Search Results (1,469)

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: Chemotherapy-induced peripheral neuropathy is a common and debilitating side effect of cancer treatment. While exercise has shown promise in alleviating this burden, it remains underutilised in clinical practice due to the lack of accessible, clinician-friendly guidance. Aim: This review aimed to synthesise current evidence on exercise interventions for managing chemotherapy-induced peripheral neuropathy and provide practical insights to support clinicians in integrating these approaches into patient care. Methods: A search was conducted across MEDLINE, CINAHL, and SPORTDiscus using keywords related to exercise and CIPN. Studies were included if they involved adults receiving neurotoxic chemotherapy and exercise-based interventions. Two authors independently screened studies and resolved conflicts with a third author. Study quality was assessed using the JBI Critical Appraisal Tools, and only studies meeting a minimum quality standard were included. A balanced sampling approach was employed. Data on study design, participant characteristics, interventions, and outcomes were extracted. Results: Eleven studies were included, covering various exercise modalities: multimodal (n = 5), yoga (n = 2), aerobic (n = 1), resistance (n = 1), balance (n = 1), and sensorimotor (n = 1). Exercise interventions, particularly multimodal exercise, significantly improved symptom severity, functionality, and quality of life (p < 0.05). The studies had high methodological quality, with randomised controlled trials scoring between 9/13 and 11/13, and quasi-experimental studies scoring 8/9 on JBI tools. Conclusions: This review highlights the significant benefits of exercise, especially multimodal exercise, for managing CIPN and provides guidance for integrating these strategies into clinical practice. Future research is needed to refine exercise prescriptions and develop standardised guidelines. 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

Current research reported that the number of clinical studies found for botulinum toxin (BoNT) key effects on biochemical biomarkers in head and neck chronic conditions linked to inflammation was very low. There are no systematic reviews of animal studies on this topic, and hence our review aimed to evaluate the quality of the preclinical evidence. We searched PubMed, Scopus, and Web of Science databases, and registries up to 29 January 2024. There were 22 eligible records, and data were available for 11 randomised controlled trials. There were concerns about the risk of bias and great variations of data obtained regarding chronic conditions, which included mostly trigeminal neuralgia. The leading biomarkers were proinflammatory cytokines (IL-1β, TNF-α) and synaptosomal-associated protein-25 (SNAP25), followed by neuron activation marker c-Fos and calcitonin gene-related peptide (CGRP). Overall, data found that BoNT significantly altered the under/over-expression of biomarkers evoked by the investigated disease models and had no effect when the levels of these biomarkers were not changed by the induced chronic conditions in animals. However, there were some mixed results and exceptions, and the certainty evidence found was very low to low. Although the sample sizes detected significant effect size (p < 0.05), most studies are based on male inferior animals, which may limit the recommendations for clinical trials. This study is registered on PROSPERO (CRD42023432411). 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

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

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

Background: This paper aims to conduct an umbrella review of the effects of physical activity programmes for older adults (aged 70 and above). Methods: Comprehensive literature searches were conducted in MEDLINE, PubMed, EMBASE, PsychINFO, and Cochrane Library databases for English SRs 2024. Inclusion criteria were systematic reviews that included randomised controlled trials examining physical activity interventions in older adults. The data extracted were participant characteristics, physical activity interventions, and outcomes examined. A synthesis of results was conducted using the PRISMA guidelines, and the quality of the studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2). Results: Ten systematic reviews on 186 research articles were included. The AMSTAR-2 revealed that 4 out of 10 reviews were of high quality and 1 out of 10 were of moderate quality. The study samples in each systematic review ranged from 6 to 1254 participants. The total overall sample size for the 10 included studies was 22,652 participants. Across the included reviews, there was mixed evidence on whether physical activity interventions could improve outcomes in older adults across various settings. Conclusions: Sample sizes and findings in each included systematic review varied. The findings of this review emphasise the importance of physical activity as a vital component in maintaining and enhancing health, as well as combating poor health as we age. It also highlights the need for a deeper understanding of the specific physical activity requirements for those aged 70 and above. Future systematic reviews may focus on streamlined reporting of dosing of physical activity and specific intervention types, such as group versus single. Full article

Background/Objectives: Despite the numerous health benefits of exclusive breastfeeding (EBF) for the infant and the mother, EBF rates in Lao People’s Democratic Republic, Lao PDR, remain at 40%. We investigate how barriers to EBF were overcome by a social transfer intervention. Methods: Data from the Social Transfers for Exclusive Breastfeeding ongoing randomised controlled trial (RCT) (n = 298) in Vientiane, Lao PDR, was used. Mothers in the RCT were randomised equally into a control group, an unconditional transfer group and a conditional transfer group and followed up to six months (n = 280). We used logistic and Cox proportional hazards regression models to investigate the association of predictor variables with EBF at six months and the risk of EBF cessation in each of the three groups. Results: Greater breastfeeding self-efficacy increased the odds of EBF at six months in both intervention groups (unconditional transfer OR 1.39 [95% CI 1.09, 1.87, p = 0.02] and conditional transfer OR 1.26 [1.01, 1.61, p = 0.05]) and reduced the risk of EBF cessation (unconditional transfer HR 0.87 [0.77, 0.98, p = 0.02]). Maternal secondary and tertiary education in the intervention groups showed higher odds of EBF at six months and lower EBF cessation risk. Participants in the intervention group that intended to exclusively breastfeed in pregnancy showed a reduced EBF cessation risk in both intervention groups. Conclusions: Social transfers helped overcome the exclusive breastfeeding barrier of a higher education level and working status and improved EBF outcomes for mothers who intended to exclusively breastfeed and wanted the pregnancy. Breastfeeding self-efficacy positively influences EBF outcome, regardless of whether the mother received a social transfer or not. Full article

Background/Objectives: Radicular pain is a frequent pathology, and disc herniation is the commonest aetiology. A meta-analysis summarising international guidelines for radicular pain, published in 2021, showed that lumbar traction’s place is still a topic of debate. In this study, our aim was to evaluate the effectiveness of lumbar tractions in treating radicular pain of discal origin in association with medical treatment versus medical treatment alone. We performed a randomised, controlled, interventional, prospective, superiority trial in Reims Hospital Rheumatology Unit. Methods: We included participants with radicular pain and concordant disc herniation with ambulatory treatment failure. Participants were randomised into two groups: medical group (analgesics, anti-inflammatories treatments, at least two epidural injections); tractions group with this medical treatment associated with lumbar tractions. The primary outcome was the difference in the proportion of participants experiencing a minimum of 25% improvement in radicular pain at one month follow-up between the two groups. Results: We included 424 participants: 211 in the tractions group and 213 in the medical group. We analysed 388 participants (194 in each group). We collected demographic and clinical data, lumbar and radicular Numeric Pain Scale at baseline, one and three months. A statistical difference was found for the primary outcome: 120/194 participants (62%) in tractions group and 98/194 participants (51%) in medical group (p = 0.024). Conclusions: To our knowledge, this is the first randomised and controlled study on this topic with these results. We can assert the superiority of lumbar tractions in association with medical treatment over medical treatment alone for radicular pain with concordant disc herniation. Full article

Background/Objectives: An increasing number of apparently healthy individuals are adhering to a gluten-free lifestyle without any underlying medical indications, although the evidence for the health benefits in these individuals remains unclear. Although it has already been shown that a low- or gluten-free diet alters the gut microbiota, few studies have examined the effects of this diet on healthy subjects. Therefore, our aim was to evaluate whether and how a prolonged low-gluten diet impacts gut microbiota composition and function in healthy adults, bearing in mind its intimate link to the host’s health. Methods: Forty healthy volunteers habitually consuming a gluten-containing diet (HGD, high-gluten diet) were included in a randomised control trial consisting of two successive 8-week dietary intervention periods on a low-gluten diet (LGD). After each 8-week period, gut microbiota composition was assessed by 16S rRNA gene sequencing, molecular quantification by qPCR, and a cultural approach, while its metabolic capacity was evaluated through measuring faecal fermentative metabolites by ¹H NMR. Results: A prolonged period of LGD for 16 weeks reduced gut microbiota richness and decreased the relative abundance of bacterial species with previously reported potential health benefits such as Akkermansia muciniphila and Bifidobacterium sp. A decrease in certain plant cell wall polysaccharide-degrading species was also observed. While there was no major modification affecting the main short-chain fatty acid profiles, the concentration of the intermediate metabolite, ethanol, was increased in faecal samples. Conclusions: A 16-week LGD significantly altered both composition and metabolic production of the gut microbiota in healthy individuals, towards a more dysbiotic profile previously linked to adverse effects on the host’s health. Therefore, the evaluation of longer-term LDG would consolidate these results and enable a more in-depth examination of its impact on the host’s physiology, immunity, and metabolism. Full article

Addressing climate change requires not only knowledge but also psychological resilience. This study examined whether integrating Mental Mode Management (MMM) self-regulation training with climate education improves pro-environmental outcomes and emotional responses to climate change. In a randomised 2 × 2 design, 44 participants were assigned to either a control group (CG; n = 21), which received a six-week climate education programme, or an experimental group (MMM; n = 23), which received the same education plus MMM training. Pro-environmental attitudes, behaviours, carbon emissions, climate change anxiety, mindfulness, and executive functions were assessed at baseline and post-intervention. A follow-up was also conducted six months later. Both groups showed increased pro-environmental attitudes post-intervention (η² = 0.3) and reduced food-related emissions (η² = 0.107). No changes were observed in pro-environmental behaviour scores or global carbon footprint. While neither intervention affected overall climate anxiety or cognitive impairment, functional impairment increased in the CG and decreased in the MMM group (η² = 0.177), with mindfulness facet acting with awareness moderating this effect. These findings contribute to sustainability research by showing that integrating climate education with psychological training enhances environmental awareness and fosters emotionally resilient engagement with climate challenges, supporting individual-level contributions to broader sustainability goals. Full article

Background and Objective: Benign prostatic hyperplasia (BPH) and urethral stricture (US) are common causes of lower urinary tract symptoms in ageing men, often requiring repeated interventions. Conventional treatments of US, such as urethrotomy and mechanical dilation, have high recurrence rates. The Optilume drug-coated balloon catheter system, which combines mechanical dilation with paclitaxel delivery, has emerged as a minimally invasive alternative. This systematic review assesses its efficacy and safety in the management of BPH and US. Methods: A systematic search of PubMed was conducted for studies published between August 2020 and October 2023. Eligible studies included randomised controlled trials (RCTs), cohort studies, and case reports evaluating Optilume’s therapeutic effects. Key outcomes analysed included symptom relief, urinary flow improvement, recurrence rates, and adverse events. Results: Seven studies met the inclusion criteria, including five on US and two on BPH. The ROBUST trial series demonstrated sustained improvements in urinary flow rates and symptom scores in US patients over follow-up periods of up to four years. The EVEREST-1 and PINNACLE trials reported significant symptom relief and preserved sexual function in BPH patients, with a favourable safety profile and minimal complications. Conclusions: Optilume appears to be a promising alternative to conventional endoscopic treatments for US and BPH, offering durable symptom relief with a low complication rate. Further long-term studies are required to confirm its efficacy and cost-effectiveness in routine clinical practice. Full article

Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article