Impact of caring for someone with a rare rheumatic condition, views from patients and informal carers – the need for cat-like vigilance

Objective ANCA-associated vasculitis (AAV) is a rare multisystem disease. Modern therapeutic protocols have turned AAV from an acute frequently fatal disease into a chronic disease requiring long-term immunosuppression. Patients must often manage substantial burdens related to chronic illness and treatment-related side effects, requiring help from informal carers. This study aimed to explore the experience of patients and of informal carers of patients with AAV about the impact of managing a rare rheumatic condition. Methods A qualitative approach using semi-structured interviews was used. Interviews were conducted with a purposeful sample of 18 pairs of patients with AAV and their informal carers. The interviews were used to explore the participants’ experience and effects of caring. The interviews were recorded and transcribed as verbatim text and analysed using the framework technique. Results 18 patients (seven female) [disease: ten granulomatosis with polyangiitis (GPA); four microscopic polyangiitis (MPA); four eosinophilic granulomatosis with polyangiitis (EGPA), age range 34-78, disease duration 1- 20 years. Caregiver and patient perspectives were shared. The emerging themes were the physical and psychological impact of the disease, the need for constant vigilance and fear of the future. Conclusion Both patients and carers faced a range of challenges in managing a rare condition, from the seriousness of the illness, dealing with the emotional toll and knowing what to expect. This study offers insight into the experiences of patients and informal carers, and health care professionals should address individuals’ fears and expectations for recovery

275 Impact of caring for someone with a rare rheumatic condition: views from patients and informal carers

Background: ANCA-associated vasculitis is a rare multisystem disease. Modern therapeutic protocols have turned ANCA-associated vasculitis from an acute frequently fatal disease into a chronic disease requiring long-term immunosuppression. Patients must often manage substantial burdens related to chronic illness and treatment-related side effects. Patients often need help and support to manage their disease. The aim of this study was to explore the experience of patients and of informal carers of patients about the impact of managing a rare rheumatic condition. Methods: A qualitative approach using semi-structured interviews was used. Interviews were conducted with a purposeful sample of 18 pairs of patients with ANCA-associated vasculitis and their informal carers. The interviews were used to explore the participants experience and affects of caring. The interviews were recorded and transcribed as verbatim text and analysed using the framework technique. Results: 18 patients (seven female) [disease: ten granulomatosis with polyangiitis (GPA); four microscopic polyangiitis (MPA); four eosinophilic granulomatosis with polyangiitis (EGPA), age range 34-78, disease duration 1- 20 years. Caregiver and patient perspectives were shared. The emerging themes were the physical and psychological impact of the disease, the need for constant vigilance and fear of the future. Conclusion: Both patients and carers faced a range of challenges in managing a rare condition. From the seriousness of the illness, dealing with the emotional toll and knowing what to expect. This study offers insight into the experiences of patients and informal carers and health care professionals should address individuals’ fears and expectations for recovery. Disclosures: J.M. honoraria; Abbvie, Bristol Myres Squibb. K.G. and R.A.W. have declared no conflicts of interest

‘It’s my own fault’: Accounts and consequences of falling when living with rheumatoid arthritis

Introduction: Rheumatoid Arthritis (RA) leads to biomechanical joint changes which increases risk of falling. The consequence of falling may be physical injury. However, as important can be the psychological consequences including fear of falling. Methods: Participants were recruited from a larger prospective study which explored the incidence of falls in people with RA. Purposive sampling considered age, sex, time since diagnosis and fall history. The recruitment site was a regional hospital. Data from semi-structured qualitative interviews and, after each fall, brief telephone interviews. Thematic analysis methods were used to investigate the psychological and social impact of falling in people with RA. Results: Twelve participants were interviewed (aged 64-85, mean 74 years: 6 had fallen between 1-23 times: 6 had no reported fall in last 12 months). Data was supplemented with telephone notes from 287 post-fall telephone calls. Three themes were developed: 1) The falls Imaginary illustrates that fear of falling is not dependent on experience; 2) Agentic risk management reports on the ways people self-manage and display resilience when at risk of falling; 3) The absence of the health professional explores the ways in which people reported being unsupported by health care services. Conclusion: Fear of falling when living with RA is tangible in those who have and have not fallen. This fear may limit opportunities for full participation in life. However some people display personal resourcefulness continuing to live purposeful lives. Understanding personal responses to falling will support the development of community interventions specific to this high risk group

The prevalence of giant cell arteritis and polymyalgia rheumatica in a UK primary care population

Background: To update community-based prevalence values for Polymyalgia Rheumatic (PMR) and Giant Cell Arteritis (GCA) using case record review supplemented by population survey and subsequent clinical review. Methods: Clinical data were obtained from case records of a large primary care practice in Norfolk, UK and reviewed for diagnoses of GCA and PMR. In addition postal survey was carried out to capture potentially undiagnosed cases within the practice population. Those screening positive for potential diagnoses of GCA and PMR were invited for clinical review. A cumulative prevalence estimate was subsequently calculated on those diagnosed within the GP practice and subsequently on those fulfilling the various published classification criteria sets. The date of the database lock and mail merge was March 2013. Results: Through detailed systematic review of 5,159 GP case records, 21 patients had a recorded diagnosis of GCA and 117 had PMR . No new cases were identified among 2,227 completed questionnaires returned from the population survey of a sample of 4,728. The resulting cumulative prevalence estimate in those aged ≥55 years meeting the ACR classification criteria set for GCA was 0.25% (95% CI 0.11% to 0.39%) and for five published criteria sets for PMR ranged from 0.91% to 1.53% (95% CI ranges 0.65%, 1.87%). The prevalence of both conditions was higher in women than in men and in older age groups. Conclusion: This study provides the first UK prevalence estimate of GCA and PMR in over 30 years and is the first to apply classification criteria sets

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation

The Prevalence of Giant Cell Arteritis and Polymyalgia Rheumatica in a UK Primary Care Population

Background: Accurate population prevalence estimates for PMR and GCA are essential for health service planning. However the only data available in the UK are outdated; and estimates for other countries are based on different methods of case ascertainment and classification and vary widely. The aim of this study was provide updated prevalence figures for these conditions in the in the UK based on cases ascertained from primary care and using current definitions. Methods: Clinical data was obtained from practice records of a large general practice in Norfolk, UK. Case records were reviewed for the purposes of diagnosis and classification of GCA and PMR. To ensure that there was not a substantial undiagnosed disease burden within the practice population, the practice population aged 55 years or older was surveyed using a questionnaire designed using published cardinal features of GCA and PMR. Non-responders were sent reminders after 3 months. Questionnaire responses were risk-stratified for potential diagnoses of GCA and PMR and those at high risk reviewed by a rheumatologist. Results: A total of 6159 patients registered with the practice aged 50 years and older. Of these, 22 had a diagnosis of GCA and 117 had a diagnosis of PMR in their care record. A survey was sent to all eligible individuals aged 55 years or older (exclusion criteria included those with terminal illness, dementia or living in a nursing home). 2227 completed questionnaires were returned from the population of 4728 (97.2% with complete data). The median age of the respondents was 68 years (interquartile range 12 years), 52% were female. There were no statistical differences between the median age and gender ratio between responders and non-responders. During the time of the study no participants were identified with a new diagnosis of GCA and no new diagnoses of GCA were made at the practice. 15 participants self-reported a diagnosis of GCA (8 of who were confirmed by the practice) and 83 self-reported a diagnosis of PMR (73 confirmed by the practice). The resulting minimum prevalence estimates for those aged >55 years were 17/10 000 (95% CI 5, 29) for GCA and 154/10 000 (95% CI 119, 190) for PMR. Conclusion: This is the first prevalence estimate of GCA for the UK for 30 years and the first to apply current classification criteria. Community-derived estimates of prevalence are likely to be most representative of true disease burden. Disclosure statement: The authors have declared no conflicts of interest

A Real Headache: A Cross-Sectional Survey of Symptoms Associated with Giant Cell Arteritis in A Primary Care Setting

Background: GCA is the commonest form of large vessel vasculitis. Its association with permanent visual loss in up to 23% of patients makes prompt recognition and treatment essential. However, the high prevalence of headache and the lack of specificity of a raised ESR (two key items of the current classification criteria) pose a challenge to identify GCA appropriately in primary care. In addition, using classification criteria for the purposes of diagnosis risks the misinterpretation of inference. In this study we aimed to investigate the prevalence of symptoms associated with GCA in a general practice population with the objective of identifying key discriminating features that identify the disease in this setting. Methods: A cross-sectional survey of all individuals aged 55 years or older from a large general practice of two sites in Norfolk, UK, was carried out. The questionnaire was developed to include the full range of clinical features that have been related to GCA, identified from a literature review. All GP diagnoses of GCA identified on the GP database and clinical care records were reviewed for the purpose of case classification against 1990 ACR criteria. Key clinical features were identified through step-wise logistic discrimination adjusting for age and sex. Likelihood ratios of individual features in the final selected model were estimated. Results: The analysis is based on completed responses from 2277 individuals from an invited sample of 4728 individuals aged 50 years or older (response rate 49%). The median age was 68 years old. There was no statistical difference between responders and non-responders for age structure and gender ratio. 15 participants self-reported a diagnosis of GCA (8 of who were confirmed on their care record). Of the total responses, 2.8% of males and 6.7% of females reported having suffered severe headaches lasting longer than 7 days. In the logistic discrimination model (adjusted for age and sex) the following clinical features provided the most predictive power: headache, unexplained weight loss and early morning shoulder pain and stiffness (receiver operator characteristic = area under curve 96.8%). Likelihood ratios for individual symptoms as predictors of GCA are displayed in Table 1. Conclusion: This is the first study to survey an entire population for symptoms commonly associated with GCA in a community setting. The data show that GCA accounts for a small proportion of those with prolonged headache. As expected the co-occurrence of jaw, tongue pain and scalp tenderness with headache are important predictors of GCA in this setting. It is of particular interest that the highest positive likelihood ratio is related to unexplained weight loss. This is not included in current classification criteria but may be of diagnostic value in identifying GCA in the in the general practice setting. Disclosure statement: The authors have declared no conflicts of interest

Risk of Polymyalgic-Onset Inflammatory Arthritis in Patients Initially Diagnosed with Polymyalgia Rheumatica

Background: Previous studies from secondary care have suggested that inflammatory arthritis develops in up to 20.2% of patients with PMR within 12 months of disease onset. However, many cases of PMR are exclusively managed in the community and the true risk of subsequent inflammatory arthritis is unknown. This study aimed to determine the rate at which new cases of PMR transform to inflammatory arthritis in a population sample and to assess whether clinical factors at presentation might identify those at risk of subsequent inflammatory arthritis. Methods: The study was conducted in participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk. The cohort was established with 30 441 healthy volunteers ages 40–79 years between 1993 and 1997, recruited from 35 general practice sites across Norfolk, UK. New cases of PMR diagnosed on or after 1 January 2002 were identified by electronic record linkage, International Classification of Diseases, Tenth Revision codes and follow-up questionnaires. Inflammatory arthritis was identified from hospital records review. The end date for follow-up was 31 January 2015. Survival analysis (accounting for censoring from loss to follow-up and death) was used to calculate the cumulative risk of inflammatory arthritis. Results: A total of 298 incident diagnoses of PMR (72.5% female) were identified in the cohort. The median age at diagnosis was 75.6 years. The maximum follow-up period was 13 years (median 4.82). During 1573.6 person-years of follow-up, 31 (10.4%) participants (19 female) were diagnosed with inflammatory arthritis by a rheumatologist. The cumulative risk of new-onset inflammatory arthritis at 1, 2, 5 and 10 years was 3.9% (95% CI 2.2, 6.9), 7.4% (4.8, 11.2), 9.7% (6.6, 14.0) and 16.0% (10.6, 23.8), respectively. Males were at greater risk of developing inflammatory arthritis compared with females in the first 5 years [cumulative risk for males at 1 and 5 years: 8.9% (95% CI 4.4, 17.8) and 15.7% (9.2, 26.0), respectively; cumulative risk for females: 2.0% (95% CI 0.8, 5.2) and 7.3% (4.3, 12.3)]. There was a trend towards a greater risk of inflammatory arthritis in those with a younger age at PMR onset. The majority of participants with inflammatory arthritis were RF negative (72.7%). Conclusion: These are the first estimates from a population study that assessed the risk of inflammatory arthritis developing after a diagnosis of PMR. Patients with PMR are at sustained risk of developing inflammatory arthritis up to 10 years after diagnosis. The data suggest that males and those of younger age are at a greater risk. The finding that 10.4% of participants with PMR at baseline subsequently develop inflammatory arthritis suggests a subset of patients with PMR could benefit from the early use of DMARDs

A pilot test of a self-guided, home-based intervention to improve condom-related sexual experiences, attitudes, and behaviors among young women

Objective: to conduct a pilot test of a brief, self-guided, home-based program designed to improve male condom use attitudes and behaviors among young women.Participants: women aged 18–24 years from a large Midwestern University reporting having had penile-vaginal sex with two or more partners in the past 3 months. Sixty-seven enrolled; 91.0% completed the study.Methods: a repeated measures design was used, with assessments occurring at baseline, immediately post-intervention (T2), and 30 days subsequent (T3).Results: condom use errors and problems decreased, condom-related attitudes and self-efficacy improved, and experiences of condom-protected sex were rated more positively when comparing baseline with T2 and T3 scores. Further, the proportion of condom-protected episodes more than doubled between T1 and T3 for those in the lowest quartile for condom use at baseline.Conclusion: this low-resource, home-based program improved condom-related attitudes and promoted the correct and consistent use of condoms

B-cell receptor signaling induces proteasomal degradation of PDCD4 via MEK1/2 and mTORC1 in malignant B cells

B-cell receptor (BCR) signaling plays a major role in the pathogenesis of B-cell malignancies and is an established target for therapy, including in chronic lymphocytic leukemia cells (CLL), the most common B-cell malignancy. We previously demonstrated that activation of BCR signaling in primary CLL cells downregulated expression of PDCD4, an inhibitor of the translational initiation factor eIF4A and a potential tumor suppressor in lymphoma. Regulation of the PDCD4/eIF4A axis appeared to be important for expression of the MYC oncoprotein as MYC mRNA translation was increased following BCR stimulation and MYC protein induction was repressed by pharmacological inhibition of eIF4A. Here we show that MYC expression is also associated with PDCD4 down-regulation in CLL cells in vivo and characterize the signaling pathways that mediate BCR-induced PDCD4 down-regulation in CLL and lymphoma cells. PDCD4 downregulation was mediated by proteasomal degradation as it was inhibited by proteasome inhibitors in both primary CLL cells and B-lymphoma cell lines. In lymphoma cells, PDCD4 degradation was predominantly dependent on signaling via the AKT pathway. By contrast, in CLL cells, both ERK and AKT pathways contributed to PDCD4 down-regulation and dual inhibition using ibrutinib with either MEK1/2 or mTORC1 inhibition was required to fully reverse PDCD4 down-regulation. Consistent with this, dual inhibition of BTK with MEK1/2 or mTORC1 resulted in the strongest inhibition of BCR-induced MYC expression. This study provides important new insight into the regulation of mRNA translation in B-cell malignancies and a rationale for combinations of kinase inhibitors to target translation control and MYC expression