Quantification of racial and ethnic disparities in alcohol-related problems in light of different methodological approaches.

Aim: We applied the Institute of Medicine (IOM) definition of racial and ethnic disparities in healthcare to estimate disparities in alcohol-related problems. This estimation involved adjusting for drinking patterns, gender and age, with observed disparities further explained by socioeconomic status (SES). We compared results of five statistical approaches which use different methods for adjusting covariates.

Factors associated with placebo response rate in randomized controlled trials of antiseizure medications for focal epilepsy.

Objective: Randomized controlled trials (RCTs) are necessary to evaluate the efficacy of novel treatments for epilepsy. However, there have been concerning increases in the placebo responder rate over time. To understand these trends, we evaluated features associated with increased placebo responder rate.

Changes in US drinking and alcohol use disorders associated with social, health, and economic impacts of COVID-19.

Aims: The COVID-19 pandemic increased alcohol consumption in the USA as a result of widespread individual changes in drinking patterns. Few studies have utilized longitudinal data allowing the prediction of increased or decreased drinking from COVID-19 economic, social, and health impacts.

Methods: Data are from 1819 respondents in the 2019-20 National Alcohol Survey and a one-year follow-up in early 2021.

Global airway disease: mepolizumab simultaneously improves outcomes in severe CRSwNP and asthma.

Chronic rhinosinusitis with nasal polyps (CRSwNP) often co-exists with asthma and non-steroidal anti-inflammatory drug- exacerbated respiratory disease (N-ERD), creating a more severe phenotype and an additional burden compared with CRSwNP disease alone (1-3). The relationship between these diseases in terms of shared immunological disbalance has been coined in the literature as 'global airway disease' or 'unified airway disease' and requires integrated treatment strategies (4-6). Our post hoc analysis of the Phase III randomised, double-blind, placebo-controlled, multicentre SYNAPSE study (GSK ID: 205687; NCT03085797 (7)) assessed the efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, in simultaneously improving both CRSwNP and asthma outcomes versus placebo.

Microglial lipid phosphatase SHIP1 limits complement-mediated synaptic pruning in the healthy developing hippocampus.

The gene inositol polyphosphate-5-phosphatase D (INPP5D), which encodes the lipid phosphatase SH2-containing inositol polyphosphate 5-phosphatase 1 (SHIP1), is associated with the risk of Alzheimer's disease (AD). How it influences microglial function and brain physiology is unclear. Here, we showed that SHIP1 was enriched in early stages of healthy brain development.

Does cannabis substitute or complement alcohol after recreational cannabis legalization in the Washington State? A three-level mixed-effects modeling.

Background: Whether cannabis substitute or complement alcohol remains inconclusive. Little is known about the daily-level associations between cannabis and alcohol use by cannabis user type (medical vs. recreational use) in people who use alcohol and cannabis within a legalized environment.

Artificial Intelligence: Fundamentals and Breakthrough Applications in Epilepsy.

Artificial intelligence, machine learning, and deep learning are increasingly being used in all medical fields including for epilepsy research and clinical care. Already there have been resultant cutting-edge applications in both the clinical and research arenas of epileptology. Because there is a need to disseminate knowledge about these approaches, how to use them, their advantages, and their potential limitations, the goal of the 2023 Merritt-Putnam Symposium and of this synopsis review of that symposium has been to present the background and state of the art and then to draw conclusions on current and future applications of these approaches through the following: (1) Initially provide an explanation of the fundamental principles of artificial intelligence, machine learning, and deep learning.

Selective Deuteration and Tritiation of Pharmaceutically Relevant Sulfoximines.

Pharmaceutical-aligned research endeavors continue to diversify, including via the installation of new chemical functionality and non-classical bioisosteres within drug design. With this, an equally high demand emerges for the direct installation of isotopic substituents into these scaffolds within drug discovery programmes, as isotopologues are essential for the elucidation of the biological efficacy and metabolic fate of the active pharmaceutical ingredient (API). The sulfoximine functional group has recently become established as a high-value unit in this context; however, general and effective methods for the synthesis of deuterium (H, D) and tritium (H, T) labelled analogues have remained elusive.

Youth and Family Perspectives on Diagnosis Communication About Pediatric Functional Seizures: A Qualitative Study.

Background: This study aims to understand diagnosis communication experiences and preferences of youths with functional seizures and their parents.

Methods: Semistructured interviews with youths and their parents from a tertiary care children's hospital were conducted separately. We confirmed the diagnosis of functional seizures with the youth's treating providers.

Myoclonus After Cardiac Arrest did not Correlate with Cortical Response on Somatosensory Evoked Potentials.

Purpose: Myoclonus after anoxic brain injury is a marker of significant cerebral injury. Absent cortical signal (N20) on somatosensory evoked potentials (SSEPs) after cardiac arrest is a reliable predictor of poor neurological recovery when combined with an overall clinical picture consistent with severe widespread neurological injury. We evaluated a clinical question of if SSEP result could be predicted from other clinical and neurodiagnostic testing results in patients with post-anoxic myoclonus.

C-H Activation and Hydrogen Isotope Exchange of Aryl Carbamates Using Iridium(I) Complexes Bearing Chelating NHC-Phosphine Ligands.

Hydrogen isotope exchange (HIE) via C-H activation constitutes an efficient method for the synthesis of isotopically-enriched compounds, which are crucial components of the drug discovery process and are extensively employed in mechanistic studies. A series of iridium(I) complexes, bearing a chelating phosphine-N-heterocyclic carbene ligand, was designed and synthesized for application in the catalytic HIE of challenging N- and O-aryl carbamates. A broad range of substrates were labeled efficiently, and applicability to biologically-relevant systems was demonstrated by labeling an ʟ-tyrosine-derived carbamate with excellent levels of deuterium incorporation.

Behavioral risk factors and socioeconomic inequalities in ischemic heart disease mortality in the United States: A causal mediation analysis using record linkage data.

Background: Ischemic heart disease (IHD) is a major cause of death in the United States (US), with marked mortality inequalities. Previous studies have reported inconsistent findings regarding the contributions of behavioral risk factors (BRFs) to socioeconomic inequalities in IHD mortality. To our knowledge, no nationwide study has been conducted on this topic in the US.

Collaborative GSK-University of Strathclyde doctoral research and training programmes: Transforming approaches to industry-academia engagement.

A global biopharma company, GSK, and the University of Strathclyde have developed an expansive and transformative research and training partnership originating in chemistry-aligned disciplines, with subsequent extensive expansion across further areas of the company. This has opened unique approaches for the delivery of collaborative research innovations while also enhancing the professional development and learning of GSK personnel, in addition to other embedded researchers and collaborating scientists, on a pathway towards more rapid and efficient discovery of new medicines.

Common Critiques and Recommendations for Studies in Neurology Using Machine Learning Methods.

Machine learning (ML) methods are becoming more prevalent in the neurology literature as alternatives to traditional statistical methods to address challenges in the analysis of modern data sets. Despite the increase in the popularity of ML methods in neurology studies, some authors do not fully address all items recommended in reporting guidelines. The authors of this Research Methods article are members of the ® editorial board and have reviewed many studies using ML methods.

Metabolomic analysis combined with machine learning algorithms enables the evaluation of postharvest pecan color stability.

Nut kernel color is a crucial quality indicator affecting the consumers first impression of the product. While growing evidence suggests that plant phenolics and their derivatives are linked to nut kernel color, the compounds (biomarkers) responsible for kernel color stability during storage remain elusive. Here, pathway-based metabolomics with machine learning algorithms were employed to identify key metabolites of postharvest pecan color stability.

The relationship between alcohol availability and drink-driving policies and admissions to substance use disorder treatment during pregnancy.

Objective: Pregnancy-specific alcohol policies are widely adopted yet have limited effectiveness and established risks. It is unknown whether general population alcohol policies are effective during pregnancy. This study investigated associations between general population policies and alcohol treatment admission rates for pregnant people specifically.

The present and future of seizure detection, prediction, and forecasting with machine learning, including the future impact on clinical trials.

Seizures have a profound impact on quality of life and mortality, in part because they can be challenging both to detect and forecast. Seizure detection relies upon accurately differentiating transient neurological symptoms caused by abnormal epileptiform activity from similar symptoms with different causes. Seizure forecasting aims to identify when a person has a high or low likelihood of seizure, which is related to seizure prediction.

Demonstration of Group-Level and Individual-Level Efficacy Using Time-to-Event Designs for Clinical Trials of Antiseizure Medications.

Background And Objectives: Participants with treatment-resistant epilepsy who are randomized to add-on placebo and remain in a trial for the typical 3 to 5-month maintenance period may be at increased risk of adverse outcomes. A novel trial design has been suggested, time to prerandomization monthly seizure count (T-PSC), which would limit participants' time on ineffective therapy. We reanalyzed 11 completed trials to determine whether the primary efficacy conclusions at T-PSC matched each of the original, longer trials.

Proximal foundation anchor variations and their correlation with unplanned return to the operating room (UPROR) in children with EOS treated with magnetically controlled growing rods (MCGR).

Introduction: The evolution of MCGR technique has led to modifications in the configuration of the proximal construct to decrease the incidence of implant-related complications (IRC) and revision surgeries. However, there is no data characterizing the performance of the most used configurations reducing the risk of complications.

Methods: 487 patients were identified from an international multicenter EOS database.

Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals or no treatment in England: a retrospective cohort study.

Objective: To describe characteristics and acute clinical outcomes for patients with COVID-19 treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated patients at highest risk per National Health Service (NHS) criteria.

Methods: Retrospective study of non-hospitalized patients between 1 December 2021 and 31 May 2022, using data from the Discover-NOW dataset (North-West London). Included patients were aged ≥12 years and treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated but expected to be eligible for early treatment per NHS highest-risk criteria.

Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals, or no treatment: a retrospective cohort study.

Background: The clinical benefit of coronavirus disease 2019 (COVID-19) treatments against new circulating variants remains unclear. We sought to describe characteristics and clinical outcomes of highest risk patients with COVID-19 receiving early COVID-19 treatments in Scotland.

Methods: Retrospective cohort study of non-hospitalized patients diagnosed with COVID-19 from December 1, 2021-October 25, 2022, using Scottish administrative health data.

When the Going Gets Tough: Multimorbidity and Heavy and Binge Drinking Among Adults.

Introduction: Multimorbidity, the presence of two or more long-term health conditions in the same individual, is an emerging epidemic associated with increased morbidity and mortality. Continued drinking concurrent with alcohol-related chronic conditions, particularly with multimorbidity, is likely to further elevate health risk. This study aimed to examine the associations of multimorbidity among diabetes, hypertension, heart disease, and cancer with drinking, and moderation of these associations by age.