Adhesion barriers in gynecologic surgeries and cesarean section: An Asia-Pacific expert panel consensus recommendation.

Adhesions arising from gynecologic surgeries and cesarean sections pose substantial clinical, social, and economic challenges, leading to issues like pelvic pain, infertility, bowel obstruction, and recurring surgeries. Preventing adhesions is a pressing unmet need, hindered by difficulties in assessing postoperative adhesions and understanding barriers. To bridge adhesion prevention gaps, statements on clinical practices were synthesized to present Asia-Pacific expert perspectives on gynecologic surgery and cesarean section adhesion prevention. An expert panel of eight physicians from various healthcare settings in the Asia-Pacific region was convened and a comprehensive literature search on topics related to adhesion prevention in gynecologic surgeries and cesarean sections was performed. Information from full-text publications was used to develop draft consensus statements, with each statement assigned the highest available evidence level based on a systematic literature review and graded using the Oxford Center for Evidence-based Medicine criteria. A modified Delphi process, involving two rounds of online voting and discussions with an extended group of 109 experts, was employed to reach a consensus on six topics related to adhesion barriers. A set of 15 consensus statements were synthesized. Key topics include adhesion incidence in Asia, cesarean section complications, barrier application status, adhesion formation and prevention, absorbable barriers' effectiveness, recommendations, and future considerations. The statements provide guidance for healthcare professionals, especially in the Asia-Pacific region, to tackle the challenges posed by postoperative adhesions and improve patient outcomes. Further research is needed to enhance understanding and prevention of adhesions in this region.

Hypersomnolence is associated with non-remission of major depressive disorder.

OBJECTIVE: This study aimed to investigate the prevalence, clinical correlates and the relationship between hypersomnolence and clinical outcomes in a cohort of MDD patients. METHODS: This is a cross-sectional study of a MDD cohort in an university-affiliated adult psychiatric outpatient clinic. The diagnosis of MDD and severity of depression were ascertained by the clinician with structured clinical interviews. Each participant completed the Epworth Sleepiness Scale (ESS), 1-week sleep diary, and a battery of questionnaires that assessed usual sleep pattern, insomnia, anxiety, depression, fatigue and circadian preference. Hypersomnolence was defined as ESS score ≥14 among those reported ≥7 h of nighttime sleep. Univariate analysis and multiple logistic regression were used to analyze the relationships between the variables. RESULTS: Among 252 recruited subjects, 11 % met the criteria of hypersomnolence as defined by a ESS score ≥14 despite ≥7 h of nighttime sleep. Patients with hypersomnolence had greater depression ratings, higher rates of suicidal ideations over the past week, and more likely to meet a diagnosis of atypical depression (p < 0.05) than those without hypersomnolence. Step-wise logistic regression demonstrated that hypersomnolence was an independent risk factor associated with a 3-fold increase in the risk of depression non-remission (adjusted OR 3.13; 95 % CI 1.10-8.95; p = 0.034). CONCLUSION: Patients with hypersomnolence despite seemingly adequate sleep represent a subgroup of MDD patients who have a more severe illness profile with higher non-remission rate and suicidality. The findings highlight the importance of addressing both sleep and mood symptoms in the management of MDD.

Imaging in interventional oncology, the better you see, the better you treat.

Imaging and image processing is the fundamental pillar of interventional oncology in which diagnostic, procedure planning, treatment and follow-up are sustained. Knowing all the possibilities that the different image modalities can offer is capital to select the most appropriate and accurate guidance for interventional procedures. Despite there is a wide variability in physicians preferences and availability of the different image modalities to guide interventional procedures, it is important to recognize the advantages and limitations for each of them. In this review, we aim to provide an overview of the most frequently used image guidance modalities for interventional procedures and its typical and future applications including angiography, computed tomography (CT) and spectral CT, magnetic resonance imaging, Ultrasound and the use of hybrid systems. Finally, we resume the possible role of artificial intelligence related to image in patient selection, treatment and follow-up.

Subtyping at-risk adolescents for predicting response toward insomnia prevention program.

BACKGROUND: Previous study has shown that a brief cognitive-behavioral prevention insomnia program could reduce 71% risk of developing insomnia among at-risk adolescents. This study aimed to evaluate the differential response to insomnia prevention in subgroups of at-risk adolescents. METHODS: Adolescents with a family history of insomnia and subthreshold insomnia symptoms were randomly assigned to a 4-week insomnia prevention program or nonactive control group. Assessments were conducted at baseline, 1 week, and 6- and 12-month after the intervention. Baseline sleep, daytime, and mood profiles were used to determine different subgroups by using latent class analysis (LCA). Analyses were conducted based on the intention-to-treat approach. RESULTS: LCA identified three subgroups: (a) insomnia symptoms only, (b) insomnia symptoms with daytime sleepiness and mild anxiety, and (c) insomnia symptoms with daytime sleepiness, mild anxiety, and depression. The incidence rate of insomnia disorder over the 12-month follow-up was significantly reduced for adolescents receiving intervention in subgroup 3 compared with the controls (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.13-0.99; p = .049) and marginally for subgroup 2 (HR = 0.14; 95% CI: 0.02-1.08; p = .059). In addition, adolescents who received intervention in subgroups 2 and 3 had a reduced risk of excessive daytime sleepiness (subgroup 2: adjusted OR [AdjOR] = 0.45, 95% CI: 0.23-0.87; subgroup 3: AdjOR = 0.32, 95% CI: 0.13-0.76) and possible anxiety (subgroup 2: AdjOR = 0.47, 95% CI: 0.27-0.82; subgroup 3: AdjOR = 0.33, 95% CI: 0.14-0.78) compared with the controls over the 12-month follow-up. CONCLUSIONS: Adolescents at risk for insomnia can be classified into different subgroups according to their psychological profiles, which were associated with differential responses to the insomnia prevention program. These findings indicate the need for further phenotyping and subgrouping at-risk adolescents to develop personalized insomnia prevention.

Familial α-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the α-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying α-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an α-synucleinopathy. METHODS: In this case-control-family study, a combination of family history and family study method was used to measure the α-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of α-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls. RESULTS: There was an increase of α-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression. CONCLUSION: Patients with psy-RBD are familially predisposed to α-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying α-synucleinopathy neurodegeneration. TRIAL REGISTRATION NUMBER: NCT03595475.

School-Based Sleep Education Program for Children: A Cluster Randomized Controlled Trial.

Insufficient sleep contributes negatively to child developmental processes and neurocognitive abilities, which argues the need for implementing interventions to promote sleep health in children. In this study, we evaluated the effectiveness of a multimodal and multilevel school-based sleep education program in primary school children using a cluster randomized controlled design. Twelve schools were randomly assigned to either the sleep education or nonactive control groups. The sleep education group included a town hall seminar, small class teaching, leaflets, brochures, and a painting competition for children. Parents and teachers were invited to participate in a one-off sleep health workshop. Parental/caregiver-reported questionnaires were collected at baseline and 1-month follow-up. A total of 3769 children were included in the final analysis. There were no significant improvements observed in the sleep-wake patterns, daytime functioning, and insomnia symptoms between the two groups at follow-up, whereas the intervention group had significantly improved parental sleep knowledge than the controls (paternal: adjusted mean difference: 0.95 [95% confidence interval (CI): 0.18 to 1.71]; maternal: adjusted mean difference: 0.87 [95% CI: 0.17 to 1.57]). In addition, children receiving the intervention had a lower persistence rate of excessive beverage intake (adjusted odds ratio: 0.49 [95% CI: 0.33 to 0.73]), and experienced greater reductions in conduct problems (adjusted mean difference: 0.12 [95% CI: 0.01 to 0.24]) compared with the controls at 1-month of follow-up. Moreover, a marginally significant reduction for emotional problems in the intervention group was also observed (adjusted mean difference: 0.16 [95% CI: -0.00 to 0.32]). These findings demonstrated that school-based sleep education was effective in enhancing parental sleep knowledge and improving behavioral outcomes in children, but not sufficient in altering the children's sleep-wake patterns and sleep problems.

Psychometric Properties of the Caregiver Strain Questionnaire in a Chinese Sample of Caregivers of Children with Autism Spectrum Disorder.

The Caregiver Strain Questionnaire assesses the three dimensions of caregiver strain, namely the objective, subjective externalized and subjective internalized strain. It was validated among caregivers of children with Autism Spectrum Disorder (ASD) in the United States and Mainland China with promising psychometric properties.This study aimed to develop and validate the Chinese (traditional script) version of the Caregiver Strain Questionnaire (C-CGSQ) among 198 caregivers of children with ASD in Hong Kong. The C-CGSQ showed excellent internal consistency (α = 0.958) and test-retest reliability (Spearman's r = 0.966). Concurrent, convergent, divergent validity and a three-factor structure (consistent with previous studies) were established. The C-CGSQ demonstrated promising psychometric properties in measuring caregiver strain among caregivers of Chinese ASD children in Hong Kong.

ABE8e Corrects Pax6-Aniridic Variant in Humanized Mouse ESCs and via LNPs in Ex Vivo Cortical Neurons.

INTRODUCTION: Aniridia is a rare congenital vision-loss disease caused by heterozygous variants in the PAX6 gene. There is no vision-saving therapy, but one exciting approach is to use CRISPR/Cas9 to permanently correct the causal genomic variants. Preclinical studies to develop such a therapy in animal models face the challenge of showing efficacy when binding human DNA. Thus, we hypothesized that a CRISPR gene therapy can be developed and optimized in humanized mouse embryonic stem cells (ESCs) that will be able to distinguish between an aniridia patient variant and nonvariant chromosome and lay the foundation for human therapy. METHODS: To answer the challenge of binding human DNA, we proposed the "CRISPR Humanized Minimally Mouse Models" (CHuMMMs) strategy. Thus, we minimally humanized Pax6 exon 9, the location of the most common aniridia variant c.718C > T. We generated and characterized a nonvariant CHuMMMs mouse, and a CHuMMMs cell-based disease model, in which we tested five CRISPR enzymes for therapeutic efficacy. We then delivered the therapy via lipid nanoparticles (LNPs) to alter a second variant in ex vivo cortical primary neurons. RESULTS: We successfully established a nonvariant CHuMMMs mouse and three novel CHuMMMs aniridia cell lines. We showed that humanization did not disrupt Pax6 function in vivo, as the mouse showed no ocular phenotype. We developed and optimized a CRISPR therapeutic strategy for aniridia in the in vitro system, and found that the base editor, ABE8e, had the highest correction of the patient variant at 76.8%. In the ex vivo system, the LNP-encapsulated ABE8e ribonucleoprotein (RNP) complex altered the second patient variant and rescued 24.8% Pax6 protein expression. CONCLUSION: We demonstrated the usefulness of the CHuMMMs approach, and showed the first genomic editing by ABE8e encapsulated as an LNP-RNP. Furthermore, we laid the foundation for translation of the proposed CRISPR therapy to preclinical mouse studies and eventually patients with aniridia.

Clinical and neuroimaging markers of neurodegeneration in first-degree relatives of patients with REM sleep behavior disorder with and without isolated rapid eye movement sleep without atonia: A case-control clinical and dopamine PET study.

OBJECTIVES: The current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD). METHODS: This cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration. RESULTS: In contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001). CONCLUSION: FDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis.

Nodeless Superconductivity in Kagome Metal CsV3Sb5 with and without Time Reversal Symmetry Breaking.

The kagome metal CsV3Sb5 features an unusual competition between the charge-density-wave (CDW) order and superconductivity. Evidence for time reversal symmetry breaking (TRSB) inside the CDW phase has been accumulating. Hence, the superconductivity in CsV3Sb5 emerges from a TRSB normal state, potentially resulting in an exotic superconducting state. To reveal the pairing symmetry, we first investigate the effect of nonmagnetic impurity. Our results show that the superconducting critical temperature is insensitive to disorder, pointing to conventional s-wave superconductivity. Moreover, our measurements of the self-field critical current (Ic,sf), which is related to the London penetration depth, also confirm conventional s-wave superconductivity with strong coupling. Finally, we measure Ic,sf where the CDW order is removed by pressure and superconductivity emerges from the pristine normal state. Our results show that s-wave gap symmetry is retained, providing strong evidence for the presence of conventional s-wave superconductivity in CsV3Sb5 irrespective of the presence of the TRSB.

Ganciclovir-induced mutations are present in a diverse spectrum of post-transplant malignancies.

BACKGROUND: Ganciclovir (GCV) is widely used in solid organ and haematopoietic stem cell transplant patients for prophylaxis and treatment of cytomegalovirus. It has long been considered a mutagen and carcinogen. However, the contribution of GCV to cancer incidence and other factors that influence its mutagenicity remains unknown. METHODS: This retrospective cohort study analysed genomics data for 121,771 patients who had undergone targeted sequencing compiled by the Genomics Evidence Neoplasia Information Exchange (GENIE) or Foundation Medicine (FM). A statistical approach was developed to identify patients with GCV-associated mutational signature (GCVsig) from targeted sequenced data of tumour samples. Cell line exposure models were further used to quantify mutation burden and DNA damage caused by GCV and other antiviral and immunosuppressive drugs. RESULTS: Mutational profiles from 22 of 121,771 patient samples in the GENIE and FM cohorts showed evidence of GCVsig. A diverse range of cancers was represented. All patients with detailed clinical history available had previously undergone solid organ transplantation and received GCV and mycophenolate treatment. RAS hotspot mutations associated with GCVsig were present in 9 of the 22 samples, with all samples harbouring multiple GCV-associated protein-altering mutations in cancer driver genes. In vitro testing in cell lines showed that elevated DNA damage response and GCVsig are uniquely associated with GCV but not acyclovir, a structurally similar antiviral. Combination treatment of GCV with the immunosuppressant, mycophenolate mofetil (MMF), increased the misincorporation of GCV in genomic DNA and mutations attributed to GCVsig in cell lines and organoids. CONCLUSIONS: In summary, GCV can cause a diverse range of cancers. Its mutagenicity may be potentiated by other therapies, such as mycophenolate, commonly co-prescribed with GCV for post-transplant patients. Further investigation of the optimal use of these drugs could help reduce GCV-associated mutagenesis in post-transplant patients.

Patterned diamond anvils prepared via laser writing for electrical transport measurements of thin quantum materials under pressure.

Quantum materials exhibit intriguing properties with important scientific values and huge technological potential. Electrical transport measurements under hydrostatic pressure have been influential in unraveling the underlying physics of many quantum materials in bulk form. However, such measurements have not been applied widely to samples in the form of thin flakes, in which new phenomena can emerge, due to the difficulty in attaching fine wires to a thin sample suitable for high-pressure devices. Here, we utilize a home-built direct laser writing system to functionalize a diamond anvil to directly integrate the capability of conducting electrical transport measurements of thin flakes with a pressure cell. With our methodology, the culet of a diamond anvil is equipped with a set of custom-designed conducting tracks. We demonstrate the superiority of these tracks as electrodes for the studies of thin flakes by presenting the measurement of pressure-enhanced superconductivity and quantum oscillations in a flake of MoTe2.

Dim light melatonin patterns in unaffected offspring of parents with bipolar disorder: A case-control high-risk study.

BACKGROUND: Circadian dysregulation has long been thought to be a key component in the pathophysiology of bipolar disorder (BD). However, it remains unclear whether this dysregulation constitutes a risk factor, manifestation, or consequence of BD. This study aimed to compare dim light melatonin secretion patterns between unaffected offspring of parents with BD (OBD) and offspring of control parents (OCP). METHODS: This case-control study included unaffected OBD (mean age 14.0 years; male 50.0 %) and age- and sex-matched OCP (mean age 13.0 years; male: 43.5 %). Seventeen saliva samples were collected in dim light conditions. Dim light melatonin onset (DLMO), phase angles, and area under the curve (AUC) were calculated. RESULTS: 185 saliva samples from 12 OBD (n = 12) and 741 from OCP (n = 46) were collected. Unaffected OBD had a significant lower nocturnal melatonin level (14.8 ± 4.6 vs. 20.3 ± 11.7 pg/mL) and a smaller melatonin AUC within two hours after DLMO (35.5 ± 11.3 vs. 44.6 ± 18.1 pg/mL) but a significant larger phase angle between DLMO and sleep onset (2.2 ± 1.0 vs. 1.4 ± 1.2 h) than OCP. There was no significant between-group difference in DLMO. The graphic illustrations showed a considerably flattened melatonin secretion in unaffected OBD. LIMITATIONS: The main limitations include lack of 24-h dim melatonin secretion measurement, large age range of participants, and small sample size. CONCLUSIONS: These findings suggest that unaffected OBD already presented with circadian rhythm dysregulations. Future investigations are needed to clarify the role of abnormal melatonin secretion in the onset of BD.

Roles of the gut virome and mycobiome in faecal microbiota transplantation.

Faecal microbiota transplantation (FMT) is an innovative approach to treat diseases that are associated with gut dysbiosis, by transferring a healthy stool microbiota to a recipient with disease. Beyond the bacteriome, the human gut also harbours diverse communities of viruses and fungi, collectively known as the virome and the mycobiome. The effect of the virome and the mycobiome on the success of FMT therapy has not been appreciated until recently. In this Review, we summarise the current literature on the effects of the gut virome and mycobiome on the treatment of various diseases with FMT. We discuss the beneficial effects and health concerns of viral and fungal transfer during FMT, and highlight the roles of bacteriophages and Candida species in FMT efficacy. We also summarise the intricate relationships between the gut virome, mycobiome, bacteriome, and host immunity underlying FMT effectiveness. Future efforts should be devoted to understanding the versatile roles and the therapeutic mechanisms of viral and fungal lineages, and their combinations, in different diseases. Harnessing the gut virome, mycobiome, and bacteriome in combination is a promising prospect for the future of FMT and microbiota-based therapies.

Efficacy of Email-delivered Versus Face-to-face Group Cognitive Behavioral Therapy for Insomnia in Youths: A Randomized Controlled Trial.

PURPOSE: The purpose of the study was to compare the efficacy of group-based therapy (GT) and email-delivered self-help (ESH) cognitive behavioral therapy for insomnia (CBT-I) with the wait-list (WL) control group in youths. METHODS: The study involved an assessor-blind, parallel group randomized controlled trial in youths meeting the diagnostic criteria for insomnia disorder. Participants were randomized to one of the three groups (8-week GT, 8-week ESH, or WL). Participants in all three groups were assessed at baseline and after treatment (week 9 for the WL group). The two treatment groups were additionally assessed at one month and six months after the intervention. Treatment effects were examined using linear mixed models. RESULTS: A total of 135 youths (mean age: 20.0 ± 2.5 years, female: 67.4%) were recruited. After treatment, both active treatment groups showed significant improvements in insomnia symptoms (GT vs. WL: Cohen's d = -1.03, ESH vs. WL: d = -.63), less presleep arousal (d = -.52 to -1.47), less sleep-related dysfunctional belief (d = -.88 to -1.78), better sleep hygiene practice (d = -.79 to -.84), and improved daytime functioning (d = -.56 to -.96) compared with the WL group. In addition, GT outperformed ESH in improving maladaptive sleep-related beliefs and mood symptoms at post-treatment and 6-month follow-up. A reduction of suicidality with moderate effect size favoring GT emerged at 6-month follow-up. DISCUSSION: Our findings suggested that both group-based and email-delivered CBT-I were effective in treating youth insomnia, but group-based CBT-I showed superior effects on reducing maladaptive beliefs and mood symptoms.

Neurological manifestations in m.3243A>G-related disease triggered by metformin.

INTRODUCTION: m.3243A>G-related disease has multi-systemic manifestations including diabetes mellitus. It is uncertain whether metformin would trigger neurological manifestations of this disease. This study aims to review the diagnosis and management of m.3243A>G-related diabetes genetically confirmed by our laboratory and to evaluate the risk of metformin use triggering neurological manifestations. METHODS: Cases with m.3243A>G detected between 2009 and 2020 were reviewed. Cases with diabetes mellitus were included. Cases with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) before diabetes onset were excluded. Odds ratio was calculated for association between metformin use and newly developed neurological manifestations. RESULTS: Sixteen patients were identified. Odds ratio for metformin use was 3.50 [0.37-33.0; p = 0.3287]. One illustrative case with clear causal relationship between metformin use and neurological manifestations was described in detail. CONCLUSION: m.3243A>G-related diabetes mellitus is underdiagnosed. Red flags including positive family history, short stature, low body weight and hearing loss are often overlooked. Early diagnosis allows regular systemic assessment. In the era of precision medicine and novel therapies, it is prudent to avoid metformin as it could trigger neurological manifestations in this condition. Coenzyme Q10, DPP-IV inhibitors, SGLT2 inhibitors and GLP-1 receptor agonists may be considered.

Current status in endoscopic management of upper gastrointestinal perforations, leaks and fistulas.

Recent advancement in endoscopic closure techniques have revolutionized the treatment of gastrointestinal perforations, leaks and fistulas. Traditionally, these have been managed surgically. The treatment strategy depends on the size and location of the defect, degree of contamination, presence of healthy surrounding tissues, patients' condition and the availability of expertise. One of the basic principles of management includes providing a barricade to the flow of luminal contents across the defect. This can be achieved with a wide range of endoscopic techniques. These include endoclips, stenting, suturing, tissue adhesives and glue, and endoscopic vacuum therapy. Each method has their distinct indications and shortcomings. Often, a combination of these techniques is required. Apart from endoscopic closure, drainage procedures by the interventional radiologist and surgical management also play an important role. In this review article, the outcomes of each of these endoscopic closure techniques in the literature is provided in tables, and practical management algorithms are being proposed.

Change in circadian preference predicts sustained treatment outcomes in patients with unipolar depression and evening preference.

STUDY OBJECTIVES: Eveningness is associated with worse outcomes in depression. It remained unclear if eveningness could be altered with chronobiological therapy and whether such a change would predict long-term outcomes of depression. METHODS: Data from a randomized controlled trial of 5-week adjunctive bright light therapy with a gradual advance protocol conducted in 91 adult patients with nonseasonal unipolar depression and eveningness (Morningness-Eveningness Questionnaire, score ≤ 41) was examined. "Change of eveningness" was defined by Morningness-Eveningness Questionnaire score over 41 at posttreatment week 5 and "persistent change of eveningness" was defined as maintenance of Morningness-Eveningness Questionnaire score > 41 throughout the follow-up period from week 5 to posttreatment 5 months. RESULTS: Thirty-three participants (36%) had change of eveningness at week 5. Generalized estimating equations models showed that a change of eveningness at week 5 predicted a 2-fold increase in remission of depression over the 5-month follow up (odds ratio = 2.61 95% confidence interval 1.20-5.71, P = .016). Twenty-five participants (75.7%) had a persistent change and were more likely to achieve a remission of depression over the 5-month follow up (odds ratio = 3.18, 95% confidence interval: 1.35-7.50, P = .008). CONCLUSIONS: One-third of the patients with depression changed their evening-preference after 5-week of chronotherapeutic treatment, and such change predicted a higher likelihood of depression remission over 5 months of follow-up. CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trial Registry; Name: Adjunctive light treatment in major depressive disorder patients with evening chronotype-A randomized controlled trial; URL: https://www.chictr.org.cn/showprojen.aspx?proj=11672; Identifier: ChiCTR-IOR-15006937. CITATION: Chan JWY, Chan NY, Li SX, et al. Change in circadian preference predicts sustained treatment outcomes in patients with unipolar depression and evening preference. J Clin Sleep Med. 2022;18(2):523-531.