| 1. |
- Bengtsson, Karin, 1980, et al.
(författare)
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Comparisons between comorbid conditions and health care consumption in rheumatoid arthritis patients with or without biological disease-modifying antirheumatic drugs : a register-based study
- 2016
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Symptoms and prognosis of patients with rheumatoid arthritis (RA) have improved with more intensive therapy, including the biological disease-modifying anti-rheumatic drugs (bDMARDs). Real life data concerning how comorbidities are distributed among patients treated or not treated with bDMARDs are scarce. Our objective was to investigate differences in comorbidity and health care consumption in RA patients, with and without bDMARDs.METHODS: This cross-sectional study was performed in the Southwestern part of Sweden. Patients, aged ≥ 18 years and diagnosed with RA in secondary health care during 2009-2010, were identified in the regional health care database. Aggregated data of comorbidity and health care consumption were retrieved between 2006 and 2010. RA patients treated with bDMARDs on 31st December 2010 were identified in the Swedish Rheumatology Quality Register (SRQ), which includes the biologics register Anti-Rheumatic Therapy in Sweden (ARTIS). Descriptive, comparative, univariate and multiple logistic regression analyses were used to identify factors associated with bDMARDs.RESULTS: Seven thousand seven hundred and twelve (7712) RA patients were identified (age 64.8 ± 14.9 years, women 74.3%), of whom 1137 (14.7%) were treated with bDMARDs. Overall, the most common comorbidities were infections (69.2%), hypertension (41.1%), chronic respiratory disease (15.3%), ischemic heart disease (14.0%) and malignancy (13.7%). Patients without bDMARDs were older and had more comorbidity. In the multiple logistic regression analysis, older age, cerebrovascular and chronic respiratory disease, heart failure, depression and malignancy were all associated with no present bDMARDs. Infections were associated with bDMARDs. Patients treated with bDMARDs consumed more secondary outpatient care but less visits in primary health care compared to patients without bDMARDs.CONCLUSIONS: Patients treated with bDMARDs versus no bDMARDs were younger and had significantly lower period prevalence for most common comorbidities, with the exception of infections. Differences in comorbidities between RA patients with or without bDMARDs should be taken into consideration when evaluating effectiveness and safety of bDMARDs in ordinary care.
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| 2. |
- Cirenajwis, Helena, et al.
(författare)
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Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
- 2015
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
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| 3. |
- Cirenajwis, Helena, et al.
(författare)
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NF1-mutated melanoma tumors harbor distinct clinical and biological characteristics
- 2017
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 11:4, s. 438-451
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Tidskriftsartikel (refereegranskat)abstract
- In general, melanoma can be considered as a UV-driven disease with an aggressive metastatic course and high mutational load, with only few tumors (acral, mucosal, and uveal melanomas) not induced by sunlight and possessing a lower mutational load. The most commonly activated pathway in melanoma is the mitogen-activated protein kinase (MAPK) pathway. However, the prognostic significance of mutational stratification is unclear and needs further investigation. Here, in silico we combined mutation data from 162 melanomas subjected to targeted deep sequencing with mutation data from three published studies. Tumors from 870 patients were grouped according to BRAF, RAS, NF1 mutation or triple-wild-type status and correlated with tumor and patient characteristics. We found that the NF1-mutated subtype had a higher mutational burden and strongest UV mutation signature. Searching for co-occurring mutated genes revealed the RASopathy genes PTPN11 and RASA2, as well as another RAS domain-containing gene RASSF2 enriched in the NF1 subtype after adjustment for mutational burden. We found that a larger proportion of the NF1-mutant tumors were from males and with older age at diagnosis. Importantly, we found an increased risk of death from melanoma (disease-specific survival, DSS; HR, 1.9; 95% CI, 1.21-3.10; P = 0.046) and poor overall survival (OS; HR, 2.0; 95% CI, 1.28-2.98; P = 0.01) in the NF1 subtype, which remained significant after adjustment for age, gender, and lesion type (DSS P = 0.03, OS P = 0.06, respectively). Melanoma genomic subtypes display different biological and clinical characteristics. The poor outcome observed in the NF1 subtype highlights the need for improved characterization of this group.
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| 4. |
- Engstrand, Christina
(författare)
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Hand function in patients with Dupuytren’s disease : Assessment, results & patients’ perspectives
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Dupuytren’s Disease (DD) is a soft tissue disorder that leads to finger joint contractures affecting hand function. DD can be treated with surgery or injection and hand therapy to improve finger joint extension and thereby improve hand function. However, this does not cure the disease and recurrence is common. Previous research on DD has shown improvement in finger joint extension and in self-reported disability of the upper extremity after surgery and hand therapy for DD. However, this provides only a limited perspective on hand function, and multiple dimensions of changes in hand function (i.e. physical, psychosocial aspects and including the patients’ views of results) have not been reported as a whole.Aim: The overall aim of the thesis was to explore hand function before and after surgery and hand therapy in patients with DD, including assessment, results and patients’ perspectives.Methods: The thesis comprises three studies: Study A was a methodological study of interrater reliability in goniometry of the finger joints. Study B was a prospective cohort study with a repeated measures design. Study C was a qualitative interview study, using the model of Patient Evaluation Process and content analysis.Results: Interrater reliability was high or very high for goniometer measurement of finger joint range of motion (ROM) in patients with DD when experienced raters follow our standardized guidelines developed for the study. Changes in hand function consisted of improvement of finger joint extension while active finger flexion was significantly impaired during the first year after surgery and hand therapy. No patient reached a normal ROM, but the majority reached a functional ROM. Sensibility remained unaffected. Patients with surgery on multiple fingers had worse scar pliability than patients with surgery on a single finger. Most patients had their expectations met and were pleased or delighted with their hand function at 12 months after surgery and hand therapy. Safety issues of hand function were of greater concern than social issues. Patients reported less disability and improved health-related quality of life after surgery and hand therapy. The three variables “need to take special precautions”, “avoid using the hand in social context”, and health-related quality of life had significant importance for patients’ rating of functional recovery. Together, these variables explained 62% of the variance in functional recovery. Patients’ perspectives of undergoing a surgical intervention process were described through five categories. Previous experiences of care influenced participants’ expectations of results and the care they were about to receive. Previous experiences and expectations were used as references for appraisal of results, which concerned perceived changes in hand function, the care process, competency, and organization. Appraisal of results could also vary in relation to patient character. Appraisal of results of the intervention process influenced participants’ expectations of future hand function, health and care.Conclusions: Surgery and hand therapy for DD improve hand function and patients regain a functional ROM needed for performance of common daily activities. Despite the negative effect on finger flexion present during the first year after surgery, patients’ regards their hand function as recovered six to eight months after surgery and hand therapy. Measuring digital ROM in the finger joints with a goniometer is a reliable assessment method. However, from the patient’s perspective, it is not enough to evaluate results only in terms of digital extension or ROM. From their view, results of treatment concern consequences on daily use of the hand, what happens during the care process in terms of interaction between patient and health care provider, as well as their view of the competence and logistics of the organization providing the care.
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| 5. |
- Harbst, Katja, et al.
(författare)
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Multiregion whole-exome sequencing uncovers the genetic evolution and mutational heterogeneity of early-stage metastatic melanoma
- 2016
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Ingår i: Cancer Research. - 0008-5472. ; 76:16, s. 4765-4774
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Tidskriftsartikel (refereegranskat)abstract
- Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma biopsies from eight individual tumors. This approach revealed heterogeneous somatic mutations in the range of 3%-38% in individual tumors. Known mutations in melanoma drivers BRAF and NRAS were always ubiquitous events. Using RNA sequencing, we found that the majority of mutations were not expressed or were expressed at very low levels, and preferential expression of a particular mutated allele did not occur frequently. In addition, we found that the proportion of ultraviolet B (UVB) radiation-induced C>T transitions differed significantly (P <0.001) between early and late mutation acquisition, suggesting that different mutational processes operate during the evolution of metastatic melanoma. Finally, clinical history reports revealed that patients harboring a high degree of mutational heterogeneity were associated with more aggressive disease progression. In conclusion, our multiregion tumor-sequencing approach highlights the genetic evolution and non-UVB mutational signatures associated with melanoma development and progression, and may provide a more comprehensive perspective of patient outcome.
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| 6. |
- Kvist, Therese, et al.
(författare)
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Child maltreatment - prevalence and characteristics of mandatory reports from dental professionals to the social services
- 2017
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Ingår i: International Journal of Paediatric Dentistry. - : Wiley. - 0960-7439 .- 1365-263X. ; 27:1, s. 3-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dental professionals are required to report suspicions of child maltreatment to the social services. As yet, no studies assess the prevalence of these mandated reports from dental care services or their content.AIM: This study investigates the prevalence and characteristics of mandated reports from dental professionals to the social services. Furthermore, it analyses associations between dental professionals reporting suspicions of maltreatment with such reports from other sources.DESIGN: The study collected dental mandatory reports from within one municipality of Sweden during 2008-2014. The material consisted of a total of 147 reports by dental professionals regarding 111 children.RESULTS: The total prevalence of reports from dental care services to the social services was 1.5 per 1000 children with a significant increase between 2008 and 2011 (P < 0.001). The primary cause for a report concerned parental deficiencies in care (n = 93) and secondly, a concern for dental neglect (n = 52) (P < 0.001). Among all reports, 86% involved children with prior contacts with the social services.CONCLUSION: Reports to the social services from dental care services on suspicions of child maltreatment concern parental deficiencies (failure to attend appointments) and neglect (dental neglect). Mandated reports from dental care services often co-occur with other mandated reports.
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| 7. |
- Kvist, Therese, et al.
(författare)
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Oral health in children investigated by Social services on suspicion of child abuse and neglect
- 2018
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Ingår i: International Journal of Child Abuse & Neglect. - : Elsevier BV. - 0145-2134 .- 1873-7757. ; 76, s. 515-523
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Tidskriftsartikel (refereegranskat)abstract
- Child abuse and neglect (CAN) are likely to have negative consequences on health; however, for oral health, studies on associated outcomes are sparse. The purpose of this study was to assess oral health and oral health behaviors in relation to suspected CAN among children being investigated by the Swedish Social Services. The material comprised data from the Social Services and dental records; the sample, 86 children and 172 matched controls. The children in the study group had a higher prevalence of dental caries than the control group; in addition, levels of non-attendance and dental avoidance were high, as was parental failure to promote good oral health. We found four factors that, taken together, indicated a high probability of being investigated because of suspected CAN: prevalence of dental caries in primary teeth, fillings in permanent teeth, dental health service avoidance, and referral to specialist pediatric dentistry clinics. If all four factors were present, the cumulative probability of being investigated was 0.918. In conclusion, there is a high prevalence of dental caries, irregular attendance, and a need for referral a pediatric dental clinic among Swedish children under investigation due to suspected CAN. Social context is an important factor in assessing the risk of developing dental caries, the inclination to follow treatment plans, and the prerequisites for cooperation during treatment. Routinely requesting dental records during an investigation would provide important information for social workers on parental skills and abilities to fulfill the basic needs of children.
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| 8. |
- Lauss, Martin, et al.
(författare)
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Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma. Whole exome-and transcriptome sequencing and neoantigen prediction were applied to pre-treatment samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously progressed on other immunotherapies. We report that clinical benefit is associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load are significantly associated with improved progression-free and overall survival. Further, clinical benefit is associated with the expression of immune activation signatures including a high MHC-I antigen processing and presentation score. These results improve our understanding of mechanisms behind clinical benefit of ACT in melanoma.
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