| 1. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
|
|
| 3. |
- Pelletier, F., et al.
(författare)
-
Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
-
Tidskriftsartikel (refereegranskat)abstract
- Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
|
|
| 4. |
- Ramilowski, JA, et al.
(författare)
-
Functional annotation of human long noncoding RNAs via molecular phenotyping
- 2020
-
Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
-
Tidskriftsartikel (refereegranskat)abstract
- Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
|
|
| 5. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
-
Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
-
Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
|
|
| 6. |
- Broberg, C. S., et al.
(författare)
-
Long-Term Outcomes After Atrial Switch Operation for Transposition of the Great Arteries
- 2022
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 80:10, s. 951-963
-
Tidskriftsartikel (refereegranskat)abstract
- Background: For patients with d-loop transposition of the great arteries (d-TGA) with a systemic right ventricle after an atrial switch operation, there is a need to identify risks for end-stage heart failure outcomes. Objectives: The authors aimed to determine factors associated with survival in a large cohort of such individuals. Methods: This multicenter, retrospective cohort study included adults with d-TGA and prior atrial switch surgery seen at a congenital heart center. Clinical data from initial and most recent visits were obtained. The composite primary outcome was death, transplantation, or mechanical circulatory support (MCS). Results: From 1,168 patients (38% female, age at first visit 29 ± 7.2 years) during a median 9.2 years of follow-up, 91 (8.8% per 10 person-years) met the outcome (66 deaths, 19 transplantations, 6 MCS). Patients experiencing sudden/arrhythmic death were younger than those dying of other causes (32.6 ± 6.4 years vs 42.4 ± 6.8 years; P < 0.001). There was a long duration between sentinel clinical events and end-stage heart failure. Age, atrial arrhythmia, pacemaker, biventricular enlargement, systolic dysfunction, and tricuspid regurgitation were all associated with the primary outcome. Independent 5-year predictors of primary outcome were prior ventricular arrhythmia, heart failure admission, complex anatomy, QRS duration >120 ms, and severe right ventricle dysfunction based on echocardiography. Conclusions: For most adults with d-TGA after atrial switch, progress to end-stage heart failure or death is slow. A simplified prediction score for 5-year adverse outcome is derived to help identify those at greatest risk.
|
|
| 7. |
- Hathazi, D., et al.
(författare)
-
Metabolic shift underlies recovery in reversible infantile respiratory chain deficiency
- 2020
-
Ingår i: Embo Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 39:23
-
Tidskriftsartikel (refereegranskat)abstract
- Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6-months of age. RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only similar to 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt-tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease.
|
|
| 8. |
- van Dissel, A. C., et al.
(författare)
-
End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study
- 2023
-
Ingår i: European Heart Journal. - 0195-668X. ; 44:34, s. 3278-3291
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. Methods This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. Results From 558 patients (48% female, age at first visit 36 & PLUSMN; 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. Conclusions Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Petersson, M., et al.
(författare)
-
Patient-Reported Symptom Severity in a Nationwide Myasthenia Gravis Cohort Cross-sectional Analysis of the Swedish GEMG Study
- 2021
-
Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 97:14
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives To describe myasthenia gravis activities of daily living (MG-ADL) in relation to clinical characteristics in a large Swedish nationwide cohort. Methods In a cross-sectional prevalence cohort study, the Genes and Environment in Myasthenia Gravis study, performed from November 2018 through August 2019, patients with myasthenia gravis (MG) were invited to submit an extensive 106-item life environment questionnaire, including the MG-ADL score. Patients were classified into early-onset MG (EOMG, <50 years), late-onset MG (LOMG, >= 50 years), or thymoma-associated MG (TAMG). Comparisons of disease-specific characteristics were made between subgroups, sexes, and different MG-ADL scores. Results A total of 1,077 patients were included, yielding a 74% response rate: 505 (47%) were classified as EOMG, 520 (48%) LOMG, and 45 (4%) TAMG. Mean age at inclusion was 64.3 years (SD 15.7) and mean disease duration was 14.6 years (SD 14.0). Complete MG-ADL scores (n = 1,035) ranged from 0p to 18p, where 26% reported a score of 0p. Higher MG-ADL scores were associated with female sex, obesity, and diagnostic delay (odds ratio [OR] 1.62, 1.72, and 1.69; p(adj) = 0.017, 0.013, and 0.008) and inversely correlated with high educational attainment (OR 0.59; p(adj) = 0.02), but not with age at inclusion, disease subtype, or disease duration. Almost half of the population (47%) reported MG-ADL >= 3p, corresponding to an unsatisfactory symptom state. Discussion In this nationwide study, comprising more than 40% of the prevalent MG population in Sweden, almost half of the patients reported current disease symptoms associated with an unsatisfactory symptom state, indicating the need for improved treatment options.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Wang, SPS, et al.
(författare)
-
B-Cell NHL Subtype Risk Associated with Autoimmune Conditions and PRS
- 2022
-
Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 31:5, s. 1103-1110
-
Tidskriftsartikel (refereegranskat)
|
|
| 17. |
- Bjorn, A., et al.
(författare)
-
Review of life-cycle based methods for absolute environmental sustainability assessment and their applications
- 2020
-
Ingår i: Environmental Research Letters. - : IOP Publishing Ltd. - 1748-9326 .- 1748-9318. ; 15:8
-
Tidskriftsartikel (refereegranskat)abstract
- In many regions and at the planetary scale, human pressures on the environment exceed levels that natural systems can sustain. These pressures are caused by networks of human activities, which often extend across countries and continents due to global trade. This has led to an increasing requirement for methods that enable absolute environmental sustainability assessment (AESA) of anthropogenic systems and which have a basis in life cycle assessment (LCA). Such methods enable the comparison of environmental impacts of products, companies, nations, etc, with an assigned share of environmental carrying capacity for various impact categories. This study is the first systematic review of LCA-based AESA methods and their applications. After developing a framework for LCA-based AESA methods, we identified 45 relevant studies through an initial survey, database searches and citation analysis. We characterized these studies according to their intended application, impact categories, basis of carrying capacity estimates, spatial differentiation of environmental model and principles for assigning carrying capacity. We then characterized all method applications and synthesized their results. Based on this assessment, we present recommendations to practitioners on the selection and use of existing LCA-based AESA methods, as well as ways to perform assessments and communicate results to decision-makers. Furthermore, we identify future research priorities intended to extend coverage of all components of the proposed method framework, improve modeling and increase the applicability of methods. © 2020 The Author(s).
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Mavaddat, N, et al.
(författare)
-
Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
- 2020
-
Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 22:1, s. 8-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.MethodsA multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.ResultsThere was no association between RRSO and breast cancer forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR forBRCA2mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.ConclusionWe found no evidence that RRSO reduces breast cancer risk forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
|
|
| 22. |
|
|
| 23. |
- Rubinstein, Yaffa R., et al.
(författare)
-
The case for open science : rare diseases
- 2020
-
Ingår i: JAMIA Open. - : Oxford University Press (OUP). - 2574-2531. ; 3:3, s. 472-486
-
Forskningsöversikt (refereegranskat)abstract
- The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally.
|
|
| 24. |
- Sorelius, Karl, et al.
(författare)
-
The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting
- 2022
-
Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 78, s. 112-122
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P =.051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.
|
|
| 25. |
- Toft, A., et al.
(författare)
-
Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation
- 2023
-
Ingår i: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionIncreasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by CHMP2B mutation. MethodsCombining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish CHMP2B-FTD family. ResultsCompared with family controls, mutation carriers had significantly higher levels of complement C9, lysozyme and transcobalamin II, and lower levels of ubiquitin, cathepsin B, and amyloid precursor protein. DiscussionLower CSF ubiquitin concentrations in CHMP2B mutation carriers indicate that ubiquitin levels relate to the specific disease pathology, rather than all-cause neurodegeneration. Increased lysozyme and complement proteins may indicate innate immune activation. Altered levels of amyloid precursor protein and cathepsins have previously been associated with impaired lysosomal proteolysis in FTD. HighlightsCSF markers of proteostasis were explored in CHMP2B-mediated frontotemporal dementia (FTD).31 members of the Danish CHMP2B-FTD family were included.We used solid-phase extraction and parallel reaction monitoring mass spectrometry.Six protein levels were significantly altered in CHMP2B-FTD compared with controls.Lower CSF ubiquitin levels in patients suggest association with disease mechanisms.
|
|
| 26. |
- van den Berg, Rosanne L., et al.
(författare)
-
Digital remote assessment of speech acoustics in cognitively unimpaired adults : feasibility, reliability and associations with amyloid pathology
- 2024
-
Ingår i: Alzheimer's Research and Therapy. - 1758-9193. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer’s disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting. Methods: Fifty cognitively unimpaired adults (Age 68 ± 6.2 years, 58% female, 46% Aβ-positive) completed remote, tablet-based speech assessments (i.e., picture description, journal-prompt storytelling, verbal fluency tasks) for five days. The testing paradigm was repeated after 2–3 weeks. Acoustic speech features were automatically extracted from the voice recordings, and mean scores were calculated over the 5-day period. We assessed feasibility by adherence rates and usability ratings on the System Usability Scale (SUS) questionnaire. Test-retest reliability was examined with intraclass correlation coefficients (ICCs). We investigated the associations between acoustic features and Aβ-pathology, using linear regression models, adjusted for age, sex and education. Results: The speech assessment was feasible, indicated by 91.6% adherence and usability scores of 86.0 ± 9.9. High reliability (ICC ≥ 0.75) was found across averaged speech samples. Aβ-positive individuals displayed a higher pause-to-word ratio in picture description (B = -0.05, p = 0.040) and journal-prompt storytelling (B = -0.07, p = 0.032) than Aβ-negative individuals, although this effect lost significance after correction for multiple testing. Conclusion: Our findings support the feasibility and reliability of multi-day remote assessment of speech acoustics in cognitively unimpaired individuals with and without Aβ-pathology, which lays the foundation for the use of speech biomarkers in the context of early AD.
|
|
| 27. |
- Alarcon, Sonia, et al.
(författare)
-
Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2 ',3,4,4 ',5,5 '-heptachlorobiphenyl (PCB 180) : A postnatal follow-up study in rats
- 2021
-
Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 102, s. 109-127
-
Tidskriftsartikel (refereegranskat)abstract
- PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7-10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.
|
|
| 28. |
|
|
| 29. |
- Berg, B., et al.
(författare)
-
Development of osteoarthritis in patients with degenerative meniscal tears treated with exercise therapy or surgery : a randomized controlled trial
- 2020
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:7, s. 897-906
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate progression of individual radiographic features 5 years following exercise therapy or arthroscopic partial meniscectomy as treatment for degenerative meniscal tear. Design: Randomized controlled trial including 140 adults, aged 35–60 years, with a magnetic resonance image verified degenerative meniscal tear, and 96% without definite radiographic knee osteoarthritis. Participants were randomized to either 12-weeks of supervised exercise therapy or arthroscopic partial meniscectomy. The primary outcome was between-group difference in progression of tibiofemoral joint space narrowing and marginal osteophytes at 5 years, assessed semi-quantitatively by the OARSI atlas. Secondary outcomes included incidence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis, medial tibiofemoral fixed joint space width (quantitatively assessed), and patient-reported outcome measures. Statistical analyses were performed using a full analysis set. Per protocol and as treated analysis were also performed. Results: The risk ratios (95% CI) for progression of semi-quantitatively assessed joint space narrowing and medial and lateral osteophytes for the surgery group were 0.89 (0.55–1.44), 1.15 (0.79–1.68) and 0.77 (0.42–1.42), respectively, compared to the exercise therapy group. In secondary outcomes (full-set analysis) no statistically significant between-group differences were found. Conclusion: The study was inconclusive with respect to potential differences in progression of individual radiographic features after surgical and non-surgical treatment for degenerative meniscal tear. Further, we found no strong evidence in support of differences in development of incident radiographic knee osteoarthritis or patient-reported outcomes between exercise therapy and arthroscopic partial meniscectomy.
|
|
| 30. |
- de Haan, Anke, et al.
(författare)
-
Efficacy and moderators of efficacy of cognitive behavioural therapies with a trauma focus in children and adolescents: an individual participant data meta-analysis of randomised trials
- 2024
-
Ingår i: The Lancet Child and Adolescent Health. - 2352-4642. ; 8:1, s. 28-39
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Existing clinical trials of cognitive behavioural therapies with a trauma focus (CBTs-TF) are underpowered to examine key variables that might moderate treatment effects. We aimed to determine the efficacy of CBTs-TF for young people, relative to passive and active control conditions, and elucidate putative individual-level and treatment-level moderators. Methods: This was an individual participant data meta-analysis of published and unpublished randomised studies in young people aged 6−18 years exposed to trauma. We included studies identified by the latest UK National Institute of Health and Care Excellence guidelines (completed on Jan 29, 2018) and updated their search. The search strategy included database searches restricted to publications between Jan 1, 2018, and Nov 12, 2019; grey literature search of trial registries ClinicalTrials.gov and ISRCTN; preprint archives PsyArXiv and bioRxiv; and use of social media and emails to key authors to identify any unpublished datasets. The primary outcome was post-traumatic stress symptoms after treatment (<1 month after the final session). Predominantly, one-stage random-effects models were fitted. This study is registered with PROSPERO, CRD42019151954. Findings: We identified 38 studies; 25 studies provided individual participant data, comprising 1686 young people (mean age 13·65 years [SD 3·01]), with 802 receiving CBTs-TF and 884 a control condition. The risk-of-bias assessment indicated five studies as low risk and 20 studies with some concerns. Participants who received CBTs-TF had lower mean post-traumatic stress symptoms after treatment than those who received the control conditions, after adjusting for post-traumatic stress symptoms before treatment (b=−13·17, 95% CI −17·84 to −8·50, p<0·001, τ2=103·72). Moderation analysis indicated that this effect of CBTs-TF on post-traumatic stress symptoms post-treatment increased by 0·15 units (b=−0·15, 95% CI −0·29 to −0·01, p=0·041, τ2=0·03) for each unit increase in pre-treatment post-traumatic stress symptoms. Interpretation: This is the first individual participant data meta-analysis of young people exposed to trauma. Our findings support CBTs-TF as the first-line treatment, irrespective of age, gender, trauma characteristics, or carer involvement in treatment, with particular benefits for those with higher initial distress. Funding: Swiss National Science Foundation.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Olowoyo, J. O., et al.
(författare)
-
Blood lead concentrations in exposed forecourt attendants and taxi drivers in parts of South Africa
- 2024
-
Ingår i: Journal of Trace Elements in Medicine and Biology. - 0946-672X .- 1878-3252. ; 81
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Leaded fuel was banned in South Africa in 2006, in order to improve human health and reduce environmental pollution. Lead (Pb) has been suggested to contribute to the development of neurodegenerative disorders, and the role of respiratory exposure to Pb from petrol fumes should not be neglected in this context. In addition to Pb, petrol contains various harmful chemicals including other neurotoxic metals and hydrocarbons.Objectives and Methods: Here, we investigated concentrations of Pb and other metals in blood from petrol station forecourt attendants (n = 38), taxi drivers (n = 21), and unexposed controls (n = 36). Taxi drivers and forecourt attendants were divided into three groups each, based on number of years worked. A questionnaire was designed to investigate the health status of the participants. Blood samples were collected by medical professionals and analyzed for metal concentrations by ICP-MS.Results: A positive correlation between number of years worked and Pb blood concentrations was found. The highest Pb concentration (60.2 µg/L) was observed in a forecourt attendant who had worked 11–20 years, and the average Pb concentration in this group (24.5 µg/L) was significantly (p < 0.05) higher than in forecourt attendants who had worked 2–5 years (10.4 µg/L). Some individuals had elevated concentrations of manganese, arsenic, cadmium, chromium and cobalt, yet not significantly elevated at the group level. The blood levels of arsenic appeared to be related to smoking. Mood swings, dizziness, headaches and tiredness were reported by the workers.Conclusion: Blood Pb concentrations in petrol station forecourt attendants and taxi drivers exposed to leaded petrol are elevated and correlate to exposure time. A health monitoring program should be erected for all individuals working in these industries, and preventive measures should be implemented to eliminate metal exposure from petrol.
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Roos, K, et al.
(författare)
-
Single-cell RNA-seq analysis and cell-cluster deconvolution of the human preovulatory follicular fluid cells provide insights into the pathophysiology of ovarian hyporesponse
- 2022
-
Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13, s. 945347-
-
Tidskriftsartikel (refereegranskat)abstract
- Reduction in responsiveness to gonadotropins or hyporesponsiveness may lead to the failure of in vitro fertilization (IVF), due to a low number of retrieved oocytes. The ovarian sensitivity index (OSI) is used to reflect the ovarian responsiveness to gonadotropin stimulation before IVF. Although introduced to clinical practice already years ago, its usefulness to predict clinical outcomes requires further research. Nevertheless, pathophysiological mechanisms of ovarian hyporesponse, along with advanced maternal age and in younger women, have not been fully elucidated. Follicles consist of multiple cell types responsible for a repertoire of biological processes including responding to pituitary gonadotropins necessary for follicle growth and oocyte maturation as well as ovulation. Encouraging evidence suggests that hyporesponse could be influenced by many contributing factors, therefore, investigating the variability of ovarian follicular cell types and their gene expression in hyporesponders is highly informative for increasing their prognosis for IVF live birth. Due to advancements in single-cell analysis technologies, the role of somatic cell populations in the development of infertility of ovarian etiology can be clarified. Here, somatic cells were collected from the fluid of preovulatory ovarian follicles of patients undergoing IVF, and RNA-seq was performed to study the associations between OSI and gene expression. We identified 12 molecular pathways differentially regulated between hypo- and normoresponder patient groups (FDR<0.05) from which extracellular matrix organization, post-translational protein phosphorylation, and regulation of Insulin-like Growth Factor (IGF) transport and uptake by IGF Binding Proteins were regulated age-independently. We then generated single-cell RNA-seq data from matching follicles revealing 14 distinct cell clusters. Using cell cluster-specific deconvolution from the bulk RNA-seq data of 18 IVF patients we integrated the datasets as a novel approach and discovered that the abundance of three cell clusters significantly varied between hypo- and normoresponder groups suggesting their role in contributing to the deviations from normal ovarian response to gonadotropin stimulation. Our work uncovers new information regarding the differences in the follicular gene expression between hypo- and normoresponders. In addition, the current study fills the gap in understanding the inter-patient variability of cell types in human preovulatory follicles, as revealed by single-cell analysis of follicular fluid cells.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Strandberg, Kristin, et al.
(författare)
-
Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy
- 2020
-
Ingår i: Journal of Neuromuscular Diseases. - : IOS Press. - 2214-3599 .- 2214-3602. ; 7:3, s. 231-246
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Duchenne Muscular Dystrophy is a severe, incurable disorder caused by mutations in the dystrophin gene. The disease is characterized by decreased muscle function, impaired muscle regeneration and increased inflammation. In a clinical context, muscle deterioration, is evaluated using physical tests and analysis of muscle biopsies, which fail to accurately monitor the disease progression. Objectives: This study aims to confirm and asses the value of blood protein biomarkers as disease progression markers using one of the largest longitudinal collection of samples. Methods: A total of 560 samples, both serum and plasma, collected at three clinical sites are analyzed using a suspension bead array platform to assess 118 proteins targeted by 250 antibodies in microliter amount of samples. Results: Nine proteins are confirmed as disease progression biomarkers in both plasma and serum. Abundance of these biomarkers decreases as the disease progresses but follows different trajectories. While carbonic anhydrase 3, microtubule associated protein 4 and collagen type I alpha 1 chain decline rather constantly over time, myosin light chain 3, electron transfer flavoprotein A, troponin T, malate dehydrogenase 2, lactate dehydrogenase B and nestin plateaus in early teens. Electron transfer flavoprotein A, correlates with the outcome of 6-minutes-walking-test whereas malate dehydrogenase 2 together with myosin light chain 3, carbonic anhydrase 3 and nestin correlate with respiratory capacity. Conclusions: Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring.
|
|
| 45. |
- Tarvainen, Ilari, et al.
(författare)
-
Identification of phthalate mixture exposure targets in the human and mouse ovary in vitro
- 2023
-
Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 119
-
Tidskriftsartikel (refereegranskat)abstract
- Chemical health risk assessment is based on single chemicals, but humans and wildlife are exposed to extensive mixtures of industrial substances and pharmaceuticals. Such exposures are life-long and correlate with multiple morbidities, including infertility. How combinatorial effects of chemicals should be handled in hazard charac-terization and risk assessment are open questions. Further, test systems are missing for several relevant health outcomes including reproductive health and fertility in women. Here, our aim was to screen multiple ovarian cell models for phthalate induced effects to identify biomarkers of exposure. We used an epidemiological cohort study to define different phthalate mixtures for in vitro testing. The mixtures were then tested in five cell models representing ovarian granulosa or stromal cells, namely COV434, KGN, primary human granulosa cells, primary mouse granulosa cells, and primary human ovarian stromal cells. Exposures at epidemiologically relevant levels did not markedly elicit cytotoxicity or affect steroidogenesis in short 24-hour exposure. However, significant effects on gene expression were identified by RNA-sequencing. Altogether, the exposures changed the expression of 124 genes on the average (9-479 genes per exposure) in human cell models, without obvious concentration or mixture-dependent effects on gene numbers. The mixtures stimulated distinct changes in different cell models. Despite differences, our analyses suggest commonalities in responses towards phthalates, which forms a starting point for follow-up studies on identification and validation of candidate biomarkers that could be developed to novel assays for regulatory testing or even into clinical tests.
|
|
| 46. |
- Wijn, Stan R.W., et al.
(författare)
-
Arthroscopic meniscectomy versus non-surgical or sham treatment in patients with MRI confirmed degenerative meniscus lesions : A protocol for an individual participant data meta-analysis
- 2020
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:3
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Arthroscopic partial meniscectomy (APM) after degenerative meniscus tears is one of the most frequently performed surgeries in orthopaedics. Although several randomised controlled trials (RCTs) have been published that showed no clear benefit compared with sham treatment or non-surgical treatment, the incidence of APM remains high. The common perception by most orthopaedic surgeons is that there are subgroups of patients that do need APM to improve, and they argue that each study sample of the existing trials is not representative for the day-to-day patients in the clinic. Therefore, the objective of this individual participant data meta-analysis (IPDMA) is to assess whether there are subgroups of patients with degenerative meniscus lesions who benefit from APM in comparison with non-surgical or sham treatment. Methods and analysis: An existing systematic review will be updated to identify all RCTs worldwide that evaluated APM compared with sham treatment or non-surgical treatment in patients with knee symptoms and degenerative meniscus tears. Time and effort will be spent in contacting principal investigators of the original trials and encourage them to collaborate in this project by sharing their trial data. All individual participant data will be validated for missing data, internal data consistency, randomisation integrity and censoring patterns. After validation, all datasets will be combined and analysed using a one-staged and two-staged approach. The RCTs' characteristics will be used for the assessment of clinical homogeneity and generalisability of the findings. The most important outcome will be the difference between APM and control groups in knee pain, function and quality of life 2 years after the intervention. Other outcomes of interest will include the difference in adverse events and mental health. Ethics and dissemination: All trial data will be anonymised before it is shared with the authors. The data will be encrypted and stored on a secure server located in the Netherlands. No major ethical concerns remain. This IPDMA will provide the evidence base to update and tailor diagnostic and treatment protocols as well as (international) guidelines for patients for whom orthopaedic surgeons consider APM. The results will be submitted for publication in a peer-reviewed journal.
|
|
| 47. |
- Wijn, S. R.W., et al.
(författare)
-
Arthroscopic partial meniscectomy vs non-surgical or sham treatment in patients with MRI-confirmed degenerative meniscus tears : a systematic review and meta-analysis with individual participant data from 605 randomised patients
- 2023
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 31:5, s. 557-566
-
Forskningsöversikt (refereegranskat)abstract
- Objective: To identify subgroups of patients with magnetic resonance imaging (MRI)-confirmed degenerative meniscus tears who may benefit from arthroscopic partial meniscectomy (APM) in comparison with non-surgical or sham treatment. Methods: Individual participant data (IPD) from four RCTs were pooled (605 patients, mean age: 55 (SD: 7.5), 52.4% female) as to investigate the effectiveness of APM in patients with MRI-confirmed degenerative meniscus tears compared to non-surgical or sham treatment. Primary outcomes were knee pain, overall knee function, and health-related quality of life, at 24 months follow-up (0–100). The IPD were analysed in a one- and two-stage meta-analyses. Identification of potential subgroups was performed by testing interaction effects of predefined patient characteristics (e.g., age, gender, mechanical symptoms) and APM for each outcome. Additionally, generalized linear mixed-model trees were used for subgroup detection. Results: The APM group showed a small improvement over the non-surgical or sham group on knee pain at 24 months follow-up (2.5 points (95% CI: 0.8–4.2) and 2.2 points (95% CI: 0.9–3.6), one- and two-stage analysis, respectively). Overall knee function and health-related quality of life did not differ between the two groups. Across all outcomes, no relevant subgroup of patients who benefitted from APM was detected. The generalized linear mixed-model trees did also not identify a subgroup. Conclusions: No relevant subgroup of patients was identified that benefitted from APM compared to non-surgical or sham treatment. Since we were not able to identify any subgroup that benefitted from APM, we recommend a restrained policy regarding meniscectomy in patients with degenerative meniscus tears.
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
- Baumbach, Linda, et al.
(författare)
-
Association between received treatment elements and satisfaction with care for patients with knee osteoarthritis seen in general practice in Denmark
- 2021
-
Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis. - 0281-3432 .- 1502-7724. ; 39:2, s. 257-264
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: While education, exercise, and weight reduction when indicated, are recommended first-line treatments for knee osteoarthritis patients, they remain poorly implemented in favour of pain killer treatment, imaging and referral to surgery. A reason could be that patients are more satisfied with receiving these adjunctive treatment elements. This study aimed to investigate the associations between the received elements of care and the patient's satisfaction with the care for knee osteoarthritis in general practice.Design: Cross-sectional study.Setting: A Danish general practice.Subjects: All consecutive patients >= 30 years of age who consulted the general practitioner (GP) with chronic knee complaints during 18 months and who replied to a mailed questionnaire (n = 136).Main outcome measures: The questionnaire addressed patient's knee-related quality of life, and overall satisfaction with care, as well as reception of seven types of information, which are known quality indicators. Information on reception of adjunctive treatment elements was obtained from electronic medical records.Results: Patient satisfaction (versus neutrality/dissatisfaction) was positively associated with reception of information on: physical activity and exercise (relative risks [RR] 1.38, 95% bootstrap percentile interval [BPI] 1.02-4.33), and the relationship between weight and osteoarthritis (1.38, 1.01-4.41). No significant associations were found for the five remaining types of information and all the adjunctive treatment elements.Conclusion: Providing information as education to patients with knee osteoarthritis as part of the treatment is positively associated with satisfaction with care.
|
|
