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.

Severe asthma trajectories in adults: findings from the NORDSTAR cohort.

BACKGROUND: There is limited evidence on the pathways leading to severe asthma and we are presently unable to effectively predict the progression of the disease. We aimed to describe the longitudinal trajectories leading to severe asthma and to describe clinical events preceding disease progression in a nationwide population of patients with severe asthma. METHODS: We conducted an observational study based on Swedish data from the NORdic Dataset for aSThmA Research (NORDSTAR) research collaboration platform. We identified adult patients with severe asthma in 2018 according to the European Respiratory Society/American Thoracic Society definition and used latent class analysis to identify trajectories of asthma severity over a 10-year retrospective period from 2018. RESULTS: Among 169 128 asthma patients, we identified 4543 severe asthma patients. We identified four trajectories of severe asthma that were labelled as: trajectory 1 "consistently severe asthma" (n=389 (8.6%)), trajectory 2 "gradual onset severe asthma" (n=942 (20.7%)), trajectory 3 "intermittent severe asthma" (n=1685 (37.1%)) and trajectory 4 "sudden onset severe asthma" (n=1527 (33.6%)). "Consistently severe asthma" had a higher daily inhaled corticosteroid dose and more prevalent osteoporosis compared with the other trajectories. Patients with "gradual onset severe asthma" and "sudden onset severe asthma" developed type 2-related comorbidities concomitantly with development of severe asthma. In the latter group, this primarily occurred within 1-3 years preceding onset of severe asthma. CONCLUSIONS: Four distinct trajectories of severe asthma were identified illustrating different patterns of progression of asthma severity. This may eventually enable the development of better preventive management strategies in severe asthma.

Prevalence and management of severe asthma in the Nordic countries: findings from the NORDSTAR cohort.

Background: Real-life evidence on prevalence and management of severe asthma is limited. Nationwide population registries across the Nordic countries provide unique opportunities to describe prevalence and management patterns of severe asthma at population level. In nationwide register data from Sweden, Norway and Finland, we examined the prevalence of severe asthma and the proportion of severe asthma patients being managed in specialist care. Methods: This is a cross-sectional study based on the Nordic Dataset for Asthma Research (NORDSTAR) research collaboration platform. We identified patients with severe asthma in adults (aged ≥18 years) and in children (aged 6-17 years) in 2018 according to the European Respiratory Society/American Thoracic Society definition. Patients managed in specialist care were those with an asthma-related specialist outpatient contact (only available in Sweden and Finland). Results: Overall, we identified 598 242 patients with current asthma in Sweden, Norway and Finland in 2018. Among those, the prevalence of severe asthma was 3.5%, 5.4% and 5.2% in adults and 0.4%, 1.0%, and 0.3% in children in Sweden, Norway and Finland, respectively. In Sweden and Finland, 37% and 40% of adult patients with severe asthma and two or more exacerbations, respectively, were managed in specialist care; in children the numbers were 56% and 41%, respectively. Conclusion: In three Nordic countries, population-based nationwide data demonstrated similar prevalence of severe asthma. In children, severe asthma was a rare condition. Notably, a large proportion of patients with severe asthma were not managed by a respiratory specialist, suggesting the need for increased recognition of severe asthma in primary care.

Persistence With Biologic Treatments in Psoriasis: A Structured Literature Review of Studies Using Administrative Database and Clinical Registry Data.

BACKGROUND: Psoriasis is a chronic, autoimmune-mediated inflammatory disorder. Drug persistence is a composite measure of effectiveness, safety, and treatment satisfaction, often estimated using data from administrative databases and clinical registries. Persistence rates calculated from these two data sources appear to be systematically different. OBJECTIVE: Review and compare persistence rates of psoriasis-indicated biologics reported in registry and database studies. METHODS: A structured literature search of studies published during 2009-2019 was performed in PubMed and American Academy of Dermatology records to identify research describing persistence with biologic treatments in psoriasis patients. English language retrospective or prospective persistence studies based on database or registry data, and reporting on at least two psoriasis-indicated biologics, of which at least one was ustekinumab, secukinumab, ixekizumab or guselkumab, were included. Single-arm studies, randomized control trials, systematic literature reviews, and studies presenting stratified results only were excluded. RESULTS: A total of 37 studies (22 registry- and 15 database-derived) comprising 76,000 patients were included. On average, drug persistence collected from registry studies was 18% higher than database studies. CONCLUSION: The findings of this study may be used by practitioners to make meaningful comparisons between persistence data derived from registries and databases, and thereby improve clinical decision making. J Drugs Dermatol. 2022;21(8):881-889. doi:10.36849/JDD.6789R1.

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.

Association between surgical volumes and real-world healthcare cost when using a mesh capturing device for pelvic organ prolapse: A 5-years comparison between single- versus multicenter use.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate whether high surgical volume at a single center was associated with lower healthcare costs compared to lower surgical volume in a multicenter setting. METHODS: All patients had symptomatic and anatomical apical prolapse (POP-Q ≥ stage II) with or without cystocele and were operated on by a standard surgical procedure using the Uphold mesh. Data on time of resource use in terms of surgery time, hospital stay and re-interventions across 5 years were compared between the single center (97 patients) and multicenter (173 patients, at 24 clinics). Unit costs for surgical time, inpatient and outpatient visits were extracted from the single-center hospital's operation analysis program and prime production cost. Total costs were estimated for primary surgery and during 5-year follow-up. RESULTS: Costs for primary surgery were comparable between the single and the multicenter ($13,561 ± 2688 and $13,867 ± 1177, P = 0.29). Follow-up costs 5 years after primary surgery were 2.8 times higher at the multicenter than single center ($3262 vs. $1149, P < 0.001). Mean cost per patient over 5 years was significantly lower at the single than multicenter [$14,710 (CI: 14,168-15,252) vs. $17,128 (CI: 16,952-17,305), P < 0.001)]. CONCLUSIONS: Using a mesh kit for apical pelvic organ prolapse in a high surgical volume center was associated with reduced healthcare costs compared with a lower volume multiple-site setting. The cost reduction at the high surgical volume center increased over time because of lower surgical and medical re-intervention rates for postoperative complications and recurrence.

Corrigendum to: Persistence of biologic treatments in psoriatic arthritis: a population-based study in Sweden.

[This corrects the article DOI: 10.1093/rap/rkaa070.][This corrects the article DOI: 10.1093/rap/rkaa070.].

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.

Incidence of Psoriatic Arthritis in Patients with Skin Psoriasis and Associated Risk Factors: A Retrospective Population-based Cohort Study in Swedish Routine Clinical Care.

The incidence of psoriatic arthritis in patients with psoriasis is unclear; existing estimates differ by a factor of ten. Complete population-level data is needed to provide accurate estimates with high confidence. A total of 123,814 adults with psoriasis, free from pre-existing psoriatic arthritis, were identified in population-based data from secondary care in Sweden during 2007 to 2017. Incidence was calculated as the number of psoriatic arthritis diagnosis events per 100 patient-years. Time to diagnosis was assessed using cumulative incidence and Cox proportional hazards models to identify risk factors. Incidence of psoriatic arthritis in patients with psoriasis was 1.69 per 100 patient-years (95% confidence interval 1.65-1.72) overall, and 1.48, 3.00, and 5.49 per 100 patient-years in patients with mild, moderate and severe psoriasis, respectively. Risk of psoriatic arthritis was 3.2 times higher amongst patients with severe psoriasis compared with mild disease. Dermatologists should regularly assess risk factors for psoriatic arthritis in clinical practice in order to improve the detection of psoriatic arthritis.

Association of Skin Psoriasis and Somatic Comorbidity With the Development of Psychiatric Illness in a Nationwide Swedish Study.

Importance: Psoriasis is a complex systemic disease with skin involvement, somatic comorbidity, and psychiatric illness (PI). Although this view of psoriasis is widely accepted, potential synergies within this triad of symptoms have not been adequately investigated. Objectives: To investigate the independent association of skin psoriasis and somatic comorbidity with the development of PI and to assess whether skin psoriasis and somatic comorbidity act synergistically to produce a risk of PI that is greater than the additive associations. Design, Setting, and Participants: Participants were enrolled between January 2005 and December 2010, in this retrospective matched case-control study using secondary (ie, administrative), population-based registry data from Swedish patients in routine clinical care. The dates of analysis were March 2017 to December 2019. Participants were patients with skin psoriasis and control participants without psoriasis matched on age, sex, and municipality, who were all free of preexisting PI. Exposures: Presence of skin psoriasis and somatic comorbidity (captured through the Charlson Comorbidity Index and the Elixhauser Comorbidity Index). Main Outcomes and Measures: Risk of PI onset (composite of depression, anxiety, and suicidality) is shown using Kaplan-Meier curves stratified by the presence of skin psoriasis and somatic comorbidity. Adjusted associations of skin psoriasis and somatic comorbidity with the development of PI were analyzed using Cox proportional hazards regression models, including interactions to assess synergistic associations. The 3 components of PI were also assessed individually. Results: A total of 93 239 patients with skin psoriasis (mean [SD] age, 54 [17] years; 47 475 men [51%]) and 1 387 495 control participants (mean [SD] age, 54 [16] years; 702 332 men [51%]) were included in the study. As expected, patients with skin psoriasis were more likely to have somatic comorbidity and PI than control participants. Compared with those without skin psoriasis or somatic comorbidity, patients with psoriasis without somatic comorbidity had a 1.32 times higher risk of PI onset (hazard ratio [HR], 1.32; 95% CI, 1.27-1.36; P < .001), whereas patients with psoriasis with somatic comorbidity had a 2.56 times higher risk of PI onset (HR, 2.56; 95% CI, 2.46-2.66; P < .001). No synergistic associations of skin psoriasis and somatic comorbidity with the development of PI were found (HR, 0.93; 95% CI, 0.81-1.04; P = .21). Conclusions and Relevance: This study found that somatic comorbidity appeared to alter PI onset even more than skin psoriasis. The observed association of skin psoriasis and somatic comorbidity with the development of PI reinforces the need for proactive, holistic treatment of patients with psoriasis.

Persistence of biologic treatments in psoriatic arthritis: a population-based study in Sweden.

OBJECTIVES: TNF inhibitors (TNFis) and IL inhibitors are effective treatments for PsA. Treatment non-persistence (drug survival, discontinuation) is a measure of effectiveness, tolerability and patient satisfaction or preferences in real-world clinical practice. Persistence on these treatments is not well understood in European PsA populations. The aim of this study was to compare time to non-persistence for either ustekinumab (IL-12/23 inhibitor) or secukinumab (IL-17 inhibitor) to a reference group of adalimumab (TNFi) treatment exposures in PsA patients and identify risk factors for non-persistence. METHODS: A total of 4649 exposures of adalimumab, ustekinumab, and secukinumab in 3918 PsA patients were identified in Swedish longitudinal population-based registry data. Kaplan-Meier curves were constructed to measure treatment-specific real-world risk of non-persistence and adjusted Cox proportional hazards models were estimated to identify risk factors associated with non-persistence. RESULTS: Ustekinumab was associated with a lower risk of non-persistence relative to adalimumab in biologic-naïve [hazard ratio (HR) 0.48 (95% CI 0.33, 0.69)] and biologic-experienced patients [HR 0.65 (95% CI 0.56, 0.76)], while secukinumab was associated with a lower risk in biologic-naïve patients [HR 0.65 (95% CI 0.49, 0.86)] but a higher risk of non-persistence in biologic-experienced patients [HR 1.20 (95% CI 1.03, 1.40)]. Biologic non-persistence was also associated with female sex, axial involvement, recent disease onset, biologic treatment experience and no psoriasis. CONCLUSION: Ustekinumab exhibits a favourable treatment persistency profile relative to adalimumab overall and across lines of treatment. The performance of secukinumab is dependent on biologic experience. Persistence and risk factors for non-persistence should be accounted for when determining an optimal treatment plan for patients.

Budget impact analysis of demineralized bone matrix in combination with autograft in lumbar spinal fusion procedures for the treatment of lumbar degenerative disc disease in Spain.

OBJECTIVE: To estimate the budget impact (BI) of introducing local autograft (LA) combined with demineralized bone matrix (LA + DBM) in lumbar spinal fusion (LSF) procedures to treat lumbar degenerative disc disease (LDDD) in Spain. METHODS: A decision tree model was developed to evaluate the 4-year BI associated with introducing LA + DBM putty to replace currently available grafting methods, including iliac crest bone graft (ICBG), LA alone, and LA combined with beta-tricalcium phosphate (LA + ceramics), with 30%, 40%, and 30% market shares, respectively. The analysis was conducted for a hypothetical cohort of 100 patients with LDDD receiving LSF, assuming LA + DBM would replace 100% of the standard of care mix. The fusion rates extracted from the literature were validated by an expert panel. Costs (€2017) were obtained from different Spanish sources. Budget impact and incremental cost per successful fusion were calculated from the perspective of the Spanish National Health System (NHS). RESULTS: Over 4 years, replacing currently available options with LA + DBM for 100 patients resulted in an additional cost of €12,330 (€123/patient), and an additional 14 successful fusions, implying a cost of €881 per additional successful fusion. When costs of productivity loss were included, the introduction of LA + DBM resulted in cost savings of €70,294 (€703/patient). LIMITATIONS: The lack of high-quality, homogeneous, head-to-head research studying the efficacy of grafting procedures available to patients undergoing LSF, in addition to a lack of long-term follow-up in existing studies. Therefore, the number of fusions occurring within the model's time horizon may be underestimated. CONCLUSIONS: Acquisition costs of DBM were partially offset by costs of failed fusions, adverse events and reoperation when switching 100 hypothetical LDDD patients undergoing LSF procedures from standard of care grafting methods to LA + DBM from the perspective of the Spanish NHS. DBM cost was entirely offset when costs of lost productivity were considered.

A generic health-related quality of life instrument for assessing pelvic organ prolapse surgery: correlation with condition-specific outcome measures.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to investigate the use of a generic and globally accessible instrument for assessing health-related quality of life (HR-QoL) in pelvic organ prolapse (POP) surgery. METHODS: In a prospective multicenter setting, 207 women underwent surgery for apical prolapse [stage ≥2, Pelvic Organ Prolapse Quantificcation (POP-Q) system] with or without anterior wall defect. Demographic and surgical characteristics were collected before surgery. Results of the 15-dimensional (15D) instrument and condition-specific pelvic floor symptoms as assessed using the Pelvic Floor Distress Inventory questionnaire (PFDI-20), including its subscales Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), Colorectal-Anal Distress Inventory-8 (CRADI-8), and Urinary Distress Inventory-6 (UDI-6), were assessed preoperatively and 2 months and 1 year after surgery. RESULTS: HR-QoL as estimated by 15D was improved 1 year after surgery (p < 0.001). Prolapse-related 15D profile-index measures (excretion, discomfort, sexual activity, distress, and mobility) were significantly improved after surgery (p < 0.05-0.001). Significant inverse associations were detected between increased 15D scores and a decrease in PFDI-20 and subscale scores (p < 0.001), indicating improvements on both instruments. CONCLUSIONS: Generic HR-QoL as estimated by 15D improved significantly after apical POP surgery and correlated with improvements of condition-specific outcome measures. These results suggest that a comprehensive evaluation of global HR-QoL is valid in assessing pelvic reconstructive surgery and may provide novel and important insights into previously understudied areas, such as cost-utility and cost-effectiveness analysis after urogynecological surgery.

Repeated intermittent ulipristal acetate in the treatment of uterine fibroids: a cost-effectiveness analysis.

There are limited treatment options available for women with moderate to severe symptoms of uterine fibroids (UFs) who wish to avoid surgery. For these women, treatment with standard pharmaceuticals such as contraceptives is often insufficient to relieve symptoms, and patients may require surgery despite their wish to avoid it. Clinical trials demonstrate that ulipristal acetate 5 mg (UPA) is an effective treatment for this patient group, but its cost-effectiveness has not been assessed in this population. A decision-analytic model was developed to simulate a cohort of patients in this population under treatment with UPA followed by surgery as needed compared to treatment with iron and non-steroidal anti-inflammatory drug (NSAID) followed by surgery as needed (best supportive care, BSC). The analysis took the perspective of the National Health Service (NHS) in England, UK, and was based on the published UPA clinical trials. Results were calculated for the long-term costs and quality-adjusted life years (QALYs) for each treatment arm and combined into an incremental cost-effectiveness ratio (ICER) as the primary outcome. The impact of parameter uncertainty on the results was assessed using scenario, deterministic, and probabilistic sensitivity analyses. The results show that treating patients with the UPA strategy, instead of the BSC strategy, results in an additional cost of £1,115 and a gain of 0.087 QALYs, resulting in an ICER of £12,850. Given commonly accepted cost-effectiveness thresholds in England, the use of UPA as a repeated, intermittent treatment for women with moderate to severe symptoms of UF wishing to avoid surgery is likely to be a cost-effective intervention when compared to BSC.

How is disease severity associated with quality of life in psoriasis patients? Evidence from a longitudinal population-based study in Sweden.

BACKGROUND: Assessing the impact of disease severity on generic quality of life (QOL) is a critical step in outcomes research and in the development of decision-analytic models structured around health states defined by clinical measures. While data from routine clinical practice found in healthcare registers are increasingly used for research, more attention should be paid to understanding the relationship between clinical measures of disease severity and QOL. The purpose of this work was therefore to investigate this relationship in psoriasis using a population-based dataset. METHODS: Severity was measured by the Psoriasis Area and Severity Index (PASI), which combines severity of erythema, induration, and desquamation into a single value ranging from 0 to 72. The generic EQ-5D-3L utility instrument, under the UK tariff, was used to measure QOL. The association between PASI and EQ-5D-3L was estimated using a population-based dataset of 2674 patients with moderate to severe psoriasis enrolled over ten years in the Swedish psoriasis register (PsoReg). Given the repeated measurement of patients in the register data, a longitudinal fixed-effects model was employed to control for unobserved patient-level heterogeneity. RESULTS: Marginal changes in PASI are associated with a non-linear response in EQ-5D-3L: Moving from PASI 10 to 9 (1 to 0) is associated with an increase of 0.0135 (0.0174) in EQ-5D-3L. Furthermore, unobserved patient-level heterogeneity appears to be an important source of confounding when estimating the relationship between QOL and PASI. CONCLUSIONS: Using register data to estimate the impact of disease severity on QOL while controlling for unobserved patient-level heterogeneity shows that PASI appears to have a larger impact on QOL than previously estimated. Routine collection of generic QOL data in registers should be encouraged to enable similar applications in other disease areas. TRIAL REGISTRATION: Not applicable.