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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 ae<yen>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.

Background

Psoriatic disease, encompassing skin psoriasis and psoriatic arthritis, is a common condition affecting 2-3% of the Western population associated with reduced quality of life and increased healthcare costs. To improve patients’ lives and the stewardship of societal resources, a nuanced understanding of the associations between patient characteristics and health outcomes are needed for optimal clinical and societal decision making. While randomised clinical trials play a central role in evidence-based medicine, they have limitations relating to patient selection, follow-up duration, and idealised clinical conditions. In recent years, the role of real-world evidence in health research has grown, including in dermatology, due in part to its ability to describe and compare patients in routine clinical care. This thesis contains four analyses using Swedish real-world data describing associations between patient characteristics and outcomes in psoriatic disease.

Methods

Data from several administrative population registers in Sweden and the clinical registry PsoReg were collected for those with psoriatic disease in routine clinical care and linked at the patient level. The data include diagnoses, pharmacy dispensed medications, mortality, socioeconomic information, quality of life, and clinical severity. A matched non-psoriatic control group was also extracted.

The first analysis assessed the association between disease severity (measured by the Psoriasis Area and Severity Index [PASI]) and health-related quality of life (measured the EuroQol 5-dimension instrument [EQ-5D]) in 2,674 patients with longitudinal follow-up in PsoReg, a fixed effects regression model was deployed adjusting for confounding factors including certain types of unobserved confounding. 

Second, the independent associations of skin psoriasis and somatic comorbidity with incident psychiatric illness were described across 93,239 psoriasis patients and 1.4 million controls. Their individual contributions and synergistic interaction were assessed using a time-to-event model. Diagnosis codes were used to construct the composite psychiatric illness outcome consisting of depression, anxiety, and suicidality. Diagnosis codes were also used to create the Elixhauser and Charlson comorbidity indexes to measure somatic comorbidity. 

The third analysis assessed age-related inequities in biologic prescriptions in 1,465 patients enrolled in PsoReg using a time-to-event analysis controlling for decision-making variables including disease severity. The analysis also described the non-parametric relationship between age and incident biologic prescriptions using a kernel regression.

Finally, the fourth analysis describes rates of non-persistence in individuals with psoriatic arthritis treated with adalimumab, ustekinumab, and secukinumab using a time-to-event model. A total of 4,649 drug exposure period across 3,918 patients were assessed. Non-persistence was defined as a treatment switch or discontinuation, the latter defined as a failure to refill an existing prescription within two times the days of drug supplied.

Results

The analysis found a statistically significant, negative association between PASI and the EQ-5D (                    =-0.0186, 95% confidence interval [CI]: -0.0360, -0.0201) which was non-linear (  =0.0003, 95% confidence interval [CI]: 0.0001, 0.0004). Incremental PASI improvements for those with less skin involvement were associated with larger increases in quality of life than in those with more skin involvement. 

Skin psoriasis was found to be independently associated with the onset of psychiatric illness (hazard ratio [HR]=1.32, 95% CI: 1.27-1.36) as was somatic comorbidity (HR=2.09, 95%CI: 2.06-2.13). However, the results were compatible with a lack of synergistic effect between skin psoriasis and somatic comorbidity on psychiatric illness (HR=0.93; 95% CI: 0.81-1.04).

Older psoriasis patients appeared less likely to initiate biologic therapies than their younger counterparts after controlling for disease severity and comorbidity (HR=0.97, 95% CI: 0.95-0.99).

Individuals with psoriatic arthritis treated with ustekinumab were found to have lower rates of non-persistence compared to adalimumab (HR=0.56, 95% CI: 0.49-0.64). Secukinumab and adalimumab appeared to have similar rates of non-persistence (HR=1.01, 95% CI: 0.88-1.15), although the results differed in biologic-naïve and biologic-experienced subgroups. The definition of discontinuation was sensitive and had material effects on the results.

Conclusions

Patient characteristics appear to play an important role in a variety of health outcomes in psoriatic disease, demonstrated across four real-world settings. The utilisation of data from routine clinical care enabled the investigation of research questions that are not suitable for clinical trial contexts, providing relevance for patients in everyday clinical practice. The study designs and methodologies applied in this thesis are associated with a variety of strengths and limitations, many of which are closely linked to the observational nature of the data, which have material importance for the interpretation of the results and implications for healthcare and policy. Understanding the associations between patient characteristics and subsequent outcomes is an important element in the delivery of holistic, personalised healthcare.

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 ((sic)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 (sic)12,330 ((sic)123/patient), and an additional 14 successful fusions, implying a cost of (sic)881 per additional successful fusion. When costs of productivity loss were included, the introduction of LA + DBM resulted in cost savings of (sic)70,294 ((sic)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.

Objectives: Develop a model capable of estimating the value of a new antibiotic for use in treating last-line patients not eligible for, or having failed on, all currently available antibiotic treatments.

Methods: Ten annual cohorts of incident last-line patients (total of 314) infected with extended spectrum beta-lactamase (ESBL) -producing bacteria were modelled from the onset of the last-line infection over the course of their remaining life, in a scenario where a new antibiotic was available and one where it was not. Efficacy was measured by mortality, where 5% (95%) of patients died due to the infection in the scenario with(out) a new antibiotic. In the scenario with a new antibiotic, the mortality rate increased by 0.5% annually. Costs including lab tests, hospital stays, and productivity loss were calculated in both scenarios. Quality-adjusted life-years gained (QALYs) were estimated using weights for patients with an infection (0.61) and after recovery (0.84), in addition to disutility incurred by one caregiver per patient (-0.14). Differences in costs, QALYs, deaths, and days off work were calculated between the two arms; costs and QALYs were discounted to the present year. The value of a new antibiotic is reflected in the incremental results.

Results: In the last-line ESBL population of 314 patients over 10 years, the availability of a new antibiotic resulted in SEK 20.4 million in cost saving, 2795 QALYs gained, 273 fewer infection-caused deaths, and 2198 fewer days off work.

Conclusions: Valuation of a new antibiotic is a high public health priority due to increasing antibiotic resistance and decreasing rates of development of new antibiotics. Access to a new antibiotic for last-line patients provides a large benefit to society, using ESBL as case-study. The results are conservative as they exclude factors that are relatively difficult to estimate such as the risk of an outbreak.

NORDSTAR is a longitudinal dataset for the study of asthma comprising 3.3 million individuals and over 50 million person-years in 4 Nordic countries. The data include diagnoses, medication dispensing, use of resources and costs, socio-demographics, and mortality.

Objectives: A typical health technology assessment (HTA) submission presents a novel treatment with better effect and higher cost than the comparators, considered cost-effective if the resulting incremental cost-effectiveness ratio (ICER) is below the willingness to pay (WTP) threshold. Treatments that provide cost-savings, but less health gain, fall in the south-west (SW) quadrant of the cost-effectiveness acceptability plane (CEAP) where the threshold relates to the willingness to accept (WTA) a loss in QALY. The ICERs in SW quadrant is positive (-/-) and higher ICERs are better than lower ICERs. The WTP for a gain in health is generally less than WTA a loss in health which implies that the slope of the WTA curve is steeper than in the WTP curve. Since it is not clear how HTA authorities views ICERs in the SW quadrant, the objective of this study was to estimate the threshold for WTA for a QALY in Sweden.

Methods: A review of all reimbursement decisions published by the Dental and Pharmaceutical Benefit’s Agency (TLV) from 2013-2016 was conducted. The subset of submissions with both negative incremental costs and negative incremental QALYs were further reviewed for TLVs perspective on cost-effectiveness.

Results: Two evaluations were found: pasireotide in the acromegaly indication. The analysis resulting in a SW quadrant result equal to 6.2 million SEK was a scenario analysis conducted by TLV, which was deemed cost-effective. In the 2014 assessment of vandetanib TLV wrote a general statement that SW quadrant results should be interpreted as cost savings per QALY lost, and that SW quadrant evaluations are not as straight-forward but that the potential cost-effectiveness will depend on the WTA.

Conclusions: There are few published TLV evaluations of the cost-effectiveness of SW quadrant ICERs, and no evidence that TLV considers the SW quadrant differently from the typical submission.

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.a

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.

BACKGROUND:

Inequality in healthcare has been identified in many contexts. To the best of our knowledge, this is the first study investigating age inequity in the form of prescription patterns of biologics in psoriasis care.

OBJECTIVE:

To determine whether psoriasis patients have equitable opportunities to receive biologic medications as they age. If patients do not receive equitable treatment, a subsequent objective is to determine the magnitude of the disparity.

METHODS:

A cohort of biologic-naïve psoriasis patients were analysed using Cox proportional hazard models to measure the impact of each additional year of life on the likelihood of initiating biologic treatment, after controlling for sex, body mass index, comorbidities, disease activity, and education level. A supporting analysis used a non-parametric graphical method to study the proportion of patients initiating biologic treatment as age increases, after controlling for the same covariates.

RESULTS:

The Cox proportional hazards model results in a hazard ratio of a one year increase in age of 0.963 to 0.969 depending on calendar year stratification, which implies that an increase in age of 30 years corresponds to a reduced likelihood of initiating biologic treatment by 61.3-67.6%. The estimated proportion of patients initiating biologic medication is always decreasing as age increases, at a statistically significant level.

CONCLUSIONS:

Psoriasis patients have fewer opportunities to access biologic medications as they age. This result was shown to be applicable at all stages in a patient's life course and was not only restricted to the elderly, although it implies greater disparities as the age difference between patients increases. These results show that inequity in access to biologic treatments due to age is prevalent in clinical practice today. Further research is needed to investigate the extent to which this result is influenced by patient preferences. 

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.

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-naive [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-naive 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.

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 pound and a gain of 0.087 QALYs, resulting in an ICER of 12,850 pound. 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.

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.

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.

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.

Objectives: The willingness to pay (WTP) threshold accepted by National Institute for Health and Care Excellence (NICE) for the reimbursement of a drug is £20,000-£30,000 per quality adjusted life year (QALY). It is relevant to consider WTP when the new technology offers relative improvements in health at a higher cost, i.e. when the incremental cost-effectiveness ratio (ICER) is placed in the north-east (NE) quadrant of the cost-effectiveness acceptability plane (CEAP) or for losses in health accompanied by cost-savings (south-west [SW] quadrant). The WTP for a gain in health is generally less than the willingness to accept (WTA) a loss in health which implies that the slope of the WTA curve is steeper than in the WTP curve. The objective of this study was to evaluate whether there is evidence that NICE considers a WTA threshold in the SW quadrant that differs from the WTP threshold in the NE quadrant.

Methods: NICE technology appraisal (TA) guidance documents published June 2013-June 2016 were reviewed. Appraisal documents presenting results in the SW quadrant by the manufacturer or the Evidence Review Group (ERG) were collected and SW ICERs were extracted. The number of, and opinions related to the SW quadrant results were reviewed and summarised.

Results: Manufacturer submitted SW ICERs were found in one base-case and three scenario analyses. The ERG presented SW ICERs as scenario analyses in three TAs and once after correcting errors found in one manufacturer’s model. NICE did not consider SW ICERs of £18,300/QALY and £21,100 to 39,100/QALY to be cost-effective, while £250,000/QALY was considered cost-effective.

Conclusions: Evidence of a divergence between the WTP and WTA thresholds used by NICE was not found. The slope of the WTA threshold may be slightly steeper than WTP. Based on available evidence, the NICE WTA threshold may be between £21,100 per QALY and £250,000 per QALY.

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.

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 euro1111 (3416) and euro524 (2446) in the pM2M AD and reference cohorts, respectively. The corresponding estimate in the severe AD cohort was euro1906 (7067). Including all secondary care visits and pharmacy-dispensed medications, the pM2M AD cohort was shown to have an additional euro118.9 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.

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.

Background: Atopic dermatitis (AD) is a common inflammatory skin disease while the economic burden of AD by severity is not adequately understood.

Objective: To estimate the societal economic burden and to identify cost determinants of AD.

Methods: In this population-based, controlled cohort study in Sweden, patients with AD were identified through diagnosis codes in primary or secondary care or by dispensed medications using administrative healthcare registers. A reference cohort without AD was randomly selected from the general population. Healthcare costs (primary/secondary care visits and dispensed medication) and indirect costs (care for sick children and long-term sick leave for adults) were calculated annually. AD patients were stratified by age (paediatric [age < 12], adolescent [12 ≤ age < 18] or adult [age ≥ 18]), and severity (mild-to-moderate [M2M] or severe AD) and matched to the reference cohort.

Results: Compared with controls, the annual mean per-patient direct healthcare costs in the first year following diagnosis were €941 and €1259 higher in paediatric patients with M2M and severe AD, respectively. In the first year following diagnosis, the mean indirect cost for care of sick children was €69 and €78 higher per patient in M2M and severe AD, respectively. In adolescents with M2M and severe AD, direct healthcare costs were €816 and €1260 higher, respectively. In adults, healthcare costs were €1583 and €2963 higher in patients with M2M and severe AD, respectively and indirect costs were €148 and €263 higher compared with controls. Management of comorbid medical conditions was an important driver of incremental healthcare costs. Total incremental societal economic burden for AD was €351 and €96 million higher in patients with M2M and severe AD, respectively, compared to controls.

Conclusion: AD is associated with a significant societal economic burden primarily driven by the cost burden of M2M AD due to the high prevalence of this population. Regardless of severity level, management of non-AD comorbidities is a major driver of total costs.

Objectives: Estimate the budget impact (BI) of introducing demineralised bone matrix (DBM) combined with local bone (LB) in lumbar spinal fusion to treat lumbar degenerative disk disease in Spain. Methods: A decision tree model was developed to evaluate the 4-year BI associated with introducing LB combined with DBM putty (LB+DBM) to replace currently available treatment options including iliac crest bone graft (ICBG), LB alone, and LB combined with ceramic bone graft extenders (LB+ceramic). The market shares of the currently available treatments were 30% ICBG, 40% LB, and 30% LB+ceramic respectively. The analysis was conducted for 100 patients assuming LB+DBM would replace the currently administered treatment mix. Patients receiving DBM were administered 5cc and those receiving ceramics were administered 10cc beta-tricalcium phosphate. The model structure was based on previously published models identified through a structured literature search. The cost of DBM, ceramic, surgical procedures, adverse events, treatment failure, and reoperations were ncluded in the base-case analysis, and productivity loss was analysed in sensitivity analysis. Costs were sourced for Spain in €2017 and no discounting was applied. The model’s inputs and assumptions were validated by two Spanish clinical experts. Results: Over 4 years, replacing currently available treatments with LB+DBM spinal fusions 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. Initial procedure costs were higher for LB+DBM, but result in subsequent cost savings in terms of reoperations and adverse events. When including costs of productivity loss, the introduction of LB+DBM resulted in cost savings of €70,294 (€703/patient). Conclusions: For patients eligible for lumbar spinal fusion in Spain, replacing currently available treatments with LB+DBM results in increased costs for the payer but cost savings for society, while providing more successful fusions in both cases.

Introduction: Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic diseases that affect 1.5% to 8.5% and 8% to 21% of the Norwegian population, respectively, according to estimates in recent studies. The most common type of PsO is plaque psoriasis and the majority of patients with PsA also suffer from PsO. The disease burden of PsO and PsA are substantial and comparable to other major severe chronic diseases such as diabetes and rheumatoid arthritis. Patients with moderate to severe PsO and PsA are routinely referred from primary care to specialist care services.

Objectives: The objective of this study was to estimate the prevalence of moderate to severe plaque psoriasis and PsA, and the overlap between them, as reported diagnosis in the National Patient Registry (NPR) in Norway.

Methods: The total numbers of unique adult patients with main diagnoses of PsO and PsA (ICD-10 codes: L40+) in 2014, hospitalized or in contact with specialist services, were extracted from the NPR. Based on the Norwegian general population in 2014 (n=5,109,056), the prevalence of each disease was estimated.

Results: The prevalence of moderate to severe plaque psoriasis was estimated to 0.14%. The prevalence of PsA was estimated to 0.18%, while the prevalence of the coexistence of moderate to severe plaque psoriasis and PsA equaled 0.02%.

Conclusions: Since the milder PsO cases are treated in the primary care setting in Norway, the prevalence of plaque psoriasis reported in this study reflected the moderate to severe cases with registered visits to specialist health services. This population constitutes approximately 10% of the total PsO population, based on the literature. The results indicate that very few of the estimated prevalent PsO patients are treated by specialists. Also, to our knowledge this is the first study reporting the prevalence of PsO and PsA in specialist care services in Norway.

Objectives: Relapse-remitting multiple sclerosis (RRMS) is the most common disease course of multiple sclerosis (MS) patients. Disease activity (DA) has been shown to impact intermediate clinical outcomes including relapse rates and disease progression. However, it is unclear to what extent DA is related to ultimate health outcomes such as health-related quality of life (HRQoL). This study investigates the association between HRQoL and DA. Methods: Generic HRQoL was measured using the EQ-5D-3L utility instrument index value under the United Kingdom tariff. A cohort of 3496 adult RRMS patients enrolled in the Swedish population-based MS register during 1996-2015 (inclusive) was included from the date of first recorded EQ-5D-3L assessment (baseline). Patients were grouped according to DA within +/- 12 months of baseline. Active disease was the reference group, defined as 1+ relapse or T2 lesion. Two high disease activity groups were considered: HDA-R defined as 2+ relapses recorded within 1 year of each other, or Highly Active RRMS (HA-RRMS) defined as 9+ T2 lesions or 1+ gadolinium-enhanced T1 lesion. Patients not fulfilling any DA criteria were labelled unclassified. A general estimating equation was used to analyse the association between longitudinal EQ-5D-3L and disease activity group; adjusting for age, sex, proportion of time treated with disease modifying treatment (%DMT), and time since registry enrolment. Results: HA-RRMS was associated with a statistically significant decrease in EQ-5D-3L (coefficient -0.01, p=0.04). HDA-R and unclassified patients were not statistically significantly associated with EQ-5D-3L. Female sex and increasing age were significantly associated with decreasing EQ-5D-3L, while %DMT and time since registry enrolment were significantly associated with increasing EQ-5D-3L. Conclusions: HA-RRMS is associated with lower HRQoL over time, although it is unclear whether it is clinically significant. Additional data and modelling may be required to uncover the subtleties of the relationship between DA and HRQoL.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that has been shown to be associated with allergic comorbidities. However, studies examining comorbidities in patients with AD are incomplete, which may contribute to suboptimal care.

Objectives: The objective was to compare the risk of developing different allergic and nonallergic comorbidities among adult patients with AD to that of a matched reference cohort in Sweden.

Methods: This was a nationwide population-based cohort study using longitudinal data from primary and specialist care registers. AD patients were identified by confirmed diagnosis in primary or specialist care. A non-AD reference cohort was randomly drawn from the general population and matched 1:1 with the AD patients on age, gender, and geographical region. The risk of developing the following conditions was evaluated: asthma, food hypersensitivity, allergic rhinitis, neurological disorders, psychiatric disorders, infections, immunological & inflammatory disorders, type 1 diabetes (T1D), type 2 diabetes (T2D), endocrine & metabolic disorders, skeletal disorders, ocular disorders, cardiovascular diseases, and malignancies.

Results: This study included 107,774 AD patients [mild-to-moderate (n = 92,413) and severe (n = 15,361)] and an equally-sized reference cohort. AD patients displayed a higher risk of developing comorbid conditions for all investigated categories, except for T1D, compared with the reference cohort. The highest risk compared with the reference cohort was observed for allergic comorbidities followed by immunological & inflammatory disorders (hazard ratio: 2.15) and infections (hazard ratio: 2.01). Patients with AD also had higher risk of developing multiple comorbidities (2 or more). 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: AD patients are at an increased risk of developing many comorbidities that extend beyond allergic conditions. This study highlights the need for interdisciplinary follow-up of comorbidities in the management of AD patients to reduce overall patient burden.

Objectives: Critically appraise published health economic models evaluating treatments of bacteria resistant to antibiotics, focusing on methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.

Methods: A structured literature review was conducted in Embase, identifying relevant publications by combining search facets for MRSA or ESBL, economic models, and antibiotics, excluding publications including the terms “animal” or “farm”. All search facets were search in the abstract and title, resulting in 40 publications. Two reviewers, blinded to the other’s initial evaluation, evaluated each of the titles and abstracts and found that 25 were relevant for a full review.

Results: The absolute majority of the identified studies presented cost-effectiveness models with a decision-analytic approach and a time horizon ranging from two to four weeks. The site of infection studied was dominated by nosocomial pneumonia as well as skin and soft tissue infections caused by MRSA. Only one model concerned gram-negative pathogens. No model was identified studying ESBL as the cause of infection. The most common antibiotic agents modelled were linezolid, vancomycin, daptomycin or their combination with a median of two treatment lines modelled. One model studies the cost-effectiveness of carbapenems. Sources used for informing antibiotic efficacy data were primarily published literature, clinical trials or clinical expert opinion. The most common outcome measures modelled were direct medical costs and resource utilization as well as efficacy measured by treatment success or antibacterial usage estimates. Four models (16%) included quality-adjusted life years (QALYs) as outcome measure.

Conclusions: The cost-effectiveness of linezolid and vancomycin for treatment of MRSA has been well-studied in various types of infections. There is a need for further cost-effectiveness and cost-benefit studies on antibiotic failure in more than two treatment lines, especially in carbapenem treatment of infections caused by ESBL, as these pose a significant resistance threat today.

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.

Background: Atopic dermatitis (AD) is a complex disease with variations in severity and healthcare utilization. Examining patient pathways through analyses of longitudinal patient data provides an opportunity to describe real-world clinical patient care and evaluate healthcare access and treatment.

Objective: To describe longitudinal care pathways including health care management, treatment patterns and disease progression (by proxy measures) in patients with AD.

Materials and methods: This was a longitudinal observational study, which used linked data from national and regional healthcare registers in Sweden. Patients with AD were identified through diagnosis in primary or secondary care or by dispensed medications. Descriptive statistics for number of healthcare visits, type of dispensed drug class, rate of - and time to - referral to secondary care and treatment escalation were calculated.

Results: A total of 341 866 patients with AD distributed as 197 959 paediatric (age < 12), 36 133 adolescent (age ≥ 12- < 18) and 107 774 adult (age ≥ 18) patients were included in this study. Healthcare visits to primary and secondary care and dispensation of AD-indicated treatments were more common during the year in which managed AD care was initiated. Topical corticosteroids (TCSs) and emollients were the most frequently used treatments across all age cohorts while systemic treatment was uncommon in all age cohorts. Among patients who initiated treatment with TCSs, 18.2% escalated to TCSs with higher potency following the start of managed AD care.

Conclusions: We found that healthcare contacts and use of AD-indicated treatments were concentrated in the year during which managed AD care was initiated and decreased significantly thereafter. Since a significant proportion of patients with AD have flares and persistent AD, our results suggest that patients with AD may be monitored infrequently and are undertreated. There is a need to inform practitioners about adequate treatment options to provide individualized care, in particular for patients with persistent severe AD.

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.