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Vandana Ahluwalia,1 Tiffany L H Larsen,2 Carol A Kennedy,3 Taucha Inrig,3 Katie Lundon4 1Division of Rheumatology, Department of Internal Medicine, William Osler Health System, Brampton, ON, Canada; 2Department of Physiotherapy, Headwaters Health Care Center, Orangeville, ON, Canada; 3Musculoskeletal Health and Outcomes Research, St. Michael’s Hospital, Toronto, ON, Canada; 4Office of Continuing Professional Development and the Department of Medicine, Faculty of Medicine, University of Toronto, ON, Canada Objective: To facilitate access and improve wait times to a rheumatologist’s consultation, this study aimed to 1) determine the ability of an advanced clinician practitioner in arthritis care (ACPAC)-trained extended role practitioner (ERP) to triage patients with suspected inflammatory arthritis (IA) for priority assessment by a rheumatologist and 2) determine the impact of an ERP on access-to-care as measured by time-to-rheumatologist-assessment and time-to-treatment-decision.Materials and methods: A community-based ACPAC-trained ERP triaged new referrals for suspected IA. Patients with suspected IA were booked to see the rheumatologist on a priority basis. Diagnostic accuracy of the ERP to correctly identify priority patients; the level of agreement between ERP and rheumatologist (Kappa coefficient and percent agreement); and the time-to-treatment-decision for confirmed cases of IA were investigated. Retrospective chart review then compared time-to-rheumatologist-assessment and time-to-treatment-decision in the solo-rheumatologist versus the ERP-triage model.Results: One hundred twenty-one patients were triaged. The ERP designated 54 patients for priority assessment. The rheumatologist confirmed IA in 49/54 (90.7% positive predictive value [PPV]). Of the 121 patients, 67 patients were designated as nonpriority by the ERP, and none were determined to have IA by the rheumatologist (100% negative predictive value [NPV]). Excellent agreement was found between the ERP and the rheumatologist (Kappa coefficient 0.92, 95% CI: 0.84–0.99). In the ERP-triage model, time-from-referral-to-treatment-decision for patients with IA was 73.7 days (SD 40.4, range 12–183) compared with 124.6 days (SD 61.7, range 26–359) in the solo-rheumatologist model (40% reduction in time-to-treatment-decision).Conclusion: A well-trained and experienced ERP can shorten the time-to-Rheumatologist-assessment and time-to-treatment-decision for patients with suspected IA. Keywords: rheumatology, health services accessibility, interprofessional relations, community health services, integrated delivery systems

In an attempt to mitigate transfusion-related acute lung injury (TRALI), the Oslo Blood Center screened 1369 thrombapheresis donors for human leucocyte antigen (HLA)-specific antibodies. Anti-HLA antibodies were found in 200 donors who were deferred from donation of plasma-rich products. In a retrospective study, 2562 transfusions of thrombocytes (both apheresis and whole blood-derived) from 150 of these donors were subject to a thorough look back-investigation. Reports of 14 transfusion reactions were identified, none of which were classified as TRALI. Our study supports previous data indicating that the risk of TRALI is low. The value of screening for anti-HLA antibodies and subsequent deferral of donors with high levels of such antibodies remains questionable., (Copyright © 2024. Published by Elsevier Ltd.)

Background:  Incidence of and risk factors for bleeding in cancer patients with venous thromboembolism (VTE) treated with apixaban are poorly described., Methods:  We analyzed data from the prospective CAP study where 298 cancer patients with any type of VTE received 5 mg apixaban twice daily for 6 months, and then 2.5 mg apixaban twice daily for 30 months. For most analyses, major bleedings and clinically relevant nonmajor bleedings were merged to "clinically relevant bleedings." Risk factors were estimated by odds ratios (OR) and 95% confidence intervals (CIs)., Results:  The incidence of clinically relevant bleedings was 38% per person-year during the first 6 months of treatment, 21% per person-year from 7 to 12 months, and between 4 and 8% per person-year from 13 to 36 months. Clinically relevant bleedings were associated with age above 74 years (OR: 2.0, 95% CI: 1.0-4.1), body mass index (BMI) below 21.7 (OR: 2.3, 95% CI: 1.1-4.8), and hemoglobin at baseline below 10.5 for females (OR: 2.8, 95% CI: 1.1-7.3) and 11.1 for males (OR: 3.3, 95% CI: 1.3-8.4) during the first 6 months. Gastrointestinal (GI) or urogenital cancer was not associated with clinically relevant bleedings compared with other cancers. Among patients with luminal GI cancer, nonresected cancer had increased risk of bleeding (OR: 3.4, 95% CI: 1.0-11.6) compared with resected GI cancer., Conclusion:  There were very few bleedings while patients were on low-dose apixaban. Factors associated with bleeding in patients treated with full-dose apixaban were high age, low BMI, and low hemoglobin, and probably nonresected luminal GI cancer., Competing Interests: T.-L.L. received lecture honoraria from Pfizer and Bristol Myers Squibb. W.G. received fees for participation in advisory boards from Amgen, Novartis, Pfizer, Principia Biopharma Inc.—a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, and Cellphire. Also, received Lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi, and Bayer. Research grants from Bayer, BMS/Pfizer, and UCB. A.E.A.D. received lecture honoraria from Pfizer, Novartis, Bayer, and Bristol Myers Squibb. Also, received Consultancy honoraria from Pfizer, Bristol Myers Squibb, and MSD., (Thieme. All rights reserved.)

Aims: Patients with inflammatory joint diseases (IJD), including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) have increased rates of pulmonary embolism (PE). Non-steroidal anti-inflammatory drugs (NSAIDs) use is associated with PE in the general population. Our aim was to evaluate the association between NSAIDs use and PE in IJD patients., Methods and Results: Using individual-level registry data from the whole Norwegian population, including data from the Norwegian Patient Registry and the Norwegian Prescription Database, we: (1) evaluated PE risk in IJD compared to non-IJD individuals, (2) applied the self-controlled case series method to evaluate if PE risks were associated with use of traditional NSAIDs (tNSAIDs) and selective cox-2 inhibitors (coxibs). After a one-year wash-out period, we followed 4 660 475 adults, including 74 001 with IJD (RA: 39 050, PsA: 20 803, and axSpA: 18 591) for a median of 9.0 years. Crude PE incidence rates per 1000 patient years were 2.02 in IJD and 1.01 in non-IJD individuals. Age and sex adjusted hazard ratios for PE events were 1.57 for IJD patients compared to non-IJD. Incidence rate ratios (IRR) [95% confidence interval (CI)] for PE during tNSAIDs use were 0.78 (0.64-0.94, P = 0.010) in IJD and 1.68 (1.61-1.76, P < 0.001) in non-IJD. IRR (95% CI) for PE during coxibs use was 1.75 (1.10-2.79, P = 0.018) in IJD and 2.80 (2.47-3.18, P < 0.001) for non-IJD., Conclusion: Pulmonary embolism rates appeared to be higher in IJD than among non-IJD subjects in our study. Traditional NSAIDs may protect against PE in IJD patients, while coxibs may associated with increased PE risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: In a recent interventional study of cancer patients with newly diagnosed venous thrombosis (VT), we found a high risk of arterial thrombotic events (AT) during treatment with therapeutic doses of apixaban., Methods: Total 298 cancer patients with VT received apixaban as treatment and secondary prophylaxis for up to 36 months. AT was registered as a serious adverse event, and this is a post hoc analysis of risk factors for AT. Clinical risk factors and concomitant medication were assessed through odds ratios (OR) with 95 % confidence interval using multivariate logistic regression. Biomarkers were assessed by non-parametric testing., Results: AT occurred in 16/298 patients (5.4 %, 95 % confidence interval (CI) 3.1-8.6 %). Median leucocyte count at baseline was higher in patients with AT compared with patients without AT (11 vs. 6.8·10 9 /L, p < 0.01). Clinical factors associated with AT were pancreatic cancer (OR 13.7, 95 % CI 4.3-43.1), ovarian cancer (OR 19.3, 95 % CI 2.3-164.4), BMI <25 percentile (OR 3.1, 95 % CI 1.1-8.8) and previous VT (OR 4.4, 95 % CI 1.4-13.7). Pancreatic cancer had a cumulative incidence of AT of 36 % compared with 0.8 % for all other cancers at 6 months (p < 0.01). Non-steroidal anti-inflammatory drugs (OR 4.9, 95 % CI 1.0-26) and antiplatelet treatment (OR 3.8, 95 % CI 1.2-12.2) were associated with AT., Conclusion: In cancer patients with apixaban treated VT, pancreatic cancer was strongly associated with AT. In addition, ovarian cancer, BMI < 25 percentile, previous VT, antiplatelet treatment, non-steroidal anti-inflammatory drug use and high leucocyte count at baseline were associated with AT. The CAP study is registered with the unique identifier NCT02581176 in ClinicalTrials.gov., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: At the start of the pandemic, the Norwegian Directorate of Health and Norwegian blood banks initiated the production of COVID-19 convalescent plasma within the framework of clinical studies. In this article we describe the blood donors who participated., Material and Method: Blood donors who had recovered from COVID-19 were recruited to donate single donor plasma for the purpose of patient treatment. Data on the course of infection, leukocyte antibodies and antibody level against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) per plasma unit were registered after informed consent was obtained. We calculated a disease score defined as the total number of self-reported symptoms/findings and hospitalisation where relevant (score 0-⁠11)., Results: A total of 1644 plasma units were collected from 266 plasma donors at 12 blood banks. Median disease score was 5 (interquartile range 3-⁠6), and 15 donors had recovered from pneumonia and/or been hospitalised. A total of 599/1644 plasma units from 106/266 donors met our requirement for SARS-CoV-2 antibody content (> 60 % inhibition of virus binding to angiotensin-converting enzyme 2 (ACE2)) or positive virus neutralisation test. The antibody level in donors waned over time following infection, and showed no clear correlation with disease score., Interpretation: The number of symptoms and findings in blood donors could not predict antibody response at individual level, and antibody testing was crucial for the production of effective convalescent plasma.

Venous thromboembolism is a common complication of cancer. The prevalence varies according to cancer type and increases proportionally with the stage of cancer. In the past 15-20 years, low molecular weight heparin has been recommended as the first-line treatment. New international guidelines now allow for use of direct factor Xa inhibitors both as prophylaxis and treatment for venous thromboembolism. Prophylaxis should as a general rule only be initiated in patients with moderate to high risk. Bleeding risk assessment is important before starting anticoagulation. Both thrombosis and bleeding risk can change and should therefore be assessed on an ongoing basis. In this clinical review, use of anticoagulation therapy in cancer patients is discussed with particular emphasis on the use of direct factor Xa inhibitors.

Objective: To develop a pan-Canadian rural education road map to advance the recruitment and retention of family physicians in rural, remote, and isolated regions of Canada in order to improve access and health care outcomes for these populations., Composition of the Task Force: Members of the task force were chosen from key stakeholder groups including educators, practitioners, the College of Family Physicians of Canada education committee chairs, deans, chairs of family medicine, experts in rural education, and key decision makers. The task force members were purposefully selected to represent a mix of key perspectives needed to ensure the work produced was rigorous and of high quality. Observers from the Canadian Medical Association and Health Canada's Council on Health Workforce, and representatives from the Royal College of Physicians and Surgeons of Canada, were also invited to provide their perspectives and to encourage and coordinate multiorganization action., Methods: The task force commissioned a focused literature review of the peer-reviewed and gray literature to examine the status of rural medical education, training, and practice in relation to the health needs of rural and remote communities in Canada, and also completed an environmental scan., Report: The environmental scan included interviews with more than 100 policy makers, government representatives, providers, educators, learners, and community leaders; 17 interviews with practising rural physicians; and 2 surveys administered to all 17 faculties of medicine. The gaps identified from the focused literature review and the results of the environmental scan will be used to develop the task force's recommendations for action, highlighting the role of key partners in implementation and needed action., Conclusion: The work of the task force provides an opportunity to bring the various partners together in a coordinated way. By understanding who is responsible and the actions each stakeholder needs to take to make the recommendations a reality, the task force can lay the groundwork for developing a coordinated, comprehensive health human resource strategy that considers the integral role of medical education as a health system intervention., (Copyright© the College of Family Physicians of Canada.)

Background: Non-operative management for blunt splenic injuries was introduced to reduce the risk of overwhelming post splenectomy infection in children. To increase splenic preservation rates, splenic artery embolization (SAE) was added to our institutional treatment protocol in 2002. In the presence of clinical signs of ongoing bleeding, SAE was considered also in children. To our knowledge, the long term splenic function after SAE performed in the paediatric population has not been evaluated and constitutes the aim of the present study., Methods: A total of 11 SAE patients less than 17 years of age at the time of injury were included with 11 healthy volunteers serving as matched controls. Clinical examination, medical history, general blood counts, immunoglobulin quantifications and flowcytometric analysis of lymphocyte phenotypes were performed. Peripheral blood smears were examined for Howell-Jolly bodies (H-J bodies) and abdominal ultrasound was performed in order to assess the size and perfusion of the spleen., Results: On average 4.6 years after SAE (range 1-8 years), no significant differences could be detected between the SAE patients and their controls. Total and Pneumococcus serospecific immunoglobulins and H-J bodies did not differ between the study groups, nor did general blood counts and lymphocyte numbers, including memory B cell proportions. The ultrasound examinations revealed normal sized and well perfused spleens in the SAE patients when compared to their controls., Conclusion: This case control study indicates preserved splenic function after SAE for splenic injury in children. Mandatory immunization to prevent severe infections does not seem warranted., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The incidence of non-right-handedness was assessed among a sample of international adoptees. Neurocognitive and behavioral correlates to handedness were also examined among participants. A sample of 139 international adoptees (54 males; mean age at testing = 111.4 months ± 32.9 months) underwent a comprehensive neuropsychological evaluation, assessing verbal and visual reasoning, language, memory, attention, impulse control, processing speed, academic functioning, manual dexterity, and behavioral functioning. Over 26% of participants reported non-right-handedness. Non-right- and right-handers did not differ on demographic or orphanage specific variables. The groups were found to significantly differ on behavioral indices of attention and several neurocognitive variables, including visual memory, verbal memory, and manual dexterity of the dominant hand, with non-right-handers having worse performance. Possible mechanisms for these findings are discussed.

Background: After introducing splenic artery embolisation (SAE) in the institutional treatment protocol for splenic injury, we wanted to evaluate the effects of SAE on splenic function and assess the need for immunisation in SAE treated patients., Methods: 15 SAE patients and 14 splenectomised (SPL) patients were included and 29 healthy blood donors volunteered as controls. Clinical examination, medical history, general blood counts, immunoglobulin quantifications and flowcytometric analysis of lymphocyte phenotypes were performed. Peripheral blood smears from all patients and controls were examined for Howell-Jolly (H-J) bodies. Abdominal doppler, gray scale and contrast enhanced ultrasound (CEUS) were performed on all the SAE patients., Results: Leukocyte and platelet counts were elevated in both SAE and SPL individuals compared to controls. The proportion of memory B-lymphocytes did not differ significantly from controls in either group. In the SAE group total IgA, IgM and IgG levels as well as pneumococcal serotype specific IgG and IgM antibody levels did not differ from the control group. In the SPL group total IgA and IgG Pneumovax(®) (PPV23) antibody levels were significantly increased, and 5 of 12 pneumococcal serotype specific IgGs and IgMs were significantly elevated. H-J bodies were only detected in the SPL group. CEUS confirmed normal sized and well perfused spleens in all SAE patients., Conclusion: In our study non-operative management (NOM) of high grade splenic injuries including SAE, was followed by an increase in total leukocyte and platelet counts. Normal levels of immunoglobulins and memory B cells, absence of H-J bodies and preserved splenic size and intraparenchymal blood flow suggest that SAE has only minor impact on splenic function and that immunisation probably is unnecessary., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Recent studies have indicated that Treg contribute to the HIV type 1 (HIV-1)-related immune pathogenesis. However, it is not clear whether T cells with suppressive properties reside within the HIV-1-specific T-cell population. Here, PBMC from HIV-1-infected individuals were stimulated with a 15-mer Gag peptide pool, and HIV-1-specific T cells were enriched by virtue of their secretion of IL-10 or IFN-gamma using immunomagnetic cell-sorting. Neither the IL-10-secreting cells nor the IFN-gamma-secreting cells expressed the Treg marker FOXP3, yet the IL-10-secreting cells potently suppressed anti-CD3/CD28-induced CD4(+) as well as CD8(+) T-cell proliferative responses. As shown by intracellular cytokine staining, IL-10- and IFN-gamma-producing T cells represent distinct subsets of the HIV-1-specific T cells. Our data collectively suggest that functionally defined HIV-1-specific T-cell subsets harbor potent immunoregulatory properties that may contribute to HIV-1-associated T-cell dysfunction.

Objectives: Bioavailability of NO can be estimated by measuring the concentration of nitrate (NO(3)) in serum. However, the methods used for the measurement NO(3) in plasma or serum show a great degree of variation. Therefore, we compared two analytical methods for the measurement of NO(3) in serum., Design and Methods: The concentration of NO(3) in 600 serum samples collected from healthy individuals was determined by the HPLC and by the Griess reagent-spectroscopic method., Results: The concentration of NO(3) in the samples was 29.4+/-16.1 micromol/L and 26.2+/-14.0 micromol/L (mean+/-SD) measured by HPLC and Griess reagent-spectroscopic method respectively (p<0.0001). We detected a significant correlation between the two methods (R=0.81, p<0.0001)., Conclusions: A significant correlation between the two methods may suggest that either method can be used for the measurement of NO(3) in serum, however the Griess reagent-spectroscopic method measures lower concentrations of NO(3) than the HPLC method.

Aim: The purpose of the present study was to evaluate the effect of an ultrafiltration system on the bacteriological water quality in dental units., Design: A BIN-X UF-45R ultrafiltration system with a pore membrane of 0.03 microm was mounted at the water supply of six older dental units while six control units were disinfected with sodium hypochlorite according to a standard procedure. As the water quality in the test units deteriorated in spite of ultrafiltration the test units were subjected to chlorination at different concentrations several times during the test period., Outcome Measure: The number of colony forming units (cfu)/ml in water was determined according to European Standards on water quality., Results: While the median number of cfu/ml in control units never exceeded 7.6x10(1) the median cfu/ml in test units increased up to >1x10(5) in 3-4 days every time chlorination of the units was interrupted., Conclusion: The ultrafiltration system mounted at the water supply for six dental units was not able to control the bacteria originating from the existing biofilm in the water lines and deliver water of an acceptable quality.