Development of data processing algorithm to calculate adherence for adults with cystic fibrosis using inhaled therapy - a multi-center observational study within the CFHealthHub learning health system.

OBJECTIVES: To develop a robust algorithm to accurately calculate 'daily complete dose counts' for inhaled medicines, used in percent adherence calculations, from electronically-captured nebulizer data within the CFHealthHub Learning Health System. METHODS: A multi-center, cross-sectional study involved participants and clinicians reviewing real-world inhaled medicine usage records and triangulating them with objective nebulizer data to establish a consensus on 'daily complete dose counts.' An algorithm, which used only objective nebulizer data, was then developed using a derivation dataset and evaluated using internal validation dataset. The agreement and accuracy between the algorithm-derived and consensus-derived 'daily complete dose counts' was examined, with the consensus-derived count as the reference standard. RESULTS: Twelve people with CF participated. The algorithm derived a 'daily complete dose count' by screening out 'invalid' doses (those <60s in duration or run in cleaning mode), combining all doses starting within 120s of each other, and then screening out all doses with duration < 480s which were interrupted by power supply failure. The kappa co-efficient was 0.85 (0.71-0.91) in the derivation and 0.86 (0.77-0.94) in the validation dataset. CONCLUSIONS: The algorithm demonstrated strong agreement with the participant-clinician consensus, enhancing confidence in CFHealthHub data. Publishingdata processing methods can encourage trust in digital endpoints and serve as an exemplar for other projects.

Revision to the musculoskeletal domain of the BILAG-2004 index to incorporate ultrasound findings.

OBJECTIVES: To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. METHODS: The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. RESULTS: The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). CONCLUSIONS: Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment.

Domains and outcome measures for the assessment of limited cutaneous systemic sclerosis: an international collaborative scoping review.

OBJECTIVES: The aim of this study was to comprehensively identify instruments within relevant domains employed to assess lcSSc since the endorsement of its consensus definition in 1988. The overall objective is to inform the creation of a Combined Response Index for Scleroderma Trials Assessing lcSSc (CRISTAL). METHODS: MEDLINE and Embase were searched using terms selected to comprehensively retrieve titles and abstracts mentioning both lcSSc and dcSSc, along with those only mentioning lcSSc, SSc sine scleroderma, limited SSc and/or CREST/CRST. Because our initial assessment of the literature revealed that very few studies included only lcSSc subjects, we also assessed literature that included both cutaneous subsets. A total of 3964 titles and abstracts were screened by two reviewers, and 270 articles were selected for data extraction. RESULTS: We identified 27 domains encompassing 459 instruments. Instruments from 'Skin involvement', 'Pulmonary involvement' and 'Health-related quality of life and general functioning' were the most frequently retrieved. Among the 15 most represented instruments announced as primary end points in efficacy or effectiveness studies, 7 were clinician-reported outcomes (ROs), 7 were patient ROs, and one was a performance outcome (6 min-walk test). The mean proportion of lcSSc patients in studies of lcSSc, including studies that mention both lcSSc and dcSSc, was 56.4%, demonstrating that this subset is underrepresented in the literature, given that the prevalence of lcSSc ranges from 60% to 80% in national registries and international cohorts. CONCLUSION: This scoping literature review provides a comprehensive identification of domains and outcomes used to assess lcSSc. Our results also highlight that lcSSc is underrepresented in the literature.

Improvement with time of vascular outcomes in systemic sclerosis: a systematic review and meta-analysis study.

OBJECTIVES: Vascular disease in SSc is associated with significant morbidity and mortality. Preliminary data may lead to the suggestion of a modifiable unified-vascular endophenotype. Our aim was to determine whether the prevalence, mortality and severity of SSc-vascular disease have changed over time. METHODS: We performed a systematic review and meta-analysis of the literature in PubMed 1950-2019 related to SSc-digital ulcers (DUs), pulmonary artery hypertension (PAH) and scleroderma renal crisis (SRC). We included full-text articles and extracted study characteristics and assessed risk of bias/quality. We examined the prevalence, mortality and surrogate measures of SSc-associated vascular disease severity. RESULTS: We included 55 studies in our meta-analysis. The pooled prevalence of DUs (41.0%), PAH (9.5%) and SRC (4.9%) remained largely stable over time. There was significant improvement in PAH 1-year (P = 0.001) and SRC mortality (P < 0.001), but not PAH 3-year (P = 0.312) or 5-year (P = 0.686) mortality. The prevalence of DU healing did not significantly change (P = 0.265). There was a trend (all P = ∼0.1) towards improvement in PAH surrogates: mean pulmonary artery pressure, pulmonary vascular resistance and right atrial pressure. For SRC, there was evidence that the overall frequency of dialysis (66.7%, P = 0.297) and permanent dialysis (35.4%, P = 0.036) increased over time. CONCLUSION: Despite the heterogeneity and scarcity of the disease, there have been major improvements obtained in the various vascular complications in SSc leading to benefit in survival. This is supported by a trend towards improvement in several surrogate markers and demonstrates that progress in vascular management translates into major patient benefit.

The CFHealthHub Learning Health System: Using Real-Time Adherence Data to Support a Community of Practice to Deliver Continuous Improvement in an Archetypal Long-Term Condition.

CFHealthHub is a learning health system active in over 50% of adult CF Centres in England, supporting people with CF to develop habits of self-care around adherence to preventative inhaled therapy. This is achieved through the delivery of a behaviour change intervention, alongside collection of objective adherence data. As is common to long-term conditions, adherence to prescribed therapy is low, despite clear evidence of beneficial long-term impact on outcomes. This article explains how CFHealthHub is underpinned by coherent conceptual frameworks. We discuss how application of implementation and quality improvement strategies has facilitated CFHealthHub's progression from a pilot study to a large, randomised control trial and now to a learning health system, becoming embedded within routine care. CFHealthHub is now able to support real-time health technology assessments, quality improvement and research trials and is in the process of being implemented in routine clinical care across participating centres.

High tibial osteotomy: A review of the readability and quality of patient information on the internet.

Background: High tibial osteotomy (HTO) is a common procedure performed for unicompartmental knee osteoarthritis (OA). Patients are increasingly using the internet to research surgical procedures to help aid decision making. Our aim was to assess the readability and quality of information available to patients online relating to HTO. Methods: A systematic review of three search engines Google®, Bing®, and Yahoo® using the search terms "high tibial osteotomy" and "tibial osteotomy" separately was performed. The first three pages of results for each search engine were analyzed. Readability was assessed using the Flesch Reading Ease Scale (FRES), Flesch-Kincaid Grade level (FKGL) and the Simple Measure of Gobbledygook formula (SMOG). Quality was assessed with the DISCERN questionnaire, JAMAbenchmarks and the presence of Health on the Net Foundation Code of Conduct (HONCode). Results: Twenty-four webpages were included after duplicates (n=42) and exclusions (n=24).The overall readability was low, with a mean FRES of 53.2 (SD: 9.1), FKGL 10.7 (SD: 1.8),SMOG 10.4 (SD: 1.5). Quality was also low with a mean DISCERN score of 42 (SD: 12.3).None of the webpages fulfilled all of the JAMA benchmarking criteria and only 2/24 (8.3%)webpages possessed HONCode certification. Conclusion: The overall online information available to patient's considering HTO is of lowreadability and quality. Improving the quality and readability of patient information online willbenefit informed patient decision making before HTO surgery.

Association between central nervous system stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon: A scoping review.

The association between central nervous (CNS) stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon (RP) has received little attention to date. Our aim was to map the existing literature on aetiopathogenesis, clinical presentation and management of peripheral vasculopathy, with a focus on RP, secondary to drug therapy for ADHD. We searched the PubMed® database (01/11/1951 to 01/08/2020) and included articles written in English, which focussed on CNS stimulants used to treat ADHD and RP. The search identified 150 articles 9 of which were eligible for inclusion (70 patients). The majority of studies (n = 6) related to children or adolescents; however, adult cases were also identified. Peripheral vascular manifestations included attacks of RP (new and worsening) and cold sensitivity (acrocyanosis and perniosis). Irreversible ischaemic complications including digital autoamputation and lower limb critical digital ischaemia have also been reported. The implicated causative CNS stimulants were Methylphenidate (n = 5), Dextroamphetamine (n = 4), Atomoxetine (n = 2), and Lisdexamphetamine (n = 2). Complete resolution of RP symptoms was observed in half (n = 5) of studies upon drug cessation. Other therapeutic strategies have included dose reduction and switching to an alternative drug therapy. A potential autoimmune association has also been postulated including drug-induced autoimmunity and new cases of systemic sclerosis which have been potentially attributed to treatment. Future research is required to understand the association between CNS stimulant drug therapies for ADHD and peripheral vascular manifestations, including RP.

Domains and outcome measures for the assessment of limited cutaneous systemic sclerosis: a scoping review protocol.

INTRODUCTION: Limited cutaneous systemic sclerosis (lcSSc) is the most frequent subset of systemic sclerosis. Despite this, lcSSc is not the major focus of clinical studies. The lack of interventional studies in lcSSc is due, in part, to a paucity of relevant outcome measures to effectively evaluate this subset. A combined response index dedicated to lcSSc would facilitate development of well-designed trials and approval of new drugs. The objective of this scoping review is to perform a broad and comprehensive identification of the outcome measures (core set items) within relevant domains, which have been used so far to assess lcSSc. METHODS AND ANALYSIS: The planned scoping review will be based on the approach proposed by Arksey et al and further developed by Levac et al. Development and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews checklist and guidelines. The development of the search strategy was guided by the concepts of domains and outcomes based on the Outcome Measures in Rheumatology approach and by the different names and definitions of SSc, with a specific emphasis on their occurrence in clinical trial studies. Two databases will be searched: MEDLINE and Embase. Studies in English, published from the year 1988 onwards, will be included, since 1988 corresponds to the publication of LeRoy's first consensus definition of lcSSc. Data will be extracted and analysed using a standardised charting tool. ETHICS AND DISSEMINATION: No ethical approval is required for this study. The results will be submitted to an international peer-reviewed journal and scientific conferences, informing the discussion on which items should be included in a combined response index dedicated to lcSSc (the CRISTAL project: Combined Response Index for Scleroderma Trial Assessing lcSSc).

Bone health in idiopathic inflammatory myopathies.

OBJECTIVE: To review the extant literature relating to bone health in the idiopathic inflammatory myopathies (IIM) including both adult and juvenile patients. METHODS: A PubMed search® identified relevant studies from 1966 to 2020 in accordance with PRISMA guidelines. Two independent reviewers screened and extracted the abstracts/full manuscripts, and a third author was consulted in the case of disagreement. RESULTS: We identified 37 articles (3 review articles, 2 RCTs, 9 cross-sectional, 16 cohort and 7 case-control studies). The prevalence of osteopenia (n = 7) ranges from 7 to 75% and osteoporosis (n = 7) between 13% to 27%. The prevalence of vertebral fractures ranged from 11 to 75%. Systemic inflammation likely contributes to reduced bone mineral density (BMD) in children with IIM but data is currently lacking in adult patients. Association between with impaired BMD and Vitamin D or calcium intake and physical activity has not been demonstrated in IIM. There is no clear consensus regarding the impact of age, menopause or BMI on bone health. Gender, smoking status, disease activity and inflammatory markers are not obvious independent predictors of low BMD. Several studies have demonstrated that glucocorticoids are associated with an increased risk of low BMD. There are no specific guidelines relating to the management of bone health in adult and juvenile patients with IIM. CONCLUSION: Both adult and juvenile patients with IIM are at high risk of impaired bone health and fracture. The mechanisms behind this are likely multifactorial including systemic inflammation, glucocorticoid treatment, reduced mobility and impaired calcium/vitamin D homeostasis. There are a lack of guidelines and studies relating to the screening, prevention and treatment of impaired bone health in adult and juvenile patients with IIM. Future research is required to understand the complexity of bone health in IIM including to develop much needed disease-specific management recommendations.

A systematic review of internet-based information on dermatomyositis and polymyositis.

AIM: Patients with rheumatic diseases are increasingly using internet-based information to inform healthcare utilization and make treatment decisions. Our aim was to assess the readability and quality of internet-based information on dermatomyositis (DM) and polymyositis (PM). METHOD: Key words "Dermatomyositis" and "Polymyositis" were searched on 3 commonly used search engines (Google, Yahoo and Bing). The first 3 pages (~30) of search results were examined from each search engine. Readability of information was assessed using 4 readability formulae (Flesch Reading Ease Score, Flesch-Kincaid Grade Level, the Simplified Measure of Gobbledygook index, the Coleman-Liau index). Quality of information was assessed using the DISCERN tool, Journal of The American Medical Association (JAMA) benchmark criteria and Health on The Net Code (HoN code). We also examined Google Trends® data to determine if there were obvious temporal search patterns. RESULTS: Thirty-two websites were included in the study after duplicates were removed and exclusion criteria were applied. The overall quality was low including DISCERN with a median overall score of 38/80 (interquartile range 12.25), only 4/32 (13%) websites fulfilled all 4 JAMA benchmark criteria, and 9/32 (28%) had HoN code. Readability of information was assessed using 4 readability formulae (Flesch Reading Ease Score, Flesch-Kincaid Grade Level, the Simplified Measure of Gobbledygook index, the Coleman-Liau index. There was no obvious temporal trend in searches on analysis of Google Trends® data. CONCLUSION: The overall quality and readability of internet-based information relating to DM and PM is poor. Patients require appropriate information of high quality and readability throughout the course of their disease in order to make informed decisions on their condition including treatment.

Mobile Medical ID: A Resource for the Off-Duty Clinician.

In this case, a mobile medical ID was used to inform an off-duty clinician of highly relevant medical history when attending a pedestrian during a medical emergency. Mobile medical IDs are available on all major smartphone operating systems and provide information including, but not limited to, medical history, current medications, and allergy status. These can be accessed from lock screens, allowing access for off-duty clinicians to improve the quality of care they could provide while awaiting assistance.

Correction to: A systematic review of internet-based information for individuals with Raynaud's phenomenon and patients with systemic sclerosis.

The authors have identified an error in thier manuscript and have incorrectly referred to the overall DISCERN score for SSc and RP as 2.21 and 1.99, respectively, in the abstract and discussion. The correct DISCERN quality scores are listed in Table 2.

A systematic review of internet-based information for individuals with Raynaud's phenomenon and patients with systemic sclerosis.

INTRODUCTION: Patients are increasingly using internet-based information to inform healthcare utilization and treatment decisions. Our aim was to examine the quality and readability of internet-based information relating to Raynaud's phenomenon (RP) and systemic sclerosis (SSc). MATERIAL AND METHODS: A systematic review of three commonly used search engines (Google®, Yahoo®, and Bing®) using the terms "Raynaud's phenomenon" and "systemic sclerosis" separately. The first 30 websites per search engine were examined. Quality was assessed using the DISCERN questionnaire and readability by the Flesch-Kincaid Grade Level, SMOG Index, Coleman-Liau index, and Flesch Reading Ease score. RESULTS: Fifty-two studies (30 RP and 22 SSc) were included after duplicates and exclusion criteria were applied. The overall quality of information was low for both SSc and RP (1.99 & 2.21), including in relation to reliability of the literature and information on treatment choices. Readability for RP and SSc was also poor (i.e., the texts were difficult to read) across all of the four methods examined. CONCLUSION: Overall, RP and SSc internet-based information is of low quality and inadequate readability. The RP and SSc international community should strongly consider developing an information standard for internet-based resources for healthcare users. KEY POINTS: • Patients with SSc and RP are increasingly using internet/online sources of information and support. • RP represents an important opportunity for the early diagnosis of SSc. • The overall quality and readability of internet-based RP and SSc information is poor. • Internet-based RP and SSc information requires improvement to facilitate early diagnosis and inform shared decision-making.

Miller-Fisher Syndrome: Is the ataxia central or peripheral?

A 50-year-old man presented with a brief history of slurred speech, unsteadiness, double vision and paraesthesia. He had been unwell for 12 days with campylobacter gastroenteritis. On examination, there was ophthalmoplegia, nystagmus, areflexia and lower limb and gait ataxia. Serological testing was positive for GQ1b antibody in keeping with the diagnosis of Miller Fisher Syndrome (MFS). He was treated with two courses of intravenous immunoglobulins and made a good recovery, only displaying mild gait ataxia when reviewed in clinic 2.5 months later. There has long been a debate as to whether the ataxia in MFS originates in the cerebellum or it is more peripheral. In this case, magnetic resonance spectroscopy (MRS) revealed a reduced NAA/Cr ratio in the cerebellar vermis and right cerebral hemisphere, suggestive of cerebellar dysfunction. The NAA/Cr normalised 2.5 months later reflecting the clinical recovery. The findings on MRS suggest that the cerebellum is involved in MFS.