Multiple Imputation for Longitudinal Data: A Tutorial.

Longitudinal studies are frequently used in medical research and involve collecting repeated measures on individuals over time. Observations from the same individual are invariably correlated and thus an analytic approach that accounts for this clustering by individual is required. While almost all research suffers from missing data, this can be particularly problematic in longitudinal studies as participation often becomes harder to maintain over time.

Antigen-specific T-cell frequency and phenotype mirrors disease activity in DRB1*04:04+ rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is associated with high-risk HLA class II alleles known as the "RA shared epitope." Among prevalent shared epitope alleles, study of DRB1*04:04 has been limited. To define relevant epitopes, we identified citrullinated peptide sequences from synovial antigens that were predicted to bind to HLA-DRB1*04:04 and utilized a systematic approach to confirm their binding and assess their recognition by CD4 T cells.

The seroprevalence of SARS-CoV-2-specific antibodies in Australian children: A cross-sectional study.

Background: Following reduction of public health and social measures concurrent with SARS-CoV-2 Omicron emergence in late 2021 in Australia, COVID-19 case notification rates rose rapidly. As rates of direct viral testing and reporting dropped, true infection rates were most likely to be underestimated.

Objective: To better understand infection rates and immunity in this population, we aimed to estimate SARS-CoV-2 seroprevalence in Australians aged 0-19 years.

Gaps in the usage and reporting of multiple imputation for incomplete data: findings from a scoping review of observational studies addressing causal questions.

Background: Missing data are common in observational studies and often occur in several of the variables required when estimating a causal effect, i.e. the exposure, outcome and/or variables used to control for confounding.

GaN Surface Passivation by MoS Coating.

In this study, we investigate the impact of two-dimensional MoS coating on the optical properties of surface GaN/AlGaN quantum wells (QWs). A strong enhancement in GaN QW light emission is observed with monolayer-MoS coating, yielding luminescence intensity comparable to that from a QW capped by an AlGaN barrier. Our results demonstrate that MoS, despite its quite different nature from III-nitride semiconductors, acts as an effective barrier for surface GaN QWs and suppresses spatially localized intrinsic surface states.

T cells promote distinct transcriptional programs of cutaneous inflammatory disease in keratinocytes and dermal fibroblasts.

T cells and structural cells coordinate appropriate inflammatory responses and restoration of barrier integrity following insult. Dysfunctional T cells precipitate skin pathology occurring alongside altered structural cell frequencies and transcriptional states, but to what extent different T cells promote disease-associated changes remains unclear. We show that functionally diverse circulating and skin-resident CD4CLA T cell populations promote distinct transcriptional outcomes in human keratinocytes and fibroblasts associated with inflamed or healthy tissue.

Origin of giant enhancement of phase contrast in electron holography of modulation-doped n-type GaN.

The electron optical phase contrast probed by electron holography at n-n GaN doping steps is found to exhibit a giant enhancement, in sharp contrast to the always smaller than expected phase contrast reported for p-n junctions. We unravel the physical origin of the giant enhancement by combining off-axis electron holography data with self-consistent electrostatic potential calculations. The predominant contribution to the phase contrast is shown to arise from the doping dependent screening length of the surface Fermi-level pinning, which is induced by FIB-implanted carbon point defects below the outer amorphous shell.

Long-term outcomes of early exposure to repeated general anaesthesia in children with cystic fibrosis (CF-GAIN): a multicentre, open-label, randomised controlled phase 4 trial.

Background: Long-term effects of early, recurrent human exposure to general anaesthesia remain unknown. The Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) trial provided an opportunity to examine this issue in children randomly assigned in infancy to either repeated bronchoalveolar-lavage (BAL)-directed therapy with general anaesthesia or standard care with no planned lavages up to 5 years of age when all children received BAL-directed therapy under general anaesthesia.

Methods: This multicentre, randomised, open-label phase 4 trial (CF-GAIN) used the original ACFBAL trial randomisation at 3·6 months (SD 1·6) to BAL-directed therapy or standard-care groups to assess the impact of general anaesthesia exposures over early childhood.

Analysis and Reporting of Randomized Trials in Cleft Palate Surgery: Learning from the Timing of Primary Surgery (TOPS) Trial.

The Timing of Primary Surgery (TOPS) trial was published August 2023 in the New England Journal of Medicine and is a milestone achievement for a study focused on cleft palate. Due to the complexity of outcome reporting in cleft and the rarity of such comparative trials, TOPS presents a useful opportunity to critically review the design, analysis and reporting strategies utilised. This perspective article focused on the inclusion of participants, the choice of the primary outcome measure and the analysis of ordinal data within the trial.

Recoverability and estimation of causal effects under typical multivariable missingness mechanisms.

In the context of missing data, the identifiability or "recoverability" of the average causal effect (ACE) depends not only on the usual causal assumptions but also on missingness assumptions that can be depicted by adding variable-specific missingness indicators to causal diagrams, creating missingness directed acyclic graphs (m-DAGs). Previous research described canonical m-DAGs, representing typical multivariable missingness mechanisms in epidemiological studies, and examined mathematically the recoverability of the ACE in each case. However, this work assumed no effect modification and did not investigate methods for estimation across such scenarios.

Important roles of coarse particles in pasting and gelling performance of different pulse flours under high-temperature heating.

Dehulled pea, lentil, and faba bean grains were milled into flours with 0.5- to 2.5-mm sieves.

Handling missing data when estimating causal effects with targeted maximum likelihood estimation.

Targeted maximum likelihood estimation (TMLE) is increasingly used for doubly robust causal inference, but how missing data should be handled when using TMLE with data-adaptive approaches is unclear. Based on data (1992-1998) from the Victorian Adolescent Health Cohort Study, we conducted a simulation study to evaluate 8 missing-data methods in this context: complete-case analysis, extended TMLE incorporating an outcome-missingness model, the missing covariate missing indicator method, and 5 multiple imputation (MI) approaches using parametric or machine-learning models. We considered 6 scenarios that varied in terms of exposure/outcome generation models (presence of confounder-confounder interactions) and missingness mechanisms (whether outcome influenced missingness in other variables and presence of interaction/nonlinear terms in missingness models).

A comparison of strategies for selecting auxiliary variables for multiple imputation.

Multiple imputation (MI) is a popular method for handling missing data. Auxiliary variables can be added to the imputation model(s) to improve MI estimates. However, the choice of which auxiliary variables to include is not always straightforward.

The Efficacy of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Phase 3 Randomized Placebo-Controlled Clinical Trial.

Background: Neurokinin receptor 1 antagonists are effective in reducing nausea and vomiting in chemotherapy-induced emesis. We investigated the safety and efficacy of tradipitant, a neurokinin receptor 1 antagonist, in patients with idiopathic and diabetic gastroparesis.

Methods: A total of 201 adults with gastroparesis were randomly assigned to oral tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks.

On the use of multiple imputation to address data missing by design as well as unintended missing data in case-cohort studies with a binary endpoint.

Background: Case-cohort studies are conducted within cohort studies, with the defining feature that collection of exposure data is limited to a subset of the cohort, leading to a large proportion of missing data by design. Standard analysis uses inverse probability weighting (IPW) to address this intended missing data, but little research has been conducted into how best to perform analysis when there is also unintended missingness. Multiple imputation (MI) has become a default standard for handling unintended missingness and is typically used in combination with IPW to handle the intended missingness due to the case-control sampling.

Characteristics and outcomes of children receiving intensive care therapy within 12 hours following a medical emergency team event.

To describe characteristics and outcomes of children requiring intensive care therapy (ICT) within 12 hours following a medical emergency team (MET) event. Retrospective cohort study. Quaternary paediatric hospital.

The forgotten girls: the state of evidence for health interventions for pregnant adolescents and their newborns in low-income and middle-income countries.

Every year, an estimated 21 million girls aged 15-19 years become pregnant in low-income and middle-income countries (LMICs). Policy responses have focused on reducing the adolescent birth rate whereas efforts to support pregnant adolescents have developed more slowly. We did a systematic review of interventions addressing any health-related outcome for pregnant adolescents and their newborn babies in LMICs and mapped its results to a framework describing high-quality health systems for pregnant adolescents.

Emotional symptoms and inflammatory biomarkers in childhood: Associations in two Australian birth cohorts.

Background: An increasing body of evidence supports associations between inflammation and mental health difficulties, but the onset and directionality of these relationships are unclear.

Methods: Data sources: Barwon Infant Study (BIS; n = 500 4-year-olds) and Longitudinal Study of Australian Children (LSAC; n = 1099 10-13-year-olds).

Measures: Strengths and Difficulties Questionnaire emotional symptoms at 4, 10-11 and 12-13 years, and circulating levels of two inflammatory biomarkers, high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls (GlycA), at 4 and 11-12 years.

Investigation of the Impact of Point Defects in InGaN/GaN Quantum Wells with High Dislocation Densities.

In this work, we report on the efficiency of single InGaN/GaN quantum wells (QWs) grown on thin (<1 µm) GaN buffer layers on silicon (111) substrates exhibiting very high threading dislocation (TD) densities. Despite this high defect density, we show that QW emission efficiency significantly increases upon the insertion of an In-containing underlayer, whose role is to prevent the introduction of point defects during the growth of InGaN QWs. Hence, we demonstrate that point defects play a key role in limiting InGaN QW efficiency, even in samples where their density (2-3 × 109 cm-2) is much lower than that of TD (2-3 × 1010 cm-2).

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified.

Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age.

Design, Setting, And Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries.

Effectiveness of asthma preventer dispensing for preventing childhood asthma readmissions: a multisite cohort linkage study.

Objectives: To (1) describe the dispensing of asthma preventers at hospital discharge and estimate its effect on hospital readmissions, and (2) estimate the effect of community asthma preventer dispensing on readmissions for the subgroup of children who were not prescribed an asthma preventer at discharge.

Design: Multisite cohort study with linked administrative data.

Participants: Children aged 3-18 years admitted with asthma to a tertiary paediatric, mixed paediatric and adult, or regional hospital between 2017 and 2018.

Success of blinding a procedural intervention in a randomised controlled trial in preterm infants receiving respiratory support.

Background: Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed.

Methods: To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25-28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a 'study team' uninvolved in clinical care including decision-making.