 contributions were made on CONITEC's webpage, most of them against the preliminary decision. As a result, CONITEC commissioned a study to assess the effectiveness of IFN-ß-1a-IM among Brazilian patients in routine clinical care. The second assessment involved an 11-year follow-up of a non-concurrent cohort of 12,154 MS patients developed by deterministic-probabilistic linkage of SUS administrative databases. The real-world assessment further demonstrated that IFN-ß-1a-IM users had a statistically higher risk of treatment failure, defined as treatment switching or relapse treatment or death, with the assessment showing that IFN-ß-1a-IM was inferior to the other IFN-ßs and to glatiramer acetate in both direct and indirect analysis. In the drug ranking with 40,000 simulations, IFN-ß-1a-IM was the worst option, with a success rate of only 152/40,000. Following this, CONITEC decided to exclude the intramuscular presentation of IFN-ß from the current MS treatment guidelines, giving patients who are currently on this treatment the option of continuing until treatment failure. In conclusion, we believe this is the first example of this new disinvestment process in action, providing an exemplar for other treatments in Brazil as well as other countries.

Building a national Infection Intelligence Platform to improve antimicrobial stewardship and drive better patient outcomes: the Scottish experience.

Background: The better use of new and emerging data streams to understand the epidemiology of infectious disease and to inform and evaluate antimicrobial stewardship improvement programmes is paramount in the global fight against antimicrobial resistance. Objectives: To create a national informatics platform that synergizes the wealth of disjointed, infection-related health data, building an intelligence capability that allows rapid enquiry, generation of new knowledge and feedback to clinicians and policy makers. Methods: A multi-stakeholder community, led by the Scottish Antimicrobial Prescribing Group, secured government funding to deliver a national programme of work centred on three key aspects: (i) technical platform development with record linkage capability across multiple datasets; (ii) a proportionate governance approach to enhance responsiveness; and (iii) generation of new evidence to guide clinical practice. Results: The National Health Service Scotland Infection Intelligence Platform (IIP) is now hosted within the national health data repository to assure resilience and sustainability. New technical solutions include simplified 'data views' of complex, linked datasets and embedded statistical programs to enhance capability. These developments have enabled responsiveness, flexibility and robustness in conducting population-based studies including a focus on intended and unintended effects of antimicrobial stewardship interventions and quantification of infection risk factors and clinical outcomes. Conclusions: We have completed the build and test phase of IIP, overcoming the technical and governance challenges, and produced new capability in infection informatics, generating new evidence for improved clinical practice. This provides a foundation for expansion and opportunity for global collaborations.

Use of direct oral anticoagulants in patients with atrial fibrillation in Scotland: Applying a coherent framework to drug utilisation studies.

PURPOSE: To report the use of direct oral anticoagulants (DOACs) for stroke prevention in patients with atrial fibrillation in Scotland and advocate the standardisation of drug utilisation research methods. METHODS: Retrospective cohort study using linked administrative data. Patients included those with a diagnosis of atrial fibrillation (confirmed in hospital) who received a first prescription for a DOAC (dabigatran, rivaroxaban, or apixaban) from September 2011 to June 2014. Drug utilisation measures included discontinuation, persistence, and adherence. RESULTS: A total of 5398 patients (mean CHA2 DS2 -VASc score 2.98 [SD 1.71], 89.7% with ≥5 concomitant medicines) were treated with DOACs for a median of 228 days (interquartile range 105-425). Of 35.6% who discontinued DOAC treatment, 11.0% switched to warfarin, and 48.3% reinitiated DOACs. Persistence after 12 and 18 months was 75.9% and 69.8%, respectively. Differences between individual DOACs were observed: Discontinuation rates ranged from 20.4% (apixaban) to 60.6% (dabigatran) and 12 months persistence from 60.1% (dabigatran) to 85.5% (apixaban). Adherence to treatment with all DOACs was good: Overall DOAC median medication refill adherence was 102.9% (interquartile range 88.9%-115.5%), and 82.3% of patients had a medication refill adherence > 80%. CONCLUSIONS: In Scotland, adherence to DOAC treatment was good, and switching from DOAC to warfarin was low. However, discontinuation and persistence rates were variable-although treatment interruptions were often temporary. To decrease the inconsistencies in drug utilisation methods and facilitate meaningful study comparison, the use of a coherent framework-using a combination of discontinuation, persistence, and adherence-and the standardisation of measurements is advocated.