International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Blood-brain barrier breakdown in brain ischemia: Insights from MRI perfusion imaging.

Brain ischemia is a major cause of neurological dysfunction and mortality worldwide. It occurs not only acutely, such as in acute ischemic stroke (AIS), but also in chronic conditions like cerebral small vessel disease (cSVD). Any other conditions resulting in brain hypoperfusion can also lead to ischemia.

Molecular basis for plasma membrane recruitment of PI4KA by EFR3.

The lipid kinase phosphatidylinositol 4 kinase III α (PI4KIIIα/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B.

Patient perceptions of barriers to effective migraine management in Aotearoa New Zealand.

Introduction Migraine is a complex neurological condition which requires evidence based treatment, tailored to the individual. International evidence shows that treatment is often sub-optimal, but the experience of people with migraine in NZ is unknown. Aim This study aimed to describe the barriers people with migraine disease face when seeking care for their condition in Aotearoa New Zealand (NZ).

Validation of administrative health data for the identification of endometriosis diagnosis.

Study Question: How do endometriosis diagnoses and subtypes reported in administrative health data compare with surgically confirmed disease?

Summary Answer: For endometriosis diagnosis, we observed substantial agreement and high sensitivity and specificity between administrative health data-International Classification of Diseases (ICD) 9 codes-and surgically confirmed diagnoses among participants who underwent gynecologic laparoscopy or laparotomy.

What Is Known Already: Several studies have assessed the validity of self-reported endometriosis in comparison to medical record reporting, finding strong confirmation. We previously reported high inter- and intra-surgeon agreement for endometriosis diagnosis in the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.

The Ross procedure for recurrently failed aortic valve procedures.

The Ross procedure provides young patients with unrepairable aortic valve disease with a living pulmonary autograft that confers significant survival benefit and improved quality of life. However, the procedure is complicated, and surgeons can be reluctant to offer it as a solution, especially in complex re-operative scenarios. We present a young patient with symptomatic, severe aortic insufficiency who had undergone two failed aortic valve procedures for congenital bicuspid aortic valve disease within the prior year.

Diaci v3.0: chromosome-level assembly, de novo transcriptome, and manual annotation of Diaphorina citri, insect vector of Huanglongbing.

Background: Diaphorina citri is an insect vector of "Candidatus Liberibacter asiaticus" (CLas), the gram-negative bacterial pathogen associated with citrus greening disease. Control measures rely on pesticides with negative impacts on the environment, natural ecosystems, and human and animal health. In contrast, gene-targeting methods have the potential to specifically target the vector species and/or reduce pathogen transmission.

The pattern of anti-IL-6 versus non-anti-IL-6 biologic disease modifying anti-rheumatic drugs use in patients with rheumatoid arthritis in Wales, UK: a real-world study using electronic health records.

Objective: Investigating factors associated with drug initiation and discontinuation in patients treated with anti-IL-6 biologic DMARDs (bDMARDs) (tocilizumab or sarilumab) non-anti-IL-6 (anti-TNF, B or T cell therapies) bDMARDs for RA.

Methods: A retrospective cohort study of patients with the diagnosis of RA in the Secure Anonymised Information Linkage Databank, comprising primary and secondary care and specialist rheumatology clinic records for >90% of the population in Wales, UK. Patients initiated on first bDMARD treatment, discontinuation and clinical outcomes including infection and hospitalisation were analysed using Cox regression analysis.

Placental Pathology and Blood Pressure at Age 7: A Longitudinal Discordant Twin Analysis.

Background: Evidence suggests that the intrauterine environment shapes offspring cardiovascular disease risk. Although placental dysfunction may be an important pathophysiologic pathway, numerous parental and pregnancy characteristics that influence offspring blood pressure are strong confounders of the mechanistic role of the placenta in observational analyses of singletons. Therefore, we leverage twin- and sibling-based comparison designs to determine whether placental pathology is associated with offspring blood pressure at age 7 while mitigating major sources of confounding.

The relationship between non-communicable disease risk and mental wellbeing in adolescence: a cross-sectional study utilising objective measures in Indonesia.

Background: Risk factors for non-communicable diseases (NCDs, cardiovascular diseases, cancers, chronic respiratory diseases, diabetes, and mental disorders) arise in adolescence but are mostly framed as relevant to health in adulthood; little is known about the relationship between co-occurring NCD risks and mental wellbeing in young people. This study aims to describe the prevalence and co-occurrence of distinct NCD risk factors, and how they relate to current mental wellbeing amongst adolescents in Indonesia, a young and populous country where NCD burden is increasing rapidly.

Methods: We assessed NCD risk and mental wellbeing amongst 1,331 school-based 16-18-year-olds in Jakarta (N = 609) and South Sulawesi (N = 722).

The Urgency Numeric Rating Scale: Psychometric Evaluation in Adults with Crohn's Disease.

Introduction: Bowel urgency has recently been recognized as a Crohn's disease (CD) symptom that substantially impacts patients' quality of life. The Urgency NRS is a single-item patient-reported outcome measure assessing bowel urgency severity in the past 24 h (0-10 scale). We aimed to evaluate the psychometric properties of the Urgency Numeric Rating Scale (NRS) in adults with moderately to severely active CD and to estimate thresholds for meaningful improvement and bowel urgency remission.

Management, outcomes and predictors of mortality of Cryptococcus infection in patients without HIV: a multicentre study in 46 hospitals from Australia and New Zealand.

Background: Limited data exist regarding outcomes of cryptococcosis in patients without HIV with few studies having compared outcomes of Cryptococcus gattii, versus C. neoformans, infection.

Methods: We conducted a retrospective study in 46 Australian and New Zealand hospitals to determine the outcomes of cryptococcosis in patients without HIV diagnosed between 2015 and 2019, and compared outcomes of C.

Association Between Patient-Reported Pain and Remission or Low Disease Activity in Patients with Rheumatoid Arthritis: Data from RA-BE-REAL Prospective Observational Study.

Introduction: We aim to assess the association of patient-reported pain and remission or low disease activity (LDA) at 3 months (M) in patients receiving baricitinib or other treatments in RA-BE-REAL.

Methods: RA-BE-REAL reports on patients with rheumatoid arthritis (RA) who were prescribed, for the first time, baricitinib (cohort A) or a tumour necrosis factor inhibitor (TNFi) (cohort B-TNFi) or any other mode of action (OMA) (cohort B-OMA). Pain was measured using the visual analogue scale (VAS) (0-100 mm) and clinically meaningful pain improvement thresholds of ≥ 30%, ≥ 50% and ≥ 70% from baseline to 3, 6, 12 and 24 M.

Cerebrospinal Fluid and Serum Neuron-Specific Enolase in Niemann-Pick Disease Type C1.

Niemann-Pick disease, type C1 (NPC1) is an ultra rare, autosomal recessive disorder characterized by impaired intracellular cholesterol trafficking. This study assessed neuron-specific enolase (NSE) as a biomarker for disease status and treatment response in individuals with NPC1. We also evaluated the concordance between serum and cerebrospinal fluid (CSF) NSE measurements.

Renal Disease in Cats and Dogs-Lessons Learned from Text-Mined Trends in Humans.

Chronic kidney disease (CKD) is characterised by progressive kidney damage and encompasses a broad range of renal pathologies and aetiologies. In humans, CKD is an increasing global health problem, in particular in the western world, while in cats and dogs, CKD is one of the leading causes of mortality and morbidity. Here, we aimed to develop an enhanced understanding of the knowledge base related to the pathophysiology of renal disease and CKD in cats and dogs.

CXCR2 immunomodulatory therapy protects against microstructural white matter injury and gait abnormalities but does not mitigate deficits of cognition in a preclinical model of cerebral palsy.

Minimizing central nervous system (CNS) injury from preterm birth depends upon understanding the critical pathways that underlie essential neurodevelopmental and CNS pathophysiology. Signaling by chemokine (C-X-C motif) ligand 1 (CXCL1) through its cognate receptor, CXCR2 [(C-X-C motif) receptor 2] is essential for neurodevelopment. Increased CXCR2 signaling, however, is implicated in a variety of uterine and neuropathologies, and their role in the CNS injury associated with perinatal brain injury is poorly defined.

Unwanted or negative treatment reactions in digital psychological interventions for adolescents with chronic pain.

Objective: Reports of pain clinical trials evaluating psychological treatments often lack sufficient details on the potential and actual harm resulting from intervention. We aimed to understand how frequent and intense treatment reactions, conceptualized as unwanted symptoms, were in three clinical trials of digital Cognitive Behavioral Therapy (CBT) for adolescents with: (1) chronic primary pain, (2) sickle cell disease, and (3) chronic pancreatitis. We also aimed to understand any differences by demographic and clinical variables.

Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study.

Objective: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP) natural history study.

Effects Of E-Cigarette Warning Labels About Mental Health Consequences Of Nicotine Addiction Among Young Adults In The Us: Results From A Randomized Controlled Experiment.

Introduction: Since 2016, the U.S. Food and Drug Administration (FDA) has required e-cigarette packaging and advertising to bear the warning: "WARNING: THIS PRODUCT CONTAINS NICOTINE.

Long COVID in healthcare workers: longitudinal mixed-methods study.

Background: Healthcare workers (HCWs) report higher rates of long coronavirus disease (COVID) (LC) than other occupational groups. It is still unclear whether LC is a lifelong condition. Workforce shortfalls are apparent due to sick leave, reduced hours and lower productivity.

Phase Ib/II study of imprime PGG and pembrolizumab in patients with previously treated advanced non-small cell lung cancer (NSCLC): BTCRC LUN 15-017.

Background: Therapeutic strategies to engage anti-tumor innate immunity are still underdeveloped. Imprime PGG (imprime), a pathogen-associated molecular pattern (PAMP), through pattern recognition receptors, successfully illicit a broad-based innate immune response in preclinical models against various cancers. We aimed to study safety and efficacy of imprime in combination with pembrolizumab in advanced stage non-small cell lung cancer (NSCLC).

Further delineation of the SCAF4-associated neurodevelopmental disorder.

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder.

Molecular features of the serological IgG repertoire elicited by egg-based, cell-based, or recombinant haemagglutinin-based seasonal influenza vaccines: a comparative, prospective, observational cohort study.

Background: Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response.

Methods: In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA).