Feasibility of collecting longitudinal patient-reported outcomes in individuals with relapsed or refractory large B-cell lymphoma who received chimeric antigen receptor T-cell (CART) therapy.

PURPOSE: Chimeric antigen receptor T-cell (CART) therapy has shown clinical efficacy in refractory and relapsed large B-cell lymphomas, but is associated with serious acute and long-term toxicities. To understand the patient perspective, we measured a patient-reported outcome (PRO), specifically, health-related quality of life (HRQoL), at multiple time points over one year. METHODS: This was a prospective feasibility study of a cohort of patients who were eligible for standard of care CART therapy, tisagenlecleucel. Demographic data and disease characteristics were collected. HRQoL was measured using FACT-Lym at baseline, and months 1, 3, 6 and 12. FACT-Lym includes FACT-G (physical, social, emotional and functional well-being domains), plus a lymphoma subscale. RESULTS: Thirty-four of 35 patients approached, consented to participate. Two of them did not receive their infusion due to progressive disease. 50% were female and median age was 62 (23-77). Twenty-nine patients (91%) completed baseline FACT-Lym and 20 of 21 (95%) eligible patients completed 12-month FACT-Lym. 52% completed all 4 post-baseline FACT-Lym measures. Exploratory analyses for changes in FACT-Lym scores are reported. CONCLUSION: It is feasible to measure longitudinal PROs in patients who receive CART therapy. This study will inform future studies in evaluating the patient perspective on CART therapy.

Beyond activity patterns: The complex process of activity management among individuals with chronic musculoskeletal pain after an orthopaedic trauma.

CONTEXT: Individuals must change the way they perform activities in response to chronic pain. In the literature, three activity patterns are commonly described: avoidance, pacing, and persistence. Many studies have explored these activity patterns. However, little research has delved into the factors that lead people to adopt a particular activity behaviour. This study aimed to explore the relationship that people with chronic musculoskeletal pain have with activity and highlight the factors underlying their practices. METHODS: The qualitative study was conducted by researchers in the social sciences, physiotherapy, psychology, and rehabilitation medicine. Observations of vocational workshops and semi-structured interviews were conducted with 33 persons undergoing rehabilitation for chronic musculoskeletal pain after an accident. RESULTS: Patients' declarations and actions show that any one patient will alternate between activity patterns: the same person may adopt a strategy of avoidance, pacing or persistence depending on the context, the importance of the activity, personal objectives, and representations of self, pain, and activity. The decision to engage in a particular behaviour is based on a process of self-negotiation weighted by the circumstances, the nature of the activity, the importance attached to it, and the individual's perceived ability. CONCLUSION: Our study emphasized the complexity of physical, social, and contextual factors that intervene in the relationship toward activity. Rather than favouring pacing, the therapist's role in rehabilitation might be to reinforce the reflexive process and the patient's adaptability in approaching the activity, to foster the capacity to find flexible solutions. SIGNIFICANCE: Patients choose an activity pattern (avoidance, pacing, persistence) according to the challenges they face in their daily lives. Context, representations of self and activity, as well as goals sought influence these choices. Some patients report having learned to adapt their activity management strategies. Therefore, therapeutic approaches in the rehabilitation context could focus on these adaptive capacities to offer patients optimal pain and activity management and develop their ability to use different strategies according to the circumstance.

Home and nearby nature: Uncovering relational flows between domestic and natural spaces in three countries during COVID-19.

This paper addresses the role of living spaces, neighborhood environments, and access to nearby nature in shaping individual experiences of health and well-being during the first wave of the COVID-19 pandemic. Key data is drawn from the GreenCOVID study across Spain, England and Ireland. The survey gathered contextual information about home environments, neighborhood spaces, and access to nature elements, and standardized measures of health and wellbeing between April and July 2020 (n = 3,127). The paper used qualitative data from the survey to document flows between home and nearby nature. These were framed as barriers/mediators with specific focus on differing interpretations of home as both trap and refuge, with additional dimensions of loss, disruption and interruption shaping the broad responses to the pandemic. By contrast nearby nature was an enabler/moderator of health and wellbeing, offering healthy flows between home and nature as well as respite and additional health-enabling factors. Differences were identified between the three countries but important commonalities emerged too, recognising the role nature plays as an asset both within and immediately beyond the home. The use of flow as metaphor also recognises the importance of embodiment and the elastic nature of connections between home and nearby nature for wellbeing. More broadly, flow provides a valuable way to trace affective relational geographers to develop a wider understanding of assemblages of health during pandemics.

A WC/WO star exploding within an expanding carbon-oxygen-neon nebula.

The final fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf-Rayet stars1 emit strong and rapidly expanding winds with speeds greater than 1,000 kilometres per second. A fraction of this population is also helium-depleted, with spectra dominated by highly ionized emission lines of carbon and oxygen (types WC/WO). Evidence indicates that the most commonly observed supernova explosions that lack hydrogen and helium (types Ib/Ic) cannot result from massive WC/WO stars2,3, leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosion4. Here we report observations of SN 2019hgp, beginning about a day after the explosion. Its short rise time and rapid decline place it among an emerging population of rapidly evolving transients5-8. Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen and neon. Narrow absorption features show that this material is expanding at high velocities (greater than 1,500 kilometres per second), requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive Wolf-Rayet stars may be the progenitors of some rapidly evolving transients.

Demodex: a skin resident in man and his best friend.

Demodex mites are microscopic arachnids found in the normal skin of many mammals. In humans, it is well established that Demodex mite density is higher in patients with the skin condition rosacea, and treatment with acaricidal agents is effective in resolving symptoms. However, pathophysiology of rosacea is complex and multifactorial. In dogs, demodicosis is a significant veterinary issue, particularly the generalized form of the disease which can be fatal if untreated. In each species, clinical and molecular studies have shown that the host's immunological interactions with Demodex mites are an important, but not fully understood, aspect of how Demodex can live in the skin either as a harmless commensal organism or as a pathogenic agent. This review outlines the role of Demodex mites in humans and dogs, considering morphology, prevalence, symptoms, diagnosis, histology treatment and pathogenesis.

Canadian perspective on managing multiple myeloma during the COVID-19 pandemic: lessons learned and future considerations.

The coronavirus disease 2019 (covid-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 has necessitated changes to the way patients with chronic diseases are managed. Given that patients with multiple myeloma are at increased risk of covid-19 infection and related complications, national bodies and experts around the globe have made recommendations for risk mitigation strategies for those vulnerable patients. Understandably, because of the novelty of the virus, many of the proposed risk mitigation strategies have thus far been reactionary and cannot be supported by strong evidence. In this editorial, we highlight some of the risk mitigation strategies implemented at our institutions across Canada during the first wave of covid-19, and we discuss the considerations that should be made when managing patients during the second wave and beyond.

Fluorine-18 labelled prostate-specific membrane antigen (PSMA)-1007 positron-emission tomography-computed tomography: normal patterns, pearls, and pitfalls.

Prostate-specific membrane antigen (PSMA)-based positron-emission tomography (PET)-computed tomography (CT) has shown great promise in prostate cancer imaging. This technique has demonstrated particular utility in the staging of high-risk primary cancer and in the localisation of recurrent disease. The use of fluorine-18 PSMA-1007 is advantageous, as it is excreted via the hepatobiliary system rather than urinary and the longer half-life of fluorine-18 compared to gallium tracers, allows for PSMA imaging in centres without a gallium generator. However, imaging with this tracer is not without flaws and areas of ambiguity remain. In this article, the biodistribution, clinical indications, and pearls of 18F-PSMA-1007 PET-CT in patients with prostate cancer will be discussed, as well as the potential pitfalls in the reporting of these studies.

Evaluation of Demodex mite viability using motility and scattered light intensity.

Demodex mites have been suggested to have a role in various cutaneous and ocular disorders pathogenesis, such as rosacea or blepharitis. Evaluation of potential treatments with anti-Demodex effects is difficult because the viability of living mites needs to be evaluated during their exposure to the agent being tested. Mite viability is currently based solely on their observed movement. However, this method of assessing viability has significant limitations as mites may be resting, immobile or paralysed at any given observation point giving the observer a false impression of the organism's death. To overcome this limitation we evaluated a new quantitative method of evaluating the viability of Demodex mites by using scattered light intensity (SLI). We demonstrated that when combined with observation of mite motility, SLI provided increased accuracy of the evaluation of viability of mites being studied. This new viability assay will help address the technical challenges of mite viability experiments. Accurate evaluation of mite viability will enhance mite biology research and allow for more accurate in vitro toxicity assays of proposed anti-mite agents.

Evaluation of subcutaneous rituximab administration on Canadian systemic therapy suites.

Background: Non-Hodgkin lymphoma (nhl) is the most common hematologic malignancy. Diffuse large B-cell lymphoma (dlbcl) and follicular lymphoma (fl) constitute 55% of new nhl cases and are initially treated with rituximab-based chemoimmunotherapy. Relative to intravenous (IV) rituximab, a subcutaneous (sc) formulation approved in 2016 has comparable pharmacokinetics, efficacy, and safety, and a greatly reduced administration time; it is also preferred by patients. The objective of the present study was to estimate the effect (on systemic therapy suite time and on the costs of drug acquisition and administration) of implementing sc rituximab in the initial chemoimmunotherapy for fl and dlbcl over 3 years in the Canadian market. Methods: An Excel (Microsoft Corporation, Redmond, WA, U.S.A.)-based model was created with a population size based on epidemiologic data and current rituximab use, duration of use considering initial therapy, time savings for sc rituximab administration from published studies, costs from standard Canadian sources, and assumed uptake in implementing provinces of 65%, 75%, and 80% over 3 years. Key parameters and sensitivity analysis values were validated by clinical experts located in various Canadian jurisdictions. Costs are reported in 2017 Canadian dollars from the perspective of the health care system. Results: More than 3 years after implementation of sc rituximab, we estimated that 5762 Canadians would be receiving sc rituximab, resulting in savings of 128,715 hours in systemic therapy suite time and approximately $40 million in drug and administration costs. Sensitivity analyses suggest that the model is most sensitive to sc market uptake, number of induction therapy cycles, and eligible patients. Conclusions: Subcutaneous administration of rituximab can significantly reduce systemic therapy suite time and achieve substantial savings in drug and administration costs.

Comparison of Advanced Imaging Resources, Radiology Workforce, and Payment Methodologies between the United States and Canada.

The purpose of this Practice Perspectives was to review the United States and Canadian approaches to health care access and payment for advanced imaging. The historical background, governmental role, workforce, coding, payment, radiologic challenges, cost, resource intensity, and overall outcomes in longevity are reviewed.

Low magnesium intake is associated with increased knee pain in subjects with radiographic knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: As magnesium mediates bone and muscle metabolism, inflammation, and pain signaling, we aimed to evaluate whether magnesium intake is associated with knee pain and function in radiographic knee osteoarthritis (OA). METHODS: We investigated the associations between knee pain/function metrics and magnesium intake from food and supplements in 2548 Osteoarthritis Initiative cohort participants with prevalent radiographic knee OA (Kellgren-Lawrence score ≥2). Magnesium intake was assessed by Food Frequency Questionnaire (FFQ) at baseline. WOMAC and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were reported annually with total follow up of 48 months. Analyses used linear mixed models. RESULTS: Among participants with baseline radiographic knee OA the mean total magnesium intake was 309.9 mg/day (SD 132.6) for men, and 287.9 mg/day (SD 118.1) for women, with 68% of men and 44% of women below the estimated average requirement. Subjects with lower magnesium intake had worse knee OA pain and function scores, throughout the 48 months (P < 0.001). After adjustment for age, sex, race, body mass index (BMI), calorie intake, fiber intake, pain medication use, physical activity, renal insufficiency, smoking, and alcohol use, lower magnesium intake remained associated with worse pain and function outcomes (1.4 points higher WOMAC and 1.5 points lower KOOS scores for every 50 mg of daily magnesium intake, P < 0.05). Fiber intake was an effect modifier (P for interaction <0.05). The association between magnesium intake and knee pain and function scores was strongest among subjects with low fiber intake. CONCLUSION: Lower magnesium intake was associated with worse pain and function in knee OA, especially among individuals with low fiber intake.

Swope Supernova Survey 2017a (SSS17a), the optical counterpart to a gravitational wave source.

On 17 August 2017, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and the Virgo interferometer detected gravitational waves (GWs) emanating from a binary neutron star merger, GW170817. Nearly simultaneously, the Fermi and INTEGRAL (INTErnational Gamma-Ray Astrophysics Laboratory) telescopes detected a gamma-ray transient, GRB 170817A. At 10.9 hours after the GW trigger, we discovered a transient and fading optical source, Swope Supernova Survey 2017a (SSS17a), coincident with GW170817. SSS17a is located in NGC 4993, an S0 galaxy at a distance of 40 megaparsecs. The precise location of GW170817 provides an opportunity to probe the nature of these cataclysmic events by combining electromagnetic and GW observations.

Electromagnetic evidence that SSS17a is the result of a binary neutron star merger.

Eleven hours after the detection of gravitational wave source GW170817 by the Laser Interferometer Gravitational-Wave Observatory and Virgo Interferometers, an associated optical transient, SSS17a, was identified in the galaxy NGC 4993. Although the gravitational wave data indicate that GW170817 is consistent with the merger of two compact objects, the electromagnetic observations provide independent constraints on the nature of that system. We synthesize the optical to near-infrared photometry and spectroscopy of SSS17a collected by the One-Meter Two-Hemisphere collaboration, finding that SSS17a is unlike other known transients. The source is best described by theoretical models of a kilonova consisting of radioactive elements produced by rapid neutron capture (the r-process). We conclude that SSS17a was the result of a binary neutron star merger, reinforcing the gravitational wave result.

Early spectra of the gravitational wave source GW170817: Evolution of a neutron star merger.

On 17 August 2017, Swope Supernova Survey 2017a (SSS17a) was discovered as the optical counterpart of the binary neutron star gravitational wave event GW170817. We report time-series spectroscopy of SSS17a from 11.75 hours until 8.5 days after the merger. Over the first hour of observations, the ejecta rapidly expanded and cooled. Applying blackbody fits to the spectra, we measured the photosphere cooling from [Formula: see text] to [Formula: see text] kelvin, and determined a photospheric velocity of roughly 30% of the speed of light. The spectra of SSS17a began displaying broad features after 1.46 days and evolved qualitatively over each subsequent day, with distinct blue (early-time) and red (late-time) components. The late-time component is consistent with theoretical models of r-process-enriched neutron star ejecta, whereas the blue component requires high-velocity, lanthanide-free material.

Light curves of the neutron star merger GW170817/SSS17a: Implications for r-process nucleosynthesis.

On 17 August 2017, gravitational waves (GWs) were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB 170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was subsequently identified as the counterpart of this event. We present ultraviolet, optical, and infrared light curves of SSS17a extending from 10.9 hours to 18 days postmerger. We constrain the radioactively powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in rapid neutron capture (r-process) nucleosynthesis in the universe.

Renal Consequences of Diabetes After Kidney Donation.

Whether diabetes after kidney donation is associated with an accelerated GFR decay in the remaining kidney has not been studied. We determined the incidence of diabetes in kidney donors, and compared GFR change over time in diabetic to nondiabetic donors, in addition to the effect of diabetes mellitus (DM) on the development of proteinuria, hypertension, and end-stage renal disease (ESRD). Of the 4014 donors, 309 (7.7%) developed diabetes at a median age of 56.0 years and after a median of 18 years after donation. The difference in annual estimated GFR (eGFR) change between diabetic and nondiabetic donors in the 7 years before the development of DM was -0.08 mL/min/year; p = 0.51. After DM development, the difference was -1.10 mL/min/year for diabetic donors with hypertension and proteinuria, p < 0.001; -0.19 for diabetic donors with hypertension but no proteinuria, p = 0.29; -0.75 mL/min/year for diabetic donors with proteinuria but no hypertension, p = 0.19; and -0.09 mL/min/year for diabetic donors without proteinuria or hypertension, p = 0.63. When DM was considered as a time-dependent covariate, it was associated with the development of proteinuria (hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.89-3.70; p < 0.001) and hypertension (HR 2.19, 95% CI 1.74-2.75; p < 0.001). It was not, however, associated with ESRD. eGFR decline after DM development exceeds that of nondiabetic donors only in diabetic donors with concomitant proteinuria and hypertension.

Clinical audit effectively bridges the evidence-practice gap in chronic subdural haematoma management.

BACKGROUND: Placement of a subdural drain after drainage of chronic subdural haematoma (CSDH) has been shown to reduce the rate of recurrence in several randomised controlled trials (RCT). The most recently published RCT was from Cambridge, UK, in 2009. Despite class I evidence for the use of subdural drains, it is unclear whether these results have been translated into clinical practice. In this clinical audit we review the use of subdural drains in our institution before and after the publication of the 2009 RCT results. METHODS: A longitudinal retrospective study was performed on all adults having burr holes for CSDH between January 2009 and January 2014. Case notes were analysed to determine subdural drain use, re-operation for CSDH recurrence and post-operative complications. The audit loop was closed with data collected from August 2015 to January 2016. RESULTS: Thirty-one per cent of patients had subdural drains placed at operation. Drain placement was associated with lower reoperation rates (8% vs. 17%, p = 0.021) without increasing complication rates. Drain usage doubled after publication of the Santarius et al. (2009) trial but we observed persisting and significant variability in drain utilisation by supervising consultants. The use of drains in the department increased from 35% to 75% of all cases after presentation of these results. CONCLUSIONS: The use of subdural drains in our unit reduced recurrence rates following drainage of CSDH and reproduced the results of a 2009 clinical trial. Although the use of subdural drains doubled in the post-trial epoch, significant variability remains in practice. Clinical audit provided an effective tool necessary to drive the implementation of subdural drain placement in our unit.

Is the endoscopic third ventriculostomy success score an appropriate tool to inform clinical decision-making?

INTRODUCTION: The endoscopic third ventriculostomy success score (ETVSS) is a model, which provides each patient with a prediction of the outcome of endoscopic third ventriculostomy. The objective of this study was to determine if there is clinical value to the use of the ETVSS in the decision for ETV. METHODS: Prospectively collected data on all ETV procedures with the Republic of Ireland in children ≤16 years of age, totalling 112, from 2008 to 2014 was analysed. The percentage chance of success at six months was retrospectively calculated according to the ETVSS. A multivariable model, comprising the risk factors from the ETVSS - age, aetiology and previous shunt - was created and its performance compared to that of the ETVSS. RESULTS: The ETVSS achieved an AUC of 0.61 (95% CI: 0.49-0.71) with a sensitivity and specificity of 50% and 76%, respectively, at its optimal cutoff. The ETVSS was not significantly well calibrated in this cohort and there was a limited net benefit on decision curve analysis in comparison with the strategy of performing ETV in all patients. The multivariable model achieved an AUC of 0.67 (95% CI: 0.56-0.78), was well calibrated and was associated with a superior net benefit over that of the ETVSS. CONCLUSION: The ETVSS represents the future of patient risk stratification with an easy to use, individualised approach for each patient. The ETVSS has performed adequately in this study. However, through the addition of novel risk factors, the continuous updating of the model and recalibration where needed, the ETVSS can become a tool that the paediatric neurosurgeon cannot do without.