To identify the strategies and contextual factors that enable optimal engagement of patients in the design, delivery, and evaluation of health services.
We searched MEDLINE, EMBASE, CINAHL, Cochrane, ...Scopus, PsychINFO, Social Science Abstracts, EBSCO, and ISI Web of Science from 1990 to 2016 for empirical studies addressing the active participation of patients, caregivers, or families in the design, delivery and evaluation of health services to improve quality of care. Thematic analysis was used to identify (1) strategies and contextual factors that enable optimal engagement of patients, (2) outcomes of patient engagement, and (3) patients' experiences of being engaged.
Forty-eight studies were included. Strategies and contextual factors that enable patient engagement were thematically grouped and related to techniques to enhance design, recruitment, involvement and leadership action, and those aimed to creating a receptive context. Reported outcomes ranged from educational or tool development and informed policy or planning documents (discrete products) to enhanced care processes or service delivery and governance (care process or structural outcomes). The level of engagement appears to influence the outcomes of service redesign-discrete products largely derived from low-level engagement (consultative unidirectional feedback)-whereas care process or structural outcomes mainly derived from high-level engagement (co-design or partnership strategies). A minority of studies formally evaluated patients' experiences of the engagement process (n = 12; 25%). While most experiences were positive-increased self-esteem, feeling empowered, or independent-some patients sought greater involvement and felt that their involvement was important but tokenistic, especially when their requests were denied or decisions had already been made.
Patient engagement can inform patient and provider education and policies, as well as enhance service delivery and governance. Additional evidence is needed to understand patients' experiences of the engagement process and whether these outcomes translate into improved quality of care.
N/A (data extraction completed prior to registration on PROSPERO).
Background
Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS‐CoV‐2 infection. The biological mechanisms ...underlying this “long COVID” syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and microvascular immunothrombosis in acute COVID‐19.
Objectives
To assess whether endothelial cell activation may be sustained in convalescent COVID‐19 patients and contribute to long COVID pathogenesis.
Patients and Methods
Fifty patients were reviewed at a median of 68 days following SARS‐CoV‐2 infection. In addition to clinical workup, acute phase markers, endothelial cell (EC) activation and NETosis parameters and thrombin generation were assessed.
Results
Thrombin generation assays revealed significantly shorter lag times (p < .0001, 95% CI −2.57 to −1.02 min), increased endogenous thrombin potential (p = .04, 95% CI 15–416 nM/min), and peak thrombin (p < .0001, 95% CI 39–93 nM) in convalescent COVID‐19 patients. These prothrombotic changes were independent of ongoing acute phase response or active NETosis. Importantly, EC biomarkers including von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), and factor VIII were significantly elevated in convalescent COVID‐19 compared with controls (p = .004, 95% CI 0.09–0.57 IU/ml; p = .009, 95% CI 0.06–0.5 IU/ml; p = .04, 95% CI 0.03–0.44 IU/ml, respectively). In addition, plasma soluble thrombomodulin levels were significantly elevated in convalescent COVID‐19 (p = .02, 95% CI 0.01–2.7 ng/ml). Sustained endotheliopathy was more frequent in older, comorbid patients, and those requiring hospitalization. Finally, both plasma VWF:Ag and VWFpp levels correlated inversely with 6‐min walk tests.
Conclusions
Collectively, our findings demonstrate that sustained endotheliopathy is common in convalescent COVID‐19 and raise the intriguing possibility that this may contribute to long COVID pathogenesis.
Recent studies have demonstrated that only 30% of patients referred for assessment of a possible bleeding tendency will eventually be diagnosed with a mild bleeding disorder (MBD) such as von ...Willebrand disease (VWD) or platelet function defect (PFD). Rather, most of these patients will be diagnosed with bleeding disorder of unknown cause (BDUC). There remains an important unmet need to define consensus regarding the clinical and laboratory criteria necessary for a formal BDUC diagnosis. Accumulating recent data suggest that BDUC is being diagnosed with increasing frequency. Objective assessment of bleeding phenotype using a standardized bleeding assessment tool (BAT) therefore represents a fundamental first step in the diagnosis of BDUC. Because BDUC is a diagnosis by exclusion, accurate quantification of bleeding phenotype is critical because this will be the primary determinant on which a diagnosis of BDUC is reached. Importantly, BAT scores suggest that patients with BDUC display bleeding phenotypes comparable to those seen in patients with VWD or PFD. Despite the prevalence of BDUC, diagnosis and management of these patients commonly pose significant clinical dilemmas. We consider these challenges in the context of a number of typical case studies, discuss the available evidence, and outline our approach to the management of these patients.
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Background
Consistent with fulminant endothelial cell activation, elevated plasma von Willebrand factor (VWF) antigen levels have been reported in patients with COVID‐19. The multimeric size and ...function of VWF are normally regulated through A Disintegrin And Metalloprotease with ThrombSpondin Motif type 1 motif, member 13 (ADAMTS‐13)‐‐mediated proteolysis.
Objectives
This study investigated the hypothesis that ADAMTS‐13 regulation of VWF multimer distribution may be impaired in severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) infection contributing to the observed microvascular thrombosis.
Patients and Methods
Patients with COVID‐19 (n = 23) were recruited from the Beaumont Hospital Intensive Care Unit (ICU) in Dublin. Plasma VWF antigen, multimer distribution, ADAMTS‐13 activity, and known inhibitors thereof were assessed.
Results
We observed markedly increased VWF collagen‐binding activity in patients with severe COVID‐19 compared to controls (median 509.1 versus 94.3 IU/dl). Conversely, plasma ADAMTS‐13 activity was significantly reduced (median 68.2 IU/dl). In keeping with an increase in VWF:ADAMTS‐13 ratio, abnormalities in VWF multimer distribution were common in patients with COVID‐19, with reductions in high molecular weight VWF multimers. Terminal sialylation regulates VWF susceptibility to proteolysis by ADAMTS‐13 and other proteases. We observed that both N‐ and O‐linked sialylation were altered in severe COVID‐19. Furthermore, plasma levels of the ADAMTS‐13 inhibitors interleukin‐6, thrombospondin‐1, and platelet factor 4 were significantly elevated.
Conclusions
These findings support the hypothesis that SARS‐CoV‐2 is associated with profound quantitative and qualitative increases in plasma VWF levels, and a multifactorial down‐regulation in ADAMTS‐13 function. Further studies will be required to determine whether therapeutic interventions to correct ADAMTS‐13‐VWF multimer dysfunction may be useful in COVID‐microvascular thrombosis and angiopathy.
Policy Points
Considerable investments have been made to build high‐performing primary care systems in Canada. However, little is known about the extent to which change has occurred over the last ...decade with implementing programs and policies across all 13 provincial and territorial jurisdictions.
There is significant variation in the degree of implementation of structural features of high‐performing primary care systems across Canada. This study provides evidence on the state of primary care reform in Canada and offers insights into the opportunities based on changes that governments elsewhere have made to advance primary care transformation.
Context
Despite significant investments to transform primary care, Canada lags behind its peers in providing timely access to regular doctors or places of care, timely access to care, developing interprofessional teams, and communication across health care settings. This study examines changes over the last decade (2012 to 2021) in policies across 13 provincial and territorial jurisdictions that address the structural features of high‐performing primary care systems.
Methods
A multiple comparative case study approach was used to explore changes in primary care delivery across 13 Canadian jurisdictions. Each case consisted of (1) qualitative interviews with academics, provincial health care leaders, and health care professionals and (2) a literature review of policies and innovations. Data for each case were thematically analyzed within and across cases, using 12 structural features of high‐performing primary care systems to describe each case and assess changes over time.
Findings
The most significant changes include adopting electronic medical records, investments in quality improvement training and support, and developing interprofessional teams. Progress was more limited in implementing primary care governance mechanisms, system coordination, patient enrollment, and payment models. The rate of change was slowest for patient engagement, leadership development, performance measurement, research capacity, and systematic evaluation of innovation.
Conclusions
Progress toward building high‐performing primary care systems in Canada has been slow and variable, with limited change in the organization and delivery of primary care. Canada's experience can inform innovation internationally by demonstrating how preexisting policy legacies constrain the possibilities for widespread primary care reform, with progress less pronounced in the attributes that impact physician autonomy. To accelerate primary care transformation in Canada and abroad, a national strategy and performance measurement framework is needed based on meaningful engagement of patients and other stakeholders. This must be accompanied by targeted funding investments and building strong data infrastructure for performance measurement to support rigorous research.
Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated ...angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell (EC) activation and angiogenic disturbance. Additionally, we postulate that ongoing immune cell dysfunction may be linked to sustained EC and coagulation activation.
Fifty patients were reviewed at a minimum of 6 weeks following acute COVID-19. ADAMTS-13, Weibel Palade Body (WPB) proteins, and angiogenesis-related proteins were assessed and clinical evaluation and immunophenotyping performed. Comparisons were made with healthy controls (n = 20) and acute COVID-19 patients (n = 36).
ADAMTS-13 levels were reduced (p = 0.009) and the VWF-ADAMTS-13 ratio was increased in convalescence (p = 0.0004). Levels of platelet factor 4 (PF4), a putative protector of VWF, were also elevated (p = 0.0001). A non-significant increase in WPB proteins Angiopoietin-2 (Ang-2) and Osteoprotegerin (OPG) was observed in convalescent patients and WPB markers correlated with EC parameters. Enhanced expression of 21 angiogenesis-related proteins was observed in convalescent COVID-19. Finally, immunophenotyping revealed significantly elevated intermediate monocytes and activated CD4+ and CD8+ T cells in convalescence, which correlated with thrombin generation and endotheliopathy markers, respectively.
Our data provide insights into sustained EC activation, dysregulated angiogenesis, and VWF/ADAMTS-13 axis imbalance in convalescent COVID-19. In keeping with the pivotal role of immunothrombosis in acute COVID-19, our findings support the hypothesis that abnormal T cell and monocyte populations may be important in the context of persistent EC activation and hemostatic dysfunction during convalescence.
BackgroundThe Measurement and Monitoring of Safety Framework (MMSF) aims to move beyond a narrow focus on measurement and past harmful events as the major focus for safety in healthcare ...organisations. There is limited evidence of MMSF implementation and impact.ObjectiveWe aimed to examine participants’ perspectives and experiences to increase understanding of the adaptive work of implementing the MMSF through a learning collaborative programme in diverse healthcare contexts across Canada.MethodsThe Collaborative consisted of 11 teams from seven provinces. We conducted a qualitative study involving interviews with 36 participants, observations of 5 sites and learning sessions, and collection of documents.ResultsCollaborative sessions and coaching allowed participants to explore reliability, sensitivity to operations, anticipation and preparedness, and integration and learning, in addition to past harm, and move beyond a project and measurement oriented safety approach. Participants noted the importance of time dedicated to engaging stakeholders in talk about MMSF concepts and their significance to their settings, prior to moving to implementing the Framework into practice. While participants generally started with a small number of ways of integrating the MMSF into practice such as rounds or huddles, many teams continued to experiment with incorporating the MMSF into a range of practices. Participants reported changes in thinking about safety, discussions and behaviours, which were perceived to impact healthcare processes. However, participants also reported challenges to sharing the Framework broadly and moving beyond its surface implementation, and difficulties with its sustained and widespread use given misalignments with existing quality and safety processes.ConclusionThe MMSF requires a dramatic departure from traditional safety strategies that focus on discrete problems and emphasise measurement. MMSF implementation requires extensive discussion, coaching and experimentation. Future implementation should consider engaging local leaders and coaches and an organisation or system approach to enable broader reach and systemic change.
•These two randomized controlled trials addressed the question, is brexpiprazole efficacious, safe, and well tolerated for the treatment of agitation in Alzheimer's dementia (AAD)?•In Study 1, ...brexpiprazole 2 mg/day (fixed dose) was superior to placebo in terms of improvement of agitated behaviors (measured using the Cohen-Mansfield Agitation Inventory), with good tolerability. In Study 2, brexpiprazole 0.5–2 mg/day (flexible dose) was numerically superior to placebo (a non-statistically significant difference); the subgroup that was titrated to brexpiprazole 2 mg/day achieved nominal superiority compared with similarly titrated placebo patients.•These studies provide evidence that brexpiprazole 2 mg/day has the potential to be an efficacious, safe, and well-tolerated treatment for AAD, a clinical condition with a high burden and no FDA-approved treatments.
To assess the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer's dementia (AAD).
Two 12-week, randomized, double-blind, placebo-controlled, parallel-arm studies (NCT01862640; NCT01922258).
Study 1: 81 sites in 7 countries. Study 2: 62 sites in 9 countries.
Patients with AAD (Study 1: 433 randomized; Study 2: 270 randomized) in a care facility or community-based setting. Stable Alzheimer disease medications were permitted.
Study 1 (fixed dose): brexpiprazole 2 mg/day, brexpiprazole 1 mg/day, or placebo (1:1:1) for 12 weeks. Study 2 (flexible dose): brexpiprazole 0.5–2 mg/day or placebo (1:1) for 12 weeks.
Cohen-Mansfield Agitation Inventory (CMAI) (Total score range: 29–203; higher scores indicate more frequent agitated behaviors), and Clinical Global Impression – Severity of illness (CGI-S) as related to agitation. Safety was also assessed.
In Study 1, brexpiprazole 2 mg/day demonstrated statistically significantly greater improvement in CMAI Total score from baseline to Week 12 than placebo (adjusted mean difference, −3.77; confidence limits, –7.38, –0.17; t(316) = –2.06; p = 0.040; MMRM). Brexpiprazole 1 mg/day did not show meaningful separation from placebo (0.23; −3.40, 3.86; t(314) = 0.12; p = 0.90; MMRM). In Study 2, brexpiprazole 0.5–2 mg/day did not achieve statistical superiority over placebo (–2.34; –5.49, 0.82; t(230) = −1.46; p = 0.15; MMRM). However, a benefit was observed in post hoc analyses among patients titrated to the maximum brexpiprazole dose of 2 mg/day compared with similarly titrated placebo patients (−5.06; −8.99, −1.13; t(144) = −2.54; p = 0.012; MMRM). On the CGI-S, a greater numerical improvement than placebo was demonstrated for brexpiprazole 2 mg/day in Study 1 (−0.16; −0.39, 0.06; t(337) = −1.42; nominal p = 0.16; MMRM), and a greater improvement for brexpiprazole 0.5–2 mg/day in Study 2 (−0.31; −0.55, −0.06; t(222) = −2.42; nominal p = 0.016; MMRM). In Study 1, treatment-emergent adverse events (TEAEs) with incidence ≥5% among patients receiving brexpiprazole 2 mg/day were headache (9.3% versus 8.1% with placebo), insomnia (5.7% versus 4.4%), dizziness (5.7% versus 3.0%), and urinary tract infection (5.0% versus 1.5%). In Study 2, TEAEs with incidence ≥5% among patients receiving brexpiprazole 0.5–2 mg/day were headache (7.6% versus 12.4% with placebo) and somnolence (6.1% versus 3.6%). In both studies, the majority of TEAEs were mild or moderate in severity.
Brexpiprazole 2 mg/day has the potential to be efficacious, safe, and well tolerated in the treatment of AAD.
Background The Hawthorne effect, or behaviour change due to awareness of being observed, is assumed to inflate hand hygiene compliance rates as measured by direct observation but there are limited ...data to support this. Objective To determine whether the presence of hand hygiene auditors was associated with an increase in hand hygiene events as measured by a real-time location system (RTLS). Methods The RTLS recorded all uses of alcohol-based hand rub and soap for 8 months in two units in an academic acute care hospital. The RTLS also tracked the movement of hospital hand hygiene auditors. Rates of hand hygiene events per dispenser per hour as measured by the RTLS were compared for dispensers within sight of auditors and those not exposed to auditors. Results The hand hygiene event rate in dispensers visible to auditors (3.75/dispenser/h) was significantly higher than in dispensers not visible to the auditors at the same time (1.48; p=0.001) and in the same dispensers during the week prior (1.07; p<0.001). The rate increased significantly when auditors were present compared with 1–5 min prior to the auditors’ arrival (1.50; p=0.009). There were no significant changes inside patient rooms. Conclusions Hand hygiene event rates were approximately threefold higher in hallways within eyesight of an auditor compared with when no auditor was visible and the increase occurred after the auditors’ arrival. This is consistent with the existence of a Hawthorne effect localised to areas where the auditor is visible and calls into question the accuracy of publicly reported hospital hand hygiene compliance rates.
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