| 1. |
- Lundstedt, Staffan, et al.
(författare)
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First intercomparison study on the analysis of oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) and nitrogen heterocyclic polycyclic aromatic compounds (N-PACs) in contaminated soil
- 2014
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 57, s. 83-92
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Forskningsöversikt (refereegranskat)abstract
- Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) and nitrogen heterocyclic polycyclic aromatic compounds (N-PACs) are toxic, highly leachable and often abundant at sites that are also contaminated with PAHs. However, due to lack of regulations and standardized methods for their analysis, they are seldom included in monitoring and risk-assessment programs. This intercomparison study constitutes an important step in the harmonization of the analytical methods currently used, and may also be considered a first step towards the certification of reference materials for these compounds. The results showed that the participants were able to determine oxy-PAHs with accuracy similar to PAHs, with average determined mass fractions agreeing well with the known levels in a spiked soil and acceptable inter- and intra-laboratory precisions for all soils analyzed. For the N-PACs, the results were less satisfactory, and have to be improved by using analytical methods more specifically optimized for these compounds.
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| 2. |
- Gialluisi, A, et al.
(författare)
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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 77-
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Tidskriftsartikel (refereegranskat)abstract
- Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562–3468). We observed a genome-wide significant effect (p < 1 × 10−8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 × 10−9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 × 10−8). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 × 10−8) and with all the cognitive traits tested (p = 3.07 × 10−8), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p ~ [10−5–10−7]) and negatively associated with ADHD PRS (p ~ [10−8−10−17]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.
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| 3. |
- Gialluisi, A, et al.
(författare)
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Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:7, s. 3004-3017
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Tidskriftsartikel (refereegranskat)abstract
- Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10−6) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (atpT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63];p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45];p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 × 10−4), educational attainment (0.86[0.82; 0.91];p = 2 × 10−7), and intelligence (0.72[0.68; 0.76];p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
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| 4. |
- Kamstrup, P, et al.
(författare)
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Biomarkers of Clot Activation and Degradation and Risk of Future Major Cardiovascular Events in Acute Exacerbation of COPD: A Cohort Sub-Study in a Randomized Trial Population
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65–1.48), VWF-N: HR 1.56 (95% CI 1.07–2.27), and VWF-A: HR 0.78 (95% CI 0.52–1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population.
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| 7. |
- Drude, Natascha Ingrid, et al.
(författare)
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Planning preclinical confirmatory multicenter trials to strengthen translation from basic to clinical research : a multi-stakeholder workshop report
- 2022
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Ingår i: Translational Medicine Communications. - : Springer Nature. - 2396-832X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Clinical translation from bench to bedside often remains challenging even despite promising preclinical evidence. Among many drivers like biological complexity or poorly understood disease pathology, preclinical evidence often lacks desired robustness. Reasons include low sample sizes, selective reporting, publication bias, and consequently inflated effect sizes. In this context, there is growing consensus that confirmatory multicenter studies -by weeding out false positives- represent an important step in strengthening and generating preclinical evidence before moving on to clinical research. However, there is little guidance on what such a preclinical confirmatory study entails and when it should be conducted in the research trajectory. To close this gap, we organized a workshop to bring together statisticians, clinicians, preclinical scientists, and meta-researcher to discuss and develop recommendations that are solution-oriented and feasible for practitioners. Herein, we summarize and review current approaches and outline strategies that provide decision-critical guidance on when to start and subsequently how to plan a confirmatory study. We define a set of minimum criteria and strategies to strengthen validity before engaging in a confirmatory preclinical trial, including sample size considerations that take the inherent uncertainty of initial (exploratory) studies into account. Beyond this specific guidance, we highlight knowledge gaps that require further research and discuss the role of confirmatory studies in translational biomedical research. In conclusion, this workshop report highlights the need for close interaction and open and honest debate between statisticians, preclinical scientists, meta-researchers (that conduct research on research), and clinicians already at an early stage of a given preclinical research trajectory.
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| 14. |
- Schriever, T, et al.
(författare)
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Residual flexion deformity after scaphoid nonunion surgery: 7-year follow-up study
- 2023
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Ingår i: The Journal of hand surgery, European volume. - : SAGE Publications. - 2043-6289. ; 48:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- The clinical implication of a residual flexion deformity following surgery for scaphoid nonunion is unclear. Sixty-three patients who underwent scaphoid nonunion surgery were assessed after a mean of 7 years (range 5–10) to analyse the outcomes based on the presence of residual scaphoid deformity. Primary outcome was Disabilities of the Arm, Shoulder and Hand score. Secondary outcomes were Patient-Rated Wrist Evaluation score, wrist range of motion and strength. Patients were dichotomized to residual deformity or no deformity. Scaphoid deformity was calculated from CT scans based on the median difference between the height–length ratio of the operated versus the uninjured scaphoid. There were no differences between residual deformity ( n = 33) and no deformity ( n = 30) in any outcome variables, except for wrist extension which was slightly worse in the deformity group. The deformity group had a greater number of radiographic osteoarthritis, but all cases were mild, and osteoarthritis did not correlate to a worse outcome. We conclude that residual scaphoid deformity has no relevant negative impact on mid-term wrist function. Level of evidence: IV
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| 15. |
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| 16. |
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| 17. |
- Soliveres, Santiago, et al.
(författare)
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Biodiversity at multiple trophic levels is needed for ecosystem multifunctionality
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7617, s. 456-459
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Tidskriftsartikel (refereegranskat)abstract
- Many experiments have shown that loss of biodiversity reduces the capacity of ecosystems to provide the multiple services on which humans depend. However, experiments necessarily simplify the complexity of natural ecosystems and will normally control for other important drivers of ecosystem functioning, such as the environment or land use. In addition, existing studies typically focus on the diversity of single trophic groups, neglecting the fact that biodiversity loss occurs across many taxa and that the functional effects of any trophic group may depend on the abundance and diversity of others. Here we report analysis of the relationships between the species richness and abundance of nine trophic groups, including 4,600 above- and below-ground taxa, and 14 ecosystem services and functions and with their simultaneous provision (or multifunctionality) in 150 grasslands. We show that high species richness in multiple trophic groups (multitrophic richness) had stronger positive effects on ecosystem services than richness in any individual trophic group; this includes plant species richness, the most widely used measure of biodiversity. On average, three trophic groups influenced each ecosystem service, with each trophic group influencing at least one service. Multitrophic richness was particularly beneficial for 'regulating' and 'cultural' services, and for multifunctionality, whereas a change in the total abundance of species or biomass in multiple trophic groups (the multitrophic abundance) positively affected supporting services. Multitrophic richness and abundance drove ecosystem functioning as strongly as abiotic conditions and land-use intensity, extending previous experimental results to real-world ecosystems. Primary producers, herbivorous insects and microbial decomposers seem to be particularly important drivers of ecosystem functioning, as shown by the strong and frequent positive associations of their richness or abundance with multiple ecosystem services. Our results show that multitrophic richness and abundance support ecosystem functioning, and demonstrate that a focus on single groups has led to researchers to greatly underestimate the functional importance of biodiversity.
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| 18. |
- Soliveres, Santiago, et al.
(författare)
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Locally rare species influence grassland ecosystem multifunctionality
- 2016
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Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 371:1694
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Tidskriftsartikel (refereegranskat)abstract
- Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above-and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities.
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| 19. |
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| 20. |
- Sward, E, et al.
(författare)
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Effects of intra-articular Platelet-Rich Plasma (PRP) injections on osteoarthritis in the thumb basal joint and scaphoidtrapeziotrapezoidal joint
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:3, s. e0264203-
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Tidskriftsartikel (refereegranskat)abstract
- Intra-articular injection of platelet rich plasma (PRP) has been reported to decrease pain and improve function in knee osteoarthritis. There are few reports on the effect of PRP in the treatment of osteoarthritis in the hand. Our aim was to evaluate the effect of PRP-injections on pain and functional outcome in the short-term for osteoarthritis in the thumb basal joint and scaphoidtrapeziotrapezoidal (STT) joint. A retrospective analysis was performed of 29 patients treated with intra-articular PRP injection for painful osteoarthritis in the thumb basal joint (21 patients) or STT joint (eight patients). The patients received two consecutive, radiologically guided PRP injections at an interval of 3–4 weeks. Pain at rest and on load (numerical rating scale (NRS) 0–10), Patient-rated Wrist and Hand Evaluation (PRWHE) score (0–100), grip strength (Jamar) and key pinch were recorded pre-injection and 3 months after the second injection. Mean age was 63 (range 34–86) years and 17 patients were women. We used generalized estimating equations (GEE) to analyze the effect on the outcome variables. Possible predictors were included in the model (high pain level pre-injection, gender, age, manually demanding work, affected joint (thumb base or STT) and use of analgesic). The GEE analysis showed that PRP injections had no effect on reported pain, PRWHE score, grip strength or key pinch. 16/28 patients experience a positive effect according to a yes/no question. The short-term effect of PRP for osteoarthritis in the thumb base and STT-joint is doubtful and needs to be properly investigated in placebo-controlled studies.
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| 21. |
- Sward, EM, et al.
(författare)
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The impact of psychological factors on outcome after salvage surgery for wrist osteoarthritis
- 2022
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Ingår i: The Journal of hand surgery, European volume. - : SAGE Publications. - 2043-6289. ; 47:8, s. 805-811
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Tidskriftsartikel (refereegranskat)abstract
- This prospective longitudinal study of 80 patients analysed the effect of preoperative pain catastrophizing, anxiety, depression and sense of coherence on the Disabilities of the Arm, Shoulder and Hand, Patient-Rated Wrist Evaluation, quality of life, grip strength and range of motion during the first year after salvage surgery for wrist osteoarthritis. Generalized estimating equations were used to analyse the effect of the psychological factors on the outcome variables. Pain catastrophizing or a tendency for anxiety preoperatively had a strong negative impact on postoperative Disabilities of the Arm, Shoulder and Hand and Patient-Rated Wrist Evaluation. Anxiety also predicted a lower postoperative quality of life, whereas pain catastrophizing had a negative impact on grip strength. Sense of coherence did not influence the outcome. Level of evidence: II
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| 22. |
- Swärd, Elin M., et al.
(författare)
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The epidemiology of scaphoid fractures in Sweden : a nationwide registry study
- 2019
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Ingår i: Journal of Hand Surgery: European Volume. - : SAGE Publications. - 1753-1934 .- 2043-6289. ; 44:7, s. 697-701
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Tidskriftsartikel (refereegranskat)abstract
- The epidemiology of scaphoid fractures has been described in limited populations, and incidence reports have been inconsistent. We investigated the nationwide incidence of scaphoid fractures by evaluating data on 34,377 patients in the Swedish National Patient Register for the years 2006–2015 regarding diagnosis, age, sex and treatment. The data were validated in 300 random patients, and incidence rates were adjusted accordingly. Forty-one per cent of the initially diagnosed fractures were false positives. The adjusted true fracture incidence rate was 22 per 100,000 person-years. During the decade studied incidence rates decreased in younger men and increased in middle-aged women. The incidence of surgical treatment vs. non-operative treatment did not change over time. Men were treated surgically more often than women (6% vs. 3%) and had a greater risk for nonunion (3% vs. 1%).
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| 23. |
- Swärd, E, et al.
(författare)
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Structural Changes in the Posterior Interosseous Nerve from Patients with Wrist Osteoarthritis and Asymptomatic Controls
- 2020
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Ingår i: Journal of wrist surgery. - : Georg Thieme Verlag KG. - 2163-3916 .- 2163-3924. ; 9:6, s. 481-486
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Tidskriftsartikel (refereegranskat)abstract
- Background Posttraumatic morphological changes have been described in the posterior interosseous nerve (PIN) after mild wrist trauma, and it has been suggested that posttraumatic nerve changes may contribute to wrist pain. PIN excision has shown to relieve pain in some patients with wrist osteoarthritis. However, is not known if PINs from osteoarthritic wrist have pathological features.Objective The aim of this study was to investigate whether PINs from osteoarthritic wrists show morphological changes that are not present in healthy wrists.Materials and Methods PINs resected from 15 osteoarthritic wrists were analyzed with light microscopy regarding morphological changes and compared with five asymptomatic controls without osteoarthritis.Results No significant differences in fascicular area, myelinated fiber density or myelinated fiber diameter were found. However, most patients and controls exhibited some degree of pathology, and a few samples from both groups exhibited severe pathological changes.Conclusions Our findings of morphological changes in both patients with osteoarthritis and asymptomatic controls suggest that pathological changes of unknown significance might exist in the general population in the PIN at wrist level. We believe that the observed structural nerve changes in the PIN are unlikely to contribute to the symptoms of pain. Further studies of the normal histological appearance of the terminal PIN are needed.Level of Evidence This is Level II study.
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| 26. |
- Wilcke, MK, et al.
(författare)
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Trapeziectomy with or without a tendon-based adjunct: a registry-based study of 650 thumbs
- 2022
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Ingår i: The Journal of hand surgery, European volume. - : SAGE Publications. - 2043-6289. ; 47:7, s. 728-733
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to assess the outcomes after simple trapeziectomy and trapeziectomy with ligament reconstruction and/or tendon interposition based on data in the Swedish national healthcare quality registry for hand surgery (HAKIR). Six-hundred and fifty thumbs were included, and 265 were assessed up to 12 months after operation. There was significant and clinically relevant improvement in patient-reported measures (pain on load, pain on motion without load, pain at rest, stiffness, weakness, and ability to perform activities of daily living and the Quick Disabilities of the Arm, Shoulder and Hand score) and objective measures (strength and thumb mobility) at 3 and 12 months for all procedures. The use of the abductor pollicis longus tendon had better improvement in some respects compared with the use of flexor carpi radialis or extensor carpi radialis tendons. However, overall, the use of a tendon adjuncts yielded no better outcomes than simple trapeziectomy. Level of evidence: III
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| 27. |
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