Technology-Enabled Self-Management of Chronic Obstructive Pulmonary Disease With or Without Asynchronous Remote Monitoring: Randomized Controlled Trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and leads to frequent hospital admissions and emergency department (ED) visits. COPD exacerbations are an important patient outcome, and reducing their frequency would result in significant cost savings. Remote monitoring and self-monitoring could both help patients manage their symptoms and reduce the frequency of exacerbations, but they have different resource implications and have not been directly compared. OBJECTIVE: This study aims to compare the effectiveness of implementing a technology-enabled self-monitoring program versus a technology-enabled remote monitoring program in patients with COPD compared with a standard care group. METHODS: We conducted a 3-arm randomized controlled trial evaluating the effectiveness of a remote monitoring and a self-monitoring program relative to standard care. Patients with COPD were recruited from outpatient clinics and a pulmonary rehabilitation program. Patients in both interventions used a Bluetooth-enabled device kit to monitor oxygen saturation, blood pressure, temperature, weight, and symptoms, but only patients in the remote monitoring group were monitored by a respiratory therapist. All patients were assessed at baseline and at 3 and 6 months after program initiation. Outcomes included self-management skills, as measured by the Partners in Health (PIH) Scale; patient symptoms measured with the St George's Respiratory Questionnaire (SGRQ); and the Bristol COPD Knowledge Questionnaire (BCKQ). Patients were also asked to self-report on health system use, and data on health use were collected from the hospital. RESULTS: A total of 122 patients participated in the study: 40 in the standard care, 41 in the self-monitoring, and 41 in the remote monitoring groups. Although all 3 groups improved in PIH scores, BCKQ scores, and SGRQ impact scores, there were no significant differences among any of the groups. No effects were observed on the SGRQ activity or symptom scores or on hospitalizations, ED visits, or clinic visits. CONCLUSIONS: Despite regular use of the technology, patients with COPD assigned to remote monitoring or self-monitoring did not have any improvement in patient outcomes such as self-management skills, knowledge, or symptoms, or in health care use compared with each other or with a standard care group. This may be owing to low health care use at baseline, the lack of structured educational components in the intervention groups, and the lack of integration of the action plan with the technology. TRIAL REGISTRATION: ClinicalTrials.gov NCT03741855; https://clinicaltrials.gov/ct2/show/ NCT03741855.

Technology-Enabled Self-Monitoring of Chronic Obstructive Pulmonary Disease With or Without Asynchronous Remote Monitoring: Protocol for a Randomized Controlled Trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality worldwide. Reducing the number of COPD exacerbations is an important patient outcome and a major cost-saving approach. Both technology-enabled self-monitoring (SM) and remote monitoring (RM) programs have the potential to reduce exacerbations, but they have not been directly compared with each other. As RM is a more resource-intensive strategy, it is important to understand whether it is more effective than SM. OBJECTIVE: The objective of this study is to evaluate the impact of SM and RM on self-management behaviors, COPD disease knowledge, and respiratory status relative to standard care (SC). METHODS: This was a 3-arm open-label randomized controlled trial comparing SM, RM, and SC completed in an outpatient COPD clinic in a community hospital. Patients in the SM and RM groups recorded their vital signs (oxygen, blood pressure, temperature, and weight) and symptoms with the Cloud DX platform every day and were provided with a COPD action plan. Patients in the RM group also received access to a respiratory therapist (RT). The RT monitored their vital signs intermittently and contacted them when their vitals varied outside of predetermined thresholds. The RT also contacted patients once a week irrespective of their vital signs or symptoms. All patients were randomized to 1 of the 3 groups and assessed at baseline and 3 and 6 months after program initiation. The primary outcome was the Partners in Health scale, which measures self-management skills. Secondary outcomes included the St. George's Respiratory Questionnaire, Bristol COPD Knowledge Questionnaire, COPD Assessment Test, and modified-Medical Research Council Breathlessness Scale. Patients were also asked to self-report on health system usage. RESULTS: A total of 122 patients participated in the study, 40 in the SC, 41 in the SM, and 41 in the RM groups. Out of those patients, 7 in the SC, 5 in the SM, and 6 in the RM groups did not complete the study. There were no significant differences in the rates of study completion among the groups (P=.80). CONCLUSIONS: Both SM and RM have shown promise in reducing acute care utilization and exacerbation frequencies. As far as we are aware, no studies to date have directly compared technology-enabled self-management with RM programs in COPD patients. We believe that this study will be an important contribution to the literature. TRIAL REGISTRATION: ClinicalTrials.gov NCT03741855; https://clinicaltrials.gov/ct2/show/NCT03741855. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13920.

Later-onset rheumatoid factor negative polyarticular juvenile idiopathic arthritis (JIA): a unique patient group?

OBJECTIVES: To determine the two-year outcome of patients with later-onset polyarticular rheumatoid factor (RF) negative (-) juvenile idiopathic arthritis (JIA), and predictors of outcome. METHODS: All patients ages 10 to16 years diagnosed and followed in the Rheumatology Clinic at SickKids Hospital with the diagnosis of polyarticular RF- JIA were eligible for study. A retrospective chart analysis was performed and number of active joints, medications, laboratory information and childhood health assessment questionnaire scores were recorded at diagnosis, and 6, 12, and 24 months following diagnosis. RESULTS: As early as 6 months after diagnosis the mean number of active joints decreased from 16 to < 10, with 50% of the patients having < 5 active joints. The predominant joints affected were the wrist, knee, and small joints of the hand. The only predictor of active joint count at the 2-year follow-up was initial presenting active joint count as classified as mild, moderate, or severe. Sex, age, and laboratory results at presentation did not show any correlation with active joint count at 2 years. Majority of patients were treated with non-steroidal anti-inflammatory drugs (98%) and at least one disease-modifying anti-rheumatic drug (56%). CONCLUSIONS: The two-year outcome of patients with late-onset RF- polyarticular JIA was very good with the majority of patients having minimally active disease at last follow-up. Presence of significant polyarthritis at presentation was the only feature associated with long-term joint activity. Sex and lab results did not show any correlation with active joint in this cohort of RF-JIA patients.

Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis.

The risk of venous thromboembolic events is thought to be highest in patients with membranous nephropathy. This association has been recently questioned, and it is not known whether this simply reflects the severity of proteinuria. To better understand the relationship between histologic diagnosis and the risk of venous thromboembolic events we evaluated patients in the Toronto Glomerulonephritis Registry. Of 1313 patients with idiopathic glomerulonephritis, 395 were diagnosed with membranous nephropathy, 370 with focal segmental glomerulosclerosis (FSGS), and 548 with immunoglobulin-A nephropathy (IgAN). Risk factors were evaluated by Cox proportional hazards for 53 image-confirmed venous thromboembolic events in 44 patients during a median follow-up of 63 months. The risk was highest in patients with membranous nephropathy and FSGS (hazard ratios of 22 and 7.8, respectively) referenced to patients with IgAN. Following adjustment for gender, cancer history, proteinuria, and serum albumin by multivariable analysis, the histologic subtype remained an independent risk for venous thromboembolic events. This risk was still highest in patients with membranous nephropathy followed by FSGS with adjusted hazard ratios of 10.8 and 5.9, respectively. Thus, in this large cohort, histologic diagnosis was an independent risk factor for venous thromboembolic events. Further studies are needed to discover mechanisms responsible for this high risk in patients with membranous nephropathy.

Venous thromboembolism in patients with membranous nephropathy.

BACKGROUND AND OBJECTIVES: The aims of this study were to determine the frequency of venous thromboembolic events in a large cohort of patients with idiopathic membranous nephropathy and to identify predisposing risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied patients with biopsy-proven membranous nephropathy from the Glomerular Disease Collaborative Network (n=412) and the Toronto Glomerulonephritis Registry (n=486) inception cohorts. The cohorts were pooled after establishing similar baseline characteristics (total n=898). Clinically apparent and radiologically confirmed venous thromboembolic events were identified. Potential risk factors were evaluated using multivariable logistic regression models. RESULTS: Sixty-five (7.2%) subjects had at least one venous thromboembolic event, and this rate did not differ significantly between registries. Most venous thromboembolic events occurred within 2 years of first clinical assessment (median time to VTE = 3.8 months). After adjusting for age, sex, proteinuria, and immunosuppressive therapy, hypoalbuminemia at diagnosis was the only independent predictor of a venous thromboembolic event. Each 1.0 g/dl reduction in serum albumin was associated with a 2.13-fold increased risk of VTE. An albumin level <2.8 g/dl was the threshold below which risk for a venous thromboembolic event was greatest. CONCLUSIONS: We conclude that clinically apparent venous thromboembolic events occur in about 7% of patients with membranous nephropathy. Hypoalbuminemia, particularly <2.8 g/dl, is the most significant independent predictor of venous thrombotic risk.

Galectin-3-mediated xenoactivation of human monocytes.

BACKGROUND: Delayed xenograft rejection (DXR) remains a roadblock to successful xenotransplantation. A feature of DXR is early recruitment of monocytes to the xenograft. Naïve human monocytes can recognize and adhere to unstimulated porcine aortic endothelial cells (PAEC) more than human aortic endothelial cells, partly due to endothelial expression of the xenoantigen galactose-alpha(1,3)galactose-beta(1,4)GlcNAc-R (alpha-gal). Previous work from our laboratory has implicated galectin-3 as a candidate molecule on monocytes involved in initial recognition and adhesion of human monocytes to PAEC. METHODS: Flow cytometry was used to analyze monocyte activation and galectin-3 accumulation in PAEC. Reactive oxygen intermediate production was analyzed using dihydrorhodamine measured in a fluorescence plate reader. Western blotting was performed to determine galectin-3 secretion and expression by human monocytes. Immunofluorescence staining for the tight junction protein zona occludens-1 was used as a measure of PAEC monolayer integrity. RESULTS: We demonstrate that galectin-3 can be secreted from monocyte intracellular stores on contact with alpha-gal. Soluble galectin-3 binds PAEC partly by expression of alpha-gal. Binding is reduced on endothelium derived from alpha-gal knockout animals, but not completely. Competing terminal sugars expressed on human aortic endothelial cells such as sialic acid, may block galectin-3 binding. Furthermore, soluble galectin-3 activates monocytes in an autocrine/paracrine manner. Blocking galectin-3 reduces the activation of human monocytes. Finally, the inhibition of galectin-3 reduces monocyte-mediated endothelial injury on co-culture with PAEC. CONCLUSION: Galectin-3 plays a role in human monocyte activation and adhesion in the presence of PAEC, which may contribute to DXR. Additional transgenic strategies targeting galectin-3 ligands on porcine endothelium may be required to achieve optimal xenograft survival.

Human monocytes recognize porcine endothelium via the interaction of galectin 3 and alpha-GAL.

Monocytes are one of the key inflammatory cells recruited to xenografts and play an important role in delayed xenograft rejection. Previous studies have demonstrated the ability of monocytes to bind to the major xenoantigen Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R; however, the receptor that mediates this interaction has yet to be identified. We provide evidence that it is Galectin-3, a approximately 30-kDa lectin that recognizes beta-galactosides (Gal-beta(1-3/4)GlcNAc) and plays diverse roles in many physiological and pathological events. Human monocyte binding is strikingly increased on porcine aortic endothelial cells (PAEC), which express high levels of Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R, compared with human aortic endothelial cells. Human monocytes obtained from healthy donors bind to Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R at variable intensities. This variation of binding intensity was consistent and reproducible in individual donors. Galectin-3 is mainly expressed in human monocytes, not lymphocytes. Purified Galectin-3 is able to bind directly to Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R. Galectin-3 can also be affinity isolated from monocytes (and not lymphocytes) using an Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R-biotin/streptavidin-bead pull-down system. Soluble Galectin-3 binds preferentially to PAEC vs human aortic endothelial cells, and this binding can be inhibited by lactose, indicating dependence on the carbohydrate recognition domain of Galectin-3. Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R is at least partly responsible for this phenomenon, as binding decreased after digestion of PAEC with alpha-galactosidase. Furthermore, monocytes pretreated with a blocking anti-Galectin-3 Ab show decreased adhesion to PAEC when compared with isotype control in a parallel plate flow chamber perfusion assay. Thus, we conclude that Galectin-3 expressed in human monocytes is a receptor for the major xenoantigen (Gal-alpha(1,3)Gal-beta(1,4)GlcNAc-R), expressed on porcine endothelial cells.