THE EMERGENCE OF FIBROMYALGIA FOLLOWING ACUTE COVID-19 INFECTION

BackgroundThe exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, different infections including hepatitis C virus, Human immunodeficiency virus and Lyme disease have already been implicated with the development of FM after their acute phase[1]. Imbalance between pro-inflammatory and anti-inflammatory cytokines has been suggested as a possible mechanism that facilitates the neuropathic pain[2].ObjectivesTo investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19) and to identify possible risk factors.MethodsWe performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors.ResultsThe study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52-72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4-5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM (OR 3.65, p=0.002). In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM (OR 1.19, p<0.001 and OR 0.92, p<0.001, respectively).ConclusionFM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM.References[1]Buskila D, Atzeni F, Sarzi-Puttini P. Etiology of fibromyalgia: the possible role of infection and vaccination. Autoimmun Rev. 2008;8: 41-43. https://doi.org/10.1016/j.autrev.2008.07.023[2]Amital M, Ben-Shabat N, Amital H, Buskila D, Cohen AD, Amital D. COVID-19 associated hospitalization in 571 patients with fibromyalgia—A population-based study. PLoS ONE. 2021:16: e0261772. https://doi.org/10.1371/journal.pone.0261772Acknowledgements:NIL.Disclosure of InterestsNone Declared.

REFERRAL BEHAVIOUR OF PRIMARY CARE DOCTORS TO RHEUMATOLOGY CLINIC IN MALAYSIA

BackgroundThe workload at rheumatology clinics have been growing relentlessly and an audit on new.referrals helps to identify referral behaviour of primary care doctors and improvement can be done by providing further training.ObjectivesTo audit on new referral cases to rheumatology clinic from 2020-2022 and to identify new cases with misdiagnosis for future training purpose.MethodsThis was a retrospective study. The medical records of all new referral to rheumatology clinic Hospital Sultan Ismail and Hospital Pakar Sultanah Fatimah from 1st January 2020 to 31th November 2022 were reviewed. The referral diagnosis and final diagnosis were identified and analysed.ResultsThere were total of 927 new cases referral throughout the 35 months during Covid-19pandemic. Majority of them were diagnosed to have rheumatoid arthritis (217/927)followed by systemic lupus erythematosus (190/927), psoriatic arthritis (147/927),gout (62/927), osteoarthritis (58/927), systemic sclerosis (25/927), ankylosing spondylitis (25/927), soft tissue rheumatism (24/927), Sjogren syndrome (24/927),mixed connective tissue disease (14/927), vasculitis (11/927), fibromyalgia (10/927),polymyositis (7/927) and miscellaneous (39/927).45 out of the new cases were diagnosed as unlikely rheumatic diseases. There were 29pending cases awaiting final diagnosis.212 of the referrals were identified as misdiagnosis with the highest as nodal osteoarthritis.(55/212) followed by unlikely rheumatic disease (43/212), soft tissue rheumatism (24/212),psoriatic arthritis (20/212), Sjogren syndrome (14/212), gout (8/212), rheumatoid arthritis (7/212), fibromyalgia (6/212), systemic lupus erythematosus (5/212), ankylosing spondylitis (4/212), mixed connective tissue disease (3/212), systemic sclerosis (2/212), polymyositis (2/212) and others (19/212): diffuse idiopathic skeletal hyperostosis, hypermobility syndrome, RS3PE syndrome, idiopathic uveitis, graft versus host disease, juvenile idiopathic arthritis, antiphospholipid syndrome, hypothyroidism, post streptococcal arthritis, prolapsed intervertebral disc, cerebrovascular disease, traumatic sternoclavicular joint subluxation, ledderhose disease, paraspinal muscle spasm and viral myalgia).ConclusionNodal osteoarthritis and soft tissue rheumatism can be great mimicker for inflammatory.arthritis and if wrongly diagnosed will lead to unnecessary anxiety or wrong treatment. More training is needed to improve clinical skills amongst primary care doctors.ReferencesNA.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

RHEUMATOLOGISTS BEWARE OF LOW ALP: A CASE OF HYPOPHOSPHATASIA MISDIAGNOSED AS FIBROMYALGIA, CAUSING LONG DIAGNOSTIC DELAY

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.

REAL WORLD EXPERIENCE OF MODERATE DISEASE ACTIVITY STATE (MDAS) RA PATIENTS OVER 4-YEAR FOLLOW-UP

BackgroundIn recent years despite improved therapies for RA, there is an increased awareness of persistent pain in people with RA. Before the pandemic we assessed a large group of patients with RA with comprehensive joint ultrasound (US) and for presence of fibromyalgia (FM) meeting 2010 ACR diagnostic criteria. When combinations of synovitis and/or FM were made we noted 4 groups of patients. As well as some with only FM, we also noted a group we believe had peripheral non-inflammatory pain, a new concept in RA. Here we investigate if these different groups change over time in our T2T routine care pathway.ObjectivesTo assess the progress and outcomes patients with RA with different well defined pain states during 4 years of follow up including the COVID19 pandemic.MethodsThe TITRATE-ULTRASOUND patient cohort categorised patients with RA into 4 groups depending on the presence or absence FM and the presence or absence of power doppler synovitis (PD, defined as positive PD signal in ≥2 joints in a 44 joint US). We identified 72 patients with active RA (DAS28 3.2 – 5.1) from this cohort with sufficient clinical data during the study period and collected the following data on each follow up encounter: visit type, treatment changes and disease activity measures. In the COVID19 pandemic follow up visits were largely virtual without the ability to collect physician assessed disease activity scores. Progress assessment was performed as to whether the patient had improved, no change or worse with a numerical value of +1, 0 and -1 at each visit to calculate a score tracking patient progress during the pandemic. Statistical analysis was performed using 1-way ANOVA to assess for difference between the 4 groups.Results72 patients with were assigned into the following categories: FM-PD-, 12 (peripheral pain group);FM-PD+,18;FM+PD-, 29;FM+PD+, 13. Table 1 shows baseline characteristics of the 4 groups and reveals no significant difference by ANOVA between the 4 groups in total visits, face to face visits, telephone visits, tender joint count, treatment escalations, steroid prescriptions, csDMARD prescriptions, and progress score. Biologic prescriptions did vary significantly between the groups (p = 0.009).Table 1.FM-PD- (n=12)FM-PD+ (n=18)FM+PD- (n=29)FM+PD+ (n=13)ANOVA p-valueFemale (n, %)10 (83%)13 (72%)24 (83%)13 (92%)CCP+ve (n, %)4 (33%)12 (67%)14 (48%)6 (46%)Disease duration (years) (mean, SEM)11.04 (2.676)16.19 (2.889)12.29 (1.709)16.23 (3.340)On csDMARD (n, %)11 (92%)15 (83%)24 (83%)10 (77%)On bDMARD (n, %)4 (33%)5 (28%)7 (24%)8 (61.5%)Baseline DAS28 (mean, SEM)4.412 (0.1641)4.344 (0.1177)4.192 (0.08910)4.366 (0.1461)Total visits (mean, SEM)11.67 (2.647)10.50 (2.031)8.724 (1.039)8.308 (1.407)0.533F2F visits (mean, SEM)7.909 (2.164)7.944 (1.924)5.793 (1.033)5.769 (1.311)0.5959Telephone visits (mean, SEM)4.417 (1.474)2.556 (0.3154)2.931 (0.3327)2.538 (0.6162)0.2268Tender joint count (mean, SEM)3.604 (1.101)3.506 (0.6177)5.376 (0.6899)4.603 (1.246)0.3179Treatment escalations (mean, SEM)2.917 (1.062)3.722 (1.028)2.000 (0.5526)1.615 (0.6257)0.2671Steroid prescriptions (mean, SEM)1.833 (0.7160)1.611 (0.5310)1.000 (0.3908)0.7692 (0.5329)0.503csDMARD prescriptions (mean, SEM)0.7500 (0.3046)0.7778 (0.2070)0.5185 (0.1634)0.3636 (0.2787)0.5789Biologic prescriptions (mean, SEM)0.3333 (0.2247)1.778 (0.6291)0.3793 (0.1257)0.3077 (0.2371)0.009Progress score (mean, SEM)-1.167 (1.461)0.6111 (0.3889)-0.1379 (0.2366)0.4615 (0.6265)0.2579ConclusionOver the follow-up period we show the management of RA patients without active power doppler synovitis or fibromyalgia did not differ significantly from other categories of patients. Similar numbers of visits, treatment escalations, csDMARDs and corticosteroid prescriptions were observed. This illustrates how it can be difficult to define the specific causes of disease activity without access to US. Despite similar management strategies, FM-PD- patients tended towards worse progress scores, suggesting a potential unmet need in such patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of In erestsMark Gibson: None declared, Nadia Ladha Hassan: None declared, L Bruce Kirkham Speakers bureau: Abbvie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, UCB, Grant/research support from: Eli Lilly.

ADVERSE EVENTS AFTER VACCINATION FOR SARS-CoV2 IN A CASE SERIES OF FIBROMYALGIA PATIENTS VERSUS HEALTHY CONTROLS

BackgroundFibromyalgia (FM) is a chronic widespread pain syndrome of unknown origin that leads to hypersensitivity for physical, chemical and/or psychic triggers. Vaccination, as an inflammatory stimulus and as a psychologically stressful act, could represent a challenge for these patients.ObjectivesWe aimed to investigate the incidence of adverse reactions after vaccination for Sars-Cov2 in a series of FM patients versus healthy controls.MethodsWe recruited 65 consecutive FM patients classified according to the 2016 ACR diagnostic criteria¹ (M/F: 5/60;mean age 53.6 +/-12.5 years), without other associated rheumatologic conditions, and 65 age/sex-matched healthy controls.All patients filled a questionnaire in order to investigate eventual adverse events occurring up to 6 months after administration of a Sars-Cov2 vaccine. The questionnaire was divided into two parts: the first part included the patient's demographic information, the vaccine type performed and the anamnestic data. In the second part, the individuals described all new symptoms or signs occurred after the first, the second or the third dose of Sars-Cov2 vaccine.ResultsOverall, FM patients reported a higher frequency of adverse events after Sars-Cov2 vaccination in comparison with healthy controls. In particular, 44/65 FM patients vs. 11/65 controls complained of exacerbation of diffuse pain (p<0.001). Fatigue, diarrhea, sweating, tingles, headache, dizziness, transient respiratory discomfort, and paroxysmal vision blurring were also more frequent in FM patients than controls (47/65 vs. 30/65, p=0.004;6/65 vs. 0/65, p=0.028;18/65 vs. 8/65, p=0.047;20/65 vs. 0/65, p<0.001;22/65 vs. 9/65, p=0.013;21/65 vs. 5/65, p<0.001;10/65 vs 1/65, p=0.009;17/65 vs. 2/65, p< 0.001, respectively).No significant difference between FM and the control group as regards fever was reported (24/65 vs. 30/65;p=0.7).Interestingly, swelling at the injection vaccine site was more commonly reported in controls (9/65 vs. 20/65;p=0.034).Finally, one case of Bell's palsy was registered in the FM series while one case of myocarditis in the control group.ConclusionFM patients showed an increased frequency of adverse events to Sars-Cov2 vaccination compared to healthy controls. In particular, all the symptoms reported seemed to be associated with the functional hypersensitivity that characterizes FM.Reference[1]Wolfe F, et Al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016 Dec;46(3):319-329.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Evaluation of pain, disease activity, anxiety, depression, and neuropathic pain levels after COVID-19 infection in fibromyalgia patients.

BACKGROUND: Psychological stressors may cause mental disorders such as anxiety, depression, and post-traumatic stress disorders and fibromyalgia (FM) patients could be affected by these stressors. AIM: To evaluate pain, disease activity, anxiety, depression, and neuropathic pain levels after COVID-19 infection in patients with FM. METHODS: According to the 2016 American College of Rheumatology (ACR) criteria, fifty-seven patients with FM alone and 77 patients with FM and recovering from COVID-19 infection were recruited to the study (group 1: patients with FM alone and group 2: patients with FM and recovering from COVID-19). Demographic and clinical characteristics were recorded. The pain level was determined by the Numerical Rating Scale (NRS), the pain regions by the Widespread Pain Index (WPI) of the 2016 ACR criteria, the severity of the symptoms by the Symptom Severity Scale (SSS) of the 2016 ACR criteria, the disease activity by the Fibromyalgia Impact Questionnaire (FIQ), the anxiety and depression levels by the Hospital Anxiety and Depression Scale (HADS), and the neuropathic pain level by Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale (LANSS). RESULTS: Age, height, weight, Body Mass Index (BMI), and the duration of FM diagnosis were similar in both groups (p > 0.05). NRS, FIQ, HADS depression scale, and SSS and LANSS scores were similar between group 1 and group 2 (p > 0.05). HADS anxiety score and WPI were significantly increased in group 2 (p = 0.026 and p = 0.024 respectively). CONCLUSIONS: Anxiety and widespread pain levels were higher in patients with FM and recovering from COVID-19 infection.

Rheumatology and Long COVID: lessons from the study of fibromyalgia.

Rheumatology, such as other subspecialties, has both a unique perspective to offer as well as an evolving role to play in the global COVID-19 pandemic. Our field has already contributed meaningfully to the development and repurposing of many of the immune-based therapeutics which are now standard treatments for severe forms of the disease as well as to the understanding of the epidemiology, risk factors and natural history of COVID-19 in immune-mediated inflammatory diseases. Still in evolution is our potential to contribute to burgeoning research efforts in the next phase of the pandemic: the syndrome of postacute sequelae of COVID-19 or Long COVID. While our field brings many assets to the study of Long COVID including our expertise in the investigation of chronic inflammation and autoimmunity, our Viewpoint focuses on the strong similarities between fibromyalgia (FM) and Long COVID. While one can speculate on how embracing and confident practising rheumatologists already are regarding these interrelationships, we assert that in the emerging field of Long COVID the potential lessons from the field of fibromyalgia care and research have been underappreciated and marginalised and most importantly now deserve a critical appraisal.

Post-Acute COVID-19 Joint Pain and New Onset of Rheumatic Musculoskeletal Diseases: A Systematic Review.

As the number of reports of post-acute COVID-19 musculoskeletal manifestations is rapidly rising, it is important to summarize the current available literature in order to shed light on this new and not fully understood phenomenon. Therefore, we conducted a systematic review to provide an updated picture of post-acute COVID-19 musculoskeletal manifestations of potential rheumatological interest, with a particular focus on joint pain, new onset of rheumatic musculoskeletal diseases and presence of autoantibodies related to inflammatory arthritis such as rheumatoid factor and anti-citrullinated protein antibodies. We included 54 original papers in our systematic review. The prevalence of arthralgia was found to range from 2% to 65% within a time frame varying from 4 weeks to 12 months after acute SARS-CoV-2 infection. Inflammatory arthritis was also reported with various clinical phenotypes such as symmetrical polyarthritis with RA-like pattern similar to other prototypical viral arthritis, polymyalgia-like symptoms, or acute monoarthritis and oligoarthritis of large joints resembling reactive arthritis. Moreover, high figures of post-COVID-19 patients fulfilling the classification criteria for fibromyalgia were found, ranging from 31% to 40%. Finally, the available literature about prevalence of rheumatoid factor and anti-citrullinated protein antibodies was largely inconsistent. In conclusion, manifestations of rheumatological interest such as joint pain, new-onset inflammatory arthritis and fibromyalgia are frequently reported after COVID-19, highlighting the potential role of SARS-CoV-2 as a trigger for the development of autoimmune conditions and rheumatic musculoskeletal diseases.

Girft in Action: Advanced Practice Physiotherapist and Advanced Practice Nurse Expertise Provides Valuable Triage and Assessment Clinics for Non-Urgent Rheumatology Referrals

Background/Aims Rheumatology referrals classified as non-urgent/routine are commonly non-inflammatory conditions or medically non-urgent and can have significant waiting times for appointments. These waits were further escalated by the COVID-19 pandemic. Early intervention for noninflammatory conditions can be crucial to good outcomes and long wait-times can have significant adverse impacts while appropriate care pathways are determined. Recent UK GIRFT recommendations include using non-medical health professional expertise in assessment and management pathways to support right place, right time, right care. This study evaluated effectiveness, impacts and patient experiences of Advanced Practice Physiotherapist (APP) and Advanced Practice Nurse (APN) Triage and Assessment Clinics for routine new referrals. Methods The non-urgent/routine referral waiting list was e-triaged by a Rheumatology APP and APN supported by clinical record searches. Patients were contacted by telephone to update on clinical status and appointment requirements determined. Triage criteria were applied to determine new referrals suitable for APP and APN Rheumatology clinics, which included low likelihood of inflammatory disease or new referrals for known diagnosis/stable conditions. Clinics were undertaken with collocated Consultant clinical supervision. Assessment findings were discussed and management agreed, or seen if needed. With waiting list attrition, clinics were expanded to include Consultantdetermined stable condition reviews and follow-up reviews for nonsuspected inflammatory disease. Results At 01 July 2021, 214 new routine referrals were waiting a Consultant appointment (n=103 over 2yrs). Since service initiation, clinic outcomes to date include: 69% (n=243/358) new routine referrals discharged to GP or directed to right pathway with information, advice and self-management resources;8% (n=29) escalated to urgent;3% (11/358) with medical complexity remained on Consultant waitlist. Most common presentations seen included: Osteoarthritis (general or hand);Back and other spinal pain;Fibromyalgia;Persistent Fatigue and Widespread Pain;JHS/hEDS;Positive ANA without clinical features;Musculoskeletal conditions- other. To date, no patients have been re-referred and 329 new patient and 89 follow-up Consultant direct consultations have been spared. There is currently no wait-time for non-urgent/routine appointments. Patient experience feedback on the service has offered a 100% recommendation to continue and expressed highly positive experiences with the MDT approach. Patients value the breadth of expertise and care support, and the timely, thorough and professional service provided. Conclusion Rheumatology non-urgent/routine new referrals with low probability of underlying autoimmune conditions may be effectively and efficiently managed in a collaborative model using an advanced practice physiotherapist and nurse. This innovation has expanded a traditionally medical pathway to an MDT model utilising value-adding nonmedical expertise in service delivery. It has enhanced interdisciplinary learning and is a valued, collaborative approach to patient care. The initiative provides support to GIRFT recommendations of using an MDT skill-set to support improved patient access, service efficiencies and earlier intervention.

Intestinal microbiota, pain, dementia

The review is dedicated the interconnection between neurodegenerative diseases, chronic pain and gut microbiota's structure and function. The gut microbiota's role in gut-brain axis, neuroimmune interaction is considered. The modern data about gut dysbiosis in Alzheimer disease, Parkinson disease, osteoarthrosis, neuropathic pain in COVID infection, muscular-skeletal pain in fibromyalgia, irritable bowel syndrome et cetera are provided. The gut microbiota's modification by means of pre and probiotics in combination with medicines and diet modification can be used for the treatment of chronic pain and dementia.Copyright © T.M. MANEVICH.

Trends for Opioid Prescriptions and the Impact of the Covid-19 Pandemic among Patients with Rheumatic and Musculoskeletal Diseases between 2006 and 2021

Background/Aims Rheumatic and musculoskeletal diseases (RMDs) are some of the most common indications for prescribed opioids. It is unclear how opioid prescribing has changed in the UK for RMDs, especially during the COVID-19 pandemic with limited healthcare access and cancelled elective-surgical interventions, which could impact prescribing in either direction. We aimed to investigate trends in opioid prescribing in RMDs and assess the impact of the pandemic in the UK. Methods Adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), systemic lupus erythematosus (SLE), osteoarthritis (OA) and fibromyalgia with opioid prescriptions between 01/Jan/2006-31/Aug/2021 without prior cancer in the UK Clinical Practice Research Datalink (CPRD) were included. We calculated ageand gender-standardised yearly rates of people with opioid prescriptions between 2006-2021, and identified change points in trends by checking whether the rate of change of standardised rates crossed zero. For people with opioid prescriptions, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006-2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of people with opioid prescriptions between Jan/2015-Aug/2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. Results We included 1,313,519 patients: 36,932 with RA, 12,649 with PsA, 6,811 with AxSpA, 6,423 with SLE, 1,255,999 with OA, and 66,944 with fibromyalgia. People with opioid prescriptions increased from 2006 to 2018 for OA, to 2019 for RA, AxSpA and SLE, to 2020 for PsA, and to 2021 for fibromyalgia, and all plateaued/decreased afterwards. OA patients on opioids increased from 466.8/10,000 persons in 2006 to a peak of 703.0 in 2018, followed by a decline to 575.3 in 2021. From 2006 to 2021, there was a 4.5-fold increase in fibromyalgia opioid users (17.7 vs.78.5/10,000 persons). In this period, MME/day increased for all RMDs, with the highest for fibromyalgia (>=35). During COVID-19 lockdowns, RA, PsA and fibromyalgia showed significant changes in the trend of people with opioid prescriptions. With a decreasing trend for RA (-0.001,95%CI=-0.002,-0.001) and a decreasing-to-flat curve for PsA (0.0010,95%CI=0.0006,0.0015) prepandemic until Feb/2020, the trends changed by -0.005 (95%CI=-0.008,-0.002) for RA and -0.003 (95%CI=-0.006,-0.0003) for PsA, leading to steeper decreasing trends during the pandemic (Mar/2020-Aug/2021). Fibromyalgia, conversely, had an increasing trend (0.009,95%CI=0.008,0.009) pre-pandemic, and this trend started decreasing by -0.009 (95%CI=-0.011,-0.006) during the pandemic. Conclusion The plateauing/decreasing trend of people with opioid prescriptions in RMDs after 2018 may reflect the efforts to tackle the rising opioid prescribing in UK primary care. Of all RMDs, fibromyalgia patients had the highest MME/day throughout the study period. COVID-19 lockdowns contribute to fewer people on opioids for most RMDs, reassuring there was no sudden increase in opioid prescribing during the pandemic.

42nd Scientific Meeting of the German Society for Magnesium Research

The proceedings contain 23 papers. The topics discussed include: Mg and skeletal system: a link to osteoporosis and osteoarthritis;a putative impact of IL-6 on the expression of magnesiotropic genes through the activation of the JAK/STAT3 pathway;magnesium in pain therapy - historical notes and current aspects;Alzheimer's-associated variant rs708727 might be connected to dementia in Parkinson's disease;effect of magnesium citrate supplementation on the brain tissue of patients with Miyoshi dysferlinopathy measured by 31P magnetic resonance spectroscopy;clinical status of magnesium implants;Ionized magnesium: update 2022;magnesium in the treatment of selected types of muscular dystrophy;magnesium speciation analysis in blood serum;epigenetically-induced modulation of the HPA axis might improve resilience to chronic stress;magnesium status in patients with fibromyalgia syndrome;and post-covid-syndrome and transient microvascular pathology in pulse-wave-analysis - association with Mg/Ca ratio and magnesium therapy-options.

British Neuropsychiatry Annual Meeting 2021

The proceedings contain 40 papers. The topics discussed include: sex, bugs microwave attacks: how bad science, mating insects psychogenic illness created an international incident with Cuba;Covid-19 and neuropsychiatry;clinical update on delirium;fibromyalgia and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS): an interoceptive predictive coding model of pain and fatigue expression;when the spark goes out: the neurology of apathy and motivation;is subjective cognitive decline (SCD) a better marker of susceptibility to functional cognitive disorder (FCD) than to neurodegeneration?: the caerphilly prospective study;temporal and spectral dynamics of reward and risk processing in the amygdala revealed with stereo-EEG recordings in epilepsy;a systematic review of extra-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis;and stimulation of the ventrolateral prefrontal cortex speeds up evidence accumulation in conflictual-uncertain environments.

Impact of medical disorders

Physicians have observed the connection between many medical disorders and sleep for centuries. Our current understanding of the interplay between sleep and sickness has advanced as we have grown in our knowledge of sleep physiology. There is often a bidirectional relationship between the two. It is commonly understood that illness may cause poor sleep. Still, it is becoming more apparent that poor sleep can negatively affect various physiologic processes in other organ systems. As we work to improve our patient's overall health, an understanding of this interplay will be vitally important for clinicians and researchers alike. © 2023 Elsevier Inc. All rights reserved

Centering Group Treatment for Women With Interstitial Cystitis/Bladder Pain Syndrome: A Prospective, Parallel-Group Cohort Study

Importance: Women with interstitial cystitis/bladder pain syndrome (ICBPS) face isolation and treatment challenges. Group medical visits using Centering models have successfully treated other conditions but have not been explored in ICBPS. Objective(s): This study aimed to describe ICBPS pain and symptom control comparing standard treatment alone versus standard treatment augmented with Centering visits. Study Design: This prospective cohort study recruited women with ICBPS receiving standard care (control) or standard care augmented with group Centering. We administered validated questionnaires at baseline and monthly for 12 months. The primary outcome was change in the pain numerical rating scale, with Patient-Reported Outcomes Measurement Information System Pain Interference Scale and Bladder Pain/Interstitial Cystitis Symptom Score change as secondary measures. Result(s): We enrolled 45 women (20 Centering, 25 controls). Centering had significantly better numerical rating scale pain scores at 1 month (mean difference [diff], -3.45) and 2 months (mean diff, -3.58), better Patient-Reported Outcomes Measurement Information System Pain Interference Scale scores at 1 month (mean diff, -10.62) and 2 months (mean diff, -9.63), and better Bladder Pain/Interstitial Cystitis Symptom Score scores at 2 months (mean diff, -13.19), and 3 months (mean diff, -12.3) compared with controls. In modeling, treatment group (Centering or control) and educational levels were both associated with all the outcomes of interest. Beyond 6 months, there were too few participants for meaningful analyses. Conclusion(s): Women with ICBPS participating in a Centering group have, in the short term, less pain, pain interference, and ICBPS-specific symptoms than patients with usual care alone. Larger studies with more follow-up are needed to determine if this treatment effect extends over time.Copyright © 2022 American Urogynecologic Society. All rights reserved.

"Long COVID-19" and viral "fibromyalgia-ness": Suggesting a mechanistic role for fascial myofibroblasts (Nineveh, the shadow is in the fascia).

The coronavirus pandemic has led to a wave of chronic disease cases; "Long COVID-19" is recognized as a new medical entity and resembles "fibromyalgia" which, likewise, lacks a clear mechanism. Observational studies indicate that up to 30%-40% of convalescent COVID-19 patients develop chronic widespread pain and fatigue and fulfill the 2016 diagnostic criteria for "fibromyalgia." A recent study suggested a theoretical neuro-biomechanical model (coined "Fascial Armoring") to help explain the pathogenesis and cellular pathway of fibromyalgia, pointing toward mechanical abnormalities in connective tissue and fascia, driven by contractile myo/fibroblasts and altered extracellular matrix remodeling with downstream corresponding neurophysiological aberrations. This may help explain several of fibromyalgia's manifestations such as pain, distribution of pain, trigger points/tender spots, hyperalgesia, chronic fatigue, cardiovascular abnormalities, metabolic abnormalities, autonomic abnormalities, small fiber neuropathy, various psychosomatic symptoms, lack of obvious inflammation, and silent imaging investigations. Pro-inflammatory and pro-fibrotic pathways provide input into this mechanism via stimulation of proto/myofibroblasts. In this hypothesis and theory paper the theoretical model of Fascial Armoring is presented to help explain the pathogenesis and manifestations of "long COVID-19" as a disease of immuno-rheumo-psycho-neurology. The model is also used to make testable experimental predictions on investigations and predict risk and relieving factors.

Post-COVID-19 fibromyalgia syndrome: A report of two case

COVID-19 is a viral infection caused by SARS-CoV-2 that primarily targets the respiratory system. COVID-19 may be followed in some patients by post-COV-ID-19 syndrome, fatigue, anxiety, and musculoskeletal pain. These symptoms may be associated with other symptoms, resulting in a constellation of symptoms consistent with fibromyalgia syndrome (FMS). Two patients were evaluated at the rheumatology outpatient clinic for diffuse persistent musculoskeletal pain after COVID-19 infection. Patients presented with generalized musculoskeletal pain, fatigue, anxiety, depression, headache, hand paresthesia, and non-restorative sleep. General examination and various laboratory investigations, including autoimmune profile and radiological investigation, were normal. After examining eighteen tender points, both patients fulfilled the 1990 ACR classification criteria for FMS. Post-COVID-19 FMS should be considered during the management of post-COVID-19 syndrome to alleviate pain and prevent worsening of symptoms during the COVID-19 pandemic.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Using a Single Irb for Nih-Funded Multisite Trials

As clinical trials evolve, the oversight by Institutional Review Boards (IRBs) has also evolved to meet everexpanding needs for both efficiency and changing regulatory requirements in the protection of human subjects. The most significant regulatory change to occur was the change to the Revised Common Rule Research Provision (45 CFR 46.114(b)) that went into effect on 20 January 2020, requiring all cooperative research subject to the Common Rule to use a single Institutional Review Board (sIRB) to review the research. Since the Common Rule affects all federally funded research, clinical trialists performing multicenter trials using federal grants are now required to use an sIRB instead of individual IRBs at each research site in their trials. For those multicenter trialists, using an sIRB offers efficiencies in time and effort which can aid in bringing trial results to fruition both faster and at a lower cost while still providing protection to human subjects. While commercial sIRBs have been available for many years, sIRBs placed at academic institutions and health care systems are relatively new. They can offer the benefit of lower cost for trialists within an institution, and better overall trial management by having more frequent communication and discussion regarding trial issues as well as improved safety management through aggregate safety review. They can also offer increased speed of research review with cooperative planning between trialist and the sIRB representatives. This session will focus on the use of sIRBs from various perspectives to give the view from an academic sIRB, from end users of both an academic sIRB and a health system IRB, and guidance from a clinical regulatory specialist regarding maintaining a trial master file while using an sIRB. Mr. Jarrod Feld from the University of Iowa will present from his perspective as the External IRB Coordinator at the University of Iowa. Mr. Feld coordinates reliance and compliance for University of Iowa human research studies which use the University of Iowa Institutional Review Board as their sIRB, and studies where Iowa relies on another institutional IRB. Mr. Feld also provides guidance to investigators on using an sIRB. Using his experience, Mr. Feld will outline the nature of reliance agreements, discuss working with a range of local IRBs to develop understanding regarding the reliance program and outline best practices for using an sIRB, and discuss enhanced safety management oversight when using an sIRB for large multisite trial. Ms. Tina Neill-Hudson from the University of Iowa will present from her experience as the sIRB Liaison for both the Acute to Chronic Pain Signature (A2CPS) Consortium, an NIH (National Institutes of Health)- funded multisite observational trial, and the Fibromyalgia and TENS in Physical Therapy Study (FM TIPS) study, an NIH-funded embedded pragmatic clinical trial. Ms. Neill-Hudson works with relying sites on completing the necessary regulatory documents needed for reliance agreements and sIRB approval. Ms. Neill-Hudson will discuss the process for obtaining reliance for institutions who may or may not have local IRB oversight and provide examples of specific steps and procedures for obtaining sIRB approval in a timely manner. Ms. Neill-Hudson will speak to the importance of having an sIRB liaison on the study team and the use of SMART IRB. Ms. Catherine Gladden from MassGeneral Brigham will present on using an sIRB for multicenter NIHfunded trials. Ms. Gladden will discuss the use of a Consortium-level reliance agreement and role of the local IRBs. Ms. Gladden oversees the sIRB liaison team at the Coordinating Center for the NeuroNEXT Network and works with the sIRB and local IRBs to ensure local policies and requirements are followed while maintaining compliance with the sIRB and the NeuroNEXT reliance agreement. Ms. Gladden will be discussing best practices for using an sIRB in a multicenter trial and discuss the experience of using an sIRB in the safety management plan. Ms. Cynthia Diltz from the University of Iowa wi l present on the topic of managing a trial master file while using an sIRB. Ms. Diltz will speak on her experience with electronic trial master files versus hard copy master files, and in using commercial software for trial master file management. Using an electronic trial master file is a necessity in the scheme of using an sIRB to assist sponsors and individual clinical research sites to view Institutional Review Board documents in real time and to provide a single storage location for documentation of Institutional Review Board approvals and activities such as continuing review. This session is timely due to the change to the Common Rule mandating the use of an sIRB for all research subject to the Common Rule, which has the most significant impact on trialists at academic institutions and health care systems. In an era of the need for timely study results for use in addressing urgent public health policy concerns, using an sIRB is becoming a necessity. The speed with which clinical trials need to be managed by an IRB has accelerated during recent public health care crises, notably the COVID-19 pandemic. In addition, it is likely that there will be changes to local IRBs as the norm becomes using an sIRB for any research subject to the Common Rule. Investigators and clinical site staff will require education on the evolution of human subject's protection and research review happening at an sIRB instead of within their local IRBs, and assistance in understanding the process and planning for success will be crucial.

Impact of coronavirus disease 2019 (COVID-19) pandemic on attitude, behavior, and mental health of patients with rheumatic diseases

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has become a global health, social, and economic crisis. Healthcare professionals, patients, healthy individuals, and the whole community are under inevitable psychological pressure which may cause different psychological problems as fear, anxiety, depression, and insomnia. The aim was to assess the impact of the COVID19 pandemic on the attitude, behavior, and mental health of rheumatic patients and to compare them with healthy individuals. This is a case-control study, 360 participants were included and divided into a patient group composed of 180 patients with rheumatic diseases, and a control group composed of 180 healthy people. Data were collected via a self-administered structured questionnaire designed on Google forms. It was sent to participants via social networks and emails to different rheumatic patients and healthy individuals. Mental health was measured by the 5-item Brief Symptom Rating Scale (BSRS-5).ResultsThe mean age of cases and control were (35.05 ± 8.79 vs 34.56 ± 9.06) years. In comparing attitudes and behavior toward COVID 19, there was a statistically significant difference (p ≤ 0.05) between both groups regarding washing hands, going outdoors, wearing masks and gloves outdoors, and staying in their rooms. Patients depended mainly on telehealth more than usual where about 50% used either phone calls, internet or sent their relatives to their physicians;moreover, 20% did not contact their physicians at all the past few months. There was a statistically significant difference (p ≤ 0.05) between both groups regarding feeling angry/irritated, inferior and insomniac. The BSRS-5 total score and being defined as a psychiatric case (according to the BSRS-5 scale) also differed significantly between patients and controls. Systemic lupus erythematosus (SLE) patients showed more adherence to their medications and stayed mostly at home and they have higher BSRS scores.ConclusionPatients with rheumatic diseases show comparable degrees of anxiety and depression to healthy individuals, but higher distress symptoms and panic in the form of anger, irritability, and insomnia. They have a significantly higher sense of inferiority and a higher total BSRS compared to controls. SLE patients show more adherence to their medications and stay mostly at home as a reflection of feeling more vulnerable. Moreover, they have higher degrees of psychological affection in the form of higher BSRS scores. Abandoning drug purchasing without medical prescription is necessary in Egypt to protect our patients from unnecessary drug shortages adding to their fear and anxiety. Mental health should be addressed in the same manner we deal with the infectious disease itself, being of no less importance. Mental health professionals, social workers, and support groups need to provide psychological support to vulnerable populations, including patients with rheumatic diseases. Rheumatologists should be aware of the need for psychiatric consultation for their patients whenever necessary.

Covid-19 Fatigue: Diagnosis and Treatment for the Osteopathic Physician

The novel coronavirus disease 2019 (COVID-19) has given rise to a global pandemic, as well as a multitude of long-term sequelae that continue to perplex physicians around the world, including in the United States. Among the most common and impactful long-haul symptoms experienced by survivors is COVID-19 fatigue. This review will use long COVID-19, post-acute COVID-19 syndrome (PCS), and PostAcute Sequelae of COVID-19 (PASC) as synonymous terms to refer to the chronic symptomatology;chronic fatigue associated with PASC will be referred to as COVID-19 fatigue. While the knowledge and research on the exact pathophysiological mechanisms involved in the disease is still limited, parallels have been drawn between fatigue as a component of long COVID-19 and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Current studies suggest applying principles of pathophysiology, diagnosis, and treatment similar to those for ME/CFS in order to aid in managing chronic fatigue in COVID-19 survivors, particularly in the primary care setting. The osteopathic family physician can use the proposed pharmacologic agents, along with osteopathic manipulative treatment (OMT), as therapeutic modalities that can be tailored to each patient's unique case. Nevertheless, research on proven successful treatments is still scarce. For that reason, it is essential that COVID-19 fatigue is recognized early, especially since its longitudinal impacts may be debilitating for many. This review of the available literature on COVID-19 fatigue aims to help provide quality care and lessen the disease burden experienced by patients.Copyright © 2023 by the American College of Osteopathic Family Physicians. All rights reserved.