Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 541
Filtrar
1.
Eur Respir J ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38548291

RESUMEN

RATIONALE: Differences in the pharyngeal site-of-collapse influences efficacy of non-CPAP therapies for obstructive sleep apnoea (OSA). Notably, complete concentric collapse at the palate (CCCp) during drug-induced sleep endoscopy (DISE) is associated with reduced efficacy of hypoglossal nerve stimulation, but CCCp is currently not recognisable using polysomnography. Here we develop a means to estimate DISE-based site-of-collapse using overnight polysomnography. METHODS: 182 OSA patients provided DISE and polysomnography data. Six polysomnographic flow-shape characteristics (mean during hypopnoeas) were identified as candidate predictors of CCCp (primary outcome variable, N=44/182), including inspiratory skewness and inspiratory scoopiness. Multivariable logistic regression combined the six characteristics to predict clear presence (N=22) versus absence (N=128) of CCCp (partial collapse and concurrent tongue-base collapse excluded). Odds ratios for actual CCCp between predicted subgroups were quantified after cross-validation. Secondary analyses examined complete lateral wall, tongue-base, or epiglottis collapse. External validation was performed on a separate dataset (Ntotal=466). RESULTS: CCCp was characterised by greater scoopiness (ß=1.5±0.6 per 2SD, multivariable estimate±se) and skewness (ß=11.4±2.4) compared to non-CCCp. Odds ratio [95%CI] for CCCp in predicted positive versus negative subgroups was 5.0[1.9-13.1]. The same characteristics provided significant cross-validated prediction of lateral wall (OR=6.3[2.4-16.5]), tongue-base (3.2[1.4-7.3]), and epiglottis (4.4[1.5-12.4]) collapse. CCCp and lateral wall collapse shared similar characteristics (skewed, scoopy), diametrically opposed to tongue-base and epiglottis collapse characteristics. External validation confirmed model prediction. CONCLUSIONS: The current study provides a means to recognise patients with likely CCCp or other DISE-based site-of-collapse categories using routine polysomnography. Since site-of-collapse influences therapeutic responses, polysomnographic airflow shape analysis could facilitate precision site-specific OSA interventions.

2.
Sleep Med ; 117: 95-98, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38518588

RESUMEN

INTRODUCTION: Custom-made titratable mandibular advancement device (MAD) treatment can nowadays be considered a promising first-line treatment in patients with mild to severe obstructive sleep apnea (OSA). Specific manufacturing designs and titration mechanisms of MAD are on the market, characterized by their titration approach, vertical opening, and materials selection. The wing-designed MAD (SomnoDent® Flex™, SomnoMed Ltd, Sydney, Australia) has a lateral screw mechanism to advance the lower jaw in incremental steps of 0.1 up to 6.0 mm. The newer uniquely designed custom-made MAD with passive mouth closing (SomnoDent® Avant™ SomnoMed Ltd, Sydney, Australia) has a frontal exchangeable advancement strap of fixed lengths as a specific titration mechanism, all supporting freedom of lateral movement. We aimed to assess the associations between the type of MAD prescribed and OSA treatment outcome. METHODS: Data from 209 patients (165 male, mean age 53.9 (±10.9) years, median baseline BMI and AHI 27.02 [24.8; 29.7] kg/m2 and 22.8 [17.7; 31.6]/hour sleep, respectively) were collected. Of this cohort, 91 patients with the traditional, wing-based SomnoDent® Flex™ and 118 patients with SomnoDent® Avant™. All patients were diagnosed with a type 1 polysomnography demonstrating moderate to severe OSA (15 ≤ AHI ≤65 per hour sleep). The selected MAD was fitted in the so-called maximal comfortable protrusion. After 3 months of subjective titration until resolution of subjective symptoms and/or achieving physical limits, a checkup with validated home sleep monitoring was conducted. Treatment success was defined as "AHI reduction ≥50% with MAD compared to baseline AHI and AHI with MAD <10 events per hour". RESULTS: These real-world data set showed that 67% of patients achieved treatment success, with a statistically significant reduction in AHI from 22.8 [17.7; 31.6] to 7.45 [3.4; 15.0]/h sleep. The SomnoDent® Avant™ achieved 75% treatment success versus 56% for the traditional, wing-based SomnoDent® Flex™ (P < 0.05). Overall, AHI reduction was 70% for SomnoDent® Avant™ (P < 0.05) vs. 63% for SomnoDent® Flex™ (P < 0.05). CONCLUSIONS: This study shows that choice of MAD design can impact the treatment outcome and could become an important consideration in selecting the type of MAD for personalized treatment for OSA patients. While the results of the traditional wing-based MAD design were comparable to the therapeutic outcome with other titratable, custom-made MADs, the MAD with the passive mouth closing feature showed significantly greater reduction in total AHI potentially due to encouraged nasal breathing, reduced mouth breathing and lesser vertical opening thereby decreasing the probability of tongue base collapse.


Asunto(s)
Avance Mandibular , Apnea Obstructiva del Sueño , Humanos , Masculino , Persona de Mediana Edad , Apnea Obstructiva del Sueño/terapia , Ferulas Oclusales , Resultado del Tratamiento , Sueño
3.
PLoS One ; 19(3): e0299990, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38451976

RESUMEN

OBJECTIVES: To evaluate secondary intention wound healing in the horse's limbs when treated with the synthetic epidermis spray (Novacika®, Cohesive S.A.S, France) or with a standard bandaging technique. METHODS: Six Standardbred mares were included in the study. Four 2.5 x 2.5 cm full-thickness skin wounds were created on each thoracic limb. Two wounds were located on the dorsoproximal aspect of the cannon bone and the other two at the dorsoproximal aspect of the fetlock. Six hours after creation, wounds were randomly treated with synthetic epidermis spray or standard bandaging. The wounds were assessed every 4 days by gross visual assessment and using a 3D imaging camera. Analysis was performed with a 3D imaging application. RESULTS: Out of 46 wounds, 22 showed exuberant granulation tissue and were part of the standard bandaging group. Whether the wounds were treated with synthetic epidermis spray or standard bandaging, the time for healing was the same. CONCLUSION: The synthetic epidermis spray studied in this model has allowed healing without the production of exuberant granulation tissue but did not reduce the median wound healing time compared to a standard bandaging technique. The synthetic epidermis spray is potentially an interesting alternative for the management of secondary intention wound healing of superficial and non-infected distal limb wounds in adult horses on economical and practical aspects. However, all statistical inference (p-values especially) must be interpreted with caution, given the size of the sample.


Asunto(s)
Intención , Enfermedades de la Piel , Animales , Femenino , Epidermis , Miembro Anterior , Caballos , Cicatrización de Heridas
4.
Int J Parasitol ; 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38492780

RESUMEN

Lactate dehydrogenase (LDH) from Schistosoma mansoni has peculiar properties for a eukaryotic LDH. Schistosomal LDH (SmLDH) isolated from schistosomes, and the recombinantly expressed protein, are strongly inhibited by ATP, which is neutralized by fructose-1,6-bisphosphate (FBP). In the conserved FBP/anion binding site we identified two residues in SmLDH (Val187 and Tyr190) that differ from the conserved residues in LDHs of other eukaryotes, but are identical to conserved residues in FBP-sensitive prokaryotic LDHs. Three-dimensional (3D) models were generated to compare the structure of SmLDH with other LDHs. These models indicated that residues Val187, and especially Tyr190, play a crucial role in the interaction of FBP with the anion pocket of SmLDH. These 3D models of SmLDH are also consistent with a competitive model of SmLDH inhibition in which ATP (inhibitor) and FBP (activator) compete for binding in a well-defined anion pocket. The model of bound ATP predicts a distortion of the nearby key catalytic residue His195, resulting in enzyme inhibition. To investigate a possible physiological role of this allosteric regulation of LDH in schistosomes we made a kinetic model in which the allosteric regulation of the glycolytic enzymes can be varied. The model showed that inhibition of LDH by ATP prevents fermentation to lactate in the free-living stages in water and ensures complete oxidation via the Krebs cycle of the endogenous glycogen reserves. This mechanism of allosteric inhibition by ATP prevents the untimely depletion of these glycogen reserves, the only fuel of the free-living cercariae. Neutralization by FBP of this ATP inhibition of LDH prevents accumulation of glycolytic intermediates when S. mansoni schistosomula are confronted with the sudden large increase in glucose availability upon penetration of the final host. It appears that the LDH of S. mansoni is special and well suited to deal with the variations in glucose availability the parasite encounters during its life cycle.

5.
Vet Sci ; 11(1)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38275923

RESUMEN

The temporary ligation of the common carotid artery is performed as an emergency aid in cases of guttural pouch mycosis. Its usefulness is put into perspective after an anatomical summary of arterial vascularization involving a guttural pouch. It helps to better understand the need for the cranial (cerebral) and caudal (cardiac) occlusion of an arterial rupture by embolization in order to achieve maximum success in preventing and treating an hemorrhage. Topical oxygen therapy used alone or in a multimodal approach with embolization surgery is performed to promote healing of the inflammatory and mycotic lesions observed when an individual is affected. In conclusion, this three-step therapeutic approach should enable the equine practitioner to better orient their decision tree when faced with this condition which, while rare, can be potentially fatal if poorly treated.

7.
Vet Surg ; 53(3): 468-476, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37650370

RESUMEN

OBJECTIVE: To report findings, outcome and determine variables associated with survival in horses with acquired inguinal hernia (AIH). STUDY DESIGN: Retrospective study. ANIMALS: A total of 98 cases in 97 horses. METHODS: The medical records (2005-2020) of horses diagnosed with AIH were reviewed. Retrieved data included signalment, history, clinical variables, surgical aspects, postoperative complications, and short- and long-term outcomes. Logistic regression analyses were used to determine factors associated with short-term survival (p < .05). RESULTS: Manual reduction was attempted in a third of the cases (32/98, 33%) and emergency surgery to reduce the hernia was performed in 64 of 98 (65%) cases. Concurrent small intestinal (SI) volvulus was identified in 26 (26/98, 27%) cases. Castration was the most common technique used to prevent recurrence (64/94, 68%). Overall AIH recurrence rate was 11% (11/98). A total of 59 (59/98, 60%) cases survived to hospital discharge and 49 of 52 (94%) cases were still alive after 12 months. Cases admitted within 10 h of colic signs had increased odds of survival (72%) compared to those admitted after 10 h (26%; p < .001). Draft breeds (p = .021), high heart rate on admission (p = .001) and concurrent SI volvulus (p = .048) were associated with reduced survival to hospital discharge. CONCLUSIONS: Horses with AIH had a higher risk of concurrent SI volvulus and lower survival than reported. Draft breeds, high heart rate on admission and concurrent SI volvulus were associated with reduced short-term survival. CLINICAL SIGNIFICANCE: The results of this study should help in prognostication for horses with AIH.


Asunto(s)
Cólico , Hernia Inguinal , Enfermedades de los Caballos , Vólvulo Intestinal , Animales , Caballos , Hernia Inguinal/veterinaria , Vólvulo Intestinal/veterinaria , Pronóstico , Estudios Retrospectivos , Intestino Delgado/cirugía , Complicaciones Posoperatorias/veterinaria , Enfermedades de los Caballos/cirugía , Cólico/veterinaria
8.
Eur Arch Otorhinolaryngol ; 281(5): 2281-2291, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38052757

RESUMEN

PURPOSE: Recent literature suggests that tinnitus can impact cognition, but results were varied due to a diversity in investigated aspects of cognition and utilized tests, as well as the possible influence of confounding factors. The purpose of this study was to assess the impact of tinnitus loudness on cognition by use of a within-subjects design in patients with a cochlear implant (CI). In this population, tinnitus loudness can be modulated by switching the CI on or off as CI is known to highly suppress tinnitus. METHODS: A total of 18 CI users completed two versions of the Repeatable Battery for Assessment of Neuropsychological Status for Hearing Impaired individuals (RBANS-H), once in unaided condition and once in best aided condition. Tinnitus suppression was defined as a difference in score on a visual-analogue scale (VAS) of at least one point out of ten between these two conditions. RESULTS: No significant differences in RBANS-H scores were found between the suppression and no suppression group, nor for the suppression group alone. No significant correlations between tinnitus loudness and RBANS-H were found, neither for the suppression group alone, nor for the group as a whole. CONCLUSION: The current study shows no significant effect of tinnitus loudness on cognition, which contradicts previous literature. This discrepancy could be explained by the use of a within-subjects design, which controls for confounding factors. Future research should include a larger and more diverse study sample to draw definitive conclusions on this topic.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Acúfeno , Humanos , Implantación Coclear/métodos , Acúfeno/cirugía , Cognición
9.
J Craniomaxillofac Surg ; 52(1): 85-92, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38129189

RESUMEN

The secondary alveolar bone grafting (SABG) step restores the continuity of the alveolar bone necessary for dentition. Faced with the complications of autografts, synthetic biomaterials such as Bioglass (BG) 45S5 have been proposed. The objective was to evaluate the success rate of SABG with the addition of BG 45S5 and to highlight the prognostic factors. Patients who underwent operation between 2015 and 2021 and had follow-up cone-beam computed tomography (CBCT) were analyzed. Multivariate analysis was performed to determine factors influencing radiographic success. A total of 102 SABG were analyzed. They were unilateral total cleft lip and palate (49, 48.0%). The mean age at surgery was 9.32 ± 3.09 years. Surgeries were performed mainly outside a syndromic context and without a family history after orthodontic preparation. The radiographic success rate at 1 year was 80.4%. Mixed dentition stage (odds ratio [OR] = 7.3, p = 0.024), absence of syndromic context (OR = 20.7, p = 0.024) and female sex (OR = 4.88, p = 0.021) were factors predictive of surgical success. The use of BG 45S5 instead of autograft is relevant for SABG, with a 1-year success rate of over 80%. The stage of mixed dentition, the absence of syndromic context, and female sex were factors for good prognosis.


Asunto(s)
Injerto de Hueso Alveolar , Cerámica , Labio Leporino , Fisura del Paladar , Vidrio , Humanos , Femenino , Niño , Labio Leporino/cirugía , Estudios Retrospectivos , Fisura del Paladar/cirugía , Injerto de Hueso Alveolar/métodos , Trasplante Óseo/métodos
10.
BMC Med Educ ; 23(1): 861, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37957668

RESUMEN

BACKGROUND: Peer-assisted learning (PAL) - where students take up a teaching role at an early stage of their training-is widely used in medical curricula. Many qualitative studies have investigated the perceptions and benefits of PAL, but no studies have longitudinally explored how peer teachers experienced their development. This could allow for a better understanding of PAL. In this study, we explored the perceived impact of being a peer teacher on the development of personal and professional competencies as a medical student. METHODS: We longitudinally conducted semi-structured interviews with peer teachers, during their 2-year teaching period in the skills lab at the University of Antwerp and applied descriptive thematic analysis. RESULTS: In total we gathered 47 interviews in 13 peer teachers (9 female, 4 male,. 1-7 interviews each). Peer teachers reported an increase in self-confidence, which gradually transformed into self-efficacy in clinical and teaching skills., Participants told us to be inspired by the previous generation of peer teachers. Their motivation shifted from personal benefits to benefiting others while becoming a role model themselves. The peer teachers illustrated how they developed maturity by integrating different CanMEDS roles. They grew in reflection, changed/transformed an initial mark-driven study drive into more patient-centered ambitions, and started developing a personal style. CONCLUSIONS: Our study suggests that being a peer teacher leads to more self-efficacy, in clinical and teaching skills, to become a role model with as motivation to benefit others and to grow towards a good doctor maturity. Although the task is to teach peers, this opportunity nurtures the practice and integration of various CanMEDS roles, not only that of scholar but also communicator, collaborator and leader, thereby positively influencing their personal and professional development and their identity as a doctor (professional role).


Asunto(s)
Educación de Pregrado en Medicina , Estudiantes de Medicina , Humanos , Masculino , Femenino , Curriculum , Grupo Paritario , Investigación Cualitativa , Enseñanza
11.
Front Neurol ; 14: 1278508, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38020642

RESUMEN

Introduction: In challenging listening situations, speech perception with a cochlear implant (CI) remains demanding and requires high levels of listening effort, which can lead to increased levels of listening-related fatigue. The body of literature on these topics increases as the number of CI users rises. This scoping review aims to provide an overview of the existing literature on listening effort, fatigue, and listening-related fatigue among CI users and the measurement techniques to evaluate them. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements were used to conduct the scoping review. The search was performed on PubMed, Scopus, and Web of Science to identify all relevant studies. Results: In total, 24 studies were included and suggests that CI users experience higher levels of listening effort when compared to normal hearing controls using scales, questionnaires and electroencephalogram measurements. However, executing dual-task paradigms did not reveal any difference in listening effort between both groups. Uncertainty exists regarding the difference in listening effort between unilateral, bilateral, and bimodal CI users with bilateral hearing loss due to ambiguous results. Only five studies were eligible for the research on fatigue and listening-related fatigue. Additionally, studies using objective measurement methods were lacking. Discussion: This scoping review highlights the necessity for additional research on these topics. Moreover, there is a need for guidelines on how listening effort, fatigue, and listening-related fatigue should be measured to allow for study results that are comparable and support optimal rehabilitation strategies.

12.
Biomolecules ; 13(11)2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-38002303

RESUMEN

Zebrafish are increasingly becoming an important model organism for studying the pathophysiological mechanisms of human diseases and investigating how these mechanisms can be effectively targeted using compounds that may open avenues to novel treatments for patients. The zebrafish skeleton has been particularly instrumental in modeling bone diseases as-contrary to other model organisms-the lower load on the skeleton of an aquatic animal enables mutants to survive to early adulthood. In this respect, the axial skeletons of zebrafish have been a good read-out for congenital spinal deformities such as scoliosis and degenerative disorders such as osteoporosis and osteoarthritis, in which aberrant mineralization in humans is reflected in the respective zebrafish models. Interestingly, there have been several reports of hereditary multisystemic diseases that do not affect the vertebral column in human patients, while the corresponding zebrafish models systematically show anomalies in mineralization and morphology of the spine as their leading or, in some cases, only phenotype. In this review, we describe such examples, highlighting the underlying mechanisms, the already-used or potential power of these models to help us understand and amend the mineralization process, and the outstanding questions on how and why this specific axial type of aberrant mineralization occurs in these disease models.


Asunto(s)
Investigación Farmacéutica , Escoliosis , Animales , Humanos , Adulto , Pez Cebra/genética , Columna Vertebral , Proteínas de Pez Cebra/genética
13.
PLoS One ; 18(10): e0293077, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37847703

RESUMEN

BACKGROUND: No distinctive clinical signs of Ebola virus disease (EVD) have prompted the development of rapid screening tools or called for a new approach to screening suspected Ebola cases. New screening approaches require evidence of clinical benefit and economic efficiency. As of now, no evidence or defined algorithm exists. OBJECTIVE: To evaluate, from a healthcare perspective, the efficiency of incorporating Ebola prediction scores and rapid diagnostic tests into the EVD screening algorithm during an outbreak. METHODS: We collected data on rapid diagnostic tests (RDTs) and prediction scores' accuracy measurements, e.g., sensitivity and specificity, and the cost of case management and RDT screening in EVD suspect cases. The overall cost of healthcare services (PPE, procedure time, and standard-of-care (SOC) costs) per suspected patient and diagnostic confirmation of EVD were calculated. We also collected the EVD prevalence among suspects from the literature. We created an analytical decision model to assess the efficiency of eight screening strategies: 1) Screening suspect cases with the WHO case definition for Ebola suspects, 2) Screening suspect cases with the ECPS at -3 points of cut-off, 3) Screening suspect cases with the ECPS as a joint test, 4) Screening suspect cases with the ECPS as a conditional test, 5) Screening suspect cases with the WHO case definition, then QuickNavi™-Ebola RDT, 6) Screening suspect cases with the ECPS at -3 points of cut-off and QuickNavi™-Ebola RDT, 7) Screening suspect cases with the ECPS as a conditional test and QuickNavi™-Ebola RDT, and 8) Screening suspect cases with the ECPS as a joint test and QuickNavi™-Ebola RDT. We performed a cost-effectiveness analysis to identify an algorithm that minimizes the cost per patient correctly classified. We performed a one-way and probabilistic sensitivity analysis to test the robustness of our findings. RESULTS: Our analysis found dual ECPS as a conditional test with the QuickNavi™-Ebola RDT algorithm to be the most cost-effective screening algorithm for EVD, with an effectiveness of 0.86. The cost-effectiveness ratio was 106.7 USD per patient correctly classified. The following algorithms, the ECPS as a conditional test with an effectiveness of 0.80 and an efficiency of 111.5 USD per patient correctly classified and the ECPS as a joint test with the QuickNavi™-Ebola RDT algorithm with an effectiveness of 0.81 and a cost-effectiveness ratio of 131.5 USD per patient correctly classified. These findings were sensitive to variations in the prevalence of EVD in suspected population and the sensitivity of the QuickNavi™-Ebola RDT. CONCLUSIONS: Findings from this study showed that prediction scores and RDT could improve Ebola screening. The use of the ECPS as a conditional test algorithm and the dual ECPS as a conditional test and then the QuickNavi™-Ebola RDT algorithm are the best screening choices because they are more efficient and lower the number of confirmation tests and overall care costs during an EBOV epidemic.


Asunto(s)
Fiebre Hemorrágica Ebola , Humanos , Fiebre Hemorrágica Ebola/diagnóstico , Fiebre Hemorrágica Ebola/epidemiología , Análisis Costo-Beneficio , Prueba de Diagnóstico Rápido , Sensibilidad y Especificidad , Algoritmos , Pruebas Diagnósticas de Rutina/métodos
14.
Biomedicines ; 11(10)2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37893046

RESUMEN

Previous studies revealed a link between inflammation and overactivation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling in syndromes associated with aging. Pseudoxanthoma elasticum (PXE), a rare autosomal-recessive disorder, arises from mutations in ATP-binding cassette subfamily C member 6 (ABCC6). On a molecular level, PXE shares similarities with Hutchinson-Gilford progeria syndrome, such as increased activity of senescence-associated- beta-galactosidase or high expression of inflammatory factors. Thus, this study's aim was the evaluation of activated STAT3 and the influence of JAK1/2-inhibitor baricitinib (BA) on inflammatory processes such as the complement system in PXE. Analysis of activation of STAT3 was performed by immunofluorescence and Western blot, while inflammatory processes and complement system factors were determined based on mRNA expression and protein level. Our results assume overactivation of JAK/STAT3 signaling, increased expression levels of several complement factors and high C3 protein concentration in the sera of PXE patients. Supplementation with BA reduces JAK/STAT3 activation and partly reduces inflammation as well as the gene expression of complement factors belonging to the C1 complex and C3 convertase in PXE fibroblasts. Our results indicate a link between JAK/STAT3 signaling and complement activation contributing to the proinflammatory phenotype in PXE fibroblasts.

16.
Lancet Neurol ; 22(10): 890-899, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37739572

RESUMEN

BACKGROUND: Drug repurposing could provide novel treatment options for Duchenne muscular dystrophy. Because tamoxifen-an oestrogen receptor regulator-reduced signs of muscular pathology in a Duchenne muscular dystrophy mouse model, we aimed to assess the safety and efficacy of tamoxifen in humans as an adjunct to corticosteroid therapy over a period of 48 weeks. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 12 study centres in seven European countries. We enrolled ambulant boys aged 6·5-12·0 years with a genetically confirmed diagnosis of Duchenne muscular dystrophy and who were on stable corticosteroid treatment for more than 6 months. Exclusion criteria included ophthalmological disorders, including cataracts, and haematological disorders. We randomly assigned (1:1) participants using an online randomisation tool to either 20 mg tamoxifen orally per day or matched placebo, stratified by centre and corticosteroid intake. Participants, caregivers, and clinical investigators were masked to treatment assignments. Tamoxifen was taken in addition to standard care with corticosteroids, and participants attended study visits for examinations every 12 weeks. The primary efficacy outcome was the change from baseline to week 48 in scores on the D1 domain of the Motor Function Measure in the intention-to-treat population (defined as all patients who fulfilled the inclusion criteria and began treatment). This study is registered with ClinicalTrials.gov (NCT03354039) and is completed. FINDINGS: Between May 24, 2018, and Oct 14, 2020, 95 boys were screened for inclusion, and 82 met inclusion criteria and were initially enrolled into the study. Three boys were excluded after initial screening due to cataract diagnosis or revoked consent directly after screening, but before randomisation. A further boy assigned to the placebo group did not begin treatment. Therefore, 40 individuals assigned tamoxifen and 38 allocated placebo were included in the intention-to-treat population. The primary efficacy outcome did not differ significantly between tamoxifen (-3·05%, 95% CI -7·02 to 0·91) and placebo (-6·15%, -9·19 to -3·11; 2·90% difference, -3·02 to 8·82, p=0·33). Severe adverse events occurred in two participants: one participant who received tamoxifen had a fall, and one who received placebo suffered a panic attack. No deaths or life-threatening serious adverse events occurred. Viral infections were the most common adverse events. INTERPRETATION: Tamoxifen was safe and well tolerated, but no difference between groups was reported for the primary efficacy endpoint. Slower disease progression, defined by loss of motor function over time, was indicated in the tamoxifen group compared with the placebo group, but differences in outcome measures were neither clinically nor statistically significant. Currently, we cannot recommend the use of tamoxifen in daily clinical practice as a treatment option for boys with Duchenne muscular dystrophy due to insufficient clinical evidence. FUNDING: Thomi Hopf Foundation, ERA-Net, Swiss National Science Foundation, Duchenne UK, Joining Jack, Duchenne Parent Project, Duchenne Parent Project Spain, Fondation Suisse de Recherche sur les Maladies Musculaires, Association Monegasque contre les Myopathies.


Asunto(s)
Distrofia Muscular de Duchenne , Masculino , Animales , Ratones , Humanos , Distrofia Muscular de Duchenne/tratamiento farmacológico , Método Doble Ciego , Modelos Animales de Enfermedad , Reposicionamiento de Medicamentos , Etnicidad
17.
J Clin Sleep Med ; 19(12): 2035-2041, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37539639

RESUMEN

STUDY OBJECTIVES: Treatment-emergent central sleep apnea (TECSA) describes the appearance or persistence of central sleep apnea while undergoing treatment for obstructive sleep apnea. TECSA is well studied in continuous positive airway pressure therapy with an estimated prevalence of 8%. Based on a few case reports, mandibular advancement devices (MAD) may also provoke TECSA. This study aims to gain insight into the prevalence of TECSA with MAD therapy. METHODS: This retrospective study includes a total of 129 patients with moderate to severe obstructive sleep apnea who were treated with a custom-made titratable MAD. Baseline and follow-up sleep studies were compared to identify patients with TECSA. Since different diagnostic criteria to define TECSA are used in literature, prevalence was calculated according to three definitions (TECSA-1, -2, and -3). Demographics, MAD treatment variables, and findings of the diagnostic polysomnography were compared between TECSA and non-TECSA patients to identify possible predictors. RESULTS: Depending on the definition used, TECSA was found in 3.1%-7.8% of patients undergoing MAD therapy. TECSA patients had a higher apnea index (9.2 vs 2.0 events/h, P = .042), central apnea-hypopnea index (4.1 vs 0.2 events/h, P = .045) and oxygen desaturation index (23.9 vs 16.3 events/h, P = .018) at baseline compared to non-TECSA patients. No differences were found in demographics and treatment variables. CONCLUSIONS: These findings demonstrate that TECSA also occurs in patients starting MAD treatment. Patients with TECSA had a higher apnea index, central apnea-hypopnea index, and oxygen desaturation index at baseline compared to non-TECSA patients. CITATION: Hellemans S, Van de Perck E, Braem MJ, Verbraecken J, Dieltjens M, Vanderveken OM. The prevalence of treatment-emergent central sleep apnea with mandibular advancement device therapy. J Clin Sleep Med. 2023;19(12):2035-2041.


Asunto(s)
Avance Mandibular , Apnea Central del Sueño , Apnea Obstructiva del Sueño , Humanos , Ferulas Oclusales , Apnea Central del Sueño/epidemiología , Apnea Central del Sueño/terapia , Estudios Retrospectivos , Prevalencia , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapia , Oxígeno , Resultado del Tratamiento
19.
Laryngoscope ; 133(12): 3619-3627, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37366240

RESUMEN

OBJECTIVE: To quantitatively investigate the effect of mandibular advancement devices (MADs) on pharyngeal airway dimensions in a transverse plane as measured during drug-induced sleep endoscopy (DISE). METHODS: Data from 56 patients, treated with MAD at 75% maximal protrusion and with baseline Apnea-Hypopnea Index ≥10 events/h, were analyzed. For each patient, three snapshots were selected from DISE video footage at baseline, with MAD presence, and during chin lift, resulting in 498 images (168/168/162, baseline/MAD/chin lift). Cross-sectional areas, anteroposterior (AP) and laterolateral (LL) dimensions on both retroglossal and retro-epiglottic levels were measured. To define the effect of MAD and chin lift on pharyngeal dimensions, linear mixed-effect models were built. Associations between MAD treatment response and pharyngeal expansion (MAD/chin lift) were determined. RESULTS: Significant differences were found between retroglossal cross-sectional areas, AP, and LL dimensions at baseline and with MAD presence. At a retro-epiglottic level, only LL dimensions differed significantly with MAD presence compared to baseline, with significant relation of LL expansion ratio to treatment response (p = 0.0176). After adjusting the response definition for the sleeping position, greater retroglossal expansion ratios were seen in responders (1.32 ± 0.48) compared to non-responders (1.11 ± 0.32) (p = 0.0441). No significant association was found between response and pharyngeal expansion by chin lift. CONCLUSION: Our observations highlight the additional value of quantitative pharyngeal airway measurements during DISE with MAD presence in evaluating MAD treatment outcome. These findings demonstrate an increase in retroglossal airway dimensions during DISE, with MAD presence, and more pronounced increase in retroglossal expansion ratios in MAD treatment responders compared to non-responders after sleeping position correction. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3619-3627, 2023.


Asunto(s)
Avance Mandibular , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/terapia , Polisomnografía , Sueño , Resultado del Tratamiento , Endoscopía/métodos
20.
Magn Reson Med ; 90(3): 875-893, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37154400

RESUMEN

PURPOSE: To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on-resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient-recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases. METHODS: The proposed framework consists of SPGR sequences prepared with simultaneous dual-offset frequency-saturation pulses to cancel out dipolar order and associated relaxation (T1D ) effects in Z-spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction [MPF], T2,f , T2,b , R, and free pool T1 ). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single-point qMT methodology for combined estimation of MPF and T1 . RESULTS: Bland-Altman analyses demonstrated a systematic underestimation of MPF (-2.5% and -1.3%, on average, in white and gray matter, respectively) and overestimation of T1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored. Reproducibility of the proposed framework is excellent (ΔMPF = -0.03% and ΔT1 = -19.0 ms). The single-point methodology yielded consistent MPF and T1 values with respective maximum relative average bias of -0.15% and -3.5 ms found in white matter. CONCLUSION: The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT-SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility.


Asunto(s)
Imagen por Resonancia Magnética , Sustancia Blanca , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/métodos , Sustancia Blanca/diagnóstico por imagen , Sustancia Gris , Modelos Teóricos , Protones , Sustancias Macromoleculares , Encéfalo/diagnóstico por imagen
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...