ABSTRACT
BACKGROUND: There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/- systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. METHODS: We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high-quality systematic reviews. FINDINGS: We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS + HIPEC + systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy probably decreases all-cause mortality compared to CRS + systemic chemotherapy. For colorectal cancer, CRS + HIPEC + systemic chemotherapy probably results in little to no difference in all-cause mortality and may increase the serious adverse events proportions compared to CRS +/- systemic chemotherapy, but probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone. INTERPRETATION: The role of CRS + HIPEC in gastric peritoneal metastases is uncertain. CRS + HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS + systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. PROSPERO REGISTRATION: CRD42019130504.
Subject(s)
Colorectal Neoplasms , Cytoreduction Surgical Procedures , Hyperthermic Intraperitoneal Chemotherapy , Ovarian Neoplasms , Peritoneal Neoplasms , Randomized Controlled Trials as Topic , Stomach Neoplasms , Humans , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Female , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/therapy , Combined Modality Therapy , Hyperthermia, Induced/methodsABSTRACT
BACKGROUND: Patients with severe mental illness (SMI) and comorbid physical conditions were often associated with higher risks of mortality and hospital readmission. In this study, we aim to examine the association of cardiovascular metabolic risk factor measurements with risks of psychiatric readmissions among in-hospital patients with severe mental illness (SMI). METHODS: We collected the longitudinal information of laboratory investigations, blood pressure and body mass index (BMI) among in-hospital patients who had been diagnosed with schizophrenia, major depression disorder or bipolar disorder and with comorbid diagnosis of hypertension, hyperlipidemia or diabetes from Jan 2014 to Jan 2019. The primary outcome was time to first psychiatric readmission. Cox proportional hazard model was utilized to calculate the hazard risks (HR) of cardiovascular metabolic risk factors with psychiatric readmission. RESULTS: A total of 5,256 patients were included in the analysis. Compared to patients with normal blood parameters, patients with aberrant tests of high-density dyslipidemia (HDL) and diastolic blood pressure (DBP) during in-hospitalization period were associated with higher risks to first psychiatric readmission [ HR (Hazard Ratio), 1.37 95% Confidence interval (CI), 1.03-1.83 for HDL and HR, 1.32 (95% CI, 1.04-1.67])for DBP]. Compared to patients with optimal monitoring, patients with suboptimal monitoring of blood lipids and blood pressure during in-hospitalization period or recommended window period of cardiovascular disease (CVD) risk management were associated with higher risks to first psychiatric readmission. CONCLUSIONS: Aberrant cardiovascular metabolic blood test and blood pressure and missing measurements among in-hospital patients with SMI were associated with increased risks of psychiatric readmissions. This calls for more active screening and monitoring of CVD risk factors for those in-hospital patients in need.
Subject(s)
Depressive Disorder, Major , Mental Disorders , Hospitals , Humans , Mental Disorders/complications , Mental Disorders/diagnosis , Mental Disorders/epidemiology , Patient Readmission , Retrospective Studies , Risk FactorsABSTRACT
According to many studies, addressing the religious and spiritual (R/S) needs of patient's increase patient satisfaction. One area of interest is how patient self-perceived level of religiosity and spirituality (R/S) influences hospital needs. In this cross-sectional study, 195 inpatients at a non-faith-based academic hospital in Toledo, OH, USA completed surveys examining self-perceived R/S levels, as well as how those R/S levels impacted preferred services, conversations, and experiences in the hospital. Patients with no religious identity (self-identified as atheist, agnostic, or no religion) were less likely to report discussions about R/S needs than religious respondents (16.7% vs. 47.3%, p = 0.039). Nevertheless, such patients were just as likely to want a R/S conversation started by their healthcare provider (75% vs. 56%, p = 0.241). Those with no R/S identity were more likely to report presumed negative assumptions by hospital staff (25% vs. 0%, p < 0.001). Our data suggests that even for a nonreligious population, it is important to consider R/S needs.
Subject(s)
Religion , Spirituality , Cross-Sectional Studies , Health Personnel , Hospitals , HumansABSTRACT
BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients. METHODS: In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. RESULTS: The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235-57.671] and CD8+T [HR: 10.883; 95%CI: 3.277-36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients. CONCLUSIONS: Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient's disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients. TRIAL REGISTRATION: Prognostic Factors of Patients With COVID-19, NCT04292964 . Registered 03 March 2020. Retrospectively registered.
Subject(s)
CD4-Positive T-Lymphocytes/cytology , COVID-19/blood , SARS-CoV-2/immunology , Adult , Aged , CD8-Positive T-Lymphocytes/cytology , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Comorbidity , Female , Follow-Up Studies , Hospitalization , Humans , Lymphocyte Count , Male , Middle Aged , Pandemics , Patient Discharge , Prognosis , Retrospective Studies , SARS-CoV-2/geneticsABSTRACT
OBJECTIVE: The effect of lithium therapy during Electroconvulsive Therapy (ECT) on cognition and treatment effectiveness is unclear. In this study, we compare the cognitive and symptomatic outcomes of patients undergoing ECT with and without lithium in a large tertiary psychiatric institution. METHODS: Patients with predominantly manic or mixed episodes on lithium were propensity score matched with controls. Cognition was assessed using the Montreal Cognitive Assessment (MoCA), while severity of symptoms was assessed using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression-Severity Scale. Quality of life was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) and EuroQol Five Dimension (EQ-5D). Linear mixed-effects modeling and conditional logistic regression were conducted as appropriate. RESULTS: 87 patients were included in the study. There was no significant difference in cognitive and symptomatic outcomes for patients receiving ECT with or without lithium after 6 sessions of ECT. CONCLUSIONS: Concurrent lithium administration during the initial acute ECT course was not associated with differential cognitive or symptomatic outcomes. Lithium administration should not be a contraindication for appropriate acute ECT treatment in patients. Larger controlled studies to confirm these findings are warranted.
Subject(s)
Electroconvulsive Therapy , Lithium , Electroconvulsive Therapy/methods , Humans , Lithium/therapeutic use , Psychiatric Status Rating Scales , Quality of Life , Retrospective Studies , Singapore , Treatment OutcomeABSTRACT
OBJECTIVES: Switching of ECT electrode modality is commonly done in clinical practice but outcomes are unclear. We aimed to compare the clinical outcomes between ECT modality switchers and nonswitchers in a large tertiary psychiatric institution over 1 year. METHODS: Brief Psychiatric Rating Scale (BPRS), Montgomery-Åsberg Depression Rating Scale (MADRS) and Montreal Cognitive Assessment (MoCA) were used to assess symptoms and cognition. General linear regression was utilized to compare the change of BPRS or MADRS and MoCA score among switchers vs nonswitchers. RESULTS: 21.5% of 209 patients switched ECT. Baseline BPRS scores were lower among nonswitchers. Response rate in schizophrenia, depression and mania were higher for nonswitchers (69.6%, 81.35% and 84.8% respectively / 9.2 (SD 3.3) sessions) compared to switchers (53.8%, 0% and 66.7% respectively / 10.6 (SD 4.5) sessions). Most common ECT switches were Bifrontal (BF) to Bitemporal (BT) (schizophrenia), UB RUL (ultrabrief right unilateral) to BT (depression), and UB RUL to BT / BF (mania). There was no significant difference in the change of BPRS and MoCA scores between nonswitchers and switchers. However, there was significantly more improvement of MADRS scores among nonswitchers [adjusted mean ± SE: (-26.4 ± 2.8)] compared with switchers (-10.6) ±6.6). CONCLUSIONS: ECT switching was commonly done and may result in better or worse outcomes than not switching depending on diagnosis. Controlled trials are required to address this urgent clinical issue.
Subject(s)
Electroconvulsive Therapy , Schizophrenia , Humans , Mood Disorders/therapy , Pilot Projects , Schizophrenia/therapy , Schizophrenia, Treatment-Resistant , Treatment OutcomeABSTRACT
BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.
Subject(s)
Coronavirus Infections , Hospital Mortality , Natriuretic Peptide, Brain/analysis , Pandemics , Peptide Fragments/analysis , Pneumonia, Viral , Adult , Aged , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Humans , Male , Middle Aged , Mortality , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Predictive Value of Tests , Prognosis , Reference Values , Retrospective Studies , Risk Factors , SARS-CoV-2ABSTRACT
BACKGROUND: There is a lack of studies exploring associations between sleep and quality of life (QOL) among patients with schizophrenia who have limited exposure to antipsychotics and are in the early stage of their illness. Our study investigates the association of poor sleep quality and its components with domains of QOL amongst patients with first episode psychosis (FEP). METHODS: Data was utilized from a longitudinal study that examined sleep, smoking and alcohol use amongst patients with FEP who were enrolled in the Early Psychosis Intervention Programme (EPIP). The data were collected during the patients' baseline visit; i.e., within 3 months of admission into the EPIP. The Pittsburgh Sleep Quality Index (PSQI) was employed to examine sleep quality and its 7 components over the last month. The WHO quality of life-BREF was used to examine QOL and its 4 domains: physical health, psychological, social relationship, and environment. Clinical data such as Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores were obtained from a clinical data base. Linear regression analyses were conducted to investigate the association between poor sleep quality and the domains of QOL. RESULTS: Amongst the 280 recruited patients, 62.9% suffered from poor sleep quality. Poor sleep quality was associated with significantly lower scores in all domains of QOL, despite controlling for socio-demographics and clinical variables. Respondents with higher scores in subjective sleep quality and daytime dysfunction were associated with lower scores in the physical health and social relationship domain. Furthermore, respondents with higher scores in subjective sleep quality, sleep latency and daytime dysfunction were associated with lower scores in the psychological domain of QOL. Finally, respondents with higher scores in subjective sleep quality were associated with lower scores in the environment domain of QOL. CONCLUSIONS: Our findings highlight the importance of monitoring sleep quality amongst patients with FEP to improve their QOL. Clinical programmes should also pay more attention to sleep components in order to maintain satisfactory QOL amongst patients with FEP. Future interventions should focus on improving the relevant sleep components to ensure better treatment outcomes.
Subject(s)
Quality of Life , Schizophrenia/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep/physiology , Adult , Antipsychotic Agents/adverse effects , Female , Humans , Longitudinal Studies , Male , Middle Aged , Schizophrenia/drug therapy , Sleep Initiation and Maintenance Disorders/diagnosis , Young AdultABSTRACT
BACKGROUND: The goal of clinicians and healthcare workers providing treatment to patients with psychiatric disorders, has shifted over time from focusing on the symptoms alone towards functional improvement. In this study, we aimed to compare the subjective quality of life (QoL) among patients with schizophrenia spectrum disorders and major depressive disorder (MDD). METHODS: QoL scores were collected using 36-item Short Form Survey Instrument. QoL scores were compared between 203 outpatients with schizophrenia spectrum disorders and 185 outpatients with MDD using analysis of covariance. The Positive and Negative Syndrome Scale was administered to assess the severity of psychiatric symptoms among patients with schizophrenia and Personal Health Questionnaire-8 items was utilized to assess the severity of depressive symptoms among patients with MDD. The correlation coefficient (r) of socio-demographic factors and core psychiatric symptoms with QoL were analyzed using multiple linear regression. RESULTS: As compared to patients with MDD, patients with schizophrenia reported better health scores in all QoL subdomains, except for physical function (PF). Among patients with schizophrenia, old age was correlated with better mental health (MH, r = 0.35) and PF (r = 0.37). Compared to those of Chinese ethnicity, those of Malay, Indian and other ethnicity were correlated with worse PF (r = - 0.43 for Malays; r = - 0.30 for Indians and r = - 0.34 for other ethnicities). Longer duration of mental illness was correlated with worse MH (r = - 0.30), worse PF (r = - 0.38) and worse scores on role limitations due to physical health problems (RP, r = - 0.30). Among patients with MDD, older age was correlated with worse PF (r = - 0.33) and patients without comorbid physical illness reported less bodily pain (r = 0.45) and better general health (r = 0.34). Moreover, all psychiatric symptoms among patients with schizophrenia were negatively correlated with QoL, but the strength of the correlation was less than that between depressive symptoms and QoL among patients with MDD. CONCLUSION: Patients with schizophrenia generally reported better QoL as compared to patients with MDD. The correlates of QoL differed between patients with schizophrenia and patients with MDD. This study adds to the understanding of QoL among patients with mental illnesses and may aid in better management of these patients with different psychiatric diagnoses.
Subject(s)
Depressive Disorder, Major/psychology , Quality of Life/psychology , Schizophrenic Psychology , Adolescent , Adult , Aged , Comorbidity , Diagnostic Self Evaluation , Female , Humans , Linear Models , Male , Middle Aged , Outpatients/psychology , Severity of Illness Index , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor ß (TGFß) signaling. METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFß1 receptor kinase inhibitor), A-83-01 (TGFß type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h. The mesenchymal-epithelial transition was shown by down-regulation of mesenchymal genes (Slug, Zinc Finger E-box Binding Homeobox 1 ZEB1, integrin α5 ITGA5 and vimentin VIM) and up-regulation of epithelial genes (E-cadherin, Epithelial Cell Adhesion Molecule EpCAM, Zonula Occludens-1 ZO-1, occludin, deltaN p63 δNp63, Transcription Factor 4 TCF4 and Twist Family bHLH Transcription Factor TWIST), compared to untreated ADSCs. Cell morphology and stress fiber pattern were examined and the treated cells became less migratory in scratch wound closure assay. The formation of cell junction complexes was observed under transmission electron microscopy. Global gene expression using GeneChip® Human Genome U133 Array (Affymetrix) showed that the treatment up-regulated 540 genes (containing genes for cell cycle, cytoskeleton reorganization, chemotaxis, epithelium development and regulation of cell migration) and down-regulated 483 genes. CONCLUSION: Human ADSCs were transited to epithelial lineage by inhibiting GSK3 and TGFß signaling. It can be an adult stem cell source for epithelial cell-based therapy.
Subject(s)
Adipocytes/drug effects , Enzyme Inhibitors/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Glycogen Synthase Kinase 3/genetics , Mesenchymal Stem Cells/drug effects , Transforming Growth Factor beta1/genetics , Xenopus Proteins/genetics , Adipocytes/cytology , Adipocytes/metabolism , Adipose Tissue/cytology , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Antigens, CD , Cadherins/genetics , Cadherins/metabolism , Cell Movement/drug effects , Epithelial Cell Adhesion Molecule/genetics , Epithelial Cell Adhesion Molecule/metabolism , Gene Expression Regulation , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/metabolism , Humans , Integrin alpha5/genetics , Integrin alpha5/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Occludin/genetics , Occludin/metabolism , Primary Cell Culture , Pyrazoles/pharmacology , Pyridines/pharmacology , Pyrimidines/pharmacology , Snail Family Transcription Factors/genetics , Snail Family Transcription Factors/metabolism , Thiosemicarbazones/pharmacology , Transforming Growth Factor beta1/antagonists & inhibitors , Transforming Growth Factor beta1/metabolism , Tranylcypromine/pharmacology , Tretinoin/pharmacology , Valproic Acid/pharmacology , Vimentin/genetics , Vimentin/metabolism , Xenopus Proteins/antagonists & inhibitors , Xenopus Proteins/metabolism , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism , Zonula Occludens-1 Protein/genetics , Zonula Occludens-1 Protein/metabolismABSTRACT
Titanium (Ti) is a promising candidate biomaterial for an artificial corneal skirt. Antimicrobial peptide (AMP) immobilization may improve the bactericidal effect of the Ti substrate. In this study, we tested the bactericidal efficacy of a functionalized Ti surface in a rabbit keratitis model. A corneal stromal pocket was created by a femtosecond laser. The Ti films were then inserted into the pocket, and Staphylococcus aureus or Pseudomonas aeruginosa was inoculated into the pocket above the implant films. The corneas with Ti-AMP implants were compared with the corneas implanted with unprotected Ti by slit lamp observation and anterior segment optical coherence tomography (AS-OCT). Inflammatory responses were evaluated by bacterium counting, hematoxylin-eosin staining, and immunostaining. There was a lower incidence and a lesser extent of infection on rabbit corneas with Ti-AMP implants than on those with unprotected Ti implants. The bactericidal effect of AMP against S. aureus was comparable to that of postoperative prophylactic antibiotic treatment; hence, SESB2V AMP bound to the Ti implant provided functional activity in vivo, but its efficacy was greater against S. aureus than against P. aeruginosa. This work suggests that SESB2V AMP can be successfully functionalized in a rabbit keratitis model to prevent perioperative corneal infection.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Antimicrobial Cationic Peptides/administration & dosage , Corneal Transplantation/adverse effects , Pseudomonas Infections/prevention & control , Staphylococcal Infections/prevention & control , Surgical Wound Infection/prevention & control , Animals , Anti-Bacterial Agents/therapeutic use , Antimicrobial Cationic Peptides/therapeutic use , Rabbits , Slit Lamp , Titanium , Tomography, Optical CoherenceABSTRACT
Introduction: Repetitive transcranial magnetic stimulation (rTMS) is used for treatment-resistant major depressive disorder (MDD) and obsessive-compulsive disorder (OCD), but there are few studies on patient outcomes in Southeast Asia. In this study, we describe the clinical profile and outcome of patients with MDD and OCD treated with rTMS in Singapore. Method: A naturalistic retrospective study of 71 patients (inpatient and outpatient) who received rTMS treatment between June 2018 and April 2023 was conducted. The depressive and obsessive outcome rating scales used were clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS), Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Clinical Global Impressions-Severity (CGI-S) and self-rated Depression Anxiety and Stress Scale-21 (DASS-21). Results: Clinician-rated and self-rated mood and general condition improved significantly. MADRS mean score improved from 28.1 (standard deviation [SD] 7.3) to 20.7 (SD 10.1) (P<0.0001) (20.8% response rate/17% remission rate). CGI-S mean 4.6 (SD 0.8) improved to 3.3 (SD 1.2) (P<0.0001). DASS-21 total mean improved from 67.3 (SD 24.6) to 49.6 (SD 28.0) (P<0.0001). Y-BOCS mean score displayed a trend towards improvement from 30.1 (SD 7.5) to 27.2 (SD 6.9) (P=0.799). However, 44.4% of patients with OCD responded with a minimal 20% reduction in baseline Y-BOCS. Moreover, the subgroup of 35.8% of patients with less than 30 rTMS sessions had contributed disproportionately to nonresponse (85.7%). Patients who received rTMS treatment (>30 sessions) had a trend of larger improvement of MADRS score when compared to patients with (≤30 sessions) (9.4 [SD 9.7] versus 3.8 [SD 12.3] [P=0.078]). Conclusion: Response and remission rates for MDD and OCD suggest patients have a good response to rTMS treatment. Dosing longer rTMS sessions after an acute course helps to maximise effectiveness. Further research to determine predictors of outcome and characterise clinical features of late responders to target treatment more effectively is recommended.
Subject(s)
Depressive Disorder, Major , Obsessive-Compulsive Disorder , Transcranial Magnetic Stimulation , Humans , Obsessive-Compulsive Disorder/therapy , Transcranial Magnetic Stimulation/methods , Singapore , Depressive Disorder, Major/therapy , Male , Female , Retrospective Studies , Adult , Middle Aged , Treatment Outcome , Psychiatric Status Rating Scales , Young Adult , Depressive Disorder, Treatment-Resistant/therapyABSTRACT
This study compared the effects of implanting two interpenetrating polymer networks (IPNs) into rabbit corneas. The first (Implant 1) was based on PEG-diacrylate, the second (Implant 2) was based on PEG-diacrylamide. There were inserted into deep stromal pockets created using a manual surgical technique for either 3 or 6 months. The implanted corneas were compared with normal and sham-operated corneas through slit lamp observation, anterior segment optical coherence tomography, in vivo confocal scanning and histological examination. Corneas with Implant 1 (based on PEG-diacrylate) developed diffuse haze, ulcers and opacities within 3 months, while corneas with Implant 2 (based on PEG-diacrylamide) remained clear at 6 months. They also exhibited normal numbers of epithelial cell layers, without any immune cell infiltration, inflammation, oedema or neovascularisation at post-operative 6 month. Morphological studies showed transient epithelial layer thinning over the hydrogel inserted area and elevated keratocyte activity at 3 months; however, the epithelium thickness and keratocyte morphology were improved at 6 months. Implant 2 exhibited superior in vivo biocompatibility and higher optical clarity than Implant 1. PEG-diacrylamide-based IPN hydrogel is therefore a potential candidate for corneal inlays to correct refractive error.
Subject(s)
Biocompatible Materials , Corneal Transplantation , Polyethylene Glycols/chemistry , Animals , Corneal Topography , Rabbits , Tomography, Optical CoherenceABSTRACT
Electroconvulsive Therapy (ECT) is an effective treatment for mood and psychotic disorders but there is growing evidence of treatment resistant to ECT. Our study aimed to investigate the relationship between the number of previous illness episodes and the symptomatic improvement after acute ECT treatment. We conducted a retrospective naturalistic cohort analysis of patients' ECT registry data from March 2017 to February 2023. We categorized the number of previous illness episodes into "0-3â³ and ">3 episodes", paired T-tests were used to compare the changes in scores of clinical assessments, generalized linear models were used to analyze the association between the number of previous illness episodes and change in symptomatic scores. A total of 1137 patients were included for analysis. There was a significant global improvement in psychiatric symptoms (CGI) after 6 ECT treatments across five indications. We observed that compared to patients with less previous illness episodes, patients with more than 3 previous illness episodes had 30% lower chance of response to acute ECT treatment. Thus, our study suggests that use ECT earlier in the course of illness is associated with greater response and support offering ECT earlier in the disease course.
Subject(s)
Catatonia , Electroconvulsive Therapy , Psychotic Disorders , Humans , Mania , Depression , Retrospective Studies , Catatonia/therapy , Psychotic Disorders/therapy , Treatment OutcomeABSTRACT
OBJECTIVE: There is limited literature examining the effect of early electroconvulsive therapy(ECT) on the length of stay(LOS), especially for psychotic disorders. This study aimed to evaluate the association between early ECT and LOS in three main groups of patients with bipolar, depressive and primary psychotic disorders. METHOD: A retrospective descriptive analysis of 464 patients who received inpatient ECT from May 2017 to March 2021 in a large tertiary psychiatric institution was conducted. Early ECT was defined as ECT done before the mean number of days from admission to initiation of ECT by diagnosis. The main outcome measure was LOS, which was examined by diagnosis between the early and late ECT groups, using a linear regression model with adjustment factors chosen based on univariate analysis. RESULTS: A strong, significant association was found between early ECT and a shorter LOS (ß -28.3, 95 % CI -33.6 to -23.0, p < 0.001), even after accounting for adjustment factors. This association was consistent in all three diagnosis groups: bipolar disorders (ß -14.5, 95 % CI -20.1 to -9.0, p < 0.001), major depressive disorder (ß -18.2, 95 % CI -27.1 to -9.3, p < 0.001) and psychotic disorders (ß -39.0, 95 % CI -46.8 to -31.2, p < 0.001). There was no significant difference in the 30-day readmission rates between the early and late ECT groups trans-diagnostically. CONCLUSION: Early ECT is strongly associated with a shorter LOS across a range of diagnostic indications including major depressive disorder, bipolar disorder and schizophrenia. ECT can be considered earlier in treatment-decision algorithms and may offer a reduction in LOS.
Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Electroconvulsive Therapy , Psychotic Disorders , Humans , Depressive Disorder, Major/therapy , Bipolar Disorder/psychology , Length of Stay , Retrospective Studies , Psychotic Disorders/therapy , Psychotic Disorders/diagnosis , Treatment OutcomeABSTRACT
The Nucleosome Remodelling and Deacetylase (NuRD) complex represents one of the major chromatin remodelling complexes in mammalian cells, uniquely coupling the ability to "open" the chromatin by inducing nucleosome sliding with histone deacetylase activity. At the core of the NuRD complex are a family of ATPases named CHDs that utilise the energy produced by the hydrolysis of the ATP to induce chromatin structural changes. Recent studies have highlighted the prominent role played by the NuRD in regulating gene expression during brain development and in maintaining neuronal circuitry in the adult cerebellum. Importantly, components of the NuRD complex have been found to carry mutations that profoundly affect neurological and cognitive development in humans. Here, we discuss recent literature concerning the molecular structure of NuRD complexes and how the subunit composition and numerous permutations greatly determine their functions in the nervous system. We will also discuss the role of the CHD family members in an array of neurodevelopmental disorders. Special emphasis will be given to the mechanisms that regulate the NuRD complex composition and assembly in the cortex and how subtle mutations may result in profound defects of brain development and the adult nervous system.
Subject(s)
Mi-2 Nucleosome Remodeling and Deacetylase Complex , Nucleosomes , Animals , Humans , Mi-2 Nucleosome Remodeling and Deacetylase Complex/genetics , Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism , Chromatin , Chromatin Assembly and Disassembly , Mammals/metabolismABSTRACT
INTRODUCTION: Previous studies on the effects of electroconvulsive therapy (ECT) on cognition in schizophrenia have been inconclusive. This study aimed to identify factors that may predict cognitive improvement or deterioration in patients with schizophrenia after-ECT. MATERIALS & METHODS: Patients with schizophrenia or schizoaffective disorder with predominantly positive psychotic symptoms, who were treated with ECT at the Institute of Mental Health (IMH), Singapore, between January 2016 and January 2018, were assessed. Montreal Cognitive Assessment (MoCA), Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Function (GAF) were performed before and after ECT. Patients with clinically significant improvement, deterioration or no change in MoCA scores were compared on demographics, concurrent clinical treatment and ECT parameters. RESULTS: Of the 125 patients analysed, 57 (45.6%), 36 (28.8%) and 32 (25.6%) showed improvements, deterioration and no change in cognition respectively. Age and voluntary admission predicted MoCA deterioration. Lower pre-ECT MoCA and female sex predicted MoCA improvement. Patients showed improvements in GAF, BPRS and BPRS subscale scores on average, except for the MoCA deterioration group, who did not show statistically significant improvement in negative symptom scores. Sensitivity analysis showed that nearly half the patients (48.3%) who were initially unable to complete MoCA pre-ECT were able to complete MoCA post-ECT. CONCLUSIONS: The majority of patients with schizophrenia demonstrate improved cognition with ECT. Patients with poor cognition pre-ECT are more likely to see improvement post-ECT. Advanced age may be a risk factor for cognitive deterioration. Finally, improvements in cognition may be associated with improvements in negative symptoms.
Subject(s)
Electroconvulsive Therapy , Psychotic Disorders , Schizophrenia , Humans , Female , Schizophrenia/complications , Schizophrenia/therapy , Electroconvulsive Therapy/adverse effects , Psychotic Disorders/complications , Psychotic Disorders/therapy , Academies and Institutes , CognitionABSTRACT
BACKGROUND: The transdiagnostic effect of continuation/maintenance ECT (CM-ECT) across mood and psychotic disorders on hospital psychiatric readmission risk and total direct cost remains unclear. METHODS: A naturalistic retrospective analysis of 540 patients who received inpatient acute ECT treatment from May 2017 to Mar 2021 in a tertiary psychiatric institution. Patients were assessed with validated clinical rating scales pre-ECT and after the first 6 treatments of a course of inpatient acute ECT. After discharge, patients who continued with CM-ECT were compared with those not receiving CM-ECT using survival analysis of hospital readmission. Total direct cost (hospitalisation and ECT treatment cost) was also analysed. All patients were subjected to a standard post-discharge monitoring program with case managers checking in on the patients regularly after discharge and ensuring they were given an outpatient appointment within a month of discharge. RESULTS: Both cohorts had significant improvement in their rating scales scores after their first six 6 sessions of inpatient acute ECT. Patients who continued with CM-ECT after completing their inpatient acute ECT (mean number of acute ECT: N = 9.9, SD 5.3), had a significantly lower risk of readmission [adjusted hazard ratio of 0.68 (95 % CI: 0.49-0.94, p = 0.020)]. Patients who received CM-ECT also had a significantly lower average total direct cost compared to those who did not (SGD$35,259 vs SGD$61,337). For patients with mood disorders, the CM-ECT group had a significantly lower inpatient ECT cost, hospitalisation cost and total direct costs compared to those without CM-ECT. LIMITATIONS: The naturalistic study cannot prove a causal relationship between CM-ECT and reduced readmission and lower healthcare costs. CONCLUSION: CM-ECT is associated with lower readmission risks and lower total direct healthcare costs for the treatment of mood and psychotic disorders, especially for mood disorders.
Subject(s)
Bipolar Disorder , Electroconvulsive Therapy , Psychotic Disorders , Humans , Bipolar Disorder/psychology , Retrospective Studies , Patient Readmission , Outpatients , Aftercare , Patient Discharge , Psychotic Disorders/therapy , Psychotic Disorders/psychology , Treatment OutcomeABSTRACT
PURPOSE: To investigate the role of Tafazzin (TAZ) protein in regulating the proliferation of normal human conjunctiva epithelial cells and epithelial cells from pterygium tissue. METHODS: Conjunctiva epithelial cells were cultured in keratinocytes growth medium and treated with transformation growth factor ß (TGFß) to analyze the expression and translocation of TAZ protein by immunostaining and BrdU analysis. Immortalized conjunctiva epithelial cells (NHC) were treated with TGFß, targeting siRNA, TGFß receptor antibody or TGFß receptor inhibitor, to study the involvement of TAZ and TGFß signaling pathway in conjunctiva cell proliferation by cell adhesion assay. Conjunctiva tissues from a normal human eye and an eye with pterygium disease were collected for histological analyses and western blot to evaluate the TAZ protein expression in vivo. RESULTS: TAZ expression was upregulated in mitotic conjunctiva epithelial cells, proliferating conjunctiva epithelial cells, TGFß treated conjunctiva epithelial cells and human pterygium epithelium. TAZ siRNA induced less conjunctiva epithelial cell growth. Moreover, TGFß receptor antibody and TGFß receptor inhibitor rescued this anti-proliferative effect of TAZ siRNA. CONCLUSIONS: TAZ is involved in human conjunctiva epithelial cells proliferation via regulating TGFß signaling pathway.
Subject(s)
Conjunctiva/metabolism , Epithelial Cells/metabolism , Pterygium/genetics , Signal Transduction/genetics , Transcription Factors/genetics , Acyltransferases , Antibodies/pharmacology , Cell Adhesion/drug effects , Cell Proliferation/drug effects , Conjunctiva/cytology , Conjunctiva/drug effects , Epithelial Cells/cytology , Epithelial Cells/drug effects , Gene Expression Regulation/drug effects , Humans , Mitosis/genetics , Primary Cell Culture , Protein Transport/drug effects , Pterygium/metabolism , Pterygium/pathology , RNA, Small Interfering/genetics , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Receptors, Transforming Growth Factor beta/genetics , Signal Transduction/drug effects , Transcription Factors/metabolism , Transforming Growth Factor beta/pharmacologyABSTRACT
Case series on osteo-odonto keratoprosthesis (OOKP) published in English from 1950-June 2010 were identified in Medline/PubMed. Indications for surgery, visual acuity, anatomical survival, complication and repeat surgery rates were compared among the different studies. Our own case series is a retrospective review of all OOKP surgeries performed in our center from February 2004-July 2011. Eight case series including our own were systematically reviewed. Sample sizes ranged from 4-181 eyes. The most common indications for surgery were severe cases of Stevens-Johnson syndrome and thermal and chemical burns that were unamenable to other forms of surgery or had had previous surgical failure. Anatomical survival rate in all the studies was 87.8% (range 67-100%) at 5 years, and three studies showed survival rates of 81.0% (range 65-98%) at 20 years. Visual acuity was more than 6/18 in 52% (range 46-72%) of the eyes with OOKP surgery. The most common intraoperative complication was vitreous hemorrhage (0-52%) and the most common long-term blinding complication was glaucoma (7-47%). Endophthalmitis rates ranged from 2-8%. The most common repeat surgical procedure was mucosal trimming due to mucosal overgrowth at the optical cylinder and mucosal grafting for extrusion of the OOKP or mucosal ulceration. Of the available biological and synthetic keratoprosthesis, OOKP appears to be an excellent option for the treatment of end-stage corneal diseases.