Increased IgA-mediated responses to the gut paracellular pathway and blood-brain barrier proteins predict delirium due to hip fracture in older adults.

Introduction: Delirium is accompanied by immune response system activation, which may, in theory, cause a breakdown of the gut barrier and blood-brain barrier (BBB). Some results suggest that the BBB is compromised in delirium, but there is no data regarding the gut barrier. This study investigates whether delirium is associated with impaired BBB and gut barriers in elderly adults undergoing hip fracture surgery. Methods: We recruited 59 older adults and measured peak Delirium Rating Scale (DRS) scores 2-3 days after surgery, and assessed plasma IgG/IgA levels (using ELISA techniques) for zonulin, occludin, claudin-6, ß-catenin, actin (indicating damage to the gut paracellular pathway), claudin-5 and S100B (reflecting BBB damage), bacterial cytolethal distending toxin (CDT), LPS-binding protein (LBP), lipopolysaccharides (LPS), Porphyromonas gingivalis, and Helicobacter pylori. Results: Results from univariate analyses showed that delirium is linked to increased IgA responses to all the self-epitopes and antigens listed above, except for LPS. Part of the variance (between 45-48.3%) in the peak DRS score measured 2-3 days post-surgery was explained by independent effects of IgA directed to LPS and LBP (or bacterial CDT), baseline DRS scores, and previous mild stroke. Increased IgA reactivity to the paracellular pathway and BBB proteins and bacterial antigens is significantly associated with the activation of M1 macrophage, T helper-1, and 17 cytokine profiles. Conclusion: Heightened bacterial translocation, disruption of the tight and adherens junctions of the gut and BBB barriers, elevated CDT and LPS load in the bloodstream, and aberrations in cell-cell interactions may be risk factors for delirium.

Reactivity to neural tissue epitopes, aquaporin 4 and heat shock protein 60 is associated with activated immune-inflammatory pathways and the onset of delirium following hip fracture surgery.

OBJECTIVES: Activation of the immune-inflammatory response system (IRS) and a deficiency in the compensatory immunoregulatory system (CIRS), neuronal injuries, and alterations in the glutamate receptor (GlutaR), aquaporin-4 (AQP4) and heat shock protein 60 (HSP60) are involved in delirium. Increased serum levels of neurofilament protein (NFP), glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) are biomarkers of neuronal injury. This investigation delineates whether elevated IgA/IgG reactivity against those self-antigens is associated with delirium severity and IRS activation. METHODS: We measured peak Delirium Rating Scale (DRS) scores on days 2 and 3 following surgery in 59 hip fractured older adults, and IgA and IgG antibody levels against MBP, NFP, GFAP and myelin oligodendrocyte glycoprotein (MOG), metabotropic glutamate receptors mGluRs 1 and 5, N-Methyl-D-Aspartate receptor (NMDAR) GLU1 (NR1) and GLU2 (NR2), APQ4 and HSP60. RESULTS: The IgA antibody levels against those self-antigens, especially GFAP, MBP and HSP60, strongly predict peak DRS scores on days 2 and 3 post-surgery. IgA reactivity against NMDAR and baseline DRS scores explained 40.6% of the variance in peak DRS scores, while IgA against NMDAR, IgG against MBP and age explained 29.1% of the variance in the IRS/CIRS ratio. There was no correlation between DRS scores and IgG directed against other self-antigens. CONCLUSIONS: Increased IgA levels against neuronal self-antigens, AQP4 and HSP60 are risk factors for delirium. Polyreactive antibody-associated breakdown of immune tolerance, IRS activation and injuries in the neuronal cytoskeleton, oligodendrocytes, astrocytes, glial cells, and myelin sheath are involved in the pathophysiology of delirium.

The Validity and Reliability of the Chula COVID-19 Psychosocial Home Isolation Evaluation Tool (CCPHIET).

BACKGROUND: The growing number of cases presenting with COVID-19 during the pandemic has led to a significant shortage of hospital beds. Many patients may not require hospitalization and can be clinically observed in home settings. We have identified a set of psychosocial factors that correlate with unsuccessful home isolation (HI), which in turn might negatively affect the transmission control in the community. Therefore, we developed the Chula COVID-19 Psychosocial Home Isolation Evaluation Tool (CCPHIET), a new screening tool for assessing the psychosocial suitability for HI. This study examines the CCPHIET's validity and reliability. METHODS: This cross-sectional descriptive study included COVID-19 patients who were deemed to be medically safe for 14-days of HI. The CCPHIET is comprised of eight clinical domains pertinent to HI behavioral compliance and risk for non-adherence. We explored its statistical validity and reliability and discussed the potential utility of this tool. RESULTS: A total of 65 COVID-19 patients participated in this study. Most patients (58.5%) were deemed to be appropriate candidates for HI according to the CCPHIET. The results of this study demonstrate that the CCPHIET has an acceptable content validity (IOC index > 0.5), moderate internal consistency (Cronbach's alpha = 0.611) and substantial to excellent inter-rater reliability (Intraclass correlation coefficient = 0.944, Cohen's kappa= 0.627). CONCLUSIONS: CCPHIET is an easy-to-use tool for assessing the psychosocial suitability of patients advised for at-home isolation with mild and asymptomatic COVID-19. Its implementation can assist clinicians in identifying and redirecting resources to patients at the highest risk for breaking quarantine and save on unnecessary, costly absolute institutional quarantine for those deemed to be psychosocially fit for full adherence.

Delirium due to hip fracture is associated with activated immune-inflammatory pathways and a reduction in negative immunoregulatory mechanisms.

BACKGROUND: The objectives of this study were to delineate whether delirium in older adults is associated with activation of the immune-inflammatory response system (IRS) as indicated by activation of M1, T helper (Th)1, and Th17 profiles, and/or by reduced activities of the compensatory immunoregulatory system (CIRS), including Th2 and T regulatory profiles. METHODS: We recruited 65 older adult patients with a low energy impact hip fracture who underwent hip fracture operation. The CAM-ICU and the Delirium Rating Scale, Revised-98-Thai version (DRS-R-98) were assessed pre-operatively and 1, 2 and 3 days after surgery. Blood samples (day 1 and 2) post-surgery were assayed for cytokines/chemokines using a MultiPlex assay and the neutrophil/lymphocyte ratio. RESULTS: We found that delirium and/or the DRS-R-98 score were associated with IRS activation as indicated by activated M1, Th1, Th17 and T cell growth profiles and by attenuated CIRS functions. The most important IRS biomarkers were CXCL8, interleukin (IL)-6, and tumor necrosis factor-α, and the most important CIRS biomarkers were IL-4 and soluble IL-1 receptor antagonist. We found that 42.5% of the variance in the actual changes in the DRS-R-98 score (averaged from day 1 to day 3) was explained by T cell growth factors, baseline DRS-R-98 scores and age. An increase in the NLR reflects overall IRS, M1, Th1, Th17, and Th2 activation. CONCLUSIONS: Post-hip surgery delirium is associated with activated IRS pathways and appears especially in patients with lowered CIRS functions.

Immune, Blood Cell, and Blood Gas Biomarkers of Delirium in Elderly Individuals with Hip Fracture Surgery.

BACKGROUND: Postoperative delirium in elderly people with hip fracture is associated with various adverse clinical outcomes. Nevertheless, the pathophysiological processes underpinning delirium have remained elusive. OBJECTIVES: The aim of this study was to explore the associations between delirium and its features and immune-inflammatory and blood gas biomarkers. METHODS: In this prospective study, we examined 65 patients who underwent a hip fracture surgery and assessed the Confusion Assessment Method for the Intensive Care Unit, Richmond Agitation-Sedation Scale (RASS), and Delirium Rating Scale Revised-98 (DRS-R-98) before and during 4 days after the surgery. Complete blood count and venous blood gas markers were obtained at the same time points. RESULTS: Delirium was observed in 19 patients and was accompanied by significantly increased pO2, number of white blood cells, neutrophil percentage, and neutrophil/lymphocyte ratio, and lower mean platelet volume (MPV) after adjusting for age, central nervous system (CNS) disease, blood loss during surgery, sleep disorders, and body mass index. The severity of delirium was associated with lowered number of platelets and MPV. Psychomotor disorders were associated with lower bicarbonate levels. The requirement of physical restraint of the patients was predicted by increased percentages of neutrophils and lymphocytes. Prior CNS disease was together with these biomarkers a significant predictor of delirium and severity of delirium. CONCLUSION: Delirium and psychomotor disorders following hip fracture and surgery may be caused by immune-inflammatory and oxidative stress pathways probably attributable to an aseptic inflammatory process.

The Psychosocial Assessment of Transplant Candidates: Internal Consistency, Interrater Reliability, and Content Validity of the Thai Version of the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT-Thai Version).

BACKGROUND: Standardized pretransplant psychosocial assessment is critically needed in Thailand to optimize medical and psychosocial outcomes after transplantation. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive and evidence-based tool that has demonstrated excellent reliability and predictive value in many psychosocial transplant studies. We translated the SIPAT into Thai and explored the validity and reliability of the SIPAT-Thai version among Thai transplant recipients. METHODS: We translated the original SIPAT into Thai following the World Health Organization's standard forward-backward translation procedure and then cross-sectionally assessed its validity and reliability in 110 Thai solid organ transplant candidates. The correlation between background data, total, and sectional scoring results of SIPAT-Thai were also analyzed. RESULTS: The SIPAT-Thai demonstrated moderate to good reliability, which was represented by internal consistency with a Cronbach α of .751 and interrater reliability with a κ value at 0.767. The index of item-objective congruence value was 0.94, indicating good the content validity. CONCLUSIONS: The SIPAT-Thai was systematically translated and shown to have acceptable validity and a moderate to good reliability index. The use of the SIPAT-Thai would provide a standardized, evidence-based, and a more systematic pretransplant psychosocial evaluation process for transplant candidates in Thailand.

Integration of mental health services into HIV healthcare facilities among Thai adolescents and young adults living with HIV.

INTRODUCTION: To assess the burden of depression, anxiety and suicidality; and to determine the impact of integrated mental health and HIV services on treatment outcomes among Thai adolescents and young adults living with HIV (AYHIV). METHODS: A multicentre prospective cohort study was conducted among AYHIV (15 to 25 years), and age- and sex-matched HIV-uninfected adolescents and young adults (HUAY). The Patient Health Questionnaire 9-item (PHQ-9) and Generalized Anxiety Disorder 7-item scales (GAD-7) were used as screening tools for depressive and anxiety symptoms respectively. History of lifetime and recent suicidal ideations/attempts were ascertained. Elevated mental health screening scores were defined as having either significant depressive symptoms (PHQ-9 ≥9), significant anxiety symptoms (GAD-7 ≥10) or suicidality (lifetime; and recent [within two weeks]). Participants meeting these criteria were referred to psychiatrists for confirmatory diagnosis and mental health services. Follow-up assessment with PHQ-9 and GAD-7 was performed one year after psychiatric referral. RESULTS: From February to April 2018, 150 AYHIV and 150 HUAY were enrolled, median age was 19.0 (IQR:16.8 to 21.8) years and 56% lived in urban areas. Among AYHIV, 73% had HIV RNA <50 copies/mL, and median CD4 count was 580 (IQR:376 to 744) cells/mm3 . At enrolment, 31 AYHIV (21%; 95%CI:14% to 28%) had elevated mental health screening scores; 17 (11%) significant depressive symptoms, 11 (7%) significant anxiety symptoms and 21 (14%) suicidality. Seven AYHIV (5%) had all three co-existing conditions. These prevalences were not substantially different from HUAY. Urban living increased risk, whereas older age decreased risk of elevated mental health screening scores (p < 0.05). All AYHIV with elevated mental health screening scores were referred to study psychiatrists, and 19 (13%; 95%CI: 8% to 19%) had psychiatrist-confirmed mental health disorders (MHDs), including adjustment disorder (n = 5), major depression (n = 4), anxiety disorders (n = 2), post-traumatic stress disorder (n = 1) and mixed MHDs (n = 4). One year after psychiatric referral, 42% of AYHIV who received mental health services demonstrated an absence of significant mental health symptoms from the reassessments, and 26% had an improved score. CONCLUSIONS: With the significant burden of MHDs among AYHIV, an integration of mental health services, including mental health screenings, and psychiatric consultation and referral, is critically needed and should be scaled up in HIV healthcare facilities.

A case of atypical tardive seizure activity during an initial ECT titration series.

Electroconvulsive therapy (ECT) has been used in this country for more than 70 years, is still the most effective treatment in all of psychiatry, and is considered a very safe procedure to have under general anesthesia. Although most patients tolerate this procedure very well without complications, prolonged and/or tardive seizures or even status epilepticus can develop, which is a rare but serious complication of ECT. Tardive seizures are typically associated with electroencephalographic evidence of ictal activity and motor manifestations of the tonic-clonic activity. Whereas there are instances of nonconvulsive status epilepticus after ECT, this is the first report of a patient developing autonomic and motor manifestations of a tardive seizure without electroencephalographic evidence of seizure activity during the initial titration series to establish seizure threshold for a course of ECT.