Search Results (6,714)

The efficacy of botulinum toxin A (BoNT) in alleviating motor symptoms of cervical dystonia (CD) has been well established, and it is the treatment of choice in this disease. Lately, the effect of BoNT on non-motor symptoms (NMS) such as cognitive function, depression, anxiety, pain, and sleep disturbance has been observed in patients with CD. A comprehensive clinical and functional assessment of motor (dystonia severity, gait) and non-motor symptoms (cognitive functions, depression, anxiety, sleep, and pain) has been performed in a total of 34 adult patients with cervical dystonia before and after BoNT treatment. Results have also been compared to a control group. Significant improvements in the scales assessing dystonia severity have been observed, which is in line with previous studies on the effect of BoNT on motor symptoms in dystonia. Interestingly, the results also clearly indicate that BoNT has a positive effect on NMS. Among the studied non-motor domains, depression and cognitive functions improved the most after the treatment procedure. The study highlights the potential of BoNT to positively influence non-motor symptoms in patients with cervical dystonia, although its effect on various NMS is not equal. Full article

Objective: Visceral leishmaniasis (VL), a Neglected Tropical Disease caused by Leishmania donovani, remains insufficiently addressed by current therapies due to high toxicity, poor efficacy, and immunosuppressive complications. This study aimed to identify and characterize repurposed drugs that simultaneously target parasite-encoded and host-associated mechanisms essential for VL pathogenesis. Methods: Two complementary in silico drug repurposing strategies were employed. The first method utilized electron–ion interaction potential (EIIP) screening followed by molecular docking and molecular dynamics (MD) simulations targeting two L. donovani proteins: Rab5a and pteridine reductase 1 (PTR1). The second approach employed network-based drug repurposing using the Drugst.One platform, prioritizing candidates via STAT3-associated gene networks. Predicted drug–target complexes were validated by 100 ns MD simulations, and pharmacokinetic parameters were assessed via ADMET profiling using QikProp v7.0 and SwissADME web server. Results: Entecavir and valganciclovir showed strong binding to Rab5a and PTR1, respectively, with Glide Scores of −9.36 and −9.10 kcal/mol, and corresponding MM-GBSA ΔG_bind values of −14.00 and −13.25 kcal/mol, confirming their stable interactions and repurposing potential. Network-based analysis identified nifuroxazide as the top candidate targeting the host JAK2/TYK2–STAT3 axis, with high stability confirmed in MD simulations. Nifuroxazide also displayed the most favorable ADMET profile, including oral bioavailability, membrane permeability, and absence of PAINS alerts. Conclusions: This study highlights the potential of guanine analogs such as entecavir and valganciclovir, and the nitrofuran derivative nifuroxazide, as promising multi-target drug repurposing candidates for VL. Their mechanisms support a dual strategy targeting both parasite biology and host immunoregulation, warranting further preclinical investigation. Full article

Background: Hip fractures represent a major clinical challenge, particularly in elderly and frail patients, where postoperative pain control must balance effective analgesia with motor preservation to facilitate early mobilization. Various regional anesthesia techniques are used in this setting, including the pericapsular nerve group (PENG) block, fascia iliaca compartment block (FICB), femoral nerve block (FNB), and quadratus lumborum block (QLB), yet optimal strategies remain debated. Objectives: To systematically review the efficacy, safety, and clinical applicability of major regional anesthesia techniques for pain management in hip fractures, including considerations of fracture type, surgical approach, and functional outcomes. Methods: A systematic literature search was conducted following PRISMA 2020 guidelines in PubMed, Scopus, Web of Science, and the virtual library of the Hospital Central de la Defensa “Gómez Ulla” up to March 2025. Inclusion criteria were RCTs, systematic reviews, and meta-analyses evaluating regional anesthesia for hip surgery in adults. Risk of bias in RCTs was assessed using RoB 2.0, and certainty of evidence was evaluated using the GRADE approach. Results: Twenty-nine studies were included, comprising RCTs, systematic reviews, and meta-analyses. PENG block demonstrated superior motor preservation and reduced opioid consumption compared to FICB and FNB, particularly in intracapsular fractures and anterior surgical approaches. FICB and combination strategies (PENG+LFCN or sciatic block) may provide broader analgesic coverage in extracapsular fractures or posterior approaches. The overall risk of bias across RCTs was predominantly low, and certainty of evidence ranged from moderate to high for key outcomes. No significant safety concerns were identified across techniques, although reporting of adverse events was inconsistent. Conclusions: PENG block appears to offer a favorable balance of analgesia and motor preservation in hip fracture surgery, particularly for intracapsular fractures. For extracapsular fractures or posterior approaches, combination strategies may enhance analgesic coverage. Selection of block technique should be tailored to fracture type, surgical approach, and patient-specific functional goals. Full article

Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and characterized a novel lidocaine and epinephrine co-loaded liquid crystalline precursor system (LCPS) for topical anesthesia. The formulation was structurally characterized using polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological behavior was assessed through continuous and oscillatory rheological analyses. Texture profile analysis, in vitro mucoadhesive force evaluation, in vitro drug release and permeation studies, and an in vivo toxicity assay using the chicken chorioallantoic membrane (CAM) model were also conducted. Results: PLM and SAXS confirmed the transition of the LCPS from a microemulsion to a lamellar liquid crystalline structure upon contact with artificial saliva. This transition enhanced formulation consistency by over 100 times and tripled mucoadhesion strength. The LCPS also provided controlled drug release, reducing permeation flow by 93% compared to the commercial formulation. Importantly, the CAM assay indicated that the LCPS exhibited similar toxicity to the commercial product. Conclusions: The developed LCPS demonstrated promising physicochemical and biological properties for topical anesthesia, including enhanced mucoadhesion, controlled drug delivery, and acceptable biocompatibility. These findings support its potential for in vivo application and future clinical use to reduce pain during dental anesthesia procedures. Full article

Background: Electrocardiograms (EKGs) are essential tools in emergency medicine, often used to evaluate chest pain, dyspnea, and other symptoms suggestive of cardiac dysfunction. Yet, EKGs are not universally administered to all emergency department (ED) patients. Understanding and predicting which patients receive an EKG may offer insights into clinical decision making, resource allocation, and potential disparities in care. This study examines whether integrating structured clinical data with free-text patient narratives can improve prediction of EKG utilization in the ED. Methods: We conducted a retrospective observational study to predict electrocardiogram (EKG) utilization using data from 13,115 adult emergency department (ED) visits in the nationally representative 2021 National Hospital Ambulatory Medical Care Survey–Emergency Department (NHAMCS-ED), leveraging both structured features—demographics, vital signs, comorbidities, arrival mode, and triage acuity, with the most influential selected via Lasso regression—and unstructured patient narratives transformed into numerical embeddings using Clinical-BERT. Four supervised learning models—Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF) and Extreme Gradient Boosting (XGB)—were trained on three inputs (structured data only, text embeddings only, and a late-fusion combined model); hyperparameters were optimized by grid search with 5-fold cross-validation; performance was evaluated via AUROC, accuracy, sensitivity, specificity and precision; and interpretability was assessed using SHAP values and Permutation Feature Importance. Results: EKGs were administered in 30.6% of adult ED visits. Patients who received EKGs were more likely to be older, White, Medicare-insured, and to present with abnormal vital signs or higher triage severity. Across all models, the combined data approach yielded superior predictive performance. The SVM and LR achieved the highest area under the ROC curve (AUC = 0.860 and 0.861) when using both structured and unstructured data, compared to 0.772 with structured data alone and 0.823 and 0.822 with unstructured data alone. Similar improvements were observed in accuracy, sensitivity, and specificity. Conclusions: Integrating structured clinical data with patient narratives significantly enhances the ability to predict EKG utilization in the emergency department. These findings support a personalized medicine framework by demonstrating how multimodal data integration can enable individualized, real-time decision support in the ED. Full article

Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] years) with herniated discs and LBP, alongside healthy controls, to investigate changes in the extracellular matrix (ECM) and neurochemical alterations. Disc degeneration was assessed using MRI (Pfirrmann grading) and histology (Sive’s criteria). Histochemical and immunohistochemical methods were used to evaluate aggrecan content, calcification, and the expression of nerve growth factor (NGF), substance P (SP), and S-100 protein. MRI findings included Pfirrmann grades V (30.55%), IV (61.11%), III (5.56%), and II (2.78%). Severe histological degeneration (10–12 points) was observed in three patients. Aggrecan depletion correlated with longer pain duration (r = 0.449, p = 0.031). NGF expression was significantly elevated in degenerated discs (p = 0.0287) and strongly correlated with SP (r = 0.785, p = 5.268 × 10⁻⁹). Free nerve endings were identified in 5 cases. ECM calcification, present in 36.1% of patients, was significantly associated with radiculopathy (r = 0.664, p = 0.005). The observed co-localization of NGF and SP suggests a synergistic role in pain development. These results indicate that in young individuals, aggrecan loss, neurochemical imbalance, and ECM calcification are key contributors to DDD and chronic LBP. Full article

Background: Fear of falling (FOF) is a significant concern among older adults, especially after total knee arthroplasty (TKA). FOF can limit daily activities, reduce quality of life, and hinder recovery. This study aimed to investigate the prevalence, severity, and impacts of FOF in patients undergoing TKA and identify factors contributing to increased FOF. Methods: A prospective observational study was conducted at King Abdulaziz Medical City in Riyadh, Saudi Arabia, from April 2024 to December 2024. This study included 52 participants aged 20 to 75 years who had undergone primary TKA. Data were collected at two time points: after TKA and at three months post-surgery. The Short Falls Efficacy Scale-International (SFES-I) was used to assess the severity of FOF, and the Short Form 36 (SF-36) was used to measure the quality of life. Descriptive statistics, t-tests, and logistic regression were used for analysis. Results: This study included 52 participants (mean age: 63.77 ± 6.65 years; 82.7% female). Post-TKA, all participants exhibited high FOF (mean SFES-I score: 56.75 ± 8.30). After three months, the mean SFES-I score decreased significantly to 49.04 ± 12.45 (t = 4.408, p < 0.05). Post-TKA, SF-36 showed significant improvements in the physical function, role of physical limitations, bodily pain, vitality, social function, role of emotional limitations, and mental health subdomains. Bilateral total knee arthroplasty, body mass index, and some SF-36 subcomponents—such as general health, vitality, and role of emotional limitations—were identified as factors leading to increased FOF. Conclusions: FOF remains prevalent and severe in TKA patients, even at three months post-surgery, affecting rehabilitation outcomes. Early identification and tailored interventions for FOF should be considered essential components of comprehensive TKA recovery programs. Full article

Study Design: Prospective observational study. Background: Lumbar spinal stenosis (LSS) impairs balance and gait function, increasing fall risk and limiting quality of life. Although postoperative recovery of balance is clinically important, longitudinal data using multidimensional balance assessments are limited. Methods: A prospective cohort study was conducted in 101 patients (mean age 74.9 ± 6.9 years) undergoing surgery for LSS. The Brief Balance Evaluation Systems Test (Brief BESTest), Oswestry Disability Index (ODI), Modified Falls Efficacy Scale (MFES), Zurich Claudication Questionnaire (ZCQ), and Visual Analog Scales (VAS) for pain/numbness were evaluated preoperatively and at 6 and 12 months postoperatively. Changes over time and correlations between Brief BESTest and PROMs were analyzed. Results: The total Brief BESTest score significantly improved from 13.3 ± 5.3 preoperatively to 16.1 ± 5.1 at 6 months and 16.0 ± 5.1 at 12 months (p < 0.01). Subdomains including Anticipatory Adjustments, Postural Responses, Sensory Orientation, and Stability in Gait improved significantly, while Stability Limits did not. At 12 months postoperatively, ODI decreased by 19.1%, ZCQ symptom and function scores improved by 0.8 and 0.9 points, respectively, and VAS scores improved by 17.1 mm for low back pain, 26.5 mm for lower limb pain, and 19.5 mm for numbness, all showing marked improvements from baseline. MFES also increased significantly postoperatively. The Brief BESTest score correlated significantly with MFES and ZCQ-PFS at baseline, and with ODI, ZCQ, and VAS scores at 12 months. Conclusions: Balance ability in LSS patients improved after surgery, as measured by the Brief BESTest, with clinically meaningful changes maintained for 12 months. Improvements in balance were significantly associated with reductions in pain, disability, and fear of falling, suggesting the Brief BESTest is a comprehensive indicator of postoperative recovery. Full article

Background: Quality care of individuals with sickle cell disease (SCD) is dependent upon education of the providers on their care team. Previous studies demonstrate lack of resident and provider comfort regarding care of patients with SCD, yet none have assessed these in medical students. Objective: This study aims to evaluate the adequacy of the research instrument for measuring medical students’ knowledge, confidence, and comfort regarding SCD and related complications prior to wider distribution. Methods: A self-assessment survey was distributed to medical students at two universities to evaluate their knowledge, confidence, and comfort in general SCD topics, in all clinical settings, and regarding common complications. Results: Of the 98 responses, knowledge (p < 0.001) and confidence (p = 0.02) were significantly different between topics, including epidemiology and genetics, pathophysiology, and treatment options. For “treatment options”, there were significant differences in knowledge (p = 0.02) and confidence (p = 0.02) between medical students at different levels of training. Students felt least knowledgeable and least comfortable with care of pregnant women and most knowledgeable and most comfortable with acute pain management. Caring for patients with specific SCD-related conditions increased knowledge and comfort across all domains. Conclusions: This instrument was adequate for measuring knowledge, confidence, and comfort in caring for those with SCD across all clinical settings. We identified a lack of knowledge, confidence, and comfort regarding treatment for those with SCD starting early in medical careers, which improves after caring for patients with various complications. Thus, educating and providing SCD patient experiences is crucial for medical student management confidence related to SCD. Full article

Background/Objectives: Adult Spinal Deformity (ASD) is a pathologic malalignment of the spine that can lead to significant reductions in quality of life, functional limitations, and increased morbidity. While poor mental health is commonly observed among patients undergoing ASD surgery, its impact on surgical outcomes remains poorly understood. We conducted a systematic review and meta-analysis to examine the association between preoperative mental health and outcomes following surgical correction for ASD. Methods: A comprehensive search of MEDLINE, Embase, Web of Science, and Scopus was performed from inception to April 2025 to identify studies investigating the relationship between preoperative mental health and postoperative health-related quality of life outcomes or complications. Data was pooled using a restricted maximum likelihood (REML) random-effects model. Heterogeneity was assessed using Cochran’s Q statistic, and between-study variance was reported as τ². Study quality was assessed with the Newcastle–Ottawa Scale, and risk of bias was evaluated using the ROBINS-I tool. Results: Twenty-four studies comprising a total of 248,427 patients met inclusion criteria. In pooled analyses, patients with poor preoperative mental health showed comparable improvements in health-related quality of life measures after surgery (standardized mean difference [SMD] −0.04, 95% CI −0.30 to 0.22; I² = 91.5%, τ² = 0.42) and in pain scores (SMD −0.15, 95% CI −0.42 to 0.11; I² = 71.8%, τ² = 0.09). However, patients with poor mental health had significantly higher odds of postoperative complications (odds ratio [OR] 1.44, 95% CI 1.23 to 1.67; I² = 97.4%, τ² = 0.08). These patients also demonstrated worse preoperative disease severity (SMD –0.94, 95% CI −1.41 to −0.47; I² = 95.5%, τ² = 1.64) and worse postoperative disease severity (SMD –0.34, 95% CI −0.44 to −0.25; I² = 48.9%, τ² = 0.03). Conclusions: While patients with poor preoperative mental health have a greater disease severity both before and after ASD surgery, they appear to experience comparable benefits from surgical intervention compared to those without. Recognizing and managing mental health may be useful in preoperative management of ASD patients. Further prospective studies to further elucidate these associations are necessary. Full article

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Objective: This study aimed to improve the understanding of the lives of patients with chronic neuropathic pain planned for invasive motor cortex stimulation (iMCS) and assess their expectations towards this intervention and its impact. Methods: Semi-structured face-to-face interviews were conducted until saturation of data was reached. Patients were recruited from one university medical center in the Netherlands. All interviews were audio-recorded, transcribed verbatim, and subjected to thematic analysis using iterative and inductive coding by two researchers independently. Results: Fifteen patients were included (11 females; mean age 63 ± 9.4 yrs). Analysis of the coded interviews revealed seven themes: (1) the consequences of living with chronic neuropathic pain; (2) loss of autonomy and performing usual activities; (3) balancing energy and mood; (4) intimacy; (5) feeling understood and accepted; (6) meaning of life; and (7) the expectations of iMCS treatment. Conclusions: This is the first qualitative study that describes the suffering of patients with chronic neuropathic pain, and their expectations prior to invasive brain stimulation. Significant themes in the lives of patients with chronic pain have been brought to light. The findings strengthen communication between physicians, caregivers, and patients. Practice Implications: The insights gathered from the interviews create a structured framework for comprehending the values and expectations of patients living with central pain and reveal the impact of symptoms due to the central pain. This knowledge improves the communication between physicians and caregivers on one side and the patient on the other side. Furthermore, the framework enhances the capacity for shared decision-making, particularly in managing expectations related to iMCS. Full article

Background: Dentinal hypersensitivity (DH) significantly impacts oral health-related quality of life. While global prevalence estimates range from 10–15%, region-specific data from Saudi Arabia remain limited. This study also aligns with Saudi Vision 2030’s mental health initiatives, as DH-associated anxiety impacts overall well-being. This study assessed DH prevalence and quality of life impact among Saudi adults. Methods: A cross-sectional online survey was conducted among 748 Saudi adults aged ≥ 18 years between April and May. Data were collected using a validated Arabic Dentinal Hypersensitivity Experience Questionnaire (DHEQ) alongside socio-demographic variables. Participants reporting DH symptoms within 12 months were included in impact analyses. Descriptive statistics and one-way ANOVA examined associations between DHEQ scores and participant characteristics. Results: Self-reported DH prevalence was 54.3% (n = 406), substantially exceeding global estimates. Among affected individuals, mean DHEQ score was 0.56 ± 0.19, indicating moderate-to-substantial quality-of-life impact. Functional limitations were most affected, particularly enjoyment of eating and drinking (0.72 ± 0.21). Significant associations were identified between higher DHEQ scores and age extremes (<18 and >35 years; p < 0.001), higher income levels (p = 0.032), fewer teeth (p = 0.040), and dental pain presence (p = 0.009). Sex, residence, education, and employment showed no significant associations. Conclusions: More than half of Saudi adults reported DH symptoms, representing a significant public health concern with substantial quality of life implications. Prevalence substantially exceeds global estimates, highlighting the need for targeted interventions. Age, income, tooth count, and pain presence emerged as key factors. These findings support developing population-specific prevention strategies, particularly targeting younger and older adults with tooth loss. Full article

Background: Multisegmental lumbar degenerative disease (ms-LDD) is a common condition in older adults, often requiring surgical intervention. While rigid stabilization remains the gold standard, it is associated with complications such as adjacent segment disease (ASD), higher blood loss, and longer recovery times. The Dynesys dynamic stabilization system offers an alternative by preserving motion while stabilizing the spine. However, data comparing Dynesys with fusion in multisegmental cases are limited. Objective: This study evaluates the clinical and radiographic outcomes of Dynesys dynamic stabilization versus rigid stabilization in the treatment of ms-LDD. Methods: A retrospective analysis was conducted on 53 patients (mean age: 62.25 ± 15.37 years) who underwent either Dynesys dynamic stabilization (n = 27) or PLIF (n = 26) for ms-LDD involving at least seven motion segments. Clinical outcomes were assessed using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), while radiological parameters such as lumbar lordosis (LL), sagittal vertical axis (SVA), and spinopelvic parameters (pelvic incidence, pelvic tilt and, sacral slope) were analyzed. A two-stage surgical approach was employed in the Dynesys group to enhance osseointegration, particularly in elderly osteoporotic patients. Results: Both groups showed significant improvements in VAS and ODI scores postoperatively (p < 0.001), with no significant differences between them. However, the Dynesys group demonstrated superior sagittal alignment correction, with a significant increase in LL (p < 0.002) and a significant decrease in SVA (p < 0.0015), whereas changes in the rigid stabilization group were not statistically significant. Additionally, the Dynesys group had fewer complications, including a lower incidence of ASD (0 vs. 6 cases). The two-stage technique facilitated improved screw osseointegration and reduced surgical risks in osteoporotic patients. Conclusions: Dynesys dynamic stabilization is an effective alternative to rigid stabilization in ms-LDD, offering comparable pain relief and functional improvement while preserving motion and reducing ASD risk. The two-stage approach enhances long-term stability, making it particularly suitable for elderly or osteoporotic patients. Further long-term studies are needed to confirm these findings. Full article

Background: Pain is a problem faced by critically ill surgical patients and has a major impact on their outcomes. Pain assessment is therefore essential for effective pain management, with a combination of pharmacological and non-pharmacological treatment. Clinical supervision, supported by models such as SafeCare, can improve professional development, safety and the quality of care in intensive care units. Objectives: This study aimed to: (1) assess current pain assessment practices in a polyvalent Intensive Care Unit (ICU) in the Porto district; (2) identify nurses’ training needs regarding the Clinical Supervision-Sensitive Indicator—Pain; and (3) evaluate the impact of clinical supervision sessions on pain assessment practices. Methods: A quantitative, quasi-experimental, cross-sectional study with a pre- and post-intervention design was conducted. Based on the SafeCare model, it included a situational diagnosis, 6 clinical supervision sessions (February 2023), and outcome evaluation via nursing record audits (November 2022 and May 2023) in 31 total critical ill patients. Pain was assessed using standardised tools, in line with institutional protocols. Data was analysed using Software Statistical Package for the Social Sciences v25.0. Results: Pain was highly prevalent in the first 24 h, decreasing during hospitalisation. Generalised acute abdominal pain predominated, with mild to moderate intensity, and was exacerbated by wound care and mobilisation/positioning. Pain management combined pharmacological and non-pharmacological treatment. There was an improvement in all the parameters of the pain indicator post-intervention. Conclusions: Despite routine assessments, gaps remained in reassessing pain post-analgesia and during invasive procedures. Targeted clinical supervision and ongoing training proved effective in improving compliance with protocols and supporting safer, more consistent pain management. Full article