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There is considerable interest in the role of neuroimmune processes in neuropsychiatric presentations among young people seeking mental health, neurological, paediatric and rheumatological services. The increasing availability of new immunotherapies, particularly monoclonal antibodies, introduces challenges in effectively and appropriately selecting candidates for immunotherapies. Neuroimmune-mediated neuropsychiatric syndromes (NIMNPS) typically include two broad types: i) ‘autoimmune encephalitis’, characterised by acute or subacute onset, neurological signs such as seizures, delirium or motor features and severe psychotic or major mood phenomena. Anti-N-methyl-D-aspartate receptor encephalitis was a pioneering clinical example, but various other autoantibodies have since been associated with this phenotype; and ii) atypical mood or psychotic syndromes with sub-acute or insidious onset, moderately severe atypical mood or psychotic symptoms, autonomic dysregulation, narcolepsy-like features, poor response to conventional treatments and adverse (notably motor) effects from psychotropic medications. Diagnosis of NIMNPS requires clinical or laboratory evidence of direct brain involvement, though autoantibodies are not always detectable. Given the broad and controversial diagnostic criteria for NIMNPS, we propose standardised clinical criteria for identifying ‘possible cases’, followed by laboratory, neuropsychological and brain imaging tests to confirm ‘probable’ cases suitable for immunotherapy. We emphasise rapid clinical and informed co-decision-making with young people and their families and loved ones. While immunotherapy holds promise for symptom alleviation, highly-personalised approaches and long-term management are essential. Future research should validate our proposed criteria, establish optimal, standardised yet personalised immunotherapy strategies that balance between clinical benefit and risks, and identify predictive markers of treatment response.
Metabolic and inflammatory dysfunction is prevalent in middle-aged people with major mood disorders, but less is known about young people. We investigated the trajectories of sensitive metabolic (Homeostatic Model Assessment for Insulin Resistance [HOMA2-IR]) and inflammatory markers (C-reactive protein [CRP]) in 155 young people (26.9 ± 5.6 years) accessing mental health services. We examined demographic and clinical correlates, longitudinal trajectories and relationships with specific illness subtypes. Additionally, we compared the HOMA2-IR with fasting blood glucose (FBG) for sensitivity. We observed a significant increase in HOMA2-IR and CRP over time with higher baseline levels predicting greater increases, although the rate of increase diminished in those with higher baseline levels. Body mass index predicted increases in HOMA2-IR (p < 0.001), but not CRP (p = 0.135). Multinomial logistic regression revealed that higher HOMA2-IR levels were associated with 2.3-fold increased odds of the “circadian-bipolar spectrum” subtype (p = 0.033), while higher CRP levels were associated with a reduced risk of the “neurodevelopmental psychosis” subtype (p = 0.033). Standard FBG measures were insensitive in detecting early metabolic dysregulation in young people with depression. The study supports the use of more sensitive markers of metabolic dysfunction to address the longitudinal relationships between immune-metabolic dysregulation and mood disorders in young people.
Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021.
Methods:
CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively.
Results:
Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles.
Conclusions:
To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.
One of the most used, but poorly defined, terms in the management of clinical depression is that of treatment-resistant depression (TRD) (McIntyre et al., 2023). It implies that persons with major depression have received a range of appropriate psychological, medical or physical treatments (at appropriate doses and for appropriate durations) but have not experienced a significant clinical response. Intrinsically, it does not require consideration as to whether those treatments provided were relevant to their age or developmental stage, clinical phenotype, interpersonal or social context, or personal illness trajectory. These broader clinical considerations often influence initial and subsequent treatment choices.
The recognised heterogeneity of clinical cohorts of people with depression and other mood disorders has been held to be one of the central reasons why so many studies of causation, neurobiological or psychological correlates, or the effectiveness of treatments have failed to yield significant findings or be easily replicated by independent groups.
Performance validity tests (PVTs) provide a methodological approach to detecting credible neurocognitive performances. This proves invaluable to the diagnostic process, as it allows neuropsychologists to objectively determine if an evaluation reflects a patient’s true neurocognitive abilities or if external factors are impacting the results. However, their addition to a testing battery can increase an already lengthy evaluation. As such, there is a need for sensitive but less time intensive PVTs. The purpose of this study is to validate the Coin-in-Hand (CIH) procedure as a quick and effective PVT within a veteran population.
Participants and Methods:
68 English-speaking patients were identified from an outpatient neuropsychological assessment dataset. Performances were correlated to the well- validated Reliable Digit Span (RDS), and several other soft indicators of task engagement including expanded COWAT, BVMT-False Alarms (FA), WCST Failure to Maintain Set (FTM), TOMM, and the RBANS Effort Index (EI). All participants attempted CIH and RDS, testing was discontinued if 2 or more PVTs were invalid. An AUC analysis was conducted to determine how well the CIH discriminated between valid and invalid performance and determine the tests optimal cut-off score (sensitivity > 0.90 while maintaining the highest possible specificity). Logistic Regression was conducted to determine how well the CIH predicted performance validity.
Results:
Subject mean(SD) age and education were 55.25 (16.06) and 13.41 (2.55) years, respectively. 17% female, 60% Caucasian, and 32% Black. Descriptive statistics for each of the other performance validity tests were gathered. The CIH demonstrated low diagnostic accuracy (AUC = .66; p >.05; CI = .51 -.81); a cut score of <8 resulted in a sensitivity of .96 and a specificty of .64. Logistic Regression showed that CIH performance significantly predicted performance validity (X2 = -0.93; df = 1; N = 68; p < .05), accounting for 18-28% of the variance in performance classification (Cox & Snell R2 = .18; Nagelkerke R2 = .28). It correctly classified 96% of valid performers, but only correctly classified 35% of invalid performers, with an overall correct prediction rate of 83%. A predicted chase in log odds (B= -.93) and odd ratio [Exp (B) =.40] indicated that every unit increase in CIH score was associated with a decrease probability of performance invalidity. Logistic regression was also used to calculate the probability of performance invalidity at each possible CIH score (Table 1).
Conclusions:
Results suggests that poor performance on CIH does not necessarily equate to invalid performances, but instead, should act as a screener to cue neuropsychologists working with Veterans that additional PVTs should be considered. Overall, it was determined that CIH was able to correctly predict 35% of invalid performers and 96% of valid performers, with an overall correct prediction rate of 83%, suggesting the procedure may be too simple to be an effective standalone PVT for clinical use. These results also highlight that every correct response on the CIH was associated with a decreased probability of performance invalidity. Additionally, an AUC analysis determined the tests optimal cut off score to be <8, suggesting that shortening the procedure may be as effective as giving the full 10 trials.
Explore the relationship between a motor programming and sequencing procedure and informant rating of patients' functional abilities, especially driving. The Fist-Edge-Palm (FEP; Luria, 1970; 1980) task has previously demonstrated merit distinguishing between healthy controls and those with neurodegenerative processes (Weiner et al., 2011). However, associations between FEP performance and informant-rated functional status, particularly driving ability, have been minimally reported. This exploratory review examined the relationship between FEP, informant-rated driving ability, overall functional impairment, and neurocognitive diagnostic severity.
Participants and Methods:
41 Veterans seen in a South-Central VA Memory Clinic between 08/2020 and 07/2022 served as participants. Neuropsychological assessment included gathering demographic information, chairside neurobehavioral examination (including FEP), cognitive testing, and collateral informant completed Functional Activities Questionnaire (FAQ). Diagnostic severity [no diagnosis, mild cognitive impairment (MCI), dementia (MNCD)] was determined based on the patient's cognitive and functional deficits as measured by neuropsychological testing and informant-rated functional deficits. Correlational analyses were conducted to examine the strength of possible relationships between FEP performance, diagnostic severity, informant-rated functional status including driving impairment. Linear regression analyses determined the extent to which diagnostic severity and FEP performance predict informant-reported driving and ADL impairments
Results:
Participants were 97.5% male, 78% white, 22% black. Diagnostically, 3 patients received no diagnoses, 14 with MCI, and 24 with MNCD. Spearman rank correlations were computed; FEP performance was moderately negatively correlated with diagnostic severity [rho = -.35; p < .05] and driving impairment [rho = -.31; p < .05]. Diagnostic severity was moderately positively correlated with driving [rho= .44; p < .05] and total functional [rho = .65; p < .05] impairment. Total functional impairment positively correlated with reported driving impairment [rho = .58; p < .05]. Simple linear regressions tested if FEP performance and diagnostic severity independently predicted informant-reported driving and functional impairment. FEP performance predicted diagnostic severity (R2 = .12, p < .05) and reported driving impairment severity (R2 = .10, p <.05) but did not predict total functional impairment severity (R2 = .06, p = .14). Diagnostic severity predicted both informant-reported driving impairment severity (R2 = .16, p <.05) and functional severity (R2 = .30, p < .05). Multiple regression tested if diagnostic severity and FEP performance together was more predictive of driving and functional impairment than individually; the overall model was predictive of driving (R2 = .19, p < .05) and total functional (R2 = .30, p < .05) impairment, but only diagnostic severity significantly predicted reported driving (B = .63, p < .05) and functional (B = 6.25, p < .05) impairments.
Conclusions:
FEP performance was associated with diagnosis and collateral informant concerns of patient driving ability but not statistically related to overall functional impairment or nondriving related ADLs. FEP demonstrates utility in identification of patients demonstrating concerning driving fitness per collateral informants and diagnostic severity due to rapidity of administration, ease of instructing providers, and implementation in a wide variety of clinical settings when a caregiver or informant may not be available. Future directions include explaining the relationship between FEP and driving ability and exploring associations between FEP and other neuropsychological instruments.
Given the global prevalence of depression and other major mood disorders, the evidence of increasing rates among younger cohorts, the limited capacity of most treatment systems to respond to increasing demands for care, and the reality that services do not connect with a large proportion of those living with depressive disorders, a greater emphasis is being placed on our capacity to prevent the onset, recurrence, or persistence of these disabling conditions (Herrman et al., 2022).
A clinical concept that has been taken up with some enthusiasm in mental health services for young people experiencing major mental disorders is that of clinical staging, with the emphasis on identifying and intervening in youth with various ‘at-risk’, ‘sub-threshold’ or ‘attenuated’ syndromes, before the onset of first major episodes (Shah et al 2020). While these concepts were initially developed within the rather focused context of major psychotic disorders, they are now being deployed much more widely and applied to young people presenting with a variety of mental disorders (Hickie et al 2019; Shah 2019).
In both population-based and clinical cohorts, cross-sectional and longitudinal studies have reported associations between a range of non-specific markers of immune activation (e.g., pro-inflammatory cytokines) or chronic inflammation (e.g., C-reactive protein [CRP]) and depressive and other mood disorders (Dowlati et al. 2010; Hickie et al. 2018; Khandaker et al. 2017; Orsolini et al. 2022; Valkanova et al. 2013). The clinico-pathological significance, and directional relationships, of these associations tended to be downplayed as the systemic levels of these inflammatory markers were not in the ranges typical of active infective, inflammatory or significant autoimmune diseases.
The field of therapeutic interventions available for depression and other mood disorders has been radically transformed over the last decade by the introduction of a range of new brain stimulation therapies. There is strong professional and public interest in the relative efficacy, and side effect profiles, of these approaches compared with conventional pharmacotherapy and older methods such as electro-convulsive therapy (Brunoni et al., 2022; Fitzgerald, 2021; Fitzgerald et al., 2022).
Much attention in recent years has focused on the extent to which the risk of metabolic disturbances, and most fundamentally of glucose and insulin, are prevalent among those treated for depressive and other mood disorders (Osimo et al., 2021; Scott et al., 2019; Tickell et al., 2022). Public concern has also focused on the increased rates of premature mortality in those with chronic depression and other major mental disorders, with a significant proportion of that risk being due to early-onset cardiovascular disease (particularly among women). A common assumption is that much of this risk is a consequence of medical treatments for depression, and their possible adverse effects such as increased risk of diabetes, presumably mediated by long-term weight gain.
One of the greatest global threats to mental health and wellbeing is the already discernible impact of climate change on local communities, particularly those living in the most vulnerable places on the planet, as well as the predicted impacts globally over the next 25–50 years (Romanello et al., 2021). Impacts have already been reported in those communities which have been devastated, often repeatedly, by extreme weather events (floods, cyclones, drought, bushfires, etc.) (Obradovich et al., 2018). These include massive social dislocation, loss of social connections and breakdowns in education, employment, economic and housing security – all factors known to increase the risk of common mental health conditions including anxiety, depression and other mood disorders.
The most basic distinction between depressive (and other mood) disorders and other major mental disorders is the notion that they are primarily mood or affective disorders and not fundamentally perturbations of other cognitive, perceptual, motor, communication, impulse, sleep−wake, fear-response, arousal, developmental or personality functions. The primacy of mood or affective state is captured in the ‘core’ criteria for major depression (depressed mood or loss of pleasure) and the other major mood disorders (e.g., for dysthymia – prolonged depressed mood) (American Psychiatric Association, 2013). For bipolar disorder, while the presence of manic features (with increased motor activity) (Scott et al., 2017) is the core element, the depressive phase is described in similar terms, with the emphasis on the same shared features of major depression (i.e., depressed mood or loss of pleasure).
Primary youth mental health services in Australia have increased access to care for young people, yet the longer-term outcomes and utilisation of other health services among these populations is unclear.
Aims
To describe the emergency department presentation patterns of a help-seeking youth mental health cohort.
Method
Data linkage was performed to extract Emergency Department Data Collection registry data (i.e. emergency department presentations, pattern of re-presentations) for a transdiagnostic cohort of 7024 youths (aged 12–30 years) who presented to mental health services. Outcome measures were pattern of presentations and reason for presentations (i.e. mental illness; suicidal behaviours and self-harm; alcohol and substance use; accident and injury; physical illness; and other).
Results
During the follow-up period, 5372 (76.5%) had at least one emergency department presentation. The presentation rate was lower for males (IRR = 0.87, 95% CI 0.86–0.89) and highest among those aged 18 to 24 (IRR = 1.117, 95% CI 1.086–1.148). Almost one-third (31.12%) had an emergency department presentation that was directly associated with mental illness or substance use, and the most common reasons for presentation were for physical illness and accident or injury. Index visits for mental illness or substance use were associated with a higher rate of re-presentation.
Conclusions
Most young people presenting to primary mental health services also utilised emergency services. The preventable and repeated nature of many presentations suggests that reducing the ongoing secondary risks of mental disorders (i.e. substance misuse, suicidality, physical illness) could substantially improve the mental and physical health outcomes of young people.
The needs of young people attending mental healthcare can be complex and often span multiple domains (e.g., social, emotional and physical health factors). These factors often complicate treatment approaches and contribute to poorer outcomes in youth mental health. We aimed to identify how these factors interact over time by modelling the temporal dependencies between these transdiagnostic social, emotional and physical health factors among young people presenting for youth mental healthcare.
Methods
Dynamic Bayesian networks were used to examine the relationship between mental health factors across multiple domains (social and occupational function, self-harm and suicidality, alcohol and substance use, physical health and psychiatric syndromes) in a longitudinal cohort of 2663 young people accessing youth mental health services. Two networks were developed: (1) ‘initial network’, that shows the conditional dependencies between factors at first presentation, and a (2) ‘transition network’, how factors are dependent longitudinally.
Results
The ‘initial network’ identified that childhood disorders tend to precede adolescent depression which itself was associated with three distinct pathways or illness trajectories; (1) anxiety disorder; (2) bipolar disorder, manic-like experiences, circadian disturbances and psychosis-like experiences; (3) self-harm and suicidality to alcohol and substance use or functioning. The ‘transition network’ identified that over time social and occupational function had the largest effect on self-harm and suicidality, with direct effects on ideation (relative risk [RR], 1.79; CI, 1.59–1.99) and self-harm (RR, 1.32; CI, 1.22–1.41), and an indirect effect on attempts (RR, 2.10; CI, 1.69–2.50). Suicide ideation had a direct effect on future suicide attempts (RR, 4.37; CI, 3.28–5.43) and self-harm (RR, 2.78; CI, 2.55–3.01). Alcohol and substance use, physical health and psychiatric syndromes (e.g., depression and anxiety, at-risk mental states) were independent domains whereby all direct effects remained within each domain over time.
Conclusions
This study identified probable temporal dependencies between domains, which has causal interpretations, and therefore can provide insight into their differential role over the course of illness. This work identified social, emotional and physical health factors that may be important early intervention and prevention targets. Improving social and occupational function may be a critical target due to its impacts longitudinally on self-harm and suicidality. The conditional independence of alcohol and substance use supports the need for specific interventions to target these comorbidities.
Peltigera globulata Miadl. & Magain, a new species in the P. ponojensis/monticola species complex of section Peltigera, is formally described. This clade was previously given the interim designation Peltigera sp. 17. It is found in sun-exposed and xeric habitats at high altitudes in Peru and Ecuador. Peltigera globulata can be easily recognized by its irregularly globulated margins covered mostly by thick, white pruina, somewhat resembling the sorediate thallus margins of P. soredians, another South American species from section Peltigera. The hypervariable region of ITS1 (ITS1-HR), which is in general highly variable among species of section Peltigera, does not have diagnostic value for species identification within the P. ponojensis/monticola complex. Nevertheless, no significant level of gene flow was detected among eight lineages representing a clade of putative species (including P. globulata) within this complex. ITS sequences from the holotype specimens of P. monticola Vitik. (collected in 1979) and P. soredians Vitik. (collected in 1981) and lectotype specimens of P. antarctica C. W. Dodge (collected in 1941) and P. aubertii C. W. Dodge (collected in 1952) were successfully obtained through Sanger and Illumina metagenomic sequencing. BLAST results of these sequences revealed that the type specimen of P. monticola falls within the P. monticola/ponojensis 7 clade, which represents P. monticola s. str., and confirmed that the type specimen of P. aubertii falls within a clade identified previously as P. aubertii based on morphology. The ITS sequence from the type specimen of P. soredians, which superficially resembles P. globulata, confirms its placement in the P. rufescens clade. Finally, we discovered that the name P. antarctica was erroneously applied to a lineage in the P. ponojensis/monticola clade. The ITS sequence from the type specimen of P. antarctica represents a lineage within the P. rufescens clade, which is sister to the P. ponojensis/monticola clade.
Newcastle disease (ND) is a notifiable disease affecting chickens and other avian species caused by virulent strains of Avian paramyxovirus type 1 (APMV-1). While outbreaks of ND can have devastating consequences, avirulent strains of APMV-1 generally cause subclinical infections or mild disease. However, viruses can cause different levels of disease in different species and virulence can evolve following cross-species transmission events. This report describes the detection of three cases of avirulent APMV-1 infection in Great Britain (GB). Case 1 emerged from the ‘testing to exclude’ scheme in chickens in Shropshire while cases 2 and 3 were made directly from notifiable avian disease investigations in chicken broilers in Herefordshire and on premises in Wiltshire containing ducks and mixed species, respectively). Class II/genotype I.1.1 APMV-1 from case 1 shared 99.94% identity to the Queensland V4 strain of APMV-1. Class II/genotype II APMV-1 was detected from case 2 while the class II/genotype I.2 virus from case 3 aligned closely with strains isolated from Anseriformes. Exclusion of ND through rapid detection of avirulent APMV-1 is important where clinical signs caused by avirulent or virulent APMV-1s could be ambiguous. Understanding the diversity of APMV-1s circulating in GB is critical to understanding disease threat from these adaptable viruses.