We show that many graphs with bounded treewidth can be described as subgraphs of the strong product of a graph with smaller treewidth and a bounded-size complete graph. To this end, define the underlying treewidth of a graph class $\mathcal{G}$ to be the minimum non-negative integer $c$ such that, for some function $f$, for every graph $G \in \mathcal{G}$ there is a graph $H$ with $\textrm{tw}(H) \leqslant c$ such that $G$ is isomorphic to a subgraph of $H \boxtimes K_{f(\textrm{tw}(G))}$. We introduce disjointed coverings of graphs and show they determine the underlying treewidth of any graph class. Using this result, we prove that the class of planar graphs has underlying treewidth $3$; the class of $K_{s,t}$-minor-free graphs has underlying treewidth $s$ (for $t \geqslant \max \{s,3\}$); and the class of $K_t$-minor-free graphs has underlying treewidth $t-2$. In general, we prove that a monotone class has bounded underlying treewidth if and only if it excludes some fixed topological minor. We also study the underlying treewidth of graph classes defined by an excluded subgraph or excluded induced subgraph. We show that the class of graphs with no $H$ subgraph has bounded underlying treewidth if and only if every component of $H$ is a subdivided star, and that the class of graphs with no induced $H$ subgraph has bounded underlying treewidth if and only if every component of $H$ is a star.

Background: The presence of intraluminal thrombi (ILT) in acutely symptomatic carotid stenosis (“hot carotid”) represents a therapeutic dilemma for physicians. With little evidence to guide treatment, current ILT management approaches rely on individual or institutional preferences. Methods: This mixed methods study analyzed themes from semi-structured interviews with 22 stroke physicians from 16 centers, paired with a worldwide case-based survey of 628 stroke physicians conducted through the “Practice Current” section of Neurology: Clinical Practice. Results: In the thematic analysis of the interviews and quantitative analysis of the survey, participants favoured using anticoagulation with or without antiplatelet agents in patients with ILT (463/628, 74%). Despite a preference for anticoagulation, uncertainty regarding optimal antithrombotic management was noted in the thematic analysis. Additional themes identified included a preference for re-imaging patients in 3-5 days after initiating treatment to look for complete or partial clot resolution, at which point most experts would then be comfortable proceeding with revascularization if indicated, though uncertainty regarding the optimal timing of revascularization was noted. Conclusions: In cases of ILT in the “hot carotid” practice patterns of global experts show a preference for using anticoagulation and reimaging patients in 3-5 days, though there is considerable equipoise regarding the most appropriate management of these patients.

Background: Little evidence exists to guide the management of symptomatic non-stenotic carotid disease (SyNC). SyNC, which refers to carotid lesions with less than 50% artery stenosis, has been increasingly implicated as a cause of stroke and TIA. Methods: Semi-structured interviews with 22 stroke physicians from 16 centers were conducted as part of the Hot Carotid Qualitative Study. This study explored decision-making approaches, opinions and attitudes regarding the management of symptomatic carotid disease. Presented here are a subset of results related to the decision to revascularize patients with SyNC. Results: Thematic analysis revealed equipoise in the decision to revascularize patients with SyNC. Participants discussed a desire to use imaging features (e.g plaque rupture and plaque morphology) to inform the decision to revascularize, though significant uncertainty remains in appraising the risk conferred by certain features. Experts support further study to better understand the use of these features in risk appraisal for patients with SyNC. Conclusions: The decision to revascularize patients with SyNC is an area with significant equipoise. Experts identify the use of imaging features as an important tool in informing the decision to pursue revascularization in patients with SyNC though more study is required in this area to better inform practice.

The incidences of both breast cancer and obesity are rising in the UK. Obesity increases the risk of developing breast cancer in the postmenopausal population and leads to worse outcomes in those of all ages treated for early-stage breast cancer. In this review we explore the multifactorial reasons behind this association and the clinical trial evidence for the benefits of physical activity and dietary interventions in the early and metastatic patient groups. As more people with breast cancer are cured, and those with metastatic disease are living longer, cancer survivorship is becoming increasingly important. Therefore, ensuring the long-term implications of cancer and cancer treatment are addressed is vital. Although there remains a lack of definitive evidence that deliberate weight loss after a diagnosis of breast cancer reduces disease recurrence, a number of studies have reported benefits of weight loss and of physical activity. However, the limited data currently available mean that clinicians remain unclear on the optimal lifestyle advice to give their patients. Further high-quality research is needed to provide this evidence base, which will be required to optimise clinical care and for the commissioning of lifestyle interventions in the UK in breast cancer survivors.

A crucial reckoning was initiated when the COVID-19 pandemic began to expose and intensify long-standing racial/ethnic health inequities, all while various sectors of society pursued racial justice reform. As a result, there has been a contextual shift towards broader recognition of systemic racism, and not race, as the shared foundational driver of both societal maladies. This confluence of issues is of particular relevance to Black populations disproportionately affected by the pandemic and racial injustice. In response, institutions have initiated diversity, equity, and inclusion (DEI) efforts as a way forward. This article considers how the dual pandemic climate of COVID-19-related health inequities and the racial justice movement could exacerbate the “time and effort tax” on Black faculty to engage in DEI efforts in academia and biomedicine. We discuss the impact of this “tax” on career advancement and well-being, and introduce an operational framework for considering the interconnected influence of systemic racism, the dual pandemics, and DEI work on the experience of Black faculty. If not meaningfully addressed, the “time and effort tax” could contribute to Black and other underrepresented minority faculty leaving academia and biomedicine – consequently, the very diversity, equity, and inclusion work meant to increase representation could decrease it.

Background: There are uncertainties regarding the optimal management of acutely symptomatic carotid stenosis (“hot carotids”). We sought to explore the approaches of stroke physicians to anti-thrombotic management, imaging, and revascularization in patients with “hot carotids”. Methods: We used a qualitative descriptive methodology to examine decision-making approaches of physicians regarding the management of hot carotids. We conducted semi-structured interviews with 22 stroke physicians from various specialties in 16 centers across 4 continents. Results: Important themes regarding anti-thrombotic included limitations of existing clinical trial evidence, competing physician preferences, antiplatelet therapy while awaiting revascularization and various regional differences. Timely imaging availability, breadth of information gained, and surgeon/interventionalist preferences were important themes influencing the choice of imaging modality. The choice of revascularization intervention was influenced by healthcare system factors such as use of multidisciplinary review and operating room/angiography suite availability, and patient factors like age and infarct size. Many themes related to uncertainties in the management of hot carotids were also discussed. Conclusions: Our study revealed themes that are important to international stroke experts. We highlight common and divergent practices while underscoring important areas of clinical equipoise and uncertainty. Teams designing international carotid trials may wish to accommodate identified variations in practice patterns and areas of uncertainty.

Health technology assessment (HTA) agencies are considering adopting a lifecycle approach to assessments to address uncertainties in the evidence base at launch and to revisit the clinical and economic value of therapies in a dynamic clinical landscape. For reassessments of therapies post launch, HTA agencies are looking to real-world evidence (RWE) to enhance the clinical and economic evidence base, though challenges and concerns in using RWE in decision-making exists. Stakeholders are embarking on demonstration projects to address the challenges and concerns and to further define when and how RWE can be used in HTA decision making. The Institute for Clinical and Economic Review piloted a 24-month observational RWE reassessment. Key learnings from this pilot include identifying the benefits and challenges with using RWE in reassessments and considerations on prioritizing and selecting topics relevant for RWE updates.

Background: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention is well-established, uncertainties remain regarding the optimal anti-thrombotic regimen for acutely symptomatic carotid stenosis (“hot carotid”), particularly as patients await revascularization. We sought to explore the approaches of stroke physicians to peri-procedural anti-thrombotic management of patients with “hot carotids”. Methods: We conducted semi-structured interviews regarding “hot carotid” management with purposive sampling of 20 stroke physicians from 14 centres in North America, Europe, Asia, and Australia. We identified key themes using conventional qualitative content analysis. Results: Important themes revealed from our discussion included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and single vs dual antiplatelet therapy (DAPT) while awaiting revascularization. Areas of uncertainty included the management of stroke while on aspirin, implications of non-stenotic features of carotid disease (intraluminal thrombus, plaque morphology), the role of newer anti-platelet agents or anticoagulants, platelet aggregation testing, and how soon to start DAPT. Conclusions: Our qualitative analysis revealed themes that were important to stakeholders in stroke care. Teams designing international trials will have to accommodate identified variations in anti-thrombotic practice patterns and take into consideration areas of uncertainty, such as newer anti-thrombotic agents, and the implication of non-stenotic features of carotid disease.

Background: Evidence informing the choice between endarterectomy and stenting for acutely symptomatic carotid stenosis (“hot carotid”) is dated, and uncertainties remain regarding the optimal imaging modality. We sought to explore the thoughts of stroke physicians regarding the perioperative management of patients with acute symptomatic carotid stenosis. Methods: We conducted semi-structured interviews regarding “hot carotid” management with purposive sampling of 20 stroke physicians from 14 centres in North America, Europe, Asia, and Australia. We identified key themes using conventional qualitative content analysis. Results: Timely imaging availability, breadth of information gained, and surgeon/interventionalist preference emerged as important themes informing the choice of imaging modality. Multidisciplinary decision making, operating room/angiography suite availability, and implications of patient age and infarct size were important themes related to the choice of revascularization. Areas of uncertainty included utility of carotid plaque imaging, timing of revascularization, and the role of intervention with borderline stenosis or intraluminal thrombus. Conclusions: Our qualitative analysis revealed themes that were important to stroke experts. Teams designing international trials will have to accommodate identified variations in practice patterns and take into consideration areas of uncertainty, such as timing of revascularization, imaging of carotid plaque and non-stenotic features of carotid disease (intraluminal thrombus, plaque morphology).

Background: Patients with acutely symptomatic carotid stenosis (“hot carotid”) have high up-front risk of recurrent strokes. Uncertainties remain regarding optimal anti-thrombotic management, particularly while awaiting revascularization with endarterectomy or stenting (CEA/CAS). Methods: We administered a worldwide electronic survey through Neurology: Clinical Practice. Respondents chose their preferred antithrombotic regimen (1) in a general case of acutely symptomatic carotid stenosis, (2) if the patient was already on aspirin, or (3) had associated intraluminal thrombus(ILT). Responses among different groups were compared using multivariable logistic regression. Results: We received 668 responses from 71 countries. Most respondents favoured CEA(69.1%) over CAS, an aspirin-containing regimen(88.5%), and a clopidogrel-containing regimen(64.4%) if already on aspirin. Monotherapy was favoured by 54.4-70.6% across scenarios. The preferred dual therapy was low-dose aspirin(75-100mg) plus clopidogrel(22.2%), or high-dose aspirin(160-325mg) plus clopidogrel if already on aspirin(12.2%). Respondents favouring CAS more often chose ≥2 agents (adjusted odds-ratio[aOR] vs CEA: 2.00, 95%CI 1.36-2.95,p=0.001) or clopidogrel-containing regimens (aOR:1.77,1.16-2.70,p=0.008). Respondents from Europe less commonly chose multiple agents (aOR vs United States/Canada: 0.57,0.35–0.93,p=0.023) while those from Asia more often favored multi-agent regimens (aOR:1.95,1.11–3.43,p=0.020). Conclusions: Our results highlight the heterogeneous anti-thrombotic management of hot carotids. Future trials should likely include high-dose aspirin monotherapy or low-dose aspirin/clopidogrel dual-therapy as a comparator arm to stimulate enrolment.

A Mediterranean-style eating pattern (MED-EP) may include moderate red meat intake. However, it is unknown if the pro-atherogenic metabolite trimethylamine N-oxide (TMAO) is affected by the amount of red meat consumed with a MED-EP. The results presented are from a secondary, retrospective objective of an investigator-blinded, randomised, crossover, controlled feeding trial (two 5-week interventions separated by a 4-week washout) to determine if a MED-EP with 200 g unprocessed lean red meat/week (MED-CONTROL) reduces circulating TMAO concentrations compared to a MED-EP with 500 g unprocessed lean red meat/week (MED-RED). Participants were seventy-seven women and twelve men (n 39 total) who were either overweight or obese (BMI: mean (30·5) (sem 0·3) kg/m2). Serum samples were obtained following an overnight fast both before (pre) and after (post) each intervention. Fasting serum TMAO, choline, carnitine and betaine concentrations were measured using a targeted liquid chromatography-MS. Data were analysed to assess if (a) TMAO and related metabolites differed by intervention and (b) if changes in TMAO were associated with changes in Framingham 10-year risk score. Serum TMAO was lower post-intervention following MED-CONTROL compared with MED-RED intervention (post-MED-CONTROL 3·1 (sem 0·2) µmv. post-MED-RED 5·0 (sem 0·5) µm, P < 0·001), and decreased following MED-CONTROL (pre- v. post-MED-CONTROL, P = 0·025). Exploratory analysis using mixed model ANCOVA identified a positive association between changes in TMAO and changes in homoeostatic model assessment of insulin resistance (P = 0·036). These results suggest that lower amounts of red meat intake lead to lower TMAO concentrations in the context of a MED-EP.

New Zealand has a strategy of eliminating SARS-CoV-2 that has resulted in a low incidence of reported coronavirus-19 disease (COVID-19). The aim of this study was to describe the spread of SARS-CoV-2 in New Zealand via a nationwide serosurvey of blood donors. Samples (n = 9806) were collected over a month-long period (3 December 2020–6 January 2021) from donors aged 16–88 years. The sample population was geographically spread, covering 16 of 20 district health board regions. A series of Spike-based immunoassays were utilised, and the serological testing algorithm was optimised for specificity given New Zealand is a low prevalence setting. Eighteen samples were seropositive for SARS-CoV-2 antibodies, six of which were retrospectively matched to previously confirmed COVID-19 cases. A further four were from donors that travelled to settings with a high risk of SARS-CoV-2 exposure, suggesting likely infection outside New Zealand. The remaining eight seropositive samples were from seven different district health regions for a true seroprevalence estimate, adjusted for test sensitivity and specificity, of 0.103% (95% confidence interval, 0.09–0.12%). The very low seroprevalence is consistent with limited undetected community transmission and provides robust, serological evidence to support New Zealand's successful elimination strategy for COVID-19.

Introduction: The Cunningham reduction method for anterior shoulder dislocation offers an atraumatic alternative to traditional reduction techniques without the inconvenience and risk of procedural sedation and analgesia (PSA). Unfortunately, success rates as low as 27% have limited widespread use of this method. Inhaled methoxyflurane (I-MEOF) offers a rapidly administered, minimally invasive option for short-term analgesia. We conducted a pilot study to evaluate the feasibility of studying whether I-MEOF increased success rates for atraumatic reduction of anterior shoulder dislocation. Methods: A convenience sample of 20 patients with uncomplicated anterior shoulder dislocations were offered the Cunningham reduction method supported by methoxyflurane analgesia under the guidance of an advanced care paramedic. Operators were instructed to limit their attempt to the Cunningham method. Outcomes included success rate without the requirement for PSA, time to discharge, and operator and patient satisfaction with the procedure. Results: 20 patients received I-MEOF and an attempt at Cunningham reduction. 80% of patients were male, median age was 38.6 (range 18-71), and 55% were first dislocations of that joint. 35% (8/20 patients) had reduction successfully achieved by the Cunningham method under I-MEOF analgesia. The remainder proceeded to closed reduction under PSA. All patients had eventual successful reduction in the ED. 60% of operators reported good to excellent satisfaction with the process, with inadequate muscle relaxation being identified as the primary cause of failed initial attempts. 80% of patients reported good to excellent satisfaction. Conclusion: Success with the Cunningham technique was marginally increased with the use of I-MEOF, although 65% of patients still required PSA to facilitate reduction. The process was generally met with satisfaction by both providers and patients, suggesting that early administration of analgesia is appreciated. Moreover, one-third of patients had reduction achieved atraumatically without need for further intervention. A larger, randomized study may identify patient characteristics which make this reduction method more likely to be successful.