Sex differences in cerebral blood flow among adolescents with bipolar disorder.

BACKGROUND: Abnormalities in cerebral blood flow (CBF) are common in bipolar disorder (BD). Despite known differences in CBF between healthy adolescent males and females, sex differences in CBF among adolescents with BD have never been studied. OBJECTIVE: To examine sex differences in CBF among adolescents with BD versus healthy controls (HC). METHODS: CBF images were acquired using arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) in 123 adolescents (72 BD: 30M, 42F; 51 HC: 22M, 29F) matched for age (13-20 years). Whole brain voxel-wise analysis was performed in a general linear model with sex and diagnosis as fixed factors, sex-diagnosis interaction effect, and age as a covariate. We tested for main effects of sex, diagnosis, and their interaction. Results were thresholded at cluster forming p = 0.0125, with posthoc Bonferroni correction (p = 0.05/4 groups). RESULTS: A main effect of diagnosis (BD > HC) was observed in the superior longitudinal fasciculus (SLF), underlying the left precentral gyrus (F =10.24 (3), p < 0.0001). A main effect of sex (F > M) on CBF was detected in the precuneus/posterior cingulate cortex (PCC), left frontal and occipital poles, left thalamus, left SLF, and right inferior longitudinal fasciculus (ILF). No regions demonstrated a significant sex-by-diagnosis interaction. Exploratory pairwise testing in regions with a main effect of sex revealed greater CBF in females with BD versus HC in the precuneus/PCC (F = 7.1 (3), p < 0.01). CONCLUSION: Greater CBF in female adolescents with BD versus HC in the precuneus/PCC may reflect the role of this region in the neurobiological sex differences of adolescent-onset BD. Larger studies targeting underlying mechanisms, such as mitochondrial dysfunction or oxidative stress, are warranted.

Prescribed fire increases plant-pollinator network robustness to losses of rare native forbs.

Restoration efforts often focus on changing the composition and structure of invaded plant communities, with two implicit assumptions: (1) functional interactions with species of other trophic levels, such as pollinators, will reassemble automatically when native plant diversity is restored and (2) restored communities will be more resilient to future stressors. However, the impact of restoration activities on pollinator richness, plant-pollinator interaction network structure, and network robustness is incompletely understood. Leveraging a restoration chronosequence in Pacific Northwest prairies, we examined the effects of restoration-focused prescribed fire and native forb replanting on floral resources, pollinator visitation, and plant-pollinator network structure. We then simulated the effects of plant species loss/removal scenarios on secondary extinction cascades in the networks. Specifically, we explored three management-relevant plant loss scenarios (removal of an abundant exotic forb, removal of an abundant forb designated a noxious weed, and loss of the rarest native forb) and compared them to control scenarios. Pyrodiversity and proportion of area recently burned increased the abundance and diversity of floral resources, with concomitant increases in pollinator visitation and diversity. Pyrodiversity also decreased network connectance and nestedness, increased modularity, and buffered networks against secondary extinction cascades. Rare forbs contributed disproportionately to network robustness in less restored prairies, while removal of typical "problem" plants like exotic and noxious species had relatively small impacts on network robustness, particularly in prairies with a long history of restoration activities. Restoration actions aimed mainly at improving the diversity and abundance of pollinator-provisioning plants may also produce plant-pollinator networks with increased resilience to plant species losses.

Self-harm among youth during the first 28 months of the COVID-19 pandemic in Ontario, Canada: a population-based study.

BACKGROUND: Youth have reported worsening mental health during the COVID-19 pandemic. We sought to evaluate rates of pediatric acute care visits for self-harm during the pandemic according to age, sex and mental health service use. METHODS: We conducted a population-based, repeated cross-sectional study using linked health administrative data sets to measure monthly rates of emergency department visits and hospital admissions for self-harm among youth aged 10-17 years between Jan. 1, 2017, and June 30, 2022, in Ontario, Canada. We modelled expected rates of acute care visits for self-harm after the pandemic onset based on prepandemic rates. We reported relative differences between observed and expected monthly rates overall and by age group (10-13 yr and 14-17 yr), sex and mental health service use (new and continuing). RESULTS: In this population of about 1.3 million children and adolescents, rates of acute care visits for self-harm during the pandemic were higher than expected for emergency department visits (0.27/1000 population v. 0.21/1000 population; adjusted rate ratio [RR] 1.29, 95% confidence interval [CI] 1.19-1.39) and hospital admissions (0.74/10 000 population v. 0.43/10 000 population, adjusted RR 1.72, 95% CI 1.46-2.03). This increase was primarily observed among females. Rates of emergency department visits and hospital admissions for self-harm were higher than expected for both those aged 10-13 years and those aged 14-17 years, as well as for both those new to the mental health system and those already engaged in care. INTERPRETATION: Rates of acute care visits for self-harm among children and adolescents were higher than expected during the first 2 and a half years of the COVID-19 pandemic, particularly among females. These findings support the need for accessible and intensive prevention efforts and mental health supports in this population.

Feasibility and Utility of Routine Point-of-Care Gastric Ultrasonography in Patients Undergoing Upper Gastrointestinal Endoscopy Procedures: A Prospective Cohort Study.

OBJECTIVES: Previous studies have indicated that point-of-care ultrasonography (POCUS) of the gastric antrum can predict the adequacy of fasting before surgery and anesthesia. The aim of this study was to evaluate the utility of gastric POCUS in patients undergoing upper gastrointestinal (GI) endoscopy procedures. METHODS: We performed a single-center cohort study in patients undergoing upper GI endoscopy. Consenting patient's gastric antrum was scanned before anesthetic care for endoscopy to determine the cross-sectional area (CSA) and qualitatively determine safe and unsafe contents. Further, an estimate of residual gastric volume was determined using the formula and the nomogram methods. Subsequently, gastric secretions aspirated during endoscopy were quantified and further correlated with nomogram and formula-based assessments. No patient required a change in the primary anesthetic plan except for using rapid sequence induction in those with unsafe contents on POCUS scans. RESULTS: Qualitative ultrasound measurements consistently determined safe and unsafe gastric residual contents in 83 patients enrolled in the study. Unsafe contents were determined by qualitative scans in 4 out of 83 cases (5%) despite adequate fasting status. Quantitatively, only a moderate correlation was demonstrated between measured gastric volumes and nomogram (r = .40, 95% CI: 0.20, 0.57; P = .0002) or formula-based (r = .38, 95% CI: 0.17, 0.55; P = .0004) determinations of residual gastric volumes. CONCLUSION: In daily clinical practice, qualitative POCUS determination of residual gastric content is a feasible and useful technique to identify patients at risk of aspiration before upper GI endoscopy procedures.

Equipment Setup and Artifact Removal for Simultaneous Electroencephalogram and Functional Magnetic Resonance Imaging for Clinical Review in Epilepsy.

Simultaneous electroencephalogram and functional magnetic resonance imaging (EEG-fMRI) is a unique combined technique that provides synergy in the understanding and localization of seizure onset in epilepsy. However, reported experimental protocols for EEG-fMRI recordings fail to address details about conducting such procedures on epilepsy patients. In addition, these protocols are limited solely to research settings. To fill the gap between patient monitoring in an epilepsy monitoring unit (EMU) and conducting research with an epilepsy patient, we introduce a unique EEG-fMRI recording protocol of epilepsy during the interictal period. The use of an MR conditional electrode set, which can also be used in the EMU for a simultaneous scalp EEG and video recording, allows an easy transition of EEG recordings from the EMU to the scanning room for concurrent EEG-fMRI recordings. Details on the recording procedures using this specific MR conditional electrode set are provided. In addition, the study explains step-by-step EEG processing procedures to remove the imaging artifacts, which can then be used for clinical review. This experimental protocol promotes an amendment to the conventional EEG-fMRI recording for enhanced applicability in both clinical (i.e., EMU) and research settings. Furthermore, this protocol provides the potential to expand this modality to postictal EEG-fMRI recordings in the clinical setting.

Proof-of-concept randomized controlled trial of single-session nitrous oxide treatment for refractory bipolar depression: Focus on cerebrovascular target engagement.

BACKGROUND: There remain few efficacious treatments for bipolar depression, which dominates the course of bipolar disorder (BD). Despite multiple studies reporting associations between depression and cerebral blood flow (CBF), little is known regarding CBF as a treatment target, or predictor and/or indicator of treatment response, in BD. Nitrous oxide, an anesthetic gas with vasoactive and putative antidepressant properties, has a long history as a neuroimaging probe. We undertook an experimental medicine paradigm, coupling in-scanner single-session nitrous oxide treatment of bipolar depression with repeated measures of CBF. METHODS: In this double-blind randomized controlled trial, 25 adults with BD I/II and current treatment-refractory depression received either: (1) nitrous oxide (20 min at 25% concentration) plus intravenous saline (n = 12), or (2) medical air plus intravenous midazolam (2 mg total; n = 13). Study outcomes included changes in depression severity (Montgomery-Asberg Depression Rating Scale scores, primary) and changes in CBF (via arterial spin labeling magnetic resonance imaging). RESULTS: There were no significant between-group differences in 24-h post-treatment MADRS change or treatment response. However, the nitrous oxide group had significantly greater same-day reductions in depression severity. Lower baseline regional CBF predicted greater 24-h post-treatment MADRS reductions with nitrous oxide but not midazolam. In region-of-interest and voxel-wise analyses, there was a pattern of regional CBF reductions following treatment with midazolam versus nitrous oxide. CONCLUSIONS: Present findings, while tentative and based on secondary endpoints, suggest differential associations of nitrous oxide versus midazolam with bipolar depression severity and cerebral hemodynamics. Larger studies integrating neuroimaging targets and repeated nitrous oxide treatment sessions are warranted.

Resting-state functional connectivity indicators of risk and resilience for self-harm in adolescent bipolar disorder.

BACKGROUND: Suicide is the second leading cause of death in all youth and among adults with bipolar disorder (BD). The risk of suicide in BD is among the highest of all psychiatric conditions. Self-harm, including suicide attempts and non-suicidal self-injury, is a leading risk factor for suicide. Neuroimaging studies suggest reward circuits are implicated in both BD and self-harm; however, studies have yet to examine self-harm related resting-state functional connectivity (rsFC) phenotypes within adolescent BD. METHODS: Resting-state fMRI data were analyzed for 141 adolescents, ages 13-20 years, including 38 with BD and lifetime self-harm (BDSH+), 33 with BD and no self-harm (BDSH-), and 70 healthy controls (HC). The dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC) and amygdala were examined as regions of interest in seed-to-voxel analyses. A general linear model was used to explore the bivariate correlations for each seed. RESULTS: BDSH- had increased positive rsFC between the left amygdala and left lateral occipital cortex, and between the right dlPFC and right frontal pole, and increased negative rsFC between the left amygdala and left superior frontal gyrus compared to BDSH+ and HC. BDSH+ had increased positive rsFC of the right OFC with the precuneus and left paracingulate gyrus compared to BDSH- and HC. CONCLUSIONS: This study provides preliminary evidence of altered reward-related rsFC in relation to self-harm in adolescents with BD. Between-group differences conveyed a combination of putative risk and resilience connectivity patterns. Future studies are warranted to evaluate changes in rsFC in response to treatment and related changes in self-harm.

Clinical correlates of suicidality and self-injurious behaviour among Canadian adolescents with bipolar disorder.

There is high risk of suicidality in bipolar disorder (BD), particularly in early onset cases. The literature regarding correlates and putative predictors of suicide attempts (SA), non-suicidal self-injury (NSSI) and suicidal ideation (SI) among youth with BD remains sparse. Participants included 197 adolescents with BD, divided into 4 groups: SA (with or without NSSI), NSSI (with or without SI), SI only, and comparison group (CG; no SA/NSSI/SI). Diagnoses, treatment, and suicidality measures were determined via semi-structured interviews, conducted between 2009 and 2017. Univariate analyses were followed by multinomial regression. Overall, 73.6% of participants had history of SA, NSSI, and/or SI. In comparison to CG, SA and NSSI were each associated with BD-II/-NOS (odds ratio [OR] = 15.99, p = 0.002; OR = 16.76, p = 0.003), female sex (OR = 6.89, p = 0.006; OR = 3.76, p = 0.02), and emotion dysregulation (OR = 1.10, p < 0.001; OR = 1.07, p = 0.004). NSSI and SI were each associated with most severe lifetime depression (OR = 1.10, p = 0.01; OR = 1.10, p = 0.01). SA and SI were associated with psychiatric hospitalization (OR = 19.45, p = 0.001; OR = 6.09, p = 0.03). SA was associated with poorer global functioning at most severe episode (OR = 0.88, p = 0.008). NSSI was associated with not living with both natural parents (OR = 0.22, p = 0.009). Study limitations include cross-sectional and retrospective design, stringent cut-offs for SA and NSSI, and recruitment from a tertiary clinical setting. Three quarters of adolescents with BD have had suicidality and/or self-injury. SA and NSSI were most similar to one another, and most different from CG, supporting the broader construct of self-harm. Future research should address the gap in knowledge regarding how sex differences and neurobiology are associated with the observed clinical differences.

Prevalence and correlates of childhood-onset bipolar disorder among adolescents.

AIM: Early-onset bipolar disorder (BD) is associated with a more severe illness as well as a number of clinical factors among adults. Early-onset can be categorized as childhood- (age < 13) or adolescent- (age ≥ 13) onset, with the two displaying different clinical profiles. We set out to examine differences in clinical, and familial characteristics among adolescents with childhood- versus adolescent-onset BD. METHODS: The study included 195 adolescents with BD, ages 14-18 years. Age of onset was determined retrospectively by self-report. Participants completed the semi-structured K-SADS-PL diagnostic interviews along with self-reported dimensional scales. Analyses examined between-group differences for clinical and familial variables. Variables associated with age of onset at p < 0.1 in univariate analyses were evaluated in a logistic regression model. RESULTS: Approximately one-fifth of participants had childhood-onset BD (n = 35; 17.9%). A number of clinical and familial factors were significantly associated with childhood-onset BD. However, there were no significant differences in depressive and manic symptom severity. In multivariate analyses, the variables most strongly associated with childhood-onset were police contact, and family history of suicidal ideation. Smoking and psychiatric hospitalization were associated with adolescent-onset. CONCLUSIONS: In this large clinical sample of adolescents with BD, one-fifth reported childhood-onset BD. Correlates of childhood-onset generally aligned with those observed in the literature. Future research is warranted to better understand the genetic and environmental implications of high familial loading of psychopathology associated with childhood-onset, and to integrate age-related treatment and prevention strategies.

Suicide Assessment and Prevention in Bipolar Disorder: How Current Evidence Can Inform Clinical Practice.

Bipolar disorder is associated with a considerable risk of suicide, and this fact must be incorporated into management of all patients with the condition. This article highlights the importance of a more nuanced understanding of the factors associated with the increased risk of suicidal behavior in people diagnosed as having bipolar disorder and interventions that could mitigate it. Several sociodemographic, clinical, environmental, and other variables have been associated with suicide attempts or deaths in bipolar disorder. Youths with bipolar disorder are a particularly vulnerable group, and their trajectory of illness could be modified by early interventions. Several medications have been studied regarding their relationship to suicide risk in bipolar disorder, and interventional psychiatry is a newer area of research focus. Finally, community-based approaches can be incorporated into a comprehensive approach to suicide prevention. This article summarizes the current understanding of key variables that can help inform a clinical risk assessment of individuals and interventions that can be employed in suicide prevention in bipolar disorder.

Factors Associated With Sleep Disturbance Amongst Youth With Bipolar Disorder.

Background: While sleep disturbances and their impact on functioning are well-established in adults with bipolar disorder (BD), little is known about this topic in youth. Objective: This study investigates the prevalence and correlates of sleep disturbance among youth with BD. Methods: The study included 103 youth (72 BD, 31 healthy controls [HC]), ages 14-20 years. Study measures included a semi-structured diagnostic interview and the Pittsburgh Sleep Quality Index (PSQI). PSQI yields a global score and 7 subscale scores. Analyses examined between group differences in PSQI scores, and correlates of PSQI within BD. Results: BD youth had significantly higher (worse) global sleep scores, and higher scores on 5/7 subscales (quality, latency, disturbance, sleep medication use, daytime dysfunction). In univariate analyses, poorer sleep quality was associated with higher lifetime and current depression severity, mixed mood state, self-reported affective lability, and borderline personality traits. Lifetime lithium treatment and euthymic mood state were associated with better sleep scores. In multivariate analyses, greater current depression severity and self-reported affective lability were most robustly associated with poor sleep quality. Conclusions: Converging with data from adults, present findings indicate greater sleep disturbance among youth with BD versus HC. Also convergent with adults with BD, mood disturbance, whether depression severity or emotional lability, comprised the predominant correlates of sleep disturbance among youth with BD. Future research is warranted to better understand the temporal association between sleep disturbance and its correlates in youth with BD. Relatedly, interventions that address both mood and sleep disturbances may help improve overall functioning.

Contexte: Bien que les perturbations du sommeil et leur effet sur le fonctionnement soient bien établies chez les adultes souffrant du trouble bipolaire (TB). Nous en savons peu à ce sujet chez les jeunes. Objectif: La présente étude investigue la prévalence et les corrélats de la perturbation du sommeil chez les jeunes souffrant du TB. Méthodes: L'étude comprenait 103 jeunes (72 TB, 31 témoins en santé [TS]), âgés de 14 à 20 ans. Les mesures de l'étude étaient notamment une entrevue diagnostique semi-structurée et l'Index de Qualité du Sommeil de Pittsburgh (IQSP). L'IQSP donne un score global et 7 scores de sous-échelles. Les analyses ont examiné entre les différences de groupes dans les scores IQSP, et les corrélats d'IQSP dans le TB. Résultats: Les jeunes souffrant de TB avaient des scores de sommeil globaux significativement plus élevés (pires), et des scores plus élevés à 5/7 sous-échelles (qualité, latence, perturbation, utilisation de médicament pour dormir, dysfonction diurne). Dans les analyses univariées, la mauvaise qualité du sommeil était associée à la gravité de la dépression de durée de vie et actuelle, à l'état de l'humeur mixte, à la labilité affective auto-déclarée, et aux traits de la personnalité limite. Le traitement au lithium de durée de vie et l'état de l'humeur euthymique étaient associés avec de meilleurs scores de sommeil. Dans les analyses multivariées, une plus grande gravité de la dépression actuelle et de la labilité affective auto-déclarée étaient très robustement associées à une mauvaise qualité du sommeil. Conclusions: Convergeant avec les données des adultes, les résultats actuels indiquent une plus grande perturbation du sommeil chez les jeunes souffrant du TB contre les TS. Convergeant également avec les adultes souffrant de TB, la perturbation de l'humeur, que ce soit par la gravité de la dépression ou la labilité émotionnelle, comprenait les corrélats prédominants de la perturbation du sommeil chez les jeunes souffrant de TB. La future recherche est justifiée pour mieux comprendre l'association temporelle entre la perturbation du sommeil et ses corrélats chez les jeunes souffrant du TB. Étant liées, les interventions qui abordent l'humeur et les perturbations du sommeil peuvent aider à améliorer le fonctionnement général.

Taste Perceptions of Common Pediatric Antibiotic Suspensions and Associated Prescribing Patterns in Medical Residents.

OBJECTIVE: Palatability of medication is an important factor for adherence, especially in pediatric populations that tend to use oral suspensions for antibiotic therapy. Our study is the first to evaluate the impact of taste on prescribing patterns of antibiotic suspensions. The objective was to determine if taste testing common antibiotic suspensions altered prescribing patterns of medical residents, through data extracted from the electronic health record. METHODS: After assessing 5 "primer" tastes (sweet, salty, bitter, sour, umami [savory]), residents were randomized to sample 6 antibiotic suspensions to rate their taste perception. A 12-month retrospective and prospective analysis of outpatient prescribing practices of the residents followed, and the results were compared to the resident cohort randomized to no taste test. RESULTS: The 43 residents prescribed 207 liquid antibiotic prescriptions for 176 patients, with no difference in patient characteristics between residents in the taste test versus non-taste test group. Although amoxicillin was most preferable and amoxicillin-clavulanate least, the only significant finding was a greater prescribing rate of cefdinir among those who had tasted it and an inverse relationship between cephalexin taste preference and percentage prescribing amoxicillin in the taste group. Residents who tasted were poor in identifying primer tastes, but this did not impact prescribing patterns. CONCLUSIONS: Among 6 commonly prescribed antibiotic suspensions, amoxicillin remains a highly preferred taste among prescribers. Interestingly, after the taste test there was a significantly greater prescribing rate of cefdinir among those who had tasted it and somewhat lower prescribing rate for amoxicillin-clavulanate.

Comorbid Eating Disorders in a Sample of Youth With Bipolar Disorder: Elevated Burden of Dimensional and Categorical Psychopathology.

Objective: There is growing recognition of the importance of comorbid eating disorders (ED) among individuals with bipolar disorder (BD). However, most studies on this topic have focused on adult samples, and little is known regarding comorbid ED among youth with BD.Methods: The sample included 197 youth with DSM-IV BD (BD-I, BD-II, or BD-NOS [not otherwise specified]), aged 13-20 years and recruited from a subspecialized clinic within a tertiary academic health sciences center from 2009 to 2017. Univariate analyses examined demographic and clinical variables among participants with versus without lifetime DSM-IV ED. Variables significant at P < .10 were entered into a backward stepwise regression.Results: Fifty-six participants (28.4%) had lifetime DSM-IV ED (3.6% anorexia nervosa, 8.1% bulimia nervosa, 16.8% ED not otherwise specified). Significant correlates of lifetime ED were female sex (P < .001), BD-II subtype (P = .03), suicidal ideation (P = .006), suicide attempts (P = .004), non-suicidal self-injury (P < .001), sexual abuse (P = .02), cigarette smoking (P = .001), anxiety disorders (P = .004), posttraumatic stress disorder (P = .004), substance use disorders (P = .006), history of individual therapy (P = .01), and family history of anxiety (P = .01). Significant correlates of no lifetime ED were BD-I subtype (P < .001) and lifetime lithium use (P = .01). The ED group had significantly more severe lifetime depression (P < .001) and significantly more self-reported affective lability (P < .001) and borderline personality traits (P < .001). In multivariate analysis, the most robust predictors of lifetime ED were female sex (odds ratio [OR] = 4.61, P = .004), BD-I subtype (OR = 0.21, P = .03), cigarette smoking (OR = 2.78, P = .02), individual therapy (OR = 3.92, P = .03), family history of anxiety (OR = 2.86, P = .02), and borderline personality traits (OR = 1.01, P = .009).Conclusions: ED are common among youth with BD and associated with adverse clinical characteristics, many of which converge with prior adult literature. Future studies evaluating specific ED subtypes are warranted, as are treatment studies targeting comorbid ED in youth with BD.

Addition of four doses of rituximab to standard induction chemotherapy in adult patients with precursor B-cell acute lymphoblastic leukaemia (UKALL14): a phase 3, multicentre, randomised controlled trial.

BACKGROUND: Treatment for adults with acute lymphoblastic leukaemia requires improvement. UKALL14 was a UK National Cancer Research Institute Adult ALL group study that aimed to determine the benefit of adding the anti-CD20 monoclonal antibody, rituximab, to the therapy of adults with de novo B-precursor acute lymphoblastic leukaemia. METHODS: This was an investigator-initiated, phase 3, randomised controlled trial done in all UK National Health Service Centres treating patients with acute lymphoblastic leukaemia (65 centres). Patients were aged 25-65 years with de-novo BCR-ABL1-negative acute lymphoblastic leukaemia. Patients with de-novo BCR-ABL1-positive acute lymphoblastic leukaemia were eligible if they were aged 19-65 years. Participants were randomly assigned (1:1) to standard-of-care induction therapy or standard-of-care induction therapy plus four doses of intravenous rituximab (375 mg/m2 on days 3, 10, 17, and 24). Randomisation used minimisation and was stratified by sex, age, and white blood cell count. No masking was used for patients, clinicians, or staff (including the trial statistician), although the central laboratory analysing minimal residual disease and CD20 was masked to treatment allocation. The primary endpoint was event-free survival in the intention-to-treat population. Safety was assessed in all participants who started trial treatment. This study is registered with ClincialTrials.gov, NCT01085617. FINDINGS: Between April 19, 2012, and July 10, 2017, 586 patients were randomly assigned to standard of care (n=292) or standard of care plus rituximab (n=294). Nine patients were excluded from the final analysis due to misdiagnosis (standard of care n=4, standard of care plus rituximab n=5). In the standard-of-care group, median age was 45 years (IQR 22-65), 159 (55%) of 292 participants were male, 128 (44%) were female, one (<1%) was intersex, and 143 (59%) of 244 participants had high-risk cytogenetics. In the standard-of-care plus rituximab group, median age was 46 years (IQR 23-65), 159 (55%) of 294 participants were male, 130 (45%) were female, and 140 (60%) of 235 participants had high-risk cytogenetics. After a median follow-up of 53·7 months (IQR 40·3-70·4), 3-year event-free survival was 43·7% (95% CI 37·8-49·5) for standard of care versus 51·4% (45·4-57·1) for standard of care plus rituximab (hazard ratio [HR] 0·85 [95% CI 0·69-1·06]; p=0·14). The most common adverse events were infections and cytopenias, with no difference between the groups in the rates of adverse events. There were 11 (4%) fatal (grade 5) events in induction phases 1 and 2 in the standard-of-care group and 13 (5%) events in the standard-of-care plus rituximab group). 3-year non-relapse mortality was 23·7% (95% CI 19·0-29·4) in the standard-of-care group versus 20·6% (16·2-25·9) in the standard-of-care plus rituximab group (HR 0·88 [95% CI 0·62-1·26]; p=0·49). INTERPRETATION: Standard of care plus four doses of rituximab did not significantly improve event-free survival over standard of care. Rituximab is beneficial in acute lymphoblastic leukaemia but four doses during induction is likely to be insufficient. FUNDING: Cancer Research UK and Blood Cancer UK.