Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery-a multicentre observational study.

Background: Outcomes after oesophagogastric cancer surgery remain poor. Cardiopulmonary exercise testing (CPET) used for risk stratification before oesophagogastric cancer surgery is based on conflicting evidence. This study explores the relationship between CPET and postoperative outcomes, specifically for patients undergoing neoadjuvant treatment. Methods: Patients undergoing oesophagogastric cancer resection and CPET (pre- or post-neoadjuvant treatment, or both) were retrospectively enrolled into a multicentre pooled cohort study. Oxygen uptake at peak exercise (VO2 peak) was compared with 1-yr postoperative survival. Secondary analyses explored relationships between patient characteristics, tumour pathology characteristics, CPET variables (absolute, relative to weight, ideal body weight, and body surface area), and postoperative outcomes (morbidity, 1-yr and 3-yr survival) were assessed using logistic regression analyses. Results: Seven UK centres recruited 611 patients completing a 3-yr postoperative follow-up period. Oesophagectomy was undertaken in 475 patients (78%). Major complications occurred in 25%, with 18% 1-yr and 43% 3-yr mortality. No association between VO2 peak or other selected CPET variables and 1-yr survival was observed in the overall cohort. In the overall cohort, the anaerobic threshold relative to ideal body weight was associated with 3-yr survival (P=0.013). Tumour characteristics (ypT/ypN/tumour regression/lymphovascular invasion/resection margin; P<0.001) and Clavien-Dindo ≥3a (P<0.001) were associated with 1-yr and 3-yr survival. On subgroup analyses, pre-neoadjuvant treatment CPET; anaerobic threshold (absolute; P=0.024, relative to ideal body weight; P=0.001, body surface area; P=0.009) and VE/VCO2 at anaerobic threshold (P=0.026) were associated with 3-yr survival. No other CPET variables (pre- or post-neoadjuvant treatment) were associated with survival. Conclusions: VO2 peak was not associated with 1-yr survival after oesophagogastric cancer resection. Tumour characteristics and major complications were associated with survival; however, only some selected pre-neoadjuvant treatment CPET variables were associated with 3-yr survival. CPET in this cohort of patients demonstrates limited outcome predictive precision. Clinical trial registration: NCT03637647.

Loss and Return of Ticklishness in Functional Neurological Disorder.

BACKGROUND: People with functional neurological disorder (FND) have abnormalities in sensory processing. Loss of ticklishness has been rarely reported. OBJECTIVES: To describe associated clinical features in people with FND and loss of ticklishness and explore correlations with sensory changes. METHODS: Retrospective audit of clinical letters of people diagnosed with FND in a tertiary clinic and further cases identified in a general neurology clinic. RESULTS: Thirty-eight patients with loss of ticklishness are described, of which most had other functional sensory symptoms and signs. It was more often localized to one limb, rather than generalized, in those with pain or weakness. Dissociation for the affected body part was often described. CONCLUSIONS: Loss of ticklishness in FND is frequently described and offers insights into mechanisms of agency, sensory processing and interoception, which are known to be altered in FND.

Individualising goal-directed haemodynamic therapy: future iterations will require novel trial designs.

Variants of perioperative cardiac output-guided haemodynamic therapy algorithms have been tested over the last few decades, without clear evidence of effectiveness. Newer approaches have focussed on individualisation of physiological targets and have been tested in early efficacy trials. Uncertainty about the benefits remains. Adoption of novel trial designs could overcome the limitations of smaller trials of this complex intervention and accelerate the exploration of future developments.

Illness perceptions, experiences of stigma and engagement in functional neurological disorder (FND): exploring the role of multidisciplinary group education sessions.

Background: A critical first step in managing functional neurological disorder (FND) is a positive diagnosis and clear explanation using an understandable illness model. Multidisciplinary group education sessions are one way to achieve this, with some evidence they improve understanding, confidence in diagnosis and outcomes with further treatment. In many conditions, illness perceptions and stigma affect distress, functioning, quality of life and engagement. Exploring relationships between these factors could lead to deeper understanding of the impact of education. Methods: Questionnaires assessing illness perceptions, quality of life, mood, anxiety, comorbidities, treatment engagement and stigma (both experienced and anticipated) were completed before, immediately and 1 month after a multidisciplinary online group education session for FND at a regional neurosciences centre. Free-text data on causal attributions and needs were also collected. Results: 166 patients attended online education sessions from January 2022 to July 2023; 61 (37%) completed presession surveys, 42 (25%) completed postsession and 35 (21%) completed 1 month postsession surveys. Patients reported multiple comorbidities, poor quality of life, functioning and high levels of stigma. Illness perception scores indicated FND as threatening, mysterious and unpredictable, with low personal or treatment control over symptoms. Illness coherence/understanding (mean difference 2.27, p<0.01, 95% CI 1.22 to 4.23) and engagement (mean difference 2.42, p<0.01, 95% CI 0.46 to 4.36) increased after the session. There were no significant changes in stigma, distress, sense of control or anticipated discrimination. Free-text analysis revealed stress and trauma as the most common causal attributions, followed by physical illnesses. Patients requested personalised formulations, practical disability advice, help with explaining the condition to others (eg, employers), peer support and treatment. Conclusion: Multidisciplinary group FND education sessions potentially improve patient understanding and engagement. Clinicians should consider the possible benefits of personalised formulations and linking to practical and peer support. Further work assessing illness perceptions is needed, such as adapting measures for FND.

Investigating psychobiological causes and mechanisms in functional seizures and functional motor symptoms: Study protocol.

INTRODUCTION: Advances have been made in understanding the aetiology of functional neurological disorder (FND); however, its pathophysiological mechanisms have not been definitively demonstrated. Evidence suggests interacting roles for altered emotional processing and interoception, elevated autonomic arousal, and dissociation, but there is limited evidence demonstrating their causal influence on specific FND symptoms. Our superordinate aim is to elucidate potentially shared and distinct aetiological factors and mechanisms in two common FND subtypes, functional seizures (FS) and functional motor symptoms (FMS). METHODS: This study has a multimodal, mixed between- and within-groups design. The target sample is 50 individuals with FS, 50 with FMS, 50 clinical controls (anxiety/depression), and 50 healthy controls. Potential aetiological factors (e.g., adverse life events, physical/mental health symptoms, dissociative tendencies, interoceptive insight/sensibility) will be assessed with a detailed medical history interview and self-report questionnaires. A laboratory session will include a neurocognitive battery, psychophysiological testing, cardiac interoception and time estimation tasks and an isometric handgrip task. A subsample will undergo magnetic resonance imaging, including structural, resting-state and task-based scans combined with psychophysiological recording. Remote monitoring with ecological momentary assessment and wearables will measure variability in FND symptoms and their potential predictors/correlates for ≥2 weeks in patients' daily lives. Longitudinal follow-ups at 3, 6, and 12-months will monitor longer-term outcomes in the clinical groups. DISCUSSION: This study employs multimodal research methods to rigorously examine several putative mechanisms in FND, at subjective/experiential, behavioural, and physiological levels. The study will test causal hypotheses about the role of altered emotional processing, autonomic arousal, dissociation and interoception in the initiation or exacerbation of FND symptoms, directly comparing these processes in FS and FMS to healthy and clinical controls. This is the first study of its kind, with potential to reveal important targets for prevention and treatment of FND in future.

Different deployments of attentional breadth selectively predict UFOV task performance in older adults.

The Useful Field of View task (UFOV) is a strong and reliable predictor of crash risk in older drivers. However, while the functional domain of attention is clearly implicated in UFOV performance, the potential role of one specific attentional process remains unclear: attentional breadth (the spatial extent of the attended region around the point of visual fixation). The goal of the present study was to systematically test the role of two distinct aspects of attentional breadth, maintaining a specific breadth of attention and resizing the attended region, in UFOV performance. To this end, 135 older adults completed the UFOV and modified Navon tasks to measure their efficiency in maintaining, contracting, and expanding the breadth of attention. We then examined individual-difference associations between these aspects of attentional breadth deployment and UFOV performance. We found that performance on UFOV Subtask 2 was associated with efficient contraction of attentional breadth (i.e., resizing the attended region to a smaller area), while Subtask 3 performance was associated with the efficiency of expanding attentional breadth (i.e., resizing the attended region to a larger area). The selectivity of these relationships appears to implicate these specific deployments of attentional breadth in how people complete the task, as it suggests that these relationships are not simply attributable to shared variance in a broader domain of cognitive functioning. The implications of these results for our understanding of UFOV, as well as future research directions that test the relative contributions of different cognitive processes in predicting task performance, are discussed.

Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study.

BACKGROUND: Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions. METHODS: International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter-rater agreement analyses were undertaken. RESULTS: Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%-88% of the FCD diagnoses were attributed to non-neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%-92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD. CONCLUSIONS: Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence-based interventions.

Specialist physiotherapy for functional motor disorder in England and Scotland (Physio4FMD): a pragmatic, multicentre, phase 3 randomised controlled trial.

BACKGROUND: Functional motor disorder-the motor variant of functional neurological disorder-is a disabling condition that is commonly associated with poor health outcomes. Pathophysiological models have inspired new treatment approaches such as specialist physiotherapy, although evidence from large randomised controlled trials is absent. We aimed to assess the clinical effectiveness of a specialist physiotherapy intervention for functional motor disorder compared with treatment as usual. METHODS: In this pragmatic, multicentre, phase 3 randomised controlled trial at 11 hospitals in England and Scotland, adults with a clinically definite diagnosis of functional motor disorder, diagnosed by a neurologist, were included. Participants were randomly assigned (1:1, stratified by site) using a remote web-based application to either specialist physiotherapy (a protocolised intervention of nine sessions plus follow-up) or treatment as usual (referral to local community neurological physiotherapy). Individuals working on data collection and analysis were masked to treatment allocation. The primary outcome was the physical functioning domain of the 36-item short form health questionnaire (SF36) at 12 months after randomisation. The primary analysis followed a modified intention-to-treat principle, using a complete case approach; participants who were unable to receive their randomised treatment due to the suspension of health-care services during the COVID-19 pandemic were excluded from the primary analysis. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN56136713, and is completed. FINDINGS: Recruitment occurred between Oct 19, 2018, and March 11, 2020, pausing during the COVID-19 lockdown, and resuming from Aug 3, 2021, to Jan 31, 2022. Of 355 participants who were enrolled, 179 were randomly assigned to specialist physiotherapy and 176 to treatment as usual. 89 participants were excluded from the primary analysis due to COVID-19 interruption to treatment (27 were assigned to specialist physiotherapy and 62 to treatment as usual). After accounting for withdrawals (n=11) and loss to follow-up (n=14), the primary analysis included data from 241 participants (138 [91%] assigned specialist physiotherapy and 103 [90%] assigned treatment as usual). Physical functioning, as assessed by SF36, did not differ significantly between groups (adjusted mean difference 3·5, 95% CI -2·3 to 9·3; p=0·23). There were no serious adverse events related to the trial interventions. 35 serious adverse events were recorded in the specialist physiotherapy group by 24 participants (17·0%), and 24 serious adverse events were recorded in the treatment as usual group by 18 participants (17·0%); one death occurred in the specialist physiotherapy group (cause of death was recorded as suicide). All were considered unrelated to specialist physiotherapy. INTERPRETATION: Although more participants who were assigned specialist physiotherapy self-rated their motor symptoms as improved and had better scores on subjective measures of mental health, the intervention did not result in better self-reported physical functioning at 12 months. Both the specialist and community neurological physiotherapy appeared to be a safe and a valued treatment for selected patients with functional motor disorder. Future research should continue to refine interventions for people with functional motor disorder and develop evidence-based methods to guide treatment triage decisions. FUNDING: National Institute for Health and Care Research and Health Technology Assessment Programme.

Individual differences in emotion-induced blindness: Are they reliable and what do they measure?

The emotion-induced-blindness (EIB) paradigm has been extensively used to investigate attentional biases to emotionally salient stimuli. However, the low reliability of EIB scores (the difference in performance between the neutral and emotionally salient condition) limits the effectiveness of the paradigm for investigating individual differences. Here, across two studies, we investigated whether we could improve the reliability of EIB scores. In Experiment 1, we introduced a mid-intensity emotionally salient stimuli condition, with the goal of obtaining a wider range of EIB magnitudes to promote reliability. In Experiment 2, we sought to reduce the attentional oddball effect, so we created a modified EIB paradigm by removing the filler images. Neither of these approaches improved the reliability of the EIB scores. Reliability for the high- and mid-intensity EIB difference scores were low, while reliability of the scores for absolute performance (neutral, high-, and mid-intensity) were high and the scores were also highly correlated, even though overall performance in the emotionally salient conditions were significantly worse than in the neutral conditions. Given these results, we can conclude that while emotionally salient stimuli impair performance in the EIB task compared with the neutral condition, the strong correlation between the emotionally salient and neutral conditions means that while EIB can be used to investigate individual differences in attentional control, it is not selective to individual differences in attentional biases to emotionally salient stimuli.

Cross-sectional evaluation of health resource use in patients with functional neurological disorders referred to a tertiary neuroscience centre.

Introduction: Functional neurological disorder (FND) is a common cause of referral to neurology services. FND has been shown to lead to significant healthcare resource use and is associated with significant disability, comorbidity and distress. This leads to substantial direct, indirect and intangible costs to the patient and society. Methods: We recruited consecutive patients with FND referred to a tertiary FND specialist clinic. We assessed health and social care resource use in the 6 months preceding their consultation through a modified version of the Client Service Receipt Inventory in the form of a postal questionnaire. The total cost was estimated by combining the number and frequency of health resource use with standard national unit costs. We also assessed indirect costs such as informal care and loss of income. Results: We collected data on 118 subjects. Patients with comorbid anxiety or depression had higher costs in the preceding 6 months, as did patients who had a longer duration of FND symptoms. Indirect costs were higher than the already substantial direct costs and a large proportion of patients with FND were receiving government support. Conclusion: This study highlights the high cost of FND to both patients and health systems. Adequate reform of the patient pathway and reorganisation of services to make diagnoses and initiate treatment more quickly would likely reduce these costs.

Reducing airborne transmissible diseases in perioperative environments.

The COVID-19 pandemic has transformed our understanding of aerosol transmissible disease and the measures required to minimise transmission. Anaesthesia providers are often in close proximity to patients and other hospital staff for prolonged periods while working in operating and procedure rooms. Although enhanced ventilation provides some protection from aerosol transmissible disease in these work areas, close proximity and long duration of exposure have the opposite effect. Surgical masks provide only minimal additional protection. Surgical patients are also at risk from viral and bacterial aerosols. Despite having recently experienced the most significant pandemic in 100 yr, we continue to lack adequate understanding of the true risks encountered from aerosol transmissible diseases in the operating room, and the best course of action to protect patients and healthcare workers from them in the future. Nevertheless, hospitals can take specific actions now by providing respirators for routine use, encouraging staff to utilise respirators routinely, establishing triggers for situations that require respirator use, educating staff concerning the prevention of aerosol transmissible diseases, and providing portable air purifiers for perioperative spaces with low levels of ventilation.

Perioperative oxygenation-what's the stress?

Oxygen is the most used drug in anaesthesia. Despite such widespread use, optimal perioperative oxygen administration remains highly controversial because of concerns about the competing harms of both hyperoxia and hypoxia. Notwithstanding a Cochrane review concluding that routinely administering a fractional inspired oxygen concentration (FiO2) >0.6 intraoperatively might increase postoperative morbidity and mortality, the World Health Organization (WHO) currently recommends all anaesthetised patients receive 0.8 FiO2 during and immediately after surgery to reduce surgical site infections. Results from the largest trial available at the time of these two reviews (suggesting long-term survival may be worse with high FiO2, particularly in patients with malignant disease) were considered 'biologically implausible' by the WHO's Guideline Development Group. In addition, the integrity of some perioperative oxygen studies has been challenged. Resolving these controversies is of fundamental importance to all perioperative clinicians. This narrative review is based on the inaugural BJA William Mapleson lecture delivered by the senior author (AC) at the 2023 annual meeting of the Royal College of Anaesthetists in Birmingham. We present the current evidence for perioperative oxygen administration and contrast this with how oxygen therapy is targeted in other specialties (e.g. intensive care medicine). We will explore whether anaesthetists follow the WHO recommendations and consider how oxygen administration affects the stress response to surgery. We reason that novel clinical trial designs in combination with targeted experimental medicine studies will be required to improve our understanding of how best to optimise individualised perioperative oxygenation-a cornerstone of anaesthesia.

What are the experiences of people with motor and sensory functional neurological disorder? A systematic review and thematic synthesis of qualitative studies.

PURPOSE: Functional neurological disorders are common, highly stigmatised and associated with significant disability. This review aimed to synthesise qualitative research exploring the experiences of people living with motor and/or sensory FND. Identifying their needs should inform service development, education for healthcare professionals and generate future research questions. METHOD: Five databases were systematically searched (Medline, PsychInfo, Web of Science, Embase and Cinahl) in November 2022, updated in June 2023. Data from included papers was extracted by two authors and studies were critically appraised using the Critical Appraisal Skills Programme (CASP). Data was thematically analysed and synthesised. RESULTS AND CONCLUSIONS: 12 papers were included in the synthesis describing the views of 156 people with FND. The overarching theme was uncertainty; about what caused FND and how to live with it. Uncertainty was underpinned by four analytic themes; challenging healthcare interactions, loss of power and control, who or what is responsible and living with a visible disability and an invisible illness. Early and clear diagnosis, validation and support for living with FND should form part of multidisciplinary care. Co-produced service development, research agendas and education for clinicians, patients and the public would reduce stigma and improve the experiences of people with FND.

A clear diagnosis and explanation of motor and/or sensory functional neurological disorder is validating and an important first step in recovery.People with motor and/or sensory functional neurological disorder experience significant disability, stigma, self-blame and functional impairment.Multidisciplinary care pathways for functional neurological disorder urgently need to be developed.There is a need for co-produced education and training for healthcare professionals which covers how to deliver diagnoses and personalised formulations, communicate concepts of applied neuroscience and challenges stigma and discrimination.

Etiological Factors and Symptom Triggers in Functional Motor Symptoms and Functional Seizures: A Pilot Investigation.

OBJECTIVE: This study examined etiological factors and symptom triggers of functional motor symptoms (FMS) or functional seizures (FS) and assessed potential relationships with relevant clinical features (i.e., functional symptoms, quality of life, and general functioning). METHODS: Seventeen participants with FMS or FS and 17 healthy control participants underwent an in-depth clinical interview and completed questionnaires assessing adverse life events, psychological and physical symptoms, alexithymia, autistic traits, illness perceptions, health-related quality of life (HRQoL), and work and social functioning. RESULTS: Participants with FMS or FS perceived various causes of the disorder, including physical symptoms (65%), emotional problems (53%), adverse life events (47%), and work-related factors (29%). Triggers of FMS and FS included physical activity or exertion (59%), stress and emotions (59%), sensory experiences (47%), and fatigue (41%). Compared with healthy control participants, participants with FMS or FS reported more adverse events during adolescence and higher levels of alexithymia, somatoform dissociation, psychological dissociation (disengagement, depersonalization, and derealization), anxiety, depression, and physical symptoms. Participants with FMS or FS had worse HRQoL than healthy control participants and impaired work and social functioning. There were inverse associations between HRQoL scores and somatoform dissociation, anxiety, and adverse life events. CONCLUSIONS: Participants with FMS or FS reported diverse biopsychosocial etiological factors and symptom triggers. Ongoing psychological symptoms and lifetime adverse experiences were associated with worse HRQoL. Future studies will examine these factors in larger samples of individuals with FMS or FS to better understand their shared and distinct etiological underpinnings.

From Software to Hardware: A Case Series of Functional Neurological Symptoms and Cerebrovascular Disease.

OBJECTIVE: Neuroimaging studies have identified alterations in both brain structure and functional connectivity in patients with functional neurological disorder (FND). For many patients, FND emerges from physical precipitating events. Nevertheless, there are a limited number of case series in the literature that describe the clinical presentation and neuroimaging correlates of FND following cerebrovascular disease. METHODS: The authors collected data from two clinics in the United Kingdom on 14 cases of acute, improving, or delayed functional neurological symptoms following cerebrovascular events. RESULTS: Most patients had functional neurological symptoms that were localized to cerebrovascular lesions, and the lesions mapped onto regions known to be part of functional networks disrupted in FND, including the thalamus, anterior cingulate gyrus, insula, and temporoparietal junction. CONCLUSIONS: The findings demonstrate that structural lesions can lead to FND symptoms, possibly explained through changes in relevant mechanistic functional networks.

A Critical Appraisal of the Whack-a-Mole and Swivel Chair Signs in the Diagnosis of Functional Movement Disorders.

BACKGROUND: The demonstration of positive signs during neurological examination is a cornerstone of the diagnosis of functional movement disorders, however, the available data supporting the diagnostic value of some of these signs is limited. OBJECTIVES: To determine the diagnostic value (sensitivity and specificity) of the "whack-a-mole" (WAM) and "swivel chair" (SC) tests in patients with functional movement disorders (FMD). METHODS: We enrolled patients with functional and organic movements in the WAM test if they exhibited tremor, dystonia, myoclonus, chorea, or tics. For the SC test, patients with a gait disorder as their primary impairment were recruited. Two blinded movement disorder specialists rated the presence of these signs in edited videos. RESULTS: Inclusion criteria were met by 42 patients with FMD and 65 patients with organic movement disorders. Both tests demonstrated high specificity (means, 78% and 96%), but their sensitivity was low (means, 52% and 37%). Interobserver agreement for the WAM sign was 0.77 in the FMD group, against 0.28 in patients with organic movement disorders, whereas Movement Disorders Clinical Practice for Review Only for the SC sign was 0.69 in both groups. CONCLUSIONS: The present study indicates that physicians must be cautious in the application and interpretation of these clinical signs in the diagnosis of functional movement disorders, and they should be carefully considered and used as necessary.