Targeting the sympathetic nervous system with the selective imidazoline receptor agonist moxonidine for the management of hypertension: an international position statement.

Hypertension is often linked with metabolic risk factors that share common pathophysiological pathways. Despite wide-spread availability of multiple drug classes, optimal blood pressure (BP) control remains challenging. Increased central sympathetic outflow is frequently neglected as a critical regulator of both circulatory and metabolic pathways and often remains unopposed therapeutically.

Recommended measurement instruments for genitourinary symptoms associated with menopause: the COMMA (Core outcomes in menopause) consortium.

Objective: The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in most bothersome symptom, distress, bother or interference of genitourinary symptoms, satisfaction with treatment, and side effects.

Methods: We conducted a systematic review to identify possible definitions and PROMs, including their measurement properties. Identified definitions and relevant PROMs with acceptable measurement properties were entered into an international consensus process involving 28 participants from 10 countries to achieve final recommendations for each core outcome.

Increased innate immune responses in adolescents with obesity and its relation to subclinical cardiovascular measures: An exploratory study.

Cardiometabolic risk accrues across the life course and childhood and adolescence are key periods for effective prevention. Obesity is associated with inflammation in adults, but pediatric data are scarce. In a cross-sectional and longitudinal study, we investigated immune cell composition and activation in 31 adolescents with obesity (41.

Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma.

Background: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.

Methods: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent.

Hemolysis events in the phase 3 PEGASUS study of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) experience complement-mediated intravascular hemolysis leading to anemia, fatigue, and potentially life-threatening thrombotic complications. Pegcetacoplan, a C3 inhibitor, demonstrated sustained improvements in hematologic and clinical parameters in the phase 3 PEGASUS trial in patients with PNH who remained anemic despite C5 inhibitor therapy. The present post hoc analysis describes 26 hemolysis adverse events (AEs) experienced in 19 patients during pegcetacoplan therapy in PEGASUS and baseline patient characteristics potentially associated with increased hemolysis risk.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.

Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.

Background: Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear.

Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging.

Background And Objectives: Mounting evidence supports sex differences in Alzheimer disease (AD) risk. Vascular and hormonal factors may together contribute to AD risk in female adults. We investigated whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a 3-year follow-up period.

How immune dynamics shape multi-season epidemics: a continuous-discrete model in one dimensional antigenic space.

We extend a previously published model for the dynamics of a single strain of an influenza-like infection. The model incorporates a waning acquired immunity to infection and punctuated antigenic drift of the virus, employing a set of coupled integral equations within a season and a discrete map between seasons. The long term behaviour of the model is demonstrated by examples where immunity to infection depends on the time since a host was last infected, and where immunity depends on the number of times that a host has been infected.

A case of successful revascularization and renal recovery after 6 days of renal artery occlusion.

A 72-year-old man with peripheral arterial disease, an atrophic left kidney, and prior right renal chimney stent as part of a complex endovascular abdominal aortic aneurysm repair presented to our emergency department with right flank pain and anuria resulting from right artery occlusion. His serum creatinine on admission was 7.5 mg/dL.

A universal molecular control for DNA, mRNA and protein expression.

The expression of genes encompasses their transcription into mRNA followed by translation into protein. In recent years, next-generation sequencing and mass spectrometry methods have profiled DNA, RNA and protein abundance in cells. However, there are currently no reference standards that are compatible across these genomic, transcriptomic and proteomic methods, and provide an integrated measure of gene expression.

Initial response and 12-month outcomes after commencing dexamethasone or vascular endothelial growth factor inhibitors for retinal vein occlusion in the FRB registry.

To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.

Accuracy of Treatment Recommendations by Pragmatic Evidence Search and Artificial Intelligence: An Exploratory Study.

There is extensive literature emerging in the field of dentistry with the aim to optimize clinical practice. Evidence-based guidelines (EBGs) are designed to collate diagnostic criteria and clinical treatment for a range of conditions based on high-quality evidence. Recently, advancements in Artificial Intelligence (AI) have instigated further queries into its applicability and integration into dentistry.

What Is a Meaningful Difference When Using Infarct Volume as the Primary Outcome?: Results From the HERMES Database.

Background: Ischemic stroke lesion volume at follow-up is an important surrogate outcome for acute stroke trials. We aimed to assess which differences in 48-hour lesion volume translate into meaningful clinical differences.

Methods: We used pooled data from 7 trials investigating the efficacy of endovascular treatment for anterior circulation large vessel occlusion in acute ischemic stroke.

Management of Sleep-Disordered Breathing in a Spinal Cord Injury Rehabilitation Center: Model of Care Adaptation and Implementation.

Background: Obstructive sleep apnea (OSA) is highly prevalent and poorly managed in spinal cord injury (SCI). Alternative management models are urgently needed to improve access to care. We previously described the unique models of three SCI rehabilitation centers that independently manage uncomplicated OSA.

International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

Background: Exacerbation frequency strongly influences treatment choices in patients with severe asthma.

Research Question: What is the extent of the variability of exacerbation rate across countries and its implications in disease management?

Study Design And Methods: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit.

Trigeneration based on the pyrolysis of rural waste in India: Environmental impact, economic feasibility and business model innovation.

Pyrolysis-based waste-to-bioenergy development has the potential to resolve some of the major challenges facing rural communities in India such as poor electrification, household air pollution, and farmland degradation and contamination. Existing understanding and analysis of the economic feasibility and environmental impact of bioenergy deployment in rural areas is limited by parameter uncertainties, and relevant business model innovation following economic evaluation is even scarcer. This paper uses findings from a new field survey of 1200 rural households to estimate the economic feasibility and environmental impact of a pyrolysis-based bioenergy trigeneration development that was designed to tackle these challenges.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

Background: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.