Armodafinil to reduce the sleepiness related side-effects of sleep restriction therapy being used to treat insomnia disorder: An open label clinical trial pilot study compared with historical controls.

Sleep restriction therapy (SRT) is an effective stand-alone behavioural intervention for insomnia disorder. However, its daytime side effects, particularly sleepiness, may be troubling for patients and/or may be a necessary part of the patient's treatment journey. This pilot trial aims to explore the potential benefit of armodafinil, a wakefulness promoter. Patients were treated with SRT with open label adjunctive armodafinil (150 mg/day). Thirty-three patients from previous studies that have undergone exactly the same SRT intervention acted as controls. The primary outcome measure was the insomnia severity index (ISI), and secondary outcomes were the Epworth sleepiness scale, sleep restriction adherence scale (SRAS), and safety from baseline through to 12 weeks. We recruited 25 patients into the trial. Data for the primary end point (ISI at 12 weeks) was available for 20 of the participants. The baseline insomnia severity index was 20.2 (SD 3.3) and decreased to 9.1 (SE 1.1), with no change, to 10.2 and 11.2 at weeks 6 and 12 respectively (all p > 0.05 compared with baseline). The insomnia severity index values for armodafinil patients were statistically inferior to historical controls at the primary time point of 12 weeks (11.2 vs. 6.7, p < 0.01). Sleep restriction therapy plus armodafinil treatment was associated with frequent minor side effects but was generally safe and acceptable to patients. Sleep restriction therapy was associated with a robust clinical response in the insomnia severity index values for insomnia patients. Based upon historical control data, armodafinil does not appear to have beneficial adjunctive effects in addition to sleep restriction therapy alone.

Insomnia as a mediating therapeutic target for depressive symptoms: A sub-analysis of participant data from two large randomized controlled trials of a digital sleep intervention.

Insomnia predicts the onset of depression, commonly co-presents with depression and often persists following depression remission. However, these conditions can be challenging to treat concurrently using depression-specific therapies. Cognitive behavioural therapy for insomnia may be an appropriate treatment to improve both insomnia and depressive symptoms. We examined the effects of a fully-automated digital cognitive behavioural therapy intervention for insomnia (Sleepio) on insomnia and depressive symptoms, and the mediating role of sleep improvement on depressive symptoms in participants from two randomized controlled trials of digital cognitive behavioural therapy for insomnia. We also explored potential moderators of intervention effects. All participants met criteria for probable insomnia disorder and had clinically significant depressive symptomatology (PHQ-9 ≥ 10; n = 3,352). Individuals allocated to treatment in both trials were provided access to digital cognitive behavioural therapy. Digital cognitive behavioural therapy significantly improved insomnia (p < .001; g = 0.76) and depressive symptoms (p < .001; g = 0.48) at post-intervention (weeks 8-10), and increased the odds (OR = 2.9; 95% CI = 2.34, 3.65) of clinically significant improvement in depressive symptoms (PHQ-9 < 10). Improvements in insomnia symptoms at mid-intervention mediated 87% of the effects on depressive symptoms at post-intervention. No variables moderated effectiveness outcomes, suggesting generalizability of these findings. Our results suggest that effects of digital cognitive behavioural therapy for insomnia extend to depressive symptoms in those with clinically significant depressive symptomatology. Insomnia may, therefore, be an important therapeutic target to assist management of depressive symptoms.

Long-term benefits of digital cognitive behavioural therapy for insomnia: Follow-up report from a randomized clinical trial.

Digital cognitive behavioural therapy (dCBT) is an effective treatment for chronic insomnia and also improves well-being and quality of life (QoL). We assessed whether these benefits are sustained and if the effects of dCBT extend to the use of sleep medication and healthcare. In total 1,711 adults (48.0 ± 13.8 years, 77.6% female) with complaints of chronic insomnia participated in a previously published randomized controlled trial (ISRCTN 60530898) comparing dCBT (n = 853) with sleep hygiene education (SHE, n = 858). At weeks 0, 4, 8, 24, 36 and 48, we assessed functional health (Patient-Reported Outcomes Measurement Information System: Global Health Scale); psychological well-being (Warwick-Edinburgh Mental Well-being Scale) and sleep-related QoL (Glasgow Sleep Impact Index), prescribed and non-prescribed sleep medication use, and healthcare utilization. At week 25, those who received SHE at baseline were offered dCBT. dCBT improved functional health (difference: 2.45, 95% confidence interval [CI]: 2.03; 2.88, Cohen's d: 0.50, p < .001), psychological well-being (difference: 4.34, 95% CI: 3.70; 4.98, Cohen's d: 0.55, p < .001) and sleep-related QoL (difference: -44.61, 95%CI: -47.17; -42.05, Cohen's d: -1.44, p < .001) at week 48 compared to baseline. At week 24 dCBT, compared to SHE, also reduced use of prescription and non-prescription sleep medication up to week 24 (adjusted rate ratio [RR]: 0.64, 95% CI: 0.42; 0.97, p = .037 and adjusted RR: 0.52, 95% CI: 0.37; 0.74, p < .0001, respectively), but not healthcare utilization. Uncontrolled follow-up suggests that these effects were sustained for non-prescribed sleep medication (RR: 0.52, 95% CI: 0.40; 0.67, p < .001). In conclusion, this study suggests that dCBT results in sustained benefits to insomnia and its daytime outcomes.

Efficacy of digital cognitive behavioral therapy for moderate-to-severe symptoms of generalized anxiety disorder: A randomized controlled trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is an efficacious intervention for generalized anxiety disorder (GAD). Digital CBT may provide a scalable means of delivering CBT at a population level. We investigated the efficacy of a novel digital CBT program in those with GAD for outcomes of anxiety, worry, depressive symptoms, sleep difficulty, wellbeing, and participant-specific quality of life. METHODS: This online, two-arm parallel-group superiority randomized controlled trial compared digital CBT with waitlist control in 256 participants with moderate-to-severe symptoms of GAD. Digital CBT (Daylight), was delivered using participants' own smartphones. Online assessments took place at baseline (Week 0; immediately preceding randomization), mid-intervention (Week 3; from randomization), post-intervention (Week 6; primary endpoint), and follow-up (Week 10). RESULTS: Overall, 256 participants were randomized and intention-to-treat analysis found Daylight reduced symptoms of anxiety compared with waitlist control at post-intervention, reflecting a large effect size (adjusted difference [95% CI]: 3.22 [2.14, 4.31], d = 1.08). Significant improvements were found for measures of worry; depressive symptoms, sleep difficulty, wellbeing, and participant-specific quality of life. CONCLUSION: Digital CBT (Daylight) appears to be safe and efficacious for symptoms of anxiety, worry, and further measures of mental health compared with waitlist control in individuals with GAD.

The Internal Consistency and Validity of the Vaccination Attitudes Examination Scale: A Replication Study.

Background: Vaccinations are important preventative health behaviors. The recently developed Vaccination Attitudes Examination (VAX) Scale aims to measure the reasons behind refusal/hesitancy regarding vaccinations. Purpose: The aim of this replication study is to conduct an independent test of the newly developed VAX Scale in the UK. We tested (a) internal consistency (Cronbach's α); (b) convergent validity by assessing its relationships with beliefs about medication, medical mistrust, and perceived sensitivity to medicines; and (c) construct validity by testing how well the VAX Scale discriminated between vaccinators and nonvaccinators. Methods: A sample of 243 UK adults completed the VAX Scale, the Beliefs About Medicines Questionnaire, the Perceived Sensitivity to Medicines Scale, and the Medical Mistrust Index, in addition to demographics of age, gender, education levels, and social deprivation. Participants were asked (a) whether they received an influenza vaccination in the past year and (b) if they had a young child, whether they had vaccinated the young child against influenza in the past year. Results: The VAX (a) demonstrated high internal consistency (α = .92); (b) was positively correlated with medical mistrust and beliefs about medicines, and less strongly correlated with perceived sensitivity to medicines; and (c) successfully differentiated parental influenza vaccinators from nonvaccinators. Conclusion: The VAX demonstrated good internal consistency, convergent validity, and construct validity in an independent UK sample. It appears to be a useful measure to help us understand the health beliefs that promote or deter vaccination behavior.

The Effect of Reciprocity Priming on Organ Donor Registration Intentions and Behavior.

BACKGROUND: Internationally the demand for organ transplants far exceeds the available supply of donated organs. PURPOSE: We examine if a digital reciprocity prime based on reciprocal altruism can be used to increase organ donor registration intentions and behavior. METHODS: Four hundred twenty participants (223 females) from England and Scotland aged 18+ who were not currently registered organ donors were randomized by block allocation using a 1:1 ratio to receive either a reciprocity prime or control message. After manipulation, they were asked to indicate their organ donation intentions and whether or not they would like to be taken to an organ donation registration and information page. RESULTS: In line with our previous work, participants primed with a reciprocity statement reported greater intent to register as an organ donor than controls (using a 7-point Likert scale where higher scores = greater intention; prime mean [SD] = 4.3 [1.6] vs. control mean [SD] = 3.7 [1.4], p ≤ .001, d = 0.4 [95% confidence interval [CI] = 0.21-0.59]). There was again however, no effect on behavior as rates of participants agreeing to receive the donation register web-link were comparable between those primed at 11% (n = 23/210) (95% CI = 7.4-16.0) and controls at 12% (n = 25/210) (95% CI = 8.1-17.1), X2 (1) = 0.09, p = .759. CONCLUSIONS: Reciprocal altruism appears useful for increasing intention towards joining the organ donation register. It does not, however, appear to increase organ donor behavior.

Can people apply 'FAST' when it really matters? A qualitative study guided by the common sense self-regulation model.

BACKGROUND: Early identification of stroke symptoms and rapid access to the emergency services increases an individual's chance of receiving thrombolytic therapy and reduces the likelihood of infirmity. The UK's national stroke campaign 'Act FAST' was developed to increase public awareness of stroke symptoms and highlighted the importance of rapid response by contacting emergency services. No study to date has assessed if and how people who experienced or witnessed stroke in line with the campaigns' symptoms of the FAST acronym (i.e., facial weakness, arm weakness, slurred speech, and time) may use this FAST in their response. METHODS: Semi-structured interviews with 13 stroke patients and witnesses were conducted. Interviews were theory-guided based on the Common Sense Self-Regulation Model, to understand the appraisal process of the onset of stroke symptoms and how this impacted on participants' ability to apply their knowledge of the FAST campaign. RESULTS: The majority of patients (n = 8/13) failed to correctly identify stroke and reported no impact of the campaign on their stroke recognition and response. Inability to identify stroke, perceiving symptoms to lack severity and lack of control contributed to a delay in seeking medical attention. CONCLUSION: Stroke witnesses and patients predominantly fail to identify stroke which suggest a lack of FAST application when it matters. Inaccurate risk perceptions and lack of physical control both play central roles in influencing the formation of illness representation not associated with an appropriate emergency response.

Sham sleep feedback delivered via actigraphy biases daytime symptom reports in people with insomnia: Implications for insomnia disorder and wearable devices.

This study investigated whether providing sham feedback about sleep to individuals with insomnia influenced daytime symptom reports, sleep-related attentional bias and psychomotor vigilance. Sixty-three participants meeting DSM-5 criteria for insomnia disorder were recruited from the community. Following baseline assessments and actigraphy briefing, participants were randomised to receive next-day sham feedback on sleep quality ("positive" vs. "negative" sleep efficiency condition). Feedback was delivered at habitual rise-time using an integrated actigraphy-diary watch to simulate wearable device behaviour. Participants completed symptom reports immediately before receiving feedback, and at 12:00 and 15:00 hr, using the experience sampling method. Following this they returned to the laboratory in the evening to complete symptom reports and computerised tests of sleep-related attentional bias and basic psychomotor vigilance. Participants randomised to negative feedback (n = 32) evidenced impaired daytime function (decreased alert cognition [d = 0.79], increased sleepiness/fatigue [d = 0.55]) in the evening compared with those given positive feedback (n = 31). Within-day trajectories revealed that the positive-feedback group, relative to the negative-feedback group, displayed a significantly greater increase in positive mood and alert cognition (from rise-time to 12:00 hr), and significantly greater decrease in sleepiness/fatigue. There were no significant between-group differences on measures of sleep-related attentional bias [d = 0.20] or psychomotor vigilance [d = 0.12]. This controlled experiment shows that sham feedback about sleep biases appraisal of daytime symptoms, highlighting a pathway connecting sleep misperception with daytime features of insomnia. Findings have important implications for wearable devices that claim to measure "objective" sleep yet may provide inaccurate data relative to gold-standard measurement.

BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros.

The Philadelphia chromosome, a chromosomal abnormality that encodes BCR-ABL1, is the defining lesion of chronic myelogenous leukaemia (CML) and a subset of acute lymphoblastic leukaemia (ALL). To define oncogenic lesions that cooperate with BCR-ABL1 to induce ALL, we performed a genome-wide analysis of diagnostic leukaemia samples from 304 individuals with ALL, including 43 BCR-ABL1 B-progenitor ALLs and 23 CML cases. IKZF1 (encoding the transcription factor Ikaros) was deleted in 83.7% of BCR-ABL1 ALL, but not in chronic-phase CML. Deletion of IKZF1 was also identified as an acquired lesion at the time of transformation of CML to ALL (lymphoid blast crisis). The IKZF1 deletions resulted in haploinsufficiency, expression of a dominant-negative Ikaros isoform, or the complete loss of Ikaros expression. Sequencing of IKZF1 deletion breakpoints suggested that aberrant RAG-mediated recombination is responsible for the deletions. These findings suggest that genetic lesions resulting in the loss of Ikaros function are an important event in the development of BCR-ABL1 ALL.

Validity and Reliability of the Turkish Version of the Sleep Condition Indicator: A Clinical Screening Instrument Based on the DSM-5 Criteria for Insomnia.

Purpose: We aimed to adapt the Turkish Sleep Condition Indicator (SCI) version and examine its psychometric properties among the general population. Methods: This study was a cross-sectional study. The item-total correlation, standard error of measurement, Cronbach's α, and McDonald's ω were used for internal consistency. We ran confirmatory factor analysis (CFA) and network analysis to confirm the factor structure. Multigroup CFA was run to assess the measurement invariance across gender, whether clinical insomnia or not, and poor sleep quality. We correlated SCI scores with Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) scores to evaluate construct validity. A receiver operating characteristic (ROC) curve analysis was conducted to calculate the cut-off score of the SCI. The temporal stability was examined with the intraclass correlation coefficient. Results: Eight hundred thirty-four participants attended. Over half of the participants were women (63.2% n = 527); the mean age was 36.15 ± 9.64. Confirmatory factor and network analysis results show that the two-factor correlated model had a good model fit for the SCI. The SCI had scalar level invariance across gender, having clinical insomnia and poor sleep quality in the Multigroup CFA. ROC curve analysis shows that the SCI has good sensitivity (90.3%) and specificity (91.8%) for cut-off ≤ 15. The intraclass correlation coefficient computed between the first and second SCI total scores was significant (r=0.80 with a 95% confidence interval from 0.78 to 0.87; p < 0.001). Conclusion: The Turkish SCI is a practical self-reported insomnia scale with good psychometric properties that can be used to screen for insomnia disorder.

Ecological momentary assessment of daytime symptoms during sleep restriction therapy for insomnia.

This study profiles changes in self-reported daytime functioning during sleep restriction therapy (SRT) for insomnia. Ecological momentary assessment (EMA) captured point-in-time symptomatology to map the time-course of symptoms. We hypothesized a deterioration (week 1) followed by improvements at week 3 of therapy relative to baseline. Nine patients with psychophysiological insomnia completed the Daytime Insomnia Symptom Scale (DISS) at rise-time, 12:00 hours, 18:00 hours and bedtime for 1 week before and 3 weeks during SRT. Four validated factors from the DISS were analyzed (alert cognition, positive mood, negative mood and sleepiness/fatigue) across 28 days yielding 17 170 data points. Factors evaluated week (baseline versus weeks 1 and 3) and time of day symptomatology. Insomnia Severity Index scores decreased significantly pre-to-post treatment (mean 18 versus 7). Reflecting acute effects of SRT, significant differences were found for all factors, except negative mood, between baseline and week 1 of SRT, suggesting adverse effects. By week 3, sleepiness/fatigue and negative mood decreased significantly compared to baseline, and positive mood showed a trend towards improvement (P = 0.06). Sleepiness/fatigue displayed a significant week × time of day interaction, explained by a reduction in sleepiness/fatigue at every daytime assessment point (except bedtime, which remained high). A significant interaction for alert cognition was associated with reduction in alertness at bedtime by week 3 and an increase in alertness at rise-time, suggesting that SRT not only improves sleep, but moderates alertness and sleepiness in therapeutic ways. Initial SRT is associated with an increase in sleepiness/fatigue and a decrease in alert cognition.

Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.

Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer.

Changes in sleep and the prevalence of probable insomnia in undergraduate university students over the course of the COVID-19 pandemic: findings from the U-Flourish cohort study.

BACKGROUND: Sleep problems associated with poor mental health and academic outcomes may have been exacerbated by the COVID-19 pandemic. AIMS: To describe sleep in undergraduate students during the COVID-19 pandemic. METHOD: This longitudinal analysis included data from 9523 students over 4 years (2018-2022), associated with different pandemic phases. Students completed a biannual survey assessing risk factors, mental health symptoms and lifestyle, using validated measures. Sleep was assessed with the Sleep Condition Indicator (SCI-8). Propensity weights and multivariable log-binomial regressions were used to compare sleep in four successive first-year cohorts. Linear mixed-effects models were used to examine changes in sleep over academic semesters and years. RESULTS: There was an overall decrease in average SCI-8 scores, indicating worsening sleep across academic years (average change -0.42 per year; P-trend < 0.001), and an increase in probable insomnia at university entry (range 18.1-29.7%; P-trend < 0.001) before and up to the peak of the pandemic. Sleep improved somewhat in autumn 2021, when restrictions loosened. Students commonly reported daytime sleep problems, including mood, energy, relationships (36-48%) and concentration, productivity, and daytime sleepiness (54-66%). There was a consistent pattern of worsening sleep over the academic year. Probable insomnia was associated with increased cannabis use and passive screen time, and reduced recreation and exercise. CONCLUSIONS: Sleep difficulties are common and persistent in students, were amplified by the pandemic and worsen over the academic year. Given the importance of sleep for well-being and academic success, a preventive focus on sleep hygiene, healthy lifestyle and low-intensity sleep interventions seems justified.

Insomnia, depression, and anxiety symptoms interact and individually impact functioning: A network and relative importance analysis in the context of insomnia.

STUDY OBJECTIVES: Insomnia, depression, and anxiety show high rates of comorbidity and functional impairment. Transdiagnostic symptom interactions may be implicated in this comorbidity. This network analysis sought to assess how symptoms of insomnia, depression, and anxiety may interact and individually predict impairment across several domains for individuals with insomnia. METHODS: Baseline psychometric data from a randomised controlled trial were analysed (N = 1711). A regularized partial correlation network was estimated from the symptom data. Centrality (symptom connectivity), community structure (symptom clustering), and bridging (inter-community connectivity) were assessed. The replicability of the network model was assessed via confirmatory analyses in a holdout sample. Separately, Shapley values were estimated to determine the relative importance of each symptom in predicting functioning (i.e., psychological wellbeing, psychosocial functioning, and physical health impairment). RESULTS: The most connected nodes were uncontrollable worrying; trouble relaxing; and depressed mood/hopelessness. Five communities were identified with trouble relaxing identified as the bridge symptom between communities. The model showed good fit in the holdout sample. Low energy and depressive affect symptoms (feelings of failure/guilt; depressed mood/hopelessness; anhedonia) were key predictors in the relative importance analysis across multiple domains of impairment. CONCLUSION: Trouble relaxing may be of clinical and transdiagnostic significance in the context of insomnia. In terms of how symptoms relate to functioning, it was clear that, while low energy and feelings of failure/guilt were prominent predictors, a range of symptoms are associated with functional impairment. Consideration of both symptoms and functional impairment across domains may be useful in determining targets for treatment. CLINICAL TRIAL REGISTRATION: This is a secondary analysis of an original clinical trial. TRIAL REGISTRATION NUMBER: ISRCTN60530898. Registry URL: https://www.isrctn.com/ISRCTN60530898.

The Relationship between Anxiety, Subjective and Objective Sleep, Chronotype and Circadian Rhythms with Depressive Symptoms in Insomnia Disorder.

Insomnia is a highly prevalent sleep disorder with strong bidirectional associations with depressive symptoms. The circadian preference for eveningness has been shown to be associated with depressive symptoms in insomnia and other mental health conditions. However, there is a lack of studies in insomnia investigating whether objective measures, such as dim light melatonin onset (DLMO) or polysomnographic (PSG) sleep, are associated with depressive symptoms. Therefore, we investigated the associations between subjective measures (questionnaires assessing anxiety, sleep quality and circadian preference, and sleep diary) and depressive symptoms and whether the addition of objective measures (DLMO, PSG parameters) would strengthen the associations with depressive symptoms. In 115 insomnia disorder patients we found that anxiety was strongly associated with depressive symptoms in a model including circadian preference, dysfunctional beliefs of sleep, and self-reported previous depressive symptoms (R2 = 0.496, p < 0.001). The addition of sleep diary measures did not strengthen the model. We also found that the addition of objective measures (DLMO, PSG parameters) did not improve the subjective associations with depressive symptoms. Our data suggest that objective circadian markers are less important in the prediction of depressive symptoms in insomnia compared to subjective measures.

Does treating insomnia with digital cognitive behavioural therapy (Sleepio) mediate improvements in anxiety for those with insomnia and comorbid anxiety? An analysis using individual participant data from two large randomised controlled trials.

BACKGROUND: Considerable comorbidity exists between insomnia and anxiety, and evidence shows that the benefits of CBT for insomnia extend to anxiety. Using data from two large trials of digital CBT (dCBT) for insomnia, we evaluated whether improving sleep is an effective treatment target to reduce both insomnia and anxiety symptoms in individuals with insomnia and clinically significant anxiety. METHODS: This was a controlled sub-analysis combining individual participant data from two previous randomised controlled trials of dCBT for insomnia (Sleepio). Participants (N = 2172) with insomnia disorder and clinically significant anxiety symptoms were included in this sub-analysis and received either dCBT or control (usual care or sleep hygiene education). Assessments were evaluated at baseline, post-intervention (week 8 or 10), and follow-up (week 22 or 24). Mediation was evaluated using structural equation models. RESULTS: dCBT for insomnia was superior to control at reducing both insomnia (Hedges' g range = 0.77-0.81; both p < 0.001) and anxiety symptoms (Hedges' g range = 0.39-0.44; both p < 0.001) at all time points. Baseline insomnia symptoms moderated the effects of dCBT on insomnia, however no variables moderated treatment effects on anxiety. Reductions in anxiety symptoms at follow-up were mediated by improvements in sleep at post-intervention (% mediated = 84 %), suggesting a causal pathway. LIMITATIONS: Participants did not have a formal anxiety disorder diagnosis and so the effects of dCBT for insomnia on anxiety may differ by anxiety disorder. CONCLUSIONS: Addressing sleep using dCBT for insomnia may serve as a treatment target from which to improve anxiety in individuals with insomnia and clinically significant comorbid anxiety. CLINICAL TRIAL REGISTRATIONS: Digital Insomnia therapy to Assist your Life as well as your Sleep (DIALS) - ISRCTN60530898 http://www.isrctn.com/ISRCTN60530898. Oxford Access for Students Improving Sleep (OASIS) - ISRCTN61272251 http://www.isrctn.com/ISRCTN61272251.

Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia.

BACKGROUND: Despite best current therapy, up to 20% of pediatric patients with acute lymphoblastic leukemia (ALL) have a relapse. Recent genomewide analyses have identified a high frequency of DNA copy-number abnormalities in ALL, but the prognostic implications of these abnormalities have not been defined. METHODS: We studied a cohort of 221 children with high-risk B-cell-progenitor ALL with the use of single-nucleotide-polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis. Children with known very-high-risk ALL subtypes (i.e., BCR-ABL1-positive ALL, hypodiploid ALL, and ALL in infants) were excluded from this cohort. A copy-number abnormality was identified as a predictor of poor outcome, and it was then tested in an independent validation cohort of 258 patients with B-cell-progenitor ALL. RESULTS: More than 50 recurring copy-number abnormalities were identified, most commonly involving genes that encode regulators of B-cell development (in 66.8% of patients in the original cohort); PAX5 was involved in 31.7% and IKZF1 in 28.6% of patients. Using copy-number abnormalities, we identified a predictor of poor outcome that was validated in the independent validation cohort. This predictor was strongly associated with alteration of IKZF1, a gene that encodes the lymphoid transcription factor IKAROS. The gene-expression signature of the group of patients with a poor outcome revealed increased expression of hematopoietic stem-cell genes and reduced expression of B-cell-lineage genes, and it was similar to the signature of BCR-ABL1-positive ALL, another high-risk subtype of ALL with a high frequency of IKZF1 deletion. CONCLUSIONS: Genetic alteration of IKZF1 is associated with a very poor outcome in B-cell-progenitor ALL.

Assessing Measurement Properties of a Simplified Chinese Version of Sleep Condition Indicator (SCI-SC) in Community Residents.

BACKGROUND: The study aimed to assess the measurement properties of a simplified Chinese version of the Sleep Condition Indicator (SCI-SC) in the community. METHODS: A psychometric evaluation through an observational cross-sectional survey design was conducted. Community residents (N = 751) in Hangzhou, China completed the SCI-SC and the simplified Chinese version of the Sleep Quality Questionnaire (SQQ) in July 2021. Data were randomly split into a development sample (N = 375) for model development by exploratory factor analysis (EFA) and a holdout sample (N = 376) for validation by confirmatory factor analysis (CFA). Multi-group CFA (MGCFA) was used to assess configural, metric, scalar, and strict measurement invariance across gender, age, marital status, body mass index (BMI), napping habits, generic exercise, hobby, and administered survey. Moreover, statistical analyses were performed to determine the reliability (alpha and omega) and construct validity of the instrument. RESULTS: Both factor analyses showed a stable solution with two dimensions of Sleep Pattern and Sleep-Related Impact. Good structural validity, robust internal consistency, and construct validity with the SQQ were demonstrated. There was evidence of strict invariance across gender, BMI, napping habits, generic exercise, hobby, and administered survey subgroups, but only metric and scalar invariances were established across age and marital status groups, respectively. CONCLUSIONS: The SCI-SC demonstrated promising psychometric properties, with high SQQ concordance and consistent structure of the original version. The SCI-SC can be used by sleep researchers as well as healthcare professionals in various contexts in detecting risks for insomnia disorder in the community.