Sporadic Creutzfeldt-Jakob disease in adults over 80 years: a 10-year review of United Kingdom surveillance.

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease with public health implications. Mean age of onset is 68 years. Age-specific incidence declines after 80 years. This may arise from under-ascertainment or other biological features of the disease. Accurate characterisation of late-onset sCJD is important for early diagnosis, avoiding unnecessary investigations and improving ascertainment for public health purposes. OBJECTIVE: To phenotype the clinical features and investigation profile of sCJD in adults >80 years. METHODS: We analysed all probable and definite sCJD cases identified by the UK National CJD Research & Surveillance Unit over a 10-year period (2011-2021). Individuals were grouped by age of onset. Clinical features and investigation profiles were compared. RESULTS: 10.3% (123/1196) had an age of onset over 80. Median survival was shorter (3.2 vs 4.3 months; P < 0.001). Pyramidal signs (48.3% vs 34.2%; P = 0.008) and akinetic mutism (55.1% vs 33.2%; P < 0.001) were more frequent. Psychiatric symptoms (26.3% vs 39.6%; P = 0.01) and cerebellar signs (65.4% vs 78.6%, P = 0.007) were less frequent. Cognitive impairment and myoclonus were highly prevalent regardless of age. Between age groups, the diagnostic sensitivity of cerebrospinal fluid real-time quaking-induced conversion (CSF RT-QuIC) (92.9% vs 91.9%, P = 0.74) was comparable, electroencephalography was superior (41.5% vs 25.4%; P = 0.006) and MRI was inferior (67.8% vs 91.4%; P < 0.001). CONCLUSIONS: Late-onset sCJD has distinct clinical features, shorter survival and a different profile of investigation sensitivity. CSF RT-QuIC, MRI brain and specialist CJD review is recommended in older adults with a rapidly progressive neurological disorder. Autopsy is valuable when the cause remains elusive.

Neurological disorders provoked by head and neck movement.

Neurologists encounter a range of neurological disorders triggered by head and neck movement, reflecting an array of underlying pathologies and producing diverse symptoms. This article provides a practically orientated review of 14 disorders and how to diagnose and manage them, including common disorders such as benign paroxysmal positional vertigo and uncommon entities such as arterial compression syndromes leading to stroke or syncope, mobile intraventricular masses and medication withdrawal states. The article considers atypical scenarios including unusual manifestations and important mimics and discusses controversial entities, as well as the risk of misattributing symptoms based on incidental imaging abnormalities. Guidelines are referenced where they exist, while in rarer situations, approaches taken in published cases are described, with the acknowledgement that management decisions are at the clinician's discretion.

Relatively rapid effects of testosterone on men's ratings of female attractiveness depend on relationship status and the attractiveness of stimulus faces.

Attractiveness judgements influence desires to initiate and maintain romantic relationships. Testosterone also predicts relationship initiation and maintenance; such effects may be driven by the hormone's modulation of attractiveness judgements, but no studies have investigated causal (and situation-dependent) effects of the hormone on these judgements. Using a placebo-controlled cross-over design, our preregistered analyses revealed order- and relationship- dependent effects: single heterosexual men judged the women as more appealing when testosterone was administered first (and placebo second), but marginally less appealing when placebo was administered first (and testosterone second). In a more complex model incorporating the women's attractiveness (as rated by an independent set of observers), however, we show that testosterone increases the appeal of women -but this effect depends upon the men's relationship status and the women's attractiveness. In partnered men (n = 53) who tend to derogate attractive alternatives (by rating them as less appealing), testosterone countered this effect, boosting the appeal of these attractive alternatives. In single men (n = 53), conversely, testosterone increased the appeal of low-attractive women. These differential effects highlight the possibility of a newly discovered mechanism whereby testosterone promotes male sexual reproduction through different routes depending on relationship status, promoting partner up- rather than down-grading when partnered and reducing choosiness when single. Further, such effects were relatively rapid [within 85 (±5) minutes], suggesting a potential non-genomic mechanism of action.

Impact of the COVID-19 pandemic on Creutzfeldt-Jakob disease surveillance and patient care in the United Kingdom.

BACKGROUND AND PURPOSE: Creutzfeldt-Jakob disease (CJD) is lethal and transmissible. We assessed the impact of the COVID-19 pandemic on UK CJD surveillance. We hypothesized that (i) disruptions prolonged diagnostic latency; (ii) autopsy rates declined; and (iii) COVID-19 infection negatively affected diagnosis, care, and survival. METHODS: We retrospectively investigated the first year of the pandemic, using the preceding year as a comparator, quantifying numbers of individuals assessed by the UK National CJD Research & Surveillance Unit for suspected CJD, time to diagnosis, disease duration, and autopsy rates. We evaluated the impact of COVID-19 status on diagnosis, care, and survival in CJD. RESULTS: A total of 148 individuals were diagnosed with CJD in the pandemic (from a total of 166 individuals assessed) compared to 141 in the comparator (from 145 assessed). No differences were identified in disease duration or time to diagnosis. Autopsy rates were unchanged. Twenty individuals had COVID-19; 60% were symptomatic, and 10% had severe disease. Disruptions in diagnosis and care were frequently identified. Forty percent of COVID-19-positive individuals died; however, COVID-19 status did not significantly alter survival duration in CJD. CONCLUSIONS: The COVID-19 pandemic has not impacted UK CJD case ascertainment or survival, but diagnostic evaluation and clinical care of individuals have been affected.

An e-Delphi study to obtain expert consensus on the level of risk associated with preventable e-prescribing events.

AIMS: We aim to seek expert opinion and gain consensus on the risks associated with a range of prescribing scenarios, preventable using e-prescribing systems, to inform the development of a simulation tool to evaluate the risk and safety of e-prescribing systems (ePRaSE). METHODS: We conducted a two-round e-Delphi survey where expert participants were asked to score pre-designed prescribing scenarios using a five-point Likert scale to ascertain the likelihood of occurrence of the prescribing event, likelihood of occurrence of harm and the severity of the harm. RESULTS: Twenty-four experts consented to participate with 15 pand 13 participants completing rounds 1 and 2, respectively. Experts agreed on the level of risk associated with 136 out of 178 clinical scenarios with 131 scenarios categorised as high or extreme risk. CONCLUSION: We identified 131 extreme or high-risk prescribing scenarios that may be prevented using e-prescribing clinical decision support. The prescribing scenarios represent a variety of categories, with drug-disease contraindications being the most frequent, representing 37 (27%) scenarios, and antimicrobial agents being the most common drug class, representing 28 (21%) of the scenarios. Our e-Delphi study has achieved expert consensus on the risk associated with a range of clinical scenarios with most of the scenarios categorised as extreme or high risk. These prescribing scenarios represent the breadth of preventable prescribing error categories involving both basic and advanced clinical decision support. We will use the findings of this study to inform the development of the e-prescribing risk and safety evaluation tool.

The impact of a novel medication scanner on administration errors in the hospital setting: a before and after feasibility study.

OBJECTIVE: The medication administration process is complex and consequently prone to errors. Closed Loop Medication Administration solutions aim to improve patient safety. We assessed the impact of a novel medication scanning device (MedEye) on the rate of medication administration errors in a large UK Hospital. METHODS: We performed a feasibility before and after study on one ward at a tertiary-care teaching hospital that used a commercial electronic prescribing and medication administration system. We conducted direct observations of nursing drug administration rounds before and after the MedEye implementation. We calculated the rate and type ('timing', 'omission' or 'other' error) of medication administration errors (MAEs) before and after the MedEye implementation. RESULTS: We observed a total of 1069 administrations before and 432 after the MedEye intervention was implemented. Data suggested that MedEye could support a reduction in MAEs. After adjusting for heterogeneity, we detected a decreasing effect of MedEye on overall errors (p = 0.0753). Non-timing errors ('omission' and 'other' errors) reduced from 51 (4.77%) to 11 (2.55%), a reduction of 46.5%, which had borderline significance at the 5% level, although this was lost after adjusting for confounders. CONCLUSIONS: This pilot study detected a decreasing effect of MedEye on overall errors and a reduction in non-timing error rates that was clinically important as such errors are more likely to be associated with harm. Further research is needed to investigate the impact on a larger sample of medications.

Experimental empathy induction promotes oxytocin increases and testosterone decreases.

Oxytocin and testosterone coordinate adaptive social behaviors with stimuli in the environment. Administration of oxytocin and testosterone is associated with increased and reduced indicators of empathy, respectively, but how levels of these hormones are jointly affected by naturalistic empathy-inducing stimuli remains unclear. In this study, salivary oxytocin and testosterone levels were measured in 173 healthy adults before and after watching a video involving a gravely ill child. Participants also completed questionnaires to assess psychological variables predicted to affect oxytocin reactivity (Autism-Spectrum Quotient, Interpersonal Reactivity Index, Empathy and Systemizing Quotients). On average, there was a 14% increase in oxytocin (p = 0.003) and 4% decrease in testosterone (p = 0.001) pre- to post-video. Opposite directional changes in hormone levels occurred together, as supported by a chi-square test (p < 0.001) and a circular statistics test (p < 0.05). Considered separately, psychological traits did not predict hormone levels or changes to any appreciable degree. However, oxytocin and testosterone changes were linked with empathy relative to systemizing such that: (1) 'Empathy Bias' was associated with a large oxytocin increase but little change in testosterone, while (2) 'Systemizing Bias' and 'Balance' between empathy and systemizing were associated with a decrease in testosterone but little change in oxytocin. These findings suggest that participants were divisible into 'high oxytocin responders' (relatively empathetic) and 'high testosterone responders' (balanced or systemizing-biased). These findings support a model of joint, opposite changes in oxytocin and testosterone under experimental empathy induction, with high, somewhat predictable, diversity in individual responses.

Does testosterone impair men's cognitive empathy? Evidence from two large-scale randomized controlled trials.

The capacity to infer others' mental states (known as 'mind reading' and 'cognitive empathy') is essential for social interactions across species, and its impairment characterizes psychopathological conditions such as autism spectrum disorder and schizophrenia. Previous studies reported that testosterone administration impaired cognitive empathy in healthy humans, and that a putative biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small sample studies with mixed evidence. We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men (n = 243 and n = 400), using two different testosterone administration protocols. We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.

Testosterone reduces the threat premium in competitive resource division.

Like other animals, humans are sensitive to facial cues of threat. Recent evidence suggests that we use this information to dynamically calibrate competitive decision-making over resources, ceding more to high-threat individuals (who appear more willing/able to retaliate) and keeping more from low-threat individuals. Little is known, however, about the biological factors that support such threat assessment and decision-making systems. In a pre-registered, double-blind, placebo-controlled, cross-over testosterone administration study ( n = 118 men), we show for the first time that testosterone reduces the effects of threat on decision-making: participants ceded more resources to high-threat (versus low-threat) individuals (replicating the 'threat premium'), but this effect was blunted by testosterone, which selectively reduced the amount of resources ceded to those highest in threat. Thus, our findings suggest that testosterone influences competitive decision-making by recalibrating the integration of threat into the decision-making process.

Using a Psychopharmacogenetic Approach To Identify the Pathways Through Which-and the People for Whom-Testosterone Promotes Aggression.

Little is known about the neurobiological pathways through which testosterone promotes aggression or about the people in whom this effect is observed. Using a psychopharmacogenetic approach, we found that testosterone increases aggression in men ( N = 308) with select personality profiles and that these effects are further enhanced among those with fewer cytosine-adenine-guanine (CAG) repeats in exon 1 of the androgen receptor (AR) gene, a polymorphism associated with increased AR efficiency. Testosterone's effects were rapid (~30 min after administration) and mediated, in part, by subjective reward associated with aggression. Testosterone thus appears to promote human aggression through an AR-related mechanism and to have stronger effects in men with the select personality profiles because it more strongly upregulates the subjective pleasure they derive from aggression. Given other evidence that testosterone regulates reward through dopaminergic pathways, and that the sensitivity of such pathways is enhanced among individuals with the personality profiles we identified, our findings may also implicate dopaminergic processes in testosterone's heterogeneous effects on aggression.

Comparison of clear and narrow outcomes on testosterone levels in social competition.

A contribution to a special issue on Hormones and Human Competition. Social competition is associated with marked emotional, behavioral and hormonal responses, including changes in testosterone levels. The strength and direction of these responses is often modulated by levels of other hormones (e.g. cortisol) and depends on psychological factors - classically, the objective outcome of a competition (win vs. loss) but also, hypothetically, the closeness of that outcome (e.g. decisive victory vs. close victory). We manipulated these two aspects of a social contest among male participants (N=166), to investigate how testosterone and affect fluctuated as a function of clear vs. narrow wins and clear vs. narrow losses. We found that losing a competition by a small margin (a narrow loss) was experienced as more pleasant than a clear loss. Among individuals with higher levels of basal cortisol, winning the competition by a narrow margin was associated with a decrease in testosterone levels. These findings are discussed within the framework of the status instability hypothesis and the growing literature on how situational and physiological factors modulate testosterone reactivity to social contests.

The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and social anxiety in a healthy population.

The neurohormone oxytocin plays a central role in human social behaviour and cognition, and oxytocin dysregulation may contribute to psychiatric disorders. However, genetic factors influencing individual variation in the oxytocinergic system remain poorly understood. We genotyped 169 healthy adults for a functional polymorphism in GTF2I (general transcription factor II-I), a gene associated with high prosociality and reduced social anxiety in Williams syndrome, a condition reported to involve high oxytocin levels and reactivity. Participants' salivary oxytocin levels were measured before and after watching a validated empathy-inducing video. Oxytocin reactivity, defined as pre- to post-video percentage change in salivary oxytocin, varied substantially and significantly between individuals with different GTF2I genotypes, with, additionally, a trend towards an interaction between genotype and sex. Individuals with more oxytocin-reactive genotypes also reported significantly lower social anxiety. These findings suggest a model whereby GTF2I has a continuum of effects on human sociality, from the extreme social phenotypes and oxytocin dysregulation associated with gene deletion in Williams syndrome, to individual differences in oxytocin reactivity and sociality associated with common polymorphisms in healthy populations.

Pre-operative obesity does not predict poorer symptom control and quality of life after lumbar disc surgery.

PURPOSE: We aimed to determine whether there was a difference in post-operative symptomatic control and quality of life (QoL) between patients who were obese (BMI >30) and non-obese (BMI <30) pre-operatively. This information may inform the decision making of Physicians and patients whether to proceed to surgery for management of symptomatic lumbar disc prolapse. METHODS: We conducted a prospective questionnaire-based study of QoL and symptom control in 120 patients with postal follow-up at 3 and 12 months after lumbar disc surgery. This study was conducted in two United Kingdom regional neurosurgical units, with ethical approval from the North of Scotland Research Ethics Service (09/S0801/7). RESULTS: 120 patients were recruited; 37 (34.5%) were obese. Follow up was 71% at 3 months and 57% at 12 months. At recruitment, both obese and non-obese patient groups had similar functional status and pain scores. At 3 and 12 months, non-obese and obese patients reported similar and significant benefits from surgery (e.g. 12 month SF-36 80.5 vs. 68.8, respectively). In non-obese and obese patients, time to return to work was 47.5 days and 53.8 days, respectively, (p = .345). After 12 months all QoL scores were significantly improved from pre-operative levels in both groups. CONCLUSIONS: Obese patients derive significant benefit from lumbar discectomy that it is similar to the benefit experienced by non-obese patients. Obese individuals may achieve excellent results from discectomy and these patients should not be refused surgery on the basis of BMI alone.

Face of a fighter: Bizygomatic width as a cue of formidability.

Humans can accurately extract information about men's formidability from their faces; however, the actual facial cues that inform these judgments have not been established. Here, through three studies, we test the hypothesis that bizygomatic width (i.e. facial width-to-height ratio, fWHR) covaries with actual physical formidability (hypothesis #1) and that humans use this cue when making assessments of formidability (hypothesis #2). Our data confirm that fWHR is predictive of actual fighting ability among professional combatants (study 1). We further show that subjects' assessments of formidability covary with the target's fWHR on natural faces (study 2), computer-generated images of strong and weak faces (study 2), and experimentally manipulated computer-generated faces (study 3). These results support the hypothesis that bizygomatic width is a cue of formidability that is assessed during agonistic encounters.

Testosterone reactivity to facial display of emotions in men and women.

Previous studies have examined testosterone's role in regulating the processing of facial displays of emotions (FDEs). However, the reciprocal process - the influence of FDEs, an evolutionarily ancient and potent class of social signals, on the secretion of testosterone - has not yet been studied. To address this gap, we examined the effects of emotional content and sex of facial stimuli in modulating endogenous testosterone fluctuations, as well as sex differences in the endocrine responses to faces. One hundred and sixty-four young healthy men and women were exposed, in a between-subjects design, to happy or angry same-sex or opposite-sex facial expressions. Results showed that in both men (n=85) and women (n=79), extended exposure to faces of the opposite sex, regardless of their apparent emotional content, was accompanied by an accumulation in salivary testosterone when compared to exposure to faces of the same sex. Furthermore, testosterone change in women exposed to angry expressions was greater than testosterone change in women exposed to happy expressions. These results add emotional facial stimuli to the collection of social signals that modulate endocrine status, and are discussed with regard to the evolutionary roles of testosterone.