Electroencephalography as a tool for assessing delirium in hospitalized patients: A single-center tertiary hospital experience.

Background: Delirium is a prevalent yet underdiagnosed disorder characterized by acute cognitive impairment. Various screening tools are available, including the Confusion Assessment Method (CAM) and 4 A's test (4AT). However, the results of these assessments may vary among raters. Therefore, we investigated the objective use of electroencephalography (EEG) in delirium and its clinical associations and predictive value. Method: This cross-sectional observational study was conducted at Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan, Malaysia, from April 2021 to April 2023. This study included patients aged ≥18 years with a preliminary diagnosis of delirium. Demographic and clinical data were collected along with EEG recordings evaluated by certified neurologists to classify abnormalities and compare the associated factors between patients with delirium with or without EEG abnormalities. Results: One hundred and twenty patients were recruited, with 80.0% displaying EEG abnormalities, mostly generalized slowing (moderate to severe) and primarily generalized slowing (mild to severe), and were characterized by theta activity. Age was significantly associated with EEG abnormalities, with patients aged 75 and older demonstrating the highest incidence (88.2%). The CAM scores were strongly correlated with EEG abnormalities (r = 0.639, P < 0.001) and was a predictor of EEG abnormalities (P < 0.012), indicating that EEG can complement clinical assessments for delirium. The Richmond Agitation and Sedation Scale (RASS) scores (r = -0.452, P < 0.001) and Barthel index (BI) (r = -0.582, P < 0.001) were negatively correlated with EEG abnormalities. Additionally, a longer hospitalization duration was associated with EEG abnormalities (r = 0.250, P = 0.006) and emerged as a predictor of such changes (P = 0.030). Conclusion: EEG abnormalities are prevalent in patients with delirium, particularly in elderly patients. CAM scores and the duration of hospitalization are valuable predictors of EEG abnormalities. EEG can be an objective tool for enhancing delirium diagnosis and prognosis, thereby facilitating timely interventions.

Why was the study done? Confusion is frequently observed among patients presenting with various medical issues. There are several tests available to assist in assessment of these patients to see if the symptoms present constitute delirium. However, there may be occasions where identifying delirium is difficult despite the tools available. Electroencephalography (EEG) may be another option to assist medical personnel in diagnosing delirium. In this study, we examine the use of EEG in identification of delirium and its clinical associations. What did the researchers do? Our team studied the use of EEG in patients admitted for various medical issues with symptoms suggestive of delirium over a 2-year period. We collected relevant clinical data and performed EEG for each participant. What did the researchers find? A total of 120 participants were involved in the study. We observe abnormal EEG findings in 80% of patients with the majority showing generalized slowing. The factors associated with EEG abnormalities are advancing age, positive Confusion Assessment Method (CAM), and duration of hospitalization. What do the findings mean? As the service is not widely available, it would not be practical to substitute existing clinical assessment tools with EEG. However, we cannot discount the importance of identifying delirium due to its association with poor clinical outcomes. Therefore, for centers that may perform EEG, it may be used as an adjunct in diagnosing delirium should any doubts arise.

Disparate effects of sclerostin deletion on alveolar bone and cellular cementum in mice.

BACKGROUND: Cellular cementum (CC) includes cementocytes, cells suspected to regulate CC formation or resorption as osteocytes do in bone. Sclerostin (SOST) is a secreted negative regulator of Wnt/ß-catenin signaling expressed by osteocytes and cementocytes. Osteocyte SOST expression reduces bone formation. We investigated the functional importance of SOST in CC compared with alveolar bone (AB) using a Sost knockout (Sost-/-) mouse model to better understand the role of cementocytes in CC. METHODS: Mandibles and femurs of Sost-/- and wild-type (WT) mice were analyzed at 42 and 120 days postnatal (dpn). Maxillary first molars were bilaterally extracted at 42 dpn and both AB healing (maxillary molar sockets) and CC apposition (mandibular first molars) were examined at 21 days post-procedure. Analyses included micro-computed tomography, histology, and immunohistochemistry. RESULTS: Femur cortical and trabecular bone and mandibular bone volumes were similarly increased in Sost-/- versus WT mice at 42 and/or 120 dpn. In contrast to previous reports, CC was not increased by Sost-/- at either age. We conducted challenge experiments on AB and CC to explore tissue-specific responses. Post-extraction AB healing was improved by Sost deletion. In contrast, experimentally-induced apposition in molars failed to stimulate increased CC formation in Sost-/- versus WT mice. Wnt pathway markers AXIN2 and DKK1, which were increased in Sost-/- versus WT AB osteocytes, were unchanged in cementocytes. CONCLUSIONS: These data indicate CC is less responsive than AB to SOST deletion. Within the study limitations, these results do not support cementocytes as critical for directing increased CC formation. PLAIN LANGUAGE SUMMARY: Sclerostin is a protein known to inhibit bone formation, and removing sclerostin leads to more bone formation. Cementum is the thin layer that covers the surface of the tooth's root. Previous studies suggest that inhibiting sclerostin can similarly increase the amount of cementum. We wanted to compare the response of cementum and bone when sclerostin is absent to understand similarities and differences between these two tissues. In this study, we removed the Sost gene (the gene which produces sclerostin) in mice. We found that mice without sclerostin have more bone in their legs and jaws. Moreover, mice without sclerostin also healed better after tooth removal compared with normal mice. Surprisingly, unlike previous studies, we found that the amount of cementum was not different in mice without sclerostin compared with normal mice. Additionally, we challenged the cementum by taking out the opposing tooth to cause the first mandibular molar to move up by building more cementum. Even with this challenge, we found no difference in the amount of cementum in mice lacking sclerostin compared with normal mice. Therefore, we conclude here that cementum is less sensitive to the absence of sclerostin compared with bone.

Frailty-aware surgical care: Validation of Hospital Frailty Risk Score (HFRS) in older surgical patients.

Introduction: Frailty has an important impact on the health outcomes of older patients, and frailty screening is recommended as part of perioperative evaluation. The Hospital Frailty Risk Score (HFRS) is a validated tool that highlights frailty risk using 109 International Classification of Diseases, 10th revision (ICD-10) codes. In this study, we aim to compare HFRS to the Charlson Comorbidity Index (CCI) and validate HFRS as a predictor of adverse outcomes in Asian patients admitted to surgical services. Method: A retrospective study of electronic health records (EHR) was undertaken in patients aged 65 years and above who were discharged from surgical services between 1 April 2022 to 31 July 2022. Patients were stratified into low (HFRS <5), interme-diate (HFRS 5-15) and high (HFRS >15) risk of frailty. Results: Those at high risk of frailty were older and more likely to be men. They were also likely to have more comorbidities and a higher CCI than those at low risk of frailty. High HFRS scores were associated with an increased risk of adverse outcomes, such as mortality, hospital length of stay (LOS) and 30-day readmission. When used in combination with CCI, there was better prediction of mortality at 90 and 270 days, and 30-day readmission. Conclusion: To our knowledge, this is the first validation of HFRS in Singapore in surgical patients and confirms that high-risk HFRS predicts long LOS (≥7days), increased unplanned hospital readmissions (both 30-day and 270-day) and increased mortality (inpatient, 10-day, 30-day, 90-day, 270-day) compared with those at low risk of frailty.

Microglia-targeted inhibition of miR-17 via mannose-coated lipid nanoparticles improves pathology and behavior in a mouse model of Alzheimer's disease.

Neuroinflammation and accumulation of Amyloid Beta (Aß) accompanied by deterioration of special memory are hallmarks of Alzheimer's disease (AD). Effective preventative and treatment options for AD are still needed. Microglia in AD brains are characterized by elevated levels of microRNA-17 (miR-17), which is accompanied by defective autophagy, Aß accumulation, and increased inflammatory cytokine production. However, the effect of targeting miR-17 on AD pathology and memory loss is not clear. To specifically inhibit miR-17 in microglia, we generated mannose-coated lipid nanoparticles (MLNPs) enclosing miR-17 antagomir (Anti-17 MLNPs), which are targeted to mannose receptors readily expressed on microglia. We used a 5XFAD mouse model (AD) that recapitulates many AD-related phenotypes observed in humans. Our results show that Anti-17 MLNPs, delivered to 5XFAD mice by intra-cisterna magna injection, specifically deliver Anti-17 to microglia. Anti-17 MLNPs downregulated miR-17 expression in microglia but not in neurons, astrocytes, and oligodendrocytes. Anti-17 MLNPs attenuated inflammation, improved autophagy, and reduced Aß burdens in the brains. Additionally, Anti-17 MLNPs reduced the deterioration in spatial memory and decreased anxiety-like behavior in 5XFAD mice. Therefore, targeting miR-17 using MLNPs is a viable strategy to prevent several AD pathologies. This selective targeting strategy delivers specific agents to microglia without the adverse off-target effects on other cell types. Additionally, this approach can be used to deliver other molecules to microglia and other immune cells in other organs.

Influenza Virus Genomic Surveillance, Arizona, USA, 2023-2024.

Influenza viruses are constantly evolving and are therefore monitored worldwide in the hope to reduce the burden of disease by annual updates to vaccine recommendations. We conducted genomic sequencing of 110 influenza A and 30 influenza B viruses from specimens collected between October 2023 and February 2024 in Arizona, USA. We identified mutations in the hemagglutinin (HA) antigenic sites as well as the neuraminidase (NA) gene in our samples. We also found no unique HA and NA mutations in vaccinated yet influenza-infected individuals. Real-time genomic sequencing surveillance is important to ensure influenza vaccine effectiveness.

Health state utility values ranges across varying stages and severity of type 2 diabetes-related complications: A systematic review.

INTRODUCTION: Health state utility values (HSUV) for Type 2 diabetes mellitus (T2DM) complications are useful in economic evaluations to determine cost effectiveness of an intervention. However, there is a lack of reference ranges for different severity and stages of individual complications. This study aimed to provide an overview of HSUV decrement ranges for common T2DM complications focusing on different severity and stages of complications. METHOD: A systematic search was conducted in MEDLINE, SCOPUS, WEB OF SCIENCE. (Jan 2000 to April 2022). Included studies for HSUV estimates were from outpatient setting, regardless of treatment types, complication stages, regions and HRQoL instruments. Health Related Quality of Life (HRQoL) outcomes was to be presented as HSUV decrement values, adjusted according to social demographics and comorbidities. Adjusted HSUV decrements were extracted and compiled according to individual complications. After which, subsequently grouped into mild or severe category for comparison. RESULTS: Searches identified 35 studies. The size of the study population ranged from 160 to 14,826. The HSUV decrement range was widest for cerebrovascular disease (stroke): -0.0060 to -0.0780 for mild stroke and -0.035 to -0.266 for severe stroke; retinopathy: mild (-0.005 to -0.0862), moderate (-0.0030 to -0.1845) and severe retinopathy (-0.023 to -0.2434); amputation: (-0.1050 to -0.2880). Different nature of complication severity defined in studies could be categorized into: those with acute nature, chronic with lasting effects, those with symptoms at early stage or those with repetitive frequency or episodes. DISCUSSION: Overview of HSUV decrement ranges across different stages of each T2DM diabetes-related complications shows that chronic complications with lasting impact such as amputation, severe stroke with sequelae and severe retinopathy with blindness were generally associated with larger HSUV decrement range. Considerable heterogeneities exist across the studies. Promoting standardized complication definitions and identifying the most influential health state stages on HSUV decrements may assist researchers for future cost-effectiveness studies.

Interventions for cold homes: a rapid review of the health impacts.

BACKGROUND: Cold homes are associated with an increased risk of adverse health outcomes for older people. To mitigate this risk, homes need to be heated to an appropriate temperature. This review aims to identify interventions designed to improve heating and temperatures within homes and summarize its impact on health, health service utilization and cost effectiveness. METHODS: A rapid review was conducted. Studies assessing the effects of structural, financial, or behavioural interventions designed to improve home temperatures of residents aged 18+ years were eligible. Searches were carried out in four databases. A search for grey literature, and backward and forward citation searching were performed. Data were summarized in a narrative synthesis and mapped using EPPI-Reviewer and EPPI-Mapper software. RESULTS: Eighteen studies reported across 19 publications were included. Structural interventions were associated with better mental health and quality of life, a reduction in health service utilization, and improvements in satisfaction with internal home temperature, social interactions and financial difficulties. The impact on physical health outcomes varied by age, gender and long-term conditions. Evidence about the impact of behavioural interventions was inconsistent. CONCLUSION: Structural improvements to increase home temperatures may offer the potential to improve some aspects of health. However, the impact on physical health, including which groups are most likely to benefit, is unclear. Key gaps include the lack of evidence about the impact of financial interventions, and the impact of all types of interventions, on quality of life, mortality and costs.

What works to support carers of older people and older carers? an international evidence map of interventions and outcomes.

BACKGROUND: Unpaid carers of older people, and older unpaid carers, experience a range of adverse outcomes. Supporting carers should therefore be a public health priority. Our understanding of what works to support carers could be enhanced if future evaluations prioritise under-researched interventions and outcomes. To support this, we aimed to: map evidence about interventions to support carers, and the outcomes evaluated; and identify key gaps in current evidence. METHODS: Evidence gap map review methods were used. Searches were carried out in three bibliographic databases for quantitative evaluations of carer interventions published in OECD high-income countries between 2013 and 2023. Interventions were eligible if they supported older carers (50 + years) of any aged recipient, or any aged carers of older people (50 + years). FINDINGS: 205 studies reported across 208 publications were included in the evidence map. The majority evaluated the impact of therapeutic and educational interventions on carer burden and carers' mental health. Some studies reported evidence about physical exercise interventions and befriending and peer support for carers, but these considered a limited range of outcomes. Few studies evaluated interventions that focused on delivering financial information and advice, pain management, and physical skills training for carers. Evaluations rarely considered the impact of interventions on carers' physical health, quality of life, and social and financial wellbeing. Very few studies considered whether interventions delivered equitable outcomes. CONCLUSION: Evidence on what works best to support carers is extensive but limited in scope. A disproportionate focus on mental health and burden outcomes neglects other important areas where carers may need support. Given the impact of caring on carers' physical health, financial and social wellbeing, future research could evaluate interventions that aim to support these outcomes. Appraisal of whether interventions deliver equitable outcomes across diverse carer populations is critical.

DNA hypomethylation promotes the expression of CASPASE-4 which exacerbates inflammation and amyloid-ß deposition in Alzheimer's disease.

Alzheimer's disease (AD) is the sixth leading cause of death in the USA. It is established that neuroinflammation contributes to the synaptic loss, neuronal death, and symptomatic decline of AD patients. Accumulating evidence suggests a critical role for microglia, innate immune phagocytes of the brain. For instance, microglia release pro-inflammatory products such as IL-1ß which is highly implicated in AD pathobiology. The mechanisms underlying the transition of microglia to proinflammatory promoters of AD remain largely unknown. To address this gap, we performed reduced representation bisulfite sequencing (RRBS) to profile global DNA methylation changes in human AD brains compared to no disease controls. We identified differential DNA methylation of CASPASE-4 (CASP4), which when expressed promotes the generation of IL-1ß and is predominantly expressed in immune cells. DNA upstream of the CASP4 transcription start site was hypomethylated in human AD brains, which was correlated with increased expression of CASP4. Furthermore, microglia from a mouse model of AD (5xFAD) express increased levels of CASP4 compared to wild-type (WT) mice. To study the role of CASP4 in AD, we developed a novel mouse model of AD lacking the mouse ortholog of CASP4 and CASP11, which is encoded by mouse Caspase-4 (5xFAD/Casp4-/-). The expression of CASP11 was associated with increased accumulation of pathologic protein aggregate amyloid-ß (Aß) and increased microglial production of IL-1ß in 5xFAD mice. Utilizing RNA-sequencing, we determined that CASP11 promotes unique transcriptomic phenotypes in 5xFAD mouse brains, including alterations of neuroinflammatory and chemokine signaling pathways. Notably, in vitro, CASP11 promoted generation of IL-1ß from macrophages in response to cytosolic Aß through cleavage of downstream effector Gasdermin D (GSDMD). Therefore, here we unravel the role for CASP11 and GSDMD in the generation of IL-1ß in response to Aß and the progression of pathologic inflammation in AD. Overall, our results demonstrate that overexpression of CASP4 due to differential DNA methylation in AD microglia contributes to the progression of AD pathobiology. Thus, we identify CASP4 as a potential target for immunotherapies for the treatment and prevention of AD.

Determinants of multimorbidity in low- and middle-income countries: A systematic review of longitudinal studies and discovery of evidence gaps.

Multimorbidity-the coexistence of at least two chronic health conditions within the same individual-is an important global health challenge. In high-income countries (HICs), multimorbidity is dominated by non-communicable diseases (NCDs); whereas, the situation may be different in low- and middle-income countries (LMICs), where chronic communicable diseases remain prominent. The aim of this systematic review was to identify determinants (including risk and protective factors) and potential mechanisms underlying multimorbidity from published longitudinal studies across diverse population-based or community-dwelling populations in LMICs. We systematically searched three electronic databases (Medline, Embase, and Global Health) using pre-defined search terms and selection criteria, complemented by hand-searching. All titles, abstracts, and full texts were independently screened by two reviewers from a pool of four researchers. Data extraction and reporting were according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality and risk of bias assessment was performed using the Newcastle-Ottawa Scale for cohort studies. Data were summarized using narrative synthesis. The search yielded 1782 records. Of the 52 full-text articles included for review, 8 longitudinal population-based studies were included for final data synthesis. Almost all studies were conducted in Asia, with only one from South America and none from Africa. All studies were published in the last decade, with half published in the year 2021. The definitions used for multimorbidity were heterogeneous, including 3-16 chronic conditions per study. The leading chronic conditions were heart disease, stroke, and diabetes, and there was a lack of consideration of mental health conditions (MHCs), infectious diseases, and undernutrition. Prospectively evaluated determinants included socio-economic status, markers of social inequities, childhood adversity, lifestyle behaviors, obesity, dyslipidemia, and disability. This review revealed a paucity of evidence from LMICs and a geographical bias in the distribution of multimorbidity research. Longitudinal research into epidemiological aspects of multimorbidity is warranted to build up scientific evidence in regions beyond Asia. Such evidence can provide a detailed picture of disease development, with important implications for community, clinical, and interventions in LMICs. The heterogeneity in study designs, exposures, outcomes, and statistical methods observed in the present review calls for greater methodological standardisation while conducting epidemiological studies on multimorbidity. The limited evidence for MHCs, infectious diseases, and undernutrition as components of multimorbidity calls for a more comprehensive definition of multimorbidity globally.

The influence of social media on student nurses: A systematic mixed-studies review.

BACKGROUND: Social media usage has been ubiquitous and extensively integrated into the daily lives of student nurses. However, there exists a paucity of understanding regarding the influence of social media on student nurses' personal and professional development. OBJECTIVE: To examine the influence of social media on student nurses' personal and professional values. DESIGN: A systematic mixed-studies review. METHODS: English language published studies were sourced from hand searches and seven electronic databases (PubMed, CINAHL, Embase, PsycINFO, ProQuest Dissertation and Theses Global, Scopus, and Web of Science) from the inception of each database to January 2023. RESULTS: Twenty-six studies were included. Two main themes and eight subthemes were derived through thematic synthesis. The first main theme, Shaping Student Nurses into Nurses, included four subthemes: 1.1) Personal Development, 1.2) Professional Development, 1.3) Advocacy, and 1.4) Networking. The second main theme, Repercussions of Social Media Usage, included four subthemes: 2.1) Frustrations, 2.2) Discriminative Feelings, 2.3) Compulsive feelings, and 2.4) Consequences of Inappropriate Usage. CONCLUSION: The ubiquitous utilization of social media among the current generation of student nurses, for personal, educational, and professional purposes, has precipitated transformative effects conducive to their holistic development. Notwithstanding the potential perils associated with privacy violation and inappropriate usage, educational institutions can develop pedagogical strategies and guidelines in collaboration with healthcare institutions and professionals, aimed at the incorporation of social media within the educational curricula and the prospective workplace environments of student nurses.

Psychological Effects on Self-Medication During the Pandemic COVID-19 in WP Labuan: A Development of Questionnaire And Pilot-Testing

Introduction: Self-Medication, which is a practice to self-treat using medicine without consulting a medical practitioner or a doctor, is a common practice and the Pandemic Covid-19 may have caused people to resort to self-medication in order to reduce the infectivity of the Covid-19. Objective: To validate and develop an instrument in Bahasa Melayu to assess the psychological distress and self-medication during pandemic Covid-19 in WP Labuan. Methods: A pilot study was conducted among 160 participants in WP Labuan. Reliability testing on internal consistency and content validity was performed on the adapted Covid-19 Peritraumatic Distress Index (CPDI) as well as domain on knowledge, practice and attitude of self-medication. Result: A panel of seven experts evaluated the research instrument for content validity and it was found to have good content item validity. The CPDI domain showed good internal consistency of Cronbach’s Alpha of 0.919. The mean (SD) CPDI score of the respondents in WP Labuan was 32.55 (15.98). 64.2% of the respondents experienced psychological distress. The variable for Area (town/countryside) was found to be statistically significant (p<0.05) to be associated with selfmedication during the pandemic. Conclusion: The instrument established sound reliability and validity and therefore, can be an effective tool for assessing psychological distress and self-medication in the Malaysian population. (AU)

Paradoxical Hyperreflexia in a Patient With Classic Guillain-Barré Syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) is a rare entity with characteristic features, including progressive ascending paralysis. Patients typically present with progressive symmetrical weakness with areflexia in bilateral lower extremities, which can be confounded by psychiatric comorbidities. This case is unusual in that the patient had paradoxical hyperreflexia and normal CSF protein levels during her initial presentation, later confirmed to be GBS. CASE PRESENTATION: Here, we describe the case of a young female with bipolar disorder who presented to the hospital with complaints of week-long bilateral lower leg weakness that started abruptly about a month after an episode of multiple stools of bloody diarrhea. The initial neurological exam revealed 4/5 bilateral lower extremity strength and near global areflexia, excluding a 3+ right patellar reflex, and CSF studies returned normal CSF protein levels.  Based on the clinical presentation of worsening ascending paralysis, electromyography (EMG) findings, and nerve conduction studies (NCS) consistent with an axonal and demyelinating neuropathy, we diagnosed her with the classic form of Guillain-Barré syndrome with paradoxical hyperreflexia. Imaging results, laboratory findings, treatment decisions, and outcomes of this case are presented.