Subjective brain fog: a four-dimensional characterization in 25,796 participants.

Importance: Brain fog is associated with significant morbidity and reduced productivity and gained increasing attention after COVID-19. However, this subjective state has not been systematically characterised. Objective: To characterise self-reported brain fog. Design: We systematically studied the cross-sectional associations between 29 a priori variables with the presence of "brain fog." The variables were grouped into four categories: demographics, symptoms and functional impairments, comorbidities and potential risk factors (including lifestyle factors), and cognitive score. Univariate methods determined the correlates of brain fog, with long-COVID and non-long-COVID subgroups. XGBoost machine learning model retrospectively characterised subjective brain fog. Bonferroni-corrected statistical significance was set at 5%. Setting: Digital application for remote data collection. Participants: 25,796 individuals over the age of 18 who downloaded and completed the application. Results: 7,280 of 25,796 individuals (28.2%) reported experiencing brain fog, who were generally older (mean brain fog 35.7 ± 11.9 years vs. 32.8 ± 11.6 years, p < 0.0001) and more likely to be female (OR = 1.2, p < 0.001). Associated symptoms and functional impairments included difficulty focusing or concentrating (OR = 3.3), feeling irritable (OR = 1.6), difficulty relaxing (OR = 1.2, all p < 0.0001), difficulty following conversations (OR = 2.2), remembering appointments (OR = 1.9), completing paperwork and performing mental arithmetic (ORs = 1.8, all p < 0.0001). Comorbidities included long-COVID-19 (OR = 3.8, p < 0.0001), concussions (OR = 2.4, p < 0.0001), and higher migraine disability assessment scores (MIDAS) (+34.1%, all p < 0.0001). Cognitive scores were marginally lower with brain fog (-0.1 std., p < 0.001). XGBoost achieved a training accuracy of 85% with cross-validated accuracy of 74%, and the features most predictive of brain fog in the model were difficulty focusing and following conversations, long-COVID, and severity of migraines. Conclusions and relevance: This is the largest study characterising subjective brain fog as an impairment of concentration associated with functional impairments in activities of daily living. Brain fog was particularly associated with a history of long-COVID-19, migraines, concussion, and with 0.1 standard deviations lower cognitive scores, especially on modified Stroop testing, suggesting impairments in the ability to inhibit cognitive interference. Further prospective studies in unselected brain fog sufferers should explore the full spectrum of brain fog symptoms to differentiate it from its associated conditions.

Surgical management of a 25-cm giant hepatic haemangioma: First case report from Bangladesh with literature review.

INTRODUCTION AND IMPORTANCE: Giant hepatic haemangioma (GHH) is defined as a hepatic haemangioma (HH) of >10 cm in diameter. Its association with thrombocytopenia and consumption coagulopathy is quite rare. CASE PRESENTATION: Here, we present a case of a 39-year-old man with a rapidly enlarging 25-cm GHH arising from the entire left hemiliver. Laboratory findings suggested pancytopenia but normal liver and renal functions. He was diagnosed with Kasabach-Merritt syndrome (KMS). After three units of aphaeretic platelet transfusion, the patient underwent left hepatectomy. Postoperative recovery was uneventful, and his regular follow-up revealed no recurrence even after two years. CLINICAL DISCUSSION: HH predominantly affects females, but males can also be affected, as seen in this case. With observation, it can grow over time, particularly in patients under 50 years of age. Surgical management should be considered when HH causes symptoms or is larger than 10 cm. The evolving understanding of GHH and the critical role of surgery are important, particularly when they complicate haematological or coagulation profiles and lead to thrombocytopenia. CONCLUSION: Our case report highlights the significance of surgical intervention in GHH, and a disease-free outcome can be expected for patients with this condition in the future. To our knowledge, this is the first such case report from Bangladesh.

Brain Mechanisms Explaining Postural Imbalance in Traumatic Brain Injury: A Systematic Review.

Introduction: Persisting imbalance and falls in community-dwelling traumatic brain injury (TBI) survivors are linked to reduced long-term survival. However, a detailed understanding of the impact of TBI upon the brain mechanisms mediating imbalance is lacking. To understand the state of the art concerning the brain mechanisms mediating imbalance in TBI, we performed a systematic review of the literature. Methods: PubMed, Web of Science, and Scopus were searched and peer-reviewed research articles in humans, with any severity of TBI (mild, moderate, severe, or concussion), which linked a postural balance assessment (objective or subjective) with brain imaging (through computed tomography, T1-weighted imaging, functional magnetic resonance imaging [fMRI], resting-state fMRI, diffusion tensor imaging, magnetic resonance spectroscopy, single-photon emission computed tomography, electroencephalography, magnetoencephalography, near-infrared spectroscopy, and evoked potentials) were included. Out of 1940 articles, 60 were retrieved and screened, and 25 articles fulfilling inclusion criteria were included. Results: The most consistent finding was the link between imbalance and the cerebellum; however, the regions within the cerebellum were inconsistent. Discussion: The lack of consistent findings could reflect that imbalance in TBI is due to a widespread brain network dysfunction, as opposed to focal cortical damage. The inconsistency in the reported findings may also be attributed to heterogeneity of methodology, including data analytical techniques, small sample sizes, and choice of control groups. Future studies should include a detailed clinical phenotyping of vestibular function in TBI patients to account for the confounding effect of peripheral vestibular disorders on imbalance and brain imaging.

Translocator protein PET imaging in temporal lobe epilepsy: A reliable test-retest study using asymmetry index.

Objective: Translocator protein (TSPO) targeting positron emission tomography (PET) imaging radioligands have potential utility in epilepsy to assess the efficacy of novel therapeutics for targeting neuroinflammation. However, previous studies in healthy volunteers have indicated limited test-retest reliability of TSPO ligands. Here, we examine test-retest measures using TSPO PET imaging in subjects with epilepsy and healthy controls, to explore whether this biomarker can be used as an endpoint in clinical trials for epilepsy. Methods: Five subjects with epilepsy and confirmed mesial temporal lobe sclerosis (mean age 36 years, 3 men) were scanned twice-on average 8 weeks apart-using a second generation TSPO targeting radioligand, [11C]PBR28. We evaluated the test-retest reliability of the volume of distribution and derived hemispheric asymmetry index of [11C]PBR28 binding in these subjects and compared the results with 8 (mean age 45, 6 men) previously studied healthy volunteers. Results: The mean (± SD) of the volume of distribution (VT), of all subjects, in patients living with epilepsy for both test and retest scans on all regions of interest (ROI) is 4.49 ± 1.54 vs. 5.89 ± 1.23 in healthy volunteers. The bias between test and retest in an asymmetry index as a percentage was small (-1.5%), and reliability is demonstrated here with Bland-Altman Plots (test mean 1.062, retest mean 2.56). In subjects with epilepsy, VT of [11C]PBR28 is higher in the (ipsilateral) hippocampal region where sclerosis is present than in the contralateral region. Conclusion: When using TSPO PET in patients with epilepsy with hippocampal sclerosis (HS), an inter-hemispheric asymmetry index in the hippocampus is a measure with good test-retest reliability. We provide estimates of test-retest variability that may be useful for estimating power where group change in VT represents the clinical outcome.

Multidrug-resistant non-typhoidal Salmonella of public health significance recovered from migratory birds in Bangladesh.

Non-typhoidal Salmonella provides an exemplar for the One Health approach as it encompasses public and animal health, food safety, and environmental considerations. The contribution of environmental aspects is currently less well-defined. The purpose of this study was to determine the carriage occurrence of non-typhoidal Salmonella in migratory birds in Bangladesh and assess the potential significance to public and animal health. Cloacal swabs (N = 453) were collected in the years 2018-2020 from Tanguar and Hakaluki Haors, important wetland ecosystems in Northeastern Bangladesh. The prevalence of Salmonella was 13.5% (61 positive swabs). Classical serotyping identified six serovars: Salmonella enterica subsp. enterica serovars Perth, Kentucky, Albany, Infantis, Weltevreden, and Brancaster. Resistance towards 14 antimicrobials was assessed by broth microdilution minimum inhibitory concentration determination and the antimicrobial resistance (AMR) genotype established by whole-genome sequencing. S. Perth and S. Weltevreden isolates were susceptible and harbored no acquired AMR genes. Isolates from the remaining serovars were multidrug resistant, commonly possessing resistance to tetracycline, ampicillin, chloramphenicol, sulfamethoxazole, trimethoprim, and ciprofloxacin. Salmonella resistant to ciprofloxacin meets WHO criteria for priority pathogens. There was excellent concordance between resistance phenotype and the presence of corresponding AMR genes, many of which reside on Salmonella Genomic Islands. High-level ciprofloxacin resistance correlated with the presence of mutations in the chromosomal gyrB and/or parC genes. The S. Kentucky isolates were ST198, a widely distributed multidrug-resistant lineage reported in humans and animals, and constituting an ongoing risk to public health worldwide. We have demonstrated that multidrug-resistant non-typhoidal Salmonella of public health significance can be recovered from migratory birds. A potential for risk can manifest through direct interaction, transmission to food-producing livestock on farms, and dissemination via the long range migratory movements of birds. Risks can be mitigated by measures including continued surveillance and implementation of good farm biosecurity practices.

Microbial Contamination and Antibiotic Resistance in Marketed Food in Bangladesh: Current Situation and Possible Improvements.

Antimicrobial resistance (AMR) is a public health problem worldwide. Bangladesh, like its neighboring countries, faces many public health challenges, including access to safe food, inadequate food surveillance, as well as increasing AMR. This study investigated bacterial contamination and the AMR profile of pathogens in marketed food in Bangladesh and explored barriers to reducing AMR in the country. We collected 366 tomatoes, 359 chicken and 249 fish samples from 732 vendors in traditional markets in urban, peri-urban and rural areas in Bangladesh, as well as from 121 modern retails in Dhaka capital to analyse Vibrio cholerae and Escherichia coli in fish, Salmonella in chicken, and Salmonella and E. coli in tomatoes. Antibiotic susceptibility against 11 antibiotics was tested using a disc diffusion test and interpreted by an automated zone inhibition reader. In addition, a qualitative study using key informant interviews was conducted to explore antimicrobial use and AMR reduction potential in Bangladesh. We found E. coli in 14.21% of tomatoes and 26.91% of fish samples, while 7.38% of tomatoes and 17.27% of chicken were positive for Salmonella, and 44.98% of fish were positive for Vibrio cholerae. In total 231/319 (72.4%) of all pathogens isolated were multidrug-resistant (MDR) (resistant to three or more antibiotic groups). Qualitative interviews revealed an inadequate surveillance system for antibiotic use and AMR in Bangladesh, especially in the agriculture sector. To be able to fully understand the human health risks from bacterial hazards in the food and the AMR situation in Bangladesh, a nationwide study with a one health approach should be conducted, within all sectors, including AMR testing as well as assessment of the antimicrobial use and its drivers.

Hierarchical clustering of prolonged post-concussive symptoms after 12 months: symptom-centric analysis and association with functional impairments.

BACKGROUND: Following a concussion, approximately 15% of individuals experience persistent symptoms that can lead to functional deficits. However, underlying symptom-clusters that persist beyond 12 months have not been adequately characterized, and their relevance to functional deficits are unclear. The aim of this study was to characterize the underlying clusters of prolonged post-concussive symptoms lasting more than 12 months, and to investigate their association with functional impairments. METHODS: Although hierarchical clustering is ideally suited in evaluating subjective symptom severities, it has not been applied to the Rivermead Post-Concussion Questionnaire (RPQ). The RPQ and functional impairments questions were administered via a smartphone application to 445 individuals who self-reported prolonged post-concussive symptoms. Symptom-clusters were obtained using agglomerative hierarchical clustering, and their association with functional deficits were investigated with sensitivity analyses, and corrected for multiple comparisons. RESULTS: Five symptom-clusters were identified: headache-related, sensitivity to light and sound, cognitive, mood-related, and sleep-fatigue. Individuals with more severe RPQ symptoms were more likely to report functional deficits (p < 0.0001). Whereas the headache and sensitivity clusters were associated with at most one impairment, at-least-mild sleeping difficulties and fatigue were associated with four, and moderate-to-severe cognitive difficulties with five (all p < 0.01). CONCLUSIONS: Symptom-clusters may be clinically useful for functional outcome stratification for targeted rehabilitation therapies. Further studies are required to replicate these findings in other cohorts and questionnaires, and to ascertain the effects of symptomatic intervention on functional outcomes.

The human brain networks mediating the vestibular sensation of self-motion.

Vestibular Agnosia - where peripheral vestibular activation triggers the usual reflex nystagmus response but with attenuated or no self-motion perception - is found in brain disease with disrupted cortical network functioning, e.g. traumatic brain injury (TBI) or neurodegeneration (Parkinson's Disease). Patients with acute focal hemispheric lesions (e.g. stroke) do not manifest vestibular agnosia. Thus, brain network mapping techniques, e.g. resting state functional MRI (rsfMRI), are needed to interrogate functional brain networks mediating vestibular agnosia. Hence, we prospectively recruited 39 acute TBI patients with preserved peripheral vestibular function and obtained self-motion perceptual thresholds during passive yaw rotations in the dark and additionally acquired whole-brain rsfMRI in the acute phase. Following quality-control checks, 26 patient scans were analyzed. Using self-motion perceptual thresholds from a matched healthy control group, 11 acute TBI patients were classified as having vestibular agnosia versus 15 with normal self-motion perception thresholds. Using independent component analysis on the rsfMRI data, we found altered functional connectivity in bilateral lingual gyrus and temporo-occipital fusiform cortex in the vestibular agnosia patients. Moreover, regions of interest analyses showed both inter-hemispheric and intra-hemispheric network disruption in vestibular agnosia. In conclusion, our results show that vestibular agnosia is mediated by bilateral anterior and posterior network dysfunction and reveal the distributed brain mechanisms mediating vestibular self-motion perception.

The effect of galvanic vestibular stimulation on postural balance in Parkinson's disease: A systematic review and meta-analysis.

People with Parkinson's disease (PD) develop postural imbalance and falls. Galvanic Vestibular Stimulation (GVS) may potentially improve postural balance in humans and hence reduce falls in PD. This systematic review and meta-analysis investigate the effects of GVS on postural balance in PD. Six separate databases and research registers were searched for cross-over design trials that evaluated the effects of GVS on postural balance in PD. We used standardized mean difference (Hedges' g) as a measure of effect size in all studies. We screened 223 studies, evaluated 14, of which five qualified for the meta-analysis. Among n = 40 patients in five studies (range n = 5 to 13), using a fixed effects model we found an effect size estimate of g = 0.43 (p < 0.001, 95% CI [0.29,0.57]). However, the test for residual heterogeneity was significant (p < 0.001), thus we used a random effects model and found a pooled effect size estimate of 0.62 (p > 0.05, 95% CI [- 0.17, 1.41], I2 = 96.21%). Egger's test was not significant and thus trim and funnel plot indicated no bias. To reduce heterogeneity, we performed sensitivity analysis and by removing one outlier study (n = 7 patients), we found an effect size estimate of 0.16 (p < 0.05, 95% CI [0.01, 0.31], I2 = 0%). Our meta-analysis found GVS has a favourable effect on postural balance in PD patients, but due to limited literature and inconsistent methodologies, this favourable effect must be interpreted with caution.

Prevalence of stroke in acute vertigo presentations: A UK tertiary stroke centre perspective.

The reported prevalence of stroke amongst patients presenting to hospital with acute vertigo and/or imbalance is c. 5%, leading to the pervasive notion amongst emergency and stroke physicians, that stroke is uncommon in this cohort. To interrogate the veracity of this notion, we systematically and retrospectively screened the electronic care records in our institution of patients referred as suspected stroke, to a hyperacute stroke service at a large tertiary referral centre. We screened 24,310 consecutive patients' electronic case records presenting to our hospital as an emergency over a 4-month period, 332 of whom were referred as suspected stroke whose case records were assessed via structured review. Of these 332 cases, 61 presented with a vestibular syndrome, i.e. having at least one of imbalance, dizziness or vertigo. Of the 61 vestibular cases, 38 (62%) were diagnosed as stroke confirmed by imaging in 25/38 or upon clinical grounds only (13/38). None of the 38 vestibular stroke cases received thrombolysis or thrombectomy treatment. In a UK urban population (2.5mn), acute vestibular syndrome cases referred to stroke services have a 50% stroke prevalence. None of the vestibular stroke cases received hyperacute stroke treatment e.g., thrombolysis, due to delay in diagnosis. The high stroke prevalence in our cohort may indicate an excessively high threshold for referring acute vestibular cases for stroke, implying a high number of missed stroke cases. We suggest that early access to vestibular neurologists in acute vestibular cases should improve the proportion of vestibular stroke cases receiving definitive stroke treatment.

High prevalence of vancomycin non-susceptible and multi-drug resistant enterococci in farmed animals and fresh retail meats in Bangladesh.

The emergence of antimicrobial resistant Enterococcus spp., a main cause of untreatable nosocomial infection, in food animals and dissemination to humans is a public health risk. The study was performed to determine the prevalence and antimicrobial resistance, and virulence characteristics of Enterococcus faecalis and Enterococcus faecium in food animals and meats in Bangladesh. Enterococcus spp., were confirmed using sodA gene specific PCR, and antimicrobial resistance and virulence properties were characterized by PCR. Enterococcus spp. were recovered from 57% of the collected samples (n = 201/352). Farm samples yielded significantly higher (p ≤ 0.05) prevalence (62%) than that of retail meat samples (41%). E. faecalis (52%) is most frequently isolated species. Greater proportions of isolates exhibited resistance to tetracycline (74%), erythromycin (65%) and ciprofloxacin (34%). Fifty-one isolates are vancomycin non-susceptible enterococci (VNSE), of which forty-seven are MDR and twenty are linezolid resistant, a last line drug for VNSE. Virulence factors such as gelatinase (gelE), aggregation factor (asa1) and sex pheromone (cpd) are detected along with vancomycin resistance gene (vanA, vanB and vanC2/C3) in VNSE isolates. The high prevalence of MDR enterococci in food animals and retail meats may cause consumers infections with concomitant reduction of available therapeutic options.

Optimizing Existing Mental Health Screening Methods in a Dementia Screening and Risk Factor App: Observational Machine Learning Study.

BACKGROUND: Mindstep is an app that aims to improve dementia screening by assessing cognition and risk factors. It considers important clinical risk factors, including prodromal symptoms, mental health disorders, and differential diagnoses of dementia. The 9-item Patient Health Questionnaire for depression (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) are widely validated and commonly used scales used in screening for depression and anxiety disorders, respectively. Shortened versions of both (PHQ-2/GAD-2) have been produced. OBJECTIVE: We sought to develop a method that maintained the brevity of these shorter questionnaires while maintaining the better precision of the original questionnaires. METHODS: Single questions were designed to encompass symptoms covered in the original questionnaires. Answers to these questions were combined with PHQ-2/GAD-2, and anonymized risk factors were collected by Mindset4Dementia from 2235 users. Machine learning models were trained to use these single questions in combination with data already collected by the app: age, response to a joke, and reporting of functional impairment to predict binary and continuous outcomes as measured using PHQ-9/GAD-7. Our model was developed with a training data set by using 10-fold cross-validation and a holdout testing data set and compared to results from using the shorter questionnaires (PHQ-2/GAD-2) alone to benchmark performance. RESULTS: We were able to achieve superior performance in predicting PHQ-9/GAD-7 screening cutoffs compared to PHQ-2 (difference in area under the curve 0.04, 95% CI 0.00-0.08, P=.02) but not GAD-2 (difference in area under the curve 0.00, 95% CI -0.02 to 0.03, P=.42). Regression models were able to accurately predict total questionnaire scores in PHQ-9 (R2=0.655, mean absolute error=2.267) and GAD-7 (R2=0.837, mean absolute error=1.780). CONCLUSIONS: We app-adapted PHQ-4 by adding brief summary questions about factors normally covered in the longer questionnaires. We additionally trained machine learning models that used the wide range of additional information already collected in Mindstep to make a short app-based screening tool for affective disorders, which appears to have superior or equivalent performance to well-established methods.

Maternal and fetal outcomes in women with cerebrovascular malformations in pregnancy: A multicentre retrospective cohort study.

OBJECTIVE: To determine maternal, obstetric and neonatal outcomes in a cohort of women with cerebrovascular malformations (CVMs) that include arterial venous malformations (AVMs) and cavernomas. DESIGN: Retrospective cohort study. SETTING: Six specialist centres managing pregnant women with neurological disorders. POPULATION: Sixty-three women with CVMs in 83 pregnancies of ≥20 completed weeks' gestation. METHODS: Retrospective case notes review. MAIN OUTCOME MEASURES: Neurological outcomes including rates of acute cerebral bleeding in pregnancy and reported seizures during pregnancy. Maternal outcomes included number of women with a livebirth and the proportion of women being delivered by caesarean section. RESULTS: Most women had a good pregnancy outcome with high rates of vaginal delivery (73%) at term. There were no maternal deaths. Six women had an acute cerebral bleed, all of whom were delivered by planned caesarean section. In total, ten women had seizures in pregnancy (of whom four also had a bleed). Six (7%) babies were admitted to a neonatal unit. There was no significant difference in outcomes between women with AVMs and those with cavernomas. CONCLUSION: In the majority of cases, pregnancy outcomes were favourable, with most women having a vaginal delivery. All cases of cerebral bleeds that occurred were at a remove from the peripartum period. TWEETABLE ABSTRACT: Women with cerebrovascular malformations have high rates of vaginal delivery.

Validation of a rapid remote digital test for impaired cognition using clinical dementia rating and mini-mental state examination: An observational research study.

Background: The Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE) are useful screening tools for mild cognitive impairment (MCI). However, these tests require qualified in-person supervision and the CDR can take up to 60 min to complete. We developed a digital cognitive screening test (M-CogScore) that can be completed remotely in under 5 min without supervision. We set out to validate M-CogScore in head-to-head comparisons with CDR and MMSE. Methods: To ascertain the validity of the M-CogScore, we enrolled participants as healthy controls or impaired cognition, matched for age, sex, and education. Participants completed the 30-item paper MMSE Second Edition Standard Version (MMSE-2), paper CDR, and smartphone-based M-CogScore. The digital M-CogScore test is based on time-normalised scores from smartphone-adapted Stroop (M-Stroop), digit-symbols (M-Symbols), and delayed recall tests (M-Memory). We used Spearman's correlation coefficient to determine the convergent validity between M-CogScore and the 30-item MMSE-2, and non-parametric tests to determine its discriminative validity with a CDR label of normal (CDR 0) or impaired cognition (CDR 0.5 or 1). M-CogScore was further compared to MMSE-2 using area under the receiver operating characteristic curves (AUC) with corresponding optimal cut-offs. Results: 72 participants completed all three tests. The M-CogScore correlated with both MMSE-2 (rho = 0.54, p < 0.0001) and impaired cognition on CDR (Mann Whitney U = 187, p < 0.001). M-CogScore achieved an AUC of 0.85 (95% bootstrapped CI [0.80, 0.91]), when differentiating between normal and impaired cognition, compared to an AUC of 0.78 [0.72, 0.84] for MMSE-2 (p = 0.21). Conclusion: Digital screening tests such as M-CogScore are desirable to aid in rapid and remote clinical cognitive evaluations. M-CogScore was significantly correlated with established cognitive tests, including CDR and MMSE-2. M-CogScore can be taken remotely without supervision, is automatically scored, has less of a ceiling effect than the MMSE-2, and takes significantly less time to complete.

A Cost Utility Analysis of Minimally Invasive Surgery with Thrombolysis Compared to Standard Medical Treatment in Spontaneous Intracerebral Haemorrhagic Stroke.

OBJECTIVES: Standard medical management of spontaneous intracerebral haemorrhage (ICH) and surgical hematoma evacuation starkly differ, and whilst landmark randomised control trials report no clinical benefit of early surgical evacuation compared with medical treatment in supratentorial ICH, minimally invasive surgery (MIS) with thrombolysis has been neglected within these studies. However, recent technological advancements in MIS have renewed interest in the surgical treatment of ICH. Several economic evaluations have focused on the benefits of MIS in ischaemic stroke management, but no economic evaluations have yet been performed comparing MIS to standard medical treatment for ICH. MATERIALS AND METHOD: All costs were sourced from the UK in GBP. Where possible, the 2019/2020 NHS reference costs were used. The MISTIE III study was used to analyse the outcomes of patients undergoing either MIS or standard medical treatment in this economic evaluation. RESULTS: The incremental cost-effectiveness ratio (ICER) for MIS was £485,240.26 for every quality-adjusted life year (QALY) gained. Although MIS resulted in a higher QALY compared to medical treatment, the gain was insignificant at 0.011 QALY. Four sensitivity analyses based on combinations of alternative EQ-5D values and categorisation of MIS outcomes, alongside alterations to the cost of significant adverse events, were performed to check the robustness of the ICER calculation. The most realistic sensitivity analysis showed a potential increase in cost effectiveness when clot size is reduced to <15ml, with the ICER falling to £74,335.57. DISCUSSION: From the perspective of the NHS, MIS with thrombolysis is not cost-effective compared to optimal medical treatment. ICER shows that intention-to-treat MIS would require a cost of £485,240.26 to gain one extra QALY, which is significantly above the NHS threshold of £30,000. Further UK studies with ICH survivor utilities, more replicable surgical technique, and the reporting of clot size reduction are indicated as the present sensitivity analysis suggests that MIS is promising. Greater detail about outcomes and complications would ensure improved cost-benefit analyses and support valid and efficient allocation of resources by the NHS.

Vestibular agnosia in traumatic brain injury and its link to imbalance.

Vestibular dysfunction, causing dizziness and imbalance, is a common yet poorly understood feature in patients with TBI. Damage to the inner ear, nerve, brainstem, cerebellum and cerebral hemispheres may all affect vestibular functioning, hence, a multi-level assessment-from reflex to perception-is required. In a previous report, postural instability was the commonest neurological feature in ambulating acute patients with TBI. During ward assessment, we also frequently observe a loss of vertigo sensation in patients with acute TBI, common inner ear conditions and a related vigorous vestibular-ocular reflex nystagmus, suggesting a 'vestibular agnosia'. Patients with vestibular agnosia were also more unbalanced; however, the link between vestibular agnosia and imbalance was confounded by the presence of inner ear conditions. We investigated the brain mechanisms of imbalance in acute TBI, its link with vestibular agnosia, and potential clinical impact, by prospective laboratory assessment of vestibular function, from reflex to perception, in patients with preserved peripheral vestibular function. Assessment included: vestibular reflex function, vestibular perception by participants' report of their passive yaw rotations in the dark, objective balance via posturography, subjective symptoms via questionnaires, and structural neuroimaging. We prospectively screened 918 acute admissions, assessed 146 and recruited 37. Compared to 37 matched controls, patients showed elevated vestibular-perceptual thresholds (patients 12.92°/s versus 3.87°/s) but normal vestibular-ocular reflex thresholds (patients 2.52°/s versus 1.78°/s). Patients with elevated vestibular-perceptual thresholds [3 standard deviations (SD) above controls' average], were designated as having vestibular agnosia, and displayed worse posturography than non-vestibular-agnosia patients, despite no difference in vestibular symptom scores. Only in patients with impaired postural control (3 SD above controls' mean), whole brain diffusion tensor voxel-wise analysis showed elevated mean diffusivity (and trend lower fractional anisotropy) in the inferior longitudinal fasciculus in the right temporal lobe that correlated with vestibular agnosia severity. Thus, impaired balance and vestibular agnosia are co-localized to the inferior longitudinal fasciculus in the right temporal lobe. Finally, a clinical audit showed a sevenfold reduction in clinician recognition of a common peripheral vestibular condition (benign paroxysmal positional vertigo) in acute patients with clinically apparent vestibular agnosia. That vestibular agnosia patients show worse balance, but without increased dizziness symptoms, explains why clinicians may miss treatable vestibular diagnoses in these patients. In conclusion, vestibular agnosia mediates imbalance in traumatic brain injury both directly via white matter tract damage in the right temporal lobe, and indirectly via reduced clinical recognition of common, treatable vestibular diagnoses.

Microglial positron emission tomography (PET) imaging in epilepsy: Applications, opportunities and pitfalls.

Neuroinflammation is increasingly implicated in epileptogenesis and epilepsy. Microglia are an important mediator of central nervous system inflammation, and the development of positron emission tomography (PET) radioligands which bind the Translocator Protein (TSPO), an outer mitochondrial membrane protein expressed by microglia, has enabled in vivo measurement of neuroinflammation. Here, we outline the principles and potential pitfalls of TSPO PET imaging in relation to epilepsy, and opportunities for using TSPO imaging as a biomarker for future anti-inflammatory based therapeutics in epilepsy.

Obtaining self-samples to diagnose curable sexually transmitted infections: a systematic review of patients' experiences.

BACKGROUND: Routine screening is key to sexually transmitted infection (STI) prevention and control. Previous studies suggest that clinic-based screening programmes capture only a small proportion of people with STIs. Self-sampling using non- or minimally invasive techniques may be beneficial for those reluctant to actively engage with conventional sampling methods. We systematically reviewed studies of patients' experiences of obtaining self-samples to diagnose curable STIs. METHODS: We conducted an electronic search of MEDLINE, EMBASE, CINAHL, PsychINFO, BNI, and Cochrane Database of Systematic Reviews to identify relevant articles published in English between January 1980 and March 2014. Studies were included if participants self-sampled for the diagnosis of a curable STI and had specifically sought participants' opinions of their experience, acceptability, preferences, or willingness to self-sample. RESULTS: The initial search yielded 558 references. Of these, 45 studies met the inclusion criteria. Thirty-six studies assessed patients' acceptability and experiences of self-sampling. Pooled results from these studies shows that self-sampling is a highly acceptable method with 85% of patients reporting the method to be well received and acceptable. Twenty-eight studies reported on ease of self-sampling; the majority of patients (88%) in these studies found self-sampling an "easy" procedure. Self-sampling was favoured compared to clinician sampling, and home sampling was preferred to clinic-based sampling. Females and older participants were more accepting of self-sampling. Only a small minority of participants (13%) reported pain during self-sampling. Participants were willing to undergo self-sampling and recommend others. Privacy and safety were the most common concerns. CONCLUSION: Self-sampling for diagnostic testing is well accepted with the majority having a positive experience and willingness to use again. Standardization of self-sampling procedures and rigorous validation of outcome measurement will lead to better comparability across studies. Future studies need to conduct rigorous economic evaluations of self-sampling to inform policy development for the management of STI.

Imaging pancreatobiliary ductal system with optical coherence tomography: A review.

An accurate, noninvasive and cost-effective method of in situ tissue evaluation during endoscopy would be highly advantageous for the detection of dysplasia or early cancer and for identifying different disease stages. Optical coherence tomography (OCT) is a noninvasive, high-resolution (1-10 µm) emerging optical imaging method with potential for identifying microscopic subsurface features in the pancreatic and biliary ductal system. Tissue microstructure of pancreaticobiliary ductal system has been successfully imaged by inserting an OCT probe through a standard endoscope operative channel. High-resolution OCT images and the technique's endoscopic compatibility have allowed for the microstructural diagnostic of the pancreatobiliary diseases. In this review, we discussed currently available pancreaticobiliary ductal imaging systems to assess the pancreatobiliary tissue microstructure and to evaluate varieties of pancreaticobiliary disorders and diseases. Results show that OCT can improve the quality of images of pancreatobiliary system during endoscopic retrograde cholangiopancheatography procedure, which may be important in distinguishing between the neoplastic and non-neoplastic lesions.