Testosterone rapidly increases men's emotion-based dehumanization of a conservatively dressed woman.

Past research has found that sexualized women are often dehumanized (i.e., attributed reduced human qualities). However, the mechanisms contributing to such dehumanization remain poorly understood. In this pre-registered experiment involving a within-subject, placebo-controlled, cross-over design, we tested whether testosterone contributes to men's (N = 120, age range: 18-38 years) dehumanization of women. After administration of intranasal testosterone or placebo gel, men watched a video of a woman wearing either modest (i.e., conservative) or revealing (i.e., sexualized) clothing (between-subjects factor) and then completed three subtle dehumanization tasks, measuring emotion-based, personality-based, and perceptual dehumanization. We hypothesized that testosterone would increase dehumanization, especially for men who watched the "sexualized-clothing" video. Instead, we found that, while men engaged in emotion-based dehumanization toward the sexualized woman both when they had testosterone and placebo, testosterone increased emotion-based dehumanization toward the conservatively dressed woman. Other forms of dehumanization were not affected by testosterone. We also explored whether personality (e.g., dominance) and biological (e.g., CAG repeat polymorphism) traits that have been found to moderate the effects of testosterone on some social behaviors also moderated the effects examined here, but we did not find any significant moderations. Overall, this experiment revealed a novel physiological mechanism affecting emotion-based dehumanization.

Player Activity and Load Profiling with Hidden Markov Models: A Novel Application in Rugby League.

Player movement in rugby league is complex, being spatiotemporal and multifaceted. Modeling this complexity to provide robust measures of player activity and load has proved difficult, with important aspects of player movement yet to be considered. These include the influence of time-varying covariates on player activity and the combination of different dimensions of player movement. Few studies have simultaneously categorized player activity into different activity states and investigated factors influencing the transition between states, or compared player activity and load profiles between matches and training. This study applied hidden Markov models (HMMs)-a data-driven, multivariate approach-to rugby league training and match GPS data to i) demonstrate how HMMs can combine multiple variables in a data-driven way to effectively categorize player movement states, ii) investigate the influence of two time-varying covariates, score difference and elapsed match time on player activity states, and iii) compare player activity and load profiles within and between training and match modalities. HMMs were fitted to player GPS, accelerometer and heart rate data of one English Super League team across 60 training sessions and 35 matches. Distinct activity states were detected for both matches and training, with transitions between states in matches influenced by score difference and elapsed time and clear differences in activity and load profiles between training and matches. HMMs can model the complexity of player movement to effectively profile player activity and load in rugby league and have the potential to facilitate new research across several sports.

We successfully derived player activity and load profiles in both training and match contexts in a data-driven and multivariate way using hidden Markov models.HMMs can be used to investigate the probability of changing between activity states as a function of time-varying covariates, augmenting current activity profiling practice.We discovered key differences between the activity and load profiles between training and matches in rugby league. In particular, a very directed high-speed running state in training that is seldom accessed by players in matches.We demonstrated how visualizing the output of HMMs can provide decision support by facilitating comparisons of activity and load profiles within and between players in matches and training.We posit that the methodology detailed in this paper can become a standardized approach to player activity and load profiling based on player movement data across multiple sports because it is flexible, data-driven, multivariate and statistically robust.

Complex Hospital-Based Electronic Prescribing-Based Intervention to Support Antimicrobial Stewardship: Qualitative Study.

BACKGROUND: Antimicrobial resistance (AMR) represents a growing concern for public health. OBJECTIVE: We sought to explore the challenges associated with development and implementation of a complex intervention designed to improve AMS in hospitals. METHODS: We conducted a qualitative evaluation of a complex AMS intervention with educational, behavioral, and technological components in 5 wards of an English hospital. At 2 weeks and 7 weeks after initiating the intervention, we interviewed 25 users of the intervention, including senior and junior prescribers, a senior nurse, a pharmacist, and a microbiologist. Topics discussed included perceived impacts of different elements of the intervention and facilitators and barriers to effective use. Interviews were supplemented by 2 observations of ward rounds to gain insights into AMS practices. Data were audio-recorded, transcribed, and inductively and deductively analyzed thematically using NVivo12. RESULTS: Tracing the adoption and impact of the various components of the intervention was difficult, as it had been introduced into a setting with competing pressures. These particularly affected behavioral and educational components (eg, training, awareness-building activities), which were often delivered ad hoc. We found that the participatory intervention design had addressed typical use cases but had not catered for edge cases that only became visible when the intervention was delivered in real-world settings (eg, variations in prescribing workflows across different specialties and conditions). CONCLUSIONS: Effective user-focused design of complex interventions to promote AMS can support acceptance and use. However, not all requirements and potential barriers to use can be fully anticipated or tested in advance of full implementation in real-world settings.

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.

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.

Characterisation of RT-QuIC negative cases from the UK National CJD Research and Surveillance programme.

INTRODUCTION: Incorporation of the real-time quaking-induced conversion (RT-QuIC) assays for diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) has transformed diagnosis largely related to its extremely high specificity. However, the test has a c.10% false-negative result and we aim to characterize the clinical features, investigation profile, and molecular subtype in this cohort of patients. METHODS: 250 individuals diagnosed with definite sporadic CJD were identified from the UK National CJD Research and Surveillance Unit from 2012 to 2023. We compared the clinical features and investigation profile in those with a negative CSF RT-QuIC to those with a positive RT-QuIC. RESULTS: 27 individuals (10.8%) were CSF RT-QuIC negative. Median age of onset was younger (62 years vs 68 years, p = 0.002), median disease duration was longer (4.4 months vs 10.5 months, p < 0.001), and these individuals were less likely to present with gait difficulties (73% vs 93%, p = 0.003) or motor symptoms (62% vs 80%, p = 0.04). The sensitivity of electroencephalography and diffusion-weighted MRI were similar in both groups. In those who were RT-QuIC negative, there was an overrepresentation of the VV1 (32% vs 1%) and MM2 molecular subtypes (21% vs 3%). Co-occurring neurodegenerative disease was found in 33% (9/27) of those who were RT-QuIC negative. CONCLUSIONS: Individuals with sporadic CJD and a negative CSF RT-QuIC present with younger age of onset, different clinical features and are over-represented with the VV1 and MM2 subtypes of sporadic CJD. Further work is required to better understand the biochemical properties contributing to RT-QuIC negative results in these cases.

Excluded and ashamed: Shame proneness interacts with social exclusion and testosterone reactivity to predict behavioral aggression.

Exclusion from social relationships is a painful experience that may threaten an individual's status and dominance. The steroid hormone testosterone, which fluctuates rapidly in response to such threats, may be implicated in subsequent behavioral action (e.g., aggressive or prosocial responses) that aims to protect or enhance one's status after exclusion. Past research, however, indicates that the link between acute changes in testosterone and behavior depend on context-relevant individual dispositions. In the context of social exclusion, an individual's level of shame proneness-characterized by a tendency to experience shame and to react submissively-is theoretically relevant to the testosterone-induced aggression relationship but has yet to be examined empirically. Here, men (n = 167) were randomly assigned to be socially included or excluded in the virtual ball-tossing game, Cyberball, after which aggressive behavior was examined using the Point Subtraction Aggression Paradigm (PSAP). Testosterone reactivity was measured via salivary hormone samples collected pre- and post-game. Moderated multiple regression analyses were run to examine the extent to which testosterone reactivity and shame proneness moderated the effect of Cyberball condition on aggression. Results revealed a significant two-way interaction between Cyberball condition and testosterone reactivity, as well as a three-way interaction including shame proneness. For individuals low in shame proneness, exclusion was associated with higher post-cyberball aggression among those who experienced a rise in testosterone but was associated with lower post-cyberball aggression among those who experienced a decrease in testosterone. For individuals high in shame proneness, however, exclusion did not meaningfully affect aggressive responses, regardless of whether they experienced an increase or decrease in testosterone. These findings extend our understanding of the moderating roles of context and disposition on the neuroendocrinology of aggression in social interaction.

ePrescribing-Based Antimicrobial Stewardship Practices in an English National Health Service Hospital: Qualitative Interview Study Among Medical Prescribers and Pharmacists.

BACKGROUND: Antimicrobial resistance, the ability of microorganisms to survive antimicrobial drugs, is a public health emergency. Although electronic prescribing (ePrescribing)-based interventions designed to reduce unnecessary antimicrobial usage exist, these often do not integrate effectively with existing workflows. As a result, ePrescribing-based interventions may have limited impact in addressing antimicrobial resistance. OBJECTIVE: We sought to understand the existing ePrescribing-based antimicrobial stewardship (AMS) practices in an English hospital preceding the implementation of functionality designed to improve AMS. METHODS: We conducted 18 semistructured interviews with medical prescribers and pharmacists with varying levels of seniority exploring current AMS practices and investigating potential areas for improvement. Participants were recruited with the help of local gatekeepers. Topic guides sought to explore both formal and informal practices surrounding AMS, and challenges and opportunities for ePrescribing-based intervention. We coded audio-recorded and transcribed data with the help of the Technology, People, Organizations, and Macroenvironmental factors framework, allowing emerging themes to be added inductively. We used NVivo 12 (QSR International) to facilitate coding. RESULTS: Antimicrobial prescribing and review processes were characterized by competing priorities and uncertainty of prescribers and reviewers around prescribing decisions. For example, medical prescribers often had to face trade-offs between individual patient benefit and more diffuse population health benefits, and the rationale for prescribing decisions was not always clear. Prescribing involved a complex set of activities carried out by various health care practitioners who each only had a partial and temporary view of the whole process, and whose relationships were characterized by deeply engrained hierarchies that shaped interactions and varied across specialties. For example, newly qualified doctors and pharmacists were hesitant to change a consultant's prescribing decision when reviewing prescriptions. Multidisciplinary communication, collaboration, and coordination promoted good AMS practices by reducing uncertainty. CONCLUSIONS: Design of ePrescribing-based interventions to improve AMS needs to take into account the multitude of actors and organizational complexities involved in the prescribing and review processes. Interventions that help reduce prescriber or reviewer uncertainty and improve multidisciplinary collaboration surrounding initial antimicrobial prescribing and subsequent prescription review are most likely to be effective. Without such attention, interventions are unlikely to fulfill their goal of improving patient outcomes and combatting antimicrobial resistance.

Barriers and Opportunities for the Use of Digital Tools in Medicines Optimization Across the Interfaces of Care: Stakeholder Interviews in the United Kingdom.

BACKGROUND: People with long-term conditions frequently transition between care settings that require information about a patient's medicines to be transferred or translated between systems. This process is currently error prone and associated with unintentional changes to medications and miscommunication, which can lead to serious patient consequences. One study estimated that approximately 250,000 serious medication errors occur in England when a patient transitions from hospital to home. Digital tools can equip health care professionals with the right information at the right time and place to support practice. OBJECTIVE: This study aimed to answer the following questions: what systems are being used to transfer information across interfaces of care within a region of England? and what are the challenges and potential opportunities for more effective cross-sector working to support medicines optimization? METHODS: A team of researchers at Newcastle University conducted a qualitative study by performing in-depth semistructured interviews with 23 key stakeholders in medicines optimization and IT between January and March 2022. The interviews lasted for approximately 1 hour. The interviews and field notes were transcribed and analyzed using the framework approach. The themes were discussed, refined, and applied systematically to the data set. Member checking was also performed. RESULTS: This study revealed themes and subthemes pertaining to 3 key areas: transfer of care issues, challenges of digital tools, and future hopes and opportunities. We identified a major complexity in terms of the number of different medicine management systems used throughout the region. There were also important challenges owing to incomplete patient records. We also highlighted the barriers related to using multiple systems and their subsequent impact on user workflow, a lack of interoperability between systems, gaps in the availability of digital data, and poor IT and change management. Finally, participants described their hopes and opportunities for the future provision of medicines optimization services, and there was a clear need for a patient-centered consolidated integrated health record for use by all health and care professionals across different sectors, bridging those working in primary, secondary, and social care. CONCLUSIONS: The effectiveness and utility of shared records depend on the data within; therefore, health care and digital leaders must support and strongly encourage the adoption of established and approved digital information standards. Specific priorities regarding understanding of the vision for pharmacy services and supporting this with appropriate funding arrangements and strategic planning of the workforce were also described. In addition, the following were identified as key enablers to harness the benefits of digital tools to support future medicines optimization: development of minimal system requirements; enhanced IT system management to reduce unnecessary repetition; and importantly, meaningful and continued collaboration with clinical and IT stakeholders to optimize systems and share good practices across care sectors.

A complex ePrescribing-based Anti-Microbial Stewardship (ePAMS+) intervention for hospitals combining technological and behavioural components: protocol for a feasibility trial.

BACKGROUND: Antimicrobial resistance is a leading global public health threat, with inappropriate use of antimicrobials in healthcare contributing to its development. Given this urgent need, we developed a complex ePrescribing-based Anti-Microbial Stewardship intervention (ePAMS+). METHODS: ePAMS+ includes educational and organisational behavioural elements, plus guideline-based clinical decision support to aid optimal antimicrobial use in hospital inpatients. ePAMS+ particularly focuses on prompt initiation of antimicrobials, followed by early review once test results are available to facilitate informed decision-making on stopping or switching where appropriate. A mixed-methods feasibility trial of ePAMS+ will take place in two NHS acute hospital care organisations. Qualitative staff interviews and observation of practice will respectively gather staff views on the technical component of ePAMS+ and information on their use of ePAMS+ in routine work. Focus groups will elicit staff and patient views on ePAMS+; one-to-one interviews will discuss antimicrobial stewardship with staff and will record patient experiences of receiving antibiotics and their thoughts on inappropriate prescribing. Qualitative data will be analysed thematically. Fidelity Index development will enable enactment of ePAMS+ to be measured objectively in a subsequent trial assessing the effectiveness of ePAMS+. Quantitative data collection will determine the feasibility of extracting data and deriving key summaries of antimicrobial prescribing; we will quantify variability in the primary outcome, number of antibiotic defined daily doses, to inform the future larger-scale trial design. DISCUSSION: This trial is essential to determine the feasibility of implementing the ePAMS+ intervention and measuring relevant outcomes, prior to evaluating its clinical and cost-effectiveness in a full scale hybrid cluster-randomised stepped-wedge clinical trial. Findings will be shared with study sites and with qualitative research participants and will be published in peer-reviewed journals and presented at academic conferences. TRIAL REGISTRATION: The qualitative and Fidelity Index research were approved by the Health and Research Authority and the North of Scotland Research Ethics Service (ref: 19/NS/0174). The feasibility trial and quantitative analysis (protocol v1.0, 15 December 2021) were approved by the London South East Research Ethics Committee (ref: 22/LO/0204) and registered with ISRCTN ( ISRCTN 13429325 ) on 24 March 2022.

Sporadic Creutzfeldt-Jakob Disease in the young (50 and below): 10-year review of United Kingdom surveillance.

INTRODUCTION: Sporadic Creutzfeldt-Jakob Disease (sCJD) is the commonest human prion disease, with a median age of onset of 68 years. We characterise the clinical, investigation, and neuropathological features in young individuals with sCJD using data from UK national CJD surveillance. METHODS: Referrals between 2011 and 2021 were examined, with definite (post-mortem confirmed) or probable sCJD cases included. Clinical features, MRI, EEG, CSF RT-QuIC, 14-3-3, PRNP sequencing and neuropathological findings were examined. We compared younger (≤ 50 years age of onset) with older individuals. Records of Non-sCJD referrals were also reviewed. RESULTS: 46 (4%) young individuals were identified (age at onset 25-50) from 1178 cases. 15 (33%) were autopsy confirmed. Psychiatric disturbance (37% vs 22%, p = 0.02) and headache (11% vs 3%, p = 0.01) at presentation, and longer disease duration (by 1.45 months, 95% CI 0.43-2.79, logrank p = 0.007) were commoner. CSF RT-QuIC showed lower sensitivity (82% vs 93%, p = 0.02). There was no difference in sensitivity of MR brain or CSF 14-3-3. There were no significant co-pathologies in autopsy-confirmed cases. For non-sCJD referrals, 41 cases were of other CJD subtypes, and 7 non-prion diagnoses. CONCLUSIONS: Young-onset sCJD is more likely to present with neuropsychiatric symptoms and headache, longer disease duration, and lower sensitivity of RT-QuIC. These findings may be driven by the underlying molecular subtypes. Our results guide the evaluation of younger individuals presenting with rapidly progressive cognitive, neuropsychiatric, and motor decline, and emphasise the need for additional vigilance for atypical features by clinicians and CJD surveillance programmes worldwide.

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.

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.

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.

Validation of Revised International Creutzfeldt-Jakob Disease Surveillance Network Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease.

Importance: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly lethal disease. Rapid, accurate diagnosis is imperative for epidemiological surveillance and public health activities to exclude treatable differentials and facilitate supportive care. In 2017, the International CJD Surveillance Network diagnostic criteria were revised to incorporate cortical ribboning on magnetic resonance imaging and the real-time quaking-induced conversion (RT-QuIC) assay, developments that require multicenter evaluation. Objective: To evaluate the accuracy of revised diagnostic criteria through the retrospective diagnosis of autopsy-confirmed cases (referred to as in-life diagnosis). Design, Setting, and Participants: This diagnostic study used a 3-year clinicopathological series using all cases of autopsy-confirmed sCJD and a noncase group with alternative neuropathological diagnoses from national surveillance centers in the United Kingdom, France, Germany, and Italy. Data were collected from January 2017 to December 2019 and analyzed from January 2020 to November 2021. Main Outcomes and Measures: Sensitivity and specificity of revised diagnostic criteria and diagnostic investigations. Secondary analyses assessing sCJD subgroups by genotype, pathological classification, disease duration, and age. Results: A total of 501 sCJD cases and 146 noncases were included. Noncase diagnoses included neurodegenerative diseases, autoimmune encephalitis, and cerebral insults such as anoxia. Participants in the sCJD cases cohort were younger (mean [SD] age, 68.8 [9.8] years vs 72.8 [10.9] years; P < .001) and had longer median (IQR) disease duration (118 [74.8-222.3] days vs 85 [51.5-205.5] days; P = .002); sex ratios were equivalent (253 [50.5%] male cases vs 74 [50.7%] male noncases). Sensitivity of revised criteria in in-life diagnosis (450 of 488 [92.2%] diagnoses; 95% CI, 89.5%-94.4%) was increased compared with prior criteria (378 of 488 [77.5%] diagnoses; 95% CI, 73.5%-81.1%; P < .001), while specificity (101 of 125 [80.8%] diagnoses; 95% CI, 72.8%-87.3%) was unchanged (102 of 125 [81.6%] diagnoses; 95% CI, 73.7%-88.0%; P > .99). Among 223 cases and 52 noncases with the full panel of investigations performed, sensitivity of revised criteria (97.8%; 95% CI, 94.9%-99.3%) was increased compared with prior criteria (76.2%; 95% CI, 70.1%-81.7%; P < .001) while specificity was unchanged (67.3%; 95% CI, 52.9%-79.7% vs 69.2%; 95% CI, 54.9%-81.3%; P > .99). In 455 cases and 111 noncases, cortical ribboning was 67.9% sensitive (95% CI, 63.4%-72.2%) and 86.5% specific (95% CI, 78.7%-92.2%). In 274 cases and 77 noncases, RT-QuIC was 91.6% sensitive (95% CI, 87.7%-94.6%) and 100% specific (95% CI, 96.2%-100%). Investigation sensitivity varied with genetic and pathological features, disease duration, and age. Conclusions and Relevance: This diagnostic study demonstrated significantly improved sensitivity of revised sCJD diagnostic criteria with unaltered specificity. The revision has enhanced diagnostic accuracy for clinical care and surveillance.

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.

The importance of ongoing international surveillance for Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS. International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD (vCJD), a disease linked to bovine spongiform encephalopathy. Control measures have now successfully contained bovine spongiform encephalopathy and the incidence of vCJD has declined, leading to questions about the requirement for ongoing surveillance. However, several lines of evidence have raised concerns that further cases of vCJD could emerge as a result of prolonged incubation and/or secondary transmission. Emerging evidence from peripheral tissue distribution studies employing high-sensitivity assays suggests that all forms of human prion disease carry a theoretical risk of iatrogenic transmission. Finally, emerging diseases, such as chronic wasting disease and camel prion disease, pose further risks to public health. In this Review, we provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance remains vital both from a public health perspective and to support essential research into disease pathophysiology, enhanced diagnostic tests and much-needed treatments.

Non-white cases of sporadic Creutzfeldt-Jakob disease: A 28 year review of United Kingdom National Surveillance Data.

AIMS: Descriptions of sporadic Creutzfeldt-Jakob disease (sCJD) in non-White populations are limited. Improved understanding may aid diagnoses and case ascertainment within surveillance programmes. We aimed to: 1) Ascertain the proportion of sCJD cases with non-White ethnicity in the United Kingdom (UK); 2) Compare clinical and investigation findings between non-White and White cases. METHODS: We analysed records of probable and definite sCJD cases assessed by the UK National CJD Research and Surveillance Unit over 28 years (1990-2017). Cases were stratified into White and non-White groups. Demographics, clinical features, investigation findings, and post-mortem numbers were compared. RESULTS: 1697 sCJD cases were included: 1642 (97%) White, 55 (3%) non-White (Asian/Asian British, Black/African/Caribbean). The proportion of non-Whites among sCJD cases is 7% lower than the proportion the non-White population make up in the UK (p < 0.001). This was not statistically significant when age-matched by ≥60 years (p = 0.071). Age at symptom onset was 4 years lower in the non-White population (p = 0.007). Clinical and investigation characteristics were otherwise similar between ethnic groupings. The proportion of non-Whites undergoing autopsy and classification as definite was 30% and 24% lower (p < 0.001) respectively in comparison to those for White cases. CONCLUSIONS: Approximately 3% of sCJD cases in the UK are non-White, despite non-Whites representing approximately 10% of the UK population. This difference was not statistically significant when age-matched at ≥60 years. Non-White cases tend to be younger and likelihood of autopsy is lower; relevant considerations for surveillance programmes. Reasons for these differences in non-White populations are unclear and merit further evaluation.

A rapid review and narrative synthesis of hospital to community pharmacy transfer of care services in England.

OBJECTIVES: A new discharge medicines service in England has been proposed for rollout in July 2020. This study aims to appraise the evidence for hospital to community pharmacy referral services in England. A rapid review methodology was adopted, findings were synthesised and reported narratively. The PubMed search engine was used and specific pharmacy journals were searched in March 2020. Studies published since 2012, reporting on transfer of care (ToC) services provided from hospitals and community pharmacies in England were included. Study data analysed included clinical outcomes; findings relating to implementation, staff and patient perceptions and experiences. Studies were assessed for risk of bias using a critical appraisal checklist. KEY FINDINGS: Ten studies met the inclusion criteria. The ToC services varied in relation to patients targeted, mode of referral, and post-discharge service provided. There were some conservative observations that ToC services were associated with reduced hospital readmission rates, however other outcomes were less well substantiated. Pharmacy staff were generally supportive of these services for patient benefit, however, patient engagement and accessibility issues have been reported. SUMMARY: There is some emerging evidence that hospital to community pharmacy referral services are associated with reduced hospital readmission. Service delivery reported in these studies highlights barriers and facilitators to patient recruitment, engagement and follow-up and limitations on recording and measuring meaningful outcomes. Future work is recommended to take advantage of the implementation and delivery of the national service that includes the analysis of patient data at scale to substantiate evidence in this area.