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To identify changes in emergency department (ED) use in Houston, TX during the mid-summer Hurricane Beryl-induced power outage to inform future targeted public health interventions.
Methods
Syndromic surveillance system ED visit daily counts for total visits, heat-related illness, carbon monoxide poisoning, acute cardiac condition, stroke, dialysis, and medication refills post-hurricane were statistically compared to the 2 weeks prior and plotted alongside the percentage of the population with power outage.
Results
Daily ED visits post-storm were statistically higher (P< 0.05) than the 2 weeks prior for total visits and acute cardiac events (Day 1, 2); heat-related illness (Day 1-3); dialysis (Day 0-3); and carbon monoxide poisoning and medication refill (Day 1-9).
Conclusions
While 50% of the city experienced power outages from high winds, total ED visits, acute cardiac events, and heat-related illness were statistically higher in the first 3 days after Beryl than expected. Houston developed targeted messaging to mitigate these events in future disasters.
Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition affecting 1 in 7 Australians ≥ 40 years(1) and is the third leading cause of death worldwide(2). COPD exacerbations are the leading cause of preventable hospital admission in Australia(3), with viral and bacterial infections being the primary cause. The gut and lungs share a mucosal immune system known as the gut-lung axis(4). The gut contains the bodies largest community of microorganisms, known as the gut microbiota, and disruption to the gut microbiota is implicated in chronic diseases such as Inflammatory Bowel Disease, obesity and type 2 diabetes(5). Dietary intake modulates the gut microbiota via several pathways. Importantly, gut microbiota produce metabolites via digestion, and these microbial metabolites can modulate the immune system, and exert both beneficial and detrimental effects systemically. Therefore, we aimed to assess the potential of gut-derived microbial metabolites to modify immune cell responses to stimuli known to induce COPD exacerbations. Gut microbial metabolites, including seven tryptophan metabolites, and one secondary bile acid were selected by literature review. In control adults (n = 8), peripheral blood mononuclear cells (PBMC) were isolated via Lymphoprep™ density gradient centrifugation and seeded 2 × 106 cells/mL. Metabolite dose-curves (1–100 μM) were generated to determine optimal concentration. Post-3-hour metabolite incubation, PBMCs were stimulated with either lipopolysaccharide (LPS) (24 hr) or influenza-A (H1N1) (48 hr). PBMC production of anti-viral and anti-inflammatory cytokines IFN-γ, IL-6, TNF-α and IL-1β was assessed by DuoSet® ELISA. Cell viability post-metabolite incubation was confirmed via MTT assay. Cytokine dose-curves following metabolite treatment and stimulation were produced (n = 4/metabolite). Metabolite concentrations were selected based on reduction of LPS-induced TNF-α and IL-1β secretion, reduced influenza-A-induced IL-6 secretion, and increased influenza-A-induced IFN-γ secretion. Optimal metabolite concentrations included: secondary bile acid lithocholic acid (1 μM), and tryptophan metabolites nicotinamide (5 μM), indole-3-acetic acid (1 μM), kynurenic acid (5 μM), 3-hydroxyanthranilic acid (10 μM). Tryptophan metabolites cinnabarinic acid was dose-dependently pro-inflammatory, and tryptamine and 2-picolinic acid had no effect. MTT assays (n = 3/metabolite) found metabolites were not cytotoxic at the concentrations tested. These data show that gut-derived microbial metabolites modify immune cell responses to infection. These findings will inform further research which will examine the effects of microbial metabolites in immune cells from adults with COPD and assess the role of the gut microbiota in infectious COPD exacerbations.
Immunoceuticals are natural products used to enhance immunity(1). Lactoferrin (Lf) is an immunoceutical supplement which has been shown to have immunomodulatory properties(2). The immuno-protective functions of Lf are of interest in older adults, as immune function declines with increasing age(3). This study examined the effects of oral Lf supplements on ex vivo immune cell responses to respiratory virus infection, circulating immune cell subsets, and systemic inflammation. Healthy adults (≥ 50 years old, n = 103) were randomised to High dose (600 mg/d) or Low dose (200 mg/d) Lf or placebo, in a 4-week, parallel, double-blinded trial. Ex vivo cytokine release of interferon (IFN)-α2, IFN-γ, interleukin (IL)-6 and tumour necrosis factor (TNF)-α) in isolated peripheral blood mononuclear cells (PBMCs) infected with rhinovirus A-16 (RV-16) and influenza A virus (H1N1), circulating immune cell subsets, and plasma IL-6, C-reactive protein (CRP) and TNF-α were assessed and analysed by multivariate regression models. Analysis included 102 participants at baseline, and 96 participants at follow up. High dose Lf decreased RV-16-induced IL-6 (p = 0.001 vs placebo), and increased RV-16-induced IFN-α2 (p = 0.041, vs low dose) in PBMCs. H1N1-induced IL-6 decreased following Low dose Lf and placebo (p = 0.009, p = 0.021 vs baseline), while High dose Lf increased H1N1-induced TNF-α (p = 0.023 vs low dose, p = 0.049 vs placebo) and decreased H1N1-induced IFN-γ (p = 0.032 vs baseline) in PBMCs. High dose Lf increased total T cells (p = 0.031), CD4+ T cells (p = 0.028) and BDCA-1 cells (p = 0.016), and decreased γδ T cells (p = 0.046) compared to placebo, while Low dose Lf reduced circulating neutrophils (p = 0.044), natural killer cells (p = 0.045), activated CD8+ T cells (p = 0.031), and γδ T cells (p = 0.031) compared to placebo. High dose Lf decreased plasma IL-6 and CRP compared to Low dose Lf (p = 0.004, p = 0.026), but not placebo. There was no difference between intervention groups in the number of adverse events. This 4-week trial in healthy, older adults showed both High and Low dose Lf interventions enhanced ex vivo immune cell responses to respiratory virus infection, with decreased pro-inflammatory cytokine and increased anti-viral cytokine release observed. Low dose Lf reduced the frequency of both pro-inflammatory and cytotoxic innate immune cells, while increased T-cell populations following High dose Lf indicate improved cellular adaptive immune responses which provide protection against infection, tumours and chronic disease. Effects on systemic inflammation were only seen following High dose Lf, suggesting higher doses of lactoferrin are required to address this outcome. Oral lactoferrin supplements are generally regarded as safe, and appear to have immunoceutical benefits in healthy, older adults.
Obesity affects > 30% of Australian adults and is a rapidly growing health concern, on both national and global scales(1). Obesity is associated with an excess of nutrients in the circulation, particularly saturated fatty acids which are thought to contribute to chronic low grade systemic inflammation(2). People with obesity are also known to have an increased risk of severe respiratory viral disease, highlighted by both the recent SARs-CoV-2 pandemic and the 2009 Influenza A H1N1 pandemic(3,4). Previously, our group has shown that consuming a meal high in saturated fatty acids can increase activation of the NLRP3 inflammasome in the airways of adults with asthma(5), while others have shown increased NLRP3 activation is implicated in the pathogenesis of severe inflammation observed during the peak of IAV-induced lung disease(6). We sought to determine the impact of dietary saturated fatty acids on the immune response of airway epithelial cells to Influenza A Virus, and to examine if this is a factor for severe respiratory viral disease outcomes. We pre-treated BCI-NS1 cells, an airway epithelial cell line, with either media or physiologically relevant concentrations of the saturated fatty acids, palmitic acid (250 μM), stearic acid (1000 μM) or pentadecanoic acid (50 μM) for 3 hours at 37°C (5% CO2). Cells were then washed with phosphate buffered saline and infected with Influenza A (H1N1pdm09) (Multiplicity of Infection 0.5) and incubated for 48 hours at 37°C (5% CO2). Cell culture supernatants were collected and assayed by Enzyme-Linked Immunosorbent assay for Interleukin (IL)-6 and Interferon (IFN)-λ. Pre-treatment with saturated fatty acids reduced IFN-λ production of virus infected cells (following palmitic acid pre-treatment IFN-λ was 7.9 pg/mL ± 4.5 (SD); n = 6, p < 0.01, following stearic acid pre-treatment IFN-λ was 10.3 pg/mL ± 7.7 (SD); n = 6, p < 0.01, and following pentadecanoic acid pre-treatment IFN-λ was 11.3 pg/mL ± 8.1 (SD); n = 6, p < 0.01, compared to cells pre-treated with media alone (42.7 pg/mL ± 14.0 (SD); n = 6). IL-6 production was unchanged by pre-treatment with saturated fatty acids prior to H1N1pdm9 infection. As previously mentioned, the excess saturated fatty acids are correlated with chronic low-grade systemic inflammation(2). This is thought to be of contribution to the worsened infection-induced outcomes in response to Influenza A. We conclude that dietary saturated fatty acids circulating in people with obesity may impair the anti-viral response of airway epithelial cells and further contribute to severe outcomes in respiratory viral disease experienced by those with obesity.
SHEA, in partnership with ASGE, APIC, AAMI, AORN, HSPA, IDSA, SGNA, and The Joint Commission, developed this multisociety infection prevention guidance document for individuals and organizations that engage in sterilization or high-level disinfection (HLD). This document follows the CDC Guideline for Disinfection and Sterilization in Healthcare Facilities. This guidance is based on a synthesis of published scientific evidence, theoretical rationale, current practices, practical considerations, writing group consensus, and consideration of potential harm when applicable. The supplementary material includes a summary of recommendations. The guidance provides an overview of the Spaulding Classification and considerations around manufacturers’ instructions for use (MIFUs). Its recommendations address: point-of-use treatment prior to sterilization or HLD, preparation of reusable medical devices at the location of processing, sterilization, and immediate use steam sterilization (IUSS), HLD of lumened and non-lumened devices, processing of reusable medical devices used with lubricating or defoaming agents, monitoring for effectiveness of processing, handling of devices after HLD, augments and alternatives to HLD, processing of investigational devices, tracking of reusable medical devices, and approaches to implementation.
Medicines routinely funded for use in Wales undergo health technology appraisal by the All Wales Medicines Strategy Group (AWMSG) or the National Institute for Health and Care Excellence (NICE). This includes pediatric license extensions (PLE) notwithstanding any existing advice in adults. A review of the PLE process was conducted with the aim of providing faster access to children’s medicines in Wales.
Methods
Data were collected for PLE appraisals of medicines previously approved for adults by the AWMSG or NICE that subsequently went through the original PLE process between January 2010 and December 2020, or a simplified PLE process between January 2021 and March 2023. Data were analyzed using descriptive statistics and a two-tailed t-test (unequal variance) to test the null hypothesis that the difference between the two means was zero. An alpha of less than 0.05 was considered significant. Feedback was obtained from relevant stakeholders including the Association of the British Pharmaceutical Industry (Wales) and the Royal College of Paediatrics and Child Health.
Results
The AWMSG issued positive recommendations for all PLE appraisals included in the data collected, and these were endorsed by the Welsh Government. Appraisals that went through the original PLE process (n=56) took a mean 229.8 days (standard deviation 55.6), whereas those that went through the simplified PLE process (n=15) took a mean 102.6 days (standard deviation 48.1; p < 0.0001). The rapid access to children’s medicines was welcomed by the Association of the British Pharmaceutical Industry and the Royal College of Paediatrics and Child Health.
Conclusions
Review of the 2020 and 2023 PLE processes facilitated faster access to clinically effective and cost-effective medicines for children in Wales. In March 2023, the AWMSG and the Welsh Government reviewed these results and agreed that because all PLE medicines were approved for use within Wales irrespective of the process used, the AWMSG would no longer be required to routinely appraise PLEs.
I respond to challenges posed by Andrew Dole, Joanna Leidenhag, Kevin Schilbrack, and Sameer Yadav. Key topics include: whether the engagement between analytic theology and the academic study of religion really is mutually beneficial, distinguishing analytic theology from science-engaged theology, restrictive methodological naturalism, and whether I misconstrue analytic theology’s ‘characteristic damage’.
Analytic Theology and the Academic Study of Religion aims to explain analytic theology to other theologians, and to scholars of religion, and to explain those other fields to analytic theologians. The book defends analytic theology from some common criticisms, but also argues that analytic theologians have much to learn from other forms of inquiry. Analytic theology is a legitimate form of theology, and a legitimate form of academic inquiry, and it can be a valuable conversation partner within the wider religious studies academy. I aim to articulate an attractive vision of analytic theology, foster a more fruitful inter-disciplinary conversation, and enable scholars across the religious studies academy to understand one another better. Analytic theology can flourish in the secular academy, and flourish as authentically Christian theology.
Evidence-based conservation can be hindered by limited field data, but historical archives have the potential to provide unique insights into conservation-relevant parameters, such as identification of suitable habitat for threatened species. The Manumea or Tooth-billed Pigeon Didunculus strigirostris has declined on Samoa and only a tiny remnant population still persists, and a key first step for conservation is to locate surviving birds. Numerous Manumea records are available from the nineteenth century onwards, and we used historical and modern records to generate a series of species distribution models to predict the distribution of suitable habitat across Samoa to guide new field searches. Manumea distribution is closely associated with forest cover or its proxies. Preferred Manumea food plants are suggested to be low-elevation trees, but elevation provides relatively low percentage contribution in most models, thus not excluding the possibility that Manumea might occur at high elevations. There is also little evidence for elevational change in records over the past century. Models based on visual versus acoustic records exhibit differences in predicted habitat suitability, suggesting that some purported acoustic records might not actually represent Manumea calls. Field searches should target areas representing high habitat suitability across all models, notably the forested central axis of Upolu.
Can the experience of being ostracized – ignored and excluded – lead to people being more open to extremism? In this chapter we review the theoretical basis and experimental evidence for such a connection. According to the temporal need-threat model (Williams, 2009), ostracism is a painful experience that threatens fundamental social needs. Extreme groups have the potential to be powerful sources of inclusion and could therefore address these needs, thereby making them especially attractive to recent targets of ostracism. We also identify a set of factors that is theoretically likely to affect this link and review evidence for the opposite causal path: People are especially likely to ostracize others who belong to extreme groups. Together, this suggests a possible negative cycle in which ostracism may push people toward extreme groups, on which they become more reliant as social contacts outside the group further ostracize them.
Edited by
Richard Williams, University of South Wales,Verity Kemp, Independent Health Emergency Planning Consultant,Keith Porter, University of Birmingham,Tim Healing, Worshipful Society of Apothecaries of London,John Drury, University of Sussex
It is usual for humans to experience distress in the aftermath of emergencies, incidents, disasters, and disease outbreaks (EIDD). The manifestation, severity, and duration of the experiences that constitute distress depend on many intrinsic and extrinsic factors. Recent research has demonstrated that distress may be more ubiquitous than was previously thought, and that some interventions, even if well meaning, may not be helpful. Amelioration for most people comes with timely, proportionate, and targeted support and the passage of time. Validation of people’s experiences and minimising the medicalisation of distress are important in helping people to return to ordinary social functioning. This chapter looks at distress related to major events, including the scientific principles, impacts, and implications for intervention. The case study draws on the experience of three members of a pre-hospital team and how a challenging case affected them all.
Edited by
Richard Williams, University of South Wales,Verity Kemp, Independent Health Emergency Planning Consultant,Keith Porter, University of Birmingham,Tim Healing, Worshipful Society of Apothecaries of London,John Drury, University of Sussex
There is increasing awareness that working within the field of pre-hospital care can have psychosocial effects on clinicians. This chapter describes a systematic review of current knowledge of the psychosocial consequences of working in pre-hospital care. A considerable amount of research has been conducted, examining in particular whether practitioners develop burnout and psychiatric disorders, especially symptoms of post-traumatic stress and post-traumatic stress disorder (PTSD), as a result of their work. However, most studies did not fully assess whether practitioners developed clinically significant symptoms.. Instead, cross-sectional surveys and self-report questionnaires were used, which considerably overestimate the incidence of these problems. Perhaps the high scores on these questionnaires indicate that practitioners who work in pre-hospital care often suffer considerable stress and distress that can be the result of daily organisational and operational hassles, a high volume of work, lack of resources, and, less than has often been thought, attending unusual and high-profile incidents.
Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.
Participants and Methods:
Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).
Results:
A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).
Conclusions:
Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:
240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:
In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:
These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models.
Methods
Participants from both the NAPLS2 and NAPLS3 samples were classified as either ‘long’ or ‘short’ symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis.
Results
The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78).
Conclusions
These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.
Predeath grief conceptualizes complex feelings of loss experienced for someone who is still living and is linked to poor emotional well-being. The Road Less Travelled program aimed to help carers of people with rarer dementias identify and process predeath grief. This study evaluated the feasibility, acceptability, and preliminary effectiveness of this program.
Design:
Pre–post interventional mixed methods study.
Setting:
Online videoconference group program for carers across the UK held in 2021.
Participants:
Nine family carers of someone living with a rare form of dementia. Eight were female and one male (mean age 58) with two facilitators.
Intervention:
The Road Less Travelled is an online, facilitated, group-based program that aims to help carers of people with rarer dementias to explore and accept feelings of grief and loss. It involved six fortnightly 2-hour sessions.
Measurements:
We collected measures for a range of well-being outcomes at baseline (T1), post-intervention (T2), and 3 months post-intervention (T3). We conducted interviews with participants and facilitators at T2.
Results:
Participant attendance was 98% across all sessions. Findings from the semistructured interviews supported the acceptability of the program and identified improvements in carer well-being. Trends in the outcome measures suggested an improvement in quality of life and a reduction in depression.
Conclusion:
The program was feasible to conduct and acceptable to participants. Qualitative reports and high attendance suggest perceived benefits to carers, including increased acceptance of grief, and support the need for a larger-scale pilot study to determine effectiveness.