10957 research outputs found
Sort by
Etripamil Nasal Spray for Recurrent Paroxysmal Supraventricular Tachycardia Conversion: Results From the NODE‐303 Open‐Label Study
Full text linkIntroduction
Etripamil is a fast‐acting intranasally self‐administered calcium‐channel blocker developed for termination of paroxysmal supraventricular tachycardia (PSVT). Prior studies have demonstrated safety and efficacy of etripamil for PSVT termination following an initial medically supervised test dose during sinus rhythm. NODE‐303 is an open‐label, single‐arm study that evaluated etripamil for multiple, at‐home PSVT episodes, without test dose before first use.
Methods
Patients applied an ECG monitor at symptom onset and self‐administered etripamil (70 mg) if a vagal maneuver was unsuccessful. ECG monitoring occurred for ≥ 1 h following study drug administration. A repeat 70‐mg dose was introduced during the study for symptoms persisting 10 min after the first dose. Safety measures included treatment‐emergent adverse events (TEAEs) and ECG arrhythmia‐surveillance. Efficacy measures were captured for PSVT termination during treatment of each of the multiple episodes.
Results
1054 perceived PSVT episodes were etripamil‐treated in 503 of 1116 patients enrolled. TEAEs within 24 h were mostly mild or moderate and localized: 30.2% of patients experienced nasal discomfort, nasal congestion (13.9%), rhinorrhea (13.1%), epistaxis (7.4%). TEAE frequencies decreased across multiple PSVT episodes and were similar for single versus repeat doses. For first PSVT episodes, 70.5% of patients converted to sinus rhythm by 60 min post etripamil (median time to conversion = 18.3 min [14.2–25.6]). Conversion in earlier episodes was consistently predictive of conversion in subsequent episodes.
Conclusions
Etripamil nasal spray self‐administered in a real‐world setting was well tolerated, effective, and had a consistent safety profile as a single‐ or repeat‐dose regimen across multiple PSVT episodes.
Trial Registration: ClinicalTrials.gov NCT0407283
Clinical impact of current evidence on cardiac troponin structure, function and release mechanisms – An up to date review
Full text linkMyocardial infarction remains a significant cause of mortality globally. High-sensitivity cardiac troponin is an essential criterion in the fourth universal definition of myocardial infarction. Our understanding of the structure and release mechanisms of troponin has been updated over the last decade, facilitated by ever more sensitive assays. This review initially outlines the structure and function of the troponin complex, then details the currently proposed mechanisms of release and elimination of troponin. It concludes by using this updated understanding to critique the current universal definition of myocardial infarction and injury
Relative Contribution of Pharmacokinetics and Immune Signatures to Clinical Outcomes in Patients With HIV-associated Cryptococcal Meningitis
Full text linkBackground
Host immune responses to HIV-associated cryptococcal meningitis are critical in disease outcome. Their interaction with antifungal drug exposure is poorly understood. This study explored associations between immune biomarkers, antifungal drug exposure, and clinical outcomes in HIV-associated cryptococcal meningitis.
Methods
We analyzed serial plasma and cerebrospinal fluid immune biomarkers from 64 participants recruited from the AMBITION-cm trial. We estimated individual-level exposure to amphotericin B, flucytosine, and fluconazole. Associations between immune biomarkers, pharmacokinetic parameters, and clinical outcomes were evaluated.
Results
An inflammatory cerebrospinal fluid response, characterized by coordination between tumor necrosis factor-α, granulocyte colony-stimulating factor, and interleukin-7 signaling, was linked to low fungal burden, low intracranial pressure, and survival. However, the value of specific immune biomarkers did not predict EFA or mortality. Exposure to amphotericin B was significantly associated with EFA.
Conclusions
Favorable clinical outcomes from HIV-associated cryptococcal meningitis are associated with coordinated inflammatory and cytotoxic responses in the central nervous system. Antifungal drug exposure was the dominant predictor of EFA
Development and evaluation of rapid, national-scale outdoor air pollution modelling and exposure assessment: Hybrid Air Dispersion Exposure System (HADES)
Full text linkImprovements in computer processing power are facilitating the development of more detailed environmental models with greater geographical coverage. We developed a national-scale model of outdoor air pollution (Hybrid Air Dispersion Exposure System − HADES) for rapid production of concentration maps of nitrogen dioxide (NO2) and ozone (O3) at very high spatial resolution (10m). The model combines dispersion modelling with satellite-derived estimates of background concentrations, land cover, and a 3-D representation of buildings, in a statistical calibration framework. We developed an emissions inventory covering England and Wales to implement the model and tested its performance using concentration data for the years 2018–2019 from fixed-site monitoring locations. In 10,000 Monte Carlo cross-validation iterations, hourly-annual average R2 values for NO2 were 0.77–0.79 (RMSE: root mean squared error of 5.3–5.7 µg/m3), and 0.87–0.89 for O3 (RMSE = 3.6–3.8 µg/m3) at the 95% confidence interval. The annual average R2 was 0.80 for NO2 (RMSE = 4.9 µg/m3) and 0.86 for O3 (RMSE = 3.2 µg/m3) from aggregating the hourly-annual estimates. The air pollution surfaces are freely available for non-commercial use. In using these surfaces for exposure assessment, all residential locations, and neighbourhoods in urban areas, are unlikely to be below the 2021 World Health Organisation Air Quality Guidelines threshold (10 µg/m3) for annual average NO2 concentrations (10 µg/m3). Rural and suburban areas are likely to exceed the peak-season 8-hour daily maximum O3 threshold (60 µg/m3)
Influenza vaccination during early pregnancy and risk of major birth defects, US Birth Defects Study To Evaluate Pregnancy exposureS, 2014–2019
Full text linkPurpose
Studies of influenza vaccination during pregnancy and major birth defects generally provide reassuring findings. To maintain public confidence, it is important to continue evaluating the safety of maternal vaccination using well characterized, population-based data. This study extended previous research to examine associations between maternal influenza vaccination and selected birth defects using data from the Birth Defects Study To Evaluate Pregnancy exposureS, a US, multisite case-control study.
Methods
Mothers of case children (diagnosed with a birth defect) and control children (without a birth defect diagnosis) were identified from population-based birth defect surveillance programs and recruited to complete a telephone interview. Data from 2675 case and 1575 control mothers (participants) with deliveries during 2014–2019 were analyzed. Influenza vaccination exposure during the critical exposure period (one month before pregnancy through the first pregnancy month [B1P1] for spina bifida or through the third pregnancy month [B1P3] for other selected birth defects) was assessed controlling for several participant covariates. Logistic regression with propensity score adjustment was used to estimate adjusted odds ratios (aORs) and 95 % confidence intervals (CIs). Several secondary analyses were conducted. A probabilistic bias analysis examined the effect of exposure misclassification.
Results
The aOR observed between B1P1 influenza vaccination exposure and spina bifida was 0.9 (95 % CI: 0.4–2.0). The aORs for B1P3 exposure and other selected birth defects examined ranged from 0.4 to 1.3, with 95 % CIs including the null except those for cleft lip ± cleft palate (aOR: 0.6; 95 % CI: 0.4–0.9) and gastroschisis (aOR: 0.4; 95 % CI: 0.2–0.7). Results from secondary analyses were similar to the primary analyses, and those from probabilistic bias analysis were similar to respective primary and secondary analyses.
Conclusion
Findings showed no statistically significant positive associations between influenza vaccination and the selected birth defects, supporting public health efforts to promote optimal vaccination coverage among pregnant women
Episiotomy and perineal trauma during childbirth in primiparous women: associations with anxiety, quality of life, vaginal and sexual symptoms in the first year postpartum
Full text linkIntroduction
Childbirth-related pelvic floor trauma is prevalent among primiparous women and can lead to significant physical and psychological consequences. While the impact of pelvic floor trauma on physical outcomes has been studied, the relationship between anxiety caused by such trauma and long-term patient-reported outcomes (PROs) such as vaginal symptoms, sexual function, and quality of life (QoL) remains underexplored. This study aims to fill this gap by investigating the association between anxiety induced by pelvic floor trauma during childbirth and these key PROs.
Methods
This prospective longitudinal cohort study analyzed data from 175 nulliparous women who delivered at term a singleton fetus in cephalic presentation and sustained some form of perineal trauma. Anxiety levels were assessed at two time points: during labor and at 12 months postpartum, using a single-item 10-point Likert scale. The other PROs were measured using the International Consultation on Incontinence Questionnaire-Vaginal Symptoms tool (ICIQ-VS).
Results
Findings revealed that higher anxiety scores at birth were associated with elevated anxiety levels at 12 months postpartum and correlated significantly with increased vaginal symptoms, sexual symptoms, and QoL. Notably, while anxiety was linked to negative physical outcomes, higher anxiety scores were also associated with improved perceived QoL, suggesting the potential role of coping mechanisms in response to childbirth trauma as well as the need for future studies using more specialized anxiety tools.
Conclusion
The study underscores the intricate relationship between psychological distress and physical health outcomes in postpartum women. Addressing both anxiety and physical symptoms through personalized care strategies may enhance recovery and overall wellbeing. Future research should explore effective interventions to mitigate anxiety, evaluate resilience and improve PROs in this population
HOW DO WE PREDICT TREATMENT RESPONSE IN OSTEOARTHRITIS ANALYSIS OF A COHORT STUDY IN PEOPLE WITH KNEE OSTEOARTHRITIS
Full text linkAmbulatory foetal ECG monitoring in low and high-risk pregnancies (AMBER2): a prospective cohort study protocol
Full text linkIntroduction
Measuring foetal heart rate (FHR) is critical for assessing foetal well-being, and traditional cardiotocography (CTG), though effective, has limitations such as cost, accessibility and observer bias. Newer non-invasive foetal ECG (NIFECG) devices offer more precise, reliable metrics for FHR variability and could enable remote monitoring, potentially improving early detection of foetal complications like hypoxia and stillbirth.
Methods and analysis
This is a single-centre prospective cohort study taking place in a tertiary maternity unit in the UK. Women with a singleton pregnancy over 26+0 weeks will be approached for participation in the control, foetal growth restriction (FGR) or diabetic groups. The NIFECG home monitoring schedule is 60 min daily for 7 days in the control group, daily from diagnosis until delivery for the FGR group, and daily from 36 weeks until delivery in the Insulin-dependent diabetic group. Longitudinal FHR raw ECG signals will be collected from participants across different gestational age ranges. Reference standards for FHR variability using metrics such as short-term variation, phase-rectified signal averaging acceleration and deceleration capacity will be established. The study will also aim to explore differences in FHR variability in FGR cases against controls and propose safety thresholds to guide decision-making for delivery.
Ethics and dissemination
Approvals have been obtained from the London Stanmore Research Ethics Committee and from the Medicines and Healthcare Regulatory Agency. The results will be published in peer-reviewed journals, presented at conferences and used by the commercial sponsor to pursue European Conformity regulatory compliance marking and future clinical studies.
Trial registration number
NCT06497205
Longitudinal gait changes in functional neurological disorder: A 12-month prospective study
Full text linkBackground
Functional gait disorder (FGD) is a subtype of functional neurological disorder (FND) characterized by abnormal walking patterns. Long-term symptom progression and factors influencing gait changes in FGD remain poorly understood.
Objectives
To investigate longitudinal changes in gait and associated symptoms over 12 months in individuals with FGD and examine whether changes in specific symptoms are associated with changes in gait.
Methods
Individuals with FND and altered gait completed an online survey at baseline and at 3-, 6-, and 12-month follow-up points. The survey collected data on symptom severity, gait changes, and standardised outcome measures. Analyses included descriptive statistics, linear mixed models, Kruskal–Wallis tests, and Spearman's rank correlations.
Results
Of 156 baseline respondents, 65 completed the 12-month follow-up. Sixteen (28.5 %) reported worsening gait, 17 (30.4 %) no change, 13 (23.2 %) improvement, and 10 (17.8 %) fluctuating gait. Linear mixed-model analyses showed no significant within-subject changes in motor or non-motor symptom severity from baseline to 12 months. Greater baseline functional seizure severity was strongly associated with poorer gait outcomes at 12 months (Rₛ = −0.750, p < 0.001, n = 17). Higher muscle rigidity severity at 12 months was also strongly associated with worse gait (Rₛ = −0.604, p < 0.001, n = 30).
Conclusion
This study provides insights into the natural course of functional gait disorder over time, based on participant self-report, revealing heterogeneous trajectories. Exploratory analyses found that functional seizure and muscle rigidity severity were associated with gait decline
Penicillin allergy de-labelling in the critical care unit: Simulations to design an intravenous drug provocation test that mirrors the plasma profile of an enteral challenge
No full textThe majority of penicillin allergy labels are incorrect and a label of penicillin allergy is associated with worse outcomes and increased use of healthcare services. Penicillin allergy assessment and de-labelling may be considered in critically ill patients. An oral penicillin challenge is a common component of most penicillin allergy protocols. In critical illness, the enteral route may not be an option and is less reliable due to altered absorption kinetics. In this study, simulations were undertaken to determine an intravenous infusion dosing schedule for critically ill patients that matches the concentration–time profile of an oral penicillin drug provocation test in the general population. These simulations may help clinicians develop procedures for intravenous infusion penicillin drug provocation tests for critically ill patients
Access Repository Dashboard
Do you manage Open Research Online? Become a CORE Member to access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard! 👇