Epidemiology, Treatment Patterns, Comorbidities, and Concomitant Medication in Patients with ADHD in Sweden: A Registry-Based Study (2018-2021).

OBJECTIVE: To evaluate treatment patterns for ADHD in Sweden. METHOD: Observational retrospective study of patients with ADHD from the Swedish National Patient Register and Prescribed Drug Register, 2018 to 2021. Cross-sectional analyses included incidence, prevalence, and psychiatric comorbidities. Longitudinal analyses (newly diagnosed patients) included medication, treatment lines, duration, time-to-treatment initiation, and switching. RESULTS: Of 243,790 patients, 84.5% received an ADHD medication. Psychiatric comorbidities were common, particularly autism among children, and depression in adults. Most frequent first-/second-line treatments were methylphenidate (MPH; 81.6%) and lisdexamfetamine dimesylate (LDX; 46.0%), respectively. In the second-line, LDX was most frequently prescribed (46.0%), followed by MPH (34.9%), then atomoxetine (7.7%). Median treatment duration was longest for LDX (10.4 months), followed by amphetamine (9.1 months). CONCLUSION: This nationwide registry study provides real-life insights into the current epidemiology of ADHD and the changing treatment landscape for patients in Sweden.

A Guide to Selecting Flexible Survival Models to Inform Economic Evaluations of Cancer Immunotherapies.

OBJECTIVES: Parametric models are routinely used to estimate the benefit of cancer drugs beyond trial follow-up. The advent of immune checkpoint inhibitors has challenged this paradigm, and emerging evidence suggests that more flexible survival models, which can better capture the shapes of complex hazard functions, might be needed for these interventions. Nevertheless, there is a need for an algorithm to help analysts decide whether flexible models are required and, if so, which should be chosen for testing. This position article has been produced to bridge this gap. METHODS: A virtual advisory board comprising 7 international experts with in-depth knowledge of survival analysis and health technology assessment was held in summer 2021. The experts discussed 24 questions across 6 topics: the current survival model selection procedure, data maturity, heterogeneity of treatment effect, cure and mortality, external evidence, and additions to existing guidelines. Their responses culminated in an algorithm to inform selection of flexible survival models. RESULTS: The algorithm consists of 8 steps and 4 questions. Key elements include the systematic identification of relevant external data, using clinical expert input at multiple points in the selection process, considering the future and the observed hazard functions, assessing the potential for long-term survivorship, and presenting results from all plausible models. CONCLUSIONS: This algorithm provides a systematic, evidence-based approach to justify the selection of survival extrapolation models for cancer immunotherapies. If followed, it should reduce the risk of selecting inappropriate models, partially addressing a key area of uncertainty in the economic evaluation of these agents.

Impact of pneumococcal conjugate vaccines on healthcare utilization and direct costs for otitis media in children ≤2 years of age in two Swedish regions.

In Sweden, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 and replaced by the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) or the 13- valent PCV (PCV13) from late 2009. We assessed the impact of PCVs on rates of antibiotic prescribing, tympanostomy tube placement (TTP), and healthcare resource utilization and direct costs of physician- diagnosed otitis media/acute otitis media (OM) in children ≤2 years of age living in Skåne (PCV7 then PHiD- CV) or Västra Götalandsregionen (VGR; PCV7 then PCV13). Retrospective cohort study using linked patient- level data from national and regional (Skåne and VGR) healthcare databases in Sweden from July 1, 2005, to December 31, 2013 (NCT02742753). Descriptive time-series analyses showed antibiotic prescriptions and TTP incidence declined after PHiD-CV/PCV13 introduction versus the pre-PCV period. The annualized mean frequencies of antibiotic use, primary care visits, outpatient visits, TTP and myringotomy procedures all decreased after PHiD-CV/PCV13 compared with pre-PCV cohorts. Annualized mean total OM-associated healthcare costs decreased in the PCV7 versus pre-PCV cohorts by 20.0% in Skåne and 10.2% in VGR, and further declined in the PHiD-CV and PCV13 cohorts (20.7% and 15.3%, respectively, relative to the PCV7 cohort), although the duration of PCV7 use differed between regions. Decreases in adjusted annualized cost ratios between cohorts per child susceptible to OM were statistically significant after PCV7 introduction and again with either PHiD-CV or PCV13 introduction in both regions. Following sequential PCV introduction, OM-related healthcare utilization and associated costs decreased in the study regions in Sweden. PLAIN LANGUAGE SUMMARY: What is the context?Otitis media is one of the most frequent reasons for healthcare visits and antibiotic use among young children. Although it is considered as a mild illness, the overall economic burden is substantial due to its high frequency.Otitis media can be caused by different bacteria including Streptococcus pneumoniae, which is also responsible for pneumonia and meningitis. Pneumococcal conjugate vaccines Prevenar (Pfizer Inc.), Synflorix (GSK), and Prevenar 13 (Pfizer Inc.) protect against pneumococcal diseases and reduce its occurrence.However, it is not known how the routine use of these vaccines may affect otitis media-related healthcare resources and costs.What is new?In this study, we assessed trends in rates of healthcare utilization and associated costs due to otitis media in young children before (2005-2008) and after (2009-2013) use of pneumococcal conjugate vaccines. The study was conducted in two Swedish regions; one used Prevenar then Synflorix, while the other used Prevenar then Prevenar 13.We found that compared to the period before pneumococcal conjugate vaccine implementation, the postpneumococcal conjugate vaccine period was associated with:What is the impact on current thinking?The use of pneumococcal conjugate vaccines effectively reduces healthcare utilization and resources associated with otitis mediaThis indirect effect on the reduction of otitis media burden provides further benefit to the implementation of pneumococcal vaccination.

The effect of pneumococcal conjugate vaccines on otitis media from 2005 to 2013 in children aged ≤5 years: a retrospective cohort study in two Swedish regions.

Seven-valent pneumococcal conjugate vaccine (PCV7) was introduced to Sweden in 2009 and replaced by pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) or 13-valent PCV (PCV13) from late 2009. A retrospective cohort study assessed the impact of PCVs on otitis media/acute otitis media (OM) in children aged ≤5 years (NCT02742753) living in Skåne (PCV7 then PHiD-CV) or Västra Götalandsregionen (PCV7 then PCV13) between 2005 and 2013 using linked regional and national databases. Time-series analyses described differences between pre-PCV and post-PCV eras. Adjusted age-period-cohort (APC) predictive models estimated vaccine effectiveness and OM incidence ratios between PCV cohorts. Time-to-first OM diagnosis was estimated in ≤2 year-olds by survival analysis using a Cox proportional hazards model. Descriptive interrupted time-series analyses showed OM incidence in ≤2 year-olds declined by 42% (Skåne) and 25% (Västra Götalandsregionen) after PHiD-CV/PCV13, respectively, versus pre-PCV, but baseline OM incidence and duration of PCV7 use differed between regions. In adjusted APC models, OM incidence decreased after PHiD-CV by 9.9% (95% confidence interval [CI]: 4.4; 15.1, p < .001) and PCV13 by 2.3% (95%CI: -3.2; 7.6, p = .401) compared with pre-PCV. Both PHiD-CV and PCV13 decreased the risk of first OM diagnosis: hazard ratio (95%CI) for PHiD-CV relative to pre-PCV 0.67 (0.65; 0.69); 0.87 (0.85; 0.89) for PCV13 relative to pre-PCV; p < .001 for both comparisons. Within the limitations of this study conducted in two large Swedish regions, descriptive time-series analyses showed that OM incidence rates declined following the introduction of PHiD-CV and PCV13; however, this reduction only reached statistical significance for PHiD-CV in the adjusted APC models.

Estimated prevalence and incidence of diagnosed ADHD and health care utilization in adults in Sweden - a longitudinal population-based register study.

BACKGROUND: Although the worldwide prevalence of attention-deficit/hyperactivity disorder (ADHD) in adults is estimated to be between 2% and 5%, it is considered to be underdiagnosed. This register study explored the prevalence of diagnosed ADHD and incidence of newly diagnosed ADHD in Swedish adults over time, and assessed comorbidities and pharmacologic treatment. METHODS: National Patient Register data were used to estimate the overall prevalence of adults (≥18 years) with a registered ADHD diagnosis from 2006 to 2011, and the incidence of newly registered diagnoses from 2007 to 2011. Data from the Prescribed Drug Register were used to estimate the mean dose of the most frequently prescribed ADHD medication. RESULTS: The estimated annual prevalence (N=44,364) of diagnosed ADHD increased from 0.58 per 1,000 persons in 2006 to 3.54 per 1,000 persons in 2011. The estimated annual incidence of newly diagnosed ADHD (N=24,921) increased from 0.39 per 1,000 persons to 0.90 per 1,000 persons between 2007 and 2011. At least one comorbidity was diagnosed in 52.6% of adults with ADHD (54.0% of newly diagnosed adults), with anxiety, substance use disorders, and depression being the most common. Among all adults with ADHD, 78.9% (65.7% of newly diagnosed adults) were prescribed ADHD medication and one-third were prescribed more than one add-on medication. Osmotic release oral system methylphenidate was the most commonly used medication. The mean daily dose was 51.5 mg, and was significantly higher in males, patients with substance use disorders, patients with drug holidays, and patients with at least one add-on medication. The most frequent concomitant medications were anxiolytics and hypnotics. CONCLUSION: In Sweden, the number of adults diagnosed with ADHD increased between 2006 and 2011, and the majority of patients were prescribed ADHD-specific medication. Over one-half of patients had psychiatric comorbidities; one-third were prescribed more than one add-on medication. Consumption of pharmacologic ADHD medication was high in specific patient subpopulations.

Prevalence, Patient Characteristics, and Pharmacological Treatment of Children, Adolescents, and Adults Diagnosed With ADHD in Sweden.

OBJECTIVE: The objective of this study was to describe the epidemiology of diagnosed ADHD and the pharmacological treatment of patients with ADHD in Sweden. Specifically, this study estimates the prevalence of patients with a newly registered diagnosis of ADHD over a 5-year period, and the prevalence of all patients with a registered ADHD diagnoses over a 6-year period in Sweden. METHOD: Two population-based registries were used as data sources for this study; the National Patient Register (NPR) and the Prescribed Drug Register (PDR). The international Classification of Diseases 10th Revison (ICD-10) was used to identify patients with ADHD. RESULTS: The annual prevalence of ADHD in the general population of Sweden was found to be 1.1 per 1,000 persons in the year 2006 increasing to 4.8 per 1,000 persons in 2011. The corresponding prevalence for newly diagnosed patients increased from 0.6 per 1,000 persons in 2007 to 1.3 per 1,000 persons in 2011. The majority of diagnosed patients received pharmacological treatment, with methylphenidate being the most common dispensed drug. Comorbidities in the autism spectrum were most common for younger patients, while substance abuse, anxiety, and personality disorder were the most common comorbidities in older patients. CONCLUSION: From 2006 to 2011, the number of patients diagnosed with ADHD has increased in Sweden over all ages. The majority of patients diagnosed with ADHD in Sweden received a pharmacological treatment regardless of age. An ADHD diagnosis was often accompanied with psychiatric comorbidity.

European Regional Differences in All-Cause Mortality and Length of Stay for Patients with Hip Fracture.

The objective of this study was to compare healthcare performance for the surgical treatment of hip fractures across and within Finland, Hungary, Italy, the Netherlands, Norway, Scotland, and Sweden. Differences in age-adjusted and sex-adjusted 30-day and one-year all-cause mortality rates following hip fracture, as well as the length of stay of the first hospital episode in acute care and during a follow up of 365 days, were investigated, and associations between selected country-level and regional-level factors with mortality and length of stay were assessed. Hungary showed the highest one-year mortality rate (mean 39.7%) and the lowest length of stay in one year (12.7 days), whereas Italy had the lowest one-year mortality rate (mean 19.1 %) and the highest length of stay (23.3 days). The observed variations were largely explained by country-specific effects rather than by regional-level factors. The results show that there should still be room for efficiency gains in the acute treatment of hip fracture, and clinicians, healthcare managers, and politicians should learn from best practices. This study demonstrates that an international comparison of acute hospital care is possible using pooled individual-level administrative data.

Costs and Quality at the Hospital Level in the Nordic Countries.

This article develops and analyzes patient register-based measures of quality for the major Nordic countries. Previous studies show that Finnish hospitals have significantly higher average productivity than hospitals in Sweden, Denmark, and Norway and also a substantial variation within each country. This paper examines whether quality differences can form part of the explanation and attempts to uncover quality-cost trade-offs. Data on costs and discharges in each diagnosis-related group for 160 acute hospitals in 2008-2009 were collected. Patient register-based measures of quality such as readmissions, mortality (in hospital or outside), and patient safety indices were developed and case-mix adjusted. Productivity is estimated using bootstrapped data envelopment analysis. Results indicate that case-mix adjustment is important, and there are significant differences in the case-mix adjusted performance measures as well as in productivity both at the national and hospital levels. For most quality indicators, the performance measures reveal room for improvement. There is a weak but statistical significant trade-off between productivity and inpatient readmissions within 30 days but a tendency that hospitals with high 30-day mortality also have higher costs. Hence, no clear cost-quality trade-off pattern was discovered. Patient registers can be used and developed to improve future quality and cost comparisons.

Patient perspectives on centralisation of low volume, highly specialised procedures in Sweden.

This study explores important considerations from a patient perspective in decisions regarding centralisation of specialised health care services. The analysis is performed in the framework of the Swedish National Board of Health and Welfare's ongoing work to evaluate and, if appropriate, centralise low volume, highly specialised, health services defined as National Specialised Medical Care. In addition to a literature review, a survey directed to members of patient associations and semi-structured interviews with patient association representatives and health care decision makers were conducted. The results showed that from a patient perspective, quality of care in terms of treatment outcomes is the most important factor in decisions regarding centralisation of low volume, highly specialised health care. The study also indicates that additional factors such as continuity of treatment and a well-functioning care pathway are highly important for patients. However, some of these factors may be dependent on the implementation process and predicting how they will evolve in case of centralisation will be difficult. Patient engagement and patient association involvement in the centralisation process is likely to be a key component in attaining patient focused care and ensuring patient satisfaction with the centralisation decisions.

Cross-country comparisons of health-care costs: the case of cancer treatment in the Nordic countries.

The objective of this study is to perform a cross-country comparison of cancer treatment costs in the Nordic countries, and to demonstrate the added value of decomposing documented costs in interpreting national differences. The study is based on individual-level data from national patient and prescription drug registers, and data on cancer prevalence from the NORDCAN database. Hospital costs were estimated on the basis of information on diagnosis-related groups (DRG) cost weights and national unit costs. Differences in per capita costs were decomposed into two stages: stage one separated the price and volume components, and stage two decomposed the volume component, relating the level of activity to service needs and availability. Differences in the per capita costs of cancer treatment between the Nordic countries may be as much as 30 per cent. National differences in the costs of treatment mirror observed differences in total health care costs. Differences in health care costs between countries may relate to different sources of variation with different policy implications. Comparisons of per capita spending alone can be misleading if the purpose is to evaluate, for example, differences in service provision and utilisation. The decomposition analysis helps to identify the relative influence of differences in the prevalence of cancer, service utilisation and productivity.

Causal inference regarding infectious aetiology of chronic conditions: a systematic review.

BACKGROUND: The global burden of disease has shifted from communicable diseases in children to chronic diseases in adults. This epidemiologic shift varies greatly by region, but in Europe, chronic conditions account for 86% of all deaths, 77% of the disease burden, and up to 80% of health care expenditures. A number of risk factors have been implicated in chronic diseases, such as exposure to infectious agents. A number of associations have been well established while others remain uncertain. METHODS AND FINDINGS: We assessed the body of evidence regarding the infectious aetiology of chronic diseases in the peer-reviewed literature over the last decade. Causality was assessed with three different criteria: First, the total number of associations documented in the literature between each infectious agent and chronic condition; second, the epidemiologic study design (quality of the study); third, evidence for the number of Hill's criteria and Koch's postulates that linked the pathogen with the chronic condition. We identified 3136 publications, of which 148 were included in the analysis. There were a total of 75 different infectious agents and 122 chronic conditions. The evidence was strong for five pathogens, based on study type, strength and number of associations; they accounted for 60% of the associations documented in the literature. They were human immunodeficiency virus, hepatitis C virus, Helicobacter pylori, hepatitis B virus, and Chlamydia pneumoniae and were collectively implicated in the aetiology of 37 different chronic conditions. Other pathogens examined were only associated with very few chronic conditions (≤ 3) and when applying the three different criteria of evidence the strength of the causality was weak. CONCLUSIONS: Prevention and treatment of these five pathogens lend themselves as effective public health intervention entry points. By concentrating research efforts on these promising areas, the human, economic, and societal burden arising from chronic conditions can be reduced.

Health care performance comparison using a disease-based approach: the EuroHOPE project.

This article describes the methodological challenges associated with disease-based international comparison of health system performance and how they have been addressed in the EuroHOPE (European Health Care Outcomes, Performance and Efficiency) project. The project uses linkable patient-level data available from national sources of Finland, Hungary, Italy, The Netherlands, Norway, Scotland and Sweden. The data allow measuring the outcome and the use of resources in uniformly-defined patient groups using standardized risk adjustment procedures in the participating countries. The project concentrates on five important disease groups: acute myocardial infarction (AMI), ischemic stroke, hip fracture, breast cancer and very low birth weight and preterm infants (VLBWI). The essentials of data gathering, the definition of the episode of care, the developed indicators concerning baseline statistics, treatment process, cost and outcomes are described. The preliminary results indicate that the disease-based approach is attractive for international performance analyses, because it produces various measures not only at country level but also at regional and hospital level across countries. The possibility of linking hospital discharge register to other databases and the availability of comprehensive register data will determine whether the approach can be expanded to other diseases and countries.

International hospital productivity comparison: experiences from the Nordic countries.

This article focuses on describing the methodological challenges intrinsic in international comparative studies of hospital productivity and how these challenges have been addressed within the context of hospital comparisons in the Nordic countries. The hospital sectors in the Nordic countries are suitable for international comparison as they exhibit similar structures in the organisation for hospital care, hold administrative data of good quality at the hospital level, apply a similar secondary patient classification system, and use similar definitions of operating costs. The results of a number of studies have suggested marked differences in hospital cost efficiency and hospital productivity across the Nordic countries and the Finnish hospitals have the highest estimates in all the analyses. Explanatory factors that were tested and seemed to be of limited importance included institutional, structural and technical. A factor that is yet to be included in the Nordic hospital productivity comparison is the quality of care. Patient-level data available from linkable national registers in each country enable the development of quality indicators and will be included in the forthcoming hospital productivity studies within the context of the EuroHOPE (European health care outcomes, performance and efficiency) project.

Cost efficiency of university hospitals in the Nordic countries: a cross-country analysis.

This paper estimates cost efficiency scores using the bootstrap bias-corrected procedure, including variables for teaching and research, for the performance of university hospitals in the Nordic countries. Previous research has shown that hospital provision of research and education interferes with patient care routines and inflates the costs of health care services, turning university hospitals into outliers in comparative productivity and efficiency analyses. The organisation of patient care, medical education and clinical research as well as available data at the university hospital level are highly similar in the Nordic countries, creating a data set of comparable decision-making units suitable for a cross-country cost efficiency analysis. The results demonstrate significant differences in university hospital cost efficiency when variables for teaching and research are entered into the analysis, both between and within the Nordic countries. The results of a second-stage analysis show that the most important explanatory variables are geographical location of the hospital and the share of discharges with a high case weight. However, a substantial amount of the variation in cost efficiency at the university hospital level remains unexplained.

Measuring cost efficiency in the Nordic hospitals--a cross-sectional comparison of public hospitals in 2002.

The aim of this study was to compare the performance of hospital care in four Nordic countries: Norway, Finland, Sweden and Denmark. Using national discharge registries and cost data from hospitals, cost efficiency in the production of somatic hospital care was calculated for public hospitals. Data were collected using harmonized definitions of inputs and outputs for 184 hospitals and data envelopment analysis was used to calculate Farrell efficiency estimates for the year 2002. Results suggest that there were marked differences in the average hospital efficiency between Nordic countries. In 2002, average efficiency was markedly higher in Finland compared to Norway and Sweden. This study found differences in cost efficiency that cannot be explained by input prices or differences in coding practices. More analysis is needed to reveal the causes of large efficiency disparities between Nordic hospitals.