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Influenza A virus in Swiss pig herds with respiratory disease: Seasonality and age dependence.

Influenza A virus (IAV) is an important respiratory pathogen in pigs and poses a zoonotic risk to humans in close contact. While IAV epidemiology has been extensively studied in large-scale production systems, data from Switzerland - characterized by small herds and limited live pig imports - remain scarce. This exploratory nationwide cross-sectional study aimed to assess the association between herd-level IAV detection and reported respiratory disease in pig herds, and to explore associations with husbandry-, animal-, and human health-related factors. Between November 2023 and April 2025, 25 Swiss pig herds with caretaker-suspected respiratory symptoms were investigated. In each herd, five nasal swabs were collected and analyzed by quantitative PCR. Herd managers completed an interview, and clinical examinations were performed. Overall, 56 % (95 % CI: 37,1 - 73,3) of herds tested positive for IAV, comparable to reports from other European countries. The estimated intra-herd detection rate was 49,6 % (95 % CI: 31,2 - 68,0). Respiratory disease outbreaks associated with IAV detection showed indications of seasonal variation, with no positive herds identified during summer. Across age groups, pigs aged 11-14 weeks had a higher likelihood of IAV detection, with 15,79-fold increased odds (95 % CI: 1,50 - 860,4), although with considerable uncertainty. The interpretation is limited by the small sample size, heterogeneous data, and reliance on single time-point qPCR detection. The results suggest that IAV detection in clinically apparent respiratory outbreaks may follow seasonal patterns in Swiss pig herds. Weaners and newly introduced fattening pigs may play a role in such respiratory outbreaks and could represent relevant targets for IAV surveillance in Switzerland. Continued monitoring and the implemen tation of appropriate control measures remain important given the virus's zoonotic potential and impact on pig health.

Animals

Driving Under the Influence of Cannabis Among U.S. Young Adults Who Use Cannabis: Evidence From the 2021-2024 National Survey on Drug Use and Health.

PURPOSE: To estimate the prevalence of driving under the influence of cannabis (DUIC) and identify associated factors among U.S. young adult drivers reporting past-year cannabis use. METHODS: This cross-sectional study analyzed pooled 2021-2024 National Survey on Drug Use and Health. The analytic data were restricted to drivers aged 18-25 years who reported past-year cannabis use (N = unweighted 17,141; weighted N = 10,814,381). The outcome was self-reported past-year DUIC. Independent variables included demographics, substance use, mental health, cannabis-related perceptions, and driving behaviors. These relationships were assessed by modified Poisson regression. RESULTS: The weighted prevalence of DUIC was 28.0%, representing approximately over three million young adults. DUIC prevalence increased with cannabis use frequency, from 2.51 times higher among those using cannabis 12-49 days (adjusted prevalence ratio [APR]: 2.51; 95% confidence interval [CI]: 2.29-2.75) to 3.63 times higher among those reporting use on 300-365 days (APR: 3.63; 95% CI: 3.60-3.76), compared with those using cannabis 1-11 days. Cannabis use disorder (APR: 2.34; 95% CI: 2.06-2.65), simultaneous alcohol and cannabis use (APR: 1.29; 95% CI: 1.28-1.30), and perceived easy cannabis availability (APR: 2.36; 95% CI: 2.33-2.39) were also associated with higher prevalence of DUIC. Nonenrollment in school and living in a state with a medical cannabis law were associated with lower DUIC prevalence. DISCUSSION: DUIC is highly prevalent among U.S. young adults who use cannabis, with a clear graded association across categories of cannabis use frequency. Public health interventions should address frequent use, cannabis use disorder, alcohol-cannabis co-use, and perceived cannabis availability.

Humans

Safety and efficacy of Meridian sinew tuina (MST) for post-surgical upper limb lymphedema: a systematic review and meta-analysis.

BACKGROUND: Complex Decongestive Therapy (CDT) is the non-operative standard for breast cancer-related lymphedema (BCRL), but many patients experience persistent subcutaneous stiffness, pain, and restricted mobility. This study systematically reviews the safety and clinical efficacy of Meridian Sinew Tuina (MST) protocols for BCRL. METHODS: Global and regional databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP) were searched from inception to January 15, 2026, with alerts monitored through April 30, 2026. Randomised controlled trials (RCTs) evaluating MST (deep tissue mobilisation along the six-hand meridian sinew [Jingjin] lines via plucking, kneading, and pressing) were included. Two reviewers independently extracted data, evaluated risk of bias using Cochrane RoB 2, and assessed evidence certainty via GRADE using a random-effects model. RESULTS: Fifteen RCTs were included. For the primary anthropometric outcome, MST significantly reduced upper limb circumference compared to controls (SMD = 1.59; 95% CI: 1.44 to 1.74; Z&#x2009;=&#x2009;20.81; p&#x2009;<&#x2009;0.0001; I2=0.0%; N&#x2009;=&#x2009;924; GRADE: Moderate certainty). The Clinical Response Efficacy Rate (&#x2265; 30% swelling reduction and symptom relief) favoured MST (RR = 1.69; 95% CI: 1.54 to 1.87; Z&#x2009;=&#x2009;10.62; p&#x2009;<&#x2009;0.0001; I2=0.0%; N&#x2009;=&#x2009;1,114; GRADE: Moderate certainty). Trial Sequential Analysis confirmed sample size sufficiency. For secondary outcomes (N&#x2009;=&#x2009;924; GRADE: Low to Very Low certainty due to performance bias and clinical heterogeneity), MST showed favourable 3-month improvements in DASH functional scores (SMD&#x2009;=&#x2009;-1.81; 95% CI: -2.11 to -1.51; I2=45.1%), pain intensity (SMD&#x2009;=&#x2009;-2.44; 95% CI: -2.93 to -1.95; I2=50.4%), and quality of life (SMD = 1.04; 95% CI: 0.79 to 1.29; I2=0.0%). No serious adverse events occurred. CONCLUSIONS: MST protocols are associated with favourable short- and mid-term reductions in upper limb swelling. However, confidence is tempered by unblinded performance bias and control group variations. MST cannot be unconditionally recommended for standalone implementation but represents a promising, optional supportive adjunctive intervention within oncological rehabilitation.

Humans

Efficacy and Safety of Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.

BACKGROUND: Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS: PubMed, Cochrane, and EMBASE were searched for randomized controlled trials (RCTs) and nonrandomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS: A total of 39,991 participants across 6 studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (relative risk [RR] = 0.84, 95% confidence interval [CI] 0.78-0.91, P < 0.001), risk of acute limb ischemia (RR = 0.65, 95% CI 0.55-0.78, P < 0.001), and thromboembolism (RR = 0.60, 95% CI 0.38-0.97, P = 0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR = 0.50, 95% CI 0.30-0.85, P = 0.003). However, its use was associated with a significantly higher risk of major bleeding (hazard ratio [HR] = 1.54, 95% CI 1.38-1.72, P < 0.001) and International Society on Thrombosis and Hemostasis-defined bleeding (RR = 1.45, 95% CI 1.19-1.76, P < 0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION: Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.

Humans

Stratified medicine with eplerenone for myocardial infarction or injury and no obstructive coronary arteries: A registry-based basket trial.

BACKGROUND: Myocardial Infarction with No Obstructive Coronary Arteries (MINOCA) or Nonischemic Myocardial Injury affects approximately 1 in 9 patients presenting with acute coronary syndrome, yet evidence-based therapies are lacking. Coronary microvascular dysfunction is implicated in the pathogenesis of suspected MINOCA, but its prevalence, prognostic implications and treatment are uncertain. The objectives are, first, to assess the prevalence of coronary microvascular dysfunction in patients with suspected MINOCA and, second, to implement endotype-informed stratified medicine involving patients with coronary microvascular dysfunction to treatment with eplerenone, a cardio- and vasculo-protective mineralocorticoid receptor antagonist. METHODS: This is a prospective, registry-based, multicenter, diagnostic study and nested, randomized, controlled, open-label, blinded-endpoint (PROBE) basket trial. Up to 400 patients with clinically suspected MINOCA and one or more cardiovascular risk factors will be enrolled into a registry-based diagnostic study. Coronary microvascular function will be assessed during invasive angiography using thermodilution. Patients with an index of coronary microvascular resistance (IMR) &#x2265; 25 will be randomized 1:1 to eplerenone (25-50 mg daily for 6 months) or standard care without eplerenone (control group) (n = 150 randomized). Final endotypes will be centrally adjudicated by a panel of blinded cardiologists. The primary outcome of the diagnostic study is the proportion of patients with IMR &#x2265; 25 during index coronary angiography. Secondary outcomes include coronary flow reserve, cardiovascular MRI parameters, patient-reported outcome measures, biomarkers of myocardial fibrosis and vascular inflammation, health outcomes and health economic assessments. The primary outcome of the randomized trial is the within-individual change in NT-proBNP at baseline, 1 month, and 6 months, based on intention-to-treat. Secondary outcomes include mechanistic blood biomarkers and patient-reported outcome measures. VALUE: This registry-based randomized trial will provide novel evidence on endotype-informed secondary prevention therapy with eplerenone for suspected MINOCA.

Humans

Associations Between Paternal Pre-Conceptional Body Mass Index and Lifestyle Factors and Offspring Weight Development.

BACKGROUND: Evidence suggests that pre-conceptional paternal factors, including BMI and diet, may influence offspring development. OBJECTIVES: We examined the associations between paternal BMI, dietary protein intake, glycemic index (GI), smoking and alcohol consumption and offspring development during the first 5&#x2009;years of life. METHODS: This secondary analysis of an RCT included 162 father-child pairs from pregnancies among women with pre-pregnancy overweight or obesity. Paternal characteristics were reported at gestational week 15, reflecting the preceding 3&#x2009;months. Offspring anthropometry was measured at birth, 6 and 18&#x2009;months, 3 and 5&#x2009;years. Associations were examined using linear mixed models and linear regression models. RESULTS: No consistent associations were found between paternal characteristics and offspring outcomes from birth to 3&#x2009;years. At age 5, higher paternal BMI was associated with higher offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;0.07 (CI: 0.03; 0.10)), fat mass index (&#x3b2;&#x2009;=&#x2009;0.07&#x2009;kg/m2 (CI: 0.02; 0.12)) and fat-free mass index (&#x3b2;&#x2009;=&#x2009;0.05&#x2009;kg/m2 (CI: 0.01; 0.08)). Lower paternal protein intake was associated with higher offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;0.54 (CI: 0.07; 1.01)) and fat-free mass index (&#x3b2;&#x2009;=&#x2009;0.60&#x2009;kg/m2 (CI: 0.13; 1.07)), while moderately higher protein intake was associated with higher waist-to-height ratio (&#x3b2;&#x2009;=&#x2009;0.03 (CI: 3.00&#x2009;&#xd7;&#x2009;10-3; 0.05)). Higher paternal GI was associated with lower offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;-0.04 (CI: -0.08; -2.14-10-3)) at age 5. Smoking and alcohol were not associated with offspring outcomes. CONCLUSION: Paternal BMI was associated with offspring outcomes at age 5&#x2009;years, while findings for paternal dietary factors were less consistent.

Humans

Detectable C-Peptide and Diabetic Ketoacidosis Risk in Type 1 Diabetes.

OBJECTIVE: To investigate whether detectable C-peptide levels in type 1 diabetes is associated with a lower risk of diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS: We analyzed the Diabetes Control and Complications Trial publicly available data repository for the association between detectable stimulated C-peptide (>0.2 nmol/mL, measured annually) and DKA incidence over an average 6.5-year follow-up. We used crude and adjusted Andersen-Gill models for recurrent DKA events with time-dependent covariates. RESULTS: Of the 1,441 participants (53% male, median age 27 years), 129 (9%) experienced 180 DKA events. Of these events, 179 (99.44%) occurred after C-peptide was &#x2264;0.2 nmol/L in the prior year and only 1 event occurred with C-peptide >0.2 nmol/L. C-peptide >0.2 nmol/L was associated with a DKA hazard ratio of 0.07 (95% CI 0.01-0.48; P = 0.007), consistent across adjusted models. CONCLUSIONS: Endogenous insulin production was significantly associated with lower DKA risk, suggesting that treatments preserving insulin production could decrease long-term DKA risk.

C-Peptide

Lung function after randomization to metformin, lifestyle intervention or placebo in the Diabetes Prevention Program Outcomes Study (DPPOS).

INTRODUCTION: Metformin and physical activity have been suggested as beneficial for chronic lung disease; however, there are no prior randomized trials. METHODS: The Diabetes Prevention Program (DPP) was a 3-year trial that randomized 3234 individuals at risk for diabetes to metformin, lifestyle intervention or placebo. After the DPP, 88% of participants enrolled in the DPP Outcomes Study that offered lifestyle intervention to all and open-label continuation of metformin. Spirometry was performed at approximately 19 and 22 years post-randomization. Lung function measures were compared in an intention-to-treat (ITT) analysis by original randomization group. Models were unadjusted and adjusted for demographics, body size, smoking and sitting/standing at spirometry. Additional analyses tested prevalence of obstruction (FEV1/FVC <70%), restrictive pattern (FVC&#x202f;<&#x202f;LLN and FEV1/FVC &#x2265;70%), preserved ratio impaired spirometry (PRISm: FEV1 <80% predicted, FEV1/FVC &#x2265;70%) and symptoms (COPD Assessment Test [CAT] score &#x2265;10). RESULTS: The 1888 participants with spirometry were a mean (&#xb1;SD) age of 68.2&#x202f;&#xb1;&#x202f;9.3 years, 70% female and 6% currently smoked and 33% had previously smoked cigarettes. Mean follow-up time was 19.0&#x202f;&#xb1;&#x202f;0.8 years. The mean FEV1 was 2.14&#x202f;&#xb1;&#x202f;0.60&#x202f;L, FVC 2.74&#x202f;&#xb1;&#x202f;0.74&#x202f;L, FEV1/FVC 78.4&#x202f;&#xb1;&#x202f;6.4%, mean BMI was 32.4&#x202f;&#xb1;&#x202f;6.7&#x202f;kg/m2 and 58% had diabetes. In both unadjusted and adjusted ITT analyses, randomization group was not associated with FEV1, FVC or FEV1/FVC. Likewise, rates of obstruction, restrictive pattern, PRISm or symptoms did not differ by randomization group. CONCLUSIONS: In this long-term follow-up after a randomized trial, we found no significant associations between randomization to metformin or lifestyle intervention and lung function or respiratory symptoms.

Humans

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 &#x3bc;g immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 &#x3bc;g/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] &#x3bc;g) compared to the bolus group (300 [200-400] &#x3bc;g; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans

Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

BACKGROUND: Metabolic syndrome is common among patients with schizophrenia, but current treatment options are limited, with metformin being the most studied. While placebo-controlled studies suggest potential benefits of topiramate, comparative efficacy and safety data are lacking. This study aimed to compare the efficacy and safety of topiramate versus metformin for treating metabolic syndrome and reducing cardiovascular risks among patients with schizophrenia. METHODS: A randomised, open-label, parallel-group clinical trial was conducted on 60 patients of schizophrenia with metabolic syndrome, randomised equally to receive either topiramate (50&#xa0;mg/day) or metformin (1000&#xa0;mg/day) for eight weeks. Primary outcome was cardiovascular risk score (QRISK3), and secondary outcomes were LDL&#x2236;HDL ratio, insulin resistance (HOMA-IR), positive and negative syndrome scale (PANSS), Montreal Cognitive Assessment (MoCA) and clinical global impression-Schizophrenia scale (CGI-SCH) scores. RESULTS: Over the study period, QRISK3 scores improved significantly in both groups [topiramate: MD&#x2009;=&#x2009;0.61 (0.02 to 1.21), p&#x2009;=&#x2009;0.04; metformin: MD&#x2009;=&#x2009;0.45 (0.07 to 0.83), p&#x2009;=&#x2009;0.02], with no significant between-group difference in unadjusted analysis (p&#x2009;=&#x2009;0.648). However, ANCOVA adjusting for baseline QRISK3 revealed a significantly greater improvement in the topiramate group (&#x3b2; = -0.324, p&#x2009;=&#x2009;0.043). Metformin showed significant within-group improvements in LDL: HDL ratio and HOMA-IR; however, ANCOVA adjusting for baseline HOMA-IR showed the between-group difference remained non-significant (&#x3b2; = -1.209, p&#x2009;=&#x2009;0.078). Both groups showed significant improvements in PANSS and CGI-SCH scores, with no significant between-group differences in MoCA scores. A moderate correlation between the QRISK3 change, the PANSS change, and the CGI-SCH-I scores was observed in the topiramate group and the total population. Regression analysis identified PANSS change as a predictor of QRISK3 improvement. CONCLUSION: Topiramate demonstrated comparable, and on adjusted analysis superior, cardiovascular risk reduction compared to metformin, supporting its use as a viable alternative in the management of metabolic syndrome in patients with schizophrenia on atypical antipsychotics, particularly where metformin is contraindicated.

Humans

Cardiometabolic Multimorbidity Increases the Risk of Hip Fracture: A Longitudinal Cohort Study Based on CHARLS.

BACKGROUND: Cardiometabolic Multimorbidity (CMM) is defined as the co-occurrence of two or more conditions among heart disease, diabetes mellitus, stroke, and hypertension. Previous studies have shown associations between cardiometabolic diseases and fragility fractures; however, the relationship between CMM and hip fractures remains unclear in the Chinese population. This study therefore aims to investigate this association in a Chinese cohort to inform fracture prevention strategies. METHODS: This prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS) collected from 2011 to 2020. Participants from the 2011 baseline survey cohort were initially included. Subsequently, individuals were sequentially excluded if they were under 45&#x2009;years of age, had incomplete baseline CMM information, had a history of hip fracture, lost to follow-up, or had missing data on confounders. Kaplan-Meier survival analysis, Cox proportional hazards regression, subgroup analyses, and sensitivity analyses were performed to evaluate the association between CMM and the risk of hip fracture. RESULTS: A total of 6314 participants aged 45&#x2009;years and older were included, of whom 544 had CMM. Over a 9-year follow-up period, 287 incident hip fractures (4.55%) were identified. Among these, 36 participants had been diagnosed with CMM at baseline, whereas 251 had not. The incidence of hip fracture was significantly higher in participants with CMM than in those without CMM (13% vs. 8%, p&#x2009;=&#x2009;0.015). After full adjustment for confounders, multivariable Cox regression showed that CMM was associated with a 70% increased risk of hip fracture (HR&#x2009;=&#x2009;1.70, 95% CI: 1.318-2.47; p&#x2009;=&#x2009;0.005). Subgroup analyses indicated that age and history of falls were significant effect modifiers. The association between CMM and hip fracture was more pronounced in participants under 60&#x2009;years old (P for interaction&#x2009;=&#x2009;0.048) and those with a history of falls (P for interaction&#x2009;=&#x2009;0.014). CONCLUSION: These findings suggest that CMM increases the risk of hip fracture, particularly among relatively younger individuals and those with a history of falls.

Humans

Eltrombopag Added to Standard Immunosuppressive Treatment as Front-Line Therapy for Severe Aplastic Anemia: Long-Term Outcomes of the Phase-3 Randomized Superiority EBMT-SAAWP RACE Study.

The RACE study (NCT02009747) compared horse antithymocyte globulin (hATG) plus cyclosporine A (CsA)&#x2009;&#xb1;&#x2009;eltrombopag as initial immunosuppressive treatment (IST) for severe aplastic anemia. Here we report the final 2-year analysis of this prospective randomized phase III study. One hundred ninety-seven treatment-naive patients were randomized to standard IST (hATG 40&#x2009;mg/kg&#x2009;&#xd7;&#x2009;4&#x2009;days and CsA 5&#x2009;mg/kg/day; arm A; n&#x2009;=&#x2009;101) or standard IST&#x2009;+&#x2009;eltrombopag at the dose of 150&#x2009;mg/day (arm B; n&#x2009;=&#x2009;96) from day +14 until 6&#x2009;months (or 3&#x2009;months, in case of complete response). The median follow-up was 23.2&#x2009;months. The 2-year cumulative incidence of complete response was significantly superior in arm B (62.4% vs. 35.3%; p&#x2009;<&#x2009;0.001). The 2-year overall survival (OS) was 86% in arm A and 91% in arm B (p&#x2009;=&#x2009;0.081), with hazard ratio (HR), adjusted for age and disease severity, of 0.54 (p&#x2009;=&#x2009;0.064). The 2-year disease-free survival (DFS) was 56% vs. 37% (adjusted HR&#x2009;=&#x2009;0.49; p&#x2009;<&#x2009;0.001), while event-free survival (EFS) was 48% vs. 32% (p&#x2009;<&#x2009;0.001), with adjusted HR&#x2009;=&#x2009;0.54 (p&#x2009;<&#x2009;0.001), both significantly superior for arm B. The cumulative incidence of relapse was comparable in the two arms, while evolution to clinical paroxysmal nocturnal hemoglobinuria was 8% in arm A and 1% in arm B (p&#x2009;=&#x2009;0.041). The risk of clonal evolution remained negligible, with one patient in arm A and two in arm B developing karyotypic abnormalities. The initial hematological response benefit of eltrombopag added to IST as front-line treatment of AA is associated with better 2-year OS, DFS, and EFS without increased risk of secondary myeloid malignancies.

Humans

The Impact of Chatbot Type and Normative Messaging on Chatbot Usage Intention Based on the Health Technology Acceptance Model: Randomized Controlled Trial.

BACKGROUND: Digital health tools, such as health chatbots, may improve access to scalable health support, but adoption remains inconsistent. Existing models do not fully integrate technology acceptance factors with health motivation factors relevant to digital health use. OBJECTIVE: This study proposed and tested the health technology acceptance model and examined whether normative message framing and chatbot type were associated with health motivation, technology acceptance, and intention to use a health chatbot. METHODS: In October 2025, we conducted a 4 &#xd7; 2 between-participants online experiment with 1000 US adults recruited from a nationally representative YouGov panel. Participants were randomized to 1 of 8 conditions varying norm message type (self-oriented, peer-oriented, expert-oriented, or family-oriented) and chatbot type (AI-powered or rule-based) in a cancer prevention and genetic risk information scenario. Outcomes included descriptive norms, injunctive norms, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, perceived ease of use, trust, privacy concerns, and usage intention. Data were analyzed using a multivariate ANOVA with Bonferroni-adjusted post hoc tests and multiple linear regression. RESULTS: Peer-oriented and family-oriented messages produced higher usage intention than expert-oriented messages, and peer-oriented messages also increased descriptive norms, injunctive norms, self-efficacy, and trust. AI-powered chatbots were associated with higher usage intention (P=.02) and greater trust (P=.008) than rule-based chatbots. In regression analyses, the model explained 50.8% of the variance in usage intention. Usage intention was positively associated with descriptive norms (&#x3b2;=0.087; P=.003), injunctive norms (&#x3b2;=0.078; P=.009), perceived susceptibility (&#x3b2;=0.051; P=.03), perceived benefits (&#x3b2;=0.253; P<.001), and trust (&#x3b2;=0.33; P<.001), and negatively associated with perceived severity (&#x3b2;=-0.047; P=.049) and privacy concerns (&#x3b2;=-0.11; P<.001). Perceived ease of use and self-efficacy were not significant predictors. CONCLUSIONS: The health technology acceptance model was a useful framework for explaining the intention to use a health chatbot by combining technology acceptance and health motivation constructs. Both social design features and chatbot design features shaped adoption-related beliefs, with peer-oriented and family-oriented framing and AI-powered chatbots showing particular promise. Trust and privacy concerns remained central determinants of intended use.

Humans

Evaluation of intravenous sedation in dental implant surgeries: A prospective cohort study.

PURPOSE: This study aimed to evaluate the impact of intravenous sedation on patient-centered outcomes during implant and bone augmentation surgeries. METHOD: A prospective observational cohort study included 40 patients undergoing placement of &#x2265;3 implants, with or without bone augmentation. Patients underwent surgery under either intravenous sedation (n = 20) or local anesthesia alone (n = 20), according to routine clinical decision-making and patient preference. The sedation group received intravenous sedation with a multimodal regimen comprising remimazolam, dexmedetomidine, alfentanil, and low-dose esketamine, whereas the control group received local anesthesia only. Patient-reported outcome measures, hemodynamic parameters (SBP, DBP, HR, SpO2), postoperative pain (0-10 scale), and OHRQoL (OHIP-14) were recorded from baseline through 7 days post-surgery. RESULTS: Intravenous sedation was associated with significantly lower intraoperative pain (0.5 [IQR: 0&#x223c;2.75] vs. 3.25 &#xb1; 2.40, p = 0.003), anxiety (1 [IQR: 0&#x223c;2.75] vs. 4 [IQR: 3&#x223c;6], p = 0.001), and experienced discomfort (2 [IQR: 1&#x223c;3.75] vs. 4.15 &#xb1; 2.16, p = 0.016), and shortened perceived treatment duration (2.90 &#xb1; 2.34 vs. 5 [IQR: 4&#x223c;5], p = 0.020). Early postoperative pain was lower in the sedation group from Days 1-4 (p = 0.003-0.010). Hemodynamic parameters were more stable under sedation, with lower SBP (116.42 &#xb1; 13.32 vs. 144.11 &#xb1; 17.42 mmHg, p < 0.001), DBP (73.21 &#xb1; 10.28 vs. 82.37 &#xb1; 11.03 mmHg, p = 0.012), and HR (71.00 [IQR: 62.50&#x223c;79.25] vs. 85.00 &#xb1; 10.72 bpm, p = 0.021). OHRQoL scores favored the sedation group in swallowing, diet, malaise, and daily activities, particularly during the first three postoperative days (p=0.006-0.040). CONCLUSION: Intravenous sedation may enhance the patient experience during implant and/or bone augmentation procedures by reducing intraoperative pain and anxiety, improving hemodynamic stability, and promoting better early-postoperative recovery and OHRQoL. These findings suggest that intravenous sedation provides a safe and effective alternative for implant dentistry surgery, particularly for anxious or pain-sensitive individuals.

Humans

Pairwise Comparative Safety and Effectiveness of Anti-TNF Blockers, Vedolizumab, and Ustekinumab During Pregnancy: A Systematic Review and Meta-Analysis.

PURPOSE: Biologic therapies, including tumor necrosis factor (TNF) blockers, vedolizumab (VDZ), and ustekinumab (UST), are generally considered safe during pregnancy in patients with inflammatory bowel disease (IBD), though comparative data remain limited. This meta-analysis examines their safety and effectiveness. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science was conducted through July 2025. Eligible studies reported maternal or neonatal outcomes in pregnant IBD patients treated with biologics. Studies were pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals. Heterogeneity was assessed using I2. Primary outcomes were preterm birth and disease activity; secondary outcomes included pregnancy and neonatal outcomes. RESULTS: Nine observational studies (n&#x2009;=&#x2009;6,054) were included. Compared to TNF blockers, VDZ was associated with a higher risk of preterm delivery (RR&#x2009;=&#x2009;1.35, 95% CI 1.04-1.75, I2&#x2009;=&#x2009;0%) and active disease (RR&#x2009;=&#x2009;1.55, 95% CI 1.01-2.40, I2&#x2009;=&#x2009;50%). UST was associated with a higher risk of active disease (RR&#x2009;=&#x2009;1.30, 95% CI 1.06-1.60, I2&#x2009;=&#x2009;0%) and congenital anomalies (RR&#x2009;=&#x2009;2.08, 95% CI 1.30-3.32, I2&#x2009;=&#x2009;0%) compared to TNF blockers. Compared to UST, VDZ was linked to increased risks of preterm birth (RR&#x2009;=&#x2009;2.60, 95% CI 1.03-6.57, I2&#x2009;=&#x2009;0%) and low birth weight (RR&#x2009;=&#x2009;2.38, 95% CI 1.01-5.60, I2&#x2009;=&#x2009;0%). No significant differences were observed for live births, abortions, hospitalizations, or neonatal infections. CONCLUSION: TNF blockers showed a favorable safety and effectiveness profile, VDZ and UST performed broadly similar, and all three biological classes appeared compatible with safe use in pregnancy to maintain effective disease control. Observed differences reflect that VDZ and UST cohorts likely had longer disease duration, prior biologic exposure, and more active disease. The results of this meta-analysis support the continuation of biologic therapy for disease control in pregnant patients with IBD. Treatment decisions should be individualized and tailored to each patient's clinical context.

Female

Systematic Review of Pharmacologic Treatment for Migraine Prevention in Adults: Report of the AAN Guidelines Subcommittee and the American Headache Society.

BACKGROUND AND OBJECTIVES: This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS: A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, &#x2265;50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS: A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION: This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

Humans

Electro-clinical efficacy and safety of midazolam in neonatal seizures: a systematic review with individual level exploratory analysis of gestational age-related treatment response.

UNLABELLED: Neonatal seizures are the most common neurological emergency during the neonatal period and are associated with increased mortality and adverse neurodevelopmental outcomes. Despite current recommendations supporting phenobarbital as first-line therapy, seizure control remains suboptimal in a large proportion of neonates, prompting the use of second-line antiseizure medications. Midazolam is increasingly administered in refractory neonatal seizures but evidence regarding its electro-clinical efficacy and safety remains limited and heterogeneous. To systematically review the available evidence on the electro-clinical efficacy and safety of midazolam in neonatal seizures and to perform an exploratory individual-level analysis investigating the association between gestational age and treatment response. A systematic review was conducted according to PRISMA 2020 guidelines. Studies including neonates with EEG- or aEEG-confirmed seizures treated with midazolam were included. Binary logistic regression was performed to assess the individual-level association between gestational age and treatment response. Eleven studies involving 146 neonates treated with midazolam were included. Electro-clinical response was observed in 101/146 neonates (69.2%), while seizure cessation was achieved in 61/146 neonates (41.8%). In an exploratory complete-case logistic regression analysis, higher gestational age appeared to be associated with a greater probability of electro-clinical response. The predicted probability curve crossed the 50% response probability at approximately 36.5&#xa0;weeks of gestation. Hypotension was the most frequently reported adverse event, while respiratory depression, sedation-related effects, and transient EEG/aEEG suppression were reported less frequently. CONCLUSIONS: Midazolam may have a role as an add-on antiseizure medication in neonatal seizures, particularly in refractory cases. However, the evidence remains limited by heterogeneity in study design, EEG monitoring strategies, outcome definitions, and incomplete individual-level data. The observed association between gestational age and response is hypothesis-generating and requires prospective validation. WHAT IS KNOWN: &#x2022; Phenobarbital often provides incomplete seizure control in neonates, making second-line antiseizure therapies necessary in refractory cases. &#x2022; Evidence supporting midazolam for neonatal seizures remains limited and heterogeneous. WHAT IS NEW: &#x2022; This systematic review summarizes the electro-clinical efficacy and safety of midazolam and includes an exploratory patient-level analysis suggesting that higher gestational age may be associated with improved treatment response. &#x2022; These findings support further prospective studies on developmental determinants of response to GABAergic therapy.

Humans

2024-2025 BNT162b2 KP.2 COVID-19 full season vaccine effectiveness from vaccine registries linked to administrative claims in two states: A cohort study in non-immunocompromised adults.

BACKGROUND: Data on effectiveness of COVID-19 vaccinations during the 2024-2025 respiratory season are limited, particularly among those with underlying medical conditions (UMC). We estimated BNT162b2 KP.2 vaccine effectiveness (VE) against COVID-19-associated hospital admission, emergency department (ED), and urgent care (UC) visits in two U.S. states. METHODS: Retrospective cohort study of non-immunocompromised adults living in Louisiana or California, with &#x2265;1&#xa0;year prior continuous enrollment in insurance plans contributing to the HealthVerity claims database beginning August 22, 2024. The effectiveness of BNT162b2 KP.2 vaccine (2024-2025 formulation, hereafter referred to as BNT162b2), measured as a time-varying exposure against hospital admission, ED, or UC encounters with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code U07.1 was calculated as 1 - adjusted hazard ratio using Cox proportional hazard models adjusted for age group, sex, state, insurance payor, presence or absence of UMCs, and pre-index healthcare utilization. Stratifications included those aged 65&#xa0;years and older, those aged 18-64&#xa0;years with UMCs, and those aged 18-64&#xa0;years without UMCs. RESULTS: The cohort included 6,256,421 individuals (93% California, 7% Louisiana); 330,565 (5%) received the BNT162b2 vaccine. Vaccinated individuals were older and had more comorbidities, wellness visits, and prior influenza vaccination. Overall, 66% of the study population had &#x2265;1 UMC; the most prevalent conditions were obesity (25%), history of immunocompromised conditions (23%), and mental health conditions (19%). COVID-19-related encounter rates for ED, UC or hospitalization were lower among vaccinated compared to unvaccinated persons (25.1 vs 36.3 per 100,000 person-months). Among all adults, VE was 37% against hospitalization, 12% against ED/UC encounters, and 16% against ED/UC/hospitalization encounters. Results were similar across age groups and UMCs. CONCLUSIONS: BNT162b2 provided protection against COVID-19-associated outcomes of ED, UC or hospitalization among non-immunocompromised U.S. adults, including those with UMCs, over the course of the 2024-2025 respiratory virus season, supporting continued vaccine recommendations. REGISTRATION: This study was posted on clinicaltrials.gov prior to analyses (NCT06923137).

Adolescent