Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aimed to identify interactions of poststroke complications using network analysis in diverse stroke samples. Data from 2185 patients were sourced from member studies of STROKOG (Stroke and Cognition Consortium), an international collaboration of stroke studies. Networks were generated for each cohort, whereby nodes represented neuropsychiatric symptoms, cognitive deficits, and disabilities on activities of daily living. Edges characterized associations between them. Centrality measures were used to identify hub items. Across cohorts, a single network of interrelated poststroke complications emerged. Networks exhibited dissociable depression, apathy, fatigue, cognitive impairment, and functional disability modules. Worry was the most central symptom across cohorts, irrespective of the depression scale used. Items relating to activities of daily living were also highly central nodes. Follow-up analysis in two studies revealed that individuals who worried had more densely connected networks than those free of worry (CASPER [Cognition and Affect after Stroke: Prospective Evaluation of Risks] study: S = 9.72, P = 0.038; SSS [Sydney Stroke Study]: S = 13.56, P = 0.069). Neuropsychiatric symptoms are highly interconnected with cognitive deficits and functional disabilities resulting from stroke. Given their central position and high level of connectedness, worry and activities of daily living have the potential to drive multimorbidity and mutual reinforcement between domains of poststroke complications. Targeting these factors early after stroke may have benefits that extend to other complications, leading to better stroke outcomes.

We aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. Patients with suspected sepsis in four intensive care units were prospectively enrolled. Human-depleted DNA was extracted from positive BC broths and sequenced using ONT (MinION). Species abundance was estimated using Kraken2, and a cloud-based system (AREScloud) provided in silico predictive antimicrobial susceptibility testing (AST) from assembled contigs. Results were compared to conventional identification and phenotypic AST. Species-level agreement between conventional methods and AST predicted from sequencing was 94.2% (49/52), increasing to 100% in monomicrobial infections. In 262 high-quality AREScloud AST predictions across 24 samples, categorical agreement (CA) was 89.3%, with major error (ME) and very major error (VME) rates of 10.5% and 12.1%, respectively. Over 90% CA was achieved for some taxa (e.g., Staphylococcus aureus) but was suboptimal for Pseudomonas aeruginosa. In 470 AST predictions across 42 samples, with both high quality and exploratory-only predictions, overall CA, ME, and VME rates were 87.7%, 8.3%, and 28.4%. VME rates were inflated by false susceptibility calls in a small number of species/antibiotic combinations with few representative resistant isolates. Time to reporting from sequencing could be achieved within 8-16 h from BC positivity. Direct sequencing from positive BC broths is feasible and can provide accurate predictive AST for some species. ONT-based approaches may be faster but significant improvements in accuracy are required before it can be considered for clinical use.IMPORTANCESepsis and bloodstream infections carry a high risk of morbidity and mortality. Rapid identification and susceptibility prediction of causative pathogens, using Nanopore sequencing direct from blood cultures, may offer clinical benefit. We assessed this approach in comparison to conventional phenotypic methods and determined the accuracy of species identification and susceptibility prediction from genomic data. While this workflow holds promise, and performed well for some common bacterial species, improvements in sequencing accuracy and more robust predictive algorithms across a diverse range of organisms are required before this can be considered for clinical use. However, results could be achieved in timeframes that are faster than conventional phenotypic methods.

The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared. There were 111,402 patients operatively managed for orthopaedic trauma, with 2,775 of these (2.5%) complicated by FRI. The development of FRI had a statistically significant association with older age, male sex, residing in rural/remote areas, Aboriginal or Torres Strait Islander background, lower socioeconomic status, road traffic accident, work-related injuries, open fractures, anatomical region (lower limb, spine, pelvis), high injury severity, requiring soft-tissue coverage, and medical comorbidities (univariate analysis). Patients with FRI had an eight-times longer median inpatient length of stay (24 days vs 3 days), and a 2.8-times higher mean estimated inpatient hospitalization cost (AU$56,565 vs AU$19,773) compared with uninfected patients. The total estimated inpatient cost of the FRI cohort to the healthcare system was AU$156.9 million over the ten-year period. The results of this study advocate for improvements in trauma care and infection management, address social determinants of health, and highlight the upside potential to improve prevention and treatment strategies.

The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6months. However, in routine care, it is often extended to 12months, despite lacking robust supporting data. GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. For glioblastoma patients, extending post-radiation temozolomide from 6 to 12months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.

Cerebral ventriculitis might be caused by Gram-negative bacteria, including ESBL producers. Temocillin may be a useful treatment option in this scenario; however, no consistent data are available regarding its penetration into the CSF. To describe the population pharmacokinetics of temocillin in plasma and CSF and to determine the probability for different simulated dosing regimens to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets in the CSF. Ten post-neurosurgical critically ill adult patients requiring continuous drainage of CSF were included in this monocentric, prospective, open-label, non-randomized study. They received 2 g loading dose temocillin over 30 min IV infusion, followed by a 6 g continuous infusion over 24 h. Total and unbound concentrations were measured in plasma (n = 88 and 86) and CSF (n = 88 and 88) samples and used to build a population PK model. Monte Carlo simulations were performed to estimate the PTA at 100% Css>MIC (steady state concentration above the MIC) in CSF. All patients were infected with Enterobacterales with temocillin MICs ≤8 mg/L. The median (min-max) temocillin penetration in CSF was 12.1% (4.3-25.5) at steady state. Temocillin unbound plasma pharmacokinetics were best described by a one-compartment model. PTA for the applied dosing regimen was >90% for bacteria with MIC ≤ 4 mg/L. The currently approved dose of 6 g by continuous infusion may be adequate for the treatment of ventriculitis by Enterobacterales with MIC ≤ 4 mg/L if considering 100% Css>MIC as the PK/PD target to reach. Higher maintenance doses could help covering higher MICs, but their safety would need to be assessed.

Introduction: The anatomy of the forefoot is complex, and the sonographic assessment to image the plantar digital nerves and exclude, diagnose or discriminate between a Morton’s neuroma and intermetatarsal bursitis can be challenging. Topic description and discussion: A good appreciation of the sonographic anatomy, technique, normal and abnormal appearances is required to undertake a sonographic assessment of the forefoot and its interspaces, particularly the plantar digital nerves. This is unpacked in this paper with associated pictorial aids. Muscles, tendons, and ligaments of the interspaces and the nearby metatarsophalangeal joints and their associated soft-tissue structures are helpful sonographic landmarks to guide imaging and assessment of the common and proper plantar digital nerves and the intermetatarsal bursa. These need to be appreciated from both dorsal and plantar sonographic approaches, in both short- and long-axis imaging planes. Conclusion: Improved understanding of the anatomy and sonographic appearances of the interspace structures can enhance the sonographic assessment of the forefoot and improve diagnosis of a Morton’s neuroma and/or intermetatarsal bursitis when present to guide patient management.

ABSTRACT Medical sonography students require a deep understanding of three-dimensional (3D) structural anatomy. In addition, they are required to identify anatomical structures from medical images. To enhance and support online anatomy learning of first year medical sonography students ‘virtual café’ sessions were designed and offered as weekly activities. They were facilitated by higher year level student peers, who provided contextualisation of anatomy learning, guided discussions about the sonography programme and generated social discussions to allow students to get to know one another. This study investigated the impact of virtual cafe sessions on the student’s experience, student learning, student satisfaction with their programme of study and future career. The results indicated scheduled peer facilitated informal student discussions afforded the opportunity for students to catch up, meet each other, talk, and learn in a non-intimidating and social manner, whilst nurturing support was offered. A culture of positive contextualised, and authentic learning was developed which improved student engagement and enthusiasm for their programme of study. Most importantly, virtual café sessions facilitated students building social connections and trust with each other, so they subsequently felt less isolated and overwhelmed, but rather gained a sense of belonging, which motivated their learning.

During the COVID-19 pandemic, many individuals sought healthcare virtually. Physiotherapy is integral in managing temporomandibular disorders (TMDs); therefore, establishing how key physical tests can be appropriately adapted to telehealth is paramount. To establish the validity and reliability of telehealth (specifically videoconferencing) assessments against in-person assessments on a battery of TMD physical tests. A repeated-measures study design was undertaken. Thirty-six adult participants (19 healthy and 17 TMD) underwent concurrent temporomandibular joint (TMJ) physiological movement measurements via videoconferencing and in-person as per standard clinical practice. Inclusion criteria included the presence of central incisors and no significant comorbidities precluding a safe telehealth examination. Participants with TMD completed seven additional pain provocation physical tests. Agreement between telehealth and in-person physiological movement measures was excellent (ICC >0.90, 95% CI: 0.53 to >0.99). Inter- and intra-rater reliability for telehealth measures indicated excellent reliability (ICC >0.97, 95% CI: 0.91 to >0.99). Exact agreement between telehealth and in-person for provocation tests ranged between 58.8% and 94.1%. Fourteen of the twenty-six individual measures produced substantial to near perfect agreement (PABAK = 0.65-0.88), seven produced moderate agreement (PABAK = 0.53), while five produced poor to fair agreement (PABAK = 0.18-0.29). There is high level of agreement between telehealth and in-person measurements of TMJ physiological movement and pain provocation tests.

Aim To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). Methods Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month–confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. Results In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57–0.73) or BRACETD (RR = 0.46; 95% CI, 0.42–0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01–1.55) and BRACETD (HR = 1.46; 95% CI, 1.16–1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65–0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91–1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. Conclusions This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

Abstract Objectives The aim of this study was to determine the diagnostic accuracy of contrast-enhanced magnetic resonance imaging (CE-MRI) for the detection of perineural spread (PNS) in head and neck cancer patients. Methods A systematic review of PubMed, Embase, Scopus, Web of Science and Cochrane Library databases was performed up to May 20, 2022. We included diagnostic accuracy studies that used CE-MRI for the diagnosis of PNS in patients with head and neck cancer, using histopathology from surgical specimens as the reference standard. Potential bias and applicability of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADUS-2) tool. Pooled joint effect sizes of sensitivity and specificity were calculated by applying bivariate random-effects meta-analysis model. Results Nine studies with 259 patients were included. The pooled sensitivity and specificity of CE-MRI for detecting PNS were 89% (95% confidence interval [CI]: 73–96) and 83% (95% CI: 73–90), respectively. Stratifying by MRI strength, 1.5 T had a higher sensitivity of 97% (95% CI: 47–100) compared with 3 T, which had a sensitivity of 83% (95% CI: 72–90). Both 1.5- and 3-T MRI had a similar specificity in detecting PNS of 85% (95% CI: 63–95) and 84% (95% CI: 75–91), respectively. Conclusions CE-MRI provides good diagnostic test accuracy for the detection of PNS in head and neck cancer. Current evidence suggests 1.5-T MRI provides greater sensitivity compared with 3-T MRI.