Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

BACKGROUND: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. OBJECTIVE: We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. METHODS: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. RESULTS: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. CONCLUSIONS: The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

In the heat of the moment: the effects of extreme temperatures on the cognitive functioning of firefighters.

Exposure to high temperatures can have detrimental effects on cognitive processing and this is concerning for firefighters who routinely work in extreme temperatures. Whilst past research has studied the effects of heat on firefighter cognition, findings are mixed, and no work has measured the time course of cognitive recovery. This study compared working memory, vigilance, and cognitive flexibility of 37 firefighters before and after they engaged in a live-fire training exercise with temperatures exceeding 115 °C. To assess recovery, cognition was measured on exiting the fire, then 20- and 40-minutes post-fire. Results showed impaired vigilance and cognitive flexibility (increased errors, slower responses) immediately after the fire, but recovery at 20-minutes. These findings indicate that a live indoor fire negatively impacts cognitive processing, but this effect is relatively short-lived and return to baseline functioning is seen 20-minutes after exiting the fire. The findings could be used to inform re-entry and cooling decisions.

Acute heat stress may affect cognitive processing, posing a health and safety risk to firefighters. This study demonstrates impaired cognition following a firefighter training exercise in temperatures exceeding 115 °C. Cognition recovered as core body temperature returned to normal, providing evidence for a 20-minute cooling period following exposure to extreme heat.

Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes. METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups. FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (ß 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity. INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation. FUNDING: None.

Exploring the carry-over of top-down attentional settings in dynamic conditions.

A top-down attentional set can persist from a relevant task to an irrelevant task, influencing allocation of attentional resources, visual search, and performance. While this "carry-over" effect has been found across numerous experiments, past studies have utilised paradigms that present similar tasks to the same spatial location. The present research explored whether attentional settings persist in more dynamic situations. In Experiment 1, participants played a computer game that encouraged a horizontal, vertical, or random spread of search. After 10 or 30 s, they moved 90° to their right and monitored a driving video for hazards. Eye movements to the videos were not affected by the characteristics of the preceding game, revealing no carry-over of attentional settings. One possible explanation for this was the visuospatial shift between the tasks. To explore this further, Experiment 2 adopted a similar paradigm to previous research; participants searched horizontal, vertical, or random letter strings before completing an image search. In one block the tasks were presented to the same screen, and in one block the tasks were presented to different screens (incorporating a 90° visuospatial shift mid-trial). Carry-over was found in the one-screen block, with a significantly wider horizontal search and a narrower vertical search in the pictures after a horizontal letter search. However, there was no carry-over from the letter to the picture task in the two-screen block. This indicates the flexibility of attentional control in dynamic situations, and it is suggested that persistence of attentional settings will be most costly under stable conditions.

AbobotulinumtoxinA is effective in patients with urinary incontinence due to neurogenic detrusor overactivity regardless of spinal cord injury or multiple sclerosis etiology: Pooled analysis of two phase III randomized studies (CONTENT1 and CONTENT2).

BACKGROUND: Neurogenic detrusor overactivity incontinence (NDOI) is often inadequately managed with oral therapy. OBJECTIVE: To assess efficacy and safety of abobotulinumtoxinA (aboBoNT-A; Dysport®; Ipsen Ltd.) according to etiology of NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two phase III, randomized, double-blind studies (CONTENT1 [NCT02660138] conducted in Asia, Europe and North America; CONTENT2 [NCT02660359] conducted in the Americas, Asia, Europe and Oceania) both included patients with spinal cord injury (SCI) or multiple sclerosis (MS), with inadequately managed NDOI, regularly performing clean intermittent catheterization (CIC). INTERVENTION: Patients in CONTENT1 and CONTENT2 received aboBoNT-A injections 600 U (n = 162)/800 U (n = 161), or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint: mean change from baseline in number of NDOI episodes/week at Week 6. Secondary endpoints: proportion of patients with no NDOI episodes; incontinence-related quality of life (I-QoL); urodynamic parameters; and time-to-retreatment. Safety was also assessed. Statistical analyses were conducted for pooled populations by etiology (aboBoNT-A doses vs. placebo). RESULTS AND LIMITATIONS: Of 485 randomized patients, 341 (70%) and 144 (30%) had SCI and MS etiologies, respectively. A significant reduction was observed in mean NDOI episodes/week at Week 6 with both aboBoNT-A doses versus placebo in the SCI (all p < 0.001) and MS (all p < 0.01) groups, as well as significant improvements in I-QoL and urodynamic parameters. Median time-to-retreatment was longer in patients with MS (48-62 weeks across doses) than those with SCI (39-44 weeks). Safety data were similar between etiologies. Urinary tract infection was the most frequent adverse event; similar numbers were reported across treatment groups. CONCLUSIONS: AboBoNT-A was well tolerated and significantly improved continence and bladder function, and QoL, in patients with SCI or MS with NDOI performing regular CIC. PATIENT SUMMARY: AboBoNT-A injections improved QoL, symptoms, and bladder function in patients with SCI or MS with bladder muscle overactivity that causes incontinence.

Psychosocial and medical factors associated with intrathecal baclofen pump explants: A case series.

PURPOSE: The goal of this retrospective chart review study was to explore factors that contributed to consideration of or actual pump explantation in pediatric patients with intrathecal baclofen (ITB) pumps. METHODS: Medical records of 30 patients with ITB pumps were reviewed. Quantitative data, including demographic, clinical, psychosocial, and service utilization variables were culled from the records. Qualitative data were collected from clinic visit notes, pump-related follow-up phone calls, and any pump-related emergency room visits. RESULTS: Of those reviewed, six underwent ITB pump explantation, and two considered explantation. Factors contributing to pump explantation or consideration of explantation included the following: postoperative infection, pump malfunction, non-adherence, anxiety/behavioral factors impacting the patient's tolerance of the pump, distance to the medical provider, frequency of required pump refill appointments, lack or perceived lack of intrathecal baclofen effect, and difficulty transitioning to adult care providers. CONCLUSION: Due to the complex care regimen associated with ITB pumps and various psychosocial and logistical factors that impact treatment success, a standardized multidisciplinary pre-implantation education, screening, and assessment process should be developed. Such a process would ensure that patients/families receive appropriate education, including proactively identifying treatment barriers and potential complications, possibly minimizing dissatisfaction with treatment and the need for explantation.

Do extreme temperatures affect cognition? A short review of the impact of acute heat stress on cognitive performance of firefighters.

Research shows that exposure to high environmental temperatures can affect task performance. Theoretical explanations outline that heat is a source of stress that competes for limited-capacity resources, therefore if a task is resource-intensive, and/or if heat stress is extreme, performance will suffer. One occupation in which individuals complete demanding tasks and make difficult decisions, often in temperatures exceeding 200°C, is firefighting. Yet very little is currently known about the impact of heat stress on the cognitive functioning of firefighters. This short review summarizes the limited research in this area, focusing on studies that measured cognition of firefighters following a realistic training exercise. The findings are mixed with evidence that heat stress improves, impairs, and has no impact on cognitive functioning. While there are differences in the firefighting activities utilized, and the temperatures that participants were exposed to, it is argued that the varied findings can be attributed to the tasks used to assess cognitive processing, and the cognitive functions being measured. In accordance with the wider field of research, it is concluded that complex functioning, such as sustained attention, vigilance, and working memory is negatively impacted by acute exposure to extreme heat. Greater understanding of factors affecting cognition would inform safety practices and more research is needed to understand how and when heat stress may influence cognition in firefighting scenarios.

Liquid AbobotulinumtoxinA: Pooled Data From Two Double-Blind, Randomized, Placebo-Controlled Phase III Studies of Glabellar Line Treatment.

BACKGROUND: AbobotulinumtoxinA (aboBoNT-A) solution is a new ready-to-use formulation developed to reduce preparation time and improve reproducibility of injections. OBJECTIVE: To further evaluate treatment of moderate-to-severe glabellar lines (GLs) using pooled data from 2 Phase III studies. METHODS: Following double-blind treatment with 50 U aboBoNT-A solution (n = 251) or placebo (n = 123), GL severity was assessed by investigators (ILA) and subjects (SSA). Other assessments included subject-reported time to onset, subject satisfaction, FACE-Q, and adverse events. RESULTS: One month after aboBoNT-A solution treatment, 88% had none-or-mild GLs at maximum frown and 93% had ≥1-grade improvement in ILA (similar for SSA), 24% to 27% remaining improved at Month 6. Glabellar lines responder rates remained higher than placebo throughout Month 6 ( p < .001). Almost two-thirds of subjects reported onset within 3 days, nearly a quarter reporting effect by Day 1. Subject satisfaction with GL appearance, and FACE-Q satisfaction with facial appearance overall and psychological well-being were also improved over placebo throughout Month 6, p < .05. Treatment-related adverse events were nonserious and mild or moderate. CONCLUSION: Pooled analysis confirmed a duration of effect on GLs of up to 6 months for aboBoNT-A solution, with onset starting within 24 hours, high subject satisfaction, and improved psychological well-being. The treatment was well tolerated.

Efficacy and Safety of AbobotulinumtoxinA in Patients with Neurogenic Detrusor Overactivity Incontinence Performing Regular Clean Intermittent Catheterization: Pooled Results from Two Phase 3 Randomized Studies (CONTENT1 and CONTENT2).

BACKGROUND: For patients with neurogenic detrusor overactivity incontinence (NDOI), treatment with oral medications is often unsatisfactory. OBJECTIVE: To assess the efficacy and safety of abobotulinumtoxinA (aboBoNT-A) for NDOI. DESIGN, SETTING, AND PARTICIPANTS: Two randomized, double-blind phase 3 studies (CONTENT1, NCT02660138; CONTENT2, NCT02660359) enrolled patients with NDOI who were regularly performing clean intermittent catheterization (CIC) and were inadequately managed with oral therapy. Pooled results from the first placebo-controlled treatment cycle are reported. INTERVENTION: Patients received injections of aboBoNT-A 600 U (n = 162) or 800 U (n = 161) or placebo (n = 162) into the detrusor muscle. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the mean change from baseline in NDOI episodes per week at week 6. Secondary endpoints reported are the proportion of patients with no NDOI episodes, the volume per void, urodynamic parameters, and quality of life (QoL). Safety was also assessed. Statistical analyses were conducted for the pooled study populations (each aboBoNT-A dose vs placebo). RESULTS AND LIMITATIONS: At week 6, NDOI episodes per week were significantly reduced in each aboBoNT-A group versus placebo (both p < 0.001) and the volume per void had significantly increased. Approximately one-third of patients in each aboBoNT-A dose group reported no NDOI episodes versus 3% of patients in the placebo group. Reductions in urinary incontinence (UI) were reflected in significantly greater improvements in UI-related QoL in the aboBoNT-A groups versus placebo. Urodynamic parameters (bladder capacity and detrusor pressure) were significantly improved with each aboBoNT-A dose versus placebo. Each aboBoNT-A dose was well tolerated. Symptomatic urinary tract infection was the most frequent treatment-emergent adverse event, with incidence comparable across the aboBoNT-A and placebo groups. The studies were terminated prematurely owing to slow recruitment and were not designed for statistical comparison between the two aboBoNT-A doses. CONCLUSIONS: Intradetrusor aboBoNT-A is an effective treatment and alternative option for patients with NDOI who have an inadequate response to oral anticholinergics and are already performing CIC. PATIENT SUMMARY: In patients with bladder muscle overactivity caused by neurological conditions (multiple sclerosis or spinal cord injury) and resulting in urinary incontinence, abobotulinumtoxinA injections improved their symptoms and bladder function, with no unexpected effects.

The influence of stimuli valence, extraversion, and emotion regulation on visual search within real-world scenes.

Affective traits, including extraversion and emotion regulation, are important considerations in clinical psychology due to their associations with the occurrence of affective disorders. Previously, emotional real-world scenes have been shown to influence visual search. However, it is currently unknown whether extraversion and emotion regulation can influence visual search towards neutral targets embedded within real-world scenes, or whether these traits can impact the effect of emotional stimuli on visual search. An opportunity sample of healthy individuals had trait levels of extraversion and emotion regulation recorded before completing a visual search task. Participants more accurately identified search targets in neutral images compared to positive images, whilst response times were slower in negative images. Importantly, individuals with higher trait levels of expressive suppression displayed faster identification of search targets regardless of the emotional valence of the stimuli. Extraversion and cognitive reappraisal did not influence visual search. These findings add to our understanding regarding the influence of extraversion, cognitive reappraisal, and expressive suppression on our ability to allocate attention during visual search when viewing real-world scenes.

Long-term Efficacy and Safety of Liquid AbobotulinumtoxinA Formulation for Moderate-to-Severe Glabellar Lines: A Phase III, Double-Blind, Randomized, Placebo-Controlled and Open-Label Study.

BACKGROUND: A ready-to-use liquid formulation of abobotulinumtoxinA (aboBoNT-A solution) has been developed. OBJECTIVES: The aim of this study was to assess the long-term efficacy and safety of aboBoNT-A solution for the treatment of glabellar lines. METHODS: This was a multicenter, multinational, Phase III study (NCT02493946), with randomized double-blind placebo-controlled (DBPC; 2:1 aboBoNT-A solution 50 U/placebo) and open-label (4 cycles aboBoNT-A solution) periods; additional patients were recruited into the open-label period. Patients were 18 to 65 years old, BoNT-naïve, and dissatisfied/very dissatisfied with moderate/severe glabellar lines at maximum frown. Investigator's live assessment (primary endpoint)/subject's self-assessment of glabellar line severity at maximum frown, patient satisfaction with glabellar line appearance, and FACE-Q patient-reported scales (facial appearance overall, psychological well-being, aging) were assessed. Adverse events were monitored. Analyses were performed on DBPC and long-term analysis (LTA; all patients receiving ≥1 aboBoNT-A solution injection) populations. RESULTS: Responder rates for the investigator's live assessment, the subject's self-assessment, and patient satisfaction were consistent at Day 29 postinjection across repeat LTA cycles (82.2%-87.8%, 62.8%-80.6%, and 72.2%-87.8%, respectively), with statistically significantly higher responder rates vs placebo (DBPC cycle: 81.6% vs 0.8%, 68.1% vs 2.3%, and 83.1% vs 5.7%, respectively; all P < 0.0001). Consistent improvements on FACE-Q scales occurred with repeat cycles (DBPC cycle: aboBoNT-A solution vs placebo, P < 0.0001). No new or unexpected adverse events, or neutralizing antibodies, were observed. CONCLUSIONS: These results support the long-term efficacy and safety of aboBoNT-A solution, and its superiority over placebo, for treatment of glabellar lines in adults.

Muscle Selection and Dosing in a Phase 3, Pivotal Study of AbobotulinumtoxinA Injection in Upper Limb Muscles in Children With Cerebral Palsy.

Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy. Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle group (PTMG, wrist or elbow flexors) and additional muscles tailored to clinical presentation. During Cycles 2-4, children received doses of 8 U/kg or 16 U/kg and investigators could change the PTMG and other muscles to be injected. Injection of muscles in the other upper limb and lower limbs was also permitted in cycles 2-4, with the total body dose not to exceed 30 U/kg or 1,000 U (whichever was lower) in the case of upper and lower limb treatment. Results: 212 children were randomized, of which 210 received ≥1 abobotulinumtoxinA injection. Per protocol, the elbow and wrist flexors were the most commonly injected upper limb muscles. Across all 4 cycles, the brachialis was injected in 89.5% of children (dose range 0.8-6 U/kg), the brachioradialis in 83.8% (0.4-3 U/kg), the flexor carpi ulnaris in 82.4% (0.5-3 U/kg) and the flexor carpi radialis in 79.5% (0.5-4 U/kg). Other frequently injected upper limb muscles were the pronator teres(70.0%, 0.3-3 U/kg). adductor pollicis (54.3%, 0.3-1 U/kg), pronator quadratus (44.8%, 0.1-2 U/kg), flexor digitorum superficialis (39.0%, 0.5-4 U/kg), flexor digitorum profundus (28.6%, 0.5-2 U), flexor pollicis brevis/opponens pollicis (27.6%, 0.3-1 U/kg) and biceps (27.1%, 0.5-6 U/kg). AbobotulinumtoxinA was well-tolerated at these doses; muscular weakness was reported in 4.3% of children in the 8 U/kg group and 5.7% in the 16 U/kg group. Conclusions: These data provide information on the pattern of injected muscles and dose ranges used in this study, which were well-tolerated. Per protocol, most children received injections into the elbow and wrist flexors. However, there was a wide variety of other upper limb muscles injected as physicians tailored injection patterns to clinical need.

Interactive influences of emotion and extraversion on visual attention.

INTRODUCTION: Emotion has been shown to influence selective visual attention. However, studies in this field have revealed contradictory findings regarding the nature of this influence. One possible explanation for the variation in findings is that affective inter-individual differences impact both attention and emotion and may therefore moderate any influence of emotion on attention. The current work is a novel investigation of the effects of induced emotional states and the traits of extraversion and neuroticism on visual attention. This allowed a direct investigation of any impact of extraversion and neuroticism on the way in which emotion influences attention. METHODS: Participants were induced into positive, neutral, and negative emotional states before completing a change detection flicker task in which they were required to locate a change to a real-world scene as quickly and accurately as possible. RESULTS: Participants scoring higher in extraversion were more accurate but slower at detecting changes. Importantly, this was particularly evident when induced into a negative emotional state compared to a neutral emotional state. Neuroticism had no impact on attention. CONCLUSIONS: The current study provides evidence that extraversion can moderate the influence of negative emotion upon visual attention and may help to explain some of the contradictory findings in this research area. When considered independently, increased trait levels of extraversion were associated with improved change detection. Individuals higher in extraversion appear better equipped to regulate negative emotion compared to individuals lower in extraversion, supporting research linking extraversion to affective reactivity and models of psychopathology.

Comparison of the Pharmacokinetic Profiles of Trientine Tetrahydrochloride and Trientine Dihydrochloride in Healthy Subjects.

BACKGROUND AND OBJECTIVE: Wilson disease (WD) is an autosomal recessive inherited disorder of copper metabolism. Chelation of excessive copper is recommended but data on the pharmacokinetics of trientine are limited. The aim of this study was to compare the pharmacokinetics of a new trientine tetrahydrochloride formulation (TETA 4HCl) with those of an established trientine dihydrochloride (TETA 2HCl) salt. METHODS: A randomised single-centre crossover study to evaluate the pharmacokinetics, safety and tolerability of two different oral formulations of trientine (TETA 4HCl tablets vs TETA 2HCl capsules) in 23 healthy adult subjects receiving a single dose equivalent to 600 mg of trientine base was performed. RESULTS: Following oral administration, the median time to reach maximum plasma concentration (Tmax) was 2.00 h (TETA 4HCl) and 3.00 h (TETA 2HCl). The rate (maximum plasma concentration [Cmax]) and extent (area under the plasma concentration-time curve from time zero to infinity [AUC0-∞]) of absorption of the active moiety, trientine, were greater (by approximately 68% and 56%, respectively) for TETA 4HCl than for the TETA 2HCl formulation. The two formulations presented a similar terminal elimination rate (λz) and a similar terminal half-life (t½) for trientine. Differences between TETA 4HCl and TETA 2HCl in the levels of the two main mono- and diacetylated metabolites were less than seen for trientine. For both tested formulations, healthy male volunteers demonstrated higher trientine plasma levels but lower mono- and diacetylated metabolite levels compared with females, with no sex differences in terminal half-life (t½) observed. Single oral doses of both formulations were safe and well tolerated. CONCLUSIONS: Compared with an identical dose of a TETA 2HCl formulation, the TETA 4HCl formulation provided more rapid absorption of trientine and greater systemic exposure in healthy subjects. Clinical Trials Number EudraCT # 2015-002199-25.

Carry-over of attentional settings between distinct tasks: A transient effect independent of top-down contextual biases.

Top-down attentional settings can persist between two unrelated tasks, influencing visual attention and performance. This study investigated whether top-down contextual information in a second task could moderate this "attentional inertia" effect. Forty participants searched through letter strings arranged horizontally, vertically, or randomly and then made a judgement about road, nature, or fractal images. Eye movements were recorded to the picture search and findings showed greater horizontal search in the pictures following horizontal letter strings and narrower horizontal search following vertical letter strings, but only in the first 1000 ms. This shows a brief persistence of attentional settings, consistent with past findings. Crucially, attentional inertia did not vary according to image type. This indicates that top-down contextual biases within a scene have limited impact on the persistence of previously relevant, but now irrelevant, attentional settings.

An outbreak of adenovirus D8 keratoconjunctivitis in Leicester, United Kingdom, from March to August 2019.

We report a large epidemic (n = 126) of keratoconjunctivitis predominantly with two lineages of adenovirus (AdV) type D8 in patients seen in eye casualty between march and August 2019. Other AdV species identified by viral sequencing included B, C, and E. Despite various features of more severe eye disease being present, these were not significantly different between the different AdV species, with similar rates of pseudomembrane formation and keratitis observed in patients with AdV species B as for those with AdV species D.

Commentary: Do we need new parenting programmes for different cultural groups or should we adapt those that already exist: a commentary on Ward et al. (2019).

This paper By Ward et al. (Journal of Child Psychology and Psychiatry, 2019) in the issue of the JCPP, is an excellent example of preparing a new programme for parents with children at high risk of present and future behaviour problems. It was to be delivered in a very deprived population in a township in South Africa. We discuss the paper but also raise questions about developing new programmes when they are already successful programmes available and discuss whether it is time for programme developers to meet to discuss what works best and for whom.

End of season influenza vaccine effectiveness in primary care in adults and children in the United Kingdom in 2018/19.

2018/19 was the first season of introduction of a newly licensed adjuvanted influenza vaccine (aTIV) for adults aged 65 years and over and the sixth season in the roll-out of a childhood influenza vaccination programme with a quadrivalent live attenuated influenza vaccine (LAIV). The season saw mainly A(H1N1)pdm09 and latterly A(H3N2) circulation. End-of-season adjusted vaccine effectiveness (aVE) estimates against laboratory confirmed influenza infection in primary care were calculated using the test negative case control method adjusting for key confounders. End-of-season aVE was 44.3% (95% CI: 26.8, 57.7) against all laboratory-confirmed influenza; 45.7% (95% CI: 26.0, 60.1) against influenza A(H1N1)pdm09 and 35.1% (95% CI: -3.7,59.3) against A(H3N2). Overall aVE was 49.9% (95%CI: -13.7, 77.9) for all those ≥ 65 years of age and 62.0% (95% CI: 3.4, 85.0) for those who received aTIV. Overall aVE for 2-17 year olds receiving LAIV was 48.6% (95% CI: -4.4, 74.7). The paper provides evidence of overall significant influenza VE in 2018/19, most notably against influenza A(H1N1)pdm09, however, as seen in 2017/18, there was reduced, non-significant VE against A(H3N2). aTIV provided significant protection for those 65 years of age and over.

Adenovirus Type 7 causing severe lower respiratory tract infection in immunocompetent adults: a comparison of two contrasting cases from an intensive care unit in North West England.

OBJECTIVES: Severe lower respiratory tract infection caused by adenovirus is well described in immunocompromised hosts and can cause significant morbidity and mortality. We compare and contrast the clinical presentation, radiological, and virological features of two rare cases in immunocompetent adults admitted to an intensive care unit in a large, teaching hospital in North West England. We then provide a concise, comprehensive literature review. METHODS: The first case was a 35-year old female asthmatic who presented with respiratory distress and pneumonitis during peak influenza season, and recovered after a prolonged hospital stay. The second case was a 73-year old male who presented with diarrhoea, vomiting, and general malaise outside of influenza season, developed respiratory compromise, and died. Adenovirus type 7 was identified in bronchoalveolar lavages and plasma samples of both patients, each of whom received cidofovir. No other infectious aetiology was identified. RESULTS: Clinical and radiological features of severe lower respiratory tract adenoviral infection are similar to other infectious causes of pneumonia and ARDS, including severe influenza. This can create diagnostic uncertainty, especially during influenza season. Positive adenovirus polymerase chain reaction results can support a diagnosis of severe lower respiratory tract adenovirus infection in patients with a clinically compatible syndrome and no other identified aetiology, with higher viral loads being associated with worse prognosis. Although treatment is predominantly supportive, early use of cidofovir may improve outcomes. CONCLUSIONS: These rare cases highlight that severe lower respiratory tract adenoviral infection should be considered in the differential diagnoses of immunocompetent patients presenting with pneumonia and ARDS.

Robot-assisted Laparoscopic Nephroureterectomy for a Nephrogenic Adenoma of Ureter.

Nephrogenic adenoma is a rare and benign tumour of the urinary tract thought to be caused by metaplastic change of native urothelial tissue. The majority of cases arise in the bladder, with very few cases affecting the ureter reported in the literature. Herein, we describe the presentation, diagnostic challenges, and the eventual management of a nephrogenic adenoma of the ureter by robot-assisted laparoscopic nephroureterectomy. Urologists and pathologists should be aware of the potential diagnostic and management pitfalls associated with this rare tumour, as well as the sparsity of evidence with respect to follow-up.