BACKGROUND:Food allergy (FA) significantly impairs health-related quality of life (HRQL), yet its key determinants remain unclear. This study aimed to identify factors associated with poor HRQL in FA using machine-learning analysis. METHODS:Within the Spanish multicentre BIOGRIAL study, well-phenotyped patients with IgE-mediated FA were enrolled. Participants aged ≥ 8 y were included to allow self-completion of the Food Allergy Quality of Life Questionnaire (FAQLQ). Clinical variables included atopic comorbidities, number and type of food allergies, age at onset, FA duration, need for urgent treatment, and reaction severity graded with the Food Allergy Severity Score. Poor FA-HRQL was defined as FAQLQ ≥ 5 (range 1-7). Determinants were identified using logistic regression and decision trees. RESULTS:A total of 502 patients were included (63.9% female, 86% adults, 7.4% adolescents, 6.6% children). Median FAQLQ was 4.55. Adults and females had poorer FA-HRQL than younger participants and males, respectively. Logistic regression identified female sex, multiple allergies, severe reactions, and vegetable allergy as independent predictors. Decision trees identified adult age, female sex, number of food allergies, need for urgent care, reaction severity, and FA onset < 18 y as determinants of poor FA-HRQL. Adult females with ≥ 7 food allergies had the worst FA-HRQL (mean FAQLQ 5.93), and 79% of patients with FAQLQ ≥ 5 were adult females. CONCLUSIONS:HRQL of people with FA is impaired by multiple determinants that should be addressed through psychosocial support, dietary management and education. Being female was the determinant with the highest negative impact, and adult women with multiple FAs have the poorest FA-HRQL and require targeted personalised interventions.
ABSTRACT Background Anti‐CGRP antibodies are effective and safe in real‐world migraine management, but guidelines recommend discontinuation after 12–18 months due to limited long‐term data and remaining uncertainties regarding optimal treatment duration and sustained safety, highlighting the need for large‐scale long‐term real‐world evidence. This study evaluated their safety and effectiveness in patients treated for ≥2 years. Methods This multicenter retrospective study included patients from 13 headache units who received the same anti‐CGRP antibody for ≥24 months, excluding discontinuation periods. Baseline characteristics, monthly headache days (MHD), monthly migraine days (MMD), and adverse events (AEs) were recorded at baseline, 6 months, 1, 2, 3, and 4 years. Descriptive statistics were used to summarize clinical characteristics, and appropriate parametric or non‐parametric tests were applied for group comparisons. Multivariate analyses were performed to explore associations between baseline variables and long‐term treatment response. Results A total of 454 patients (91% female, mean age 48) were analyzed, with follow‐up at 2 years (n = 454), 3 years (n = 135), and 4 years (n = 17). Treatments included erenumab (39%), galcanezumab (34%), and fremanezumab (27%). Fifty‐seven percent maintained continuous therapy, while 43% restarted after discontinuation. Sustained reductions in MHD and MMD were observed at 2, 3, and 4 years (MHD from 20 to 6, 6, 5/MMD from 14 to 4, 4, and 2). Medication overuse decreased from 78% to 13%, 20%, and 18%. Loss of effectiveness occurred in 4.2% after 2 years. AEs appeared in <20%, mostly mild (>80%), leading to discontinuation in 0.4%. Multivariate analysis showed that shorter disease duration prior to anti‐CGRP initiation, earlier anti‐CGRP initiation, and greater MHD/MMD reduction at 6 months were associated with better long‐term outcomes. Conclusions Anti‐CGRP mAbs demonstrate sustained long‐term safety and effectiveness, with consistent reduction in headache and migraine days and lower medication overuse. Early initiation and greater initial improvement predict better long‐term outcomes. Findings support extending therapy beyond 12–18 months, supporting optimization of clinical protocols.
Tauopathies, such as Alzheimer's disease (AD), are neurodegenerative disorders marked by abnormal intraneuronal aggregates of phosphorylated Tau protein. Unfortunately, no effective treatment is currently available. Since extracellular Tau (eTau) is essential for the spread of cerebral tauopathy, immunotherapy approaches using specific antibodies against Tau have been investigated. However, these strategies have shown limited applicability and benefit. Because previous in vitro studies reported that dephosphorylation of eTau by tissue-nonspecific alkaline phosphatase (TNAP) enhances its neurotoxicity, here we evaluate how neuronal TNAP contributes to Tau-induced neurotoxicity in vivo. To address this, we generated new transgenic mouse lines using Cre-lox technology to i) specifically delete TNAP in excitatory neurons of P301S mice, a well-characterized tauopathy model, or ii) induce neuronal TNAP overexpression in WT mice. Moreover, we compare the in vivo spreading capacity of phospho-eTau and dephospho-eTau-induced neurotoxicity. Our findings show that neuronal TNAP deletion in P301S mice reduces i) neuronal and synaptic loss, ii) the number of neurons with neurofibrillary tangles (NFTs), iii) reactive astrogliosis and microgliosis, and iv) brain calcifications; collectively, these changes lead to v) improved memory function in these mice. Conversely, overexpression of neuronal TNAP in WT mice alone is sufficient to cause i) loss of thalamic neurons and synaptic contacts, ii) formation of intracellular NFTs, iii) reactive gliosis, iv) brain calcifications, and v) memory impairment. These results demonstrate that neuronal TNAP promotes Tau-induced neurotoxicity spreading by facilitating eTau dephosphorylation, which confirms this ectoenzyme as a promising therapeutic target for tauopathies.
BACKGROUND:The consumption of plant-based food has lately largely increased, raising concerns about allergic reactions from ingredients which are currently not subject to mandatory labelling. METHODS:We analysed the frequency and severity of allergic reactions to non-mandatory labelled allergenic foods (pea, lentil, bean, chickpea, fenugreek, pine nut, sunflower-, poppy-, pumpkin seed, buckwheat) from two large European cohorts: The Anaphylaxis Registry (NORA) and EuroPrevall outpatient clinic study. Severity was assessed using the Food Allergy Severity Score (FASS) and compared with reactions to mandatory labelled allergenic foods. RESULTS:Among 589 reactions from both cohorts, sunflower seed was the most frequent trigger (n = 126). In NORA, pine nut (1.0% of food-induced allergic reactions) was most common followed by pea and buckwheat (0.7% each); in EuroPrevall, sunflower seed (1.2%), poppy seed (0.6%) and lentil (0.6%) predominated. After adjusting for age and sex, the severity of reactions to mandatory labelled seeds and legumes (excluding peanut) were not different (nFASS median: 4.39 vs. 4.43 and 4.56 vs. 4.49). Whereas, cereal-induced reactions (6.47) were significantly more severe than buckwheat (4.77). In Nora, the number of reactions to fenugreek and pumpkin seed were 7.4- and 3.7-fold higher in 2015-2022 versus 2007-2014. CONCLUSION:Non-mandatory labelled allergenic foods were identified to cause severe allergic reactions in two large European cohorts. The frequent involvement of sunflower seed, pine nut, pea and lentil, but also rising numbers of reactions to fenugreek and pumpkin seed, indicates their potential risk. These allergenic foods warrant close monitoring and consideration in future allergen labelling revisions.
