Search Results (352)

Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic review aims to analyze the cost-effectiveness and cost-utility profiles of the European Medicines Agency-authorized ATMPs for treating rare diseases. Methods: A systematic review was conducted following PRISMA guidelines. Studies were identified by searching PubMed, Embase, Web of Science, and ProQuest scientific databases. Economic evaluations reporting incremental cost-effectiveness/utility ratios (ICERs/ICURs) for ATMPs were included. Costs were standardized to 2023 Euros, and a cost-effectiveness plane was constructed to evaluate the results against willingness-to-pay (WTP) thresholds of EUR 50,000, EUR 100,000, and EUR 150,000 per QALY, as part of a sensitivity analysis. Results: A total of 61 studies met the inclusion criteria. ATMPs for rare blood diseases, such as tisagenlecleucel and axicabtagene ciloleucel, were found to be cost-effective in a majority of studies, with incremental QALYs ranging from 1.5 to 10 per patient over lifetime horizon. Tisagenlecleucel demonstrated a positive cost-effectiveness profile in the treatment of acute lymphoblastic leukemia (58%), while axicabtagene ciloleucel showed a positive profile in the treatment of diffuse large B-cell lymphoma (85%). Onasemnogene abeparvovec for spinal muscular atrophy (SMA) showed uncertain cost-effectiveness results, and voretigene neparvovec for retinal diseases was not cost-effective in 40% of studies, with incremental QALYs around 1.3 and high costs exceeding the WTP threshold set. Conclusions: ATMPs in treating rare diseases show promising economic potential, but cost-effectiveness varies across indications. Policymakers must balance innovation with system sustainability, using refined models and the long-term impact on patient outcomes. Full article

Background: Despite significant advancements in diabetes care, many individuals with type 2 diabetes (T2D) do not receive optimal care and treatment. Digital interventions promoting behavioral changes have shown promising long-term results in supporting healthier lifestyles but are not implemented in most healthcare offerings, maybe due to lack of general practice support and collaboration. This study evaluates the efficacy of the Digital, Individualized, and Collaborative Treatment of T2D in General Practice Based on Decision Aid (DICTA), a randomized controlled trial integrating a patient-centered smartphone application for lifestyle support in conjunction with a clinical decision support (CDS) tool to assist general practitioners (GPs) in optimizing antidiabetic treatment. Methods: The present randomized controlled trial aims to recruit 400 individuals with T2D from approximately 70 GP clinics (GPCs) in Denmark. The GPCs will be cluster-randomized in a 2:3 ratio to intervention or control groups. The intervention group will receive one year of individualized eHealth lifestyle coaching via a smartphone application, guided by patient-reported outcomes (PROs). Alongside this, the GPCs will have access to the CDS tool to optimize pharmacological decision-making through electronic health records. The control group will receive usual care for one year, followed by the same intervention in the second year. Results: The primary outcome is the one-year change in estimated ten-year cardiovascular risk, assessed by SCORE2-Diabetes calculated from age, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, age at diabetes diagnosis, HbA1c, and eGFR. Conclusions: If effective, DICTA could offer a scalable, digital-first approach for improving T2D management in primary care by combining patient-centered lifestyle coaching with real-time pharmacological clinical decision support. Full article

The designs of clinical trials of drugs for rare diseases are challenged by health technology assessment organisations and payers. Phase II pivotal studies, single-arm or open-label designs, the extensive use of non-final endpoints, and the limited use of patient-reported outcomes (PROs) are the main points of contention. The evidence on the actual design of these trials is limited, but corroborates the concerns of the above. Our aim is to scrutinise whether the design of pivotal studies of drugs for rare diseases to be launched into the Italian market by 2026 present similar issues. The drugs and the relevant pivotal studies were retrieved from Biomedtracker and US and European clinical trial databases. We identified 154 new drugs for rare diseases. Single-arm designs account for 36% of trials. Almost 50% of randomised control trials (RCTs) are designed using an active comparator and 61% are double-blinded. Primary endpoints are mostly (82%) surrogate. A total of 59% of studies include PROs. Our findings were partially expected (e.g., extensive use of surrogate endpoints) and partially not (e.g., RCTs and an active comparator), considering previous studies on the same topic. Having more head-to-head studies may reduce uncertainty concerning evidence at market launch, but different issues persist, including the still limited role of PROs. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is characterized by chronic relapsing and remitting inflammation of the gastrointestinal tract. Fecal microbiota transplantation (FMT) has emerged as an FDA-approved treatment for recurrent Clostridioides difficile infections (CDIs), with promising potential in patients with IBD. This manuscript aimed to provide a comprehensive and updated review of the available literature on fecal microbiota transplantation, its clinical use in IBD in general, as well as in patients with IBD and CDI. Methods: An extensive literature search was performed from October 2024 to March 2025. All publications available within PubMed, Medline, Embase, Google Scholar, and Cochrane databases were reviewed. All original articles, case reports, review articles, systematic reviews, and meta-analyses were included. Qualitative and quantitative data were both extracted. Discussion: Intestinal microbiota is an integral part of the human body, and dysbiosis (an imbalance in the gut’s microbial community) has been linked with several pathologies. Dysbiosis in IBD is marked by reduced beneficial bacteria and increased pro-inflammatory pathogens, contributing to mucosal damage and immune dysregulation. FMT has emerged as a solution to dysbiosis, with the first case recorded in 1917. FMT has been successful in treating patients with CDI. The diagnostic value of the gut microbiome is currently being explored as a possible therapeutic approach to IBD. Several studies have assessed FMT in patients with IBD and CDI with promising results in both ulcerative colitis (UC) and Crohn’s disease (CD) but varying efficacy based on administration routes, donor selection, and processing methods. In the context of recurrent CDI in patients with IBD, FMT demonstrates a high cure rate and potential benefit in concurrently improving IBD activity. However, risks such as IBD flare-ups post-FMT remain a concern. Conclusions: FMT holds promising potential in the management of CDI in patients with IBD. By restoring microbial diversity and correcting dysbiosis, FMT offers a novel, microbiota-targeted alternative to conventional therapies. While data support its efficacy in improving disease remission, variability in outcomes underscores the need for standardized protocols and additional large-scale, controlled studies. Continued research efforts into donor selection, treatment regimens, and long-term safety will be critical to optimizing FMT’s role in IBD and CDI care as well as improving patient outcomes. Full article

Background/Objectives: Hemiarthroplasty (HA) and Reverse Total Shoulder Arthroplasty (RTSA) are both reliable treatment options for complex proximal humerus fractures. The role of the subscapularis tendon is well-defined in HA, whereas it plays a controversial role in RTSA. The purpose of our study is to evaluate its role in patients with proximal humerus fractures treated with HA and RTSA and investigate its association with clinical outcomes. Methods: Sixty-eight consecutive patients with proximal humeral fracture were prospectively enrolled into the study from June 2015 to May 2020 (RTSA = 36; HA = 32). Pre- and postoperative shoulder CT scans were performed to measure the subscapularis muscle cross-sectional area (SMCSA) and the supraspinatus fossa cross-sectional area (SFCSA). The SMCSA/SFCSA ratio was employed to normalize measurements against individual patient anatomy. Patient reported outcomes (PROs) and range of motion (ROM) were evaluated at the final follow-up. Results: The RTSA group demonstrated superior patient-reported outcomes (PROs) and range of motion (ROM) compared to the HA group. Notably, the Constant Score was significantly higher in the RTSA group (58.00 vs. 38.50; p = 0.0001), as well as forward flexion (147.50° vs. 90.00°; p < 0.0001). A postoperative reduction in subscapularis size of >35% occurred more frequently in RTSA patients (55.6%) than in HA patients (25%) (p = 0.01). The loss of subscapularis surface was greater in the RTSA patients (p = 0.018). Conclusions: RTSA demonstrated better results compared to HA, providing better ROM and PROs. Postoperative reduction in subscapularis size was significantly higher in RTSA compared to HA. Subscapularis condition seems to show no correlation with functional outcome in RTSA. Full article

Objectives: To identify clinical, functional, laboratory, and patient-reported parameters associated with medium-term risk of hospitalization or death among older adults attending a multidisciplinary outpatient clinic, and to assess the predictive performance of these measures for individual risk stratification. Methods: In this cohort study, 350 adults aged ≥65 years were assessed at baseline and followed for an average of 8 months. The primary outcome was a composite of hospitalization or all-cause mortality. Parameters assessed included frailty and comorbidity measures, functional parameters, such as gait speed and grip strength, laboratory biomarkers, and patient-reported measures, such as quality of life (QoL, assessed on a Likert scale) and the presence of depressive symptoms. Predictive performance was evaluated using univariable logistic regression and multivariable modeling. Discriminative ability was assessed via area under the ROC curve (AUC), and selected models were internally validated using repeated k-fold cross-validation. Results: Overall, 40 participants (11.4%) experienced hospitalization or death. Traditional clinical risk indicators, including frailty and comorbidity scores, were significantly associated with the outcome. Patient-reported QoL (AUC = 0.74) and Geriatric Depression Scale (GDS) scores (AUC = 0.67) demonstrated useful overall discriminatory ability, with high specificities at optimal cut-offs, suggesting they could act as “red flags” for adverse outcomes. However, the limited sensitivities of individual predictors underscore the need for more comprehensive screening instruments with improved ability to identify at-risk individuals earlier. A multivariable model that incorporated several predictors did not outperform QoL alone (AUC = 0.79), with cross-validation confirming comparable discriminative performance. Conclusions: Patient-reported measures—particularly quality of life and depressive symptoms—are valuable predictors of hospitalization or death and may enhance traditional frailty and comorbidity assessments in outpatient geriatric care. Future work should focus on developing or integrating screening tools with greater sensitivity to optimize early risk detection and guide preventive interventions. Full article

Background: Cognitive impairment (CI) is a common and disabling symptom in patients with relapsing–remitting multiple sclerosis (RRMS), potentially emerging at any stage, including preclinical phases. Despite its impact on quality of life, CI often goes unrecognized, as clinical follow-up typically focuses on motor and sensory symptoms. Validated tools, such as the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and patient-reported outcomes (PROs), should be integrated into routine evaluations beyond the Expanded Disability Status Scale (EDSS). Objective: The objective of this study was to evaluate cognitive impairment and quality of life in patients with RRMS using the BICAMS and PROs. Methods: This cross-sectional, descriptive study included patients with RRMS under follow-up at a tertiary hospital in San Luis Potosí, Mexico. Participants underwent cognitive screening with the BICAMS battery and completed the MSQoL-54 (quality of life), FSMC (fatigue), and MSIS-29 (functional impact) scales. Statistical analyses included ANOVA, the Kruskal–Wallis test, and Pearson correlations. Results: Nineteen patients were evaluated (73.7% female, mean age 36.5 ± 8.9 years). BICAMS results showed variable cognitive performance, with no significant differences across treatment groups for processing speed (p = 0.222), verbal memory (p = 0.082), or visuospatial memory (p = 0.311). A significant correlation was found between verbal and visuospatial memory (r = 0.668, p = 0.002). Total quality of life differed significantly across treatments (F = 8.007, p = 0.029), with a strong correlation between overall quality of life and general health perception (r = 0.793, p < 0.001). Fatigue and MSIS scores showed no association with treatment. Conclusions: Cognitive impairment is common in RRMS and can be detected using brief assessment tools, such as the BICAMS. Incorporating cognitive screening and PROs into clinical practice is essential to guide comprehensive management. Full article

Background: A growing body of evidence suggests that diet can modify Parkinson’s disease (PD) outcomes, although there is disagreement about what should be included and excluded in such a diet. Existing evidence suggests that adherence to the MIND and Mediterranean (MEDI) diets are associated with reduced PD symptoms, but only a few variables from the adherence scales are responsible for the statistically observed improvement. Objectives: The goal was to use patient-reported outcomes in a large cohort to identify the foods and dietary patterns (PRO diet) most strongly associated with the fewest PD symptoms over time, and to develop a composite adherence scale to enable comparisons between MEDI, MIND, and PRO. Methods: Data were obtained from the prospective longitudinal natural history study and from Modifiable Variables in Parkinsonism (MVP)—a study designed to identify behaviors associated with patient-reported outcomes (PRO-PD). Upon the completion of the binary and food frequency data collection, using various predictive models and considering congruence with historical data, the PRO diet was created via an iterative process. Our goal was to create a new scale and compare its performance to the existing MIND and MEDI scores. The comparison was made at baseline, using the regression models for PRO-PD and the different scales as the predictors. The models were compared via the Akaike Information Criterion (AIC). To examine whether baseline adherence levels predicted subsequent symptom trajectories, the baseline PRO diet adherence and subsequent slope of progression were evaluated. Results: Data from 2290 individuals with PD were available for this analysis. The Mediterranean and MIND diets showed almost identical effects. For both the diets, the effect they had on non-motor symptoms was about twice the effect on motor symptoms. The slopes for the total PRO-PD for MEDI, MIND, and PRO-21 were −64.20467, −64.04220, and −28.61995, respectively. The AIC value differences were substantial (>2), indicating meaningful improvements in the model fit for total PRO-PD, as follows: MEDI: 28,897.24, MIND: 28,793.08, and PRO-21: 27,500.71. The subset of individuals who were most adherent to the PRO-21 diet at baseline had the slowest subsequent progression, as measured by a 43% reduced PRO-PD slope, compared to the less adherent groups. Conclusions: The PRO-21 outperformed the MIND and MEDI diets in the model fit, overcoming the ceiling effects and showing orders of magnitude and superior explanatory power for variance in PD outcomes, despite the smaller per-unit effect sizes. However, its rigorous demands may introduce barriers related to cost, feasibility, and sustainability, underscoring the need for future intervention trials to assess real-world feasibility, adherence, side effects, and clinical impact. Full article

Background: Electronic patient-reported outcomes (ePROs) enable real-time symptom monitoring and early intervention in oncology. Large language models (LLMs), when combined with retrieval-augmented generation (RAG), offer scalable Artificial Intelligence (AI)-driven education tailored to individual patient needs. However, few studies have examined the feasibility and clinical impact of integrating ePRO with LLM-RAG feedback during radiotherapy in high-toxicity settings such as head and neck cancer. Methods: This prospective observational study enrolled 42 patients with head and neck cancer undergoing radiotherapy from January to December 2024. Patients completed ePRO entries twice weekly using a web-based platform. Following each entry, an LLM-RAG system (Gemini 1.5-based) generated real-time educational feedback using National Comprehensive Cancer Network (NCCN) guidelines and institutional resources. Primary outcomes included percentage weight loss and treatment interruption days. Statistical analyses included t-tests, linear regression, and receiver operating characteristic (ROC) analysis. A threshold of ≥6 ePRO entries was used for subgroup analysis. Results: Patients had a mean age of 53.6 years and submitted an average of 8.0 ePRO entries. Frequent ePRO users (≥6 entries) had significantly less weight loss (4.45% vs. 7.57%, p = 0.021) and fewer treatment interruptions (0.67 vs. 2.50 days, p = 0.002). Chemotherapy, moderate-to-severe pain, and lower ePRO submission frequency were associated with greater weight loss. ePRO submission frequency was negatively correlated with both weight loss and treatment interruption days. The most commonly reported symptoms were appetite loss, fatigue, and nausea. Conclusions: Integrating LLM-RAG feedback with ePRO systems is feasible and may enhance symptom control, treatment continuity, and patient engagement in head and neck cancer radiotherapy. Further studies are warranted to validate the clinical benefits of AI-supported ePRO platforms in routine care. Full article

Background/Objectives: Diabetes mellitus is defined as a group of metabolic diseases characterized by chronically elevated blood glucose levels. This condition influences the course of orthodontic treatment, as it affects various clinical aspects of the patient that must be taken into consideration prior to initiation. Therefore, achieving adequate control and management of diabetic patients undergoing orthodontic therapy is essential. This article presents a qualitative synthesis of studies addressing how diabetes affects orthodontic treatments, emphasizing the importance of understanding the necessary considerations prior to initiating treatment and how to manage potential complications. Methods: This systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A database search was performed on 5 May 2025, in PubMed, Scopus, Scielo, and The Cochrane Library, using terms related to “diabetes mellitus” and “orthodontic treatments”. Studies meeting the search criteria were included, particularly those that were published in the past ten years and reported on the influence of diabetes on orthodontic treatment. The quality of the case–control studies was assessed using the Newcastle–Ottawa Scale (NOS); for cross-sectional studies, the Joanna Briggs Institute (JBI) critical appraisal checklist was used; and for experimental studies, the SYRCLE’s Risk of Bias Tool was applied. Results: Fourteen studies ultimately met the inclusion criteria. The evidence showed that diabetes increases gingival bleeding due to elevated levels of advanced glycation end-products (AGEs) and pro-inflammatory cytokines; reduces the efficiency of tooth movement; increases root resorption and affects bone remodeling; and compromises both periodontal and pulpal responses, thereby hindering tissue regeneration. It was also observed that the use of insulin or antidiabetic agents such as metformin may partially mitigate these adverse effects. Conclusions: This systematic review reveals a clear relationship between diabetes and various clinical aspects that influence the progression of orthodontic treatments. Nonetheless, further studies are needed to better understand the impact of this systemic condition on dental treatment outcomes. Full article

Tooth wear is a growing oral health concern with implications for function, esthetics, and psychological well-being, ultimately affecting oral health-related quality of life (OHRQoL). While clinical indices assess tooth wear severity, they fail to capture patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs). This narrative review aims to identify and synthesize the use of PROs and PROMs used in adults with tooth wear and to map their assessed domains against the Wilson and Cleary model of health outcomes, highlighting gaps and guiding the development of condition-specific instruments. A comprehensive search of the literature was conducted across PubMed, MEDLINE, and Embase. Studies involving PROMs in adults with tooth wear were included. Extracted data encompassed psychometric properties and domains assessed. PROMs such as the OHIP, OES, OIDP, and QMFQ have been frequently used, focusing on functional limitation, esthetic perception, and psychological distress. However, no single instrument comprehensively addresses all relevant domains of the Wilson and Cleary model. Moreover, variation in tools and constructs limits comparability across studies and clinical settings. Existing PROMs capture only partial aspects of the patient experience related to tooth wear. When mapping these instruments to a validated theoretical model, significant gaps become evident, especially in terms of general health perceptions and overall quality of life metrics. To improve the evaluation and management of tooth wear in clinical settings, it is essential to create a condition-specific PROM based on a solid conceptual framework. Full article

Background & Aims: treat-to-target approach is essential for improving outcomes in inflammatory bowel disease (IBD). This study aimed to assess real-world achievement in objective monitoring (clinical, biomarker, and endoscopic assessments) and the correlation between patient-reported outcomes (PROs) and treatment targets. Methods: This retrospective study included consecutive IBD patients from January 2020 to December 2024. Disease activity was assessed using the Harvey-Bradshaw Index (HBI), partial Mayo score, PRO2, and PRO3, along with C-reactive protein (CRP) levels and endoscopic scores (SES-CD, MES). Clinical outcomes were evaluated at baseline, 1 year, and 2 years. Results: Among 112 IBD patients (55% with CD, median age at diagnosis: 45.2 years), clinical remission rates at baseline, 1 year, and 2 years were; CD: 75.8%, 70.0%, and 55.8%; UC: 84.0%, 79.5%, and 81.4%. CRP normalization rates at the same time points were; CD: 54.8%, 41.7%, and 63.8% UC: 78.0%, 70.5%, and 81.8%. Endoscopic remission rates were; CD: 58.1%, 50.0%, and 50.0%, UC: 71.4%, 64.5%, and 51.7% Flare-ups were more frequent in CD than in UC (32% vs. 20%), with an 8.1% rate of IBD-related surgery. In CD, PRO2 and PRO3 strongly correlated with clinical remission (AUC = 0.885 and 0.881), moderately with biomarkers (AUC = 0.737 and 0.755), and modestly with endoscopic remission (AUC = 0.695 and 0.685). In UC, PRO2 showed a strong correlation with clinical remission (AUC = 0.972) and moderate correlations with biomarkers (AUC = 0.653) and endoscopy (AUC = 0.783). Conclusions: Clinical remission was more frequent in UC than in CD. PROs showed a strong correlation with clinical remission but only moderate associations with biomarkers and endoscopic remission in both CD and UC. Full article

(1) Background: Esthetic regenerative medicine is increasingly in demand for facial and neck rejuvenation due to its proven efficacy, safety profile, and minimal downtime. This study aimed to evaluate the role of standardized assessment tools in optimizing the outcomes of non-invasive regenerative esthetic technologies, both during the treatment course and in follow-up. (2) Methods: A literature review of the main articles published in peer-reviewed journals was conducted to identify high-quality studies addressing the use of validated esthetic scales and questionnaires (patient-reported outcomes) for evaluating the effectiveness of non-invasive regenerative treatments for the face and neck using accessible clinical tools such as photographs and 3D facial scanning. (3) Results: Clinician-reported outcomes (CROs) can be collected using standardized and reproducible photographic documentation and facial scans. The esthetic scales and classifications target both specific facial areas (e.g., upper third, perioral, periorbital) and overall skin appearance. Furthermore, advanced software allows overlay facial scan analysis and wrinkle mapping for precise quantification of improvements. In addition to objective CROs, patient-reported outcomes (PROs) offer essential insights into perceived esthetic changes, satisfaction, and emotional well-being, completing a multidimensional evaluation of treatment efficacy. (4) Conclusions: Standardized evaluation protocols based on accessible tools such as clinical photographs, 3D facial scans, and validated PRO questionnaires are essential for guiding effective, personalized regenerative treatments. Their integration into routine practice enhances clinical decision-making and patient satisfaction. While advanced tools like dermal probes may further refine assessments, they require specific expertise and resources and may be less practical for daily clinical use. Full article

Background/Objectives: Rho-associated coiled-coil-containing protein kinase inhibitors (ROCKis) have now become known as modulators of corneal endothelial wound repair and cell survival. However, evidence remains fragmented across laboratory and clinical reports. We performed a systematic review to synthesize preclinical and clinical data on ROCKis in corneal disease, assess their efficacy and safety, and identify research gaps. Methods: We searched PubMed, Web of Science, Scopus, and Google Scholar (until May 2025) for English-language original studies evaluating ROCKis in corneal models or patients. Inclusion criteria encompassed in vitro, ex vivo, in vivo, and clinical trials reporting functional outcomes (endothelial cell density, wound closure, visual acuity). Results: Thirty-one studies met criteria: 14 preclinical studies and 17 clinical studies. Preclinical models (rabbit, porcine, human explants) uniformly showed ROCKis (Y-27632, Ripasudil, Netarsudil, H-1152) accelerate corneal endothelial cell proliferation, migration, and restoration of a hexagonal monolayer with improved barrier and pump function over days to weeks. In 17 clinical investigations, topical Ripasudil or Netarsudil and cultured cell injections achieved significant corneal thinning, endothelial cell density and central corneal thickness changes, and visual acuity improvements (≥2 lines) with minimal adverse events. Overall bias was moderate in non-randomized studies and low in the RCTs. Conclusions: ROCKis demonstrate consistent pro-regenerative effects on corneal endothelium in multiple models and show promising clinical efficacy in Fuchs endothelial dystrophy and pseudophakic endothelial failure. Future work should explore novel delivery systems and larger controlled trials to optimize dosing, safety, and long-term outcomes. Full article

Objectives: This study explored the health-related quality of life (HRQoL), psychological health, and patient-reported outcomes (PROs) of patients with amyotrophic lateral sclerosis (ALS) in China, providing insights for enhancing clinical care. Methods: A cross-sectional study was conducted among Chinese ALS patients between February and May 2024. Demographics, clinical characteristics, and PROs were assessed. HRQoL and psychological health were evaluated via the 5-item amyotrophic lateral sclerosis assessment questionnaire (ALSAQ-5) and the 4-item patient health questionnaire (PHQ-4), respectively. Spearman’s rank correlation, multiple linear regression, and the Kruskal–Wallis H test were used to analyze associations between clinical factors, HRQoL, and psychological health. Results: A total of 237 participants aged 46–65 years (63.3%) were included. The mean ALSAQ-5 score was 64.86±19.34, indicating an impaired HRQoL, whereas the mean PHQ-4 score (5.82 ± 4.10,) suggested varied degree of anxiety and depression. Age, disease duration, ALS severity, fatigue, stress, and pain severity, and respiratory support were significantly associated with HRQoL (p < 0.05). Age, stress severity, and pain severity were significant predictors of psychological distress (p < 0.01). Patients reported diagnostic delay, profound lifestyle changes (96.4%), fear of paralysis (84.8%), and death (49.8%). Most patients (80.6%) expressed a strong desire to stop ALS progression, prioritizing treatments that improve breathing, muscle weakness, swallowing, and mobility issues. Conclusions: ALS profoundly impacts patients’ HRQoL and psychological health. Integrating PROs into clinical care strategies is crucial for improving patient outcomes and guiding treatment priorities. Full article