ABSTRACT
BackgroundHypophosphatasia(HPP), a rare, inherited metabolic disease featuring low serum alkaline phosphatase (ALP) activity due to ALPL (encoding tissue non-specific alkaline phosphatase) gene mutation[1,2]. A wide-ranging clinical spectrum is often seen due to defective mineralisation affecting teeth, bones, joints and muscles[1]. This disease has a prevalence of 1/6370 in Europe and is often misdiagnosed and underdiagnosed with a diagnostic delay of more than ten years[1] The treatment is often supportive for milder cases and enzyme replacement therapy in severe cases.ObjectivesTo share this case to raise awareness among Rheumatologists.MethodsThis 58-year-old Caucasian female had her first HPP symptom as early eruption of deciduous teeth, along with recurrent dental infections and gum problems. She was diagnosed with flat feet at age five, had a big toe fracture at sixteen, followed by a metatarsal fracture. She experienced leg muscle cramps and aches, affecting her performance in sport during school life.At the age of thirty she began noticing weakness in arms and legs, which progressed over the years. She faced significant early morning stiffness along with painful ribs, hips, knees, shoulders, and small joints of feet when walking.She was diagnosed with Fibromyalgia at the age of forty-four. The following ten years she met numerous specialists including rheumatologist, pain specialist and physiotherapists. She was also diagnosed with early osteoarthritis, pernicious anaemia, hyperlipidemia, functional neurological syndrome, and central sensitization syndrome. She had multiple trials of steroids and opioids, all of which were stopped either due to side effects or inefficiency.A major flare of symptoms five years ago rendered her bedbound for three months, following which a chemical pathologist noticed a persistent low ALP levels and decided to investigate for HPP. It took another four years to complete these investigations due to the coronavirus pandemic.Currently, she is unable to weight bear or climb stairs and must stay indoors or in bed during flareup. She moved into a ground floor flat at the age of 54 and use a walking stick occasionally. By 58, she is unable to work and had given up her own business due to pain, weakness, and disability.ResultsOn clinical assessment, her height is 160 cm, faced difficulty getting up from chair, has an antalgic waddling gait, with a 6-minute walking distance of 60 metre, stopped after three minutes, and had a Brief Pain Inventory pain severity score of 7/10. Her ALP level is 24 U/L and PLP/PA ratio is 18.8 (ref < 5), and genetic testing showed heterozygous missense variant of ALPL gene mutation.ConclusionIt took more than forty years to reach a conclusive diagnosis of childhood onset HPP. Low ALP level is a signature of HPP and warrants investigations. Diagnosis can be challenging due to the rareness and variable presentation, however recognition of HPP features is crucial for timely referral, optimal disease management and potential improvement in quality of life.References[1]Högler W, Langman C, Gomes da Silva H, Fang S, Linglart A, Ozono K, Petryk A, Rockman-Greenberg C, Seefried L, Kishnani PS. Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC Musculoskelet Disord. 2019 Feb 14;20(1):80. doi:10.1186/s12891-019- 2420-8. PMID: 30764793;PMCID: PMC6376686.[2]Injean P, Lee S, Downey C. Hypophosphatasia May Be Misdiagnosed as Fibromyalgia: A Single Center Experience []. Arthritis Rheumatol. 2020;72 (suppl 10). https://acrs.org//hypophosphatasia-may-be-misdiagnosed-as- ibromyalgia-a-single-center-experience/. Accessed January 14, 2023.[3]Lefever E, Witters P, Gielen E, Vanclooster A, Meersseman W, Morava E, Cassiman D, Laurent MR. Hypophosphatasia in Adults: Clinical Spectrum and Its Association With Genetics and Metabolic Substrates. J Clin Densitom. 2020 Jul-Sep;23(3):340- 48. doi: 10.1016/j.jocd.2018.12.006. Epub 2018 Dec 21. PMID: 30655187.Acknowledgements:N L.Disclosure of InterestsNone Declared.
ABSTRACT
Background/Aims Baricitinib is the most common Janus Kinase inhibitor (JAKi) used in the treatment of rheumatological conditions. Whilst randomised controlled trials have demonstrated the efficacy and safety profile of baricitinib, real-world data on the experience of JAKi use in clinical practice is lacking. The aim of this analysis was to evaluate baricitinib use in a real-world patient population in South London. Methods We looked at two rheumatology departments in South London (St George's Hospital;a tertiary teaching centre and Kingston Hospital;a district general hospital). All patients prescribed baricitinib between January 2017 to June 2022 were included. A retrospective assessment of electronic patient notes was performed to evaluate disease activity (determined by DAS-28 scores at baseline, 3-6 months and presently);adverse effects including side effects, rates of and reasons for discontinuation;and prescribing practice, including previous use of other biological disease modifying anti-rheumatic drugs (bDMARDs). Baseline data including age, gender, co-morbidities and rheumatological diagnoses were also included. Results 233 patients were included in this evaluation, with seropositive rheumatoid arthritis being the most common diagnosis (58%) and with a significant female population (87%). Baricitinib improved average DAS-28 scores from 5.75 (range 3.57-8.3) at baseline to 3.23 (range 0.28-7.49) at 3-6 months post-baricitinib, with the most recent DAS-28 score of 2.90 (range 0.56-6.77). Rates of adverse effects were low as shown in Table 1. Baricitinib was discontinued in 60/233 patients, with average duration to discontinuation of 9.5 months. The most common reasons for discontinuation were: ineffective disease control (28/60), recurrent bacterial infection (5/60), deranged liver function (3/60) and venous thromboembolism (2/60). Eight patients died whilst taking baricitinib. Where documented, the causes of death were Covid-19 (4/8) and malignancy (1/8). 110 out of 233 patients had received other bDMARDs before starting baricitinib. Documented reasons for baricitinib choice over tumour necrosis factor inhibitors (TNFi) included: previous lack of response to TNFi (89/233), contra-indication to TNFi (11/233) and preference of oral route (10/ 233). Conclusion Our real-world study of JAKi use shows that baricitinib is efficacious in the treatment of rheumatological conditions. Moreover, baricitinib is well tolerated, with low rates of adverse effects and subsequent discontinuation. (Table Presented).
ABSTRACT
Media as the core source of information and knowledge disperse in the society, its effect on the learning, understanding and analysing about the society in the human minds and cognition is certainly impacted. In focal to the visual media such as advertisement, movies, video etc., it enunciates and indicates a high level of learning process and social learning. Media has a huge impact on the different aspects of cognition in the population, especially on the age category of teenagers and young adults. With the current situation of covid 19, there has been a paradigm shift within the educational sector, forcing visual media as the key source of education and learning, with many countries utilizing remote learning or digital learning to cope with the current educational crisis. This study therefore aims to investigate and understand the impact of the visual media and different video learning platforms in improvement of the social cognition and learning among student. Questionnaire survey method was employed as a tool to collect data from the sample of 250 students between the age group of 16 – 25 and a sample of 155 teachers with the experience of 1 -10 + years in the field of education across UAE and India. The result indicates that the student population showcase a keen interest and participation on the information and knowledge dispersed through screens such as movies and presentation rather than the content published such as newspaper and books. It helps students foster self-awareness, cultural value, cognitive skills and moral wellbeing with the help of visual media. © 2021 Institute of Physics Publishing. All rights reserved.