Search PubMedSearch

SEARCH · Search PubMed

Results for “Prospective study”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

1,802 records · Page 20Linked to original sources

Novel histopathologic findings in abdominoscrotal hydrocele: Clues to pathogenesis.

PURPOSE: To evaluate whether underlying histological alterations in hydrocele sac wall can provide an explanation of difference in abdominoscrotal hydrocele (ASH) and communicating hydrocele (CH) behavior. The aim of this study is to assess the immunohistopathologic characteristics of CH and ASH sac walls in pediatric patients. METHODS: In a retrospective case-control study, patients diagnosed with ASH or CH underwent surgical management at a tertiary pediatric center. Samples of ASH or CH wall sac were obtained for histopathologic evaluations, especially for contractile units and fibromuscular components. These assessments comprised Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining for smooth muscle actin (SMA), Myogenin and Caldesmon (H-CALD) to identify and quantify the presence of cells with striated or smooth muscle origins. All patient's imaging, clinical and demographic data were evaluated. All statistical analysis performed using SPSS software and p-value of <0.05 considered as the level of significance. RESULTS: Among 38 patients in our case-control study, 14 (36.84%) patients referred with bilateral hydrocele. The intra-operative observation of all ASH cases indicated no patent processus vaginalis. The IHC evaluations of ASH and CH specimens demonstrated that there is a significantly higher expression of SMA (median 5.73% versus 0.56%, P-Value <0.001), H-CALD (median 9.28% versus 0.18%, P-Value <0.001) in comparison to those of CH. CONCLUSION: The higher expression of smooth muscle and myofibroblast origins in the ASH wall suggests the potential of consistent contractility, which likely affects the secretion-reabsorption imbalance. Performing histologic studies can enhance our understanding of ASH pathogenesis and clinical characteristics.

Humans

Global Seroprevalence of Q Fever Antibodies to Coxiella burnetii in Children and Adolescents : A Systematic Review and Meta-analysis.

OBJECTIVE: To comprehensively determine global estimates of Q fever seroprevalence in children and adolescents by conducting a systematic review and meta-analysis. DATA SOURCES: Searches of published articles in MEDLINE, Embase and Scopus databases were conducted from inception until February 2025. STUDY SELECTION: Cross-sectional studies reporting seroprevalence of Q fever/ Coxiella burnetii antibodies, using any established laboratory test, in any population of healthy children and adolescents <20 years old were included. The quality of eligible articles was assessed using a modified Newcastle-Ottawa Scale. DATA EXTRACTION: Data from eligible articles were extracted using a standardized form, which included year of publication, year(s) the study was conducted, numbers of antibody-positive cases/specific population, age, country, geographic region, serology test used and antibody titer cutoff value. DATA SYNTHESIS: DerSimonian and Laird random effects models were used to calculate pooled seroprevalence estimates and 95% confidence intervals in data from 41 eligible articles reporting 42 studies comprising 9841 children and adolescents. Q fever seroprevalence was observed in multiple countries across 7 geographic regions, and varied markedly between countries and regions, with the highest estimate observed by an individual country in Ethiopia (45%) and by region in the Middle East (14%). Seroprevalence estimates were higher in older children and adolescents &#x2265;10 years (15%) compared with younger children <10 years of age (8%). CONCLUSION: Despite varying geographical prevalence, our findings demonstrate that widespread exposure to Q fever antigens occurs across multiple global regions in children and adolescents to potentially serious C. burnetii infection, indicating that diagnostic surveillance and preventive measures should be considered in both endemic and previously unreported areas.

Humans

Shared Medical Appointments for Substance Use Disorders: A Systematic Review.

BACKGROUND: Shared medical appointments (SMAs) integrate group-based clinical care with individual medical management and are increasingly used in the treatment of substance use disorders (SUDs) to improve access, engagement, and care coordination. However, their use, outcomes, and implementation in SUD care have not been systematically synthesized. METHODS: We conducted a systematic review registered with PROSPERO (CRD42025639504). MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Central were searched from database inception through September 2025. Randomized controlled trials, observational studies, and qualitative studies examining SMAs among adults with SUDs were included. Outcomes of interest included treatment engagement and retention, substance use outcomes, mental health and patient-reported outcomes, and implementation characteristics. Study quality was assessed across quantitative and qualitative designs, and findings were synthesized descriptively. RESULTS: Fourteen studies, representing approximately 578 participants, met inclusion criteria. Twelve studies focused exclusively on opioid use disorder, 1 included both alcohol and opioid use disorders, and 1 did not specify substance type. Treatment retention was reported in 6 studies, with a median 6-month retention of 72.9%. Three studies reported reductions in substance use outcomes, and 2 reported improvements in depression or anxiety. Qualitative studies consistently described high patient satisfaction, peer support, and shared accountability. Implementation studies demonstrated feasibility across diverse outpatient settings, with substantial heterogeneity across study designs and outcomes. CONCLUSIONS: SMAs appear feasible and acceptable for addiction care and may support treatment retention and patient experience. Evidence remains heterogeneous and largely observational, highlighting the need for rigorous comparative studies to better define effectiveness and implementation.

Humans

The transverse preputial onlay island flap: A reliable option for repair of small-glans hypospadias.

BACKGROUND: The Transverse Preputial Onlay Island Flap (TPOIF) technique is frequently used in cases with mild chordee and small glans. This study's objective was to evaluate the surgical outcomes of this technique at our center. MATERIALS AND METHODS: This study consisted of hypospadias patients diagnosed with small glans (diameter <14 mm) and mild chordee (<30&#xb0;), underwent TPOIF urethroplasty. RESULTS: A total of 64 cases were included in this study. The mean glans diameter was 10.6 mm. The complication rate was 9.4 %. CONCLUSIONS: The TPOIF technique provides encouraging results for treating hypospadias with small glans, though larger studies are needed.

Humans

Clinical characteristics and outcomes of post-stroke seizures following reperfusion therapy: a retrospective single-center study.

BACKGROUND: Post-stroke seizures (PSS) are a recognized complication of ischemic stroke and may adversely affect functional outcomes and survival; however, their characteristics in patients receiving contemporary reperfusion therapy remain incompletely defined. We aimed to describe the clinical characteristics, treatment patterns, and outcomes of patients who developed PSS following reperfusion therapy and to compare early- and late-onset seizure subgroups. METHODS: This single-center retrospective study included adult patients with acute ischemic stroke treated with intravenous thrombolysis (IV-tPA), mechanical thrombectomy (MT), or combined therapy between January 2020 and September 2025. Early seizures were defined as occurring within 7&#xa0;days of stroke onset. Clinical, radiological, and treatment-related variables were analyzed, and functional outcome was assessed using the modified Rankin Scale at 3&#xa0;months. RESULTS: Of 1242 patients who received reperfusion therapy, 53 (4.27&#xa0;%; 95&#xa0;% CI 3.28-5.54) developed PSS. Observed seizure rates were 3.39&#xa0;% in the MT group, 4.06&#xa0;% in the IV-tPA group, and 7.02&#xa0;% in the combined therapy group; these observed rates did not differ significantly across treatment modalities. Early seizures occurred in 23 patients and late seizures in 30. No significant differences were found between early- and late-onset seizure subgroups in demographic characteristics, vascular risk factors, stroke severity, reperfusion success, or clinical outcomes, with the exception of an isolated, exploratory difference in stroke laterality. Three-month mortality among patients with PSS was 45.28&#xa0;% (95&#xa0;% CI 32.66-58.55), and in-hospital mortality was 20.75&#xa0;%. CONCLUSIONS: In this single-center cohort, the incidence of PSS after reperfusion therapy was comparable to previously reported rates, with no marked differences across treatment modalities. The high mortality among patients with PSS likely reflects underlying stroke severity rather than a treatment-specific risk.

Humans

Corneal Epithelial Alterations Associated With Cyclin-Dependent Kinase 4/6 Inhibitor Therapy in Hormone Receptor-Positive Breast Cancer.

IMPORTANCE: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are standard therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. By blocking the G1/S cell-cycle transition, these agents may impair renewal of the corneal epithelium. No controlled study has systematically evaluated corneal epithelial changes in patients receiving CDK4/6 inhibitors. OBJECTIVE: To determine whether CDK4/6 inhibitor-based therapy is associated with cornealepithelial alterations independent of aromatase inhibitor exposure and tear film dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Retrospective comparative cross-sectional study at a tertiary ophthalmology center. A total of 132 women were enrolled: 45 receiving a CDK4/6 inhibitor plus an aromatase inhibitor (CDKAI group), 44 receiving aromatase inhibitor monotherapy (AI group), and 43 age-matched postmenopausal controls without systemic oncologic therapy. EXPOSURES: CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) combined with an aromatase inhibitor; aromatase inhibitor alone; or no systemic oncologic therapy. MAIN OUTCOMES AND MEASURES: Prevalence and severity of punctate epitheliopathy and vortex keratopathy, assessed by a masked ophthalmologist. Secondary outcomes included Schirmer I test, tear film break-up time, and Ocular Surface Disease Index (OSDI). RESULTS: PE was present in 44.4% of eyes in the CDKAI group vs 4.7% in the AI group and 2.3% in controls (&#x3c7;&#xb2; = 34.31; P < .001). All moderate (13.3%) and severe/complicated (8.9%) PE cases occurred exclusively in the CDKAI group. Vortex keratopathy was observed in 13.3% of CDKAI patients and in none of the other groups (P = .025). Schirmer values, tear film break-up time, and OSDI scores did not differ among groups (all P > .05). Within the CDKAI group, PE was not associated with treatment duration (P = .963) or tear film parameters. CONCLUSIONS AND RELEVANCE: In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of PE and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Symptom scores were low, although OSDI interpretation was limited by incomplete responses. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

Humans

Comprehensive study on pesticide residues and mycotoxins in freeze-dried strawberries and raspberries.

Freeze-dried fruit has gained popularity because it preserves the flavour and nutritional value of fresh fruit while providing extended shelf life. Despite this, there are concerns regarding its chemical safety. This study evaluated 58 freeze-dried fruit products from the Czech retail market, focusing on potential contamination. Pesticide residues and mycotoxins were determined using LC-MS/MS and GC-MS/MS. Overall, 111 pesticide residues (or their metabolites) and 3 mycotoxins were quantified. After applying processing factors, 12 pesticide residues exceeded EU maximum residue limits. Prohibited substances, including carbofuran, omethoate, and haloxyfop, were detected. Tenuazonic acid was found in 71% of samples, while alternariol and tentoxin were detected less frequently. More than half (54%) of strawberry samples contained 10 or more pesticide residues, indicating potential cumulative exposure concerns, particularly for children with lower body weight. These findings highlight the need for continued monitoring of freeze-dried fruits and further assessment of dietary exposure.

Pesticide Residues

CL16019, A Combination of Cissus quadrangularis and Boswellia serrata Extracts Promotes the Healing of Distal Radius Fractures: A Multicentric, Randomized, Open-Label Study.

OBJECTIVE: Distal radius fracture (DRF) is the most frequent injury to the upper limb. Complications include nonunion, wrist stiffness and instability, local discomfort, and tendon irritation. The purpose of the current open-label clinical study was to evaluate the safety, efficacy, and tolerability of CL16019, an herbal formulation of Cissus quadrangularis and Boswellia serrata extract, in accelerating fracture healing in volunteers with DRFs. METHODS: Fifty participants (both male and female; age: 30-50 years) with type I, IIA, or IIB DRFs (as per Lidstrom classification) were equally randomized and treated with standard treatment (ST) or ST + CL16019 for 60 days. The primary efficacy outcome was the radiographical bone fracture healing rate as scored by the Radius Union Scoring System (RUSS). Pain, swelling, and tenderness were among the clinical characteristics evaluated using the visual analog scale (VAS). Wrist function improvements were assessed using the Patient-Rated Wrist Evaluation Questionnaire (PRWEQ). The intergroup and intragroup results were analyzed using a paired t-test and an analysis of covariance model, respectively. RESULTS: The RUSS scores for the ST and ST + CL16019 groups at the end of the trial were 5.54 &#xb1; 1.77 and 7.96 &#xb1; 0.20, respectively, with a p-value <0.0001. In addition, the CL16019 volunteers showed substantial (p < 0.05) declines in their VAS and PRWEQ scores. The ST + CL16019 group demonstrated higher Physician Global Assessment and Subject Global Assessment scores. CONCLUSIONS: Supplementation of CL16019 along with standard therapy was found to enhance the bone fracture healing rate, possibly by accelerating the callus formation rate and enhancing cortical bridging. These findings imply that CL16019 might be a good adjunctive in addition to ST for the faster healing of DRFs. The trial was registered with the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2021/12/039006, on December 29, 2021.

Humans

Evaluation of Physical and Mental Workload and Transfusion Time in Trauma Resuscitation.

BACKGROUND: Trauma resuscitation is time sensitive and complex. Whole blood (WB) and blood components are standard treatments for trauma related hemorrhage, yet their nursing workload and transfusion time have not been well evaluated. PURPOSE: To assess feasibility of a simulation-based crossover trial and obtain preliminary estimates comparing nursing workload and transfusion completion time between WB and blood component administration. METHODS: A randomized crossover pilot study using in situ simulation was conducted with experienced trauma nurses. Time-motion analysis measured transfusion completion time, and the National Aeronautical and Space Administration Task Load Index assessed workload domains. RESULTS: Strong feasibility was demonstrated across recruitment, retention, adherence, and completion. WB was associated with significantly shorter transfusion time, lower overall workload and mental demand, less effort, and better perceived performance. CONCLUSIONS: These findings support the feasibility and justify a fully powered trial. WB may improve resuscitation efficiency and reduce cognitive burden, with potential implications for patient outcomes and nursing workflow.

Humans

Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study.

Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE-942 study (ClinicalTrials.gov identifier: NCT03897881). Eligible patients with resected stage IIIB to IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks. The primary end point was recurrence-free survival (RFS); secondary end points included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), the median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5-76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (hazard ratio [HR], 0.510 [95% CI, 0.294 to 0.887) and DMFS (HR, 0.411 [95% CI, 0.200 to 0.843]), with a favorable trend in overall survival (HR, 0.471 [95% CI, 0.165 to 1.345]) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After a 5-year follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.

Humans

Lower urinary tract evaluation in children with cerebral palsy: A crossectional study.

INTRODUCTION: Cerebral palsy (CP) is a chronic, non-progressive motor disorder affecting voluntary movement and posture. Lower urinary tract (LUT) dysfunction is highly prevalent in children with CP. This study aims to evaluate LUT function in children with CP. MATERIAL AND METHODS: This cross-sectional study was conducted at a tertiary care hospital. Patients aged 5-18 years with established CP diagnosis were included. Evaluation included clinical history, physical examination, urinary ultrasonography with post-void residual (PVR) measurement, and urodynamic studies when indicated. Patients were categorized into three groups; group-1 (LUT dysfunction), group-2 (symptomatic), and group-3 (asymptomatic) for analysis. RESULTS: The study included 97 children with CP (41 girls, 56 boys; median age 8 years). Of the patients, 61.8% were ambulatory (GMFCS I-III) and 38.2% were non-ambulatory (GMFCS IV-V). At least one LUT symptom was detected in 75.3% of patients. Incontinence was the most common symptom at 69.1%. Incontinence prevalence was significantly higher in non-ambulatory patients (81.1% vs 61.7%, p = 0.044). Invasive urodynamics was performed in 19 patients, and LUT dysfunction was diagnosed in 89.5% of them (19.3% of the entire population). Prematurity rate was significantly higher in patients with LUT dysfunction (94.1% vs 64.8%, p = 0.017). Binary logistic regression analysis identified elevated PVR as the strongest independent risk factor for LUT dysfunction (OR = 108, p < 0.001). Abnormal urinary frequency (OR = 14.9, p = 0.022) and quadriplegia (OR = 10.3, p = 0.016) were other independent risk factors. ROC analysis determined the optimal cut-off value for PVR as 19 mL (sensitivity 58.82%, specificity 94.92%). In the intergroup analysis, multinomial logistic regression identified elevated PVR as the strongest predictor (Group-1 vs Group-2: OR = 101; Group-1 vs Group-3: OR = 24, both p < 0.003). Lower gestational age was also an independent risk factor in both comparisons (OR = 1.25-1.26, p < 0.020). DISCUSSION: This study demonstrates LUT dysfunction affects 19.3% of children with CP, strongly correlating with motor impairment severity. Elevated PVR emerged as the strongest independent predictor (OR = 108), offering a practical non-invasive screening tool. Our proposed urodynamic criteria achieved 94.7% diagnostic yield, enabling selective evaluation. Limitations include single-center design and cross-sectional methodology without longitudinal follow-up. These findings support integrating systematic urological assessment into standard CP care for early intervention. CONCLUSION: LUT dysfunction prevalence is high in children with CP, and symptom frequency increases with higher GMFCS levels. Elevated PVR is the strongest predictor, with a clinically applicable cut-off value of 19 mL. Particularly in quadriplegic, non-ambulatory, and premature patients, close follow-up and urodynamic evaluation when necessary should be performed with a multidisciplinary approach.

Humans

Sexual Abuse in Girls Aged &#x2264;14: A Retrospective Observational Swiss Study.

INTRODUCTION: Child sexual abuse (CSA) is a critical public health concern with enduring physical and psychological consequences. OBJECTIVE: This study aimed to describe the sociodemographic profiles, contextual circumstances, and clinical findings of reported CSA cases involving girls aged &#x2264;14, recorded between 2018 and 2021 at two university hospitals in Switzerland: Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois - CHUV) and Geneva University Hospitals (H&#xf4;pitaux Universitaires de Gen&#xe8;ve - HUG) to inform prevention and intervention strategies. METHODS: This retrospective observational study included 95 cases identified through forensic consultations at CHUV and HUG. All eligible cases recorded between 2018 and 2021 were analyzed. Collected data included sociodemographic characteristics, assault circumstances, perpetrator-victim relationship, and clinical findings. RESULTS: The median age of children exposed to sexual assault was 7 years (IQR 4-14). Intra-familial abuse predominated among premenarcheal girls (41.7%), while postmenarcheal girls were more frequently assaulted by non-familial perpetrators (76.2%) and experienced higher rates of physical violence (47.6%). Genital lesions were documented in 41% of cases, with a higher prevalence among younger patients, and were rarely specific to CSA. CONCLUSION: This study provides a detailed descriptive overview of CSA cases involving girls aged &#x2264;14 in two Swiss cantons. It highlights age-related patterns in perpetrator profiles, assault characteristics, and clinical findings. Prevention strategies should be age-specific, addressing intra-familial risk in younger children and peer-related or situational vulnerabilities in adolescents. These findings support the implementation of standardized forensic practices, improved surveillance systems, and targeted prevention and care strategies.

Child sexual abuse Intra-familial abuse Pediatric

Preparation and study of non-thrombotic and biostable sulfobetaine-modified small-diameter polyurethane vascular grafts.

A novel sulfobetaine-modified polysiloxane-polycarbonate polyurethane (ZSiPCU) was synthesized. In vitro characterizations revealed that polysiloxane surface enrichment endowed the material with excellent biostability. Importantly, sulfobetaine zwitterions formed a robust hydration layer, effectively suppressing protein adsorption and platelet adhesion to ensure outstanding hemocompatibility. Furthermore, the material supported the adhesion and proliferation of vascular endothelial cells, confirming its cytocompatibility, while its elastomeric matrix provided rapid mechanical self-sealing capabilities. Electrospun ZSiPCU grafts were evaluated in a 3-month rat abdominal aorta model, maintaining high patency rates and facilitating in situ luminal endothelialization and smooth muscle cell remodeling. Additionally, superior puncture resistance of the grafts was demonstrated by puncture tests, with complete hemostasis achieved within 2&#x202f;mins through mechanical self-sealing.

Polyurethanes

Temporal Trends and Spatial Variation in Preterm Prelabour Rupture of Membranes: A Population-Based Study.

OBJECTIVE: To describe the temporal trends in Preterm prelabour rupture of membranes (PPROM) in metropolitan France and the geographical distribution at the administrative division level. DESIGN: Exploratory population-based study using administrative data of the French National Health Data System. SETTING: Metropolitan France, 2015 to 2023. POPULATION: Pregnancy with a diagnosis of PROM before 37 SA. METHODS: Annual crude incidence of PPROM was calculated by dividing the number of pregnancies with PPROM diagnosis by the number of live births recorded during the same period. Annual trend was estimated by a binomial negative mixed model. Smoothed standardised incidence ratios were estimated based on a BYM2 model, which accounts for spatial variability between departments. MAIN OUTCOME: PPROM cases, defined as pregnancies with first hospitalizations with a diagnosis of PROM before 37&#x2009;weeks. RESULTS: Over the study period, we included 150&#x2009;615 PPROM cases representing 16&#x2009;735 (&#xb1;596) per year. Incidence of PPROM cases showed an ascending trend over time (incidence rate ratio 1.023 per year; 95% CI: 1.017-1.030) with an annual crude incidence ranging from 2.2% in 2015 to 2.7% in 2023. A decrease in the incidence was observed in 2020 relative to other years (incidence rate ratio 0.903, 95% CI: 0.887-0.920). A map of smoothed SIRs of PPROM cases at the French administrative division level revealed geographical inequalities. CONCLUSIONS: This first population-based study describing PPROM cases in metropolitan France paves the way for further studies to explore environmental hypotheses. Identifying temporal and geographical disparities in PPROM incidence is relevant to public health policy and practice as such disparities argue for the development of targeted prevention strategies in high-risk areas.

French national health data system

Water intake, switching between bites and sips, and drinking behavior are associated with food intake across meals varying in spiciness: A secondary analysis of two randomized crossover studies.

Widespread nutrition advice instructs consumers to drink water with meals to increase fullness and reduce energy intake. However, recent data indicates greater water intake is associated with more food intake at a meal, not less. Switching between meal components (e.g., alternating between food and water), has also been associated with increased food intake at a pasta meal, but it remains unclear whether this applies to other foods. In a secondary analysis, we pooled existing data from 2 crossover experiments (total n&#xa0;=&#xa0;86) where adults ate an ad libitum lunch consisting of 650&#xa0;g of beef chili (n&#xa0;=&#xa0;52) or chicken tikka masala (n&#xa0;=&#xa0;34) with 450&#xa0;g of water twice in the laboratory while being video-recorded. For both experiments, the spiciness of the lunch was varied by adding different ratios of hot:sweet paprika. Videos were coded to measure sip number, sip size (g/sip), drinking rate (g/min), and number of switches between bites of food and sips of water. As we previously reported, increasing spiciness slowed eating rate and reduced food intake; in secondary analyses described here, the reduction in food intake was not moderated by water intake, switching, or drinking behaviors (all p&#xa0;>&#xa0;0.73). Notably, across all meals, greater water intake (p&#xa0;<&#xa0;0.001) and switching (p&#xa0;=&#xa0;0.02) associated with greater food intake. Overall, individuals ate more when they drank more and switched between bites and sips more often, highlighting the potential influence of water and drinking behaviors on food consumption. This finding challenges the widespread dietary advice to drink water with meals to reduce food intake.

Humans

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans

Specialized pro-resolving mediator (SPM)-enriched supplementation modulates inflammatory biomarkers in patients with symptomatic knee osteoarthritis: Blood plasma analysis from the GAUDI study.

BACKGROUND: Osteoarthritis (OA) is a leading cause of chronic pain and functional impairment, associated with persistent inflammation, potentially due to impaired resolution. Specialized pro-resolving lipid mediators (SPMs) regulate inflammation resolution and restore homeostasis. The GAUDI study previously demonstrated that SPM supplementation reduces pain and improves quality of life (QoL) in patients with knee OA. This analysis assesses the impact of SPM supplementation on inflammatory biomarkers (IB) and SPM levels and their relationship with clinical outcomes. METHODS: This is a secondary analysis of the GAUDI trial, a randomized, multicenter, double-blind, placebo-controlled study conducted in Spain in adults with symptomatic knee OA who received daily supplementation with SPMs or placebo for 12 weeks. Endpoints included changes in plasma IB and SPM levels and their correlation with clinical outcomes. RESULTS: Changes in IL-1 (15.9 vs. -1.1 pg/ml, p-value: 0.051) and IL-18 (10.3 vs. -1.4 pg/ml, p-value: 0.29) showed a tendency toward reduction in the SPM group compared to the placebo group. Changes in IL-1 and IL-8 positively correlated (r = 0.707, p-value: 0.005 and r = 0.551, p-value: 0.04; respectively) with changes in WOMAC score and negatively correlated (r = -0.797, p-value <0.001 and r = -0.804, p-value <0.001; respectively) with changes in EuroQoL-5 VAS score. Changes in IL-1 (r = 0.554, p-value: 0.048) and IL-6 (r = 0.631, p-value: 0.014 and r = 0.572, p-value: 0.031) correlated with changes in OMERACT-OARSI pain score. No significant differences in IB levels were observed between groups during the intervention. Minor changes in SPM levels point to metabolic pathways at work with SPM supplementation. In patients with a BMI &#x2265;25 kg/m&#xb2;, most IB tended to decrease following SPM consumption. CONCLUSIONS: This analysis suggests a potential association between SPM supplementation, decreased inflammation, and improved pain and QoL in patients with knee OA. Subtle changes in blood plasma SPM levels were detected that indicate, through bioinformatics analysis, a pathway-specific metabolome activation induced by SPM supplementation. TRIAL REGISTRATION: NCT05633849. Registered December 1st, 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849.

Humans

"It was good because they have a relationship with us": A qualitative study on low-threshold buprenorphine treatment at syringe services programs.

INTRODUCTION: Syringe service programs (SSPs) reach people who inject drugs with opioid use disorder (OUD) and are novel "low-threshold" venues to initiate buprenorphine treatment. The study investigated patients' experiences with SSP-initiated buprenorphine treatment, which could aid in improving buprenorphine treatment delivery at SSPs. METHODS: The study included 12 participants who completed qualitative exit interviews after a randomized controlled trial of buprenorphine treatment at SSPs. In the parent study, participants received buprenorphine treatment through an onsite model at an SSP or enhanced referral to a community health center based on the randomization sequence. Most participants started taking buprenorphine at home. Exit interviews included participants from both study arms, and the semi-structured interview guide focused on their experiences with clinicians, experiences initiating buprenorphine, prior experiences with OUD treatment, and perceptions about continuing buprenorphine treatment. Four researchers iteratively read, coded, and discussed each transcript, then they derived recurring themes using thematic analysis. RESULTS: Participants were mostly male, middle-aged, and 50% identified as Latino. Four main themes related to buprenorphine treatment initiation: 1) Onsite treatment facilitated buprenorphine prescription, but some participants also expressed a need for additional support; 2) Precipitated withdrawal complicated participants' buprenorphine initiation in both arms; 3) Participants largely experienced the SSPs as affirming and welcoming; and 4) Developing strong relationships with healthcare providers was critical to successful buprenorphine treatment initiation. CONCLUSIONS: The SSP-based model provided rapid access to buprenorphine prescriptions, but precipitated withdrawal was a common complication. Some participants desired additional support and guidance when they started taking buprenorphine at home. The findings point to a "low-threshold, high-touch" approach where participants receive expedited access to buprenorphine providers at SSPs but also additional support throughout the initiation process to avoid and/or manage precipitated withdrawal. Despite some challenges, SSP-based buprenorphine treatment was highly valued by study participants.

Humans