ABSTRACT
Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.
Subject(s)
Memory, Short-Term , Parietal Lobe , Prefrontal Cortex , Schizophrenia , Transcranial Direct Current Stimulation , Humans , Memory, Short-Term/physiology , Transcranial Direct Current Stimulation/methods , Schizophrenia/therapy , Schizophrenia/physiopathology , Male , Female , Adult , Double-Blind Method , Parietal Lobe/physiopathology , Prefrontal Cortex/physiopathology , Dorsolateral Prefrontal Cortex/physiology , Middle Aged , Treatment Outcome , Cognition/physiology , Young Adult , Neuropsychological TestsABSTRACT
Single-cell RNA-seq (scRNA-seq) is widely used for transcriptome profiling, but most analyses focus on gene-level events, with less attention devoted to alternative splicing. Here, we present scASfind, a novel computational method to allow for quantitative analysis of cell type-specific splicing events using full-length scRNA-seq data. ScASfind utilizes an efficient data structure to store the percent spliced-in value for each splicing event. This makes it possible to exhaustively search for patterns among all differential splicing events, allowing us to identify marker events, mutually exclusive events, and events involving large blocks of exons that are specific to one or more cell types.
Subject(s)
Alternative Splicing , RNA-Seq , Single-Cell Gene Expression Analysis , Animals , Humans , Computational Biology/methods , Data Mining , Exons , Gene Expression Profiling/methods , RNA-Seq/methods , SoftwareABSTRACT
PURPOSE OF REVIEW: Higher degrees of myopia are currently being treated with refractive surgery. However, there is limited characterization and outcomes data for this cohort. This article aims to review the literature on highly myopic patients who had refractive surgery and present a retrospective analysis of 149 patients (270 eyes) with high to extreme myopia (≤-5.0D SE) who underwent refractive surgery [laser-assisted subepithelial keratomileusis (LASIK), photorefractive keratectomy (PRK), or implantable collamer lense (ICL)] at a single practice. RECENT FINDINGS: There is substantial literature on the efficacy of LASIK, PRK, and phakic intraocular lenses for refractive error correction, but a dearth of studies on patients with high to extreme myopia undergoing different types of refractive surgery. Our study reveals that this cohort of patients has excellent outcomes with minimal complications. SUMMARY: Our study reveals that the average preoperative myopia was highest in ICL patients (-10.03D), followed by PRK (-7.21D), and LASIK (-7.04D) patients. Not surprisingly, eyes with high myopia and thin corneas were offered and elected ICLs for their procedure. Highly myopic patients achieved outcomes consistent with data reported in the literature- average postoperative uncorrected visual acuity was 20/20 for LASIK and ICL eyes and 20/25 for PRK eyes.
Subject(s)
Photorefractive Keratectomy , Visual Acuity , Humans , Visual Acuity/physiology , Treatment Outcome , Photorefractive Keratectomy/methods , Lens Implantation, Intraocular/methods , Keratomileusis, Laser In Situ/methods , Refraction, Ocular/physiology , Retrospective Studies , Myopia, Degenerative/surgery , Myopia, Degenerative/physiopathology , Myopia/surgery , Myopia/physiopathology , Phakic Intraocular Lenses , Adult , Male , FemaleABSTRACT
BACKGROUND: Acute neurological manifestation is a common complication of acute Coronavirus Disease 2019 (COVID-19) disease. This retrospective cohort study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization. METHODS AND FINDINGS: Patients hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection between 03/01/2020 and 4/16/2020 in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to 01/23/2023 (3 years post-COVID-19). This cohort consisted of 414 patients with COVID-19 with significant neurological manifestations and 1,199 propensity-matched patients (for age and COVID-19 severity score) with COVID-19 without neurological manifestations. Neurological involvement during the acute phase included acute stroke, new or recrudescent seizures, anatomic brain lesions, presence of altered mentation with evidence for impaired cognition or arousal, and neuro-COVID-19 complex (headache, anosmia, ageusia, chemesthesis, vertigo, presyncope, paresthesias, cranial nerve abnormalities, ataxia, dysautonomia, and skeletal muscle injury with normal orientation and arousal signs). There were no significant group differences in female sex composition (44.93% versus 48.21%, p = 0.249), ICU and IMV status, white, not Hispanic (6.52% versus 7.84%, p = 0.380), and Hispanic (33.57% versus 38.20%, p = 0.093), except black non-Hispanic (42.51% versus 36.03%, p = 0.019). Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were neuroimaging findings (hemorrhage, active and prior stroke, mass effect, microhemorrhages, white matter changes, microvascular disease (MVD), and volume loss). More patients in the neurological cohort were discharged to acute rehabilitation (10.39% versus 3.34%, p < 0.001) or skilled nursing facilities (35.75% versus 25.35%, p < 0.001) and fewer to home (50.24% versus 66.64%, p < 0.001) than matched controls. Incidence of readmission for any reason (65.70% versus 60.72%, p = 0.036), stroke (6.28% versus 2.34%, p < 0.001), and MACE (20.53% versus 16.51%, p = 0.032) was higher in the neurological cohort post-discharge. Per Kaplan-Meier univariate survival curve analysis, such patients in the neurological cohort were more likely to die post-discharge compared to controls (hazard ratio: 2.346, (95% confidence interval (CI) [1.586, 3.470]; p < 0.001)). Across both cohorts, the major causes of death post-discharge were heart disease (13.79% neurological, 15.38% control), sepsis (8.63%, 17.58%), influenza and pneumonia (13.79%, 9.89%), COVID-19 (10.34%, 7.69%), and acute respiratory distress syndrome (ARDS) (10.34%, 6.59%). Factors associated with mortality after leaving the hospital involved the neurological cohort (odds ratio (OR): 1.802 (95% CI [1.237, 2.608]; p = 0.002)), discharge disposition (OR: 1.508 (95% CI [1.276, 1.775]; p < 0.001)), congestive heart failure (OR: 2.281 (95% CI [1.429, 3.593]; p < 0.001)), higher COVID-19 severity score (OR: 1.177 (95% CI [1.062, 1.304]; p = 0.002)), and older age (OR: 1.027 (95% CI [1.010, 1.044]; p = 0.002)). There were no group differences in radiological findings, except that the neurological cohort showed significantly more age-adjusted brain volume loss (p = 0.045) than controls. The study's patient cohort was limited to patients infected with COVID-19 during the first wave of the pandemic, when hospitals were overburdened, vaccines were not yet available, and treatments were limited. Patient profiles might differ when interrogating subsequent waves. CONCLUSIONS: Patients with COVID-19 with neurological manifestations had worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for patients with COVID-19 with neurological manifestations, as their disease course involving initial neurological manifestations is associated with enhanced morbidity and mortality.
Subject(s)
COVID-19 , Stroke , Humans , Female , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , SARS-CoV-2 , Retrospective Studies , Follow-Up Studies , Aftercare , Patient Discharge , Seizures , Stroke/epidemiologyABSTRACT
BACKGROUND: Regulation of transcription is central to the emergence of new cell types during development, and it often involves activation of genes via proximal and distal regulatory regions. The activity of regulatory elements is determined by transcription factors (TFs) and epigenetic marks, but despite extensive mapping of such patterns, the extraction of regulatory principles remains challenging. RESULTS: Here we study differentially and similarly expressed genes along with their associated epigenomic profiles, chromatin accessibility and DNA methylation, during lineage specification at gastrulation in mice. Comparison of the three lineages allows us to identify genomic and epigenomic features that distinguish the two classes of genes. We show that differentially expressed genes are primarily regulated by distal elements, while similarly expressed genes are controlled by proximal housekeeping regulatory programs. Differentially expressed genes are relatively isolated within topologically associated domains, while similarly expressed genes tend to be located in gene clusters. Transcription of differentially expressed genes is associated with differentially open chromatin at distal elements including enhancers, while that of similarly expressed genes is associated with ubiquitously accessible chromatin at promoters. CONCLUSION: Based on these associations of (linearly) distal genes' transcription start sites (TSSs) and putative enhancers for developmental genes, our findings allow us to link putative enhancers to their target promoters and to infer lineage-specific repertoires of putative driver transcription factors, within which we define subgroups of pioneers and co-operators.
Subject(s)
Epigenomics , Genes, Essential , Animals , Mice , Chromatin/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Gene Expression ProfilingABSTRACT
Recent innovations in single-cell RNA-sequencing (scRNA-seq) provide the technology to investigate biological questions at cellular resolution. Pooling cells from multiple individuals has become a common strategy, and droplets can subsequently be assigned to a specific individual by leveraging their inherent genetic differences. An implicit challenge with scRNA-seq is the occurrence of doublets-droplets containing two or more cells. We develop Demuxafy, a framework to enhance donor assignment and doublet removal through the consensus intersection of multiple demultiplexing and doublet detecting methods. Demuxafy significantly improves droplet assignment by separating singlets from doublets and classifying the correct individual.
Subject(s)
Single-Cell Analysis , Humans , Single-Cell Analysis/methods , Sequence Analysis, RNA/methodsABSTRACT
INTRODUCTION: This study examined the psychological wellbeing of Healthcare Workers (HCWs) during COVID-19 in a mental health setting, associations of psychosocial wellbeing with coping style, and ways that organisations can mitigate the psychosocial burden on HCWs. METHODS: Thirty-seven Mental HCWs (MHCWs) from infected and non-infected wards (control group), were recruited and assessed at three timepoints. Psychological wellbeing, perceived cohesion, and coping style (Brief-COPE) were assessed. Reports on individual coping and feedback on the organisation were collected through in-depth interview. Comparison between infected and non-infected wards, as well as comparison of psychosocial measures and perceived cohesion, across the three timepoints were made. As there were no significant changes in coping styles across the timepoints, Timepoint 1 (T1) coping style was used to correlate with the psychosocial measures across all timepoints. Thematic analysis was used for qualitative data. RESULTS: MHCWs from infected wards reported significantly higher levels of stress, χ2(1) = 6.74, p = 0.009, effect size: medium (ε2 = 0.198), and more severe sleep disturbance (PSQI), χ2(1) = 6.20, p = 0.013, effect size: medium (ε2 = 0.182), as compared to the control group at T2. They also engaged in more problem-focused coping (T2 and T3) and emotion-focused coping (T2). As expected, negative coping style was correlated with negative outcomes except problem-focused coping that was correlated with both negative (sleep disturbance and anxiety symptoms) and positive outcomes (wellbeing). Emotion-focused coping was moderately correlated (Tb = 0.348, p<0.017) with higher levels of wellbeing at T2. Thematic analyses revealed MHCWs felt supported by the responsiveness of the institution, emotional and informational support, and the availability from direct leaders, presence of team and hospital leaders on the ground, helped build trust and confidence in the leadership. CONCLUSIONS: MHCWs experienced significantly higher levels of stress and sleep disturbance during COVID-19. The ways that organizations can offset the psychological burden of pandemics on MHCWs are discussed.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Mental Health , Adaptation, Psychological , Psychological Well-Being , Stress, Psychological/psychology , Health Personnel/psychologyABSTRACT
Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.
Subject(s)
Brain , Machine Learning , Magnetic Resonance Imaging , Neuroimaging , Psychotic Disorders , Humans , Psychotic Disorders/pathology , Psychotic Disorders/diagnostic imaging , Magnetic Resonance Imaging/methods , Male , Female , Brain/pathology , Brain/diagnostic imaging , Neuroimaging/methods , Adult , Young Adult , Adolescent , Prodromal SymptomsABSTRACT
OBJECTIVE: Lower white matter integrity of frontal-subcortical circuitry has been associated with late-life depression in normally aging older adults and with the presence of multiple sclerosis (MS). Frontal-striatal white matter tracts involved in executive, cognitive, emotion, and motor function may underlie depression in older adults with MS. The present study examined the association between depression score and frontal-striatal white matter integrity in older adults with MS and controls. METHODS: Older adults with MS (OAMS) (n = 67, mean age = 64.55 ± 3.89) and controls (n = 74, mean age = 69.04 ± 6.32) underwent brain MRI, cognitive assessment, psychological, and motoric testing. Depression was assessed through the 30-item Geriatric Depression Scale. Fractional anisotropy (FA) was extracted from two bilateral tracts: dorsolateral prefrontal cortex to putamen nucleus (DLPFC-pn) and dorsolateral prefrontal cortex to caudate nucleus (DLPFC-cn). RESULTS: OAMS reported significantly worse (i.e., higher) depression symptoms (ß = .357, p < .001) compared to healthy controls. Adjusted moderation analyses revealed, via group by FA interactions, significantly stronger associations between FA of the left DLPFC-pn tract and total depression (B = - 61.70, p = .011) among OAMS compared to controls. Conditional effects revealed that lower FA of the left DLPFC-pn was significantly associated with worse (i.e., higher) depression symptoms (b = - 38.0, p = .028) only among OAMS. The other three tracts were not significant in moderation models. CONCLUSIONS: We provided first evidence that lower white matter integrity of the left DLPFC-pn tract was related to worse depression in older adults with MS.
Subject(s)
Depression , Multiple Sclerosis , White Matter , Humans , Male , Aged , Female , Depression/diagnostic imaging , Depression/pathology , Middle Aged , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Multiple Sclerosis/complications , White Matter/diagnostic imaging , White Matter/pathology , Diffusion Tensor Imaging , Corpus Striatum/diagnostic imaging , Corpus Striatum/pathology , Neural Pathways/diagnostic imaging , Neural Pathways/pathology , Magnetic Resonance ImagingABSTRACT
OBJECTIVE: Stroke has a major impact on a person's life. While much research exists on stroke prevention and treatment, explorations into psychosocial recovery needs are lacking. This review critically consolidates the challenges and needs of stroke survivors and develops a trajectory that encapsulates their journey from illness to recovery. DATA SOURCES: Six major databases were searched, including Academic Search Premier, CINAHL, Global Health, Medline, PsycArticles, and PsycINFO. METHODS: This review adhered to the PRISMA guidelines and employed the PICo (population, phenomena of interest, context) framework to screen for relevant qualitative reviews published between 1 January 2010 and 31 August 2023. Following full-text screening and the assessment of methodological quality using a modified version of the Assessment of Multiple Systematic Reviews scale, a total of 17 reviews were included for thematic synthesis. RESULTS: Included reviews referenced 400 qualitative primary studies involving more than 5623 stroke survivors. Data synthesis revealed 18 themes that were further organized into six conceptual categories: (1) The unfamiliar body, (2) compassionate healthcare system, (3) holistic rehabilitation, (4) intrapersonal strength, (5) interpersonal relations, and (6) thriving forward to form the psychosocial rehabilitation trajectory of stroke survivor (PReTS) model. The model recognizes the losses that can occur after a stroke and emphasizes the essentiality of addressing psycho-socio-emotional and spiritual needs alongside physical impairments. CONCLUSION: The PReTS model is the first to highlight stroke survivors' losses, recovery journeys, and psychosocial needs. The conceptualization serves to inform and advance stroke rehabilitation practices with holistic and wellness recovery research.
Subject(s)
Psychiatric Rehabilitation , Stroke Rehabilitation , Stroke , Humans , Systematic Reviews as Topic , Stroke/diagnosis , Stroke/psychology , Qualitative Research , Survivors/psychologyABSTRACT
The quality of carbohydrates has metabolic consequences in people with prediabetes. However, the causality of short-chain fermentable carbohydrate intakes and metabolic parameters has not been explored in the prediabetic or diabetic population. We investigated associations between different types of carbohydrates, including fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAPs), and polysaccharides (dietary fibre), and body composition and glucose/insulin responses in subjects with prediabetes. In this prospective cross-sectional study, 177 subjects with impaired glucose tolerance (IGT) (mean age: 60 (54-62) years, 41% men) underwent an assessment of body composition and completed six-point oral glucose tolerance tests (OGTT), Homeostatic Model Assessment of Insulin Resistance (HOMA2-IR), insulin sensitivity, detailed 3-day food records, and physical activity questionnaire. Daily habitual FODMAP intake decreased progressively with increasing BMI, ranging from 7.9 (6.2-12.7) g/d in subjects with normal BMI and 6.6 (4.6-9.9) g/d in subjects with overweight to 5.8 (3.8-9.0) g/d in subjects with obesity (p = 0.038). After adjustment for age and gender, galactooligosaccharides (GOSs) were negatively correlated with body fat (Standardised Beta coefficient ß = -0.156, p = 0.006) and positively associated with insulin sensitivity (ß = 0.243, p = 0.001). This remained significant after adjustment for macronutrients, fibre, and physical activity (p = 0.035 and p = 0.010, respectively). In individuals with IGT, higher dietary GOS intake was associated with lower body fat and higher insulin sensitivity independent of macronutrients and fibre intake, calling for interventional studies to evaluate the effect of FODMAP intake in prediabetes.
Subject(s)
Glucose Intolerance , Insulin Resistance , Prediabetic State , Male , Humans , Middle Aged , Female , Prospective Studies , Cross-Sectional Studies , Oligosaccharides , Adipose Tissue , HexosesABSTRACT
Malignant peritoneal mesothelioma (MPeM) is a rare malignancy with historically poor prognosis. Recent research has started to reveal increasingly prevalent genetic mutations seen in this malignancy. Here, we report a case of complete clinical remission of unresectable, metastatic MPeM with systemic chemotherapy. Immunohistochemistry of our patient's malignant cytology sample showed loss of Breast Cancer Gene 1-associated protein-1 expression (BAP1). The patient had synchronous diagnoses of primary squamous cell carcinoma of the anus, benign schwannoma and meningioma. Following the completion of 18 cycles of pemetrexed and bevacizumab, the patient has remained in clinical remission for 8 months. We examine the unusual susceptibility of unresectable MPeM to systemic chemotherapy and attribute susceptibility to the molecular milieu created by mutations in multiple DNA repair pathways. We encourage increased testing for and analysis of mutations in DNA repair pathways to improve future treatment outcomes in this rare malignancy.
Subject(s)
Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Peritoneal Neoplasms , Humans , Bevacizumab/therapeutic use , Pemetrexed/therapeutic use , Lung Neoplasms/pathology , Mesothelioma, Malignant/drug therapy , Mesothelioma/drug therapy , Mesothelioma/genetics , Mesothelioma/diagnosis , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/pathology , Mutation , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/therapeutic use , Tumor Suppressor Proteins/geneticsABSTRACT
Introduction: COVID-19 restrictions and lockdown measures have led to impact on the mental health and social service delivery, including the rapid adoption of digital solutions to mental healthcare delivery in Singapore. This study aims to rapidly document the quantitative and qualitative impact of the pandemic restrictions on mental health and social services. Method: This descriptive mixed-methods study consisted of a survey arm and a qualitative arm. Providers and clients from eligible mental health organisations and social service agencies were recruited. The respondents completed a survey on changes to their service delivery and the extent of impact of the pandemic on their clients. In-depth interviews were also conducted with representatives of the organisations and clients. Results: There were 31 organisation representatives to the survey, while 16 providers and 3 clients participated in the in-depth interviews. In the survey arm, all representatives reported pivoting to remote means of delivering care during the lockdown. An increase in new client referrals and more domestic violence were reported from primary and community health partners respondents who made up 55.5% of health partners respondents. Three distinct response themes were recorded in the in-depth interviews: impact on clients, impact on service provision and impact on mental health landscape. Conclusion: Two key findings are distilled: (1) mental health and social services have been challenged to meet the evolving demands brought about by the pandemic; (2) more societal attention is needed on mental health and social services. The findings indicate a necessary need for extensive studies on COVID-19 that can inform policies to build a more pandemic-resilient nation.
Subject(s)
COVID-19 , Mental Health Services , Social Work , Humans , Singapore/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Mental Health Services/organization & administration , Social Work/organization & administration , Qualitative Research , Mental Health , Surveys and Questionnaires , SARS-CoV-2 , Female , Male , Pandemics , AdultABSTRACT
Negative symptoms in schizophrenia impose a significant burden with limited effective pharmacological treatment options. Recent trials have shown preliminary evidence for the efficacy of using intermittent theta burst stimulation (iTBS) in treating negative symptoms in schizophrenia. We aim to systematically review the current evidence of iTBS in the treatment of the negative symptoms of schizophrenia as an augmentation therapy. The study protocol was developed and registered on Prospero (registration ID: 323381). MEDLINE, EMBASE, Web of Science (Scopus), PsycINFO and Wan Fang databases were searched for sham-controlled, randomized trials of iTBS among patients with schizophrenia. The mean difference in major outcome assessments for negative symptoms was calculated. The quality of evidence was assessed using the Cochrane Risk of Bias Tool (version 1) and the GRADE system. Moreover, 12 studies including a total of 637 participants were included. Compared to sham treatment, the pooled analysis was in favor of iTBS treatment for negative symptoms (mean weight effect size: 0.59, p = 0.03) but not for positive symptoms (mean weight effect size: 0.01, p = 0.91) and depressive symptoms (mean weight effect size: 0.35, p = 0.16). A significant treatment effect was also observed on the iTBS target site left dorsal prefrontal cortex (mean weight effect size: 0.86, p = 0.007) and for stimulation with 80% motor threshold (mean weight effect size: 0.86, p = 0.02). Thus, our synthesized data support iTBS as a potential treatment for negative symptoms among patients with schizophrenia. However, the long-term efficacy and safety issues of iTBS in a larger population have yet to be examined.
ABSTRACT
Introduction: This study aimed to propose criteria for negative symptoms remission (NSR) in schizophrenia using the Brief Negative Symptom Scale (BNSS).Material and methods: 274 participants were assessed on the Positive and Negative Syndrome Scale (PANSS), BNSS and Social and Occupational Functioning Assessment Scale (SOFAS). Two criteria for NSR on the BNSS were proposed NSR based on the BNSS domains scores (NSRBNSS_DOMAINS) and NSR based on 5 key items of the BNSS (NSRBNSS_5ITEMS). A SOFAS score of 61 and above was considered as functional remission (FR). Logistic regressions were run to examine the association between FR and NSR. Receiver operating characteristic (ROC) curve analysis was performed for the NSR criteria on FR. Kappa agreement statistic was used to evaluate the agreement between the two NSR criteria.Results: Eighty-nine (32.5%) participants fulfilled NSRBNSS_DOMAINS criterion whereas 70 (25.6%) participants fulfilled NSRBNSS_5ITEMS criterion. The two NSR criteria had substantial agreement (Kappa statistic=0.797) with each other. Sixty-one (25.3%) participants were in FR. FR was significantly associated with NSR, irrespective of the criterion used. To predict FR, the Area Under the Curve for NSRBNSS_DOMAINS and NSRBNSS_5ITEMS were 0.761 (CI: 0.6960.826, p<0.001) and 0.723 (CI: 0.6560.790, p<0.001), respectively. Hence, both NSR criteria demonstrated a fair ability to discriminate between functional remitters and non-remitters. Conclusions: Depending on the setting and needs, clinicians and researchers might employ either the full BNSS or an abbreviated 5-item BNSS scale to identify NSR in schizophrenia. More research is needed to further examine the validity of these criteria in schizophrenia. (AU)
Introducción: El objetivo de este estudio fue proponer criterios para la remisión de síntomas negativos (NSR) en la esquizofrenia utilizando la Escala Breve de Síntomas Negativos (BNSS). Material y métodos: 274 participantes fueron evaluados con la Escala de Síndrome Positivo y Negativo (PANSS), BNSS y la Escala de Evaluación del Funcionamiento Social y Ocupacional (SOFAS). Se propusieron dos criterios para NSR en el BNSS: NSR basado en las puntuaciones de los dominios BNSS (NSRBNSS_DOMAINS) y NSR basado en 5 elementos clave del BNSS (NSRBNSS_5ITEMS). Una puntuación SOFAS de 61 y superior se consideró como remisión funcional (FR). Se realizaron regresiones logísticas para examinar la asociación entre FR y NSR. El análisis de la curva de características operativas del receptor (ROC) se realizó para los criterios NSR en FR. Se utilizó la estadística de concordancia Kappa para evaluar la concordancia entre los dos criterios de NSR.Resultados: Ochenta y nueve (32,5%) participantes cumplieron el criterio NSRBNSS_DOMAINS mientras que 70 (25,6%) participantes cumplieron el criterio NSRBNSS_5ITEMS. Los dos criterios de NSR tuvieron un acuerdo sustancial (estadística Kappa = 0,797) entre sí. Sesenta y un (25,3%) participantes estaban en FR. La FR se asoció significativamente con la NSR, independientemente del criterio utilizado. Para predecir la FR, el área bajo la curva para NSRBNSS_DOMAINS y NSRBNSS_5ITEMS fueron 0,761 (IC: 0,696-0,826, p <0,001) y 0,723 (IC: 0,656-0,790, p <0,001), respectivamente. Por lo tanto, ambos criterios NSR demostraron una capacidad adecuada para discriminar entre remitentes funcionales y no remitentes. Conclusiones: Dependiendo del entorno y las necesidades, los médicos e investigadores pueden emplear la BNSS completa o una escala BNSS abreviada de 5 ítems para identificar la NSR en la esquizofrenia. Se necesita más investigación para examinar a fondo la validez de estos criterios en la esquizofrenia. (AU)