Background:A phase 3b extension of the ZOE-50/70 trials evaluated long-term efficacy, immunogenicity, and safety of the recombinant zoster vaccine (RZV) in participants ≥50 years, with a 6-year follow-up after completion of the primary studies. A subset of participants was evaluated for immunogenicity and safety of 1 or 2 additional doses administered 5-6 years after primary vaccination. Methods:Participants were randomized to 1 additional dose (1-additional dose group, n = 61), 2 additional doses (revaccination group, n = 60), or no additional vaccination (control, n = 119). Humoral and cell-mediated immunity were evaluated by antiglycoprotein E (gE) antibodies, gE-specific CD4[2+] T-cells, and memory B-cells. Reactogenicity was evaluated for 7 days postvaccination and overall safety was evaluated throughout the study. NCT02723773. Results:Anti-gE geometric mean concentrations (GMCs) were 10 000-11 500 mIU/mL in all groups preadditional vaccination. Geometric mean concentrations peaked at 1 month after 1 dose (73 834.4 and 79 419.8 mIU/mL in the 1-additional dose and revaccination groups, respectively), declined at Year 1, but remained above preadditional vaccination levels thereafter. Geometric mean concentration was 64 603.0 mIU/mL 1 month after the second dose in the revaccination group. Geometric mean concentrations in the control group were 8825.4 mIU/mL at Year 1 and 6858.8 mIU/mL at Year 6. The frequency of gE-specific CD4[2+] T-cells and memory B-cells followed a similar pattern. Pain and fatigue were the most common solicited adverse events. No serious adverse events related to RZV were reported. Conclusions:A single additional RZV dose elicited strong and durable humoral and cell-mediated anamnestic responses, with a reactogenicity and safety profile as established in primary studies. Clinical Trial Registration:NCT02723773.
The anatomical site of gluteal administration may influence the pharmacokinetics and tolerability of long-acting cabotegravir (CAB) plus rilpivirine (RPV), but direct comparisons between dorsogluteal (DG) and ventrogluteal (VG) injections are limited. In this prospective intra-individual crossover study, 152 adults with HIV receiving injectable CAB and RPV were switched from DG to VG administration. A total of 842 trough and 131 one-month postinjection plasma samples were analyzed. VG delivery was associated with higher one-month post-dose concentrations for both drugs (median CAB 1280 vs. 834 ng/mL, p < 0.001; RPV 148 vs. 126 ng/mL, p = 0.043). At trough, CAB concentrations were lower with VG injections (573 vs 664 ng/mL, p < 0.001), whereas RPV levels did not differ significantly (131 vs 123 ng/mL, p = 0.461). Although uncommon, a higher proportion (6.9% vs. 1.5%, p = 0.001) of CAB trough samples fell below the protein-adjusted inhibitory concentration 90 threshold in the VG group. VG administration resulted in lower variability in pooled CAB and RPV trough concentrations, both intra-patient (standard deviation ratio 0.92; p = 0.041) and inter-patient (0.80; p = 0.001), compared with DG injections. Detectable HIV-1 RNA (≥50 copies/mL) was rare and comparable between injection sites, with no confirmed virologic failures. Participants reported better tolerability with VG injections, which were associated with fewer local symptoms and were preferred by 67% of respondents. Ventrogluteal administration is associated with more consistent pharmacokinetics and improved tolerability, supporting its use as the preferred site for long-acting CAB/RPV. Although CAB trough levels were modestly lower and occasionally fell below predefined thresholds with VG injection, this did not impact virologic outcomes, reinforcing its clinical suitability in most settings.
Purpose: To explore anatomically adjusted point-to-point relationships between macular sensitivity and intraretinal layer thickness in healthy and glaucomatous eyes using combined optical coherence tomography (OCT) and microperimetry. Methods: Seventy-two eyes were included (27 healthy controls and 45 eyes with primary open-angle glaucoma). Retinal sensitivity was assessed using MP-1 microperimetry, and retinal structure was evaluated with Spectralis OCT. Automatic segmentations included macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), GCL + IPL, ganglion cell complex (mRNFL + GCL + IPL), and the outer retinal layer. Microperimetry maps were anatomically aligned with OCT grids using vascular landmarks, and ganglion cell displacement was considered when analyzing inner retinal layers. Thickness measurements were obtained at corresponding anatomical points, and structure-function associations were assessed using Spearman correlation analysis to generate spatial correlation maps. Results: Almost no significant pointwise correlations were detected in healthy eyes across any retinal segmentation. In glaucomatous eyes, significant positive correlations were observed for inner retinal layers, whereas no significant associations were found for the outer retinal layer. Distinct spatial patterns were identified, with peripheral correlations for mRNFL and paracentral temporal correlations for GCL, IPL, and GCL + IPL. The highest number of significant associations was observed for the ganglion cell complex. Conclusions: Anatomically adjusted pointwise analysis revealed localized and heterogeneous patterns of macular structure-function coupling predominantly involving ganglion cell-related layers in glaucoma. High-resolution mapping may uncover spatial relationships that are partially obscured by regional or spatially averaged approaches and should be interpreted as a complementary exploratory strategy rather than a replacement for established regional analyses.
Background Population ageing and the rise in chronic diseases are driving a shift from residential models to home care where family carers play a key role. Although education programmes have shown benefits, limited attention has been paid to how family caregivers can be effectively trained to prevent unintentional mistakes in home care and to how they should be prepared to respond to them related to the care they provide.Objectives This scoping review aims to examine education programmes that enhance family caregivers’ knowledge and skills to promote safe home care, prevent unintentional mistakes and mitigate their impact on both care recipients and family caregivers.Design This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) methodology for scoping reviews.Data sources Comprehensive searches were conducted in PubMed, Scopus and Embase in April 2024.Eligibility criteria The review included studies on family caregivers in home-based care, focusing on education programmes promoting safe practices; quantitative, qualitative and mixed-methods designs were eligible while studies on professional care or unrelated to home safety were excluded.Data extraction and synthesis Extracted data included study characteristics, education type, target population and safety-related outcomes, which were summarised descriptively to map the available evidence.Results 31 studies on home safety education programmes for family caregivers across oncological, neurological, chronic and paediatric conditions were identified, mostly from the USA and conducted in hospital, home and other health and care facilities. Randomised controlled trials predominated and were generally high quality. Education programmes targeting technical, daily living and self-care skills improved caregiver burden, knowledge, preparedness and quality of life although physical health outcomes showed limited change.Conclusions Evidence indicates that structured education programmes enhance family caregivers’ knowledge, preparedness, competence and psychological well-being, supporting safer home care. While current education programmes are mostly short-term and caregiver-centred, this review identifies core technical, daily life and self-care competencies to guide future education programmes, highlighting the need for co-designed, rigorously evaluated education programmes that include patient safety outcomes and caregiver emotional support.
e20581 Background: Immune checkpoint inhibitors (ICIs) have transformed care for advanced non-small cell lung cancer (aNSCLC), but predictive biomarkers remain imperfect. We previously developed a multimodal immunotherapy response score (MIRS), which integrated ctDNA epigenomic signatures with microsatellite instability (MSI) and tumor mutational burden (TMB) from a single blood draw, and validated its use as a predictive biomarker for ICI response. In this study, we assess the ability of MIRS to predict clinical outcomes in real-world patients treated with ICIs. Methods: MIRS was trained and validated using de-identified patient data from InfinityAI Data Library and expressed as percentile based on MIRS distribution with >20,000 aNSCLC samples. In this study, we validated the signature in an independent cohort of 32 aNSCLC patients by analyzing baseline plasma on Guardant360 Liquid (Guardant Health, Palo Alto, CA); 27/32 received PD-1/PD-L1 monotherapy and 7/32 had tumor PD-L1 TPS <1%. Patients with MIRS ≥50% were defined as MIRS-High. The primary endpoint was real-world progression-free survival (rwPFS). We fitted Cox proportional hazards models (adjusted for covariates such as sex, age, tissue PD-L1 expression, histologic subtype, ECOG, TNM stage and baseline methylation tumor fraction) and reported adjusted hazard ratios (aHR) with 95% CIs. Median rwPFS was estimated by Kaplan–Meier method. Model discrimination was summarized using concordance index (c-index). Results: MIRS-High patients (18/32) had significantly longer rwPFS (median 15.1 vs 7.2 months; aHR 0.24, 95% CI 0.07–0.82, p=0.02; c-index = 0.80). As a continuous variable, MIRS percentile was associated with improved rwPFS (p=0.04). Stratification by PD-L1 ≥50% (n=14) showed a consistent, but not statistically significant trend toward longer rwPFS (aHR 0.60, 95% CI 0.19–1.87, p=0.38; c-index = 0.75). When both biomarkers were combined, patients with PD-L1 ≥50% or MIRS-High (n=25) had significantly longer rwPFS (aHR 0.24, 95% CI 0.07–0.90, p=0.034). All complete responses (n=4) were MIRS-High (median MIRS score of 80th percentile in aNSCLC); patients with progressive disease (n=6) had a median MIRS of 27th percentile in aNSCLC (partial responders (n=15) had a median of 51th percentile in aNSCLC, and stable disease cases (n=7) had median of 55th percentile in aNSCLC). Conclusions: Patients with MIRS-High scores had a 76% lower adjusted hazard of progression or death even after accounting for key covariates. Additionally, all complete responses were MIRS-High and MIRS was associated with significantly improved PFS compared to known biomarkers such as tissue-based PDL1. These data indicate that the multimodal score taken via a single baseline blood sample strongly predicts ICI benefit and may be useful in ICI vs chemo combination decisions pending further ongoing validation.
