| 1. |
- Gustavsson, Anders, et al.
(författare)
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Cost of disorders of the brain in Europe 2010.
- 2011
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Ingår i: European Neuropsychopharmacology. - Amsterdam : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:10, s. 718-79
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.RESULTS: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.
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| 2. |
- Aulin, Cecilia, 1979-
(författare)
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Extracellular Matrix Based Materials for Tissue Engineering
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition. The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.
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| 3. |
- Lewerin, Catharina, 1961, et al.
(författare)
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Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden.
- 2014
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 25:1, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based study on cobalamin status and incident fractures in elderly men (n=790) with an average follow-up of 5.9years, we found that low levels of metabolically active and total cobalamins predict incident fractures, independently of body mass index (BMI), bone mineral density (BMD), plasma total homocysteine (tHcy), and cystatin C.
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| 4. |
- Abtahi, Jahan, et al.
(författare)
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Bisphosphonate coating might improve fixation of dental implants in the maxilla: A pilot study
- 2010
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Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier Science B.V., Amsterdam. - 0901-5027 .- 1399-0020. ; 39:7, s. 673-677
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Tidskriftsartikel (refereegranskat)abstract
- This pilot study evaluates the clinical stability of bisphosphonate-coated dental implants placed using a two-stage surgical procedure in five patients. Each patient received seven regular Brånemark implants, one of which was coated with bisphosphonate in a fibrinogen matrix. The coated implant was inserted where the bone was expected to have the least favourable quality. The level of the marginal bone around each implant was measured by intraoral periapical radiographs and implant stability was recorded using resonance frequency measurements. Frequency values (ISQ) were obtained peroperatively before flap closure and after 6 months at abutment connection. At abutment connection the bisphosphonate-coated implants were removed en bloc in two patients for histological examination. An animal experiment had previously confirmed that gamma-sterilization did not reduce bioactivity of the bisphosphonate coating. In each patient, the bisphosphonate-coated implant showed the largest improvement in ISQ level of all implants. Their values at the start tended to be lower, and the absolute value at 6 months did not differ. No complications occurred with the coated implants. Histology showed no abnormalities. Improvement in ISQ values was an expected effect of the bisphosphonate coating, but could be due to the choice of insertion site. This finding warrants a randomized, blinded study.
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| 5. |
- Ohlin, Maria, 1987, et al.
(författare)
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Duration of sickness absence following a bicycle crash, by injury type and injured body region: A nationwide register-based study
- 2018
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Ingår i: Journal of Transport & Health. - : Elsevier BV. - 2214-1405 .- 2214-1413. ; 9, s. 275-281
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, bicycle injuries have increased but little is known about the relation of such injures to sickness absence (SA). The aim of this study was to investigate duration of SA > 14 days after a bicycle crash, in general and by injury type and injured body region. A population-based study was conducted, including all individuals living in Sweden, aged 16-64 years, who in 2009-2011 had in-or specialized outpatient medical care due to a new injury from a bicycle crash (n = 22,045), excluding those already on SA or full-time disability pension at the time of the crash. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for a new SA were estimated by logistic regression. In total, 4387 (20%) had new SA in connection to the crash. SA was most common among individuals aged 55-64 years (32%), and more common among women (23%) than men (18%). Fractures was the injury type with the highest OR for SA across all durations, but highest for 30-89 days (8.09; CI 6.30-10.39). Spine and back was the body region with the highest OR for SA >= 90 days (11.98; CI 7.38-19.46), followed by Traumatic Brain Injuries (6.64; CI 4.01-10.98), and injuries to lower extremities (5.28; CI 3.58-7.78). For 235 individuals (5%) the SA spell lasted >= 180 days. Among those cases, the most commonly injured body regions were lower leg (21%) followed by shoulder and upper arm (17%), and Traumatic Brain Injuries (15%). In conclusion, the duration of SA varied with type of injury and injured body region. Among the very long SA spells, common injuries were injuries to the lower leg, to the shoulder and upper arm, and traumatic brain injuries.
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| 6. |
- Kjeldgård, Linnea, 1985-, et al.
(författare)
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Bicycle crashes and sickness absence - a population-based Swedish register study of all individuals of working ages
- 2019
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Ingår i: Bmc Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn recent years, bicycle injuries have increased, yet little is known about the impact of such injures on sickness absence (SA) and disability pension (DP). The aim was to explore SA and DP among individuals of working ages injured in a bicycle crash.MethodA nationwide register-based study, including all individuals aged 16-64years and living in Sweden, who in 2010 had in- or specialized out-patient healthcare (including emergency units) after a bicycle crash. Information on age, sex, sociodemographics, SA, DP, crash type, injury type, and injured body region was used. We analyzed individuals with no SA or DP, with ongoing SA or full-time DP already at the time of the crash, and with new SA >14days in connection to the crash. Crude and adjusted odds ratios (OR) with 95% confidence intervals for new SA were estimated by logistic regression.ResultsIn total, 7643 individuals had healthcare due to a new bicycle crash (of which 85% were single-bicycle crashes). Among all, 10% were already on SA or full-time DP at the time of the crash, while 18% had a new SA spell. The most common types of injuries were external injuries (38%) and fractures (37%). The body region most frequently injured was the upper extremities (43%). Women had higher OR (1.40; 1.23-1.58) for new SA than men, as did older individuals compared with younger (OR 2.50; 2.02-3.09, for ages: 55-64 vs. 25-34). The injury types with the highest ORs for new SA, compared with the reference group external injuries was fractures (8.04; 6.62-9.77) and internal injuries (7.34; 3.67-14.66). Individuals with traumatic brain injury and injuries to the vertebral column and spinal cord had higher ORs for SA compared with other head, face, and neck injuries (2.72; 1.19-6.22 and 3.53; 2.24-5.55, respectively).ConclusionsIn this explorative nationwide study of new bicycle crashes among individuals of working ages, 18% had a new SA spell in connection to the crash while 10% were already on SA or DP. The ORs for new SA were higher among women, older individuals, and among individuals with a fracture.
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| 7. |
- Zheng, Hou-Feng, et al.
(författare)
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WNT16 influences bone mineral density, Cortical bone thickness, bone strength, and Osteoporotic fracture risk
- 2012
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Ingår i: PLoS genetics. - SAN FRANCISCO, USA : PUBLIC LIBRARY SCIENCE. - 1553-7404. ; 8:7, s. e1002745-
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10(-12), and -0.16 SD per G allele, P = 1.2×10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10(-6) and rs2707466: OR = 1.22, P = 7.2×10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10(-13)
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| 8. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 9. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 10. |
- Fältström, Anne, et al.
(författare)
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Functional Performance Among Active Female Soccer Players After Unilateral Primary Anterior Cruciate Ligament Reconstruction Compared With Knee-Healthy Controls
- 2017
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Ingår i: American Journal of Sports Medicine. - : Sage Publications. - 0363-5465 .- 1552-3365. ; 45:2, s. 377-385
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Tidskriftsartikel (refereegranskat)abstract
- Background: Good functional performance with limb symmetry is believed to be important to minimize the risk of injury after a return to pivoting and contact sports after anterior cruciate ligament reconstruction (ACLR).Purpose: This study aimed to investigate any side-to-side limb differences in functional performance and movement asymmetries in female soccer players with a primary unilateral anterior cruciate ligament (ACL)–reconstructed knee and to compare these players with knee-healthy controls from the same soccer teams.Study Design: Cross-sectional study; Level of evidence, 3.Methods: This study included 77 active female soccer players at a median of 18 months after ACLR (interquartile range [IQR], 14.5 months; range, 7-39 months) and 77 knee-healthy female soccer players. The mean age was 20.1 ± 2.3 years for players with an ACL-reconstructed knee and 19.5 ± 2.2 years for controls. We used a battery of tests to assess postural control (Star Excursion Balance Test) and hop performance (1-legged hop for distance, 5-jump test, and side hop). Movement asymmetries in the lower limbs and trunk were assessed with the drop vertical jump and the tuck jump using 2-dimensional analyses.Results: The reconstructed and uninvolved limbs did not differ in any of the tests. In the 5-jump test, players with an ACL-reconstructed knee performed worse than controls (mean 8.75 ± 1.05 m vs 9.09 ± 0.89 m; P = .034). On the drop vertical jump test, the ACL-reconstructed limb had significantly less knee valgus motion in the frontal plane (median 0.028 m [IQR, 0.049 m] vs 0.045 m [IQR, 0.043 m]; P = .004) and a lower probability of a high knee abduction moment (pKAM) (median 69.2% [IQR, 44.4%] vs 79.8% [IQR, 44.8%]; P = .043) compared with the control players’ matched limb (for leg dominance). Results showed that 9% to 49% of players in both groups performed outside recommended guidelines on the different tests. Only 14 players with an ACL-reconstructed knee (18%) and 15 controls (19%) had results that met the recommended guidelines for all 5 tests (P = .837).Conclusion: The reconstructed and uninvolved limbs did not differ, and players with an ACL-reconstructed knee and controls differed only minimally on the functional performance tests, indicating similar function. It is worth noting that many players with an ACL-reconstructed knee and controls had movement asymmetries and a high pKAM pattern, which have previously been associated with an increased risk for both primary and secondary ACL injury in female athletes.
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