Comorbidities in childhood atopic dermatitis: A population-based study.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is associated with allergic comorbidities. However, studies examining comorbidities in childhood AD are incomplete, which may contribute to suboptimal care. OBJECTIVE: The objective was to compare the risk of developing different allergic and non-allergic comorbidities among children with AD to that of a matched non-AD reference cohort in Sweden. METHODS: This was a nationwide population-based cohort study using longitudinal data from primary and specialist care registers. Patients with AD were identified by confirmed diagnosis in primary or specialist care. The non-AD reference cohort was randomly drawn from the general population and matched 1:1 with the AD patients. The risk of developing the following conditions was evaluated: hypersensitivity and allergic disorders, neurological disorders, psychiatric disorders, infections, immunological and inflammatory disorders, Type 1 diabetes (T1D), endocrine and metabolic disorders, skeletal disorders, ocular disorders and malignancies. RESULTS: This study included 165,145 patients with AD (mild-to-moderate [n = 126,681] and severe [n = 38,464]) and an equally sized reference cohort. Patients with AD displayed a higher risk of developing comorbid conditions for all investigated categories, except for T1D and skeletal disorders, compared with the reference cohort. The highest risk compared with the reference cohort was observed for hypersensitivity and allergic disorders (hazard ratio [HR]: 3.87), followed by malignancies (HR: 2.53) and immunological and inflammatory disorders (HR: 2.36). Patients with AD also had higher risk of developing multiple comorbidities (≥2). The risk of comorbidity onset increased alongside AD severity and patients with active AD were associated with increased risk of comorbidity onset compared with patients in remission. CONCLUSIONS: The clinical burden of AD is substantial for children with AD and patients are at an increased risk of developing several comorbid conditions extending beyond the atopic march. Our results also showed a positive association between worsening severity of AD and an increased risk of comorbidity onset.

Validation of Patient Identification Algorithms for Atopic Dermatitis Using Healthcare Databases.

INTRODUCTION: The use of real-world data offers a possibility to perform large-scale epidemiological studies in actual clinical settings. Despite their many advantages, administrative databases were not designed to be used in research, and the validation of diagnoses and treatments in administrative databases is needed. The primary objective of this study was to validate an existing algorithm based on dispensed prescriptions and diagnoses of skin conditions to identify pediatric patients with atopic dermatitis (AD), using a diagnosis of AD in primary care as a gold standard. METHODS: Retrospective observational data were collected from nation-wide secondary care and pharmacy-dispensed medication databases and two regional primary care databases in Sweden. An existing algorithm and a Modified algorithm, using skin-specific diagnoses from secondary care and/or pharmacy-dispensed prescriptions to identify patients with AD, were assessed. To verify the presence of AD, diagnoses from primary care were used in the base case and complemented with diagnoses from secondary care in a sensitivity analysis. RESULTS: The sensitivity (30.0%) and positive predictive value (PPV) (40.7%) of the existing algorithm were low in the pediatric patient population when using primary care data only but increased when secondary care visits were also included in the Modified algorithm (sensitivity, 62.1%; PPV, 66.3%). The specificity of the two algorithms was high in both the base case and sensitivity analysis (95.1% and 94.1%). In the adult population, sensitivity and PPV were 20.4% and 8.7%, respectively, and increased to 48.3% and 16.9% when secondary care visits were also included in the Modified algorithm. CONCLUSION: The Modified algorithm can be used to identify pediatric AD populations using primary and secondary administrative data with acceptable sensitivity and specificity, but further modifications are needed to accurately identify adult patients with AD.

Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting.

Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9-6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5-9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score -1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (-3.0 to -0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD-fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Clinical and Economic Burden of Pediatric Mild-to-Moderate Atopic Dermatitis: A Population-Based Nested Case-Control Study in Sweden.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by pruritic, eczematous lesions. Recent evidence suggests that AD may be a systemic disorder, implying that management of this disease extends beyond merely controlling symptoms associated with AD. Even though this disease is highly prevalent in children and patients typically present with mild-to-moderate symptoms, the disease burden is not well established. METHODS: A large, retrospective cohort study of Swedish population data was conducted to compare the clinical burden in terms of healthcare resource use and direct medical costs for pediatric mild-to-moderate (pM2M) AD patients (≤ 14 years of age, N = 87,721) with matched controls. The burden of a severe AD cohort was also evaluated. Severity of AD was defined by treatment usage and systemic treatment was used as a proxy for severe AD. A robust approach was used by including any type of secondary care visits known to be more common in AD patients than in the general population; however, data for primary care visits were not available. RESULTS: For healthcare resource use, the incidence rate ratio (pM2M AD versus reference cohort) of secondary care visits ranged from 1.56 to 2.35 during each of 5 years after AD onset (all p < 0.001), with largest differences seen in years 1-2. The average direct medical cost (SD) was €1111 (3416) and €524 (2446) in the pM2M AD and reference cohorts, respectively. The corresponding estimate in the severe AD cohort was €1906 (7067). Including all secondary care visits and pharmacy-dispensed medications, the pM2M AD cohort was shown to have an additional €118.9 million in direct medical costs over 5 years compared with the reference cohort. CONCLUSIONS: This study shows significant clinical and economic burden of pM2M AD with important secondary care resource utilization, suggesting a need for further research to increase treatment options and improve the management of these patients.

History of Previous Fracture and Imminent Fracture Risk in Swedish Women Aged 55 to 90 Years Presenting With a Fragility Fracture.

The term "fracture cascade" refers to the sequence of fragility fractures resulting from the increased fracture risk that occurs with aging and following fractures. Here, we evaluate the sequence of previous fractures in women aged 55 to 90 years presenting with a fragility fracture and subsequent (12 to 24 months) fracture incidence. In this retrospective, observational study, women aged 55 to 90 years with an "index" fragility fracture in 2013 were identified from Swedish national registries. A history of previous fractures (2001 to 2012) and osteoporosis treatment was used to characterize fracture cascade patterns. Cumulative incidence of new fractures within 12 to 24 months following the index fracture, based on index fracture type and age, were used to describe the risk of subsequent fractures. A total of 35,146 women with a mean age of 73.8 years were included (7180 hip, 2786 clinical vertebral, and 25,180 nonhip/nonvertebral [NHNV] index fractures); 38% of women with hip, 38% with clinical vertebral, and 25% with NHNV index fractures had one or more previous fractures. Across all index fracture types, the proportion of women with any previous fracture increased with age; 34% to 46% of index hip or clinical vertebral fractures in women ≥70 years were not their first fracture. Following any index fracture, cumulative incidence of a new fracture over 24 months was over 11% (index clinical vertebral 18%; index hip 14%). Osteoporosis treatment rates were low both in patients with (27%) and without (18%) a previous fracture. These descriptive data demonstrate that almost one-third of women aged 55 to 90 years suffering a new fracture have had a previous fragility fracture. Fracture location influences incidence and type of subsequent fracture during the 24 months following a fragility fracture, with clinical vertebral fractures carrying the greatest imminent fracture risk. These data highlight the clinical impact and need for early, effective treatment soon after any fragility fracture. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Incorporating the Environmental Impact into a Budget Impact Analysis: The Example of Adopting RESPIMAT® Re-usable Inhaler.

BACKGROUND: RESPIMAT® re-usable enables patients to re-use the inhaler and its availability therefore reduces the number of inhalers and associated wastage. OBJECTIVE: The objective of this study was to perform an economic evaluation that incorporates the ecological impact of adopting RESPIMAT re-usable into the healthcare system in Germany. METHODS: Inhaler costs and environmental impact over 5 years in Germany in a scenario with RESPIMAT re-usable compared to a scenario without RESPIMAT re-usable were estimated using a budget impact model. The carbon emissions were derived for each treatment pattern considering the whole life cycle (cradle-to-grave) of the inhaler product. The cost of carbon emissions was estimated using a societal cost per ton of carbon emission. RESULTS: By introducing RESPIMAT re-usable in Germany, it was estimated that by 2023, the number of inhalers used would have decreased by 5,748,750 compared to a scenario without RESPIMAT re-usable. In addition, this measure would reduce the environmental burden of inhaler use while at the same time reducing medical cost of inhalers. CONCLUSIONS: Adopting RESPIMAT® re-usable to the national healthcare services may be a cost-saving option, which has the additional benefit of reducing the societal cost of carbon emissions.

Elimination of hepatitis C virus in Germany: modelling the cost-effectiveness of HCV screening strategies.

BACKGROUND: Chronic hepatitis C is a major public health burden. With new interferon-free direct-acting agents (showing sustained viral response rates of more than 98%), elimination of HCV seems feasible for the first time. However, as HCV infection often remains undiagnosed, screening is crucial for improving health outcomes of HCV-patients. Our aim was to assess the long-term cost-effectiveness of a nationwide screening strategy in Germany. METHODS: We used a Markov cohort model to simulate disease progression and examine long-term population outcomes, HCV associated costs and cost-effectiveness of HCV screening. The model divides the total population into three subpopulations: general population (GEP), people who inject drugs (PWID) and HIV-infected men who have sex with men (MSM), with total infection numbers being highest in GEP, but new infections occurring only in PWIDs and MSM. The model compares four alternative screening strategies (no/basic/advanced/total screening) differing in participation and treatment rates. RESULTS: Total number of HCV-infected patients declined from 275,000 in 2015 to between 125,000 (no screening) and 14,000 (total screening) in 2040. Similarly, lost quality adjusted life years (QALYs) were 320,000 QALYs lower, while costs were 2.4 billion EUR higher in total screening compared to no screening. While incremental cost-effectiveness ratio (ICER) increased sharply in GEP and MSM with more comprehensive strategies (30,000 EUR per QALY for total vs. advanced screening), ICER decreased in PWIDs (30 EUR per QALY for total vs. advanced screening). CONCLUSIONS: Screening is key to have an efficient decline of the HCV-infected population in Germany. Recommendation for an overall population screening is to screen the total PWID subpopulation, and to apply less comprehensive advanced screening for MSM and GEP.

A Budget Impact Model to Estimate the Environmental Impact of Adopting RESPIMAT® Re-usable in the Nordics and Benelux.

INTRODUCTION: The healthcare sector contributes 5-8% of the global greenhouse gas emissions. Global and regional organizations and governments have started to design and implement measures to reduce global greenhouse gas emissions in the healthcare sector, e.g. by green public procurement policies and inclusion of ecological considerations in the decision-making process for purchasing and funding of healthcare technologies. The objective of this study was to perform budget impact analysis of adopting RESPIMAT re-usable in the Nordics and Benelux that considered both the traditional healthcare costs as well as the environmental impact. METHODS: Inhaler costs and environmental impact over 5 years in the Nordics and Benelux in a scenario with RESPIMAT re-usable compared to a scenario without RESPIMAT re-usable were estimated using an budget impact model. RESPIMAT re-usable enables patients to re-use the inhaler device and its availability therefore reduces the number of inhalers and associated wastage. The carbon emissions were derived for each treatment pattern considering the whole life cycle (cradle-to-grave) of the inhaler product. The cost of carbon emissions was estimated using a societal cost per ton of carbon emission. RESULTS: Progressively introducing RESPIMAT re-usable in the Nordics and Benelux was estimated to decrease the number of inhalers used by 2023 by 7,466,621 compared to a scenario without RESPIMAT re-usable, which would result in a reduction of the environmental burden of inhaler use of 4717 tCO2e and a decrease in societal cost of €205,888. CONCLUSIONS: Adopting RESPIMAT re-usable would lead to a substantial reduction in CO2 emissions, leading to savings from a societal perspective. FUNDING: Boehringer Ingelheim.

Differing impact of clinical factors on the risk of fracture in younger and older women in the general population and an osteoporosis clinic population.

This study assesses the impact of risk factors for fracture in women aged 80+ and 60-79. The results suggest that risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort. PURPOSE: This study assesses whether the impact of classical risk factors for fracture due to osteoporosis is different in women aged 80+ and women aged 60-79. Since most prior research on the contribution of risk factors is based on patients below 80 years of age, this study aims to fill this knowledge gap to increase the accuracy of risk assessment in the oldest old. METHODS: Retrospective, observational cohort study using Swedish national health register data and BMD data from osteoporosis clinics. Women aged at least 60 were identified from a random sample of the general population and from the BMD databases and allocated to two populations representing patients at different stages of risk assessment. The relative impact of risk factors on fracture risk was assessed using multivariate competing risk regression with fracture as outcome and death as competing event. RESULTS: A total of 163,329 women were included from the general population (52,499 aged 80+) and 22,378 from the BMD databases (4563 aged 80+). The clinical risk factors with relatively highest effect on fracture risk in the older patients were prior fracture and hip T-score below - 2.5 SD. Other included risk factors showed lower impact in the older compared to the younger strata. CONCLUSIONS: This study confirms our understanding of the key risk factors for fracture: age, prior fracture, and a low T-score. Regarding remaining risk factors, risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort.

Cost-Effectiveness of Intervention Thresholds for the Treatment of Osteoporosis Based on FRAX(®) in Portugal.

Cost-effective intervention thresholds (ITs) based on FRAX(®) were determined for Portugal. Assuming a willingness to pay (WTP) of €32,000 per quality-adjusted life years (QALYs), treatment with generic alendronate is cost effective for men and women aged 50 years or more, with 10-year probabilities for major osteoporotic fractures and hip above 8.8 and 2.5 %, respectively. The aim of the present study was to identify the 10-year probabilities of a major and hip osteoporotic fracture using FRAX(®) validated for Portugal, above which pharmacologic interventions become cost effective in the Portuguese context. A previously developed and validated state transition Markov cohort model was populated with epidemiologic, economic and quality-of-life fracture data from Portugal. Cost-effectiveness of FRAX(®)-based ITs was calculated for generic alendronate and proprietary zoledronic acid, denosumab and teriparatide were compared to "no intervention", assuming a WTP of €32,000 (two times national Gross Domestic Product per capita) per QALYs. In the Portuguese epidemiological and economic context, treatment with generic alendronate was cost effective for men and women aged 50 years or more, with 10-year probabilities at or above 8.8 % for major osteoporotic fractures and 2.5 % for hip fractures. Cost-effective threshold 10-year probabilities for major osteoporotic and hip fractures were higher for zoledronic acid (20.4 and 10.1 %), denosumab (34.9 and 10.1 %) and teriparatide (77.8 and 62.6 %), respectively. A tool is provided to perform the calculation of cost-effective ITs for different medications, according to age group and diverse levels of WTP. Cost-effective ITs, for different medications, age groups and WTP, based on 10-year probabilities of major and hip fracture probabilities calculated with FRAX are provided.