Nanopore sequencing of influenza A and B in Oxfordshire and the United Kingdom, 2022-23.

OBJECTIVES: We evaluated Nanopore sequencing for influenza surveillance. METHODS: Influenza A and B PCR-positive samples from hospital patients in Oxfordshire, UK, and a UK-wide population survey from winter 2022-23 underwent Nanopore sequencing following targeted rt-PCR amplification. RESULTS: From 941 infections, successful sequencing was achieved in 292/388 (75 %) available Oxfordshire samples: 231 (79 %) A/H3N2, 53 (18 %) A/H1N1, and 8 (3 %) B/Victoria and in 53/113 (47 %) UK-wide samples. Sequencing was more successful at lower Ct values. Most same-sample replicate sequences had identical haemagglutinin segments (124/141, 88 %); 36/39 (92 %) Illumina vs. Nanopore comparisons were identical, and 3 (8 %) differed by 1 variant. Comparison of Oxfordshire and UK-wide sequences showed frequent inter-regional transmission. Infections were closely-related to 2022-23 vaccine strains. Only one sample had a neuraminidase inhibitor resistance mutation. 849/941 (90 %) Oxfordshire infections were community-acquired. 63/88 (72 %) potentially healthcare-associated cases shared a hospital ward with ≥ 1 known infectious case. 33 epidemiologically-plausible transmission links had sequencing data for both source and recipient: 8 were within ≤ 5 SNPs, of these, 5 (63 %) involved potential sources that were also hospital-acquired. CONCLUSIONS: Nanopore influenza sequencing was reproducible and antiviral resistance rare. Inter-regional transmission was common; most infections were genomically similar. Hospital-acquired infections are likely an important source of nosocomial transmission and should be prioritised for infection prevention and control.

Impact of gender, ethnicity and social deprivation on access to surgical or transcatheter aortic valve replacement in aortic stenosis: a retrospective database study in England.

OBJECTIVE: To assess gender, ethnicity, and deprivation-based differences in provision of aortic valve replacement (AVR) in England for adults with aortic stenosis (AS). METHODS: We retrospectively identified adults with AS from the English Hospital Episode Statistics (HES) between April 2016 and March 2019 and those who subsequently had an AVR. We separately used HES-linked Clinical Practice Research Datalink (CPRD) to identify people with AVR and evaluate the timeliness of their procedure (CPRD-AVR cohort). ORs for AVR in people with an AS diagnosis were estimated using multivariable logistic regression adjusted for age, region and comorbidity. AVR was considered timely if performed electively and without evidence of cardiac decompensation before AVR. RESULTS: 183 591 adults with AS were identified in HES; of these, 31 436 underwent AVR. The CPRD-AVR cohort comprised 10 069 adults. Women had lower odds of receiving AVR compared with men (OR 0.65; 95% CI 0.63 to 0.66); as did people of black (OR 0.70; 95% CI 0.60 to 0.82) or South Asian (OR 0.75; 95% CI 0.69 to 0.82) compared with people of white ethnicities. People in the most deprived areas were less likely to receive AVR than the least deprived areas (OR 0.8; 95% CI 0.75 to 0.86). Timely AVR occurred in 65% of those of white ethnicities compared with 55% of both those of black and South Asian ethnicities. 77% of the least deprived had a timely procedure compared with 58% of the most deprived; there was no gender difference. CONCLUSIONS: In this large, national dataset, female gender, black or South Asian ethnicities and high deprivation were associated with significantly reduced odds of receiving AVR in England. A lower proportion of people of minority ethnicities or high deprivation had a timely procedure. Public health initiatives may be required to increase clinician and public awareness of unconscious biases towards minority and vulnerable populations to ensure timely AVR for everyone.

Evaluation of sequence hybridization for respiratory viruses using the Twist Bioscience Respiratory Virus Research panel and the OneCodex Respiratory Virus sequence analysis workflow.

Respiratory viral infections are a major global clinical problem, and rapid, cheap, scalable and agnostic diagnostic tests that capture genome-level information on viral variation are urgently needed. Metagenomic approaches would be ideal, but remain currently limited in that much of the genetic content in respiratory samples is human, and amplifying and sequencing the viral/pathogen component in an unbiased manner is challenging. PCR-based tests, including those which detect multiple pathogens, are already widely used, but do not capture information on strain-level variation; tests with larger viral repertoires are also expensive on a per-test basis. One intermediate approach is the use of large panels of viral probes or 'baits', which target or 'capture' sequences representing complete genomes amongst several different common viral pathogens; these are then amplified, sequenced and analysed with a sequence analysis workflow. Here we evaluate one such commercial bait capture method (the Twist Bioscience Respiratory Virus Research Panel) and sequence analysis workflow (OneCodex), using control (simulated) and patient samples head-to-head with a validated multiplex PCR clinical diagnostic test (BioFire FilmArray). We highlight the limited sensitivity and specificity of the joint Twist Bioscience/OneCodex approach, which are further reduced by shortening workflow times and increasing sample throughput to reduce per-sample costs. These issues with performance may be driven by aspects of both the laboratory (e.g. capacity to enrich for viruses present in low numbers), bioinformatics methods used (e.g. a limited viral reference database) and thresholds adopted for calling a virus as present or absent. As a result, this workflow would require further optimization prior to any implementation for respiratory virus characterization in a routine diagnostic healthcare setting.

Comparison of Clinical and Economic Outcomes of an Optimized Lean Versus a Standard Transcatheter Aortic Valve Implantation Program (from SOLAR [Safe Outcomes Lean And Resourceful] Study).

The increasing prevalence of aortic stenosis (AS) and the increasing number of patients indicated for transcatheter aortic valve implantation (TAVI) can lead to increased hospital constraints. This study aimed to compare, from the hospital perspective, the costs, resource use, and 30-day clinical outcomes of patients who underwent TAVI under an optimized or standard clinical pathway. A single-center, retrospective study was conducted among patients with native AS who underwent TAVI between January 2018 and March 2021. Patients who underwent optimized lean TAVI were propensity-score matched 1:1 to those who underwent standard TAVI. In-hospital costs and 30-day clinical outcomes were compared between the 2 groups. A total of 182 patients (91 in each group) were included in the final analysis. Baseline covariates were well balanced after matching. Patients who underwent lean TAVI had shorter length of stay (median [interquartile range] 3.0 days [2.0 to 6.0] vs 6.0 days [5.0 to 9.0], p <0.001). Patients in the lean TAVI group incurred lower total costs than did those in the standard TAVI group (mean ± SD: $41,346 ± 10,062 vs $50,471 ± 15,115, p = 0.002). There was no between-group difference in 30-day all-cause mortality (2.2% vs 1.1%, p = 0.573) and pacemaker implantations (5.5% vs 6.6%, p = 0.788). Rates of procedural complications were comparable between groups. In conclusion, lean TAVI leads to hospital efficiencies without compromising patient safety. Efforts to streamline the TAVI procedure should be encouraged to improve access to TAVI for patients with AS, amid resource constraints.

Boston cognitive assessment (BOCA) - a comprehensive self-administered smartphone- and computer-based at-home test for longitudinal tracking of cognitive performance.

Longitudinal cognitive testing is essential for developing novel preventive interventions for dementia and Alzheimer's disease; however, the few available tools have significant practice effect and depend on an external evaluator. We developed a self-administered 10-min at-home test intended for longitudinal cognitive monitoring, Boston Cognitive Assessment or BOCA. The goal of this project was to validate BOCA. BOCA uses randomly selected non-repeating tasks to minimize practice effects. BOCA evaluates eight cognitive domains: 1) Memory/Immediate Recall, 2) Combinatorial Language Comprehension/Prefrontal Synthesis, 3) Visuospatial Reasoning/Mental rotation, 4) Executive function/Clock Test, 5) Attention, 6) Mental math, 7) Orientation, and 8) Memory/Delayed Recall. BOCA was administered to patients with cognitive impairment (n = 50) and age- and education-matched controls (n = 50). Test scores were significantly different between patients and controls (p < 0.001) suggesting good discriminative ability. The Cronbach's alpha was 0.87 implying good internal consistency. BOCA demonstrated strong correlation with Montreal Cognitive Assessment (MoCA) (R = 0.90, p < 0.001). The study revealed strong (R = 0.94, p < 0.001) test-retest reliability of the total BOCA score one week after participants' initial administration. The practice effect tested by daily BOCA administration over 10 days was insignificant (ß = 0.03, p = 0.68). The effect of the screen size tested by BOCA administration on a large computer screen and re-administration of the BOCA to the same participant on a smartphone was insignificant (ß = 0.82, p = 0.17; positive ß indicates greater score on a smartphone). BOCA has the potential to reduce the cost and improve the quality of longitudinal cognitive tracking essential for testing novel interventions designed to reduce or reverse cognitive aging. BOCA is available online gratis at www.bocatest.org .

Anterior thalamic nuclei lesions have a greater impact than mammillothalamic tract lesions on the extended hippocampal system.

The anterior thalamic nuclei (ATN), mammillary bodies and their interconnecting fiber tract, the mammillothalamic tract (MTT), are important components of an extended hippocampal circuit for episodic memory. In humans, damage to the MTT or ATN in many disorders is associated with severe anterograde amnesia and it is assumed that their influence on memory is functionally equivalent. The relative influence of these two structures on memory has not, however, been assessed explicitly. Here, a direct comparison found that only ATN lesions impaired spatial reference memory in rats. ATN lesions produced more severe deficits on spatial working memory and reduced zif268 expression to a greater degree and in more corticolimbic sites than did MTT lesions. Conversely, MTT lesions reduced NeuN cell counts in all three subregions of the MB to a greater extent than did ATN lesions, so their relative impact cannot be explained by retrograde neuropathology of the MB. Hence ATN injury causes a more critical dysfunction than would be expected by an emphasis on the indirect influence of brainstem inputs to the extended memory system. The greater ATN lesion deficits found here may represent the consequence of disruption to the direct connections of the ATN with both hippocampal and cortical sites.

Practical Classification Guidelines for Diabetes in patients treated with insulin: a cross-sectional study of the accuracy of diabetes diagnosis.

BACKGROUND: Differentiating between type 1 and type 2 diabetes is fundamental to ensuring appropriate management of patients, but can be challenging, especially when treating with insulin. The 2010 UK Practical Classification Guidelines for Diabetes were developed to help make the differentiation. AIM: To assess diagnostic accuracy of the UK guidelines against 'gold standard' definitions of type 1 and type 2 diabetes based on measured C-peptide levels. DESIGN AND SETTING: In total, 601 adults with insulin-treated diabetes and diabetes duration ≥5 years were recruited in Devon, Northamptonshire, and Leicestershire. METHOD: Baseline information and home urine sample were collected. Urinary C-peptide creatinine ratio (UCPCR) measures endogenous insulin production. Gold standard type 1 diabetes was defined as continuous insulin treatment within 3 years of diagnosis and absolute insulin deficiency (UCPCR<0.2 nmol/mmol ≥5 years post-diagnosis); all others classed as having type 2 diabetes. Diagnostic performance of the clinical criteria was assessed and other criteria explored using receiver operating characteristic (ROC) curves. RESULTS: UK guidelines correctly classified 86% of participants. Most misclassifications occurred in patients classed as having type 1 diabetes who had significant endogenous insulin levels (57 out of 601; 9%); most in those diagnosed ≥35 years and treated with insulin from diagnosis, where 37 out of 66 (56%) were misclassified. Time to insulin and age at diagnosis performed best in predicting long-term endogenous insulin production (ROC AUC = 0.904 and 0.871); BMI was a less strong predictor of diabetes type (AUC = 0.824). CONCLUSION: Current UK guidelines provide a pragmatic clinical approach to classification reflecting long-term endogenous insulin production; caution is needed in older patients commencing insulin from diagnosis, where misclassification rates are increased.

Aetiology of injuries and the need for protective equipment for surfers in the UK.

BACKGROUND: Surfing is a popular UK water-sport. Previous studies investigating surfing injuries have been principally based on trauma from large waves and reef breaks in the US and Australia. Subsequent conclusions and recommendations for the use of protective equipment in surfing may therefore not be relevant in the UK. AIMS: This study examines the aetiology of surfing injuries in the UK. METHODS: Data was collected in 2012 using a web-based survey distributed to UK surfing clubs. Surfers recorded time/experience as a surfer, number of episodes spent surfing per month, different breaks surfed and type, frequency and method of any injuries sustained whilst surfing in the UK, including treatment received. RESULTS: Completed surveys were obtained from 130 individuals, M:F division 85:45, median age 28 (range 17-65). 122 surfers reported a total of 335 injuries. Head injuries were the most common (24%) followed by ankle (19%), knee (13%), back (10%), hand/wrist (9%), elbow/shoulder (7%), trunk (7%), neck (4%), hip (4%) and genitalia (3%) injuries. Surfers collided most often with their own boards (31%). The other collisions were with rocks/coral (15%), the sea (11%), other surf boards (10%) the sea bed (7%), other water vessels (2%) and by paddle-boards (1%). Of 327 injuries, cuts/lacerations (31%) were the commonest type of injury, followed by bruises/peri-orbital ecchymoses (24%), joint/ligament sprains (15%), muscle or tendon tears/ruptures (9%), concussion (5%), fractures (3%) and teeth injuries (1%). The remaining 8 injuries were not categorized. 65% of the surfers never required professional medical treatment for their differing injuries. There were no skull fractures and no head injuries required neurosurgical intervention. CONCLUSION: Surfing injuries in the UK are common. They appear of a similar aetiology to those reported in the literature in countries with a high surfing population, but generally of a lower severity, with few requiring professional treatment, hospital admission or operative intervention. Concussion appears rare and in this study there were no head injuries that required neurosurgical intervention. Surfing helmets aim to prevent such serious head injuries; whilst they should be considered for injury prevention their routine use is unlikely to be warranted whilst surfing in the UK.

Titanium plate artefact mimicking popliteal artery dissection on digital subtraction CT angiography.

Titanium plates used for the internal fixation of long bone fractures cause significant artefact on CT scans but have not been reported to affect digital subtraction CT angiography. We present a patient with clinical suspicion of popliteal artery injury following a high tibial osteotomy. The osteotomy was stabilised with a titanium locking plate. During the digital subtraction process used to produce reconstruction CT angiography, removal of artefact caused by the titanium plate produced CT images mimicking the appearance of a popliteal artery dissection. The imaging inaccuracy was realised prior to the patient undergoing further intervention. We highlight the potential error caused by titanium plates on digital subtraction CT angiography and recommend careful analysis of such images prior to further treatment.