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Machine learning-driven Heckmatt grading in facioscapulohumeral muscular dystrophy: A novel pathway for musculoskeletal ultrasound analysis
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317561.pdf (Publisher’s version ) (Open Access)9 p
Mindfulness-based cognitive therapy for depressive symptoms: Who benefits most and how does it work?
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317648.pdf (Publisher’s version ) (Open Access)Mindfulness-Based Cognitive Therapy (MBCT) is een bewezen effectieve behandeling voor depressie, maar niet iedereen profiteert evenveel. In dit proefschrift werd onderzocht hoe en voor wie MBCT het beste werkt. Hierdoor kunnen we in de toekomst beter de juiste patiënten toewijzen aan de therapie, en deze mogelijk ook verbeteren. Een van de belangrijkste bevindingen van dit proefschrift is dat patiënten met meer zich herhalende negatieve gedachten (piekeren) en minder zelfcompassie voorafgaand aan de behandeling meer vooruitgingen met MBCT. Dit suggereert dat screening op deze factoren kan helpen om de juiste patiënten toe te wijzen aan MBCT.
Bij patiënten met depressieve klachten i.h.k.v. bipolaire stoornis bleek MBCT effectief in het verminderen van negatieve gedachten en (hieraan gekoppelde) negatieve zelf-gerelateerde geheugen-vertekening, wat eerder onderzoek in depressie bevestigt. In patiënten met chronische of terugkerende depressie onderzochten we of veranderingen in mechanismen halverwege de behandeling het behandelresultaat konden verklaren. Dit konden we echter niet met zekerheid vaststellen, wat vervolgonderzoek vereist. We onderzochten ook hoe individuele verschillen in mindfulnessvaardigheden (mindfulnessprofielen) en verandering hierin de uitkomst van MBCT beïnvloedde. Verandering van mindfulnessprofiel ging samen met betere resultaten. Dit suggereert dat MBCT mogelijk effectiever kan worden door deze beter af te stemmen op het mindfulnessprofiel van de patiënt.Radboud University, 04 april 2025Promotores : Spijker, J., Speckens, A.E.M. Co-promotores : Cladder-Micus, M.B., Geurts, D.E.M.327 p
The luminous, slow-rising orphan afterglow AT2019pim as a candidate moderately relativistic outflow
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316489.pdf (Publisher’s version ) (Open Access
Gender differences in the response to antipsychotics or mood stabilizers in patients with acute mania: An individual patient data meta-analysis of placebo-controlled studies.
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315937.pdf (Publisher’s version ) (Open Access)Evidence suggests a worse clinical course in women compared to men with bipolar disorder. However, little research has explored gender differences in the efficacy of anti-manic medication. We sought to determine whether there are gender differences in efficacy of drug treatment in acute manic episodes of bipolar I disorder, and the influence of dichotomized age as a proxy for menopausal status and baseline severity on gender differences. We performed an individual patient data meta-analysis of 10 short term placebo controlled registration trials for treatment of acute mania (N = 2199) performed between 1996 and 2007 using the (Young) Mania Rating Scale ((Y)MRS)) as outcome. We observed a difference in effect size in mean change and responder status between men and women (NNT = 6.3 vs. 5.3), with a small but significant effect of gender on treatment response (β = 0.031). The effect size was larger in women older than 47 compared to women aged 47 and under (NNT = 4.2 vs. 7.5), and to a lesser extent, larger in men over 47 years compared those aged 47 and under (NNT = 3.8 vs. 6). Results were mainly driven by differences in response in the placebo group and independent of baseline severity. These findings suggest that men and premenopausal women might have a clinically modest advantage over their women and postmenopausal counterparts in treatment with anti-manic medication. Our results were limited by our sample not including antimanic agents registered after 2007 and by the absence of direct biological information regarding sex and menopausal state. Future research should aim to replicate current findings utilizing biological confirmation on the menopausal status and test whether findings are generalizable to newer antimanic agents.01 januari 202
Which variables are associated with recruitment failure? A nationwide review on obstetrical and gynaecological multicentre RCTs (2003-2023)
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318266.pdf (Publisher’s version ) (Open Access)OBJECTIVE: We aim to assess which variables are associated with recruitment failure of obstetrical and gynaecological randomised controlled trials (RCTs), leading to an extension of the study period. DESIGN: Nationwide study. SETTING: A cohort of RCTs supported by the trial centre of the Dutch Consortium of Obstetrics and Gynaecology. POPULATION: We included 83 RCTs that recruited patients between 1 March 2003 and 1 December 2023. MAIN OUTCOME MEASURES: Main outcome was recruitment target not achieved within 6 months after the preplanned recruitment period. Secondary outcomes were recruitment target not achieved within an extension period of at least 12 months and premature termination of the trial. In all RCTs, we collected information on variables with a potential effect on recruitment failure, recorded at five levels; patient, doctor, participating centre, study organisation and study design. RESULTS: In total, 46 of 83 RCTs (55%) did not achieve their targeted recruitment within the preplanned study period with a maximal extension period of 6 months. The most relevant variables for recruitment failure in multivariable risk prediction modelling were presence of a no-treatment arm (where treatment is standard clinical practice), a compensation fee of less than €200 per included patient, funding of less than €350 000, while a preceding pilot study lowered this risk. CONCLUSIONS: We identified that the presence of a no-treatment arm, low funding and a low compensation fee per included patient were the most relevant risk factors for recruitment failure within the preplanned period, while a preceding pilot study lowered this risk. Awareness of these variables is important when designing future studies
Graded Hecke algebras, constructible sheaves and the p-adic Kazhdan-Lusztig conjecture
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316427.pdf (Publisher’s version ) (Open Access
Press-Fit Bone-Anchored Prosthesis for Patients with Short Transfemoral Amputation.
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317424.pdf (Publisher’s version ) (Open Access)BACKGROUND: This video article describes the use of a bone-anchored prosthesis in patients with high above-the-knee amputations resulting in short residual limbs, most typically from trauma, cancer, infections, or dysvascular disease. The use of a socket prosthesis is usually unsuccessful in patients with a high transfemoral amputation because such prostheses have an unstable connection and often require additional waist belts for better attachment to the short residual limb. In most cases, a bone-anchored prosthesis results in substantial improvements in wear time, mobility, and quality of life in these patients. These patients may also be excellent candidates for early osseointegration implant surgery, given the knowledge that socket prostheses are rarely successful. DESCRIPTION: This procedure is preferably performed in a single stage. After the surgical procedure, most patients stay 1 or 2 nights in the hospital, depending on the magnitude of the surgery (e.g., bilateral implantation of an osseointegration implant) and their comorbidities. Procedure steps include (1) preoperative implant planning, (2) patient positioning and setup, (3) soft-tissue correction (optional) and exposure of residual bone, (4) revision osteotomy with guided shortening, (5) preparation of the medullary canal and perpendicular cutoff plane, (6) marking of the lag screw with a custom-made aiming device and dummy prosthesis, (7) insertion of the intramedullary component with optional bone augmentation, (8) insertion of the lag screw, (9) soft-tissue contouring and closure, and (10) stoma creation and dual cone assembly. ALTERNATIVES: Simultaneous major leg amputation and implantation of an osseointegration prosthesis is not advocated as treatment. First, a rehabilitation program with a socket-suspended prosthesis should be trialed before a patient can apply for a bone-anchored prosthesis. After rehabilitation, satisfaction with a socket prosthesis may be adequate, making a bone-anchored prosthesis unnecessary; however, patients with very short residual limbs and/or irregular soft-tissue conditions may be candidates for early implantation of a bone-anchored prosthesis. Contraindications for osseointegration implant surgery are severe diabetes (with complications), severe bone deformity, immature bone, bone diseases (chronic infection or metastasis), current chemotherapy, severe vascular diseases, pain without a clear cause, body mass index of >30 kg/m(2), and smoking. RATIONALE: About half of patients with a major lower-limb amputation who use an artificial leg are able to function acceptably well with use of a socket-suspended prosthesis; however, in cases with a high transfemoral amputation level, severe limitations may be expected, resulting in reduced prosthesis use, mobility, and quality of life. In these cases, energy transfer from limb to prosthesis is poor because of the so-called pseudojoint, which is the soft-tissue interface, and gross mechanical malalignment is common. These issues lead to complications related to skin irritation and poor socket fit, resulting in decreased overall satisfaction and confidence in mobility. An osseointegration implant creates a direct skeletal connection between the residual limb and artificial leg, in which energy transfer is optimal and mechanical alignment is radically improved. EXPECTED OUTCOMES: We performed a prospective study with a 1-year follow-up(1). A total of 16 patients with a short residual limb following transfemoral amputation received a gamma-type osseointegration implant with additional lag screw fixation toward the femoral neck. Most patients were male, had a traumatic amputation, and underwent a 2-stage surgery. Prosthesis wear time and patient health-related quality of life were measured with use of the Questionnaire for Persons with a Transfemoral Amputation (QTFA) prosthetic use score and global score, respectively. Both measures improved significantly from baseline to 1-year follow-up. The global score is not applicable for patients who do not use a prosthesis. For the 8 patients (i.e., 50% of the cohort) who did not use a prosthesis at baseline, the third question of the global score (G3 Q3) was utilized instead. This question asks, "How would you summarize your overall situation as an amputee?" As measured with this question, these patients also showed a substantial improvement in quality of life from baseline to 1-year follow-up. Adverse events that can occur following this surgical procedure include infection of the soft tissues and/or bone, periprosthetic fracture, implant breakage, aseptic loosening, and redundancy of soft tissues. In our study, only soft-tissue infections occurred. All superficial soft-tissue infections were successfully treated with use of oral antibiotics. One patient with a deep soft-tissue infection required surgery for abscess drainage. One patient required additional surgery to correct redundancy of soft tissues. Dual-cone adaptor breakage occurred twice; both cases were successfully treated in an outpatient clinic setting. We concluded that the short-term results of this treatment were acceptable. Mid-term follow-up results are currently being collected. IMPORTANT TIPS: Preoperative implant planning should be guided by surgical instructions with a custom-made implant design, with the aim of performing the procedure in a single stage.The use of a traction table may be beneficialLiberally resect soft-tissue redundancy.Utilize water-cooled power sawing.Utilize fluoroscopy to guide drilling.The use of radiographic markers can help guide exact lag screw positioning.In case of little resistance during insertion of the intramedullary component, utilize bone morphogenetic protein-2 (BMP-2; Inductos), bone struts, and/or bone-impaction graftingUtilize a lag screw to increase stabilityDo not close muscle fascia over the implant.Perform a 2-stage procedure only in cases with bone reconstructions, with the stages undertaken at a 10 to 12-week interval.Perform regular postoperative assessment according to your institutional follow-up schedule. ACRONYMS AND ABBREVIATIONS: BAP = bone-anchored prosthesisOI = osseointegration implantOFI-Y = custom-made press-fit titanium bone-anchored femur implant (BADAL X; OTN Implants)FL = femur lengthOFI-C = standard press-fit titanium bone-anchored implant (BADAL-X; OTN Implants)CT = computed tomographyDCA = dual-cone adapterK-wire = Kirschner wire
The Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!
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314974.pdf (Publisher’s version ) (Open Access)Inborn errors of metabolism (IEMs) are rare genetic conditions with significant morbidity and mortality. Technological advances have increased therapeutic options, making it challenging to remain up to date. A centralized therapy knowledgebase is needed for early diagnosis and targeted treatment. This study aimed to identify all treatable IEMs through a scoping literature review, followed by data extraction and analysis according to the Treatabolome principles. Knowledge of treatable IEMs, therapeutic categories, efficacy, and evidence was integrated into the Inborn Errors of Metabolism Knowledgebase (IEMbase), an online database encompassing all IEMs. The study identified 275 treatable IEMs, 18% of all currently known 1564 IEMs, according to the International Classification of Inherited Metabolic Disorders. Disorders of fatty acid and ketone body metabolism had the highest treatability (67%), followed by disorders of vitamin and cofactor metabolism (60%), and disorders of lipoprotein metabolism (42%). The most common treatment strategies were pharmacological therapy (34%), nutritional therapy (34%), and vitamin and trace element supplementation (12%). Treatment effects were most commonly observed in nervous system abnormalities (34%), metabolism/homeostasis abnormalities (33%), and growth (7%). Predominant evidence sources included case reports with evidence levels 4 (48%) and 5 (12%), and individual cohort studies with evidence level 2b (12%). Our study generated the Metabolic Treatabolome 2024. IEMs are the largest group of monogenic disorders amenable to disease-modifying therapy. With drug repurposing efforts and advancements in gene therapies, this number will expand. IEMbase now provides up-to-date, comprehensive information on clinical and biochemical symptoms and therapeutic options, empowering patients, families, healthcare professionals, and researchers in improving patient outcomes.01 januari 202
Symmetric deformable registration of multimodal brain magnetic resonance images via appearance residuals.
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317498.pdf (Publisher’s version ) (Closed access)BACKGROUND AND OBJECTIVE: Deformable registration of multimodal brain magnetic resonance images presents significant challenges, primarily due to substantial structural variations between subjects and pronounced differences in appearance across imaging modalities. METHODS: Here, we propose to symmetrically register images from two modalities based on appearance residuals from one modality to another. Computed with simple subtraction between modalities, the appearance residuals enhance structural details and form a common representation for simplifying multimodal deformable registration. The proposed framework consists of three serially connected modules: (i) an appearance residual module, which learns intensity residual maps between modalities with a cycle-consistent loss; (ii) a deformable registration module, which predicts deformations across subjects based on appearance residuals; and (iii) a deblurring module, which enhances the warped images to match the sharpness of the original images. RESULTS: The proposed method, evaluated on two public datasets (HCP and LEMON), achieves the highest registration accuracy with topology preservation when compared with state-of-the-art methods. CONCLUSIONS: Our residual space-guided registration framework, combined with GAN-based image enhancement, provides an effective solution to the challenges of multimodal deformable registration. By mitigating intensity distribution discrepancies and improving image quality, this approach improves registration accuracy and strengthens its potential for clinical application.01 april 202