Search Results (281)

Background/Objectives: Tacrolimus, an immunosuppressant, is increasingly used topically in ophthalmology, particularly for conditions like vernal keratoconjunctivitis and post-keratoplasty rejection prophylaxis. This systematic review aims to evaluate the efficacy and safety of topical tacrolimus in these ocular conditions. Methods: A thorough search was conducted in PubMed and Cochrane Library for relevant studies published up to 16 March 2025. Studies were eligible for inclusion if they were randomized controlled trials investigating topical tacrolimus in human ocular disease, were published in English, and reported clearly defined outcomes. Exclusion criteria included non-randomized studies, animal studies, systemic treatments, non-English publications, and studies lacking clearly reported outcomes. Data regarding study design, patient demographics, intervention details, and outcomes were extracted and analyzed. The Cochrane risk-of-bias tool (RoB 2.0) was used to assess the risk of bias. Results: A total of 10 studies met the inclusion criteria, were retrieved, and were categorized as not highly biased after the risk-of-bias assessment. These studies were included in the systematic review, where a qualitative analysis took place. Our analysis revealed that the topical use of tacrolimus showed promising results, as it improved clinical signs and symptoms in most patients. In half of the studies, tacrolimus demonstrated superior efficacy compared to the control group, while in the remaining studies, it showed equivalent efficacy. Adverse effects, such as a burning sensation, were noted in 7/10 studies but were generally mild. The methodologies were somewhat heterogeneous, and some studies had small sample sizes. Conclusions: Topical tacrolimus shows promising effects in managing various ocular surface diseases. While randomized controlled trials provide evidence, further research with larger sample sizes is necessary to solidify its efficacy and safety profile compared to other immunosuppressants. Full article

(1) Background: Suicide is a worldwide leading cause of death among people with mental disorders. Psychoeducation is an integral component of mental health care that may offer patients valuable tools to understand their conditions, develop coping strategies, and engage more effectively in the treatment process. In the present scoping review, we aimed to summarize the evidence on the implementation of psychoeducational interventions in inpatient settings after suicide attempts. (2) Methods: In August 2024, we searched the Web of Knowledge (all databases), PsycINFO, and CINAHL databases following the PRISMA-ScR guidelines. We included original articles evaluating the effects of psychoeducational interventions for patients hospitalized in psychiatric settings after a suicide attempt. We provided a narrative synthesis of the study characteristics and the main findings of the included studies. (3) Results: We included five papers reporting the results of six studies, of which two were randomized controlled trials. Participants were diagnosed with diverse mental disorders, and interventions were generally short in the hospitalization phase, with follow-ups in the short or long term. Outcomes were focused on suicidal ideation, depressive symptoms, and general functioning, along with feasibility and acceptability of the intervention. Psychoeducational interventions were generally well accepted, but more evidence is needed to determine their efficacy. (4) Conclusions: Psychoeducational intervention in an inpatient psychiatric setting may be important for the prevention of future suicide attempts. Nevertheless, research on the topic is still scarce. Methodologically sound randomized controlled trials evaluating the long-term efficacy of psychoeducational interventions on suicide prevention are needed. Future research should also investigate the utility of psychoeducation in non-psychiatric inpatient settings. Full article

Obesity-related low-grade inflammation is a significant factor responsible for the development of metabolic syndrome and chronic diseases, which can begin even in early childhood. Recently, there has been growing interest in the impact of vitamin D3 supplementation on inflammatory markers in overweight and obese individuals; however, findings remain inconsistent. Therefore, we aimed to conduct a systematic review to assess the effects of vitamin D3 supplementation on inflammatory markers in overweight and obese children and adolescents, focused exclusively on the analysis of randomized controlled trials (RCTs) identified by searching PubMed, EMBASE, and Cochrane Library. The results of this study were synthesized and reported following the PRISMA statement. A total of 294 citations were identified through electronic literature searches, of which two RCTs were finally included in our systematic review. We found that vitamin D3 supplementation did not affect the changes in C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), but led to a decrease in leptin levels. The small number of studies meeting the inclusion criteria for our systematic review limits the value of the presented results, but also indicates the need for in-depth research on this topic. Full article

Background: Cannabidiol (CBD) has demonstrated potential as a therapeutic agent for muscle tension, pain, and sleep bruxism, yet its broader impact on comorbid conditions such as sleep disturbance and migraine disability remains underexplored. This study aimed to assess the effects of topical CBD on sleep quality and migraine-related disability in patients with bruxism-associated muscular pain. Methods: In a randomized, double-blind clinical trial, 60 participants with bruxism were allocated equally into three groups: control (placebo gel), 5% CBD gel, and 10% CBD gel. Participants applied the gel intraorally to the masseter muscles nightly for 30 days. Sleep quality and migraine-related disability were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Migraine Disability Assessment Scale (MIDAS), respectively. Surface electromyography (sEMG) and the Bruxoff^® device were used for objective evaluation of muscle tension and bruxism intensity. Results: Both CBD treatment groups demonstrated statistically significant improvements in PSQI and MIDAS scores compared to the control group (p < 0.001). No significant differences were observed between the 5% and 10% CBD groups, suggesting comparable efficacy. The sEMG findings corroborated a reduction in muscle tension. Improvements in sleep and migraine outcomes were positively correlated with reductions in muscle activity and pain. Conclusions: Topical CBD gel significantly improved sleep quality and reduced migraine-related disability in patients with bruxism-associated muscular pain, supporting its role as a multifaceted therapeutic option in the management of TMD and related comorbidities. Further research is needed to confirm long-term benefits and determine optimal dosing strategies. Full article

Background: Female Sexual Dysfunction (FSD) encompasses a range of conditions that can profoundly impact quality of life and intimate relationships. The primary classifications of FSD include female sexual interest and arousal disorder (FSIAD), genitopelvic pain and penetration disorder (GPPPD), female orgasmic disorder (FOD), and substance or medication-induced sexual dysfunction (SM-ISD). Despite its prevalence, FSD is often underdiagnosed and undertreated. Objectives: This scoping review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the existing literature on both U.S. Food and Drug Administration (FDA)-approved and off-label pharmacotherapies for FSD by study type, outcomes, and limitations. Eligibility Criteria: Eligible studies comprised randomized controlled trials (RCTs), systematic reviews, and cohort studies involving adult women (≥18 years) with any subtype of FSD. These studies assessed pharmacologic interventions against a comparator and reported at least one treatment efficacy outcome. Studies outside this scope were excluded. Sources of Evidence: A 25-year literature search was conducted using PubMed/MEDLINE, the Cochrane Library, reference lists of relevant articles, academic handbooks, and targeted journals. Charting Methods: Three independent reviewers screened and extracted data. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Findings were organized into summary tables and categorized by pharmaceutical agent, pertinent study information, outcomes, and limitations. Results: A total of 44 human-based pharmacologic studies met inclusion criteria. FDA-approved agents were the most thoroughly studied pharmacotherapies. Hormonal, topical, and adjunctive agents demonstrated less robust evidence. Heterogeneity in outcome measures and inadequate long-term data were common limitations. Conclusions: Pharmacologic treatment for FSD shows promise but requires further research. Individualized, multifaceted care is essential for optimizing FSD outcomes. Full article

This review explores the potential role of topical insulin drops in corneal regeneration by analyzing the mechanism of action and clinical outcomes. Corneal integrity restoration is crucial for ocular surface healing. This review synthesizes the current literature on topical insulin for neurotrophic keratopathy (NK), highlighting its mechanism of action, therapeutic potential, and clinical outcomes. Recent studies report high rates of epithelial regeneration, suggesting that topical insulin may be an effective adjunct or alternative to conventional treatments. Further randomized controlled trials are needed to confirm its long-term efficacy and optimal dosing. Methods: Considering the limited regenerative capacity of the corneal epithelium in NK and the increasing interest in novel therapy, we review the existing literature to evaluate the role and extent of topical insulin’s contribution to corneal healing by applying the PICO framework, which allows for a clear and systematic approach to literature selection and evaluation. The literature search and study selection were conducted manually following PRISMA guidelines. Conclusions: Most of the studies resulting from the selection have small samples, and there is a lack of large, randomized clinical trials. The evidence reviewed in this study suggests that topical insulin is a promising therapy for promoting corneal healing in neurotrophic keratopathy. While clinical trials have demonstrated significant epithelial regeneration, optimal dosing and long-term safety require further investigation. Compared to conventional treatments such as autologous serum or growth factor therapy, insulin eye drops provide a cost-effective alternative. Additional research through controlled trials is needed to formulate standardized therapeutic protocols and verify long-term outcomes. Full article

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. Full article

Background: Recurrent aphthous stomatitis (RAS) has been recognized as a pathology characterized by ulcerations of the oral mucosa with a wide cross-prevalence in the general population. The aim of the present investigation was to investigate a new gel formulation for the treatment of minor oral ulcers after 2 weeks of treatment. Materials and Methods: A randomized triple-blinded controlled trial was designed for the present purpose. A total of two different study groups was conceptualized: group I (placebo) and group II (active treatment). After the enrolment process, the subjects were included in a domiciliary treatment and evaluated by a blinded operator to clinical scoring and thermography assessment at the baseline, after 1 week, and 2 weeks. Results: A total of 60 patients were observed and treated in the present study. The mean age of the patients was 34.91 ± 7.27 years old for a total of 38 females and 22 males. At 1 and 2 weeks, a significant difference in clinical scoring was observed comparing group I and group II (p < 0.05). A significant reduction in pain score was detected in group II patients (p < 0.05) after the topical gel administration. Conclusions: According to the findings of this randomized trial, the gel treatment showed a significant decrease in the signs and symptoms of oral ulcerations and could be considered useful to ameliorate the clinical course of the disease. Full article

Purpose: Standard automated perimetry (SAP) remains the gold standard functional test in glaucoma, used primarily for evaluating peripheral vision loss. Central contrast sensitivity (CCS) has emerged as a potential early functional marker of glaucomatous damage. This systematic review aimed to describe the different methods used to measure CCS in randomized controlled trials (RCT) involving glaucoma patients. Methods: We searched the MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials, Epistemonikos, and ClinicalTrials.gov databases on 25 January 2023, and updated the search on 12 February 2025. Eligible studies comprised RCTs that reported CCS as an outcome in patients with glaucoma, suspected glaucoma, or ocular hypertension. No restrictions were placed on age, sex, ethnicity, geography, intervention, or publication year. Abstracts and full texts were screened independently by two reviewers. Descriptive statistics were used. No formal risk of bias assessment was performed, due to the descriptive nature of the review. Results: Of 1066 records screened, 31 studies met the eligibility criteria. The study sample size ranged from 7 to 207 (median: 23), with most studies involving primary open-angle glaucoma. Interventions were diverse, mainly involving topical medications, with timolol being the most frequent. Eleven CCS test methods were identified. Five studies did not report the method used. The CSV-1000 was the most commonly used test, being applied in 11 studies. Conclusions: CCS has been measured using a wide range of methods in glaucoma RCTs, with limited standardization. Most of the included studies were small, variably reported, and conducted over 10 years ago, suggesting a decreasing interest in CCS as an outcome measure in glaucoma RCTs. Funding: This review was funded by Oslo University Hospital and the Research Council of Norway. Registration: This review was registered on the OSF. 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

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with the multifaceted nature of addiction by targeting both peripheral metabolic and central reward pathways. This review focused on the current clinical trials and real-world evidence regarding the effects of GLP-1RAs as novel therapeutics for AUD. We also discussed early but encouraging results from clinical trials in AUD, observational and real-world evidence, safety profiles, psychiatric considerations, and future directions leading beyond GLP-1RAs. Methods: A comprehensive English-language literature search was conducted per PRISMA guidelines across PubMed, Medline, Google Scholar, Web of Science, and trial registries. Using targeted keywords, we identified relevant clinical and observational studies on GLP-1RAs for alcohol use disorder, excluding off-topic or non-English works and assessing all studies for eligibility. Results: Out of 1080 records identified, seven studies met the inclusion criteria. The findings from recent clinical trials, large-scale observational studies, and real-world evidence suggest that GLP-1RAs may significantly reduce alcohol consumption, cravings, and alcohol-related hospitalizations. Their central effect on reward processing, coupled with a generally favorable safety profile, supports their potential therapeutic role beyond metabolic disorders. Conclusions: Emerging evidence positions GLP-1RAs as a promising new pharmacologic approach for managing AUD. Ongoing and future research should prioritize larger, longer-duration randomized controlled trials that include diverse populations, with specific attention to treatment motivation, co-occurring psychiatric conditions, and long-term outcomes. Full article

This study aimed to evaluate the effects of a proprietary plant-based formulation of Astragalus membranaceus and Centella asiatica saponins (ACS) on skin health, as both a cosmetic ingredient and a functional supplement. In this randomized, double-blind, placebo-controlled trial, 150 healthy adults were assigned to groups using topical ACS cream, oral ACS capsules, combined treatments, or corresponding placebos. Skin brightness, moisture, elasticity, melanin value, pore count, texture, and collagen content were assessed over 4 to 12 weeks. After 4 weeks of topical ACS application, skin brightness improved by 2.5%, elasticity by 6.5%, melanin decreased by 5.2%, pores reduced by 10.6%, and collagen increased by 8.7% (p < 0.05). After 12 weeks of oral ACS, brightness, elasticity, texture, and collagen significantly improved (p < 0.05). The combined treatment group showed the greatest improvements, including a 4.2% increase in brightness, 12.9% increase in moisture, 9.0% elasticity increase, and a 28.5% reduction in pore count (p < 0.05). ACS, whether used topically, orally, or in combination, effectively enhances skin health and offers a natural solution for skin rejuvenation. Full article

Diabetic foot ulcers (DFUs) constitute a severe and debilitating complication of diabetes, imposing a substantial global health burden due to their intricate pathophysiology and impaired wound healing processes. Vitamin D deficiency is highly prevalent among diabetic populations, and accumulating evidence indicates its potential involvement in the pathogenesis and prognosis of DFUs. This review comprehensively explores the diverse roles of vitamin D in DFUs, encompassing its molecular mechanisms such as immunomodulation, promotion of angiogenesis, neuroprotection, and induction of antimicrobial peptides, as well as the metabolic characteristics associated with various vitamin D forms and compromised vitamin D receptor (VDR) signaling pathways. Although robust observational studies have established an association between vitamin D deficiency and adverse outcomes in DFUs, the clinical validation of supplementation efficacy through randomized controlled trials (RCTs) remains constrained by limitations such as small sample sizes, heterogeneity in study protocols, and insufficient long-term follow-up. This highlights the critical need for large-scale, high-quality studies to ascertain optimal treatment regimens and to cater to individualized patient requirements, particularly for individuals with obesity or those with renal impairments. Innovative strategies, such as the topical administration of vitamin D through intelligent delivery systems leveraging advanced biomaterials like nanofibers and hydrogels, exhibit substantial preclinical potential in enhancing stability, achieving targeted controlled release, and augmenting local biological effects, including the induction of antimicrobial peptides. Nevertheless, significant challenges persist in conclusively establishing clinical efficacy, comprehensively elucidating the underlying mechanisms, ensuring the safe translation of novel delivery systems, and developing personalized therapeutic strategies. The future success of these interventions hinges on meticulous research and interdisciplinary collaboration to seamlessly integrate validated vitamin D-based interventions into a comprehensive multidisciplinary management framework for DFUs, thereby holding promise for improving the clinical outcomes of this debilitating condition. Full article

Background/Objectives: Epigallocatechin gallate (EGCG) is the most abundant catechin in green tea. Based on results from in vitro studies, EGCG—with its wide range of beneficial properties—has been considered a promising option for the treatment of patients with various skin conditions. Methods: The aim of this systematic review, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was to evaluate the efficacy and safety of EGCG in the treatment and prevention of various types of dermatitis. Results: A search of PubMed, Embase, CENTRAL, and ClinicalTrials.gov databases identified eight trials (including four randomized trials) that investigated the use of EGCG alone (as a saline solution) for the treatment and prevention of radiation-induced dermatitis or as a component of a shampoo or cream for atopic and seborrheic scalp dermatitis. The identified single-arm and randomized controlled trials were characterized by low methodological quality, were in early phases of development, and/or included a small number of participants. The topical effect of EGCG on the severity of dermatitis was shown to depend on the type of dermatitis, concentration, and pharmaceutical form used. The administration of EGCG resulted in a significant reduction in skin symptoms in patients with radiation-induced dermatitis compared with placebo and with baseline, while in seborrheic dermatitis of the scalp, the results of shampoo with EGCG component were similar to those of active conventional treatment. The EGCG treatment was generally well tolerated, with no serious treatment-related adverse events. Conclusions: This study showed that EGCG can be a promising option for the treatment and prevention of various types of dermatitis. However, due to the small sample size, large, well-designed, randomized phase III trials are needed to confirm its safety and efficacy. Full article

Background and Objectives: The gut–liver axis plays a crucial role in the development of post-surgical infections. Surgery-induced dysbiosis can lead to increased bacterial translocation, impairing the liver’s detoxification capacity and negatively affecting surgical outcomes. Following liver surgery, approximately a third of the patients develop bacterial infections, with a high risk of bacteremia or even sepsis-related liver failure and death. The potential advantages of administering pro- or synbiotics before/after surgery remain a topic of discussion. Therefore, a systematic review of randomized clinical trials comparing patients with and without supplementation and their outcomes and effects after liver resection (LR) or liver transplantation (LT) was conducted. Materials and Methods: A computer-based search of electronic databases was conducted to gather randomized controlled trials (RCTs) that focused on probiotic/synbiotic use during the perioperative period for liver surgery patients. Two researchers independently screened the studies, extracted the data, evaluated the risk of bias, and performed a meta-analysis using RevMan Web. Results: Our research revealed 19 relevant randomized controlled studies that included a total of 1698 patients on the perioperative use of pro-/symbiotic administration in liver surgery. Eight studies were performed on liver transplantation (LT), and 11 studies were performed for liver resection (LR). The results of the meta-analysis demonstrated that the probiotic group exhibited lower rates of postoperative infectious complications (OR = 0.34; 95%CI 0.25 to 0.45; p < 0.0001), hospital stay duration (SMD = −0.13; 95%CI −0.25 to −0.00; p = 0.05), lower serum endotoxin levels (SMD = −0.39%CI −0.59 to −19; p < 0.0001), and white blood cell counts (SMD = −SMD = −0.35; 95%CI −0.56 to −0.13; p = 0.002) compared to the control group. Further, with regard to liver function, we observed significant postoperative differences in alanine aminotransferase (ALT)-levels (SMD = −0.46; 95%CI −0.63 to −0.29; p < 0.0001), aspartate aminotransferase (AST) levels (SMD = −0.53; 95%CI −0.71 to −0.34; p < 0.0001), bilirubin levels (SMD = −0.35; 95%CI −0.50 to −0.19; p < 0.0001), and international ratio (INR) levels (SMD = −0.1; 95%CI −0.12 to −0.08; p ≤ 0.0001), favoring the symbiotic group compared to the control group. Conclusions: The use of pro-/synbiotics during the perioperative period reduces the risk of postoperative infections, support postoperative liver function, and recovery and shortens hospital stays for liver surgery patients. However, they do not appear to particularly aid in inflammation reduction. Full article