Poor Adult Outcomes Research Articles

Differences in Diagnostic Characteristics and Outcomes in Adults with Malignancy-Associated and Non-Malignancy-Associated Hemophagocytic Lymphohistiocytosis (HLH)

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by life-threatening inflammation. In adults, roughly 50% of HLH manifests in association with an underlying malignancy (most commonly lymphoma), and the remaining cases are due to infection, autoimmune disease, late presentations of genetically-driven HLH, and sometimes multifactorial or idiopathic causes. Although the majority of prospective data for HLH are derived from children, survival outcomes for non-malignant causes of adult HLH (nmHLH) are thought to rival pediatric HLH; however, outcomes for malignancy-associated HLH (mHLH) appear to be substantially worse (~10-30% 5-year overall survival) in the literature. As diagnostic and prognostic models for HLH outcomes have primarily been constructed using pediatric data, attempts have been made to develop diagnostic indices applicable to adult HLH (particularly mHLH). Here, we summarize the clinical and laboratory characteristics of mHLH and nmHLH in a retrospective observational study, and evaluate the role for common diagnostic tools for adult HLH. Methods: Patients >18 years old, fulfilling at least five of the HLH-2004 diagnostic criteria with at least 3 months of follow-up (among survivors) were enrolled. All included patients received definitive HLH therapy, including cancer-directed therapy when appropriate, but those receiving only systemic steroids were excluded. Treatment-related HLH, such as HLH occurring with immune effector cell therapy or hematopoietic cell transplantation, was excluded. Clinical and laboratory parameters reflect the most recent values on or prior to diagnosis and treatment initiation. Differences between mHLH and nmHLH were assessed with two-tailed t-test or Wilcoxon test. Survival outcomes are estimated by Kaplan-Meier. Multivariate analysis was performed using Cox proportional hazards and compared using logrank test. Results: 42 adults were diagnosed with HLH requiring HLH-specific therapy (23 mHLH, 19 nmHLH) between 3/2016 and 3/2023 with a median age of 50 (range 21-75). Of the mHLH cases, 44% were due to T/NK cell lymphomas; 52% were B cell lymphomas including 26% Hodgkin. Of the nmHLH cases, most were due to infection (47%); while others were deemed to be idiopathic (26%) or genetic (16%). All patients with mHLH had fever (v 84% in nmHLH); 91% met cytopenia criteria (v 68%), and absolute neutrophil count (ANC), hemoglobin (Hgb), and platelet count (plt) were all statistically lower than in nmHLH (mean ANC 3.2 v 11.3; Hgb 7.8 v 8.5; plt 43 v 88; p<0.05). Mean soluble interleukin-2 (sIL2) level was significantly higher in mHLH (39,579 pg/mL v 18,484) after adjusting for a single outlier. All other HLH-2004 diagnostic parameters were not statistically different between mHLH and nmHLH, including ferritin and sIL2/ferritin index. All mHLH patients had an underlying lymphoma and met the optimized HLH inflammatory (OHI) index except a single patient with leukemia; 4 patients with nmHLH did not meet the OHI index. In 79% of patients, the HLH94 regimen was incorporated in the induction regimen; the remaining utilized chemotherapy or antibiotics, with and without adjunctive steroids. 4 cases proceeded to allogeneic transplantation. Relapse rates were high, with median relapse-free survival (RFS) being 37 days (23 v 47 days for mHLH and nmHLH, respectively); median overall survival (OS) was 96 days (86 v 149 days). RFS/OS was not statistically different between mHLH and nmHLH. Age was a significant predictor of OS but not RFS; no other diagnostic parameter was predictive, including degree of ferritin or sIL2 elevation. 13 patients were alive at the time of last follow-up (6 mHLH, 7 nmHLH). Conclusions: In this single center retrospective study, both mHLH and nmHLH requiring HLH-directed therapy demonstrated poor survival outcomes in adults. The degree of cytopenias and sIL2 elevation were more significant in mHLH in comparison with nmHLH. The OHI index identified all cases of lymphoma-associated HLH but neither ferritin nor sIL2 levels were predictive of survival. These data emphasize the need for therapeutic advances for management of adults with mHLH and nmHLH and continued optimization of diagnostic criteria for adult HLH.

Neurofilament light as a predictor of long- and short-term outcomes in critically ill children

PurposePlasma neurofilament light (NFL) is a marker of neuronal injury, associated with poor neurological outcomes in adults and neonates in a wide range of diseases. We sought to describe the associations between NFL at admission (NFLadm) and outcomes in a heterogenous cohort of critically ill children needing unplanned admission to the pediatric intensive care unit (PICU).Materials and methodsWe analysed prospectively collected biobank samples from critically-ill children with unplanned admissions to PICU. Samples were selected for survivors who had a 12-month follow-up with parent-completed Pediatric Quality of Life Inventory (PedsQL) scores as the primary outcome of interest.ResultsData from 52 children were analysed. The median NFL was 17.0 pg/ml (IQR 5.8–28.1). There were no significant associations between NFLadm levels and PedsQL (NFLadm-adjusted odds ratio 0.99, 95% CI 0.97, 1.02) at 12 months. NFL showed associations with outcomes at PICU discharge, such as change in functional status and need for organ support but interpretation is limited by sample size.ConclusionsAdmission NFL values were not associated with 12-month quality of life outcomes in a heterogenous cohort of children admitted to PICU.

Adult Mental Health, Substance Use Disorders, and Functional Outcomes of Children Resilient to Early Adversity.

Some children are unaffected by mental illness despite exposure to childhood adversity. These children are typically considered resilient. The objective of this study was to follow up such resilient children in adulthood to characterize mental health status, substance use, and functional outcomes. The analysis was based on the prospective, representative Great Smoky Mountains Study (N=1,420). Participants were assessed for psychiatric disorders and exposure to adversity with the structured Child and Adolescent Psychiatric Assessment interview up to eight times in childhood (ages 9-16; 6,674 observations). In total, 1,266 participants (86.3%) were followed up in adulthood at ages 25 and 30 to assess psychiatric disorders, substance use disorders, and functional outcomes. Seventy-five percent of the sample had met criteria for a psychiatric disorder or displayed subthreshold psychiatric problems by age 16. The number of adverse childhood experiences was strongly associated with childhood psychiatric status. Of children exposed to multiple adversities (N=650), 12.2% (N=63) did not display psychiatric problems. This group meets common definitions of childhood resilience. In adulthood, these individuals showing childhood resilience had greater risk of anxiety (risk ratio=2.9, 95% CI=1.0-9.1) and depressive (risk ratio=4.5, 95% CI=1.1-16.7) disorders, as well as worse physical health (means ratio=0.7, 95% CI=0.5-0.9) and financial or educational functioning (means ratio=0.6, 95% CI=0.5-0.7), compared with individuals exposed to fewer childhood adversities. These individuals showing childhood resilience did not have elevated risk for substance use disorders. Resilience to childhood adversity was uncommon. Individuals who appeared resilient in childhood were at risk for delayed poorer outcomes in adulthood. Public health efforts should prioritize minimizing early adversity exposure over promoting resilience.

Abstract 16446: The Emergency or Non-Referral Admission Was Associated With the Poor Outcome in Adults Hospitalized for the Treatment of Severe Coronary Sequelae Following Kawasaki Disease: Analysis of the Nationwide Claim-Based Dataset From Japanese Registry of All Cardiac and Vascular Diseases- Diagnosis Procedure Combination

Introduction: Kawasaki disease (KD), first reported in 1967, is a risk for ischemic heart disease if complicated by coronary sequelae. However, limited information is available regarding the follow-up status and outcomes of adults hospitalized for severe coronary sequelae resulting from KD. Hypothesis: We hypothesize that emergency or non-referral admission is related to poor outcomes in adults with KD hospitalized for severe coronary sequelae. Methods: Using a nationwide claim-based dataset from Japan, we analyzed adult patients (aged 15 and above) with KD diagnosed according to ICD10 codes, who were hospitalized for the treatment of coronary artery sequelae between April 2013 and March 2020. Treatment groups included acute coronary syndrome (ACS), catheter intervention (PCI), coronary artery bypass grafting (CABG), or the heart failure/arrhythmia group (patients treated for heart failure or arrhythmia, excluding those in the other three groups). ACS was diagnosed based on ICD-10 codes, while other diagnoses were determined using specific procedures. Results: The study comprised 850 patients, predominantly male (74%), with a median age of 34 years (IQR:20-43) and a median body mass index of 22.5 (IQR:20.0-25.4). They were divided into four groups: ACS (n=112), PCI (n=86), CABG (n=92), and the heart failure/arrhythmia group (n=560). The overall patient cohort had emergency admissions (27%) and non-referral admissions (13%), as well as heart failure (46%) and arrhythmia treatment (84%). Outcome measures included intensive care unit care (24%), median hospitalization duration of 4 days (IQR:3-13), total hospital deaths (1%), and median direct medical fees (4932600 Japanese yen). A higher percentage of emergency or non-referral admissions in the ACS or the heart failure/arrhythmia group correlated with unfavorable outcome parameters (p<.05). Conclusions: The present nationwide claim-based dataset study of adults hospitalized for severe coronary sequelae following KD, characterized by young males with normal BMI, showed that emergency or non-referral admission is associated with poor outcomes in the ACS and heart failure/arrhythmia groups. These findings support the importance of healthcare transition for such patients with KD.

RNA-Binding Protein RBM5 Plays an Essential Role in Acute Myeloid Leukemia By Activating the Oncogenic Protein HOXA9

Acute myeloid leukemia (AML) represents a type of malignant hematological disease that indicates poor outcomes in children and adults. HOXA9 overexpression is observed in 50-70% of human AML and positively correlates with poor patient outcomes. Leukemia subtypes with hallmark overexpression of HOXA9 include but are not limited to those carrying KMT2A gene rearrangements (KMT2A-r), NPM1c mutations, NUP98-fusions and EZH2 mutation. Accumulating genetic evidence also indicates that HOXA9 dysregulation is sufficient and necessary for leukemic transformation, and loss of function of HOXA9 and downstream pathways consequently impaired leukemia maintenance. Although HOXA9 is not an ideal direct candidate for therapeutic interventions, uncovering the novel regulators of HOXA9 might elucidate the HOXA9 regulation mechanism that could be exploited to identify novel therapeutic targets in HOXA9-driven leukemias. In this study, we performed genome-wide CRISPR/Cas9 screens in the HOXA9-endogenous reporter acute leukemia cells and unbiasedly identified that candidate genes are significantly enriched in RNA binding and RNA splicing regulation. An RBP protein, RBM5, was among the top essential genes. Initially, RBM5 was reported as a tumor suppressor gene in lung cancer. Thus far, the function of the encoding protein RBM5 in blood cancer remained largely unknown. To further test how RBM5 expression might correlate with AML development, we analyzed the public RNA-seq data from the TCGA clinical cancer sample datasets, RBM5 is highly expressed in AML, indicating a plausible role in AML oncogenesis. Functional validation by two individual sgRNAs against different exons of RBM5 confirmed the selectively survival essential of RBM5 in AML cell lines. Ectopic expression of sgRNA-resistant RBM5 cDNA ultimately rescued the cellular phenotype upon RBM5 loss. We utilized an alternative loss-of-function approach, RNA interference (RNAi), to further examine the functional requirement of RBM5, Two independent shRNAs targeted RBM5 mRNA in three AML cells lines. RBM5 loss significantly impaired cell growth, reduced colony numbers and triggered notable myeloid differentiation. We further transplant MOLM13 cells targeted with shRBM5 into NSG mice, and observed that RBM5 shRNAs-treated animals lagged progressively more behind with much less splenomegaly and reduced leukemia cell infiltration in bone marrow, spleen, and peripheral blood compared to the wild-type control, suggesting that RBM5 is required for AML progression in vivo. More importantly, Suppression of RBM5 in primary AML cells significantly reduced colony numbers and induced myeloid differentiation, as demonstrated by the maturation markers CD11b and CD14. In addition, the domain dropout CRISPR screen revealed that the DNA-binding domain C2H2 is required for the gene function. Integrative analysis further suggested that HOXA9 promises the direct transcriptional target of RBM5 as demonstrated by functional rescue assay and HOXA9 partially restore the gene transcriptional defect in RBM5 null leukemia cells. In summary, our innovative research reported that a new RNA-binding protein, RBM5, is required for the survival of AML through non-canonical transcriptional regulation via a complex regulatory mechanism. These data support RBM5 as a promising AML therapeutic target in future studies.

2 The Role of Flexibility in Learning in Autistic Teens

Objective:Autistic youth have impaired executive functioning (EF) and these challenges increase throughout adolescence. Deficits in EF have been associated with poor adult outcomes, decreased availability for learning, and linked to academic outcomes. Specifically, flexible problem solving is greatly reduced in autistic youth. We aim to investigate how flexibility contributes to learning in autistic youth and their typically developing peers.Participants and Methods:Participants included 44 teens with (n=22) and without (n=22) ASD. All teens were 14-18 years old (ASD M = 15.77, SD = 1.05; TD M = 15.73, SD = .96) with FSIQ 3 70 (ASD M = 105.92, SD= 16.17; TD M = 107.93, SD = 10.14). Teens with ASD met DSM-5 criteria for autism supported by the SCQ and/or ADOS-2. All participants completed the California Verbal Learning Task (Child or Third Edition) over zoom. Parents reported on their child’s flexibility skills on the Flexibility Questionnaire (FQ) which encompasses 5 subscales: routines/rituals, transitions, special interests, social flexibility, and generativity. Independent samples t-tests examined group differences in performance on the CVLT, measured by the long delay recall and learning slope. Bivariate correlations examined the relationship between learning and flexibility in the autistic group. Linear regression was used to determine how flexibility contributes to learning above and beyond age, gender, and diagnosis.Results:Autistic youth had significantly lower scores on the CVLT long-delay recall (t = 2.311, p = .026) and the learning slope (t = 1.186, p = .038) than their typically developing peers. Special interests on the FQ were related to both performance on the first trial of the CVLT (r = -.482 p = .023) and the short delay cued recall (r = -.469 p = .028) in the autistic group. Fewer transition related problems were predictive of higher scores on the CVLT above and beyond age, gender, and diagnosis (R2 = .366, B = - .088, p = .030).Conclusions:Learning was significantly lower in autistic teens compared to their typically developing peers. Additionally, autistic youth had a less steep learning slope than their typically developing peers. Autistic youth may focus on the first group of words only and don’t flexibly update their list to add new words as the trials go on. Autistic youth with more restricted interests have difficulty with the first trial due to the shifting required when starting a new unfamiliar task. Additionally, youth with a greater focus on their own interests had more difficulty on cued recall indicating that these youth may have had trouble shifting when prompted to use semantic categories. Fewer challenges with transitions were a significant predictor of learning above and beyond age, gender, and diagnosis. Previous research has shown large discrepancies between parent-report and laboratory-based tasks in autistic youth. This project highlights two unique measures of different modalities that show similarities in their ratings emphasizing their potential as good representations of overall skills. Future research should utilize a larger sample size to continue to examine the role of flexible problem solving in working memory and learning in autistic youth.

Clinical significance of serum CD155 levels in acute lymphoblastic leukemia patients

Abstract Background Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by poor outcomes in adults. Traditional diagnostic and prognostic markers take into account clinical data but also rely heavily on expensive and invasive tests such as bone marrow studies with cytogenetics. CD155 is an adhesion molecule that also modulates immune response in malignancy. Previous studies have shown that serum CD155 (sCD155) levels are higher in patients with malignancies, and have demonstrated a correlation between higher levels of sCD155 and poor outcomes. This study investigated the diagnostic and prognostic value of sCD155 in adult patients with acute lymphoblastic leukemia. Methodology 32 adult patients with acute lymphoblastic leukemia and 15 control patients were enrolled in this study. Clinical and outcome data were collected from patients and a blood sample from patients and controls was collected with ELISA testing for sCD155 levels. Results sCD155 was found to be significantly higher in patients than controls (P<0.05) and was significantly associated with bone marrow aspirate blast count. It was not associated with other clinical parameters including Sex, age, initial CBC parameter counts, presence of lymphadenopathy, presence of CNS infiltration, presence of Philadelphia chromosome, type of ALL, or risk stratification of ALL besides being associated with hepatosplenomegaly. ROC curve showed high sensitivity and specificity of sCD155 and Kaplan Meir curve showed a trend towards worse outcomes in patients with high sCD155 but it was not statistically significant. Conclusion sCD155 remains a promising marker for diagnosis of ALL but further studies are needed to confirm prognostic value.

Prospective longitudinal associations between adverse childhood experiences and adult mental health outcomes: a protocol for a systematic review and meta-analysis

BackgroundResearch cites a strong, dose–response relationship between adverse childhood experiences (ACEs) and poor adult mental health outcomes including anxiety, depression, post-traumatic stress disorder (PTSD), self-harm, suicidality, and psychotic-like experiences.AimTo systematically investigate the existence and strength of association between ACEs and adult mental health outcomes in prospective longitudinal studies. The review will focus on the outcomes: anxiety, depression, PTSD, self-harm, suicidal ideation, and psychotic-like experiences.MethodsTwelve electronic databases will be searched: Embase, PsycINFO, MEDLINE, and Global Health through the OVID interface. ProQuest will be used to search Public Affairs Information Service (PAIS), Dissertations and Theses, Sociology Database (including Sociological s and Social Services s), PTSDpubs (formerly The Published International Literature on Traumatic Stress (PILOTS) Database) and Applied Social Sciences Index and s (ASSIA). CINAHL, World Health Organisation (WHO) Global Index Medicus, and WHO Violence Info will also be searched. Eligible studies will be double screened, assessed, and their data will be extracted. Any disagreement throughout these processes will be settled by a third reviewer. If enough studies meet the criteria and the methodological quality of each study is sufficient, a meta-analysis will be conducted.AnalysisA narrative synthesis of included studies and the associations between ACEs and adult mental health will be completed. If the number of studies included per mental health outcome is two or more, a multi-level meta-analysis will be completed using odds ratio effect sizes as outcomes.DiscussionThis review will contribute to the existing body of literature supporting the long-term effects of ACEs on adult mental health. This review adds to previous reviews that have either synthesised cross-sectional associations between ACEs and mental health outcomes, synthesised longitudinal studies exploring the effect of ACEs on different physical and mental health outcomes or synthesised longitudinal studies exploring the effect of ACEs on the same mental health outcomes using different methods. This review aims to identify methodological weaknesses and knowledge gaps in current literature that can be addressed in future primary studies.Systematic review registrationThis protocol has been registered in PROSPERO (CRD42021297882).

Maternal Adverse Childhood Experiences and Young Adult Latino Children's Mental Health

Maternal adverse childhood experiences have been linked to a variety of negative health outcomes in young children; however, young adults and, specifically, young adult Latinos have been vastly understudied. This study investigates the intergenerational pathway between maternal adverse childhood experiences and behavioral health outcomes of their young adult children, as mediated through young adults' own adverse childhood experiences and maternal depression. Structural equation modeling was used to analyze data (in 2023) from mothers and their young adult children (n=398 dyads) enrolled in the Center for the Health Assessment of Mothers and Children of Salinas cohort, a primarily Latino agricultural sample. Maternal and young adult adverse childhood experiences were self-reported retrospectively during a visit at the age of 18 years (2018-2020). Young adult- and maternal-reported internalizing and maternal-reported externalizing behaviors were assessed at the age of 18 years with the Behavior Assessment for Children, second edition. Maternal depression was assessed during a visit at the age of 9 years (2010-2012) using the Center for Epidemiologic Studies Depression Scale. Maternal and young adult adverse childhood experiences were weakly but statistically significantly correlated (r=0.22). Maternal adverse childhood experiences were statistically significantly associated with maternal-reported youth internalizing symptoms (β=0.29; 95% CI=0.19, 0.38; p<0.001) and externalizing symptoms (β=0.24; 95% CI=0.14, 0.33; p<0.001) and marginally associated with youth-reported internalizing symptoms (β=0.08; 95% CI= -0.02, 0.18; p=0.13). Youth adverse childhood experiences and maternal depressive symptomatology mediated the associations between maternal adverse childhood experiences and young adult outcomes. Findings demonstrate the potential impacts of adversity across generations in Latino immigrant families, an understudied population. Understanding the mechanisms and factors associated with these pathways may lead to strategies that prevent poor mental health outcomes in young adults.

Long-term Outcomes in Orthogeriatric Co-management: a Literature Review.

Fragility fractures of the hip are one of the most important triggers of poor health outcomes in older adults. They often result in limitations in the ability of patients to care for themselves and mortality remains high. Orthogeriatric co-management may improve outcomes for this high-risk population. However, the impact on long-term results has not yet been definitively clarified. The purpose of this study was to present the influence of orthogeriatric co-management on mortality and self-care ability, as measured by the Barthel score, one year after hip fracture in people ≥60 years.A systematic literature search was performed in accordance with the process steps of identification, selection, and evaluation, with a systematic search of the MEDLINE, CINAHL Complete and Cochrane Library databases in the period from February to March 2022. Articles in English and German published between 2012 and 2022 were included. Twelve studies were finally used.Six studies demonstrated a statistically significant reduction in the one-year mortality rate. Only one of four studies evaluating self-care ability showed a significant improvement when the patient was treated on a specialised ward.Orthogeriatric co-management seems to be beneficial in positively influencing one-year mortality and self-care ability. In view of the heterogeneous results, the implementation of this care model can only be recommended to a limited extent.

Prevalence and factors associated with frailty and pre-frailty in the older adults in China: a national cross-sectional study.

Frailty increases poor clinical outcomes in older adults, the aim of this study was to investigate the prevalence and factors associated with frailty and pre-frailty in older adults in China. Data were obtained from the Sample Survey of the Aged Population in Urban and Rural China in 2015, which was a cross-sectional study involving a nationally representative sample of older adults aged 60 years or older from 31 provinces/autonomous regions/municipalities in mainland China. The frailty index (FI) based on 33 potential deficits was used to classify individuals as robust (FI < 0.12), pre-frail (FI ≧0.12 and <0.25) and frail (FI ≥0.25). A total of 208,386 older people were included in the study, and the age-sex standardised prevalence of frailty and pre-frailty among older adults in China was 9.5% (95% CI 9.4-9.7) and 46.1% (45.9-46.3) respectively. The prevalence of frailty and pre-frailty was higher in female than in male older adults, higher in rural than in urban older adults, and higher in northern China than in southern China. The multinomial analysis revealed similar risk factors for frailty and pre-frailty, including increased age, being female, living in a rural area, low educational attainment, poor marital status, living alone, difficult financial status, poor access to medical reimbursement, and living in northern China. Frailty and pre-frailty are very common among older adults in China and differ significantly between southern and northern China, men and women, and rural and urban areas. Appropriate public health prevention strategies should be developed based on identified risk factors in frail and pre-frail populations. The management of frailty and pre-frailty should be optimised according to regional and gender differences in prevalence and associated factors, such as strengthening the integrated management of chronic diseases, increasing reimbursement rates for medical costs, and focusing on vulnerable groups such as the disabled, economically disadvantaged, living alone and those with low literacy levels, in order to reduce the burden of frailty among older adults in China.

Predictors of mortality and poor renal outcomes in adults with diabetic ketoacidosis

Predictors of mortality and poor renal outcomes in adults with diabetic ketoacidosis

Associations between intrinsic capacity, functional difficulty, and fall outcomes among older adults in India

The construct of intrinsic capacity (IC) in the context of integrated care for older adults emphasizes functional assessment from a holistic perspective. It provides reliable and comparable insights on subsequent functioning and disability. Given the paucity of research on IC and health outcomes in low- and middle-income countries (LMICs), the present study examined the association of IC with geriatric conditions of functional limitations and multiple fall outcomes among older adults in India. The data used for analysis come from the first wave of the Longitudinal Aging Study in India (LASI), 2017–2018. The final sample size contains 24,136 older adults (11,871 males and 12,265 females) age 60 years or above. Multivariable binary logistic regression is employed to examine the association of IC and other explanatory factors with outcome variables of difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL), falls, fall injury, and multiple falls. Of the total sample, 24.56% of older adults were observed to be in the high IC category. The prevalence of ADL difficulty, IADL difficulty, falls, multiple falls and fall-related injury is estimated to be 19.89%, 45.00%, 12.36%, 5.49% and 5.57%, respectively. Older adults who reported high IC had a significantly lower prevalence of ADL difficulty (12.26% vs 22.38%) and IADL difficulty (31.13% vs 49.52%) than those who reported low IC. Similarly, a lower prevalence of falls (9.42% vs 13.34%), fall-related injury (4.10% vs 6.06%) and multiple falls (3.46% vs 6.16%) were reported among those who had high IC. After adjusting for a large number of confounders such as age, sex, health-related attributes and lifestyle behaviors, older adults with high IC had significantly lower odds of ADL difficulty [aOR: 0.63, CI: 0.52–0.76], IADL difficulty [aOR: 0.71, CI: 0.60–0.83], falls [aOR: 0.80, CI: 0.67–0.96], multiple falls [aOR: 0.73, CI: 0.58–0.96] and fall-related injury [aOR: 0.78, CI: 0.61–0.99]. That a high IC was independently associated with a lower risk of functional difficulty and fall outcomes in later life is of enormous value in predicting subsequent functional care needs. More specifically, the findings here imply that because regular IC monitoring can predict poor health outcomes in older adults, improvements in IC should be prioritized while formulating disability and fall prevention strategies.

Neuroticism and Stress in Older Adults: The Buffering Role of Self-Esteem.

Chronic stress is associated with accelerated aging and poor health outcomes in older adults. According to the Transactional Model of Stress (TMS), distress is experienced when one perceives the stressor, or threat, to outweigh the ability to cope. The experience of distress is correlated with trait neuroticism, which is associated with greater perceptions of stress and stress reactivity, as well as a tendency to engage in maladaptive coping strategies. However, as individual personality traits do not act in isolation, this study aimed to investigate the moderating role of self-esteem in the relationship between neuroticism and distress using a TMS framework. A total of 201 healthy older adults (Mage = 68.65 years) completed questionnaires measuring self-esteem, neuroticism, perceived stress, and positive coping. Greater neuroticism was significantly associated with less positive coping at low (b = -0.02, p < 0.001) and mean self-esteem levels (b = -0.01, p < 0.001), but not at high self-esteem levels (b = -0.01, p = 0.06). No moderating effect was found for perceived stress or overall distress. The results support the association between trait neuroticism and indices of stress and suggest a potential buffering effect of self-esteem in moderating the negative association between neuroticism and positive coping.

Brief Report: Detection of Urine Lipoarabinomannan Is Associated With Proinflammatory Innate Immune Activation, Impaired Host Defense, and Organ Dysfunction in Adults With Severe HIV-Associated Tuberculosis in Uganda.

The immunopathology of disseminated HIV-associated tuberculosis (HIV/TB), a leading cause of critical illness and death among persons living with HIV in sub-Saharan Africa, is incompletely understood. Reflective of hematogenously disseminated TB, detection of lipoarabinomannan (LAM) in urine is associated with greater bacillary burden and poor outcomes in adults with HIV/TB. We determined the relationship between detection of urine TB-LAM, organ dysfunction, and host immune responses in a prospective cohort of adults hospitalized with severe HIV/TB in Uganda. Generalized additive models were used to analyze the association between urine TB-LAM grade and concentrations of 14 soluble immune mediators. Whole-blood RNA-sequencing data were used to compare transcriptional profiles between patients with high- vs. low-grade TB-LAM results. Among 157 hospitalized persons living with HIV, 40 (25.5%) had positive urine TB-LAM testing. Higher TB-LAM grade was associated with more severe physiologic derangement, organ dysfunction, and shock. Adjusted generalized additive models showed that higher TB-LAM grade was significantly associated with higher concentrations of mediators reflecting proinflammatory innate and T-cell activation and chemotaxis (IL-8, MIF, MIP-1β/CCL4, and sIL-2Ra/sCD25). Transcriptionally, patients with higher TB-LAM grades demonstrated multifaceted impairment of antibacterial defense including reduced expression of genes encoding cytotoxic and autophagy-related proteins and impaired cross-talk between innate and cell-mediated immune effectors. Our findings add to emerging data suggesting pathobiological relationships between LAM, TB dissemination, innate cell activation, and evasion of host immunity in severe HIV/TB. Further translational studies are needed to elucidate the role for immunomodulatory therapies, in addition to optimized anti-TB treatment, in this often critically ill population.

Poor HIV-Related Outcomes In Older Adults Newly Diagnosed with HIV: A Four-Year Retrospective Analysis from A Single Site in Asia.

In resources limited settings, HIV-related services are often targeted to younger key populations though increasing reports have found adults ≥50 years now account for among the highest increase in new HIV diagnosis. We assessed the proportion of new HIV infections among older adults (≥50 years) and compared their socio-demographics, risk behaviours and HIV-related outcomes to newly diagnosed younger adults (<50 years). This retrospective analysis included all new HIV diagnosis from 2016-2019 at University of Malaya Medical Centre, Malaysia. Trends of HIV diagnosis was assessed using joinpoint regression analysis and characteristics between the older and younger adults were compared using χ2 test or Mann-Whitney U test. Kaplan-Meier analysis and log-rank test were used to compare the survival probability in both age groups. From a total of 594 new HIV diagnosis between 2016-2019, 11.5% (N=68) were among older adults with an annual percent increase of 5.50%. Older adults were more likely ethnic Indians (p<0.001), acquired HIV via heterosexual contact (p=0.001), had late presentation to care (p=0.003), and multimorbidity (p<0.001). Immunological responses after 12 months on ART were comparable in both groups. Older adults had a higher probability of death compared to younger adults (aHR 1.81, 95% CI 1.02-3.23, p=0.043) after adjusting for sex, mode of HIV transmission, late presentation to care, ART initiation and multimorbidity. Older adults diagnosed with HIV were associated with late care presentation and increased mortality. There is an urgent need to enhance uptake of HIV testing and linkage to care among older individuals in our setting.

Arrhythmia and COVID-19 in children.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection caused worldwide health problems, and coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization in March 2020. Cardiovascular complications of COVID-19 are not uncommon; among them, arrhythmia is considered a significant risk factor for poor health outcomes in adults. However, data are scarce on the arrhythmia of pediatric patients with SARS-CoV-2 infection, possibly due to their mild symptoms and low incidence of cardiovascular involvement. Multisystem inflammatory syndrome in children reportedly features increased cardiovascular involvement, but arrhythmic complications remain unidentified. Thus, here we review the epidemiology, manifestations, and outcomes of pediatric arrhythmia associated with COVID-19.

Sedentary Lifestyle Associated Hyperventilation Syndrome among Students of Karachi Quarantined Amidst COVID Out Break: A Cross Sectional Survey

Sedentary activity has been related to poor physical health outcomes in both adults and youth in previous studies. While there is growing evidence of a correlation between sedentary behavior and mental health outcomes, little is known about the risk of hyperventilation syndrome. Objective: To find out the prevalence of hyperventilation syndrome due to sedentary lifestyle among students of Karachi quarantined amidst COVID outbreak. Methods: A cross sectional online survey based questionnaire which included IPAQ (International physical activity questionnaire) to access sedentary behavior and Nijmegen questionnaire to rule out hyperventilation syndrome was used to collect data from 214 students from Karachi, Pakistan. Results: Out of the total 214 subjects, 128(59.5%) developed a sedentary behavior and 86(40%) were found non sedentary. These 128(59.5%) students were further assessed for hyperventilation out of which 114(53%) were found to be positive. Conclusions: The study concluded that 53% students of Karachi with sedentary lifestyle developed hyperventilation syndrome amidst COVID outbreak.

Longitudinal patterns of polysubstance use throughout adolescence: association with adult substance use and psychosocial outcomes controlling for preadolescent risk factors in a male cohort.

Inconsistent reports raise the question of the extent to which poor adult outcomes are associated with adolescent polysubstance use (PSU: alcohol, marijuana, other illicit drugs) above and beyond earlier risk factors. Early adulthood substance-related and psychosocial outcomes were examined in association with age 13 to 17 developmental patterns of PSU in boys from urban, low SES neighborhoods (N = 926). Three classes obtained by latent growth modeling described low/non-users (N = 565, 61.0%), lower risk PSU (later onset, occasional use, 2 ≤ substances; N = 223, 24.1%), and higher risk PSU (earlier onset, frequent use, 3 ≥ substances; N = 138, 14.9%). Preadolescent individual, familial and social predictors of adolescent PSU patterns were used as covariates. Adolescent PSU contributed to both age-24 substance-related outcomes (frequency of alcohol, drug use, and getting drunk, risky behaviors under influence, and use-related problems) and psychosocial outcomes (no high school diploma, professional or financial strain, ASP symptoms, criminal record) over and above preadolescent risk factors. Controlling for preadolescent risk factors, adolescent PSU made a more important contribution to adult substance use outcomes (increasing the risk by about 110%) than to psychosocial outcomes (16.8% risk increase). PSU classes showed poorer adjustment for all age-24 substance use, and for various psychosocial outcomes than low/non-users. Higher risk polysubstance users also reported poorer outcomes than their lower risk peers for most substance use outcomes, and for professional or financial strain and criminal record. Findings highlight the contribution of adolescent PSU in a dose-response fashion, over and above preadolescent risk factors, on both homotypic and heterotypic outcomes in early adulthood.

A case of hyponatraemia secondary to vitamin D deficiency

Hyponatraemia and Vitamin D deficiency are common conditions in older adults. Both conditions cause bone fragility and gait abnormalities, which are risk factors for falls and poor health outcomes in older adults. Vitamin D deficiency is a risk factor for osteoporosis and increases the risk for fragility fractures. Hyponatraemia, the commonest electrolyte abnormality, causes bone resorption and contributes to falls by impairing cognition and by causing gait abnormalities. Sodium homeostasis is complex and the syndrome of inappropriate antidiuretic hormone secretion (SIADH), a diagnosis of exclusion, is one of the most common causes of hyponatraemia. Instability is a feared geriatric syndrome, as falls can have devastating consequences for the older adult, leading to significant morbidity and mortality. Previous studies have shown that patients with hyponatraemia had a higher rate of vitamin D deficiency and, conversely, those with vitamin D deficiency had a higher rate of hyponatraemia. The exact pathophysiological mechanism behind this correlation is unclear but may involve bone derived hormone fibroblast growth factor 23 and the renin–angiotensin–aldosterone system. A case of an 83-year-old Asian female, who presented with an osteoporotic intertrochanteric femoral fracture following a fall, is presented. She was found to have chronic hyponatraemia and was subsequently diagnosed with SIADH due to vitamin D deficiency.