Search Results (2,003)

The evidence for photobiomodulation in reducing postoperative pain after endodontic instrumentation is classified as low or very low certainty, indicating a need for further research. Longitudinal pain assessments over 24 h are crucial, and studies should explore these pain periods. Background/Objectives: This double-blind, randomized controlled clinical trial evaluated the effect of PBM on pain following single-visit endodontic treatment of maxillary molars at 4, 8, 12, and 24 h. Primary outcomes included pain at 24 h; secondary outcomes included pain at 4, 8, and 12 h, pain during palpation/percussion, OHIP-14 analysis, and frequencies of pain. Methods: Approved by the Research Ethics Committee (5.598.290) and registered in Clinical Trials (NCT06253767), the study recruited adults (21–70 years) requiring endodontic treatment in maxillary molars. Fifty-eight molars were randomly assigned to two groups: the PBM Group (n = 29), receiving conventional endodontic treatment with PBM (100 mW, 333 mW/cm², 9 J distributed at 3 points near root apices), and the control group (n = 29), receiving conventional treatment with PBM simulation. Pain was assessed using the Visual Analog Scale. Results: Statistical analyses used chi-square and Mann–Whitney tests, with explained variance (η²). Ten participants were excluded, leaving 48 patients for analysis. No significant differences were observed in postoperative pain at 24, 4, 8, or 12 h, or in palpation/percussion or OHIP-14 scores. Pain frequencies ranged from 12.5% to 25%. Conclusions: PBM does not influence post-treatment pain in maxillary molars under these conditions. These results emphasize the importance of relying on well-designed clinical trials to guide treatment decisions, and future research should focus on personalized dosimetry adapted to the anatomical characteristics of the treated dental region to enhance the accuracy and efficacy of therapeutic protocols. Full article

Background/Objectives: Cannabidiol (CBD) is a non-intoxicating cannabinoid touted for a variety of medical benefits, including alleviation of anxiety. While legalization of hemp-derived products in the United States (containing ≤0.3% delta-9-tetrahydrocannabinol [d9-THC] by weight) has led to a rapid increase in the commercialization of hemp-derived CBD products, most therapeutic claims have not been substantiated using clinical trials. This trial aimed to assess the impact of 6 weeks of treatment with a proprietary hemp-derived, full-spectrum, high-CBD sublingual solution similar to those available in the marketplace in patients with anxiety. Methods: An open-label pilot clinical trial (NCT04286594) was conducted in 12 patients with at least moderate levels of anxiety. Patients self-administered a hemp-derived, high-CBD sublingual solution twice daily during the 6-week trial (target daily dose: 30 mg/day CBD). Clinical change over time relative to baseline was assessed for anxiety, mood, sleep, and quality of life, as well as changes in cognitive performance on measures of executive function and memory. Safety and tolerability of the study product were also evaluated. Results: Patients reported significant reductions in anxiety symptoms over time. Concurrent improvements in mood, sleep, and relevant quality of life domains were also observed, along with stable or improved performance on all neurocognitive measures. Few side effects were reported, and no serious adverse events occurred. Conclusions: These pilot findings provide initial support for the efficacy and tolerability of the hemp-derived, high-CBD product in patients with moderate-to-severe levels of anxiety. Double-blind, placebo-controlled studies are indicated to obtain robust data regarding efficacy and tolerability of these types of products for anxiety. Full article

This pilot, randomized, double-blind, placebo-controlled trial investigated the effects of branched-chain amino acids (BCAAs)—provided in a 2:1:1 ratio of leucine:isoleucine:valine—combined with exercise on fatigue, physical performance, and quality of life in older adults. Twenty participants (63% female; BMI: 35 ± 2 kg/m²; age: 70.5 ± 1.2 years) were randomized to 8 weeks of either exercise + BCAAs (100 mg/kg body weight/d) or exercise + placebo. The program included moderate aerobic and resistance training three times weekly. Physical function was assessed using handgrip strength, chair stands, gait speed, VO₂ max, and a 400 m walk. Psychological health was evaluated using the CES-D, Fatigue Assessment Scale (FAS), Insomnia Severity Index (ISI), and global pain, fatigue, and quality of life using a visual analog scale (VAS). Significant group x time interactions were found for handgrip strength (p = 0.03), chair stands (p < 0.01), and 400 m walk time (p < 0.01). Compared to exercise + placebo, exercise + BCAAs showed greater improvements in strength, mobility, and endurance, along with reductions in fatigue (−45% vs. +92%) and depressive symptoms (−29% vs. +5%). Time effects were also observed for ISI (−30%), FAS (−21%), and VAS quality of life (16%) following exercise + BCAA supplementation. These preliminary results suggest that BCAAs combined with exercise may be an effective way to improve physical performance and reduce fatigue and depressive symptoms in older adults. Full article

Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut–brain interactions. Full article

Background/Objectives: Iron deficiency without anaemia (IDNA) is common in non-dialysis-dependent chronic kidney disease (CKD) and contributes to fatigue, reduced exercise tolerance, and impaired quality of life (QoL). While intravenous (IV) iron replacement is known to benefit anaemic patients, its role in IDNA remains uncertain. This study aimed to evaluate the impact of ferric derisomaltose (FDI) on patient-reported QoL outcomes in CKD patients with IDNA. Methods: This was a post hoc analysis of the double-blind, multicentre Iron and the Heart randomised controlled trial. Fifty-four participants with IDNA (ferritin < 100 µg/L or transferrin saturation < 20% and haemoglobin 110–150 g/L) and CKD stages G3b–G5 were randomised 1:1 to receive either 1000 mg FDI (n = 26) or placebo (n = 28). An additional 10 iron-replete CKD patients served as controls. SF-36v2 QoL surveys were collected at baseline, 1 month, and 3 months. Results: SF-36v2 scores declined across all domains, but deterioration was consistently milder in the FDI group. Role physical declined by 3% in the FDI group versus 12% with placebo and 4% in controls. Bodily pain improved by 2.8% with FDI but worsened by 1.5% in the placebo group. Mental health improved by 3.4 points with FDI and declined by 2.7 points in the placebo group, creating a 6.1-point separation. While differences did not reach statistical significance, likely due to small sample size, the consistent trends favour FDI. Conclusions: IV iron may attenuate QoL decline in non-dialysis-dependent CKD patients with IDNA. These findings support the need for larger, adequately powered trials to assess patient-centred outcomes in this population. Full article

Background: Gingival recession is a common condition involving apical displacement of the gingival margin, leading to root surface exposure and associated complications such as dentin hypersensitivity and root caries. Among the most effective treatment options are the tunneling technique (TUN) and the coronally advanced flap (CAF), both combined with connective tissue grafts (CTGs). This study aimed to evaluate and compare the clinical outcomes of TUN + CTG and CAF + CTG in terms of root coverage and keratinized tissue width (KTW) over a 6–12-month follow-up. Methods: A randomized, double-blind clinical trial was conducted following CONSORT guidelines (ClinicalTrials.gov ID: NCT06228534). Participants were randomly assigned to receive either TUN + CTG or CAF + CTG. Clinical parameters, including gingival recession depth (REC) and KTW, were assessed at baseline as well as 6 months and 12 months postoperatively using a calibrated periodontal probe. Statistical analysis was performed using descriptive statistics and linear mixed models to compare outcomes over time, with a significance level set at 5%. Results: Both techniques demonstrated significant clinical improvements. At 6 months, mean root coverage was 100% in CAF + CTG cases and 97% in TUN + CTG cases, while complete root coverage (REC = 0) was observed in 100% and 89% of cases, respectively. At 12 months, root coverage remained stable, at 99% in the CAF + CTG group and 97% in the TUN + CTG group. KTW increased in both groups, with higher values observed in the CAF + CTG group (3.53 mm vs. 3.11 mm in TUN + CTG at 12 months). No significant postoperative complications were reported. Conclusions: Both TUN + CTG and CAF + CTG are safe and effective techniques for treating RT1 and RT2 gingival recession, offering high percentages of root coverage and increased KTW. While CAF + CTG achieved slightly superior coverage and tissue gain, the TUN was associated with better aesthetic outcomes and faster recovery, making it a valuable alternative in clinical practice. Full article

Background/Objective: Sepsis is a leading cause of death in noncoronary intensive care units (ICUs). Fluids for intravascular resuscitation include crystalloids and colloids. There is extensive clinical evidence on colloid use, but large trials comparing gelatine with crystalloid regimens in ICU and septic patients are lacking. This study aimed to determine whether early, protocol-driven volume resuscitation using a gelatine-based regimen achieves hemodynamic stability (HDS) more rapidly than a crystalloid-based regimen in septic patients. Methods: This prospective, controlled, randomised, double-blind, multinational phase IV study compared two parallel groups of septic patients receiving a gelatine-based regimen (Gelaspan^® 4% and Sterofundin^® ISO, B. Braun Melsungen AG each, at a 1:1 ratio) or a crystalloid regimen (Sterofundin^® ISO). Primary endpoint was time to first HDS within 48 h after randomisation. Secondary endpoints included fluid overload, fluid balance, and patient outcomes. Results: 167 patients were randomised. HDS was achieved after 4.7 h in the gelatine group and after 5.8 h in the crystalloid group (p = 0.3716). The gelatine group had a more favourable fluid balance at 24 h (medians: 3463.00 mL vs. 4164.00 mL; p = 0.0395) and less fluid overload (medians: 4296.05 vs. 5218.75%; p = 0.0217). No differences were observed in serious adverse events or mortality. Conclusions: The study provided clinical evidence of balanced gelatine solution for volume resuscitation in septic patients, although it was terminated prematurely. The early and protocol-based administration of gelatine was safe and effective in the enrolled patient population. Time to HDS was not different between groups but the gelatine-based regimen led to better fluid balance and less fluid overload. Full article

Skin aging causes reduced hydration, elasticity, and increased wrinkles. Recent safety and compliance concerns over oral collagen supplements have increased interest in plant-based alternatives like Hibiscus sabdariffa with antioxidant and anti-aging properties. However, clinical evidence regarding its efficacy remains limited. We aimed to evaluate the effects of this plant-based collagen alternative (VC-H1, Hibiscus Enzyme Extract) supplement on skin hydration, transepidermal water loss (TEWL), desquamation, elasticity, and wrinkle reduction in photoaged individuals. A randomized, double-blind, placebo-controlled clinical trial was conducted with 98 participants (aged 35–60 years) presenting with dry skin and periorbital wrinkles. Participants randomly received 1.5 g/day of VC-H1 or placebo for 12 weeks. Skin hydration, TEWL, deep moisture, keratin index, elasticity, and wrinkle parameters were assessed at baseline, 6 weeks, and 12 weeks. VC-H1 supplementation significantly increased skin hydration, reduced the TEWL and keratin index, and improved deep moisture content for those receiving it compared with the controls. Wrinkle depth significantly decreased, and skin elasticity also improved. Those in the VC-H1 group showed greater overall improvement than those in the control group. Oral VC-H1 supplementation significantly improved skin hydration, elasticity, and wrinkle reduction, suggesting its potential as a plant-based alternative to traditional collagen supplements for skin rejuvenation. Full article

Background/Objectives: This study aims to investigate the effects of caffeinated chewing gum on maximal strength, muscular power, and neural drive to the prime movers during bench press and back squat in resistance-trained men. Methods: Sixteen resistance-trained males participated in a double-blind, randomized trial, chewing either caffeinated gum (4 mg/kg) or placebo gum on two separate occasions, seven days apart. After chewing for 5 min, participants performed a maximal strength test followed by muscular power assessments at 25%, 50%, 75%, and 90% of their one-repetition maximum (1RM), completing with 3, 2, 1, and 1 repetition (s), respectively, for bench press and back squat. Surface electromyography data were recorded for each repetition. Results: Caffeinated gum did not significantly improve one-repetition maximum (1RM) for bench press (p > 0.05), but increased mean frequency (MF) and median frequency (MDF) in anterior deltoid, pectoralis major, and biceps brachii (all p < 0.05) compared to placebo. For back squat, 1RM increased with caffeinated gum, along with higher MF and MDF in vastus medialis (all p < 0.05). Caffeinated gum also improved mean and peak velocities, and mean and peak power outputs at 25–75% 1RM during the bench press (all p < 0.05), along with elevated MDF in pectoralis major and biceps brachii (all p < 0.05). Similar improvements were seen in mean and peak velocities during the back squat at 25–90% 1RM (all p < 0.05), along with higher MF and MDF in vastus medialis and increased normalized root mean square activity in gluteus maximus (all p < 0.05). Conclusions: Caffeinated chewing gum (4 mg/kg) enhanced muscular power (25–75% 1RM) in the bench press and improved maximal strength and muscular power (25–90% 1RM) in the back squat by increasing muscle recruitment in resistance-trained men. Full article

Background: This study aims to evaluate the efficacy of a combined transcranial magnetic stimulation (TMS) protocol incorporating intermittent theta burst stimulation (iTBS) and low-frequency TMS in adults diagnosed with first-episode and recurrent depressive disorders. Methods: A prospective, double-blind, parallel-group trial was conducted involving 42 participants (21 with first-episode depressive disorder and 21 with recurrent depressive disorder) recruited from Chengdu, China. All subjects received 10 sessions of TMS over two weeks. The primary outcome measure was suicidal ideation, assessed using the Beck scale for suicide ideation. Secondary outcomes included sleep quality, depressive symptoms, anhedonia, and cognitive function. Event-related potentials (ERPs) were also recorded. Data were analyzed using SPSS V.21.0, with statistical significance defined as p < 0.05. Results: Both patient groups exhibited significant reductions in suicidal ideation following the composite TMS intervention. Secondary outcomes showed significant improvements in sleep quality, overall depressive symptoms, anhedonia, and cognitive function. Notably, a significant association was found between improvements in sleep quality and depressive symptoms in the first-episode group, suggesting differential underlying mechanisms compared to recurrent depression. Limitations: The relatively short intervention and follow-up period limits the ability to assess the long-term sustainability of the observed benefits. Future studies with extended follow-up periods are warranted to evaluate the persistence of TMS effects and the potential need for maintenance sessions. Conclusions: The combined protocol of iTBS and low-frequency TMS effectively reduces suicidal ideation and improves various clinical outcomes in both first-episode and recurrent depressive disorders, indicating the effectiveness of the physical intervention, especially for the first-episode patients. These findings underscore the importance of personalized treatment strategies based on the clinical history of depressive episodes. Further research with longer follow-up periods is warranted to assess the long-term sustainability of TMS effects. Full article

Background: Reducing cardiovascular risk markers is an essential target in chronic kidney disease (CKD). Thus, this study aimed to evaluate the effect of royal jelly plus green propolis supplementation on cardiovascular disease (CVD) risk factors in patients with CKD undergoing hemodialysis (HD). Methods: This randomized, double-blind, placebo-controlled trial involved HD patients allocated to receive either royal jelly plus green propolis EPP-AF^® (100 mg RJ + 500 mg GP) or placebo capsules daily for 2 months. Before and after the intervention period, the biochemical parameters, inflammatory cytokines, and uremic toxins were measured. Results: A total of 38 HD patients completed the 2-month supplementation study, with 19 patients in each group. After 2 months, the treated group showed a significant reduction in plasma levels of IL-6 (0.78 to 0.63 pg/mL, p = 0.008) and total cholesterol (138.60 to 111.85 mg/dL, p = 0.03), whereas no changes were observed in the placebo group. Uremic toxins did not change after intervention. Conclusion: Apitherapy with RJ + GP EPP-AF^® extract significantly reduced plasma IL-6 and total cholesterol in HD patients. This supplementation shows promise as a non-pharmacological strategy to reduce cardiovascular risk markers in this population. 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

Objective: To evaluate the effect of a probiotic combination on clinical and oral microbiological parameters in patients with head and neck cancer (HNC) undergoing radiotherapy. Materials and Methods: A randomised, double-blind, placebo-controlled clinical trial was conducted with 72 HNC patients who had received radiotherapy within the past year. Participants were randomly assigned to receive either daily probiotic sachets or placebo for 30 days. Salivary parameters—including unstimulated and stimulated flow rates and pH—were evaluated alongside oral microbiota profiles, including total bacterial load and selected periodontopathogens. Assessments were performed at baseline and post-intervention using sialometry, pH analysis, bacterial culture, and quantitative real-time PCR (qPCR). Results: Sixty-one patients completed the study (31 in the probiotic group, 30 in the placebo group). Stimulated salivary flow increased significantly in the probiotic group (p = 0.0016), while unstimulated flow improved in both groups (p < 0.05). Salivary pH decreased significantly in the probiotic group (p = 0.0209); however, no intergroup differences were observed at the end of the intervention (p = 0.9839). qPCR showed significant reductions in total bacterial load (p = 0.0209) and Fusobacterium nucleatum (p = 0.0080). Culture confirmed the reduction of F. nucleatum (p = 0.0026), with a trend towards significance for total cultivable bacterial count (p = 0.0502). Conclusions: Daily supplementation with a probiotic combination may serve as a practical and well-tolerated adjunctive measure in clinical settings to improve salivary function and reduce key oral pathogens, particularly Fusobacterium nucleatum, in patients undergoing or recovering from radiotherapy for head and neck cancer. These findings support its potential integration into routine supportive care protocols to mitigate xerostomia and oral dysbiosis in this population. Full article

An explorative study was conducted to evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (SPP-004) in 10 pediatric patients with Leigh syndrome (LS) aged 3–24 months in 10 institutions between December 2014 and July 2019. The patients were randomized and allocated to the SPP-004 or placebo group for a 12-week double-blind period, followed by a 12-week open-label period with SPP-004 and then a long-term study of up to 180 weeks. The efficacy and safety were evaluated using the Newcastle Pediatric Mitochondrial Disease Scale (NPMDS) and adverse events (AEs), respectively. No significant differences were found between groups in NPMDS scores, but prolonged SPP-004 treatment stabilized or improved scores. During the initial double-blind phase, the serum lactate levels increased in the placebo group but not in the SPP-004 group. Over the period of prolonged treatment with SPP-004, the average serum lactate level gradually decreased to a normal level. One patient died due to heart failure, presumably due to an underlying disease. Overall, 7 out of 10 patients received SPP-004 without developing severe AEs until the termination of the long-term study. Given the severe symptoms and poor prognosis of pediatric LS, NPMDS scores were indicative of stabilization in pediatric LS patients treated with SPP-004. Full article

Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger’s clinical activity index, 3–10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events. Full article