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| 4. |
- Ahmad, Abrar, et al.
(author)
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Alpha 2-macroglobulin 5 bp insertion/deletion polymorphism increases the risk of recurrent venous thromboembolism
- 2018
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In: Gene Reports. - : Elsevier BV. - 2452-0144. ; 13, s. 104-109
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Journal article (peer-reviewed)abstract
- Alpha 2-macroglobulin (A2M) is a protease inhibitor that has been reported to neutralize thrombin, which may decrease the risk of thrombosis. A 5-base pairs (bp) insertion/deletion polymorphism (rs3832852) at the splice acceptor site of exon 18 has been shown to affect the binding of A2M with proteases. However, the role of this important variant in A2M in recurrent VTE is unknown. We investigated the role of 5 bp insertion/deletion polymorphism in VTE recurrence in a follow up study. A2M 5 bp insertion/deletion polymorphism was genotyped in Malmö Thrombophilia Study (MATS, n = 1465, with follow up of ~10 years) by TaqMan Allelic Discrimination assay. Univariate Cox regression analysis showed that A2M polymorphism was significantly associated with higher risk of VTE recurrence (hazard ratio [HR] = 2.61, 95% confidence interval [CI] = 1.06–6.45, P = 0.037). This association remained significant (HR = 2.61, 95% CI = 1.06–6.47, P = 0.038) even after adjusting for sex, family history of VTE, thrombophilia and acquired risk factors for VTE. In conclusion, our results indicate that patients with A2M 5 bp insertion/deletion polymorphism are at significantly higher risk of VTE recurrence and this may predict VTE recurrence.
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| 5. |
- Ahmad, Abrar, et al.
(author)
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Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism
- 2017
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 44:1, s. 130-138
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Journal article (peer-reviewed)abstract
- Recent gene knockout studies on mice have shown the role of toll-like receptor 9 (TLR9) in resolution of venous thromboembolism (VTE) through sterile inflammation. However, the role of a putative functional TLR9 polymorphism (rs5743836) in risk assessment of VTE recurrence remains unknown. The aim of our study was to investigate the TLR9 rs5743836 polymorphism in VTE patients and its association with the risk of VTE recurrence. We analyzed TLR9 rs5743836 polymorphism in Malmö thrombophilia study patients; a prospective follow-up study of 1465 VTE patients by Taqman PCR. From a total of 1465 VTE patients, those who had VTE before inclusion and those who died or had VTE recurrence during anticoagulant treatment were excluded (n = 415). Cox regression analyses were performed on the remaining 1050 VTE patients, including 126 (12.5%) patients that had recurrent VTE during follow-up period. TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 3.46, 95% CI 1.06-11.33) independent of acquired risk factors for VTE, family history, risk of thrombophilia and deep vein thrombosis (DVT) location. Similarly, in unprovoked VTE patients, TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 5.94, 95% CI 1.25-28.13) after adjusting for family history, risk of thrombophilia and DVT location. No association between TLR9 polymorphism and risk of VTE recurrence was found in male patients. Our results suggest that TLR9 rs5743836 polymorphism is an independent risk factor for VTE recurrence in female patients but not in males.
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| 6. |
- Ahmad, Abrar, et al.
(author)
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Evaluation of Expression Level of Apolipoprotein M as a Diagnostic Marker for Primary Venous Thromboembolism
- 2018
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In: Clinical and Applied Thrombosis/Hemostasis. - : SAGE Publications. - 1938-2723 .- 1076-0296. ; 24:3, s. 416-422
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Journal article (peer-reviewed)abstract
- Recently, decreased levels of apolipoprotein M (ApoM) were shown to be associated with higher risk of recurrent venous thromboembolism (VTE) in male patients. However, the role of ApoM in primary VTE is unknown. We aimed in our study to analyze the plasma levels of ApoM in patients with VTE in order to evaluate the diagnostic importance of ApoM in primary VTE. A total of 357 patients with suspected first episode of VTE were recruited prospectively in the SCORE study. Plasma samples from 307 patients were available for quantifying the plasma levels of ApoM in patients with VTE using sandwich enzyme-linked immunosorbent assay method. Among the whole population, plasma levels (mean [standard deviation]) of ApoM were not significantly different between patients with VTE (0.72 [0.20]) and non-VTE patients (0.72 [0.16]), P = .99. Similarly, in regression analyses, no significant association of ApoM plasma levels with the risk of VTE was found on univariate (odds ratio [OR] =1.0, 95% confidence interval [CI] 0.21-4.84, P = .99) and multivariate analysis (OR = 1.25, 95% CI = 0.19-8.34, P = .819) after adjusting for age, body mass index, and smoking. Moreover, results did not differ significantly after stratification of data according to sex ( P > .05). In this study, our results do not suggest a diagnostic role for ApoM plasma levels in patients with primary VTE. Moreover, the current study suggests that role of ApoM as a risk factor may differ for primary VTE and recurrent VTE in male patients.
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| 7. |
- Ahmad, Abrar, et al.
(author)
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Fat mass and obesity-associated gene rs9939609 polymorphism is a potential biomarker of recurrent venous thromboembolism in male but not in female patients
- 2018
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In: Gene. - : Elsevier BV. - 0378-1119. ; 647, s. 136-142
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Journal article (peer-reviewed)abstract
- Multiple genetic variations have been identified in FTO (fat mass and obesity-associated) gene. Among them, FTO rs9939609 polymorphism is shown to be associated with the risk of primary venous thromboembolism (VTE). However, its role in recurrent VTE is not known. The aim of our study was to investigate the association between FTO rs9939609 polymorphism and the risk of VTE recurrence in a prospective follow-up study in both male and female patients. FTO rs9939609 polymorphism (T/A) was analyzed in the Malmö thrombophilia study (MATS, followed for ~10 years) by using TaqMan PCR. MATS patients (n = 1050) were followed from the discontinuation of anticoagulant treatment until diagnosis of VTE recurrence or the end of follow-up. A total of 126 patients (12%) had VTE recurrence during follow-up. Cox regression analyses showed that sex modified the potential effect of FTO rs9939609 polymorphism on VTE recurrence. Male patients with the AA genotype for the FTO rs9939609 polymorphism had significantly higher risk of VTE recurrence as compared to the TT or AT genotypes (univariate hazard ratio [HR] = 2.05, 95% confidence interval [CI] = 1.2-3.5, P = 0.009 and adjusted HR = 2.03, 95% CI 1.2-3.6, P = 0.013). There was no association between FTO rs9939609 polymorphism and VTE recurrence in female patients. In conclusion, our results show that FTO rs9939609 polymorphism in recurrent VTE may differ according to gender and FTO polymorphism may predict VTE recurrence in male patients.
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| 8. |
- Ahmad, Abrar, et al.
(author)
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Identification of Genetic Aberrations in Thrombomodulin Gene in Patients with Recurrent Venous Thromboembolism
- 2017
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In: Clinical and Applied Thrombosis/Hemostasis. - : SAGE Publications. - 1076-0296 .- 1938-2723. ; 23:4, s. 319-328
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Journal article (peer-reviewed)abstract
- Thrombomodulin (THBD) serves as a cofactor for thrombin-mediated activation of anticoagulant protein C pathway. Genetic aberrations in THBD have been studied in arterial and venous thrombosis. However, genetic changes in THBD and their role in the risk assessment of recurrent venous thromboembolism (VTE) are not well understood. The aim of the present study was to identify the genetic aberrations in THBD and their association with the risk of VTE recurrence in a prospective population-based study. We sequenced the entire THBD gene, first in selected patients with VTE (n = 95) by Sanger sequencing and later validated those polymorphisms with minor allele frequency (MAF) ≥5% in the whole study population (n = 1465 with the follow-up period of 1998-2008) by Taqman polymerase chain reaction. In total, we identified 8 polymorphisms in THBD, and 3 polymorphisms with MAF ≥5% were further validated. No significant association between THBD polymorphisms and risk of VTE recurrence on univariate or multivariate Cox regression analysis was found (hazard ratio [HR] = 0.89, 95% confidence interval [CI] = 0.62-1.28, HR = 1.27, 95% CI = 0.88-1.85, and HR = 1.15, 95% CI = 0.80-1.66 for THBD rs1962, rs1042580, and rs3176123 polymorphisms, respectively), adjusted for family history, acquired risk factors for VTE, location of deep vein thrombosis, and risk of thrombophilia. Subanalysis of patients with unprovoked first VTE also showed no significant association of identified THBD polymorphisms with the risk of VTE recurrence. Our results show that aberrations in the THBD gene may not be useful for the assessment of VTE recurrence; however, further studies with large sample size are needed to confirm these findings.
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| 9. |
- Ahmad, Abrar, et al.
(author)
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Identification of polymorphisms in Apolipoprotein M gene and their relationship with risk of recurrent venous thromboembolism
- 2016
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In: Thrombosis and Haemostasis. - 0340-6245. ; 116:3, s. 41-432
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Journal article (peer-reviewed)abstract
- Apolipoprotein M (ApoM) plasma levels have been reported to be associated with risk of venous thromboembolism (VTE) recurrence. However, the role of genetic alterations in the ApoM gene in VTE recurrence remains unknown. The aim of this study was to identify genetic aberrations in ApoM gene in VTE recurrence and their role in prediction of VTE recurrence in a prospective follow-up study of 1465 VTE patients. During follow-up, 156 (10.6 %) patients had VTE recurrence. First screening of whole ApoM gene was performed by Sanger's sequencing in selected age and sex matched non-recurrent and recurrent patients (n=95). In total six polymorphisms were identified and two polymorphisms (rs805297 and rs9404941) with minor allele frequency (MAF) ≥5 % were further genotyped in the whole cohort by Taqman PCR. ApoM rs805297 polymorphism was significantly associated with higher risk of VTE recurrence in males but not in females on both univariate (p= 0.038, hazard ratio = 1.72, confidence interval = 1.03-2.88) and on multivariate analysis adjusted with mild and severe thrombophilia, family history, location and acquired risk factors for VTE. However, ApoM rs9404941 polymorphism showed no significant association with risk of VTE recurrence in all patients as well as in different gender groups. Moreover, ApoM rs805297 and rs9404941 polymorphisms were not associated with the ApoM plasma levels. In conclusion, for the first time we have sequenced whole ApoM gene in VTE and identified six polymorphisms. ApoM rs805297 was significantly associated with higher risk of VTE recurrence in male but not in female patients.
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| 10. |
- Ahmad, Abrar, et al.
(author)
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Risk prediction of recurrent venous thromboembolism : a multiple genetic risk model
- 2019
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 47:2, s. 216-226
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Journal article (peer-reviewed)abstract
- A single genetic biomarker is unable to accurately predict the risk for venous thromboembolism (VTE) recurrence. We aimed to: (a) develop a multiple single nucleotide polymorphisms (SNPs) model to predict the risk of VTE recurrence and (b) validate a previously described genetic risk score (GRS) and compare its performance with the model developed in this study. Twenty-two SNPs, including established and putative SNPs associated with VTE risk, were genotyped in the Malmö thrombophilia study cohort (MATS; n = 1465, follow-up ~ 10 years) by using TaqMan PCR. Out of 22-SNPs, 12 had an association with the risk of VTE recurrence and were included for calculating GRSs. The risk of VTE recurrence was calculated by stratifying patients according to number of risk alleles. In 12-SNP GRS, patients with ≥ 7 risk alleles were associated with higher risk of VTE recurrence compared to patients having ≤ 6 risk alleles. In a simplified model (8-SNP GRS), the discriminative power of 8-SNP GRS was similar to that of 12-SNP GRS based on post-test probabilities (PP). Furthermore, 8-SNP GRS further improved the risk prediction of VTE recurrence in unprovoked VTE and male patients (PP% = 15.4 vs 8.3, 17.1 vs 7.2 and 19.0 vs 7.1 for high risk groups vs low risk groups in whole population, males and unprovoked VTE patients respectively). In addition, we also validated previously described 5-SNP GRS in our cohort and found that the 8-SNP GRS performed better than the 5-SNP GRS in terms of higher PP. Our results show that a multiple SNP GRS consisting of 8-SNPs may be an effective model for prediction of VTE recurrence, particularly in unprovoked VTE and male patients.
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| 11. |
- Ahmad, Shafqat, et al.
(author)
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A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults.
- 2016
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 40:1, s. 186-190
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Journal article (peer-reviewed)abstract
- BackgroundObesity is a complex disease caused by the interplay of genetic and lifestyle factors, but identification of gene-lifestyle interactions in obesity has remained challenging. Few large-scale studies have reported use of genome-wide approaches to investigate gene-lifestyle interactions in obesity.MethodsIn the PROMIS study, a cross-sectional study based in Pakistan, we calculated BMI variance estimates (square of the residual of inverse-normal transformed BMI z-score) in 14 131 participants and conducted genome-wide heterogeneity of variance analyses (GWHVA) for this outcome. All analyses were adjusted for age, age(2), sex and genetic ancestry.ResultsThe GWHVA analyses yielded a genome-wide significance (P-value=3.1 × 10(-8)) association of the rs140133294 variant at FLJ33534 with BMI variance. In explicit tests of gene × lifestyle interaction, smoking was found to significantly modify the effect of rs140133294 on BMI (Pinteraction=0.0005), whereby the minor allele (T) was associated with lower BMI in current smokers, while positively associated with BMI in never-smokers. No interactions with physical activity were observed. Analyses of ENCODE data at the FLJ33534 locus revealed features indicative of open chromatin and high confidence DNA-binding motifs for several transcription factors, providing suggestive biological support for a mechanism of interaction.ConclusionIn summary, we have identified a novel interaction between smoking and variation at the FLJ33534 locus in relation to BMI in people from Pakistan.International Journal of Obesity accepted article preview online, 17 August 2015. doi:10.1038/ijo.2015.152.
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| 12. |
- Alégroth, Emil, 1984, et al.
(author)
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Conceptualization and evaluation of component-based testing unified with visual GUI testing: An empirical study
- 2015
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In: 2015 IEEE 8th International Conference on Software Testing, Verification and Validation, ICST 2015 - Proceedings. - 2159-4848. - 9781479971251
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Conference paper (peer-reviewed)abstract
- In this paper we present the results of a two-phase empirical study where we evaluate and compare the applicability of automated component-based Graphical User Interface (GUI) testing and Visual GUI Testing (VGT) in the tools GUITAR and a prototype tool we refer to as VGT GUITAR. First, GUI mutation operators are defined to create 18 faulty versions of an application on which both tools are then applied in an experiment. Results from 456 test case executions in each tool show, with statistical significance, that the component-based approach reports more false negatives than VGT for acceptance tests but that the VGT approach reports more false positives for system tests. Second, a case study is performed with larger open source applications, ranging from 8,803-55,006 lines of code. Results show that GUITAR is applicable in practice but has some challenges related to GUI component states. The results also show that VGT GUITAR is currently not applicable in practice and therefore requires further research and development. Based on the study's results we present areas of future work for both test approaches and conclude that the approaches have different benefits and drawbacks. The component-based approach is robust and executes tests faster than the VGT approach, with a factor of 3. However, the VGT approach can perform visual assertions and is perceived more flexible than the component- based approach. These conclusions let us hypothesize that a combination of the two approaches is the most suitable in practice and therefore warrants future research.
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| 13. |
- Calling, Susanna, et al.
(author)
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Women's Health in the Lund Area (WHILA) study. Health problems and acute myocardial infarction in women – A 17-year follow-up study
- 2018
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In: Maturitas. - : Elsevier BV. - 0378-5122. ; 115, s. 45-50
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Journal article (peer-reviewed)abstract
- Objectives: The literature has highlighted the importance of identifying symptoms predictive of acute myocardial infarction (AMI) in women, in addition to traditional cardiovascular risk factors. The objective was to study subjective health problems, in relation to later AMI, in a large sample of women, adjusted for age, educational status, smoking, waist/hip ratio, blood pressure, total cholesterol/HDL ratio, diabetes and neighbourhood socioeconomic status. Study design: From December 1995 to February 2000 a cohort of 6711 women aged 50–59 years in southern Sweden underwent a physical examination and answered a questionnaire that had 18 items on health problems such as stress symptoms, tiredness and pain. Main outcome measures: Incidence of AMI during a mean follow-up of 17 years, drawn from national registers. Results: The number of health problems showed a J-shaped relationship with AMI, with the lowest hazard ratio (HR) in women with a median of 4 health problems. The HR for AMI in women with 0 health problems was 1.58 (95% CI: 0.95–2.63) and in those with 13 problems HR 1.65 (95% CI 1.16–2.36), after adjusting for potential confounding factors. Conclusions: The presence of several health problems, including pain and stress symptoms, is associated with an increased risk of later AMI in middle-aged women. Awareness among clinicians of predictive risk factors for AMI is important for the early identification of individuals at higher risk.
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| 15. |
- Farr, W. J., et al.
(author)
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Current issues and challenges in research on virtual reality therapy for children with neurodisability
- 2016
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In: Proceedings of the 11th International Conference in Disability, Virtual Reality and Associated Technologies, Los Angeles, California, USA, 20-22 September, 2016. - 9780704915473
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Conference paper (peer-reviewed)abstract
- A PICO (population, intervention, comparison, outcome) approach is adopted to discuss issues and challenges in virtual reality therapy research in community health settings. Widespread variation within and between populations, e.g. co-morbid conditions, complicates treatment fidelity and applicability. Interventions require flexible dose and frequency to fit into children’s family circumstances, with clearly employed specialist paediatric research staff. Comparisons require adaptation to digital technology, and keep pace with development. Outcomes may overstate the impact of virtual reality therapy and technological novelty, while not fully unpacking hidden digital effects. A wide set of agreed, flexible, and patient-centred outcome measures are required to establish positive clinical baseline.
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| 16. |
- Farr, W., et al.
(author)
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Therapeutic potential and ownership of commercially available consoles in children with cerebral palsy
- 2017
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In: British Journal of Occupational Therapy. - : Sage Publications. - 0308-0226 .- 1477-6006. ; 80:2, s. 108-116
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Journal article (peer-reviewed)abstract
- Introduction:We conducted a survey amongst families of children with cerebral palsy to ascertain the ownership and therapeutic use and potential of commercial games consoles to improve motor function.Method:Three hundred families in South East England were identified through clinical records, and were requested to complete an anonymised questionnaire.Results: A total of 61 families (20% response) returned a completed questionnaire with 41 (68%) identified males and 19 (32%) identified females with cerebral palsy, with a mean age of 11 years 5 months (SD 3Y 7M). The large majority of families, 59 (97%), owned a commercial console and the child used this for 50-300 minutes a week. Returns by severity of motor impairment were: Gross Motor Function Classification System I (22%), II (32%), III (13%), IV (15%), V (18%). Consoles were used regularly for play across all Gross Motor Function Classification System categories.Conclusion: The potential of games consoles, as home-based virtual reality therapy, in improving the motor function of children with cerebral palsy should be appropriately tested in a randomised controlled trial. Wide ownership, and the relative ease with which children engage in the use of commercially-based virtual reality therapy systems, suggests potential as a means of augmenting therapy protocols, taking advantage of interest and participation patterns of families.
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| 17. |
- Fontes-Villalba, Maelán, et al.
(author)
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Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes : A randomised cross-over trial
- 2016
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In: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 15:1
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Journal article (peer-reviewed)abstract
- Background: We have previously shown that a Palaeolithic diet consisting of the typical food groups that our ancestors ate during the Palaeolithic era, improves cardiovascular disease risk factors and glucose control compared to the currently recommended diabetes diet in patients with type 2 diabetes. To elucidate the mechanisms behind these effects, we evaluated fasting plasma concentrations of glucagon, insulin, incretins, ghrelin, C-peptide and adipokines from the same study. Methods: In a randomised, open-label, cross-over study, 13 patients with type 2 diabetes were randomly assigned to eat a Palaeolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts, or a diabetes diet designed in accordance with current diabetes dietary guidelines during two consecutive 3-month periods. The patients were recruited from primary health-care units and included three women and 10 men [age (mean ± SD) 64 ± 6 years; BMI 30 ± 7 kg/m2; diabetes duration 8 ± 5 years; glycated haemoglobin 6.6 ± 0.6 % (57.3 ± 6 mmol/mol)] with unaltered diabetes treatment and stable body weight for 3 months prior to the start of the study. Outcome variables included fasting plasma concentrations of leptin, adiponectin, adipsin, visfatin, resistin, glucagon, insulin, C-peptide, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and ghrelin. Dietary intake was evaluated by use of 4-day weighed food records. Results: Seven participants started with the Palaeolithic diet and six with the diabetes diet. The Palaeolithic diet resulted in a large effect size (Cohen's d = -1.26) at lowering fasting plasma leptin levels compared to the diabetes diet [mean difference (95 % CI), -2.3 (-5.1 to 0.4) ng/ml, p = 0.023]. No statistically significant differences between the diets for the other variables, analysed in this study, were observed. Conclusions: Over a 3-month study period, a Palaeolithic diet resulted in reduced fasting plasma leptin levels, but did not change fasting levels of insulin, C-peptide, glucagon, incretins, ghrelin and adipokines compared to the currently recommended diabetes diet. Trial registration: Clinical Trials.gov NCT00435240.
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| 18. |
- Jones, C., et al.
(author)
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Experiences and needs of parents of young children with active epilepsy: A population-based study
- 2019
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In: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 90, s. 37-44
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Journal article (peer-reviewed)abstract
- The aim of the study was to gain a comprehensive understanding of the experiences and needs of parents of young children with epilepsy from a total population sample. The parents (mothers (n = 38), fathers (n = 9)) of 40/53 (75% of total population) young children (1–7 years; 23 males, 17 females) with ‘active’ epilepsy (had a seizure in the last year or taking Anti-epileptic drugs (AEDs)) were interviewed either in person or over the telephone using a semistructured interview schedule. The families were resident in the south of the UK. The interviews were audio-recorded, transcribed, and coded using thematic analysis. Thematic analysis revealed six main themes: diagnostic journey, parental perception of epilepsy management, awareness and impact of associated neurobehavioral difficulties, inconsistent availability of therapeutic and educational supports, impact on family functioning, and need for parental support. Parents reported often having difficulty accessing a professional knowledgeable about epilepsy. While parents were generally satisfied with the initial information they received about seizures and their management, they reported that the association between epilepsy and neurobehavioral issues was often not broached. These developmental/behavioral difficulties often had a bigger impact on child wellbeing and family functioning, but provision of therapeutic and educational supports for the difficulties was often very patchy. Parents noted that early onset epilepsy and associated neurobehavioral difficulties often have a very significant impact on family functioning including increased restrictions on family activities and increased financial burden. Parents would like informational and emotional support to extend beyond the time of epilepsy diagnosis. There is a clear need for comprehensive childhood epilepsy services to include provision for identification and management of child neurobehavioral needs and a focus on family-centered care. © 2018 Elsevier Inc.
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| 19. |
- Kay, J., et al.
(author)
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Earlier anterior cruciate ligament reconstruction is associated with a decreased risk of medial meniscal and articular cartilage damage in children and adolescents: a systematic review and meta-analysis
- 2018
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In: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:12, s. 3738-3753
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Journal article (peer-reviewed)abstract
- Purpose To evaluate the association between surgical timing and the incidence of secondary meniscal or chondral damage in children and adolescents with anterior cruciate ligament (ACL) ruptures. Methods Three electronic databases, PubMed, MEDLINE, and EMBASE, were systematically searched from database inception until October 16, 2017 by two reviewers independently and in duplicate. The inclusion criteria were English language studies that reported the incidence of meniscal and articular cartilage damage in children or adolescent athletes with ACL injuries as well as the timing of their ACL reconstruction (ACLR). Risk ratios were combined in a meta-analysis using a random effects model. Results A total of nine studies including 1353 children and adolescents met the inclusion criteria. The mean age of patients included was 14.2 years (range 6-19), and 45% were female. There was a significantly decreased risk of concomitant medial meniscal injury in those reconstructed early (26%) compared to those with delayed reconstruction (47%) [pooled risk ratio (RR) = 0.49, 95% CI 0.36-0.65, p < 0.00001]. There was also a significantly reduced risk of medial femoral chondral (RR = 0.48, 95% CI 0.31-0.75, p = 0.001), lateral femoral chondral (RR = 0.38, 95% CI 0.20-0.75, p = 0.005), tibial chondral (RR = 0.45, 95% CI 0.27-0.75, p = 0.002), and patellofemoral chondral (RR = 0.41, 95% CI 0.20-0.82, p = 0.01) damage in the early reconstruction group in comparison to the delayed group. Conclusion Pooled results from observational studies suggest that early ACLR results in a significantly decreased risk of secondary medial meniscal injury, as well as secondary medial, lateral, and patellofemoral compartment chondral damage in children and adolescents. This study provides clinicians with valuable information regarding the benefits of early ACL reconstruction in children and adolescents, and can be used in the decision making for athletes in this population.
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| 20. |
- Memon, Ashfaque A., et al.
(author)
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Identification of novel diagnostic biomarkers for deep venous thrombosis
- 2018
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In: British Journal of Haematology. - : Wiley. - 0007-1048. ; 181:3, s. 378-385
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Journal article (peer-reviewed)abstract
- The combination of a negative D-dimer and a Wells score can rule out, but not confirm, a diagnosis of deep venous thrombosis (DVT). We aimed to identify new diagnostic biomarkers for DVT and to investigate their relationship with hypercoagulability markers [D-dimer and activated protein C-protein C inhibitor (APC-PCI) complex]. We screened 92 cardiovascular-specific proteins in plasma samples from 45 confirmed DVT patients and 45 age- and sex-matched non-DVT patients selected from a prospective multicentre diagnostic management study (SCORE) by Proseek Multiplex CVDIII96×96. Plasma levels of 30 proteins were significantly different between DVT and non-DVT patients. After Bonferroni correction, plasma levels of seven proteins: P-selectin, transferrin receptor protein 1, von Willebrand factor, tissue factor pathway inhibitor, osteopontin (OPN), bleomycin hydrolase and ST2 protein remained significantly different. The area under curve (AUC) for these proteins ranged from 0·70 to 0·84. Furthermore, all seven identified proteins were significantly associated with markers of hypercoagulability. A combination of OPN and APC-PCI had the best ability to discriminate DVT from non-DVT patients (AUC = 0·94; sensitivity = 89% and specificity = s84%). In conclusion, we identified multiple proteins associated with markers of hypercoagulability and with a potential to become novel diagnostic biomarkers for DVT.
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| 21. |
- Memon, Ashfaque A., et al.
(author)
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Quantification of mitochondrial DNA copy number in suspected cancer patients by a well optimized ddPCR method
- 2017
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In: Biomolecular Detection and Quantification. - : Elsevier BV. - 2214-7535. ; 13, s. 32-39
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Journal article (peer-reviewed)abstract
- Changes in mitochondrial DNA (mtDNA) content is a useful clinical biomarker for various diseases, however results are controversial as several analytical factors can affect measurement of mtDNA. MtDNA is often quantified by taking ratio between a target mitochondrial gene and a reference nuclear gene (mtDNA/nDNA) using quantitative real time PCR often on two separate experiments. It measures relative levels by using external calibrator which may not be comparable across laboratories. We have developed and optimized a droplet digital PCR (ddPCR) based method for quantification of absolute copy number of both mtDNA and nDNA gene in whole blood. Finally, the role of mtDNA in suspected cancer patients referred to a cancer diagnostic center was investigated.Analytical factors which can result in false quantification of mtDNA have been optimized and both target and reference have been quantified simultaneously with intra- and inter-assay coefficient variances as 3.1% and 4.2% respectively. Quantification of mtDNA show that compared to controls, solid tumors (but not hematologic malignancies) and other diseases had significantly lower copy number of mtDNA. Higher mtDNA (highest quartile) was associated with a significantly lower risk of both solid tumors and other diseases, independent of age and sex. Receiver operating curve demonstrated that mtDNA levels could differentiate controls from patients with solid tumors and other diseases.Quantification of mtDNA by a well optimized ddPCR method showed that its depletion may be a hallmark of general illness and can be used to stratify healthy individuals from patients diagnosed with cancer and other chronic diseases.
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| 22. |
- Memon, Ashfaque A, et al.
(author)
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Role of IL-8, CRP and epidermal growth factor in depression and anxiety patients treated with mindfulness-based therapy or cognitive behavioral therapy in primary health care
- 2017
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In: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 254, s. 311-316
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Journal article (peer-reviewed)abstract
- Epidermal growth factor (EGF) and inflammatory markers have been associated with various neuro-psychiatric disorders. However, their role in mild to moderate depression and anxiety patients treated with mindfulness-based group therapy (mindfulness) or cognitive behavioral therapy (CBT) is not known. In this study we analyzed plasma levels of interleukin (IL)-6, IL-8, high sensitivity C-reactive protein (hsCRP) and EGF before (baseline) and after treatment (8 weeks) and investigated their role in response to both arms of the treatment. To cover variety of mental symptoms, treatment response was analyzed by four scales, the Montgomery-Åsberg depression rating scale (MADRS), Hospital anxiety and depression scale- Depression (HADS-D) and anxiety (HADS-A) and patients health questionnaire-9. EGF levels were significantly decreased after both mindfulness and CBT and were associated with treatment response on all scales independent of the use of tranquilizers and antidepressant treatment. Moreover, baseline EGF levels were significantly associated only with baseline scores of anxiety scale. Levels of inflammatory markers analyzed in this study, were not significantly associated with treatment response on any scale. Our findings suggest that improvement in symptoms of depression and anxiety after both mindfulness and CBT is associated with changes in EGF levels but not with the inflammatory markers.
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| 23. |
- Memon, Ashfaque A., et al.
(author)
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Soluble HER3 predicts survival in bladder cancer patients
- 2018
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In: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 15:2, s. 1783-1788
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Journal article (peer-reviewed)abstract
- The role of soluble human epidermal growth factor receptor (sHER3) in bladder cancer remains unclear. In the present study, an ELISA was developed for the quantification of sHER3 and its role was investigated in patients with bladder cancer (n=82) followed for 10 years. Furthermore, the effects of sHER3 on bladder cancer cell growth and migration were also investigated. The results demonstrated that plasma sHER3 levels were significantly higher in non-invasive tumours (Ta) compared with muscle-invasive tumours (T2-T4). Higher sHER3 levels were associated with a more improved survival rate. However multivariate Cox regression analysis, adjusted for clinical stage, grade, type and size of the tumour, demonstrated that sHER3 was not an independent biomarker of survival. Exogenous sHER3 significantly inhibited bladder cancer cell growth and migration. These results suggest that high sHER3 levels are associated with improved survival rates in patients with bladder cancer, and that sHER3 inhibits bladder cancer cell growth and migration.
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| 24. |
- Nekimken, A. L., et al.
(author)
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Pneumatic stimulation of C. elegans mechanoreceptor neurons in a microfluidic trap
- 2017
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In: Lab on a Chip - Miniaturisation for Chemistry and Biology. - : Royal Society of Chemistry (RSC). - 1473-0189 .- 1473-0197. ; 17:6, s. 1116-1127
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Journal article (peer-reviewed)abstract
- New tools for applying force to animals, tissues, and cells are critically needed in order to advance the field of mechanobiology, as few existing tools enable simultaneous imaging of tissue and cell deformation as well as cellular activity in live animals. Here, we introduce a novel microfluidic device that enables high-resolution optical imaging of cellular deformations and activity while applying precise mechanical stimuli to the surface of the worm's cuticle with a pneumatic pressure reservoir. To evaluate device performance, we compared analytical and numerical simulations conducted during the design process to empirical measurements made with fabricated devices. Leveraging the well-characterized touch receptor neurons (TRNs) with an optogenetic calcium indicator as a model mechanoreceptor neuron, we established that individual neurons can be stimulated and that the device can effectively deliver steps as well as more complex stimulus patterns. This microfluidic device is therefore a valuable platform for investigating the mechanobiology of living animals and their mechanosensitive neurons.
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| 25. |
- Nikpay, Majid, et al.
(author)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Journal article (peer-reviewed)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 26. |
- Oliveira, R., et al.
(author)
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Definition and evaluation of mutation operators for GUI-level mutation analysis
- 2015
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In: 2015 IEEE 8th International Conference on Software Testing, Verification and Validation Workshops, ICSTW 2015 - Proceedings. - 2159-4848. - 9781479918850
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Conference paper (peer-reviewed)abstract
- Automated testing has become essential in software industry to meet market demands for faster delivery and higher quality software. Testing is performed on many levels of system abstraction, from tests on source code to Graphical User Interface (GUI) tests. New testing techniques and frameworks are also continuously released to the market. Mutation analysis has been proposed as a way of assessing the quality of these new test techniques/frameworks as well as existing test suites in practice. The analysis is performed by seeding defects, referred to as mutants, into the system under test with the assumption that a technique/test suite of high quality will 'kill' the mutants. However, whilst support for mutation analysis exists for test techniques that operate on on lower levels of system abstraction, i.e. method-level mutation operators, the support for GUI-level mutation analysis is currently lacking. In this paper we perform an empirical analysis of 18 GUI-level mutation operators defined in our previous work and compare their efficiency and comprehensiveness to state-of-practice lower level mutation operators. The main findings of our analysis are (1) that traditional method-level mutation operators are not precise enough for GUI-level mutation; (2) the defined GUI-based mutation operators provide comprehensive support for GUI-level mutation; and (3) GUI-based mutation operators can be automated but are challenged by the dependencies between GUI widgets.
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| 27. |
- Reilly, C., et al.
(author)
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Global development and adaptive behaviour in children with early-onset epilepsy: a population-based case-control study
- 2019
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In: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622. ; 61:2
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Journal article (peer-reviewed)abstract
- Aim There are limited population-based data on global development and adaptive behaviour in children with early-onset epilepsy. The aims of this study were: (1) to identify the prevalence of deficits in global development and adaptive behaviour experienced by children with early-onset epilepsy; (2) to identify factors associated with such deficits; and (3) to compare the relationship between measures of neurodevelopment in the group with epilepsy to a group without epilepsy who had other neurological or neurodevelopmental difficulties. Method The Sussex Early Epilepsy and Neurobehaviour study is a prospective, community-based study involving children (1-7y) with epilepsy. We undertook comprehensive psychological assessment with participants, including measures of global development and adaptive behaviour. We compared the children with epilepsy with a sex, age, and developmentally-matched group of children without epilepsy who had neurodevelopmental or neurological difficulties using correlation matrices. Results Forty-eight children (91% of the eligible population) with epilepsy underwent assessment. Seventy-one per cent of children displayed delayed global development (SD) and 56% showed significant deficits (SD) in adaptive behaviour. Our analysis revealed that non-white ethnicity and use of polytherapy were independently associated with decreased scores on measures of global development and adaptive behaviour. The correlations between measures of developmental functioning were higher in children with epilepsy than in those without. Interpretation Children with early-onset epilepsy frequently have difficulties with global development and adaptive behaviour. The higher correlations between neurodevelopmental measures in children with epilepsy suggest that the profile in children with epilepsy is different. This may have significant implications for both neuropathology and interventions. What this paper adds Children with early-onset epilepsy are at significant risk of intellectual disability. Developmental impairment is associated with use of polytherapy but not with any seizure parameters. Developmental profiles in young children with epilepsy differ from other conditions.
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| 28. |
- Reilly, C., et al.
(author)
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Parenting stress and perceived stigma in mothers of young children with epilepsy: A case–control study
- 2018
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In: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 89, s. 112-117
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Journal article (peer-reviewed)abstract
- The aim was to provide data on parenting stress and perceived stigma in mothers (n = 47) of young children with epilepsy, and to compare findings with those of mothers (n = 48) of developmental, age- and gender-matched children with nonepilepsy-related neurodisability (neurological and/or neurodevelopmental concerns). The mothers of young children (1–7 years) with epilepsy and mothers of children with neurodisability in a defined geographical area of the UK, completed the Parenting Stress Index—4th Edition (PSI-4) and a measure of perceived stigma. Factors associated with parenting stress and stigma were analyzed using linear regression. Thirty-eight percent of mothers of children with epilepsy scored in the at-risk range (> 85th percentile) on the Total Stress score of the PSI-4 (Neurodisability 21%) (p = 0.06). Significantly more mothers of children with epilepsy scored in the at-risk range on the Parent–Child Dysfunctional Interaction subscale than mothers of children with neurodisability (Epilepsy 45% vs. Neurodisability 21%; p = 0.01), but not on the Parental Distress subscale (Epilepsy 32% vs. Neurodisability 23%; p = 0.33) or Difficult Child (Epilepsy 57% vs. Neurodisability 46%; p = 0.26) subscales. There was no statistically significant difference in perceived stigma between mothers in both groups (p = 0.51). Factors significantly associated with increased parenting stress in the group with epilepsy were child behavior difficulties (p < 0.001) and maternal sleep difficulties (p = 0.02). Lower child developmental level was the only factor independently associated with increased stigma in the group with epilepsy (p = 0.08). Mothers of young children with epilepsy report high levels of parenting stress and higher levels of difficulties with parent–child interaction compared with that of mothers of children with nonepilepsy-related neurodisability. Parenting stress and stigma in epilepsy were not associated with epilepsy factors. Efforts at reducing parenting stress and stigma should focus on interventions targeting child development and maternal sleep. © 2018 Elsevier Inc.
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| 29. |
- Sundquist, Jan, et al.
(author)
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Long-term improvements after mindfulness-based group therapy of depression, anxiety and stress and adjustment disorders : A randomized controlled trial
- 2019
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In: Early Intervention in Psychiatry. - : Wiley. - 1751-7885. ; 13:4, s. 943-952
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Journal article (peer-reviewed)abstract
- Background: Although mindfulness-based group therapies (MGTs) for depressive, anxiety or stress and adjustment disorders are promising, there is a substantial lack of knowledge regarding the long-term improvements after such therapies in these common psychiatric disorders. Methods: Two hundred and fifteen patients were randomized in a randomized clinical trial (RCT) (ClinicalTrials.gov ID: NCT01476371) conducted in 2012 at 16 primary healthcare centres in southern Sweden. The patients were randomized to MGT or treatment as usual (TAU) and completed four psychometric self-rated scales after 8 weeks of treatment. Approximately 12months after the completion of the 8-week treatment, the same scales were repeated. Ordinal and generalized linear-mixed models, adjusted for cluster effects, were used for the analysis. Results: For all four psychometric scales (MADRS-S [Montgomery-Åsberg Depression Rating Scale-S], HADS-D, HADS-A [Hospital Anxiety and Depression Scale A and D] and PHQ-9 [Patient Health Questionnaire-9]) the scores at the 1-year follow-up were significantly improved (all P values <0.001) in both groups. Furthermore, there were no significant differences between the MGT and TAU in the psychometric scores at the 1-year follow-up. Conclusions: To the best of our knowledge, this is the first RCT comparing the long-term improvements after MGT with TAU. Although it cannot be excluded that our findings are a result of the natural course of common psychiatric disorders or other factors, they suggest a long-term positive improvement after both MGT and TAU.
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| 30. |
- Sundquist, Kristina, et al.
(author)
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Polymorphisms in PARK2 and MRPL37 are associated with higher risk of recurrent venous thromboembolism in a sex-specific manner
- 2018
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In: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 46:2, s. 154-165
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Journal article (peer-reviewed)abstract
- Recent studies indicate that mitochondrial DNA (mtDNA) dysfunction is a biomarker of oxidative stress and can predict the risk of cardiovascular diseases (CVDs). Genetic variants in PARK2 (rs4708928) and MRPL37 (rs10888838) genes have been shown to be associated with altered levels of mtDNA in a sex-specific manner. However, the role of these genetic variants in risk assessment of recurrent venous thromboembolism (VTE) is unknown. We investigated the role of these polymorphisms in VTE recurrence in patients from the Malmö thrombophilia study (MATS, n = 1465), followed for ~ 10 years. Genotyping was performed by TaqMan polymerase chain reaction. Female patients with PARK2 polymorphism had significantly higher risk of VTE recurrence (Hazard ratio [HR] = 2.39, 95% confidence interval [CI] 1.09–5.24) and male patients with MRPL37 polymorphism had a significantly higher risk of VTE recurrence (HR = 1.79, 95% CI 1.01–3.17) on multivariate Cox regression analysis. Combined analysis of these polymorphism with factor V Leiden (FVL) showed that female patients with both, FVL and PARK2 polymorphism had even higher risk of VTE recurrence (HR = 4.49, 95% CI 1.58–12.75) compared to FVL or PARK2 polymorphism alone or both wild-type (reference). Similarly, male patients with both FVL and MRPL37 polymorphism had significantly higher risk of VTE recurrence (HR = 2.97, 95% CI 1.45–6.08) compared to those with FVL or MRPL37 polymorphisms alone or the reference group. Polymorphisms in nuclear genome regulating mtDNA together with FVL may be promising biomarkers for predicting VTE recurrence in a sex specific manner. The abstract should be followed by 3-4 bullet points that highlight the major findings. The final bullet point should address future research.
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| 31. |
- Wang, Xiao, et al.
(author)
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Association of mitochondrial DNA in peripheral blood with depression, anxiety and stress- and adjustment disorders in primary health care patients
- 2017
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In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X. ; 27:8, s. 751-758
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Journal article (peer-reviewed)abstract
- Mitochondrial dysfunction may result in a variety of diseases. The objectives here were to examine possible differences in mtDNA copy number between healthy controls and patients with depression, anxiety or stress- and adjustment disorders; the association between mtDNA copy number and disease severity at baseline; and the association between mtDNA copy number and response after an 8-week treatment (mindfulness, cognitive based therapy). A total of 179 patients in primary health care (age 20-64 years) with depression, anxiety and stress- and adjustment disorders, and 320 healthy controls (aged 19-70 years) were included in the study. Relative mtDNA copy number was measured using quantitative real-time PCR on peripheral blood samples. We found that the mean mtDNA copy number was significantly higher in patients compared to controls (84.9 vs 75.9, p<0.0001) at baseline. The difference in mtDNA copy number between patients and controls remained significant after controlling for age and sex (ß=8.13, p<0.0001; linear regression analysis). The mtDNA copy number was significantly associated with Patient Health Questionnaire (PHQ-9) scores (β=0.57, p=0.02) at baseline. After treatment, the change in mtDNA copy number was significantly associated with the treatment response, i.e., change in Hospital Anxiety and Depression Scale (HADS-D) and PHQ-9 scores (ß=1.00, p=0.03 and ß=0.65, p=0.04, respectively), after controlling for baseline scores, age, sex, BMI, smoking status, alcohol drinking and medication. Our findings show that mtDNA copy number is associated with symptoms of depression, anxiety and stress- and adjustment disorders and treatment response in these disorders.
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| 32. |
- Wang, Xiao, et al.
(author)
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Association of recurrent venous thromboembolism and circulating microRNAs
- 2019
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In: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 11:1
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Journal article (peer-reviewed)abstract
- Background: Patients with unprovoked first venous thromboembolism (VTE) are at a high risk of recurrence. Although circulating microRNAs (miRNAs) have been found to be associated with VTE and are markers of hypercoagulability, this study is the first to examine whether circulating miRNAs are associated with the risk of VTE recurrence. Results: A nested case-control study design was used where plasma samples were obtained from 78 patients with unprovoked VTE from the Malmö Thrombophilia Study (MATS). A total of 39 VTE patients with recurrent VTE (cases) were matched with 39 VTE patients without recurrent VTE (controls) defined by age and sex (MATS population). Plasma levels of 179 different miRNAs were evaluated in the 78 samples (after anticoagulant treatment was stopped) using qPCR. A total of 110 miRNAs were detected in all samples. Among those, 12 miRNAs (miR-15b-5p, miR-106a-5p, miR-197-3p, miR-652-3p, miR-361-5p, miR-222-3p, miR-26b-5p, miR-532-5p, miR-27b-3p, miR-21-5p, miR-103a-3p, and miR-30c-5p) were found to be associated with recurrent VTE after multiple correction test and conditional logistic regression analysis. A further analysis showed that miR-15b-5p, miR-197-3p, miR-27b-3p, and miR-30c-5p exhibited a trend over time, with a larger difference in miRNA levels between cases and controls for earlier recurrence. Of these 12 miRNAs, 8 miRNAs significantly correlated with circulating transforming growth factor β1/2 (TGFβ1/2). Three of them correlated with platelet count. Conclusion: We have identified 12 plasma miRNAs that may have the potential to serve as novel, non-invasive predictive biomarkers for VTE recurrence.
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| 33. |
- Wang, Xiao, et al.
(author)
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Diagnostic potential of plasma microRNA signatures in patients with deep-vein thrombosis
- 2016
-
In: Thrombosis and Haemostasis. - 0340-6245. ; 116:2, s. 328-336
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Journal article (peer-reviewed)abstract
- For excluding deep-vein thrombosis (DVT), a negative D-dimer and low clinical probability are used to rule out DVT. Circulating microR-NAs (miRNAs) are stably present in the plasma, serum and other body fluids. Their diagnostic function has been investigated in many diseases but not in DVT. The aims of present study were to assess the diagnostic ability of plasma miRNAs in DVT and to examine their correlation with known markers of hypercoagulability, such as D-dimer and APC-PCI complex. Plasma samples were obtained from 238 patients (aged 16-95 years) with suspected DVT included in a prospective multicentre management study (SCORE). We first performed miRNA screening of plasma samples from three plasma pools containing plasma from 12 patients with DVT and three plasma pools containing plasma from 12 patients without DVT using a microRNA Ready-to-use PCR Panel comprising 742 miRNA primer sets. Thirteen miRNAs that differentially expressed were further investigated by quantitative real-time (qRT)-PCR in the entire cohort. The plasma level of miR-424-5p (p=0.01) were significantly higher, whereas the levels of miR-136-5p (p=0.03) were significantly lower in DVT patients compared to patients without DVT. Receiver-operating characteristic curve analysis showed the area under the curve (AUC) values of 0.63 for miR-424-5p and 0.60 for miR-136-5p. The plasma level of miR-424-5p was associated with both D-dimer and APC-PCI complex levels (p<0.0001 and p=0.001, respectively). In conclusions, these findings indicate that certain miRNAs are associated with DVT and markers of hypercoagulability, though their diagnostic abilities are probably too low.
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| 34. |
- Wang, Xiao, et al.
(author)
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Leukocyte telomere length and depression, anxiety and stress and adjustment disorders in primary health care patients
- 2017
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In: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The primary aim was to examine possible differences in telomere length between primary health care patients, with depression, anxiety or stress and adjustment disorders, and healthy controls. The second aim was to examine the association between telomere length and baseline characteristics in the patients. The third aim was to examine the potential effects of the 8-week treatments (mindfulness-based group therapy or treatment as usual, i.e. mostly cognitive-based therapy) on telomere length, and to examine whether there was a difference in the potential effect on telomere length between the two groups. Methods: A total of 501 individuals including 181 patients (aged 20-64 years), with depression, anxiety and stress and adjustment disorders, and 320 healthy controls (aged 19-70 years) were recruited in the study. Patient data were collected from a randomized controlled trial comparing mindfulness-based group therapy with treatment as usual. We isolated genomic DNA from blood samples, collected at baseline and after the 8-week follow-up. Telomere length was measured by quantitative real-time (qRT)-PCR. Results: Telomere length was significantly shorter in the patients (mean = 0.77 ± 0.12,), compared to the controls (mean = 0.81 ± 0.14) (p = 0.006). The difference in telomere length remained significant after controlling for age and sex. Old age, male sex and being overweight were associated with shorter telomere length. There was no significant difference in telomere length between baseline and at the 8-week follow-up in any of the treatment groups and no difference between the two groups. Conclusion: Our findings confirm that telomere length, as compared with healthy controls, is shortened in patients with depression, anxiety and stress and adjustment disorders. In both groups (mindfulness-based group therapy or treatment as usual), the telomere length remained unchanged after the 8-week treatment/follow-up and there was no difference between the two groups. Trial registration: (ClinicalTrials.gov ID: NCT01476371 ) Registered November 11, 2011.
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| 35. |
- Zöller, Bengt, et al.
(author)
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Epidemiology of Familial Aggregation of Venous Thromboembolism
- 2016
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In: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 42:8, s. 821-832
-
Research review (peer-reviewed)abstract
- Familial aggregation (clustering) of venous thromboembolism (VTE) is the clustering of VTE within a family. Though several genes, such as antithrombin, protein C, protein S, factor V, and prothrombin are associated with the familial clustering of VTE, these loci only partially explain the familial aggregation of VTE. The epidemiology of the familial aggregation of VTE exhibits typical characteristics of complex traits. The family history of VTE in first-degree relatives is associated with a two to three times increased familial relative risk (FRR). The FRR of VTE is higher in younger individuals, increases with a number of affected relatives, decreases as the familial relationship becomes more distant, increases with severity (unprovoked), and exhibits slightly stronger male transmission (Carter effect). High FRR is observed in individuals with two or more affected siblings (FRR > 50). Because familial aggregation represents the sum of shared family environmental and genetic factors, one should not assume that evidence of familial aggregation implies genetic effects. However, studies in twins, extended families, adoptees, and spouses indicate a weak involvement of shared environmental factors to the familial aggregation of VTE. Moreover, familial aggregation of VTE fulfills the Hill's criteria for causation. In conclusion, familial aggregation of VTE signals a clinically relevant inherent predisposition for VTE.
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| 36. |
- Zöller, Bengt, et al.
(author)
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Risk of pulmonary embolism and deep venous thrombosis in patients with asthma : A nationwide case-control study from Sweden
- 2017
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 49:2
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Journal article (peer-reviewed)abstract
- Asthma is associated with an increased risk of pulmonary embolism (PE) but little is known about whether asthma is associated with an increased risk of deep venous thrombosis (DVT). The aim in this study was to determine the risk of the first event of PE, DVT or a combination of PE and DVT in patients with asthma. We conducted this nationwide case-control study using data from Swedish nationwide registries. We included 114 366 Swedish-born patients with a first hospital diagnosis of PE, 76 494 patients with DVT and 6854 patients with both PE and DVT in Sweden between 1981 and 2010. We also included five age-, sexand education-matched population controls. All previous hospital diagnoses of asthma were identified. Conditional logistic regression was used to compute odds ratios with adjustment for potential confounders. Asthma was associated with an adjusted odds ratio for PE of 1.43 (95% CI 1.37-1.50), for DVT of 1.56 (95% CI 1.47-1.65) and for combined PE and DVT of 1.60 (95% CI 1.32-1.93). Asthma was associated with an increased risk of PE, DVT and combined PE and DVT. Thus, the inflammation conferred by asthma seems to have systemic (and not just local) prothrombotic effects with increased risk of both DVT and PE.
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