Low incidence and transient elevation of autoantibodies post mRNA COVID-19 vaccination in inflammatory arthritis.

OBJECTIVES: Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls. METHODS: Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization. RESULTS: Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, P = 0.014). Incidence of de novo anti-CCP seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titre, transient, and not associated with increase in IA flares. CONCLUSIONS: In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population.

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease.

OBJECTIVE: To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. METHODS: Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response. RESULTS: Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination. CONCLUSIONS: In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

Dermatomyositis, clinically presenting with cutaneous ulcers, with histopathologic evidence of perforating collagenosis.

Dermatomyositis is a systemic, autoimmune diseasewith a variety of clinical features that often includemyositis and characteristic cutaneous findings. Asubset of patients with dermatomyositis developcutaneous ulcers, often in the setting of vasculitis orvasculopathy. We present a case of dermatomyositiswith cutaneous ulcers that show perforatingcollagenosis on histopathologic examination.Acquired reactive perforating collagenosistypically occurs in the setting of diabetes mellitus,chronic renal failure, and other pruritic conditions,and this case represents a rare association withdermatomyositis, which may ultimately be helpful inelucidating the pathophysiology of this perforatingdisorder.

Evaluation of an emergency department lean process improvement program to reduce length of stay.

STUDY OBJECTIVE: In recent years, lean principles have been applied to improve wait times in the emergency department (ED). In 2009, an ED process improvement program based on lean methods was introduced in Ontario as part of a broad strategy to reduce ED length of stay and improve patient flow. This study seeks to determine the effect of this program on ED wait times and quality of care. METHODS: We conducted a retrospective cohort study of all ED visits at program and control sites during 3 program waves from April 1, 2007, to June 30, 2011, in Ontario, Canada. Time series analyses of outcomes before and after the program and difference-in-differences analyses comparing changes in program sites with control sites were conducted. RESULTS: In before-after models among program sites alone, 90th percentile ED length of stay did not change in wave 1 (-14 minutes [95% confidence interval {CI} -47 to 20]) but decreased after wave 2 (-87 [95% CI -108 to -66]) and wave 3 (-33 [95% CI -50 to -17]); median ED length of stay decreased after wave 1 (-18 [95% CI -24 to -12]), wave 2 (-23 [95% CI -27 to -19]), and wave 3 (-15 [95% CI -18 to -12]). In all waves, decreases were observed in time to physician assessment, left-without-being-seen rates, and 72-hour ED revisit rates. In the difference-in-difference models, in which changes in program sites were compared with controls, the program was associated with no change in 90th percentile ED length of stay in wave 2 (17 [95% CI -0.2 to 33]) and increases in wave 1 (23 [95% CI 0.9 to 45]) and wave 3 (31 [95% CI 10 to 51]), modest reductions in median ED length of stay in waves 2 and 3 alone, and a decrease in time to physician assessment in wave 3 alone. CONCLUSION: Although the program reduced ED waiting times, it appeared that its benefits were diminished or disappeared when compared with that of control sites, which were exposed to system-wide initiatives such as public reporting and pay for performance. This study suggests that further evaluation of the effectiveness of lean methods in the ED is warranted before widespread implementation.

Billing And Insurance-Related Administrative Costs: A Cross-National Analysis.

Billing and insurance-related costs are a significant source of wasteful health care spending in Organization for Economic Cooperation and Development nations, but these administrative burdens vary across national systems. We executed a microlevel accounting of these costs in different national settings at six provider locations in five nations (Australia, Canada, Germany, the Netherlands, and Singapore) that supplements our prior study measuring the costs in the US. We found that billing and insurance-related costs for inpatient bills range from a low of $6 in Canada to a high of $215 in the US for an inpatient surgical bill (purchasing power parity adjusted). We created a taxonomy of billing and insurance-related activities (eligibility, coding, submission, and rework) that was applied to data from the six sites and allows cross-national comparisons. Higher costs in the US and Australia are attributed to high coding costs. Much of the savings achieved in some nations is attributable to assigning tasks to people in lower-skill job categories, although most of the savings are due to more efficient billing and insurance-related processes. Some nations also reduce these costs by offering financial counseling to patients before treatment. Our microlevel approach can identify specific cost drivers and reveal national billing features that reduce coding costs. It illustrates a valuable pathway for future research in understanding and mitigating administrative costs in health care.

Improving the patient experience through design.

Toronto's Princess Margaret Hospital (PMH) received a major financial gift to redesign its chemotherapy daycare and transfusion facilities, which were over capacity and in need of improvement, both functionally and aesthetically. PMH's vision was to create a new space and experience that was truly patient centric and world class. Meanwhile, a research team at the University of Toronto's Rotman School of Management had also received a gift from a corporate donor with a patient-focused mandate to examine ways in which healthcare in Canada could be made more patient centric. The Rotman research team was invited to work with the hospital's staff, physicians, patients and families to explore a more patient-centered approach to care.

Methotrexate Hampers Immunogenicity to BNT162b2 mRNA COVID-19 Vaccine in Immune-Mediated Inflammatory Disease.

OBJECTIVE: To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. METHODS: Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. RESULTS: Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. CONCLUSIONS: In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. KEY MESSAGES: What is already known about this subject?: The impact of COVID-19 has been felt across the globe and new hope has arisen with the approval of mRNA vaccines against the SARS-CoV-2. Studies have shown immunogenicity and efficacy rates of over 90% in the immunocompetent adult population. However, there is a lack of knowledge surrounding the response of patients with immune-mediated inflammatory diseases (IMIDs) who may also be on immunomodulatory medications.Patients with IMID have been shown to have attenuated immune responses to seasonal influenza vaccination.What does this study add?: This study looks at the humoral and cellular immune response to two doses of BNT162b2 mRNA COVID-19 Vaccine in participants with IMID (on immunomodulators) compared with healthy controls.Individuals with IMID on methotrexate demonstrate up to a 62% reduced rate of adequate immunogenicity to the BNT162b2 mRNA vaccination. Those on anti-cytokine or non-methotrexate oral medications demonstrate similar levels of immunogenicity as healthy controls (greater than 90%).Similarly, vaccination did not induce an activated CD8+ T cell response in participants on background methotrexate, unlike healthy controls and patients with IMID not receiving methotrexate.How might this impact of clinical practice or future developments?: These results suggest that patients on methotrexate may need alternate vaccination strategies such as additional doses of vaccine, dose modification of methotrexate, or even a temporary discontinuation of this drug. Further studies will be required to explore the effect of these approaches on mRNA vaccine immunogenicity.

Leading Lean: a Canadian healthcare leader's guide.

Canadian healthcare organizations are increasingly asked to do more with less, and too often this has resulted in demands on staff to simply work harder and longer. Lean methodologies, originating from Japanese industrial organizations and most notably Toyota, offer an alternative - tried and tested approaches to working smarter. Lean, with its systematic approaches to reducing waste, has found its way to Canadian healthcare organizations with promising results. This article reports on a study of five Canadian healthcare providers that have recently implemented Lean. We offer stories of success but also identify potential obstacles and ways by which they may be surmounted to provide better value for our healthcare investments.

Non-Hodgkin Lymphoma with Synovial Involvement of the Knee.

Musculoskeletal involvement occurs in approximately 25% of patients diagnosed with non-Hodgkin lymphoma (NHL). Skeletal involvement is typically secondary, with primary lymphoma of the bone being much rarer. We describe a case in which a 52-year-old man initially presented features suggestive of Lyme arthritis in his left knee. A synovial biopsy performed as part of a synovectomy procedure revealed a proliferative synovium with dense lymphoplasmacytic B cell infiltrate, suggestive of NHL. An inguinal lymph node biopsy was also performed but did not produce results pathologically similar to those of the left knee synovial biopsy.

Challenges to evidence-based prescribing in clinical practice.

Although there appears to be widespread support of evidence-based medicine as a basis for rational prescribing, the challenges to it are significant and often justified. A multitude of factors other than evidence drive clinical decision-making, including patient preferences and social circumstances, presence of disease-drug and drug-drug interactions, clinical experience, competing demands from more pressing clinical conditions, marketing and promotional activity, and system-level drug policies.

Response audit of an Internet survey of health care providers and administrators: implications for determination of response rates.

BACKGROUND: Internet survey modalities often compare unfavorably with traditional survey modalities, particularly with respect to response rates. Response to Internet surveys can be affected by the distribution options and response/collection features employed as well as the existence of automated (out-of-office) replies, automated forwarding, server rejection, and organizational or personal spam filters. However, Internet surveys also provide unparalleled opportunities to track study subjects and examine many of the factors influencing the determination of response rates. Tracking data available for Internet surveys provide detailed information and immediate feedback on a significant component of response that other survey modalities cannot match. This paper presents a response audit of a large Internet survey of more than 5000 cancer care providers and administrators in Ontario, Canada. OBJECTIVE: Building upon the CHEcklist for Reporting Results of Internet E-Surveys (CHERRIES), the main objectives of the paper are to (a) assess the impact of a range of factors on the determination of response rates for Internet surveys and (b) recommend steps for improving published descriptions of Internet survey methods. METHODS: We audited the survey response data, analyzing the factors that affected the numerator and denominator in the ultimate determination of response. We also conducted a sensitivity analysis to account for the inherent uncertainty associated with the impact of some of the factors on the response rates. RESULTS: The survey was initially sent out to 5636 health care providers and administrators. The determination of the numerator was influenced by duplicate/unattached responses and response completeness. The numerator varied from a maximum of 2031 crude (unadjusted) responses to 1849 unique views, 1769 participants, and 1616 complete responses. The determination of the denominator was influenced by forwarding of the invitation email to unknown individuals, server rejections, automated replies, spam filters, and 'opt out' options. Based on these factors, the denominator varied from a minimum of 5106 to a maximum of 5922. Considering the different assumptions for the numerator and the denominator, the sensitivity analysis resulted in a 12.5% variation in the response rate (from minimum of 27.3% to maximum of 39.8%) with a best estimate of 32.8%. CONCLUSIONS: Depending on how the numerator and denominator are chosen, the resulting response rates can vary widely. The CHERRIES statement was an important advance in identifying key characteristics of Internet surveys that can influence response rates. This response audit suggests the need to further clarify some of these factors when reporting on Internet surveys for health care providers and administrators, particularly when using commercially available Internet survey packages for specified, rather than convenience, samples.

A realist evaluation of value-based care delivery in home care: The influence of actors, autonomy and accountability.

The increasing demand for home care is occurring in tandem with the need for governments to contain health care costs, maximize appropriate resource utilization and respond to patient preferences for where they receive care. We describe the evaluation of the Integrated Client Care Project (ICCP), a government funded project designed to improve value for outcomes for patients referred to community wound care services in Ontario, Canada. We applied a realist evaluation methodology in order to unpack the influences of contextual and mechanistic choices on the intended outcomes of the ICCP implementation. We collected data through ethnographic methods including 36 months of field observation, 46 key informant interviews and contemporaneous document analysis. The findings presented here highlight how theoretical mechanisms were negatively impacted by strong contextual patterns and weak implementation which led to underwhelming outcomes. Autonomy of the participant organizations, lack of power within the implementation team to drive change, opacity of the goals of the program, and disregard for the impact of complex historical relations within the home care sector compounded to undermine the intended outcome.

The cost of pay-for-performance in healthcare: an alternative view.

George Pink and his colleagues have provided healthcare policy makers with a thorough review of pay-for-performance systems in healthcare. In general, their review suggests that pay-for-performance systems have resulted in few positive, net outcomes for health systems. Among other things, they cite the perverse incentives often generated by these systems, as well as these systems' high design and administration costs. The following article, building on research in economics, sociology and social psychology, extends their discussion by suggesting why healthcare delivery may be a uniquely difficult sector in which to rely on pay-for-performance systems. This article does not intend to shut down discussion of pay-for-performance in healthcare, but instead suggests how we might usefully think about when pay-for-performance is more or less appropriate. This analysis reveals that the healthcare delivery sector has some unique advantages over other sectors and industries.

Transforming healthcare organizations.

Change in healthcare organizations is a complex task often fraught with unforeseen challenges. Based on the experiences of a multi-site hospital, and drawing on past research on organizational change, the author provides a model to help change leaders. Although relying on Toronto's University Health Network to illustrate the change model, the model is intended to speak to change leaders implementing various types of complex changes across a range of organizations.

Transforming healthcare organizations: looking back to see the future.

With a strong sense that MOE/MAR and its implementation have been a resounding success, the authors offer a final set of insights for healthcare leaders.

Genetic analysis of families with autoimmune diabetes and thyroiditis: evidence for common and unique genes.

CONTEXT: Epidemiological data suggest a common genetic susceptibility to type 1 diabetes (T1D) and autoimmune thyroid disease (AITD). OBJECTIVE: Our objective was to identify the joint susceptibility genes for T1D and AITD. DESIGN: We conducted a family-based linkage and association study. SETTING: The study took place at an academic medical center. PARTICIPANTS: Participants included 55 multiplex families (290 individuals) in which T1D and AITD clustered (T1D-AITD families). MAIN OUTCOME MEASURES: We conducted tests for linkage and family-based associations (transmission disequilibrium test) with four candidate genes: human leukocyte antigen (HLA), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), insulin variable number of tandem repeats (VNTR), and thyroglobulin. RESULTS: Linkage evidence to HLA appeared when subjects with either T1D or AITD were considered affected [maximum LOD score (MLS), 2.2]. The major HLA haplotype contributing to the shared susceptibility was DR3-DQB1*0201, with DR3 conferring most of the shared risk. The CTLA-4 gene showed evidence for linkage only when individuals with both T1D and AITD were considered affected (MLS, 1.7), and the insulin VNTR showed evidence for linkage when individuals with either T1D or AITD were considered affected (MLS, 1.9); i.e. it may contribute to the familial aggregation of T1D and AITD. CONCLUSIONS: The HLA class II locus contributes to the shared risk for T1D and AITD, and the major HLA haplotype contributing to this association is DR3-DQB1*0201. Additional non-HLA loci contribute to the joint susceptibility to T1D and AITD, and two potential candidates include the CTLA-4 and insulin VNTR loci.

Aligning the stars: Using systems thinking to (re)design Canadian healthcare.

It has become commonplace to refer to a "Canadian healthcare system," implying some monolithic system of prevention and care, yet failing to acknowledge its various subsystems, some performing well and some not. This article argues that a more nuanced understanding of healthcare systems, based on the principles of Systems Theory, provides a useful lens to understand our current system(s) as well as those that are possible, the principles of design and the levers available to leaders and policymakers as we implement our healthcare strategies for Canada.

Improving hospital efficiency: a process model of organizational change commitments.

Improving hospital efficiency is a critical goal for managers and policy makers. We draw on participant observation of the perioperative coaching program in seven Ontario hospitals to develop knowledge of the process by which the content of change initiatives to increase hospital efficiency is defined. The coaching program was a change initiative involving the use of external facilitators with the goal of increasing perioperative efficiency. Focusing on the role of subjective understandings in shaping initiatives to improve efficiency, we show that physicians, nurses, administrators, and external facilitators all have differing frames of the problems that limit efficiency, and propose different changes that could enhance efficiency. Dynamics of strategic and contested framing ultimately shaped hospital change commitments. We build on work identifying factors that enhance the success of change efforts to improve hospital efficiency, highlighting the importance of subjective understandings and the politics of meaning-making in defining what hospitals change.