Treating obesity in children and adolescents is complex, given the dynamic nature of growth and development during this life stage. The role of pharmacological treatments in the management of pediatric obesity remains uncertain, particularly with respect to outcomes beyond weight reduction, including quality of life and long-term adverse events. To assess the benefits and harms of pharmacological interventions for the treatment of obesity in children and adolescents. We searched CENTRAL, MEDLINE, the World Health Organization (WHO) International Clinical Trials Registry Platform, and ClinicalTrials.gov on 3 July 2023 without language restrictions. In June 2025, we checked the status of ongoing studies and updated results accordingly. We included randomized controlled trials (RCTs) evaluating pharmacological interventions in children (0 to 9 years) and adolescents (10 to 19 years) with essential obesity. Eligible studies administered any medication, at any dose, as monotherapy or in combination, for at least three months and reported outcomes after a minimum follow-up of six months. Critical outcomes were change in body mass index (BMI), change in weight, any adverse events, discontinuation due to adverse events, and incidence or severity of obesity-related outcomes. Important outcomes were health-related quality of life, mental and physical well-being, and obesity-related disability. We used the RoB 2 tool to assess bias in the included RCTs. We calculated mean differences (MDs) and standardized mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, with their corresponding 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for critical outcomes and quality of life. We included 37 RCTs with a total of 4218 participants. Two were cross-over trials; 35 were parallel-group trials. We identified seven ongoing studies and six studies as awaiting classification. Of the included studies, 25 involved adolescents only. Eleven studies planned to include both children and adolescents, but only eight actually did. One study intended to include children but did not specify participants' age at inclusion. Trials randomized participants to pharmacological interventions or control alongside common baseline treatments (e.g. behavioral or lifestyle approaches, diet, and physical activity). Of the 37 included studies, 31 used placebo and six used no intervention (baseline treatment alone) as the comparator. The studies were conducted across 17 high-income, six middle-income, and three low-income countries. Length of follow-up ranged from six to 31 months, with a median of 11 months. Pharmacological interventions versus placebo Compared to placebo, pharmacological interventions (glucagon-like peptide-1 [GLP-1] receptor agonists, metformin, orlistat, sibutramine, topiramate, phentermine plus topiramate) may reduce BMI (change from baseline) by 1.80 kg/m2 (95% CI -2.36 to -1.24; I2 = 87%; 25 studies, 3091 participants; low-certainty evidence) and weight (change from baseline) by 5.47 kg (95% CI -7.45 to -3.50; I2 = 89%; 20 studies, 2380 participants; low-certainty evidence). Adverse events were frequent. Pharmacological interventions (GLP-1 agonists, sibutramine, phentermine, topiramate) likely make little to no difference in the risk of any adverse events compared to placebo (RR 1.03, 95% CI 1.00 to 1.07; I2 = 0%; 8 studies, 1877 participants; moderate-certainty evidence). Pharmacological interventions (GLP-1 agonists, metformin, orlistat, sibutramine, phentermine, topiramate) may make little to no difference in the risk of discontinuation due to adverse events, although the risk was slightly higher with the medications (RR 1.50, 95% CI 0.82 to 2.75; I2 = 17%; 13 studies, 2213 participants; low-certainty evidence). One study (46 participants), comparing sibutramine to placebo, found that there may be little to no difference in the incidence of obesity-related outcomes for adolescents with comorbidities (assessed as changes in glycemia, blood pressure, total cholesterol, and triglycerides). We were unable to pool other data on incidence or severity of obesity-related outcomes. Compared to placebo, pharmacological interventions (GLP-1 agonists, phentermine plus topiramate) likely result in little to no difference in quality of life, assessed with the Impact of Weight on Quality of Life-Kids (IWQOL) questionnaire (MD 1.02, 95% CI -1.94 to 3.98; I2 = 48%; 4 studies, 741 participants; moderate-certainty evidence). Pharmacological interventions versus no intervention Compared to no intervention, metformin may reduce BMI (change from baseline) by 1.51 kg/m2 (95% CI -2.29 to -0.73; I2 = 0%; 3 studies, 151 participants) and weight (change from baseline) by 3.20 kg (95% CI -6.12 to -0.28; 1 study, 42 participants), but the evidence for both outcomes is very uncertain. Compared to no intervention, pharmacological interventions (metformin and orlistat) may increase the risk of discontinuations due to adverse events, but the evidence is very uncertain (RR 13.70, 95% CI 0.83 to 225.43; 2 studies, 84 participants). None of the studies comparing pharmacological interventions to no intervention reported data on adverse events, obesity-related outcomes, and quality of life that could be pooled in meta-analysis. Only eight of the 37 included studies enrolled children, and data were seldom disaggregated by age, limiting the ability to draw conclusions about benefits or harms in children. This review includes clinical trials assessing the benefits and harms of pharmacological treatments - including GLP-1 agonists, metformin, orlistat, phentermine, sibutramine, and topiramate - for weight management in adolescents with obesity. Evidence suggests that pharmacological treatments may result in small reductions in BMI and weight, which could be clinically important, although effects vary by medication. Evidence on desirable and undesirable effects in children is scant. Uncertainties remain about the optimal duration of treatment, consequences of treatment discontinuation, and long-term benefits and harms, particularly considering the physiology of children and impact on growth. Studies with longer follow-up are needed to evaluate outcomes beyond BMI and weight change, including the potential effects of treatment discontinuation. The Department of Nutrition and Food Safety at the WHO commissioned and provided financial support for this work. WHO acknowledges financial support from the Norwegian Agency for Development Cooperation (NORAD), the Swedish International Development Cooperation Agency (SIDA), the Government of the Grand Duchy of Luxembourg, the Government of Germany (BMG), and the Government of Greece to the WHO Department of Nutrition and Food Safety. Our protocol is registered in PROSPERO: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433123.
Chronic kidney disease (CKD) affects approximately 850 million people worldwide and is associated with a substantial and growing symptom burden. Fatigue is one of the most common and debilitating symptoms across all stages of CKD, with prevalence far exceeding that of the general population. It profoundly affects quality of life, daily functioning, and clinical outcomes, underscoring the need to identify and evaluate effective pharmacological and non-pharmacological strategies for its management. This protocol outlines methods for a systematic review to evaluate the efficacy, safety, and perceived effectiveness of interventions for fatigue in people with CKD. We will include randomised controlled trials, non-randomised controlled trials, before-and-after studies, and qualitative evaluations in adults and children with any stage of CKD. Searches will be conducted in MEDLINE, Embase, CINAHL, Web of Science Core Collection, PsycINFO, and ClinicalTrials.gov, alongside grey literature via Google Scholar. No language or publication date restrictions will be applied. Study selection will follow a two-stage screening process, with two reviewers independently assessing titles/abstracts and then full texts using predefined eligibility criteria. Data will be extracted using a standardised form, capturing study characteristics, interventions, and outcomes. Risk of bias will be assessed with the NIH Study Quality Assessment Tools or the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Results will be synthesised narratively, and, where appropriate, pooled using meta-analysis. Certainty of the evidence for the primary outcome will be assessed using the GRADE approach and presented in a Summary of Findings table. This review will provide a comprehensive synthesis of evidence on interventions for fatigue in CKD, highlight gaps to guide future research, and inform the UK Kidney Association Symptom Guidelines.
Older adults (people aged >60 years) are often stereotyped as being asexual, reflecting a broader lack of research into the sexual lives of this age group. Few studies have examined sexual well-being among older adults in low- and middle-income countries, especially in Africa. This scoping review aims to identify and synthesize the factors that affect sexual functioning and quality of sexual life among older adults in Africa. Following the approach of Arksey and O'Malley, a scoping review was conducted on determinants affecting the quality of sexual life among older adults in Africa. Seven databases were searched: PubMed, Google Scholar, CINAHL, Scopus, Web of Science, ProQuest and AJOL. Full texts were reviewed to determine the final set of papers for inclusion. Included papers were published, with publication dates between January 2010 and January 2025. Data were extracted on the study population, study design, mean age of the study participants, aims of the study and the determinants affecting the quality of sexual life, and summarized using narrative synthesis. A total of 14,398 citations were identified in the database search, and seven studies were included in the review. The age of study participants averaged approximately 70 years. The research consisted of three qualitative and four quantitative articles. Four studies were conducted in Nigeria, and one each from South Africa, Morocco and Tanzania. Our review identified four categories of determinants influencing the quality of sexual life among older adults in Africa: psychological, sociocultural, physiological and health. Psychological determinants, including past trauma, performance anxiety and societal expectations, were identified across five studies. Sociocultural determinants, including sexual attitudes and culturally embedded behaviors, were examined in six studies, and found to shape the sexual functioning and behaviors of older adults. Physiological determinants, such as menopause and erectile dysfunction, were reported in four studies and associated with reduced sexual activity. Health determinants, including chronic conditions and pharmacological factors (medications), were identified in five studies as influencing older adults' sexual function and intimacy. Multiple, complex determinants affect the quality of sexual life among older adults in Africa. Our study findings have implications for designing sexual health services among older adults in Africa.
Pemphigus vulgaris is a rare autoimmune blistering disease characterised by recurrent mucocutaneous erosions, high symptom burden and unpredictable relapse. Current management relies mainly on pharmacological therapy and hospital-based follow-up, with limited real-time monitoring and individualised support in home-based disease management. To address these challenges, this trial aims to evaluate the effectiveness of an Intelligent Multimodal Symptom Assessment and Response System, integrating patient-reported outcomes, wearable physiological data and image-based lesion assessments, to improve symptom management and quality of life in pemphigus vulgaris patients. Primary objective is to evaluate the effectiveness of the Intelligent Multimodal Symptom Assessment and Response System in improving symptom alerting and symptom management outcomes in patients with pemphigus vulgaris. Secondary objectives are to enhance patients' self-management ability in symptom monitoring and control, to improve treatment adherence throughout the follow-up period, to promote health-related quality of life among pemphigus vulgaris patients, to assess the usability and acceptability of the system from the patients' perspective. This is a multicentre, parallel-group, randomised controlled trial. 160 participants will be randomly assigned to either the intervention group (receiving the Intelligent Multimodal Symptom Assessment and Response System) or the control group (receiving standard care). Eligible participants will be adults aged 18 years or older with a confirmed diagnosis of pemphigus vulgaris and active skin or mucosal lesions, who are able to use digital devices and provide written informed consent. Individuals with severe comorbidities, concurrent participation in other clinical trials or cognitive impairments that may interfere with study adherence will be excluded. The intervention will be delivered via a digital platform, integrating electronic patient-reported outcomes, wearable physiological data and lesion images over a 12-week follow-up period. Ethical approval was obtained from the Institutional Review Board of the School of Nursing, Fudan University (IRB 2025-07-13), the Medical Ethics Committee of the Institute of Dermatology, Chinese Academy of Medical Sciences (2025-KY-034) and the Ethics Committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (2025-452). Approvals were granted on 10 September, 18 July and 23 July 2025, respectively. This protocol is based on V1.0, 13 July 2025 of the protocol. The results of this study will be disseminated through peer-reviewed publications and academic conferences. ChiCTR2500109711.
Endometriosis is a chronic inflammatory disease presenting with debilitating symptoms strongly impacting patients' quality of life (QoL). Assessing QoL is crucial for understanding the full patient experience beyond clinical symptoms. This narrative systematic review specifically aimed to identify and describe non-pharmacological and non-surgical factors associated with QoL in women with endometriosis as reported in the literature. Following PRISMA guidelines, we systematically searched PubMed, MEDLINE, Web of Science, and Embase up to January 15, 2025, for case-control, cohort, randomized controlled trials, and cross-sectional studies. This study was registered in PROSPERO (registration number: CRD42023438457) Eligible studies assessed socio-demographic characteristics, lifestyle factors, symptoms, comorbidities, or coping strategies in relation to QoL among women with endometriosis. Twenty-one studies with a low risk of bias were included. A better QoL was related to favorable socioeconomic profiles (n = 3), high care satisfaction (n = 2), partner involvement (n = 1), healthier lifestyle habits (n = 1), and the use of coping therapeutic strategies. Poor QoL was associated with poor health (n = 5), more severe symptoms (n = 5), unhealthy lifestyle habits (n = 2), and ineffective use of coping strategies (n = 2). This review highlights a broad range of non-medical determinants of QoL, underscoring that clinical measures alone fail to capture the full patient experience. By consolidating evidence across diverse study designs, it offers a comprehensive overview of modifiable factors that could inform holistic, patient-centered approaches to endometriosis care. Further prospective and interventional studies are needed to clarify causal pathways and evaluate the effectiveness of targeted strategies to improve QoL. Endometriosis is a chronic disease affecting around 10% of women of reproductive age, associated with pain, infertility, and significant impacts on daily life. Because clinical measures alone fail to capture the full patient experience, assessing QoL is essential to understand the real burden of the disease. This review examined non-pharmacological and non-surgical factors that may be associated with QoL, such as lifestyle habits, socioeconomic conditions, health status, and coping strategies. Across 21 studies, we found that a better QoL was linked to good healthcare access, healthy habits, and effective coping mechanisms. Conversely, severe symptoms, poor health, and unhealthy lifestyles (smoking and alcohol use) were associated with worse QoL. The findings highlight the need for a more holistic approach to endometriosis care, combining psychological support, lifestyle guidance, and improved access to quality healthcare. Future research should use standardized QoL tools and robust study designs to develop evidence-based strategies that can meaningfully enhance patient well-being.
Cough is one of the most common and distressing symptoms in pediatric practice and represents a major cause of medical consultation, parental anxiety, and inappropriate medication use. Although most acute cough episodes are benign and self-limiting, they can significantly affect child's sleep, school performance, and quality of life. The COVID-19 pandemic and subsequent changes in infection patterns and immune responses have further highlighted the need to update the existing clinical guidance. This joint position paper by the Italian Society of Pediatric Allergy and Immunology (SIAIP) aims to provide a pragmatic, evidence-based update on the management of acute and post-viral cough in children and adolescents, integrating recent scientific advances and real-world clinical experiences. A multidisciplinary board of experts from SIAIP critically reviewed the literature published from 2019 to 2025 and updated the previous 2019 SIAIP document. The group achieved consensus on diagnostic and therapeutic recommendations through structured discussion and iterative revision. The document emphasizes a stepwise approach to pediatric acute cough, starting with careful history-taking, clinical evaluation, and reassurance. Non-pharmacological measures-hydration, nasal saline irrigation, and avoidance of irritants-remain the first-line management. Pharmacological therapy may be considered in selected cases where cough is particularly distressing or significantly interferes with sleep; peripherally acting, nonsedative antitussives represent a reasonable option in terms of efficacy and safety. Centrally acting antitussives and unnecessary antibiotics should be avoided. Standardized, high-quality natural medical devices-with appropriate supporting evidence-represent a valid option. Honey-based preparations can be considered as complementary options. The paper also discusses new insights into cough pathophysiology, particularly the role of airway sensory hypersensitivity and neurogenic inflammation, which are paving the way for mechanism-based treatments. This position paper provides an updated, pragmatic framework for the management of acute and post-viral cough in children and adolescents. It promotes rational drug use, integration of non-pharmacological and complementary measures, and awareness of emerging therapeutic targets. A mechanism-driven, individualized, and family-centered approach is advocated to improve clinical outcomes and quality of life for pediatric patients.
Acetylcholine-mediated modulation of pain-associated behaviors has been progressively well described. The mechanisms of cholinergic antinociception have been reported to involve the activation of nAChRs or mAChRs modulating GABAergic and/or glycinergic inhibitory transmissions. However, the functional activity of cholinesterase in pain signaling, which catabolizes ACh to choline, is not well established. We found that ACh increased the frequency and amplitude of spontaneous IPSCs in the presence of the cholinesterase inhibitor neostigmine in the rat substantia gelatinosa of the spinal trigeminal nucleus caudalis. In the absence of neostigmine, even a high concentration of ACh had no significant effect on the frequency of IPSCs. The non-hydrolysable agonist muscarine, but not nicotine, significantly increased IPSC frequency in the absence of neostigmine. The increase in IPSC frequency with ACh was blocked by strychnine, atropine, or tetrodotoxin. These results suggest that activation of the mAChR increases glycine receptor-mediated IPSC frequency in a manner dependent on an action potential generation, only when the activity of cholinesterase is inhibited by neostigmine in the substantia gelatinosa of the spinal trigeminal nucleus caudalis. The inhibition of ACh breakdown by a cholinesterase inhibitor might be important for producing analgesia through the cholinergic modulations of the nociceptive network. (200 words).
The TGF-β/Smad signaling pathway plays a central role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and is modulated by sphingolipid metabolism. Ceramide, a key intermediate in this pathway, is synthesized in various acyl-CoA chain lengths by ceramide synthases (CerS). However, the specific role of ceramide synthase 5 (CerS5) in pulmonary fibrosis remains unclear. Therefore, this study aimed to elucidate the role of CerS5 in fibrotic responses using human lung fibroblasts (HFL1), IPF-derived myofibroblasts (IPF-MyoFs), and a bleomycin-induced mouse model of pulmonary fibrosis. CerS5 knockdown attenuated TGF-β1-induced expression of α-smooth muscle actin (αSMA), collagen I, fibronectin, and phosphorylated Smad2/3 in both HFL1 cells and IPF-MyoFs. It also suppressed TGF-β1-induced nuclear translocation of Smad2/3. Notably, CerS5 knockdown reduced protein levels of Smad3 and Smad4 even in the absence of TGF-β1 stimulation. Smad4 knockdown replicated the effects of CerS5 knockdown by decreasing TGF-β1-induced expression of fibrotic markers, phosphorylated Smad2/3, and total Smad3 levels. In vivo, CerS5 knockout significantly reduced bleomycin-induced lung fibrosis and Smad3/4 expression. These findings suggest that CerS5 regulates fibrotic responses via modulation of Smad4 and the TGF-β1/Smad signaling pathway. Targeting CerS5 may therefore represent a promising therapeutic strategy for the treatment of IPF.
Chronic deep vein thrombosis (DVT) is a persistent clinical condition that often results in venous obstruction, post-thrombotic syndrome and impaired quality of life. Conventional endovascular dilation is limited by elastic recoil and high rates of restenosis caused by neointimal hyperplasia. Paclitaxel-based localized venous therapy enables targeted delivery of antiproliferative agents directly to the venous wall, offering a pharmacological strategy to suppress pathological vascular remodeling and improve long-term outcomes. To evaluate the efficacy and safety of paclitaxel-based localized venous therapy in improving long-term venous patency and reducing restenosis in patients with chronic DVT, compared with conventional angioplasty. This retrospective multicenter study analyzed patient records from three vascular centers between 2019 and 2024. A total of 245 patients with chronic DVT were included, of whom 127 received paclitaxel-based localized therapy and 118 underwent conventional angioplasty. Primary endpoints were venous patency and restenosis rates. Secondary endpoints included freedom from clinically driven reintervention and quality-of-life outcomes. Clinical and imaging follow-up was conducted at baseline and at 6, 12 and 24 months. Multivariate regression analysis was performed using SPSS version 28. At 24-month follow-up, primary venous patency was significantly higher in the paclitaxel-based therapy group than in the conventional angioplasty group (82.7% vs. 61.9%), with lower restenosis rates (11.8% vs. 29.7%). Paclitaxel-based localized therapy was associated with greater freedom from reintervention (hazard ratio 0.42; 95% CI 0.29-0.61; p < 0.001). Quality-of-life scores improved significantly in the paclitaxel group (mean difference 14.3 points; p = 0.002). No significant differences were observed in major complications or thrombotic events between groups. Paclitaxel-based localized therapy provides superior long-term venous patency, reduced restenosis and improved quality of life without compromising safety. These findings highlight the pharmaceutical relevance of localized antiproliferative drug delivery in the management of chronic venous disease.
BackgroundDementia contributes to morbidity and mortality in aging populations, with infectious diseases as frequent terminal events. In Brazil, data on causes of death in dementia and hospital-based end-of-life care are limited.ObjectiveTo describe causes of death, clinical characteristics, and pharmacological treatment patterns during the last month of life among patients with dementia hospitalized in a geriatric hospital in São Paulo, Brazil.MethodsThis retrospective observational study included all patients with clinically diagnosed dementia who died between 2015 and 2023 in a specialized geriatric hospital. Demographic, clinical, and pharmacological data were extracted from electronic medical records. Causes of death were classified using ICD-10 codes. Associations between dementia subtypes and infection-related deaths were evaluated using logistic regression adjusted for age, sex, and comorbidities. Statistical analyses were performed using R, with p < 0.05 considered significant.ResultsA total of 122 patients were included (mean age 83.6 ± 7.4 years; 61.5% female). Alzheimer's disease was the most frequent subtype (52.5%), followed by vascular (26.2%) and mixed dementia (21.3%). Infectious diseases accounted for 67.2% of deaths, mainly pneumonia (48.3%) and sepsis (18.9%). Antibiotics were prescribed in 76.2% of cases, and antipsychotics in 58.1%. Palliative care measures were documented in 41.0% of cases.ConclusionsInfectious diseases were the most frequent causes of death among hospitalized patients with dementia, with high antibiotic use and limited palliative care documentation. These findings indicate the need for integrated end-of-life protocols and improved recognition of palliative needs.
Venous leg ulcers (VLUs) are a chronic and often debilitating condition, affecting a significant number of individuals worldwide. One of the most distressing aspects of VLUs is the persistent pain they can cause, which impacts quality of life, mobility and overall wellbeing. Despite advances in wound care, VLU-related pain remains under-recognised and poorly managed. Pain in VLUs is complex and typically includes nociceptive pain from tissue damage, neuropathic pain due to nerve involvement, and probable central sensitisation. Each type requires targeted treatment, yet clinical awareness and tailored strategies are often lacking. This article explores the multifaceted nature of VLU pain and highlights the importance of a multidisciplinary approach. It reviews the evidence on pain mechanisms, patient experiences, and effective management strategies, both pharmacological and non-pharmacological. By enhancing understanding and applying best practices, health professionals can effectively address VLU-related pain, leading to improved outcomes and better quality of life for patients.
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease for which novel therapeutic approaches are urgently needed. Transforming Growth Factor-β (TGF-β) plays a central role in IPF pathogenesis by activating lung fibroblasts. Inhibitor of DNA binding (ID) proteins are regulated by TGF-β; however, their role in IPF remains poorly understood. We aimed to evaluate the regulation of ID proteins in IPF and to determine their functional role in human lung fibroblasts (HLF) in vitro and pulmonary fibrosis in vivo. ID protein expression was assessed in lungs and lung fibroblasts from mice and patients with pulmonary fibrosis. In vitro, the effects of ID1/ID3 inhibition and overexpression on HLF proliferation, migration and differentiation into myofibroblasts were evaluated. Genetic and pharmacological approaches were used in vivo to determine the role of ID1/ID3 in pulmonary fibrosis. ID1/ID3 levels were elevated in lungs and lung fibroblasts from mice and patients with pulmonary fibrosis, as well as in HLFs treated with TGF-β. ID1/ID3 knockdown reduced proliferation, migration and differentiation of healthy and IPF-derived HLFs. Bleomycin-exposed ID1/ID3 double KO mice exhibited improved lung function and reduced fibrosis compared with WT mice. Pharmacological inhibition of ID1/ID3 decreased HLF proliferation, migration and differentiation in vitro and attenuated pulmonary fibrosis in vivo. Lung-specific inhibition of ID1/ID3 using adeno-associated viruses expressing short hairpins targeting ID1 and ID3 also reversed pulmonary fibrosis in mice. Mechanistically, ID1/ID3 inhibition reduced fibroblast proliferation through regulation of cell cycle genes and attenuated fibroblast differentiation via the MEK/ERK pathway. Simultaneous inhibition of ID1 and ID3 attenuates pulmonary fibrosis. Targeting ID1/ID3 represents a potential novel therapeutic strategy for IPF.
Central disorders of hypersomnolence, a wide and heterogeneous group of neurological disorders including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), are chronic, rare, under-recognized, and disabling conditions characterized by excessive daytime sleepiness (EDS) and other symptoms adversely impacting patients' lives. Large, harmonized real-world datasets are needed to improve phenotypic characterization, diagnostic accuracy, and translational research. The Italian Registry for Narcolepsy and Central Disorders of Hypersomnolence (ReN&IS) is a national, multicenter, observational registry established in 2022. This preliminary analysis presents and compares demographic features, disease presentation, diagnostic assessment, medical comorbidities, current treatment patterns, and symptoms' evolution across diagnostic NT1, NT2, and IH groups of patients enrolled across 20 Italian referral centers. From March 2022 to September 2025, 480 cases were entered in the ReN&IS. NT1 accounted for 80.0% of cases, NT2 for 14.6%, and IH for 5.4%. NT1 showed younger age at onset and enrollment than NT2 and IH, as well as the highest burden of REM-sleep-related symptoms and clear biomarker profiles (HLA DQB1∗06:02 positivity and low cerebrospinal fluid orexin-A levels). Although most patients were treated with non-pharmacological (58-77%) and pharmacological (88-94%) interventions, residual EDS was common in the different groups (65-85%). Obesity and medical comorbidities, including cardiovascular, pulmonary, and connective tissue diseases did not significantly differ across groups. ReN&IS provides the first nationwide, real-world characterization of central disorders of hypersomnolence in Italy, highlighting diagnostic and therapeutic gaps, and offering a robust platform for future longitudinal and translational studies.
Hand-foot syndrome (HFS) is a common side effect of chemotherapy drugs such as 5-fluorouracil and capecitabine, impairing daily function and quality of life. This study aimed to compare international clinical guidelines regarding assessment and management of HFS to identify areas of consensus and divergence and evidence gaps. Guidelines were identified through PubMed (from inception to February 2025), with a supplementary search on Google. Only the most recent versions of English guidelines were included. Data extraction focused on the guideline methodology and recommendations on the prevention, assessment, and management of HFS. Each guideline was critically appraised using the AGREE II checklist. Six guidelines were identified authored by the following cancer agencies: British Columbia Cancer (BCC), European Society of Medical Oncology (ESMO), Cancer Institute NSW (eviQ), Oncology Nursing Society (ONS), United Kingdom Oncology Nursing Society and Acute Oncology (UKONS AO), and United Kingdom North Cancer Alliance (UKNCA). Regarding prevention, five of six guidelines (83%) advised avoiding chemical and physical stressors to the hands and feet and using alcohol-free moisturizer. Only ESMO, BCC, and eviQ recommended oral celecoxib to prevent capecitabine-induced HFS. ESMO and ONS recommended cooling procedures to prevent taxane-induced HFS. Likewise, BCC and eviQ recommend cooling procedures for all agents. All guidelines except ONS recommended dose suspension with grade 2 or 3 HFS and continuation when resolved or improved. ESMO and BCC recommended topical corticosteroids for grade 1 HFS, ESMO for grade 2 or 3, and eviQ for prophylactic use. Finally, BCC and ESMO suggested to consider oral dexamethasone for PEGylated doxorubicin-induced HFS. While general skin care and dose modification guideline recommendations were consistent, pharmacological recommendations varied. Guidelines are key for healthcare professionals in supporting patients with HFS. Therefore, regular updates with emerging evidence for interventions such as topical diclofenac are needed to ensure the quality of care.
Patient experience data (PED), including patient-reported outcomes (PROs), patient-reported experiences (PREs), patient preferences (PPs), and patient input, are instrumental to better understand patients' perspectives and inform decision-making. Healthcare decision-makers increasingly recognize the value of PED, but challenges impede its implementation in practice. This qualitative study aims to identify stakeholders' insights on these barriers, as well as opportunities and concrete policy ways forward for systematically implementing PED in healthcare decision-making. Semistructured interviews (n = 38) were conducted with stakeholders from healthcare industry, academia, non-profit organizations, regulatory authorities, pricing and reimbursement (P&R) agencies, and patient organizations across Europe. The interviews were transcribed ad verbatim and analysed qualitatively using thematic framework analysis. Stakeholders raised several barriers impeding the integration of PED in healthcare decision-making: (1) lack of clear European policy frameworks and guidance on standardized requirements and quality criteria for collecting and evaluating PED, particularly concerning the design and implementation of PP studies, (2) lack of validated methods and tools for collecting high-quality PED, such as validated PRO measures, and (3) limited knowledge and transparency on the assessment of PED in regulatory and P&R decision-making. Stakeholders emphasized the importance of providing training on effective patient involvement and more research on validated methods and fit-for-purpose tools. Stakeholders emphasized the importance of fostering collaboration and open dialogue among all stakeholders. Developing guidelines and a comprehensive policy strategy that clearly delineates expectations and responsibilities for each stakeholder group was seen as an important way forward. This policy- and practice-oriented qualitative study identified concrete ways to advance the systematic use of PED in healthcare decision-making. Suggested actions include developing validated and standardized methods and tools, co-created and flexible guidelines and a clear European policy framework delineating expectations and responsibilities. While there was broad alignment on the direction forward, views diverged on who should take the lead in initiating these efforts, underscoring the importance of continued coordination across stakeholder groups.
Cancer is a major global issue threatening the whole world, especially developing countries. Treatment of cancer using chemotherapy and radiotherapy has several consequences that negatively affect the quality of life of cancer patients. Bee products have numerous pharmacological effects and clinical impacts due to their extraordinary chemical composition. The objective of the current work is to shed light on preclinical studies and clinical trials of bee products, particularly propolis, honey, and royal jelly, with special emphasis on their role in reducing the complications of chemotherapy and radiotherapy by employing a variety of databases. The search used specific keywords, including "bee products", "propolis", "honey", "royal jelly", "cancer", "clinical trials", "radiotherapy", and "chemotherapy". Only peer-reviewed randomized controlled trials (RCTs) and published research papers were included. According to the literature review, bee-generated propolis, honey, and royal jelly have been used in animal models to reduce the adverse effects of radiotherapy and chemotherapy. Depending on the kind of cancer, different dosages and treatment times were used for certain bee products. Bee products are used in various forms, such as crude, in capsules, mouthwashes, tablets, and oils. Propolis, royal jelly, and honey are used at dosages up to 400 mg, 1 g, and 50 g, respectively. Clinical trials have further confirmed their efficacy in cancer treatment, either as standalone therapies or as supplements to conventional treatments. It is crucial to investigate the active mechanisms of these products further and to include them in additional clinical trials as potential cancer treatments.
Fibrocalcific aortic valve disease (FCAVD) is a progressive and multifactorial pathology that remains asymptomatic in its early stages and lacks effective pharmacological therapies. Aortic valve sclerosis (AVSc), the initial phase of FCAVD, is marked by leaflet thickening and early calcium deposition without significant hemodynamic changes. While local inflammation is known to drive valvular remodeling, recent studies suggest that systemic inflammation may also play a critical role, potentially interacting with endothelial (VEC) and interstitial cells (VIC) and thus promoting disease progression. Notably, sex differences in fibrocalcific processes have been identified, yet their mechanistic basis remains understudied. Thus, we hypothesize that systemic inflammation exacerbates endothelial dysfunction and accelerates fibrocalcific remodeling, with distinct processes in men and women, and aim to investigate how these mechanisms contribute to disease progression. A total of 238 individuals were enrolled across three groups: controls (CTRL n = 80), AVSc (n = 78), and severe aortic stenosis (AS n = 80). A broad panel of circulating cytokines was measured and analyzed with respect to sex and disease stage. To assess the functional impact of key cytokines, in vitro experiments were conducted using human VECs and VICs treated with interleukin-1β (IL-1β) and interferon-β (IFNβ). Cellular responses were evaluated via morphological analyses, gene and protein expression assays, and calcification potential under normal and pro-osteogenic conditions. Cytokine profiling revealed that AVSc patients exhibited significantly elevated levels of IL-1β compared to both CTRL and AS, with IL-1β being consistently higher in males across all stages. In vitro, IL-1β triggered endothelial-to-mesenchymal transition in VECs, promoting a pro-fibrotic and inflammatory phenotype. Sex-stratified analysis of VICs showed that IFNβ enhanced RUNX2 expression and calcification in a dose-dependent manner, with female-derived VICs being more responsive. Conversely, IFNβ exerted anti-fibrotic effects by reducing COL1A1 and ACTA2 expression, more markedly in female cells, particularly at the protein level. Our findings reveal a previously overlooked role of systemic inflammation, primarily driven by IL-1β and IFNβ, in promoting early endothelial activation and sex-specific fibrocalcific remodeling in FCAVD. These cytokines not only serve as markers of disease but also actively influence cell-specific responses, shaping the distinct aortic valve fibrocalcific patterns observed in men and women. Unraveling these mechanisms could open new avenues for developing early monitoring of circulating IL-1β and IFNβ, while informing sex-specific therapeutic strategies to modulate cytokine signaling to slow or prevent FCAVD progression.
Sarcopenia has emerged as a potential prognostic factor in patients with advanced prostate cancer (PCa), requiring interventions for its prevention and treatment. We aimed to systematically identify, critically assess and synthesize the available evidence on the effectiveness and safety of interventions for preventing or treating sarcopenia in advanced PCa patients. MEDLINE, Embase and Web of Science were searched. Randomized and non-randomized controlled trials or longitudinal observational studies with a control group focusing on PCa patients aged 60 years and older were considered. Study selection, data extraction and risk-of-bias assessment of the included studies were performed in duplicate. When possible, pooled effect estimates were calculated. Twenty studies (n = 1275) were included. Resistance training (RT) (MD = 3.22 kg; 95% CI 0.69, 5.75) and the use of antimyostatin peptibody (MD = 2.2 kg; SE 0.8%) demonstrated statistically significant prevention of lean body mass loss in men undergoing androgen deprivation therapy (ADT). Exercise improved leg press (MD = 25.17 kg; 95% CI [8.71, 41.62]), leg extension (MD = 9.63 kg; 95% CI [4.83, 14.42]), seated row (MD = 4.38 kg; 95% CI [1.54, 7.22]) and chest press strength (MD = 1.70 kg; 95% CI [-1.48, 4.88]) and enhanced patients' physical functioning in chair sit-to-stand tests (MD = -1.02 kg; 95% CI [-1.70, -0.34]). RT improved health-related quality of life (HRQoL) in both general and specific domains and also reduced somatization (MD = -0.69 kg; 95% CI [-1.32, -0.07]) and psychological distress (MD = -1.63 kg; 95% CI [-3.10, -0.15]). The findings highlight the potential benefits of RT and selected pharmacological interventions on muscle-related and functional outcomes. However, the significant heterogeneity and lack of comprehensive outcome reporting underscore the need for more standardized and long-term research through larger, well-designed randomized controlled trials with standardized measurement methods to draw conclusive evidence and enhance the reliability and applicability of findings in clinical practice.
Despite growing evidence and specific guidelines, people with knee and hip osteoarthritis often do not receive appropriate care. This review aims to identify healthcare utilisation and its predictors to optimise existing services and identify unmet needs across different healthcare systems using Andersen's Healthcare Utilisation Model as a reference. We conducted a scoping review and included studies published between 2010 and 2023 that assessed the healthcare utilisation in people with osteoarthritis. We examined general practitioner and orthopaedist consultations, physiotherapy, medication, hospitalisation and emergency department visits. PubMed, Livivo, Cochrane Library, CINAHL Complete and Web of Science were searched from January 2010 until November 2023. An updated literature search was conducted in December 2025. We analysed the included studies by means of thematic analysis and descriptive representation of quantitative data. The literature search identified 4228 articles, of which 2380 articles were included in the title/abstract screening after excluding duplicates. After the full-text screening of 97 articles, we included 39 (n=4 233 566) publications for data extraction and data synthesis. Most studies were conducted in the USA, Australia, Germany and the UK-few from Asia, Middle and South America and other European countries. Utilised healthcare services are general practitioner consultations (mean use: 43% of participants, n=6), opioid (36%, n=8) and non-steroidal anti-inflammatory drug use (42%, n=7), emergency department visits (27%, n=3), orthopaedic surgeon consultations (26%, n=4), total joint replacement surgery (26%, n=3), physiotherapy (14%, n=8), hospitalisation (11%, n=7) and psychotherapy (6%, n=2). Among predisposing characteristics, older age, female gender, ethnicity, high socioeconomic status, social support and fear of certain treatment options were related to higher healthcare utilisation. In those, gender (n=8 studies) and age (n=6 studies) were primarily discussed. Regarding enabling and need factors, increased healthcare utilisation is associated with urban residence and being insured as well as having pain and comorbidities. Results vary between countries. Against the background of existing guidelines, there is a need for promoting the utilisation of non-surgical and non-pharmacological treatments, such as physiotherapy, which have proven to be effective. Special attention should be given to predictors when promoting appropriate healthcare utilisation. Addressing the identified predictors associated with healthcare utilisation may lead to more appropriate osteoarthritis care. Further research is needed to address healthcare stakeholders' (physiotherapists, insurers, patients and practitioners) needs and roles in the process. Protocol registration on PROSPERO (CRD42023475803).
This study investigated the relationship between the HPLC fingerprint of Vinegar-Processed Schisandra (VPS) and its hepatoprotective effects, aiming to identify the main active components and establish a quality control method. An HPLC fingerprint was developed along with a quantitative analysis of multiple components using a single marker (QAMS), a total of 10 common peaks were identified. Using schisandrol A as the internal reference, relative correction factors (RCFs) and relative retention values were determined for nine other components, including gomisin D. The hepatoprotective effects of different batches of VPS-derived total lignans were evaluated in a mouse model of alcohol-induced liver injury (ALI). The extracts significantly regulated 10 pharmacological indicators, including ALT and AST, associated with ALI. Gray relational analysis and Pearson correlation analysis revealed that all 10 lignan compounds contributed to the hepatoprotective efficacy, suggesting their role as the primary pharmacologically active constituents. This study provides a scientific basis for understanding the material foundation of VPS in against ALI and offers a reliable method for quality assessment.