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Parathyroid hormone receptor agonists in the management of osteoporosis
No full textParathyroid hormone (PTH) regulates bone homeostasis. Intermittent exposure to PTH results in bone formation being greater than bone resorption, and this effect has been harnessed through the development of agonists of the PTH and PTH-related protein type 1 receptor (PTH1R) to treat osteoporosis. Teriparatide, an analogue of the first 34 amino acids of PTH, and abaloparatide, which resembles PTH-related protein (PTHrP) in structure, are PTH1R agonists currently in clinical use. Both medications have been shown to increase bone mineral density at the lumbar spine, femoral neck and total hip. Randomized controlled trials with teriparatide or abaloparatide have also provided evidence of reduction in vertebral and non-vertebral fractures. The ACTIVE trial suggested slightly greater efficacy for major osteoporotic fractures (as an exploratory end point) for abaloparatide than for teriparatide. A similar potential superiority was suggested for hip fracture in a real-world, observational study. Side effects of these medications are usually transient, and although a risk of osteosarcoma was suggested by studies using murine models, no such risk has been observed in extensive human studies. Overall, both teriparatide and abaloparatide have demonstrated convincing clinical effectiveness and cost-effectiveness, with a reassuring safety profile. Potential differences in their effects on bone mineral density and their antifracture effects offer avenues for differentiation but require further validation in appropriately designed studies
Two Seconds to Speak:Increasing Communication Speed for fMRI-Based Brain-Computer Interfaces
No full textBackground: Brain-computer interfaces (BCIs) can provide alternative, motor-independent means of communication for people who have lost motor function. A promising variant is the functional magnetic resonance imaging (fMRI)-based BCI, which exploits information on hemodynamic brain activity evoked by performing different mental tasks. However, due to the sluggish nature of the hemodynamic response, a current challenge is to make these BCIs as efficient and fast as possible to allow useful clinical application. Furthermore, there is yet no consensus on optimal mental-task selection for multi-voxel pattern analysis-based decoding, nor whether certain tasks generalize well across users, or if individualized task selection would yield a higher decoding accuracy.Methods: To increase BCI efficiency, we tested whether distributed patterns of 3T-fMRI brain activation evoked by two-second mental tasks could be reliably discriminated in 2- to 7-class classification. In addition, we identified optimal mental-task combinations for high-accuracy classification across all classes. Finally, we examined whether individualized task selection-based on subjects' previous decoding performance (accuracy-based tasks) or their subjective preference (preference-based tasks)-was superior to the other in a yes/no communication paradigm.Results: The 2-class decoding resulted in a mean accuracy of 78% and 3- to 7-class accuracies were above chance level. Mental calculation and spatial navigation were most frequently associated with the highest decoding accuracy. Furthermore, subjects could encode yes/no answers using their accuracy-based and preference-based tasks with mean accuracies of 83% and 81%, respectively. This implies that this paradigm, using short encoding durations, is well-suited to the diversity of patients and could greatly increase BCI efficiency.Impact Statement This study advances functional magnetic resonance imaging (fMRI)-based brain-computer interfaces (BCIs) by showing that brain activation evoked by two-second mental tasks can be reliably decoded with multi-voxel pattern analysis, significantly improving fMRI-BCI efficiency while still achieving high accuracy. By exploring the differentiability of seven different mental tasks, using binary and multiclass classification of up to seven classes, and individualized task selection, we provide insights into optimizing mental-task paradigms for patient-tailored fMRI-BCIs. Given the variability of cognitive abilities in motor-impaired individuals, patient-tailored BCIs with a diverse range of mental tasks are highly welcome. These findings contribute to faster, more intuitive, and less cognitively demanding hemodynamic BCIs
Don't check after a snack:body checking increases eating-related threat perception
No full textOBJECTIVE: Engaging in safety behaviours might exacerbate eating-related threat perception and fear in individuals with eating disorders. The present study tested this mechanism by manipulating eating disorder-related safety behaviours (i.e., body checking) in non-clinical women. It is expected that body checking after food intake increases eating-related threat perception and fear, reduces eating desires and lowers calorie consumption compared with control activities. METHOD: Ninety-nine non-clinical women had to eat two high-caloric snacks and were randomly assigned to one of three conditions: In the safety behaviour condition they measured body parts related to eating disorder concerns, in the body control condition participants measured body parts unrelated to eating disorder concerns and in the general control condition they measured pieces of furniture. After the manipulation, participants were again presented with (similar) high-calorie snacks, rated their fear, threat perception and eating desires, and completed a bogus taste test (ad-libitum intake). RESULTS: Participants in the safety behaviour and body control condition perceived food intake as more threatening after the manipulation than before. There was no significant change in the general control condition. Conditions did not significantly differ in fear, eating desires and calorie consumption. DISCUSSION: Checking body parts - even if it is only once and unrelated to eating disorder concerns - can increase eating-related threat perception in non-clinical women; to also affect fear, eating desires and calorie consumption, more persistent or intense safety behaviours might be necessary
Severe Symptoms Predict Residual Disease After Transitioning From High to Low Disease Activity in Axial Spondyloarthritis: A Longitudinal Study
No full textObjective: To investigate whether very high disease activity (VHDA) status or severe symptoms when in HDA state predict residual disease after achieving inactive disease/low disease activity (ID/LDA) in axial spondyloarthritis (axSpA).Methods: Prospective data from the SpA-Net registry were used. HDA was defined as an Axial Spondyloarthritis Disease Activity Score (ASDAS)≥2.1, and ID/LDA as ASDAS<2.1. VHDA (predictor 1) was defined as ASDAS>3.5, and severe symptoms when in HDA state (predictor 2) as a score ≥6/10 for fatigue, back pain and/or physical function. Residual disease (outcome) was defined as presence of ≥1 patient-experienced (fatigue, back pain and/or physical function ≥4/10) or objective disease indicator (active peripheral manifestations, active psoriasis, elevated C-reactive protein or physician's impression) after achieving ID/LDA. Associations between either predictor and residual disease were investigated using logistic regression.Results: Overall, 133 patients (58 [43.6%] female, mean age 48.8 [SD 14.5] years) were included. At the HDA time-point, 16 (12.0%) patients had VHDA status and 107 (80.5%) experienced severe symptoms. At the ID/LDA time-point, prevalence of patient-experienced and objective residual disease was 70.7% (n=94/133) and 54% (n=37/68), respectively. VHDA status when in HDA state was not associated with either form of residual disease after achieving ID/LDA. Severe symptoms were associated with patient-experienced residual disease (OR=5.09 [95%CI 1.76-14.71]), but not objective residual disease.Conclusion: Severe symptoms when in HDA state predict patient-experienced, but not objective, residual disease in axSpA, while VHDA status does not predict either form. These findings may aid in anticipating residual disease and guiding management
Evaluating the need for late angiography for complete obliteration of AVMs after endovascular treatment:collaborative AVM center experience and a systematic review
No full textBrain arteriovenous malformations (bAVMs) can be treated curatively by endovascular embolization. However, limited data exist on late recanalization rates. We investigated the rate of late bAVM recanalization following complete endovascular obliteration, confirmed by primary control angiography. We performed a single-center retrospective cohort study on late recurrences in adult patients with bAVMs after complete endovascular obliteration at a Radboud – Isala - MUMC+ (RIM) collaborative AVM center in the Netherlands between 2014 and 2022. Additionally, we conducted a systematic review to evaluate the rate of late recanalization following complete endovascular obliteration, confirmed on primary control angiography, in adults with bAVMs. The protocol for this review was registered in PROSPERO (CRD42024546875). Our retrospective study revealed 42 adult patients treated by endovascular means only; 90.5% (38 patients with mean age of 48.1 years) had confirmed complete obliteration. Both primary (6 months post-treatment) and secondary (more than 1 year post-treatment) angiographic control confirmed complete obliteration in 21 of 23 patients with complete follow-up. Mean follow-up was 47.8 months. Two late recurrences (9.5%) were detected at 5- and 6-years' follow-up imaging. Our systematic review included two studies encompassing a total of 19 patients with mean angiographical follow-up of 20.8 months. There were no late recurrences. Late bAVM recurrence after endovascular treatment with proven complete obliteration may be underestimated owing to limited long-term follow-up. Our findings suggest that after a 6-month angiographic confirmed obliteration, a 5-year angiographic imaging control is justified.</p
Effects of pharmacist care on hospitalizations in heart failure across outpatient and inpatient settings:A systematic review and meta-analysis
No full textAims Heart failure (HF) is major cause of unplanned (re)hospitalizations, especially in high-risk patients such as those recently discharged or those with worsening HF. Hospital-affiliated or clinic-based pharmacists, though underutilized, may help reduce this burden. This systematic review and meta-analysis assessed their impact on all-cause and HF hospitalizations.Methods A systematic literature search using PUBMED and EMBASE and conducted according to PRISMA guidelines identified randomized controlled trials published up to November 2024. Eligible studies evaluated the effects of pharmacy interventions on hospitalizations and mortality among patients with HF. Studies with community pharmacy- or home-based interventions were excluded. Study quality was appraised using the Cochrane risk-of-bias tool. Random-effects models were applied to derive odds ratios (OR), with heterogeneity assessed using the I2 statistic and Cochrane's Q test.Results Eleven studies were included, involving 3576 patients and a variety of pharmacist interventions. Pharmacists significantly reduced the odds of all-cause hospitalizations compared to usual care (3472 patients, 927 events; OR 0.67, 95% confidence interval [CI]: 0.49-0.92, P = 0.0119). For HF hospitalizations (3442 patients, 504 events), similar results were retrieved (OR 0.64, 95% CI: 0.48-0.87, P = 0.0038). Heterogeneity was moderate for both analyses. Sensitivity analyses supported the robustness of these two analyses. Subgroup analyses indicated greater effectiveness in outpatient settings and when extended interventions were provided.Conclusions Across inpatient and outpatient settings, pharmacist interventions in HF significantly reduced all-cause as well as HF hospitalizations. Our findings highlight the importance of integrating pharmacists into multidisciplinary teams to improve HF management for in- and outpatients
Functional near-infrared spectroscopy as a biomarker of TMS efficacy in treatment-resistant depression
No full textBackground: Reliable biomarkers for predicting treatment response and suicide risk in treatment-resistant depression (TRD) are limited. Functional near-infrared spectroscopy (fNIRS) offers a noninvasive means to assess prefrontal cortical activation linked to therapeutic outcomes. Methods: In a double-blind, randomized, sham-controlled trial, 100 inpatients with TRD received either active or sham prolonged intermittent theta-burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (DLPFC) across 2 weeks. fNIRS measured oxyhemoglobin (oxy-Hb) levels at rest and during a verbal fluency task (VFT) and two-back working memory task, both before and after aiTBS. Clinical outcomes included Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale item 3 (HAMD-3), and Beck Scale for Suicide Ideation (BSS). Results: Baseline BSS, HAMD-3, and MADRS scores did not differ between groups (all P > 0.05). Post-treatment, the active group showed significant improvements in BSS, HAMD-3, and MADRS (all P < 0.05). Active aiTBS increased oxy-Hb in the left DLPFC and right orbitofrontal cortex (OFC) during the two-back task, and in the left DLPFC, OFC, and frontopolar cortex (FPC) during the VFT. Greater left DLPFC activation during the VFT correlated with MADRS improvement, and baseline OFC activation predicted antidepressant response. No fNIRS measures predicted changes in suicidality. Conclusions: Task-evoked prefrontal activation—especially in the left DLPFC and OFC—may serve as a biomarker for antidepressant efficacy in TRD, though fNIRS did not predict suicide risk reduction.</p
Sensor-Based to Interaction-Based AI Models in Education:The JOINclusion Case Study
No full textThe integration of Artificial Intelligence (AI) in education is reshaping traditional learning environments by enabling personalized learning experiences, enhancing accessibility, and providing data-driven insights into student engagement and performance. However, the rise of AI technologies in educational settings brings complex ethical challenges, including concerns over data privacy, transparency, and equity. This paper explores the dual impact of AI on education, examining both its transformative potential and the ethical issues it presents. It discusses the role of AI models that analyse how students use the learning tools as an alternative to sensor-based approaches, which can address privacy concerns while still offering adaptive, personalized support. Furthermore, this study evaluates frameworks for ethical AI implementation, emphasizing transparency, inclusivity, and trustworthiness to support responsible AI deployment in education. By addressing key ethical considerations and regulatory standards, this paper proposes a path toward data-driven tools that enhance educational outcomes without compromising student autonomy or privacy. The findings underscore the importance of aligning AI innovations with educational values, suggesting that an ethically-centred approach to AI can promote trust and effectiveness in diverse learning contexts
Adult ependymoma:results from the Dutch Brain Tumour Registry on primary treatment and survival
No full textPurpose: Ependymomas are rare tumours of the central nervous system (CNS). This study reports real-world data regarding primary treatment and outcome for adult patients diagnosed in the Netherlands between 2014 and 2023. Methods: Diagnostic and treatment data on adult patients with a newly diagnosed ependymoma were obtained from the Dutch Brain Tumour Registry. Factors associated with incomplete resection and adjuvant radiotherapy (RT) were identified using logistic regression analyses, thereby accounting for variation between CNS regional tumour boards through mixed-effect modelling when relevant. In case of variation, case-mix adjusted ratios of tumour boards were evaluated in funnel plots. Prognostic factors for overall survival (OS) at 5 years were assessed with the Kaplan-Meier method and Cox proportional hazards regression models. Analyses were performed on multiple imputed datasets (m = 10) to account for missing data. Results: Among 575 patients, 74 (12.9%) ependymomas were located in the supratentorial region, 129 (22.5%) in the posterior fossa, and 370 (64.6%) in the spine. Incomplete resection occurred more often in posterior fossa, and in larger and metastatic/multifocal ependymomas. Adjuvant RT was administered to 47 of 173 patients with a metastatic/multifocal and/or incompletely removed WHO grade 1–2 tumour (27.2%), and to 26 of 34 patients with a WHO grade 3 ependymoma (76.5%). Adjuvant RT conferred significant survival benefit (hazard ratio 0.17, 95% confidence interval 0.06–0.53, p < 0.01) following adjustment for other factors. Conclusion: This study substantiates the benefit of adjuvant RT for selected adult patients with an ependymoma and emphasizes the need for more coordinated management across tumour boards.</p
Implementation, facilitators and barriers, of eHealth with a self-management approach for informal caregivers of people with dementia:a narrative review
No full textObjectiveseHealth and self-management interventions for informal caregivers of people with dementia show promising positive results for various health outcomes. However, their successful implementation in practice remains inconsistent. The aim of this study is to gain insight into facilitating factors and barriers of the implementation of eHealth interventions with a self-management approach for informal caregivers of people with dementia.MethodThis narrative review included a systematic search of the databases PsycINFO, PubMed and Web of Science. Papers were screened against the inclusion criteria and then the text of eligible papers was qualitatively analyzed both manually and by computer assisted software. Findings were then mapped into the Consolidated Framework for Implementation Research (CFIR).ResultsTwenty papers were selected and seven themes emerged from the qualitative analysis: (1) Organizational, financial, and structural considerations in healthcare; (2) Characteristics of the eHealth interventions; (3) Attitudinal perspectives; (4) Awareness, familiarity and confidence; (5) Resource allocation and support; (6) Personal characteristics of the informal caregivers; and (7) Wider context factors to eHealth intervention implementation. Mapping the findings into the CFIR framework revealed that little is known about the implementation process.ConclusionThe alignment of eHealth interventions with current policy objectives and digital progress underlines their importance in real-world application