Distressing psychotic-like experiences, cognitive functioning and early developmental markers in clinically referred young people aged 8-18 years.

PURPOSE: Neurocognitive difficulties and early childhood speech/motor delays are well documented amongst older adolescents and young adults considered at risk for psychosis-spectrum diagnoses. We aimed to test associations between unusual or psychotic-like experiences (PLEs), co-occurring distress/emotional symptoms, current cognitive functioning and developmental delays/difficulties in young people (aged 8-18 years) referred to Child and Adolescent Mental Health Services in South London, UK. METHODS: Study 1 examined receptive language, verbal learning and caregiver-reported speech and motor delays/difficulties in a sample of 101 clinically-referred children aged 8-14 years, comparing those reporting no PLEs (n = 19), PLEs without distress (n = 16), and PLEs with distress (n = 66). Study 2 tested associations of severity of distressing PLEs with vocabulary, perceptual reasoning, word reading and developmental delays/difficulties in a second sample of 122 adolescents aged 12-18 years with distressing PLEs. RESULTS: In Study 1, children with distressing PLEs had lower receptive language and delayed recall and higher rates of developmental delays/difficulties than the no-PLE and non-distressing PLE groups (F values: 2.3-2.8; p values: < 0.005). Receptive language (ß = 0.24, p = 0.03) and delayed recall (ß = - 0.17, p = 0.02) predicted PLE distress severity. In Study 2, the cognitive-developmental variables did not significantly predict PLE distress severity (ß values = 0.01-0.22, p values: > 0.05). CONCLUSION: Findings may be consistent with a cognitive-developmental model relating distressing PLEs in youth with difficulties in cognitive functioning. This highlights the potential utility of adjunctive cognitive strategies which target mechanisms associated with PLE distress. These could be included in cognitive-behavioural interventions offered prior to the development of an at-risk mental state in mental health, educational or public health settings.

Patient acceptability and usability of a self-administered electronic patient-reported outcome assessment in HIV care: relationship with health behaviors and outcomes.

We assessed acceptability/usability of tablet-based patient-reported outcome (PRO) assessments among patients in HIV care, and relationships with health outcomes using a modified Acceptability E-Scale (AES) within a self-administered PRO assessment. Using multivariable linear regression, we measured associations between patient characteristics and continuous combined AES score. Among 786 patients (median age=48; 91% male; 49% white; 17% Spanish-speaking) overall mean score was 26/30 points (SD: 4.4). Mean scores per dimension (max 5, 1=lowest acceptability, 5=highest): ease of use 4.7, understandability 4.7, time burden 4.3, overall satisfaction 4.3, helpfulness describing symptoms/behaviors 4.2, and enjoyability 3.8. Higher overall score was associated with race/ethnicity (+1.3 points/African-American patients (95%CI:0.3-2.3); +1.6 points/Latino patients (95%CI:0.9-2.3) compared to white patients). Patients completing PROs in Spanish scored +2.4 points on average (95%CI:1.6-3.3). Higher acceptability was associated with better quality of life (0.3 points (95%CI:0.2-0.5)) and adherence (0.4 points (95%CI:0.2-0.6)). Lower acceptability was associated with: higher depression symptoms (-0.9 points (95%CI:-1.4 to -0.4)); recent illicit opioid use (-2.0 points (95%CI:-3.9 to -0.2)); multiple recent sex partners (-0.8 points (95%CI:-1.5 to -0.1)). While patients endorsing depression symptoms, recent opioid use, condomless sex, or multiple sex partners found PROs less acceptable, overall, patients found the assessments highly acceptable and easy to use.

Reconstructing anatomy from electro-physiological data.

Here we show how it is possible to make estimates of brain structure based on MEG data. We do this by reconstructing functional estimates onto distorted cortical manifolds parameterised in terms of their spherical harmonics. We demonstrate that both empirical and simulated MEG data give rise to consistent and plausible anatomical estimates. Importantly, the estimation of structure from MEG data can be quantified in terms of millimetres from the true brain structure. We show, for simulated data, that the functional assumptions which are closer to the functional ground-truth give rise to anatomical estimates that are closer to the true anatomy.

Salivary and Serum Antibody Response Against Neisseria meningitidis After Vaccination With Conjugate Polysaccharide Vaccines in Ethiopian Volunteers.

Meningococcal conjugate vaccines induce serum antibodies crucial for protection against invasive disease. Salivary antibodies are believed to be important for hindering meningococcal acquisition and/or clearance of established carriage. In this study, we measured salivary IgA and IgG antibodies induced by vaccination with a monovalent serogroup A conjugate vaccine or a tetravalent A, C, W and Y conjugate vaccine, in comparison with antibody levels in serum. Saliva and serum samples from Ethiopian volunteers (1-29 years) collected before and eight times on a weekly basis after receiving the serogroup A conjugate vaccine, the tetravalent serogroup A, C, W and Y conjugate vaccine, or no vaccine (control group), were analysed using a multiplex microsphere immunoassay for antibody detection. Serogroup-specific IgG antibody levels in saliva increased significantly after vaccination with both vaccines. The monovalent serogroup A vaccine also induced an increase in salivary IgA antibodies. A strong correlation between serogroup-specific IgG antibodies in saliva and serum, and a somewhat lower correlation for IgA, was observed for all serogroups. There was also a strong correlation between specific secretory IgA and IgA antibodies in saliva for all serogroups. Meningococcal conjugate vaccines are able to elicit salivary antibodies against serogroup A, C, W and Y correlating with antibody levels in serum. The strong correlation between saliva and serum antibody levels indicates that saliva may be used as a surrogate of systemic antibody responses.

A Fixed-point Scheme for the Numerical Construction of Magnetohydrostatic Atmospheres in Three Dimensions.

Magnetohydrostatic models of the solar atmosphere are often based on idealized analytic solutions because the underlying equations are too difficult to solve in full generality. Numerical approaches, too, are often limited in scope and have tended to focus on the two-dimensional problem. In this article we develop a numerical method for solving the nonlinear magnetohydrostatic equations in three dimensions. Our method is a fixed-point iteration scheme that extends the method of Grad and Rubin (Proc. 2nd Int. Conf. on Peaceful Uses of Atomic Energy31, 190, 1958) to include a finite gravity force. We apply the method to a test case to demonstrate the method in general and our implementation in code in particular.

Reading front to back: MEG evidence for early feedback effects during word recognition.

Magnetoencephalography studies in humans have shown word-selective activity in the left inferior frontal gyrus (IFG) approximately 130 ms after word presentation ( Pammer et al. 2004; Cornelissen et al. 2009; Wheat et al. 2010). The role of this early frontal response is currently not known. We tested the hypothesis that the IFG provides top-down constraints on word recognition using dynamic causal modeling of magnetoencephalography data collected, while subjects viewed written words and false font stimuli. Subject-specific dipoles in left and right occipital, ventral occipitotemporal and frontal cortices were identified using Variational Bayesian Equivalent Current Dipole source reconstruction. A connectivity analysis tested how words and false font stimuli differentially modulated activity between these regions within the first 300 ms after stimulus presentation. We found that left inferior frontal activity showed stronger sensitivity to words than false font and a stronger feedback connection onto the left ventral occipitotemporal cortex (vOT) in the first 200 ms. Subsequently, the effect of words relative to false font was observed on feedforward connections from left occipital to ventral occipitotemporal and frontal regions. These findings demonstrate that left inferior frontal activity modulates vOT in the early stages of word processing and provides a mechanistic account of top-down effects during word recognition.

Theta oscillations orchestrate medial temporal lobe and neocortex in remembering autobiographical memories.

Remembering autobiographical events can be associated with detailed visual imagery. The medial temporal lobe (MTL), precuneus and prefrontal cortex are held to jointly enable such vivid retrieval, but how these regions are orchestrated remains unclear. An influential prediction from animal physiology is that neural oscillations in theta frequency may be important. In this experiment, participants prospectively collected audio recordings describing personal autobiographical episodes or semantic knowledge over 2 to 7 months. These were replayed as memory retrieval cues while recording brain activity with magnetoencephalography (MEG). We identified a peak of theta power within a left MTL region of interest during both autobiographical and General Semantic retrieval. This MTL region was selectively phase-synchronized with theta oscillations in precuneus and medial prefrontal cortex, and this synchrony was higher during autobiographical as compared to General Semantic knowledge retrieval. Higher synchrony also predicted more detailed visual imagery during retrieval. Thus, theta phase-synchrony orchestrates in humans the MTL with a distributed neocortical memory network when vividly remembering autobiographical experiences.

Algorithmic procedures for Bayesian MEG/EEG source reconstruction in SPM.

The MEG/EEG inverse problem is ill-posed, giving different source reconstructions depending on the initial assumption sets. Parametric Empirical Bayes allows one to implement most popular MEG/EEG inversion schemes (Minimum Norm, LORETA, etc.) within the same generic Bayesian framework. It also provides a cost-function in terms of the variational Free energy-an approximation to the marginal likelihood or evidence of the solution. In this manuscript, we revisit the algorithm for MEG/EEG source reconstruction with a view to providing a didactic and practical guide. The aim is to promote and help standardise the development and consolidation of other schemes within the same framework. We describe the implementation in the Statistical Parametric Mapping (SPM) software package, carefully explaining each of its stages with the help of a simple simulated data example. We focus on the Multiple Sparse Priors (MSP) model, which we compare with the well-known Minimum Norm and LORETA models, using the negative variational Free energy for model comparison. The manuscript is accompanied by Matlab scripts to allow the reader to test and explore the underlying algorithm.

Lessons learned from the design and implementation of myocardial infarction adjudication tailored for HIV clinical cohorts.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Tislelizumab versus chemotherapy as second-line treatment for European and North American patients with advanced or metastatic esophageal squamous cell carcinoma: a subgroup analysis of the randomized phase III RATIONALE-302 study.

BACKGROUND: The phase III RATIONALE-302 study evaluated tislelizumab, an anti-programmed cell death protein 1 antibody, as second-line (2L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). This prespecified exploratory analysis investigated outcomes in patients from Europe and North America (Europe/North America subgroup). PATIENTS AND METHODS: Patients with tumor progression during/after first-line systemic treatment were randomized 1 : 1 to open-label tislelizumab or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan). RESULTS: The Europe/North America subgroup comprised 108 patients (tislelizumab: n = 55; chemotherapy: n = 53). Overall survival (OS) was prolonged with tislelizumab versus chemotherapy (median: 11.2 versus 6.3 months), with a hazard ratio (HR) of 0.55 [95% confidence interval (CI) 0.35-0.87]; HR was similar irrespective of programmed death-ligand 1 score [≥10%: 0.47 (95% CI 0.18-1.21); <10%: 0.55 (95% CI 0.30-1.01)]. Median progression-free survival was 2.3 versus 2.7 months with tislelizumab versus chemotherapy [HR: 0.97 (95% CI 0.64-1.47)]. Overall response rate was greater with tislelizumab (20.0%) versus chemotherapy (11.3%), with more durable response (median duration of response: 5.1 versus 2.1 months). Tislelizumab had a favorable safety profile versus chemotherapy, with fewer patients experiencing ≥grade 3 treatment-related adverse events (13.0% versus 51.0%). Those on tislelizumab experienced less deterioration in health-related quality of life, physical functioning, and/or disease- and treatment-related symptoms (i.e. fatigue, pain, and eating problems) as compared to those on chemotherapy, per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-OES18 scores. CONCLUSIONS: As a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in European/North American ESCC patients in the randomized phase III RATIONALE-302 study.

Dynamic causal modelling of lateral interactions in the visual cortex.

This paper presents a dynamic causal model based upon neural field models of the Amari type. We consider the application of these models to non-invasive data, with a special focus on the mapping from source activity on the cortical surface to a single channel. We introduce a neural field model based upon the canonical microcircuit (CMC), in which neuronal populations are assigned to different cortical layers. We show that DCM can disambiguate between alternative (neural mass and field) models of cortical activity. However, unlike neural mass models, DCM with neural fields can address questions about neuronal microcircuitry and lateral interactions. This is because they are equipped with interlaminar connections and horizontal intra-laminar connections that are patchy in nature. These horizontal or lateral connections can be regarded as connecting macrocolumns with similar feature selectivity. Crucially, the spatial parameters governing horizontal connectivity determine the separation (width) of cortical macrocolumns. Thus we can estimate the width of macro columns, using non-invasive electromagnetic signals. We illustrate this estimation using dynamic causal models of steady-state or ongoing spectral activity measured using magnetoencephalography (MEG) in human visual cortex. Specifically, we revisit the hypothesis that the size of a macrocolumn is a key determinant of neuronal dynamics, particularly the peak gamma frequency. We are able to show a correlation, over subjects, between columnar size and peak gamma frequency - that fits comfortably with established correlations between peak gamma frequency and the size of visual cortex defined retinotopically. We also considered cortical excitability and assessed its relative influence on observed gamma activity. This example highlights the potential utility of dynamic causal modelling and neural fields in providing quantitative characterisations of spatially extended dynamics on the cortical surface - that are parameterised in terms of horizontal connections, implicit in the cortical micro-architecture and its synaptic parameters.

The Huntington's disease candidate region exhibits many different haplotypes.

Analysis of 78 Huntington's disease (HD) chromosomes with multi-allele markers revealed 26 different haplotypes, suggesting a variety of independent HD mutations. The most frequent haplotype, accounting for about one third of disease chromosomes, suggests that the disease gene is between D4S182 and D4S180. However, the paucity of an expected class of chromosomes that can be related to this major haplotype by assuming single crossovers may reflect the operation of other mechanisms in creating haplotype diversity. Some of these mechanisms sustain alternative scenarios that do not require a multiple mutational origin for HD and/or its positioning between D4S182 and D4S180.

De novo expansion of a (CAG)n repeat in sporadic Huntington's disease.

Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat in chromosome 4p16.3. We have examined nine families with potential de novo expression of the disease. With one exception, all of the affected individuals had 42 or more repeat units, well above the normal range. In four families, elderly unaffected relatives inherited the same chromosome as that containing the expanded repeat in the proband, but had repeat lengths of 34-38 units, spanning the gap between the normal and HD distributions. Thus, mutation to HD is usually associated with an expansion from an already large repeat.

Paediatric resuscitation for nurses working in Ghana: an educational intervention.

BACKGROUND: Deficiencies in the paediatric emergency systems of developing countries may contribute to avoidable paediatric mortality. Studies suggest that nurses and doctors may not be educationally prepared to provide immediate paediatric resuscitative care to acutely ill children. The purpose of this study was to determine if a 1-day World Health Organization (WHO) Emergency Triage and Assessment Treatment (ETAT) Program in paediatric resuscitation would increase Ghanaian nurses' knowledge and self-efficacy of paediatric resuscitation. METHODS: A pre-experimental, one-group, pre-test, post-test design was used to assess differences in the nurses' knowledge of paediatric resuscitation, and their perceived self-efficacy of paediatric resuscitation after completing a 1-day educational intervention in paediatric resuscitation. Forty-one nurses from a public teaching hospital in Ghana were recruited and participated in the study. RESULTS: Using a paired samples t-test, there was a statistically significant increase in the nurses' perceived self-efficacy of paediatric resuscitation in general (P < 0.000), perceived self-efficacy of bag and mask ventilation (P < 0.000), and knowledge of paediatric resuscitation (P < 0.000). CONCLUSIONS: Findings from this study suggest that a 1-day WHO ETAT Program may increase self-efficacy of paediatric resuscitation and knowledge of paediatric resuscitation. CLINICAL RELEVANCE: Policy makers in Ghana need to consider implementing education programmes in paediatric resuscitation for nurses as part of a comprehensive strategy to improve emergency systems and address preventable and avoidable infant and child mortality.

Machine Learning Differentiation of Autism Spectrum Sub-Classifications.

PURPOSE: Disorders on the autism spectrum have characteristics that can manifest as difficulties with communication, executive functioning, daily living, and more. These challenges can be mitigated with early identification. However, diagnostic criteria has changed from DSM-IV to DSM-5, which can make diagnosing a disorder on the autism spectrum complex. We evaluated machine learning to classify individuals as having one of three disorders of the autism spectrum under DSM-IV, or as non-spectrum. METHODS: We employed machine learning to analyze retrospective data from 38,560 individuals. Inputs encompassed clinical, demographic, and assessment data. RESULTS: The algorithm achieved AUROCs ranging from 0.863 to 0.980. The model correctly classified 80.5% individuals; 12.6% of individuals from this dataset were misclassified with another disorder on the autism spectrum. CONCLUSION: Machine learning can classify individuals as having a disorder on the autism spectrum or as non-spectrum using minimal data inputs.

A Potent Kalihinol Analogue Disrupts Apicoplast Function and Vesicular Trafficking in P. falciparum Malaria.

Here we report the discovery of MED6-189, a new analogue of the kalihinol family of isocyanoterpene (ICT) natural products. MED6-189 is effective against drug-sensitive and -resistant P. falciparum strains blocking both intraerythrocytic asexual replication and sexual differentiation. This compound was also effective against P. knowlesi and P. cynomolgi. In vivo efficacy studies using a humanized mouse model of malaria confirms strong efficacy of the compound in animals with no apparent hemolytic activity or apparent toxicity. Complementary chemical biology, molecular biology, genomics and cell biological analyses revealed that MED6-189 primarily targets the parasite apicoplast and acts by inhibiting lipid biogenesis and cellular trafficking. Genetic analyses in P. falciparum revealed that a mutation in PfSec13, which encodes a component of the parasite secretory machinery, reduced susceptibility to the drug. The high potency of MED6-189 in vitro and in vivo, its broad range of efficacy, excellent therapeutic profile, and unique mode of action make it an excellent addition to the antimalarial drug pipeline.

Measuring functional connectivity in MEG: a multivariate approach insensitive to linear source leakage.

A number of recent studies have begun to show the promise of magnetoencephalography (MEG) as a means to non-invasively measure functional connectivity within distributed networks in the human brain. However, a number of problems with the methodology still remain--the biggest of these being how to deal with the non-independence of voxels in source space, often termed signal leakage. In this paper we demonstrate a method by which non-zero lag cortico-cortical interactions between the power envelopes of neural oscillatory processes can be reliably identified within a multivariate statistical framework. The method is spatially unbiased, moderately conservative in false positive rate and removes linear signal leakage between seed and target voxels. We demonstrate this methodology in simulation and in real MEG data. The multivariate method offers a powerful means to capture the high dimensionality and rich information content of MEG signals in a single imaging statistic. Given a significant interaction between two areas, we go on to show how classical statistical tests can be used to quantify the importance of the data features driving the interaction.

A general Bayesian treatment for MEG source reconstruction incorporating lead field uncertainty.

There is uncertainty introduced when a cortical surface based model derived from an anatomical MRI is used to reconstruct neural activity with MEG data. This is a specific case of a problem with uncertainty in parameters on which M/EEG lead fields depend non-linearly. Here we present a general mathematical treatment of any such problem with a particular focus on co-registration. We use a Metropolis search followed by Bayesian Model Averaging over multiple sparse prior source inversions with different headlocation/orientation parameters. Based on MEG data alone we can locate the cortex to within 4mm at empirically realistic signal to noise ratios. We also show that this process gives improved posterior distributions on the estimated current distributions, and can be extended to make inference on the locations of local maxima by providing confidence intervals for each source.

The effects of tislelizumab plus chemotherapy as first-line treatment on health-related quality of life of patients with advanced squamous non-small cell lung cancer: Results from a phase 3 randomized clinical trial.

BACKGROUND: This study assessed the effects of adding tislelizumab to first-line standard-of- care chemotherapy on the health-related quality of life (HRQoL) of patients with advanced squamous non-small cell lung cancer (sq-NSCLC). PATIENTS AND METHODS: Patients in this open-label, multicenter, phase 3 RATIONALE 307 trial were randomized to one of the three arms: tislelizumab plus carboplatin and paclitaxel (Arm A), tislelizumab plus carboplatin and nab-paclitaxel (Arm B), or paclitaxel plus carboplatin (Arm C). HRQoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and the EORTC Quality of Life Questionnaire Lung Cancer 13-item module (QLQ-LC13). Mean score change from baseline at Weeks 6 and 12 in the QLQ-C30's global health status/quality of life (GHS/QoL), fatigue, and physical functioning scores and QLQ-LC13 lung cancer specific subscales were examined. Time to deterioration was estimated for the GHS/QoL score. RESULTS: A total of 355 sq-NSCLC patients received at least one dose of study drug and completed at least one HRQoL assessment. The GHS/QoL scores improved in Arms A and B relative to Arm C at Weeks 6 and 12. Arms A and B also experienced a reduction in most lung cancer-specific symptoms relative to Arm C. Time to deterioration of GHS/QoL was not reached by any of the three arms. CONCLUSIONS: The addition of tislelizumab to platinum-based chemotherapy is associated with improvements in sq-NSCLC patients' HRQoL, especially in GHS/QoL and most importantly in lung cancer-specific symptoms including coughing, dyspnea, and hemoptysis.

Tislelizumab versus chemotherapy as second-line treatment of advanced or metastatic esophageal squamous cell carcinoma (RATIONALE 302): impact on health-related quality of life.

BACKGROUND: RATIONALE 302 (NCT03430843) an open-label, phase III study of second-line treatment of advanced/metastatic esophageal squamous cell carcinoma (ESCC), reported that tislelizumab, relative to investigator-chosen chemotherapy (ICC), was associated with improvements in overall survival and a favorable safety profile. This study assessed the health-related quality of life (HRQoL) and ESCC-related symptoms of patients in RATIONALE 302. METHODS: Adults with advanced/metastatic ESCC whose disease progressed following prior systemic therapy were randomized 1 : 1 to receive either tislelizumab or ICC (paclitaxel, docetaxel, or irinotecan). HRQoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and the EuroQoL Five-Dimensions Five-Levels (EQ-5D-5L) visual analogue scale. Mixed effect modeling for repeated measurements examined changes from baseline to weeks 12 and 18. The Kaplan-Meier method was used to examine time to deterioration. RESULTS: Overall, 512 patients were randomized to tislelizumab (n = 256) or ICC (n = 256). The tislelizumab arm maintained QLQ-C30 global health status/quality whereas the ICC arm worsened at week 12 {difference in least square (LS) mean change: 5.8 [95% confidence interval (CI): 2.0-9.5], P = 0.0028} and week 18 [difference in LS mean change: 8.1 (95% CI: 3.4-12.8), P = 0.0008]. Physical functioning (week 18) and fatigue (weeks 12 and 18) worsened less in the tislelizumab compared with the ICC arm. The tislelizumab arm improved in reflux symptoms, whereas the ICC worsened at week 12 [difference in LS mean change: -4.1 (95% CI: -7.6 to -0.6), P = 0.0229]. The visual analogue scale remained consistent in the tislelizumab arm whereas it worsened in the ICC arm. The hazard of time to deterioration was lower in tislelizumab patients compared with ICC for physical functioning and reflux. CONCLUSIONS: HRQoL, including fatigue symptoms and physical functioning, was maintained in patients with advanced or metastatic ESCC receiving tislelizumab compared with ICC-treated patients. These results provide additional support for the benefits of tislelizumab in this patient population.