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Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

BACKGROUND: A bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. METHODS: We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). RESULTS: Nine studies were included (3 RCTs, 6 retrospective cohort studies; n = 148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1·08, 95% CI 1·02-1·13; p = 0·004; I2 = 44%), driven by the observational studies group (1·08, 1·02-1·14; I2 = 61%); RCTs showed a directionally consistent but non-significant RR (1·12, 0·87-1·43; I2 = 0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. CONCLUSION: Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.

Humans

The effect of zalunfiban on high sensitivity cardiac troponin and the association with clinical outcomes in patients with STEMI.

BACKGROUND: Among individuals with ST-segment elevation myocardial infarction (STEMI), a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. The impact of zalunfiban on Myocardial Infarction (MI) size and association with downstream outcomes remains unclear. METHODS: In a prespecified analysis, we studied results among study participants treated with 2 doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. RESULTS: More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation (P = .006) and more frequent Q wave development (P < .001). At coronary angiography more elevated hs-cTnT at presentation was associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P < .05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio [OR] 1.83 per log unit increase; P = .03), cardiovascular death (OR 1.83 per log unit increase; P = .03), heart failure (OR 2.74 per log unit increase; P < .001) or the composite of death and heart failure (P < .001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (P = .04) and across multiples &#x2265; 10 to &#x2265; 1,000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. CONCLUSIONS: Among patients with STEMI, more elevated concentrations of hs-cTnT are associated with worse measures of reperfusion and higher-risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size. TRIAL REGISTRATION: A phase 3 study of zalunfiban in subjects with ST-elevation MI (CELEBRATE); NCT04825743.

Humans

Effects of carbohydrate mouth rinse on psychophysiological responses, kinematic variables and technical actions during small-sided soccer games.

BACKGROUND: This study investigated the effects of carbohydrate mouth rinsing (CHOMR) on various psychophysiological, kinematic, and technical actions during 4-a-side small-sided soccer games (SSGs). METHODS: In a randomized, crossover, double-blind design, 16 young male soccer players (age: 15&#x2009;&#xb1;&#x2009;1 years; height: 172.6&#x2009;&#xb1;&#x2009;7.0&#x2009;cm; body mass: 57.8&#x2009;&#xb1;&#x2009;7.9 kg) participated in two 4-a-side SSGs separated by one week following either CHOMR or placebo (PLA). During each SSGs, heart rate (HRmean, %HR, and HRmax), rating of perceived exertion (RPE), enjoyment, visual analogue scale (VAS) to perceived mental fatigue, mood states, total distance (TD), high-speed running distance (HSRD), average metabolic power (AMP), high metabolic load distance (HMLD), sprint distance (SD), acceleration (ACC), deceleration (DEC), and technical actions (e.g. passing, tackling, shooting, and interceptions) were assessed. RESULTS: Compared with PLA, CHOMR resulted in significantly higher RPE (p&#x2009;=&#x2009;0.025, g&#x2009;=&#x2009;0.86) and significantly lower VAS scores (p&#x2009;=&#x2009;0.010, g&#x2009;=&#x2009;-0.71). In addition, the CHOMR condition showed significantly higher values for interceptions, successful tackles, unsuccessful tackles, unsuccessful shots, and goals (p&#x2009;<&#x2009;0.05, g&#x2009;=&#x2009;0.96-2.02), whereas block values were significantly higher in the PLA condition. There were no statistically significant differences in HRmean, %HR, HRmax, enjoyment, TD, HSRD, AMP, HMLD, SD, ACC, DEC, successful passes, unsuccessful passes, successful shots, or mood states between the conditions (p&#x2009;>&#x2009;0.05). CONCLUSION: The current study findings suggest that CHOMR may enhance selected technical actions and lower VAS scores during 4-a-side SSGs, although it was also associated with higher RPE and did not alter the kinematic responses. In conclusion, CHOMR was associated with higher RPE, lower mental fatigue, and selective improvements in technical actions, with no significant effects on kinematic variables or HR.

Humans

Effects of multistrain probiotic supplementation on hepatic function and anthropometric parameters in patients with metabolic dysfunction-associated steatotic liver disease: a double-blind, randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent on a global scale. The gut microbiota is integral to its pathogenesis, prompting extensive research into microbiota modulation as a potential adjunctive therapeutic strategy. AIM: The study aimed to evaluate the effect of multistrain probiotics supplementation on hepatic function in patients with MASLD in a double-blind, randomized, controlled trial. The primary outcomes were changes in Fibrosis-4 index (FIB-4) and fatty liver index (FLI). Secondary outcomes included changes in anthropometric parameters, selected biochemical markers, and other liver-related indices. METHODS: A total of 64 patients with MASLD were randomly assigned to two groups receiving either placebo (C) or a probiotic mixture (PRO) containing the following bacterial strains: 50% Lactococcus lactis Rosell-1058, 25% Lacticaseibacillus casei Rosell-215, 12.5% Lactobacillus helveticus Rosell-52, 12.5% Bifidobacterium bifidum Rosell-71 for 12 wk. RESULTS: Significant group &#xd7; time interactions were observed for FIB-4 (Q = 0.007), with reduction in the PRO group and increase in the C group (-0.05 vs. 0.10; P = 0.002). No significant interaction was found for FLI (Q = 0.942). Significant group &#xd7; time interactions were also observed for aspartate aminotransferase (-2.87 vs. 1.87 U/L; Q = 0.003) and APRI (-0.03 vs. 0.02; Q = 0.001), favoring the PRO group (P < 0.001 for both). No significant changes were observed in anthropometric parameters, glucose levels, or lipid profile. CONCLUSIONS: In patients with MASLD, the 12-wk probiotic supplementation had a modest but statistically significant effect on FIB-4, aspartate aminotransferase, and APRI, with no significant effect on FLI or anthropometric and metabolic parameters. These findings suggest that this probiotic formulation may have potential benefits for liver function in MASLD. However, long-term studies incorporating imaging-based and histological endpoints are required to determine the clinical significance of these findings.

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

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

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