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1.
JCO Oncol Pract ; : OP2300560, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38478801

ABSTRACT

PURPOSE: At our institution's cancer palliative care (PC) clinic, new referrals from oncologists were scheduled for consultation and ongoing follow-up by PC physicians without input from the patients' family physicians (FPs). FPs reported that they felt out of the loop. We implemented a quality improvement (QI) initiative aimed at systematically facilitating care coordination between FPs and PC physicians. METHODS: A coordination toolkit was sent from the PC physician to the FP whenever the PC physician received a consultation request from an oncologist. The toolkit included an introduction to the PC physician team; an opportunity for the FP to choose how best to collaborate with PC physicians to meet the patient's PC needs; and contact information for access to 24/7 PC physician support. Responses from FPs regarding their preferred level of engagement with PC determined further care planning in the clinic. We measured feasibility, response rate, and qualitative surveys of FPs about the usefulness of the intervention. RESULTS: Two hundred fourteen new consultations were eligible for a standardized letter over the 6-month implementation period. Feasibility for sending the toolkit was 90.0% and response rate for collaborative care preference from FPs was 86.0%, with median response time of 3-4 days. 78.9% of FPs indicated they would prefer ongoing consultative care by the PC physician, while 18.6% indicated that PC physician consultation was not needed, or that the FP would provide primary PC after a one-time PC physician consultation. CONCLUSION: We successfully implemented a QI initiative to improve care coordination between FPs and PC physicians for patients with cancer. The coordination toolkit can protect the patient-FP primary PC relationship and optimize specialist PC resource utilization for complex patients.

2.
Palliat Med Rep ; 5(1): 104-115, 2024.
Article in English | MEDLINE | ID: mdl-38415077

ABSTRACT

Background: Primary- and specialist-level palliative care services are needed. They should work collaboratively and synergistically. Although several service models have been described, these remain open to different interpretations and deployment. Aim: This article describes a conceptual framework, the Consultation-Shared Care-Takeover (C-S-T) Framework, its evolution and its applications. Design: An iterative process informed the development of the Framework. This included a symposium, literature searches, results from three studies, and real-life applications. Results: The C-S-T Framework represents a spectrum anchored by the Consultation model at one end, the Takeover model at the other end, and the Shared Care model in the center. Indicators, divided into five domains, help differentiate one model from the other. The domains are (1) Scope (What aspects of care are addressed by the palliative care clinician?); (2) Prescriber (Who prescribes the treatments?); (3) Communication (What communication occurs between the palliative care clinician and the patient's attending clinician?); (4) Follow-up (Who provides the follow-up visits and what is their frequency?); and (5) Most responsible practitioner (MRP) (Who is identified as MRP?). Each model demonstrates strengths, limitations, uses, and roles. Conclusions: The C-S-T Framework can be used to better describe, understand, assess, and monitor models being used by specialist palliative care teams in their interactions with primary care providers and other specialist services. Large studies are needed to test the application of the Framework on a broader scale in health care systems.

3.
Support Care Cancer ; 31(7): 404, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37341839

ABSTRACT

PURPOSE: Although early palliative care is recommended, resource limitations prevent its routine implementation. We report on the preliminary findings of a mixed methods study involving a randomized controlled trial (RCT) of Symptom screening with Targeted Early Palliative care (STEP) and qualitative interviews. METHODS: Adults with advanced solid tumors and an oncologist-estimated prognosis of 6-36 months were randomized to STEP or symptom screening alone. STEP involved symptom screening at each outpatient oncology visit; moderate to severe scores triggered an email to a palliative care nurse, who offered referral to in-person outpatient palliative care. Patient-reported outcomes of quality of life (FACT-G7; primary outcome), depression (PHQ-9), symptom control (ESAS-r-CS), and satisfaction with care (FAMCARE P-16) were measured at baseline and 2, 4, and 6 months. Semi-structured interviews were conducted with a subset of participants. RESULTS: From Aug/2019 to Mar/2020 (trial halted due to COVID-19 pandemic), 69 participants were randomized to STEP (n = 33) or usual care (n = 36). At 6 months, 45% of STEP arm patients and 17% of screening alone participants had received palliative care (p = 0.009). Nonsignificant differences for all outcomes favored STEP: difference in change scores for FACT-G7 = 1.67 (95% CI: -1.43, 4.77); ESAS-r-CS = -5.51 (-14.29, 3.27); FAMCARE P-16 = 4.10 (-0.31, 8.51); PHQ-9 = -2.41 (-5.02, 0.20). Sixteen patients completed qualitative interviews, describing symptom screening as helpful to initiate communication; triggered referral as initially jarring but ultimately beneficial; and referral to palliative care as timely. CONCLUSION: Despite lack of power for this halted trial, preliminary results favored STEP and qualitative results demonstrated acceptability. Findings will inform an RCT of combined in-person and virtual STEP.


Subject(s)
COVID-19 , Neoplasms , Adult , Humans , Palliative Care/methods , Early Detection of Cancer , Neoplasms/therapy , Neoplasms/pathology , Quality of Life
4.
J Palliat Med ; 26(3): 366-375, 2023 03.
Article in English | MEDLINE | ID: mdl-36282783

ABSTRACT

Background: The goal of the Edmonton Classification System for Cancer Pain (ECS-CP) is to create an international classification system for cancer pain. Previous studies reinforce the need for standardized training to ensure consistency across assessors. There is no universally accepted classification for neuropathic pain. Objectives: Our primary objective was to describe the prevalence of ECS-CP features in a diverse sample of advanced cancer patients, using assessors with standardized training. The secondary objectives were to: (1) determine the prevalence of neuropathic pain using the Neuropathic Pain Special Interest Group (NeuPSIG) criteria and (2) examine the relationship between specific predictors: ECS-CP features, age, Palliative Performance Scale, Morphine Equivalent Daily Dose (MEDD), setting, and pain intensity; and neuropathic pain. Methods: A total of 1050 adult patients with advanced cancer were recruited from 11 Canadian sites. A clinician completed the ECS-CP and NeuPSIG criteria, and collected additional information including demographics and pain intensity (now). All assessors received standardized training. Results: Of 1050 evaluable patients, 910 (87%) had cancer pain: nociceptive (n = 626; 68.8%); neuropathic (n = 227; 24.9%); incident (n = 329; 36.2%); psychological distress (n = 209; 23%); addictive behavior (n = 51; 5.6%); and normal cognition (n = 639; 70.2%). The frequencies of ECS-CP features and pain intensity scores varied across sites and settings, with more acute settings having higher frequencies of complex pain features. The overall frequency of neuropathic pain was 24.9%, ranging from 11% (hospices) to 34.2% (palliative outpatient clinic) across settings. Multivariate logistic regression analysis revealed that age <60 years, MEDD ≥19 mg, pain intensity ≥7/10, and incident pain were significant independent predictors of neuropathic pain (p < 0.05). Conclusion: The ECS-CP was able to detect salient pain features across settings. Furthermore, the frequencies of neuropathic pain utilizing the NeuPSIG criteria fits within the lower-end of literature estimates (13%-40%). Further research is warranted to validate the NeuPSIG criteria in cancer pain.


Subject(s)
Cancer Pain , Neoplasms , Neuralgia , Adult , Humans , Middle Aged , Palliative Care , Pain Measurement , Canada , Neoplasms/psychology
5.
Pain Rep ; 7(2): e995, 2022.
Article in English | MEDLINE | ID: mdl-35261931

ABSTRACT

Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids-such as antiepileptics and antidepressants-have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.

6.
J Natl Compr Canc Netw ; 20(4): 361-370.e3, 2021 09 07.
Article in English | MEDLINE | ID: mdl-34492632

ABSTRACT

BACKGROUND: Routine early palliative care (EPC) improves quality of life (QoL) for patients with advanced cancer, but it may not be necessary for all patients. We assessed the feasibility of Symptom screening with Targeted Early Palliative care (STEP) in a phase II trial. METHODS: Patients with advanced cancer were recruited from medical oncology clinics. Symptoms were screened at each visit using the Edmonton Symptom Assessment System-revised (ESAS-r); moderate to severe scores (screen-positive) triggered an email to a palliative care nurse, who called the patient and offered EPC. Patient-reported outcomes of QoL, depression, symptom control, and satisfaction with care were measured at baseline and at 2, 4, and 6 months. The primary aim was to determine feasibility, according to predefined criteria. Secondary aims were to assess whether STEP identified patients with worse patient-reported outcomes and whether screen-positive patients who accepted and received EPC had better outcomes over time than those who did not receive EPC. RESULTS: In total, 116 patients were enrolled, of which 89 (77%) completed screening for ≥70% of visits. Of the 70 screen-positive patients, 39 (56%) received EPC during the 6-month study and 4 (6%) received EPC after the study end. Measure completion was 76% at 2 months, 68% at 4 months, and 63% at 6 months. Among screen-negative patients, QoL, depression, and symptom control were substantially better than for screen-positive patients at baseline (all P<.0001) and remained stable over time. Among screen-positive patients, mood and symptom control improved over time for those who accepted and received EPC and worsened for those who did not receive EPC (P<.01 for trend over time), with no difference in QoL or satisfaction with care. CONCLUSIONS: STEP is feasible in ambulatory patients with advanced cancer and distinguishes between patients who remain stable without EPC and those who benefit from targeted EPC. Acceptance of the triggered EPC visit should be encouraged. CLINICALTRIALS: gov identifier: NCT04044040.


Subject(s)
Neoplasms , Quality of Life , Early Detection of Cancer , Humans , Neoplasms/diagnosis , Neoplasms/therapy , Palliative Care , Patient Reported Outcome Measures
7.
Linacre Q ; 88(2): 214-223, 2021 May.
Article in English | MEDLINE | ID: mdl-33888917

ABSTRACT

Striving to be faithful to the moral core of medicine and to spiritual, moral, and social teaching of the church, Catholic physicians see their role as an extension of the healing ministry of Jesus. When faced with a situation in which a large number of gravely ill people are seeking care, but optimal treatment such as ventilation in intensive care unit cannot be offered to all because of scarcity of resources, Catholic physicians recognize the need to consider the common good and to assign a priority to patients for whom such treatments would be most probably lifesaving. Making these evaluations, physicians will use only objective medical criteria regarding the benefits and risks to patients and will be mindful that all persons deserve equal respect for their dignity. Discrimination or prejudicial treatment against patients based on factors such as age, disability, race, gender, quality of life, and possible long-term survival cannot be morally justified. Triage process should incorporate respect for autonomy of both the patient and the professional and opportunity for an appeal of a triage decision. Other principles and values that will affect how a triage protocol is developed and applied are proportionality, equity, reciprocity, solidarity, subsidiarity, and transparency. The current coronavirus pandemic can provide valuable lessons and stimulus for reforms and renewal. SUMMARY: Catholic physicians strive to continue the healing ministry of Jesus Christ and be faithful to the moral core of medicine. In situations such as pandemic, the scarcity of personnel and technological resources create serious challenges and even moral distress. Church teachings on dignity, the common good and protection of the vulnerable help guide decisions based on public medical criteria and shared decision-making.

8.
Pain Rep ; 5(6): e856, 2020.
Article in English | MEDLINE | ID: mdl-33134752

ABSTRACT

INTRODUCTION: Pain related to cancer, and its treatment, is common, may severely impair quality of life, and imposes a burden on patients, their families and caregivers, and society. Cancer-related pain is often challenging to manage, with limitations of analgesic drugs including incomplete efficacy and dose-related adverse effects. OBJECTIVES: Given problems with, and limitations of, opioid use for cancer-related pain, the identification of nonopioid treatment strategies that could improve cancer pain care is an attractive concept. The hypothesis that combinations of mechanistically distinct analgesic drugs could provide superior analgesia and/or fewer adverse effects has been tested in several pain conditions, including in cancer-related pain. Here, we propose to review trials of nonopioid analgesic combinations for cancer-related pain. METHODS: Using a predefined literature search strategy, trials-comparing the combination of 2 or more nonopioid analgesics with at least one of the combination's individual components-will be searched on the PubMed and EMBASE databases from their inception until the date the searches are run. Outcomes will include pain intensity or relief, adverse effects, and concomitant opioid consumption. RESULTS/CONCLUSIONS: This review is expected to synthesize available evidence describing the efficacy and safety of nonopioid analgesic combinations for cancer-related pain. Furthermore, a review of this literature will serve to identify future research goals that would advance our knowledge in this area.

9.
Am J Cardiol ; 124(7): 1064-1068, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31353003

ABSTRACT

Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. However, in patients with terminal illnesses, these devices may disrupt the dying process. This study was undertaken to review our current strategies surrounding device deactivation. A retrospective chart review was performed at Kingston Health Sciences Centre of patients with an ICD who died from 2015 to 2018. Data collected included patient demographics, clinical details surrounding device implantation, patient co-morbidities leading to deactivation, time to deactivation, physical place of deactivation, and device programming information. Ethics approval was obtained from the Queen's University Health Sciences Research Ethics Board. A total of 49 patients were included for analysis. Mean age at the time of death was 77.5 years (range: 57 to 94 years) and 12.2% (6/49) were women. The indications for ICD implantation were primary prevention of sudden cardiac death in 69.4% (34/49) and secondary prevention in 30.6% (15/49). Deactivation as part of end-of-life care was performed in 32.7% of patients (16/49). Deactivations occurred in clinic in 6.1% (3/49) of patients, on hospital inpatient wards in 12.2% (6/49) of patients, and in critical care settings in 14.2% (7/49) of patients. The remaining 67.3% (33/49) of patients died with fully functioning devices in place. The most prevalent terminal diagnoses were metastatic cancer (22.4%) and end-stage congestive heart failure (20.4%). On average, patients had their devices deactivated 13 months (range: 0 to 62 months) after their terminal diagnosis was established. Once a patient was documented as Do Not Resuscitate (DNR), deactivation was discussed and carried out within a mean time of 38 days (range: 0 to 400 days). Seven patients had their device active for more than 1 month after being documented as DNR. Ten patients (20.4%) received ICD shocks after their terminal diagnosis, 9 received shocks in the month before death, and 2 received shocks after formal DNR orders were in place. Approximately one-third of patients with ICDs received deactivation of their cardioversion/defibrillation therapies as part of their end-of-life care plan. A relatively high proportion of patients (20%) received an ICD shock in the last month of life. In conclusion, addressing device programming needs, including deactivation of cardioversion/defibrillation therapies, should be considered in the context of a patient's goals of care in every patient with an ICD who has a co-existing life-limiting diagnosis.


Subject(s)
Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Resuscitation Orders , Terminal Care , Withholding Treatment , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies
10.
J Palliat Med ; 22(11): 1318-1323, 2019 11.
Article in English | MEDLINE | ID: mdl-31347940

ABSTRACT

Palliative care is an evolving field with extensive studies demonstrating its benefits to patients, families, and the health care system. Many health systems have developed or are developing palliative care programs. The Canadian Society of Palliative Care Physicians (CSPCP) is often asked to recommend how many palliative care specialists are needed to implement and support an integrated palliative care program. This information would allow health service decision makers and educational institutions to plan resources accordingly to manage the needs of their communities. The CSPCP is well positioned to answer this question, as many of its members are Directors of palliative care programs and have been responsible for creating and overseeing the pioneering work of building these programs over the past few decades. In 2017, the CSPCP commissioned a working group to develop a staffing model for specialist palliative care teams based on the interdependence of three key professional roles, an extensive literature search, key stakeholder interviews, and expert opinions. This article is the Canadian Society of Palliative Care's recommended starting point that will be further evaluated as it is utilized across Canada. For more information and to see sample calculations go to the Canadian Society of Palliative Care Physicians Staffing Model for Palliative Care Programs (https://www.cspcp.ca).


Subject(s)
Consensus , Palliative Care , Patient Care Team , Personnel Staffing and Scheduling/organization & administration , Canada , Humans
11.
CMAJ ; 191(9): E263, 2019 03 04.
Article in English | MEDLINE | ID: mdl-30833494

Subject(s)
Analgesics, Opioid
12.
J Natl Compr Canc Netw ; 16(6): 719-726, 2018 06.
Article in English | MEDLINE | ID: mdl-29891523

ABSTRACT

Background: Palliative care aims to improve suffering and quality of life for patients with life-limiting disease. This study evaluated an interdisciplinary palliative consultation team for outpatients with advanced cancer at the Tom Baker Cancer Centre. This team traditionally offered palliative medicine and recently integrated a specialized psychosocial clinician. Historic patient-reported clinical outcomes were reviewed. There were no a priori hypotheses. Methods: A total of 180 chart reviews were performed in 8 sample months in 2015 and 2016; 114 patients were included. All patients were referred for management of complex cancer symptomatology by oncology or palliative care clinicians. Patients attended initial interviews in person; palliative medicine follow-ups were largely performed by telephone, and psychosocial appointments were conducted in person for those who were interested and had psychosocial concerns. Chart review included collection of demographics, medical information, and screening for distress measures at referral, initial consult, and discharge. Results: A total of 51% of the patient sample were men, 81% were living with a partner, and 87% had an advanced cancer diagnosis. Patients were grouped based on high, moderate, or low scores for 5 symptoms (pain, fatigue, depression, anxiety, and well-being). High scores on all 5 symptoms decreased from referral to discharge. Pain and anxiety decreased in the moderate group. All 5 low scores increased significantly. Sleep, frustration/anger, sense of burdening others, and sensitivity to cold were less frequently endorsed by discharge. Conclusions: Patients who completed this interdisciplinary palliative consult service appeared to experience a reduction in their most severe symptoms. Visits to patients during existing appointments or having them attend a half-day clinic appears to have reached those referred. With interdisciplinary integration, clinicians are able to collaborate to address patient care needs. Considerations include how to further integrate palliative and psychosocial care to achieve additional benefits and ongoing monitoring of changes in symptom burden.


Subject(s)
Neoplasms/therapy , Outcome Assessment, Health Care , Palliative Care/methods , Patient-Centered Care/methods , Referral and Consultation/organization & administration , Adult , Aged , Aged, 80 and over , Ambulatory Care Facilities/organization & administration , Female , Humans , Male , Medical Oncology/methods , Middle Aged , Neoplasms/diagnosis , Neoplasms/psychology , Patient Care Team/organization & administration , Program Evaluation , Psychosocial Support Systems , Quality of Life , Severity of Illness Index
13.
J Palliat Care ; 32(3-4): 113-120, 2017.
Article in English | MEDLINE | ID: mdl-29129136

ABSTRACT

The discipline of palliative medicine in Canada started in 1975 with the coining of the term "palliative care." Shortly thereafter, the provision of clinical palliative medicine services started, although the education of the discipline lagged behind. In 1993, the Canadian Society of Palliative Care Physicians (CSPCP) started to explore the option of creating an accredited training program in palliative medicine. This article outlines the process by which, over the course of 20 years, palliative medicine training in Canada went from a mission statement of the CSPCP, to a 1 year of added competence jointly accredited by both the Royal College of Physicians and Surgeons of Canada (Royal College) and the College of Family Physicians of Canada, to a 2-year subspecialty of the Royal College with access from multiple entry routes and a formalized accrediting examination.


Subject(s)
Curriculum , Education, Medical/history , Medicine , Palliative Medicine/education , Palliative Medicine/history , Physicians, Family/education , Surgeons/education , Adult , Canada , Clinical Competence , Female , History, 20th Century , History, 21st Century , Humans , Male , Middle Aged , Young Adult
14.
CMAJ ; 187(12): 911-2, 2015 Sep 08.
Article in English | MEDLINE | ID: mdl-26351368
15.
J Palliat Med ; 18(8): 682-90, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26061030

ABSTRACT

BACKGROUND: Entrustable professional activities (EPAs) are routine tasks considered essential to a professional practice. An EPA can serve as a performance-based outcome that a clinical supervisor would progressively entrust a learner to perform. OBJECTIVE: Our aim was to identify, develop, and validate a set of EPAs for the palliative medicine discipline. METHODS: The design was a sequential qualitative and quantitative mixed methods study. A working group was convened to develop a set of EPAs. Focus groups and surveys were used for validation purposes. Palliative medicine educators and content experts from across Canada participated in both the working group as well as the focus groups. Attendees of the 2014 Canadian Society of Palliative Care Physicians (CSPCP) annual conference completed surveys. A questionnaire was used to collect survey participant sociodemographic, clinical, and academic information along with ratings of the importance of the EPAs individually and collectively. Cronbach's alpha examined internal consistency of the set of EPAs. RESULTS: Focus group participants strongly endorsed the 12 EPAs. Virtually all survey participants rated the individual EPAs as being "fairly/very important" (range 94% to 100%). Of the participants, 97% agreed that residents able to perform the set of EPAs would be practicing palliative medicine and 87% indicated strong agreement that this collective set of EPAs captures activities that all palliative medicine physicians must be able to perform. A Cronbach's alpha of 0.841 confirmed good internal consistency. CONCLUSIONS: Near uniform agreement from a national group of palliative medicine physicians provides strong validation for the set of 12 EPAs.


Subject(s)
Palliative Medicine/standards , Professional Practice/standards , Canada , Congresses as Topic , Consensus , Focus Groups , Humans , Research Design , Surveys and Questionnaires
16.
Med Educ ; 45(4): 400-6, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21401688

ABSTRACT

CONTEXT: Health care is one of many under-resourced areas in Aboriginal communities in Canada. Aboriginal people have substandard health compared with the general population, yet have less access to health care services. Not only is there a paucity of Aboriginal doctors, but it also appears that few non-Aboriginal doctors are willing or able to work in Aboriginal contexts. OBJECTIVES: This study examines the attitudes of family medicine residents towards providing health care to Aboriginal patients. The goal of this study was to assess the willingness of family medicine residents to work in Aboriginal health care and to elucidate the major factors that inform these attitudes. METHODS: We conducted a cross-sectional survey of an urban cohort of family medicine residents using a convenience sample. Our survey instrument consisted of a questionnaire comprising a mixture of open-ended and closed questions. RESULTS: Although a majority (52%, n = 27) of the family medicine residents were willing to work in Aboriginal contexts, many felt underprepared to do so (40%, n = 21). Residents who have had some exposure to Aboriginal issues and have had community experiences are more likely to state an intention to work in Aboriginal settings. CONCLUSIONS: The results of this study encourage the creation of educational experiences for medical residents that may promote a desire to work in Aboriginal communities.


Subject(s)
Attitude of Health Personnel , Education, Medical/standards , Family Practice/standards , Health Services Accessibility/standards , Health Services, Indigenous/standards , American Indian or Alaska Native/psychology , Canada/ethnology , Curriculum , Humans , Internship and Residency , Prejudice , Rural Health Services/standards
17.
Brain ; 127(Pt 12): 2649-56, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15355874

ABSTRACT

Several studies have reported beneficial effects of intravenous immunoglobulin (IVIg) in diseases of the neuroaxis. However, IVIg effects on leucocyte recruitment, a hallmark feature of autoimmunity and acute inflammation, remain largely unexplored. Using intravital microscopy, we studied the effects of IVIg on leucocyte recruitment in experimental autoimmune encephalomyelitis, a model of multiple sclerosis. In IVIg-treated mice, a significant decrease in recruitment (rolling and adhesion) was observed prior to and following disease onset, and this was concomitant with improved clinical score. Since much of the recruitment is dependent upon alpha4-integrin (ligand for VCAM-1) we used an in vitro flow chamber system and demonstrated a 60% decrease in alpha4-integrin-dependent leucocyte adhesion to immobilized VCAM-1. Finally, we used leucocytes from multiple sclerosis patients and demonstrated that IVIg treatment decreased recruitment by 60% on human endothelium. However, when we visualized the role of IVIg in a second model of brain inflammation, cerebral ischaemia-reperfusion, IVIg actually promoted the formation of platelet-leucocyte aggregates in post-ischaemic cerebral vessels. In conclusion, we report a new mechanism of action of IVIg through interference of alpha4-integrin-dependent leucocyte recruitment in both an animal model and human multiple sclerosis. We also report that IVIg will not be beneficial in all types of pro-adhesive states and may in fact be detrimental in a situation such as stroke.


Subject(s)
Cell Movement/drug effects , Encephalomyelitis, Autoimmune, Experimental/therapy , Immunoglobulins, Intravenous/therapeutic use , Leukocytes/drug effects , Multiple Sclerosis/therapy , Adult , Animals , Cell Adhesion/immunology , Cell Communication/drug effects , Cell Communication/immunology , Cell Movement/immunology , Cells, Cultured , Cerebrovascular Circulation/immunology , Encephalomyelitis, Autoimmune, Experimental/etiology , Encephalomyelitis, Autoimmune, Experimental/immunology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelium, Vascular/immunology , Female , Humans , Immunoglobulins, Intravenous/immunology , Immunoglobulins, Intravenous/toxicity , Integrin alpha4/physiology , Leukocytes/immunology , Male , Mice , Mice, Inbred C57BL , Microcirculation/immunology , Middle Aged , Multiple Sclerosis/etiology , Multiple Sclerosis/immunology , Reperfusion Injury/immunology , Stroke/immunology , Vascular Cell Adhesion Molecule-1/metabolism
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