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Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE).

AIMS: Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once-weekly semaglutide 2.0&#x2009;mg as add-on to dose-reduced insulin glargine (Sema+IGlarreduced) versus dose-titrated IGlar (IGlartitrated) on glycated haemoglobin (HbA1c), body weight (BW), daily insulin dose, and participant satisfaction. MATERIALS AND METHODS: SUSTAIN OPTIMIZE was a 40-week, phase 3b, open-label, randomised study. Adults with T2D, overweight (body mass index &#x2265;&#x2009;25&#x2009;kg/m2), and treatment with basal insulin &#x2264;&#x2009;40&#x2009;units/day were randomised 1:1 into Sema+IGlarreduced or IGlartitrated. The primary endpoint was change in HbA1c using a non-inferiority approach. Secondary endpoints assessed superiority of Sema+IGlarreduced versus IGlartitrated in reducing HbA1c, BW, daily insulin dose, and improving Diabetes Treatment Satisfaction Questionnaire change version (DTSQc) scores. RESULTS: Overall, 573 participants were randomised. Sema+IGlarreduced achieved both non-inferiority and superiority versus IGlartitrated in HbA1c reduction (estimated treatment difference [ETD]: -0.74%; 95% confidence interval [CI95]: -0.90, -0.59) and superiority in BW change (ETD: -8.5&#x2009;kg; CI95: -9.5, -7.4), relative daily insulin dose change (ETD: -121.9%; CI95: -143.1, -100.6), and DTSQc scores (ETD: 2.6; CI95: 1.6, 3.5) (p&#x2009;<&#x2009;0.0001 for all endpoints). No new safety concerns were identified. Severe hypoglycaemia was reduced (rate ratio: 0.45; CI95: 0.23, 0.87; p&#x2009;=&#x2009;0.02), while gastrointestinal events were higher for Sema+IGlarreduced (310 vs. 32 events). CONCLUSIONS: Once-weekly subcutaneous semaglutide 2.0&#x2009;mg as add-on to dose-reduced IGlar achieved superior reductions in HbA1c, BW, and daily insulin dose in people with T2D and overweight, while reducing their risk for severe hypoglycaemia compared to dose-titrated IGlar alone.

Adult

Effectiveness of Platelet Rich Plasma in Reducing Oronasal Fistula and Scar Width in Primary Cleft Lip and Palate Repair-A Systematic Review and Meta-Analysis.

This review aimed to investigate platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) efficiency in reducing oronasal fistula during primary cleft lip and palate repair. An extensive search of PubMed, Google Scholar, Global Index Medics (WHO), PubMed Scopus, Cochrane Central, Proquest was performed up to march 2025. Eligible studies included prospective RCTs and non-randomized controlled trials in human subjects. Patients aged 6-24&#x2009;months undergoing primary cleft lip and palate repair were involved. Interventions involved intraoperative use of PRP/PRF compared with controls without PRP/PRF. The primary outcome was occurrence of oronasal fistula; secondary outcomes were scar width, wound infection and postoperative bleeding with wound dehiscence. Study selection followed PRISMA guidelines, and the risk of bias was determined with the ROB-2 and ROBINS-I method of assessment. Seven studies met the required criterion and were qualitatively synthesized. Evidence suggested that PRP/PRF application was associated with a lower incidence of oronasal fistula and reduced scar width compared with controls. Additional benefits included accelerated wound healing and faster recovery. The use of autologous PRP was also reported to decrease the need for further surgical interventions. However, the certainty of evidence was limited due to small sample sizes and methodological heterogeneity. PRP and PRF show promising benefits in cleft lip and palate repair, particularly decreased fistula formation and reduced scar width. Nevertheless, current evidence is of low to very low certainty. Larger, well-designed randomized trials are required to validate the results obtained. Trial Registration: PROSPERO registration no. CRD420251032421.

Humans

Reduced FOXP3 expression and its association with genetic ancestry in neuromyelitis Optica spectrum disorder: a Colombian cohort.

BACKGROUND: Autoimmune disorders are characterized by impaired immune tolerance, largely mediated by CD4&#x207a; regulatory T cells (Tregs), whose function depends on the transcription factor FOXP3. OBJECTIVES: To compare FOXP3 expression levels between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls from Bogot&#xe1;, Colombia, and to explore their association with genetic ancestry. METHODS: FOXP3 expression was quantified from peripheral blood mononuclear cells using RNA-based analysis. Genomic ancestry proportions were estimated using ancestry-informative markers. RESULTS: FOXP3 mRNA expression was significantly reduced in NMOSD patients compared with controls (&#x223c;2.4-fold decrease in median expression; p&#x202f;=&#x202f;0.027). Lower FOXP3 mRNA expression was associated with optic neuritis (p&#x202f;=&#x202f;0.0059), but not with historical or current AQP4-IgG seropositivity. In a sensitivity analysis restricted to patients with documented historical AQP4-IgG seropositivity, the direction of reduced FOXP3 mRNA expression was preserved but did not reach statistical significance. In pre-specified exploratory ancestry-related analyses, African (p&#x202f;=&#x202f;0.035) and Amerindian ancestry (p&#x202f;=&#x202f;0.012) were associated with FOXP3 mRNA expression levels. CONCLUSIONS: Reduced FOXP3 mRNA expression in Peripheral Blood Mononuclear Cells (PBMCs) suggests an altered immune regulatory profile in NMOSD, potentially involving mechanisms beyond antibody-mediated immunity. The association between genetic ancestry and FOXP3 mRNA expression suggests that population-specific genetic background may influence immune regulatory pathways. These findings should be interpreted as exploratory and require validation in larger, clinically homogeneous cohorts.

Adolescent

Nurse-led titration models of care for heart failure reduced ejection fraction: a systematic narrative review of characteristics, patient outcomes, and healthcare resource utilization.

AIMS: Nurse-led titration (NLT) models of care assist with delivery of guideline directed medical therapy for patients with heart failure with reduced ejection fraction (HFrEF). Effectiveness of NLT is established but there is limited information of characteristics of models, patient outcomes and healthcare resource utilization. To build upon the existing evidence by providing a systematic narrative review of the literature of NLT of medications for patients with HFrEF. This review syntheses characteristics of NLT models of care, patient outcomes and healthcare resource utilization. METHODS AND RESULTS: A systematic narrative literature review with systematic search strategy, identification of results, thematic analysis and narrative synthesis. A search was conducted from 2012 to 2025 in Medline, Cinahl complete, Embase and Cochrane. Sixteen studies of NLT models of care were identified from 1944 screened records. Characteristics of models of care were participation of nurses, multidisciplinary teams, follow-up and common features of service delivery. Patient outcomes of mortality were favourable for those that received NLT. There is some evidence of changes in healthcare resource utilization; studies in which the NLT groups received more HF nurse visits and greater HF medication use also reported reduced rehospitalizations. CONCLUSION: Findings reinforce the published benefits of NLT. Additional studies examining adverse events and quality-of-life outcomes are needed to strengthen the evidence base. Several studies suggest a shift in resource use with NLT, highlighting the need for an economic evaluation to inform a cost-effective model of care.

Humans

Intravenous Tranexamic Acid Reduces Perioperative Blood Loss in Reduction Mammoplasty With Immediate Implant-Based Reconstruction: A Randomized, Triple-Blinded, Placebo-Controlled Trial.

BACKGROUND: Postoperative hematoma and oozing can compromise outcomes after reduction mammoplasty with immediate reconstruction. Intravenous (IV) tranexamic acid (TXA) is antifibrinolytic, but prospective evidence in this setting is limited. OBJECTIVES: The aim of this study was to determine whether a single pre-incision dose of IV TXA reduces perioperative blood loss and fibrinolytic activation vs placebo. METHODS: In this randomized, triple-blinded, placebo-controlled trial, 60 women (American Society of Anesthesiologists I/II, 18-75 years) undergoing bilateral reduction mammoplasty with immediate implant-based reconstruction received TXA 10&#x2005;mg/kg in 100&#x2005;mL saline or placebo 10&#x2005;min before incision. The primary outcome was total blood loss within 24&#x2005;h (intraoperative suction + swab plus drain output). Secondary outcomes were perioperative changes in hemoglobin, D-dimer and fibrinogen, and complications within 30 days. Intention-to-treat analyses were performed. RESULTS: All patients completed follow-up. Total blood loss was lower with TXA than with placebo (mean &#xb1; standard deviation: 221.1 &#xb1; 72.4 vs 298.1 &#xb1; 90.6&#x2005;mL; mean difference -77.0&#x2005;mL; 95% CI, -122.4 to -31.6; P = .001). Intraoperative loss and 24&#x2005;h drain output were also reduced. Postoperative D-dimer rise was attenuated with TXA (0.31 &#xb1; 0.15 vs 0.49 &#xb1; 0.22&#x2005;&#xb5;g/mL; P = .002); hemoglobin decline was smaller. No thromboembolic, neurologic, or allergic events occurred; no skin-flap necrosis was observed. CONCLUSIONS: Pre-incisional IV TXA safely reduces perioperative bleeding and fibrinolytic activity after reduction mammoplasty. These findings support incorporation of IV TXA into perioperative protocols. LEVEL OF EVIDENCE: 2 (THERAPEUTIC): For image description, please refer to the figure legend and surrounding text.

Humans

Efficacy of esketamine in reducing nausea and vomiting after anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative nausea and vomiting (PONV) are significant perioperative challenges. This study evaluated the efficacy of perioperative esketamine in preventing PONV. MATERIALS AND METHODS: We systematically searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to August 2025 for randomized controlled trials investigating the effect of perioperative esketamine on PONV. The primary outcome was PONV incidence. Secondary outcomes included time to first flatus, postoperative pain degree, anxiety scores, agitation, anesthesia recovery time, and post-anesthesia care unit (PACU) stay duration. Data were analyzed using RevMan 5.4 and STATA 15.0 software. Sensitivity and subgroup analyses were performed to assess result stability and explore potential sources of heterogeneity. RESULTS: Thirty-eight randomized trials (3,425 patients) were included. Esketamine reduced the risk of nausea (RR=0.69, 95% CI: 0.53-0.90) and vomiting (RR=0.75, 95% CI: 0.57-0.98), shortened time to first flatus (SMD=-0.81, 95% CI: -1.48 to -0.15), and decreased rescue analgesic needs within 2 days (SMD=0.32, 95% CI: 0.2-0.5). However, it prolonged anesthesia recovery time (SMD=0.97, 95% CI: 0.28-1.67) and PACU stay (SMD=0.76, 95% CI: 0.27-1.26). CONCLUSIONS: Perioperative esketamine may reduce PONV and aid gastrointestinal recovery, but its potential to delay anesthesia recovery and PACU discharge requires consideration. Further studies are needed to clarify its risk-benefit profile. DATE OF FIRST SUBMISSION TO PROSPERO: 10 March 2024. DATE OF THE START OF STUDY SCREENING AGAINST ELIGIBILITY CRITERIA: 21 March 2024.

Humans

The role of media in reducing and reinforcing stigma: A randomized controlled trial investigating the impact of positive and negative representations of visible difference.

OBJECTIVES: Individuals with visible differences often experience appearance-related stigma and discrimination, reinforced by negative media portrayals. In contrast, positive portrayals may challenge stereotypes and promote acceptance. This study examined whether exposure to positive, negative or neutral images of visible difference influences appearance-related stigma, body appreciation and broad conceptualizations of beauty. It was hypothesized that positive images would decrease stigma and increase body appreciation and broad conceptualizations of beauty, whereas negative images would increase stigma and reduce broad conceptualizations of beauty. DESIGN: An online randomized controlled experiment using a mixed repeated-measures design compared three conditions (positive, negative, neutral) across pre- and post-exposure. METHODS: A sample of 103 adults viewed 10 images of individuals with visible differences presented in one of three conditions: positive (positive captions), negative (villains with visible differences and negative captions) or neutral (without captions). Participants completed pre- and post-measures of appearance-related stigma, body appreciation and broad conceptualizations of beauty. Repeated-measures ANOVAs examined within- and between-group changes. RESULTS: Appearance-related stigma significantly increased in the negative condition, while remaining unchanged in the positive and neutral groups. Body appreciation significantly increased from pre- to post- across all conditions. No significant effects emerged for broad conceptualizations of beauty. CONCLUSIONS: Negative portrayals of visible difference may reinforce stigma, highlighting the need to discourage such depictions in media. While positive exposure did not significantly reduce stigma, viewing images of visible difference increased observers' body appreciation, indicating potential downward social comparison. Future research should explore strategies to strengthen stigma reduction and broaden conceptualizations of beauty.

Humans

Maternal vitamin B12 deprivation exacerbates offspring obesity by reducing early-life colonization with Bifidobacterium pseudolongum.

Vitamin B12 deficiency during pregnancy and lactation is common, yet its mechanistic impact on reproductive outcomes and offspring health remains poorly understood. Here, we show that maternal dietary vitamin B12 deprivation not only impairs maternal glucose metabolism and reproductive outcomes but also exacerbates high-fat-diet-induced obesity in offspring. These effects are mediated by gut microbiota and associated with a marked reduction of Bifidobacterium pseudolongum (B. pseudolongum) in both dams and their offspring. Maternal vitamin B12 deprivation limits early-life acquisition of B. pseudolongum in offspring during lactation, subsequently intensifying obesity and metabolic dysregulation. Early-life restoration of B. pseudolongum or its key metabolite, acetate, effectively ameliorates this aggravated obesity. Mechanistically, acetate acts through the Ffar2 receptor to upregulate Ehhadh expression. Together, these data establish that perinatal nutrition imprints long-term metabolic phenotypes in offspring via early-life acquisition of the gut microbiota, with a critical window during lactation.

Animals

Bacterial Lysates Add-On Therapy to Reduce Postoperative Recurrence in Nasal Polyps.

OBJECTIVE: This study aimed to investigate the potential role of OM-85 in reducing polyp recurrence (PR). METHODS: A single-center randomized, prospective study was performed to compare the inter-group PR rate, patient-reported outcome measures (PROMs), CT and endoscopic scores. Hundred patients were randomized to receive either add-on OM-85 (34/50) or control group (43/50); 77 participants completed the 12-month follow-up. The OM-85 group received oral treatment for 10&#x2009;days, followed by a 20-day washout (Months 1-3 and 7-9). Primary outcome was the PR rate. Secondary outcomes included PROMs, Lund-Kennedy (L-K) scores, Lund-Mackay (L-M) scores, and complete blood count (CBC) parameters. RESULTS: The PR rate was significantly lower in the OM-85 group (8.82%) than in the control group (27.91%, &#x3c7; 2&#x2009;=&#x2009;4.408, p&#x2009;=&#x2009;0.036). Univariable analysis identified pre-operative Lund-Mackay (L-M) score (p&#x2009;=&#x2009;0.008) and hyposmia VAS score (p&#x2009;=&#x2009;0.031) as significant predictors of PR. In multivariable analysis, the L-M score remained an independent predictor (OR&#x2009;=&#x2009;1.15, p&#x2009;=&#x2009;0.012), with an optimal cutoff of 10. The OM-85 group showed significant improvements in nasal obstruction, olfactory dysfunction, and mucopurulent discharge at 6 and 12&#x2009;months (p&#x2009;<&#x2009;0.05). Lund-Kennedy (L-K) score and 22-item Sinonasal Outcome Test (SNOT-22) score were also significantly improved (p&#x2009;<&#x2009;0.05). Furthermore, the OM-85 group exhibited elevated white blood cell counts and lymphocyte percentages from 6&#x2009;months onward (p&#x2009;<&#x2009;0.05). CONCLUSION: Adjuvant OM-85 may reduce postoperative PR, with improved endoscopic and symptom scores, potentially mediated by enhanced systemic immune function.

Humans

Interventions to Reduce Loneliness in Informal Caregivers of People With Dementia: A Systematic Review.

AIM: To summarize the current evidence on reducing loneliness among informal caregivers of people with dementia, such as family members or friends. DESIGN: A systematic review. METHODS: The methodological quality was evaluated using the revised Cochrane risk-of-bias tool for randomized controlled trials and the revised JBI critical appraisal checklist for quasi-experimental studies. Data were extracted as predefined and synthesized narratively. The Template for Intervention Description and Replication checklist was used to report the intervention characteristics. DATA SOURCES: Six electronic databases (MEDLINE via PubMed, EMBASE, Cochrane Library, PsycINFO, CINAHL Plus, and Web of Science Core Collection) were searched for studies published in peer-reviewed English journals from the inception of each database until 28 January 2024. RESULTS: Eight studies were included in this review, published between 2002 and 2023, with three being randomized controlled trials. All included interventions were psychosocial. Only one study reported significant improvements in loneliness. Five studies utilized remote and online interventions, such as social networking, psychotherapy, and online social support. Interventions varied in their impact on secondary outcomes, including stress, depressive symptoms, anxiety, and caregiver burden. Four studies demonstrated a positive effect on caregiver stress levels. One pilot trial reported a positive impact on depressive symptoms, and another study noted potential improvements in anxiety. One pilot study reported an average improvement in caregiver burden. CONCLUSION: While the evidence is insufficient for conclusive statements, this systematic review suggests potential benefits of interventions to reduce loneliness and improve mental health among these caregivers. It highlights the promise of remote interventions in addressing loneliness among dementia caregivers. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: The findings suggest that tailored interventions, especially those delivered remotely, can enhance the support provided to caregivers, potentially improving their mental health and overall well-being. REPORTING METHOD: This systematic review adhered to the PRISMA statement. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Humans

Randomised, Multicentre Clinical Trial Found That Hypertonic Saline Did Not Reduce the Length of Stay of Hospitalised Patients With Acute Bronchiolitis.

AIM: Bronchiolitis is a major cause of hospitalisation in young children, but the effectiveness of inhaled hypertonic saline remains unclear. We compared treating hospitalised infants with nebulised hypertonic saline or normal saline. METHOD: This multisite, double-blind RCT was conducted from 1 October 2023 to 1 April 2025 in four Polish paediatric units. Children from 5&#x2009;weeks to 24&#x2009;months, who had been hospitalised with mild-to-moderate bronchiolitis, were randomly assigned to receive nebulised 3% hypertonic saline or 0.9% normal saline until discharge. They were followed for 7&#x2009;days. RESULTS: The study comprised 181 children (55% male) with a mean age of 8.3&#x2009;&#xb1;&#x2009;6.3&#x2009;months: 90 were randomised to hypertonic saline and 91 to normal saline. The median hospital stay was 2.68 (1.92-4.03) days in the hypertonic saline group and 2.79 (1.8-3.96) days in the normal saline group. The mean difference was -0.11&#x2009;days (95% confidence interval -0.73 to 0.12, p&#x2009;=&#x2009;0.3). No differences were observed in clinical severity scores between the groups. Readmissions only occurred in the normal saline group (5.9%). CONCLUSION: Hypertonic saline inhalation did not reduce the length of hospital stay or improve clinical severity scores in hospitalised children with bronchiolitis, but it was associated with a lower risk of rehospitalisation.

Humans

Bedtime tetrahydrocannabinol ingestion reduces morning orthostatic cardiovascular reactivity in adults: An exploratory study.

Acute cannabis use and its primary psychoactive constituent tetrahydrocannabinol (THC) can induce postural dizziness, indicating increased risk of orthostatic instability. However, it is unknown if vulnerabilities persist the morning after bedtime THC consumption. This study investigated the influence of bedtime THC consumption on cardiovascular variables during an orthostatic challenge. Nine individuals with no cannabis use and eight individuals who regularly use cannabis participated in a tilt table test associated with a 3-day in-laboratory stay. Participants underwent an acclimatization day, followed by a placebo dosing day, and a 10&#x2009;mg THC dosing day. Placebo and THC pills were given 1&#x2009;h before a participant's habitual bedtime, and the tilt table test was performed ~1&#x2009;h upon awakening. Participants were instrumented with an electrocardiogram and an automated sphygmomanometer. Fluid intake and output were measured throughout the study. The morning after THC administration, individuals with no cannabis use reported a higher frequency of dizziness and exhibited a significant reduction in both diastolic blood pressure and heart rate reactivity to tilt (reactivity&#x2009;=&#x2009;tilt - baseline) compared to the morning after placebo. Our results indicate a potential increased risk for orthostatic instability the morning after cannabis consumption in individuals with no cannabis use history.

Humans

Self-selected goals outperform assigned goals in reducing mobile phone usage: Evidence from a randomized controlled trial.

Excessive smartphone use is increasingly recognized as a public-health concern, yet scalable approaches to help individuals regulate daily use remain limited. We examine whether allowing individuals to self-select reduction goals improves behavioral and psychological outcomes when incentives and average goal levels are held constant across conditions. In a twelve-week randomized controlled trial, (N&#x202f;=&#x202f;149; over 9000 person-day observations), participants were assigned to (i) a self-selected condition (choosing a 10%, 20%, or 30% reduction in daily phone use), (ii) an assigned condition (assigned a 14% reduction goal), or (iii) a no-goal control condition. Participants who selected their own goals reduced phone use by 26&#x202f;min more per day (73% larger reduction) and achieved their goals 11 percentage points more often than those assigned goals, despite identical incentives and average goal levels. Reductions in phone use and higher goal achievement were associated with improvements in perceived addiction, depressive, and anxiety symptoms. These psychological outcomes were secondary endpoints. Although the between-group estimates generally followed the same directional pattern as the behavioral outcomes, the sample size for these analyses was limited and the between-group differences were not statistically significant. These findings should therefore be interpreted with caution. Overall, the results provide causal field evidence that self-selection under this goal-setting design can improve behavioral outcomes. Allowing individuals to choose their own goals may strengthen engagement and support healthier digital behavior. Incorporating opportunities for goal-selection may represent a simple addition to digital-health and public-health interventions aimed at helping individuals moderate smartphone use and improve well-being.

Humans

Interactive gaming during inhalational induction of anesthesia reduces pediatric patient anxiety and improves induction compliance: A randomized controlled trial.

BACKGROUND: Preoperative anxiety affects up to 75% of pediatric surgical patients and is associated with adverse postoperative outcomes. Traditional anxiolytic strategies with premedication carry drawbacks including delayed recovery and paradoxical reactions, driving interest in non-pharmacologic alternatives. Audiovisual distraction represents one approach, encompassing passive methods (e.g. watching a video) and active modalities (e.g. interactive gaming). The Bedside Entertainment and Relaxation Theater (BERT) is a projection-based environment that enables audiovisual distraction during induction. Whether BERT-based interactive gaming reduces anxiety and improves induction compliance compared to standard perioperative care remains unknown. METHODS: This single-center RCT enrolled 74 pediatric patients aged 4 to 14 undergoing inhalational induction, randomized to standard care (SOC) or interactive gaming via BERT added to SOC during induction (BERT). The primary outcome was change in patient anxiety from baseline to induction, measured using the Modified Yale Preoperative Anxiety Scale (mYPAS). Secondary outcomes included caregiver anxiety, induction compliance, OR efficiency, opioid administration, and OR staff perceptions. RESULTS: Patients in the BERT group experienced significantly smaller increases in anxiety from baseline to induction than SOC (median mYPAS increase [IQR]: 0 [0 to 0] vs 10 [0 to 38], p&#xa0;<&#xa0;0.001). Induction compliance improved, with lower Induction Compliance Checklist (ICC) scores indicating fewer induction-related disruptive behaviors than SOC (median: 0 vs 1, shift -1 [95% CI: -2 to 0]; p&#xa0;=&#xa0;0.004). Caregiver anxiety increased less in the BERT group than SOC (mean STAI increase: 0.18 vs 1.89, difference&#xa0;-&#xa0;1.7, [95% CI: -3.2 to -0.26]; p&#xa0;=&#xa0;0.022). OR staff reported high acceptability, with 97% supporting continued use. No differences were observed in OR efficiency or opioid administration between groups. CONCLUSIONS: Interactive gaming via BERT attenuated increases in patient anxiety, improved induction compliance, and reduced the rise in caregiver anxiety without prolonging OR time. These findings support BERT as an effective, workflow-compatible anxiolytic strategy for pediatric inhalational induction.

Humans

Faecal Microbiota Transplantation Reduces Lesion Severity and Medication Use in Canine Atopic Dermatitis: A Randomised, Placebo-Controlled, Double-Blinded Clinical Trial.

BACKGROUND: Faecal microbiota transplantation (FMT) is an established therapy for gastrointestinal disease, yet its role in canine atopic dermatitis (cAD) remains unclear. HYPOTHESIS/OBJECTIVES: We hypothesised that adjunctive FMT improves clinical severity and reduces symptomatic medication use in dogs with cAD. The objective was to evaluate efficacy and safety versus placebo. ANIMALS: Forty-six client-owned dogs with naturally occurring cAD were enrolled from a referral hospital population; 40 completed the study (FMT n&#x2009;=&#x2009;20, placebo n&#x2009;=&#x2009;20). MATERIALS AND METHODS: Prospective, randomised, placebo-controlled, double-blinded clinical trial. Dogs received daily oral lyophilised FMT capsules for 90&#x2009;days plus three monthly rectal FMT administrations (Day [D]0, D30, D60) or placebo capsules with sham handling. Concomitant symptomatic therapies were permitted. Outcomes included Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), Medication Score (D0-90) and Owner Global Assessment of Treatment Efficacy (OGATE, D90). RESULTS: CADESI-04 scores were lower with FMT at month (M) 2 (7&#x2009;&#xb1;&#x2009;6 vs. 16&#x2009;&#xb1;&#x2009;12; p&#x2009;=&#x2009;0.006) and month 3 (8&#x2009;&#xb1;&#x2009;6 vs. 15&#x2009;&#xb1;&#x2009;12; p&#x2009;=&#x2009;0.020). Sustained responders (&#x2265;&#x2009;50% CADESI-04 improvement at M2 and M3) were more frequent with FMT (35% vs. 5%; p&#x2009;=&#x2009;0.044). In the FMT group, the medication scores were lower at M2 (16&#x2009;&#xb1;&#x2009;10 vs. 23&#x2009;&#xb1;&#x2009;11; p&#x2009;=&#x2009;0.033) and M3 (13&#x2009;&#xb1;&#x2009;10 vs. 24&#x2009;&#xb1;&#x2009;15; p&#x2009;=&#x2009;0.007) compared to placebo. PVAS decreased in both groups without between-group differences. OGATE favoured FMT (p&#x2009;=&#x2009;0.028). FMT was well tolerated. CONCLUSIONS AND CLINICAL RELEVANCE: Adjunctive FMT reduced lesion severity and medication requirements, supporting its use as a safe microbiome-based add-on therapy in cAD.

Animals

Autodissemination stations suppress Aedes notoscriptus mosquitoes and reduce Buruli ulcer risk in urban Australia: a randomized controlled field trial.

Aedes notoscriptus are mosquito vectors implicated in transmission of Mycobacterium ulcerans. This bacterium causes a destructive infection of skin and soft tissue called Buruli ulcer. Here we ran a randomized controlled trial in an urban Buruli ulcer endemic area in Melbourne, Australia to test whether autodissemination mosquito control stations, containing pyriproxyfen (larvicide) and Beauveria bassiana (entomopathogenic fungus), suppress Ae. notoscriptus populations. Six geographic areas each received 100 autodissemination stations for 8&#x2009;weeks, and six control areas received no stations between 25 January 2024 and 21 March 2024. The primary outcome measure was mosquito population numbers. After the trial, there was a 70% average reduction in mosquito egg counts among the six intervention areas compared to control areas (P&#x2009;=&#x2009;0.0076). In an ad hoc analysis, we then explored human Buruli ulcer notifications in treatment and control areas. After accounting for the 4.8-month mean incubation period, there was an 83% reduction in infection likelihood coinciding with peak intervention effect (intervention zones 1 case, control zones 6 cases, incidence ratio rate 0.167, 95% CI 0.0026-1.054, P&#x2009;=&#x2009;0.047). The effect was not observed during the same time period in the year previous or following 2024, when no interventions were undertaken. A strong correlation (R2&#x2009;=&#x2009;0.85) was observed between decreased disease risk and mosquito suppression. These data show that autodissemination traps can effectively lower urban mosquito populations and reduce the threat of Buruli ulcer in humans.

Animals

Intravenous lidocaine reduces the propofol EC50 for loss of consciousness and intraoperative anesthetic consumption in gynecological laparoscopy: A randomized controlled trial.

BACKGROUND: Intravenous lidocaine reduces propofol requirements and procedure-related adverse events. OBJECTIVES: The study aimed to test whether intravenous lidocaine would reduce the effect-site concentration of propofol required to achieve loss of consciousness and decrease propofol consumption during total intravenous anesthesia in gynecological laparoscopy. METHODS: This was a prospective, randomized, double-blind, placebo-controlled trial. Sixty patients were randomly allocated to receive either intravenous lidocaine (1.5 mg&#xb7;kg-&#xb9; bolus) followed by continuous infusion or an equal volume of saline. Propofol was administered via target-controlled infusion starting at an effect-site concentration of 3.5 &#x3bc;g/mL. The concentration was then adjusted in steps of 0.5 &#x3bc;g/mLaccording to Dixon's up-and-down sequential method: decreased if loss of consciousness was achieved, or increased if not. Loss of consciousness was defined as loss of response to verbal commands. The median effective concentration (EC50) of propofol for inducing loss of consciousness was calculated using the Dixon's up-and-down method. General anesthesia was maintained with propofol and remifentanil, guided by state entropy (target 40-60) and surgical pleth index (target 20-50). Drug consumption was normalized to anesthesia duration and body weight. RESULTS: The estimated EC50 of propofol for inducing loss of consciousness was significantly lower in the lidocaine group than in the saline group (3.32 &#x3bc;g/mL, 95% Confidence Interval (CI): 3.04-3.59 vs. 3.89 &#x3bc;g/mL, 95% CI: 3.50-4.28). Under the study protocol, the lidocaine group also required less propofol (8.62 mg&#xb7;kg-1&#xb7;h-1, 95% CI: 8.10-9.15 vs. 9.89 mg&#xb7;kg-1&#xb7;h-1, 95% CI: 9.05-10.73) and less remifentanil (0.23 &#x3bc;g&#xb7;kg-1&#xb7;min-1, 95% CI: 0.21-0.24 vs. 0.27 &#x3bc;g&#xb7;kg-1&#xb7;min-1, 95% CI: 0.24-0.30) compared with the saline group. CONCLUSION: Intravenous lidocaine reduced the propofol EC50 for Loss of Consciousness (LOC) and decreased intraoperative propofol and remifentanil consumptions in patients undergoing gynecological laparoscopy. These findings suggest a propofol- and opioid-sparing effect of intravenous lidocaine in this setting, although confirmation in larger multicenter trials is needed.

Humans

The effectiveness of protective behavioral strategies for reducing alcohol use and alcohol-related harms among adults: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Excessive alcohol consumption is a major public health concern. Protective behavioral strategies (PBS) are widely incorporated into alcohol interventions, but their effectiveness and role as mechanisms of behavior change remain unclear. This systematic review and meta-analysis evaluated the effects of PBS-based interventions on alcohol consumption, alcohol-related harms, and PBS use. METHODS: PubMed, Embase, Scopus, CINAHL, and ProQuest were searched from inception to December 2025 for randomized controlled trials (RCTs) of adults (&#x2265;18 years) delivering PBS as an active intervention component. Random-effects meta-analyses using Hedges' g examined alcohol quantity, drinking frequency, alcohol-related problems, and PBS use. RESULTS: Fifteen RCTs were included, predominantly involving young adults attending U.S. universities. PBS interventions increased protective strategy use (g=0.23, p=0.005 after outlier removal), but alcohol effects were modest: no change in quantity (g=-0.05, p=0.162), small reduction in frequency (g=-0.09, p=0.014), and marginal reduction in problems (g=-0.07, p=0.052; significant in sensitivity analysis). Subgroup findings suggested greater effects at longer follow-up and when PBS was incorporated into multi-component interventions. Evidence supporting PBS as a mechanism of change was limited and inconsistent. CONCLUSIONS: PBS-based interventions produce modest, context-dependent effects on alcohol outcomes. Most evidence comes from young U.S. university students, underscoring the need for studies in more diverse adult populations and further mechanistic research.

Humans