| 1. |
- Glasbey, JC, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Tabiri, S, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 6. |
- Bravo, L, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- de Rojas, I., et al.
(författare)
-
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
|
|
| 10. |
- Brevini, T, et al.
(författare)
-
FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
- 2023
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7950, s. 134-
-
Tidskriftsartikel (refereegranskat)abstract
- Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
|
|
| 11. |
|
|
| 12. |
- Lindberg, I., et al.
(författare)
-
Direct healthcare cost of atopic dermatitis in the Swedish population
- 2021
-
Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 141:5 Suppl., s. S45-S45
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Data quantifying population-based direct healthcare costs (DHCC) for atopic dermatitis (AD) by severity are limited. This study was designed to provide estimates for these costs. Patients were identified at first AD diagnosis in the National Patient Registry (secondary care) or in primary care (national coverage: 31%) (International Classification of Diseases-10 L20) or first dispensation of topical calcineurin inhibitor or topical corticosteroid (Anatomical Therapeutic Chemical code D11AH01/02 once; D07 twice in a year) in the Prescribed Drug Registry in 2007-17 (index) and followed until death, emigration, 31 Dec 2018 or adulthood. Patients without AD diagnosis with a record of diagnoses/treatment for other non-AD skin conditions were excluded. Patients were matched 1:1 on age, gender and region to controls. 1-year DHCC for secondary and primary care visits and filled prescriptions were compared with controls (2020€). Disease severity (mild-to-moderate [M2M] vs severe) using AD treatment and visits as proxies was assessed between index to 30 days after. 187,338 M2M (48% female; mean age 4) and 46,754 severe children (51%; 8), while 445,317 M2M (55%; 55) and 11,640 severe adults (57%; 53) were included. In children vs. controls, 1-year DHCC for secondary care, primary care and medications were respectively €72, €23, €33 million (mn) higher in M2M and €26, €4, €13 mn higher in severe; in adults vs. controls, €353, €68, €182 mn higher in M2M and €21, €2, €17 mn higher in severe (all comparisons significant, p<0.05). On population level, AD is associated with substantial economic burden, which is higher in M2M vs severe AD partially due to higher prevalence of M2M.
|
|
| 13. |
- von Kobyletzki, L., et al.
(författare)
-
Care pathways in atopic dermatitis : a retrospective population-based cohort study
- 2022
-
Ingår i: Journal of the European Academy of Dermatology and Venereology. - : John Wiley & Sons. - 0926-9959 .- 1468-3083. ; 36:9, s. 1456-1466
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Ortsäter, Gustaf, et al.
(författare)
-
Validation of Patient Identification Algorithms for Atopic Dermatitis Using Healthcare Databases
- 2022
-
Ingår i: Dermatology and Therapy. - : Adis. - 2193-8210 .- 2190-9172. ; 12, s. 545-559
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 17. |
- Thyssen, Jacob P., et al.
(författare)
-
Comorbidity burden in adult atopic dermatitis : a population-based study
- 2024
-
Ingår i: JEADV Clinical Practice. - : John Wiley & Sons. - 2768-6566. ; 3:1, s. 128-141
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 18. |
- von Kobyletzki, Laura, et al.
(författare)
-
Comorbidities in childhood atopic dermatitis : a population-based study
- 2024
-
Ingår i: Journal of the European Academy of Dermatology and Venereology. - : John Wiley & Sons. - 0926-9959 .- 1468-3083. ; 38:2, s. 354-364
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 19. |
- Battersby, Nick, et al.
(författare)
-
Evaluating the incidence of pathological complete response in current international rectal cancer practice : the barriers to widespread safe deferral of surgery
- 2018
-
Ingår i: Colorectal Disease. - : Wiley. - 1462-8910. ; 2020 Suppl 6, s. 58-68
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The mainstay of management for locally advanced rectal cancer is chemoradiotherapy followed by surgical resection. Following chemoradiotherapy, a complete response may be detected clinically and radiologically (cCR) prior to surgery or pathologically after surgery (pCR). We aim to report the overall complete pathological response (pCR) rate and the reliability of detecting a cCR by conventional pre-operative imaging.METHODS: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients treated by elective rectal resection were included. A pCR was defined as a ypT0 N0 EMVI negative primary tumour; a partial response represented any regression from baseline staging following chemoradiotherapy. The primary endpoint was the pCR rate. The secondary endpoint was agreement between post-treatment MRI restaging (yMRI) and final pathological staging.RESULTS: Of 2572 patients undergoing rectal cancer surgery in 277 participating centres across 44 countries, 673 (26.2%) underwent chemoradiotherapy and surgery. The pCR rate was 10.3% (67/649), with a partial response in 35.9% (233/649) patients. Comparison of AJCC stage determined by post-treatment yMRI with final pathology showed understaging in 13% (55/429) and overstaging in 34% (148/429). Agreement between yMRI and final pathology for T-stage, N-stage, or AJCC status were each graded as 'fair' only (n = 429, Kappa 0.25, 0.26 and 0.35 respectively).CONCLUSION: The reported pCR rate of 10% highlights the potential for non-operative management in selected cases. The limited strength of agreement between basic conventional post-chemoradiotherapy imaging assessment techniques and pathology suggest alternative markers of response should be considered, in the context of controlled clinical trials.
|
|
| 20. |
- Corden, W.M., et al.
(författare)
-
Booming Sector and De-Industrialisation in a Small Open Economy
- 1982
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper presents a theoretical analysis of the 'Dutch Disease': the phenomenon whereby a boom in one traded goods sector squeezes porfitability in other traded goods sectors, both by directly bidding resources away from them and by placing upward pressure on the exchange rate. The effects of such a boom on resource allocation and income distribution are studied in a variant of the "Australian" modek of a small open economy, under different assummptions about the degree of intersectoral factor mobility.
|
|
| 21. |
- Ortsater, Gustaf, et al.
(författare)
-
Clinical and Economic Burden of Pediatric Mild-to-Moderate Atopic Dermatitis : A Population-Based Nested Case-Control Study in Sweden
- 2021
-
Ingår i: Dermatology and Therapy. - : Springer. - 2193-8210 .- 2190-9172. ; 11, s. 161-172
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 22. |
- Ortsäter, Gustaf, et al.
(författare)
-
Societal economic burden and determinants of costs for atopic dermatitis
- 2022
-
Ingår i: JEADV Clinical Practice. - : John Wiley & Sons. - 2768-6566. ; 1:4, s. 326-343
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
