Effectiveness of eHealth therapeutic education interventions in the management of fibromyalgia: protocol for a systematic review and meta-analysis.

INTRODUCTION: Non-pharmacological approaches have shown promising results in improving symptoms and quality of life of patients with fibromyalgia. However, these approaches may not be easily accessible or feasible for everyone. eHealth interventions may offer a more convenient and cost-effective approach to reach a wider range of patients with fibromyalgia and improve their outcomes. As eHealth tools become more prevalent in clinical practice, it is crucial to understand their effectiveness, limitations and how they can be integrated into standard care to optimise clinical outcomes. This systematic review aims to evaluate the effectiveness of eHealth therapeutic education interventions in managing fibromyalgia. METHODS AND ANALYSIS: Randomised controlled trials including eHealth therapeutic education interventions for individuals ≥18 years old with fibromyalgia, published in English or Spanish, will be retrieved by searching the databases PubMed, CINAHL Plus, EMBASE, Scopus, ISI Web of Science, PsycINFO and the Cochrane Central Register of Controlled Trials. Covidence software will be used for the selection of studies and data extraction. The risk of bias and the certainty of evidence will be assessed using the Cochrane Risk of Bias Assessment tool. We plan to perform a meta-analysis contingent on the number of studies retrieved and the interstudy heterogeneity, which will be explored with I2 statistics. ETHICS AND DISSEMINATION: This protocol and the subsequent systematic review will not collect individual-level data and do not require approval by an ethical committee. We intend to disseminate the study results via peer-reviewed scientific journals and relevant (inter)national conferences. PROSPERO REGISTRATION NUMBER: CRD42022343373.

Fibromyalgia: one year in review 2022.

Fibromyalgia syndrome (FM) is a chronic widespread pain syndrome characterised by fatigue, sleep disturbances and many idiopathic pain symptoms. The aim of this review is to describe and summarise the most recent findings concerning the diagnosis, aetiopathogenesis and treatment of fibromyalgia syndrome published between January 2021 and January 2022 and appearing on PubMed database. In particular, last year's literature focused on the impact of COVID-19 pandemic on FM patients, on new aetiopathogenetic horizons and the last conclusions about pharmacological and non-pharmacological interventions.

Could the fibromyalgia syndrome be triggered or enhanced by COVID-19?

Fibromyalgia (FM) is a complex disease with an uncertain aetiology and intricate pathophysiology. Although its genesis is not fully explained, potential environmental factors, such as viral infections might trigger FM or worsen patients' clinical outcomes. The SARS-CoV-2 virus may affect central and peripheral nervous systems, leading to musculoskeletal, neurological, and psychological disturbances. These symptoms might persist at least 12 months beyond the recovery, often referred to as post-COVID syndrome, which resembles FM syndrome. In this sense, we argued the potential consequences of COVID-19 exclusively on FM syndrome. First, we have described post-COVID syndrome and its painful symptoms. Afterwards, we argued whether FM syndrome could be triggered or enhanced by COVID-19 infection or by numerous and persistent stressors imposed daily by the pandemic setting (isolation, uncertainty, depression, mental stress, generalized anxiety, and fear of the virus). In addition, we have demonstrated similarities between pathophysiological mechanisms and cardinal symptoms of FM and COVID-19, speculating that SARS-CoV-2 might represent a critical mediator of FM or an exacerbator of its symptoms once both syndromes share similar mechanisms and complaints. Therefore, pharmacologic and non-pharmacological approaches commonly used to treat FM could serve as strategic therapies to attenuate painful and neurological manifestations of post-COVID syndrome. Although it is still theoretical, clinicians and researchers should be alert of patients who develop symptoms similar to FM or those who had their FM symptoms increased post-COVID to manage them better.

Covid-19 and post-acute sick leave: a hybrid register and questionnaire study in the adult Danish population (preprint)

Long covid follows 10-20% of first-time SARS-CoV-2 infections, but the societal burden of long covid and risk factors for the condition are not well-understood. Here, we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which included 37,482 RT-PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index and alpha waves. An additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave was defined as >1 month of sick leave within the period 1-9 months after the RT-PCR test date. Being female, [≥]50 years, and having certain pre-existing conditions such as fibromyalgia increased risks for taking substantial sick leave. Further research exploring this heterogeneity is urgently needed and may provide important evidence for more targeted preventative strategies.

Blood transcriptome and machine learning identified the crosstalk between COVID-19 and fibromyalgia: a preliminary study.

OBJECTIVES: The COVID-19 pandemic caused by SARS-CoV-2 has seriously threatened the human health. Growing evidence shows that COVID-19 patients who recovery will persist with symptoms of fibromyalgia (FM). However, the common molecular mechanism between COVID-19 and FM remains unclear. METHODS: We obtained blood transcriptome data of COVID-19 (GSE177477) and FM (GSE67311) patients from GEO database, respectively. Subsequently, we applied Limma, GSEA, Wikipathway, KEGG, GO, and machine learning analysis to confirm the common pathogenesis between COVID-19 and FM, and screened key genes for the diagnosis of COVID-19 related FM. RESULTS: A total of 2505 differentially expressed genes (DEGs) were identified in the FM dataset. Functional enrichment analysis revealed that the occurrence of FM was intimately associated with viral infection. Moreover, WGCNA analysis identified 243 genes firmly associated with the pathological process of COVID-19. Subsequently, 50 common genes were screened between COVID-19 and FM, and functional enrichment analysis of these common genes primarily involved in immunerelated pathways. Among these common genes, 3 key genes were recognised by machine learning for the diagnosis of COVID-19 related FM. We also developed a diagnostic nomogram to predict the risk of FM occurrence which showed excellent predictive performance. Finally, we found that these 3 key genes were closely relevant to immune cells and screened potential drugs that interacted with the key genes. CONCLUSIONS: Our study revealed the bridge role of immune dysregulation between COVID-19 and fibromyalgia, and screened underlying biomarkers to provide new clues for further clinical research.

The possible onset of fibromyalgia following acute COVID-19 infection.

INTRODUCTION: The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19). METHODS: We 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. RESULTS: The 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). CONCLUSIONS: FM 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.

Effects of the COVID-19 Pandemic on Individuals with Fibromyalgia - a Systematic Scoping Review Protocol (preprint)

Objective: The objectives of this review are to systematically search databases and identify studies that examined the effects of COVID-19 pandemic on symptomatology of adults who had fibromyalgia prior to the pandemic, in order to map the existing knowledge and identify knowledge gaps. Introduction: The COVID-19 pandemic has affected people worldwide in multiple ways. Some suffered infection of varying severity and many experienced stressors associated with quarantine restrictions, lockdowns, and the consequences of social distancing. An initial literature search indicates that the pandemic had different and sometime contradicting effects on individuals with fibromyalgia; while some people experienced worsening of symptoms, others reported symptom relief because of the reduced pace and demands of daily life. Inclusion criteria: Any studies that explored the experience of adults with fibromyalgia syndrome during the COVID-19 pandemic. We will review only studies with participants who were diagnosed with fibromyalgia prior to the pandemic. Methods: Following a pilot search, we developed a full search strategy for Medline, Embase, CINAHL and PsycInfo. The reference list of all included sources of evidence will be screened for additional studies. Sources of unpublished studies to be searched: clinical trial.gov, OPENGREY.EU and MedRxiv. Studies in any language will be included. Abstracts will be screened for inclusion by two reviewers. Similarly, two independent reviewers will systematically extract the data from the included articles. Disagreements in any stage will be resolved through consensus. The results will be presented in tables and will be accompanied by a narrative analysis.

Genetic risk factors for ME/CFS identified using combinatorial analysis.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help to alleviate some of these issues for patients. METHODS: We applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case-control design with 1000 cycles of fully random permutation. Results from this study were supported by a series of replication and cohort comparison experiments, including use of disjoint Verbal Interview CFS, post-viral fatigue syndrome and fibromyalgia cohorts also derived from UK Biobank, and compared results for overlap and reproducibility. RESULTS: Combinatorial analysis revealed 199 SNPs mapping to 14 genes that were significantly associated with 91% of the cases in the ME/CFS population. These SNPs were found to stratify by shared cases into 15 clusters (communities) made up of 84 high-order combinations of between 3 and 5 SNPs. p-values for these communities range from 2.3 × 10-10 to 1.6 × 10-72. Many of the genes identified are linked to the key cellular mechanisms hypothesized to underpin ME/CFS, including vulnerabilities to stress and/or infection, mitochondrial dysfunction, sleep disturbance and autoimmune development. We identified 3 of the critical SNPs replicated in the post-viral fatigue syndrome cohort and 2 SNPs replicated in the fibromyalgia cohort. We also noted similarities with genes associated with multiple sclerosis and long COVID, which share some symptoms and potentially a viral infection trigger with ME/CFS. CONCLUSIONS: This study provides the first detailed genetic insights into the pathophysiological mechanisms underpinning ME/CFS and offers new approaches for better diagnosis and treatment of patients.

Severe acute infection and chronic pulmonary disease are risk factors for developing post-COVID-19 conditions (preprint)

Post-COVID-19 conditions, also known as long COVID, has significantly impacted the lives of many individuals, but the risk factors for this condition are poorly understood. In this study, we performed a retrospective EHR analysis of 89,843 individuals at a multi-state health system in the United States with PCR-confirmed COVID-19, including 1,086 patients diagnosed with long COVID and 1,086 matched controls not diagnosed with long COVID. For these two cohorts, we evaluated a wide range of clinical covariates, including laboratory tests, medication orders, phenotypes recorded in the clinical notes, and outcomes. We found that chronic pulmonary disease (CPD) was significantly more common as a pre-existing condition for the long COVID cohort than the control cohort (odds ratio: 1.9, 95% CI: [1.5, 2.6]). Additionally, long-COVID patients were more likely to have a history of migraine (odds ratio: 2.2, 95% CI: [1.6, 3.1]) and fibromyalgia (odds ratio: 2.3, 95% CI: [1.3, 3.8]). During the acute infection phase, the following lab measurements were abnormal in the long COVID cohort: high triglycerides (meanlongCOVID: 278.5 mg/dL vs. meancontrol: 141.4 mg/dL), low HDL cholesterol levels (meanlongCOVID: 38.4 mg/dL vs. meancontrol: 52.5 mg/dL), and high neutrophil-lymphocyte ratio (meanlongCOVID: 10.7 vs. meancontrol: 7.2). The hospitalization rate during the acute infection phase was also higher in the long COVID cohort compared to the control cohort (ratelongCOVID: 5% vs. ratecontrol: 1%). Overall, this study suggests that the severity of acute infection and a history of CPD, migraine, CFS, or fibromyalgia may be risk factors for long COVID symptoms. Our findings motivate clinical studies to evaluate whether suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.

The effect of novel coronavirus disease-2019 (COVID-19) on fibromyalgia syndrome.

OBJECTIVES: Fibromyalgia syndrome (FM) is a complex disease that is mainly characterised by chronic widespread pain, fatigue and sleep disturbances and may be precipitated or worsened by many stressors. The aim of this study was to observe the behaviour of FM symptoms during the course of coronavirus disease 2019 (COVID-19). METHODS: Patients who had been diagnosed as having FM for ≥3 months were recruited between February and May 2020. The collected data were age, sex, educational level and marital status; height and weight; and the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status 2019 (FASmod), and the Polysymptomatic Distress Scale (PDS). The patients were divided into those with or without concomitant COVID-19 infection. RESULTS: Eight hundred and ninety-seven (93%) of the 965 patients (881 women [91.3%] and 84 men [8.7%]) were followed up on an outpatient basis because of FM and 68 (7.0%) were either followed up as out-patients or hospitalised because of COVID-19. There was no difference in the sociodemographic data of the two groups, but there were statistically significant between-group differences in the results of the clinimetric tests. The major differences between the score of the items (those with the greatest disease impact) were the following related symptoms: sleep quality (FIQR15), fatigue/energy (FIQR13), pain (FIQR12), stiffness (FIQR14). CONCLUSIONS: The mean total and subdomain scores of all the tests were significantly higher in the patients with COVID-19, which suggests that global FM symptoms are more severe in patients with infection. Further studies of the post-COVID19 patients are being carried out in order to discover whether the worsened symptomatology continues because of their hypersensitised state.

Cost analysis of chronic pain due to musculoskeletal disorders in Chile.

The magnitude of the cost of chronic pain has been a matter of concern in many countries worldwide. The high prevalence, the cost it implies for the health system, productivity, and absenteeism need to be addressed urgently. Studies have begun describing this problem in Chile, but there is still a debt in highlighting its importance and urgency on contributing to chronic pain financial coverage. This study objective is to estimate the expected cost of chronic pain and its related musculoskeletal diseases in the Chilean adult population. We conducted a mathematical decision model exercise, Markov Model, to estimate costs and consequences. Patients were classified into severe, moderate, and mild pain groups, restricted to five diseases: knee osteoarthritis, hip osteoarthritis, lower back pain, shoulder pain, and fibromyalgia. Data analysis considered a set of transition probabilities to estimate the total cost, sick leave payment, and productivity losses. Results show that the total annual cost for chronic pain in Chile is USD 943,413,490, corresponding an 80% to the five diseases studied. The highest costs are related to therapeutic management, followed by productivity losses and sick leave days. Low back pain and fibromyalgia are both the costlier chronic pain-related musculoskeletal diseases. We can conclude that the magnitude of the cost in our country's approach to chronic pain is related to increased productivity losses and sick leave payments. Incorporating actions to ensure access and financial coverage and new care strategies that reorganize care delivery to more integrated and comprehensive care could potentially impact costs in both patients and the health system. Finally, the impact of the COVID-19 pandemic will probably deepen even more this problem.

A rapid evidence map of womens health (preprint)

The rapid evidence map focuses on identifying the nature and extent of published literature on the following topic areas: healthcare professionals communication with women about womens health issues and broader health problems during clinical encounters; access to specialist healthcare; endometriosis; menopause; womens health and mental health issues, and mental health issues associated with specific conditions related to menopause or menstrual health (adenomyosis; endometriosis; fibroids; heavy menstrual bleeding, polycystic ovary syndrome and premenstrual dysphoric disorder). The purpose of this rapid evidence map was to identify research gaps and priorities that will be beneficial to womens health in Wales. The rapid evidence map uses abbreviated systematic mapping or scoping review methods to provide a description of the nature, characteristics and volume of the available evidence. There is a lack of primary and secondary research that explores communication between women and healthcare professionals within primary and secondary care settings. Secondary research evidence exists but there are gaps in the evidence base regarding access to services providing minor gynaecological procedures and pain management, or care for menstrual health and wellbeing, endometriosis, polycystic ovarian syndrome, menopause, heart conditions, autoimmune diseases, hypermobility spectrum disorders, myalgic encephalomyelitis, long COVID, fibromyalgia, skin conditions, or palliative and end of life care, which are priority areas identified by the Womens Health Wales Coalition (2022). There are no active funding calls exploring these topics. Regarding endometriosis, there is a lack of review evidence regarding education and resources for health care professionals and doctors to reduce diagnostic times and improve care. There is an evidence gap for primary research regarding information, support interventions and tools for women with endometriosis to help them manage their symptoms and improve their quality of life. A substantial amount of secondary evidence exists on menopause along with a plethora of research priorities around treatment and symptom management. It was beyond the scope of this work to determine if any research had been conducted in these priority areas since the production of the guidelines and recommendations. There is a lack of research recommendations and review evidence that address mental health issues and specific issues that affect a womens menstrual health such as adenomyosis, fibroids, heavy menstrual bleeding and premenstrual dysphoric disorder. Funding statement The Wales Centre for Evidence Based Care was funded for this work by the Wales COVID-19 Evidence Centre, itself funded by Health and Care Research Wales on behalf of Welsh Government. Wales COVID-19 Evidence Centre (WCEC) Rapid Evidence Map: Women’s health Report number – REM 00045 (October 2022) Rapid Evidence Map Details Review conducted by Wales Centre For Evidence Based Care Review Team ▪ Deborah Edwards ▪ Judit Csontos ▪ Elizabeth Gillen Review submitted to the WCEC October 2022 Stakeholder consultation meeting 24 th October 2022 Rapid Evidence Map report issued by the WCEC November 2022 WCEC Team ▪ Adrian Edwards, Ruth Lewis, Alison Cooper, Micaela Gal involved in drafting the topline summary, reviewing, editing, publication process. This review should be cited as REM00045. Wales COVID-19 Evidence Centre, Rapid Evidence map: Womens health. October 2022 Disclaimer The views expressed in this publication are those of the authors, not necessarily Health and Care Research Wales. The WCEC and authors of this work declare that they have no conflict of interest. Rapid Evidence Map: Women’s health Report number – REM00045 (October 2022) TOPLINE SUMMARY What are Rapid Evidence Maps? Our Rapid Evidence Maps (REMs) use abbreviated systematic mapping or scoping review methods to provide a description of the nature, characteristics and volume of the available evidence for a particular policy domain or research question. They are mainly based on the assessment of abstracts and incorporate an a priori protocol, systematic search, screening, and minimal data extraction. They may sometimes include critical appraisal, but no evidence synthesis is conducted. Priority is given, where feasible, to studies representing robust evidence synthesis. They are designed and used primarily to identify a substantial focus for a rapid review, and key research gaps in the evidence-base . ( N . B. Evidence maps are not suitable to support evidence-informed policy development, as they do not include a synthesis of the results .) Who is this summary for? Health and Care Research Wales Background / Aim of Rapid Evidence Map (REM) The Welsh Government Research and Development Division intends to run a commissioned funding call on understanding and tackling gender inequalities in health and social care in Wales. The purpose of this REM was to identify research gaps and priorities that will be beneficial to women’s health in Wales to inform the proposed funding call. It was decided, based on a preliminary review of the literature, feedback from an NHS public consultation exercise in Wales, and further discussion with the stakeholder group, that the REM would focus on identifying the nature and extent of the literature on the following prioritised topic areas: healthcare professionals’ communication with women about women’s health issues and broader health problems during clinical encounters; access to specialist healthcare ; endometriosis ; menopause ; women’s health and mental health issues, and mental health issues associated with specific conditions related to menopause or menstrual health (adenomyosis; endometriosis; fibroids; heavy menstrual bleeding, polycystic ovary syndrome and premenstrual dysphoric disorder). Research gaps in other areas and health conditions, in which women might also experience inequality, were not explored in this REM. Key Findings Extent of the evidence base ▪ Communication within health care encounters The evidence base included one systematic review (of endometriosis) and nine primary studies. The primary studies focused on breast cancer (n=2), maternal medicine (n=3), perinatal mental health (n=1), gynaecological conditions (n=1), and non-specific conditions (n=2). Three studies focused on specific populations: urban Africans, Iraqi Muslim refugees, and undocumented migrants. Planned and ongoing NIHR funded projects include clinicians’ perspectives of listening to women’s health, menstrual and gynaecological conditions, menopause, and women’s cancers ▪ Access to specialist healthcare The evidence base consisted of 19 reviews and 9 protocols. Conditions covered were maternal medicine (n=8), sexual and reproductive health (n=5), cancer and cancer screening (n=4), perinatal mental health (n=4), mental health (n=2), HIV (n=2), and non-specific conditions (n=3). Specific populations investigated were refugees or displaced people (n=6), those in differing social, economic, and environmental circumstances (n=4), physical disabilities (n=3), homeless (n=2), migrants (n=2), experiencing intimate partner violence (n=1), and minority ethnicity black (n=1). The reviews focused on barriers and facilitators (n=10), barriers (n=5), experiences (n=3), mapping the evidence (n=3), factors (n=2), management (n=1), facilitators (n=1), predictors (n=1), associations (n=1), and prevalence (n=1). ▪ Endometriosis The evidence base included 121 systematic reviews covering different topics including medical management (n=22), surgical management (n=15), biology/molecular (n=12), risk factors (n=11), and comorbid conditions (n=9). Research priorities were identified by the James Lind Alliance (JLA), NICE guideline, a Wales-specific primary study (Boivin et al 2018), and researchers within the field (n=2). Recent UK funding calls were identified covering laboratory research, aetiology of endometriosis and uterine disorders, and medical and surgical management. ▪ Menopause The evidence base included 108 systematic reviews covering different topics including hormonal therapies (n=17), homeopathic therapies (n=13), non-hormonal therapies (n=10), genitourinary symptoms of menopause (n=7), alternative therapies (n=6), and lifestyle interventions (n=6). Research priorities were identified as part of a NICE guideline, by the British Menopause Society, and researchers within the field (n=3). Recent UK funding calls were identified covering reproductive and menopausal health, testosterone for the treatment of symptoms, women’s reproductive health in the workplace, and women’s health hub landscape. ▪ Women’s health and mental health issues The evidence base included 37 reviews covering: perinatal mental health (n=23), general mental health (n=9), polycystic ovary syndrome (n=3), and intimate partner violence (n=2). Some reviews focused on specific populations including women in prison, women in inpatient mental health services, mental health of migrants and refugee women, and mental health of women from different minority groups. Recent UK funding calls were identified covering: young women’s mental health, women and partners who have experienced pregnancy not ending in live births, and perimenopause and the risk of psychiatric disorders. ▪ Mental health issues associated with specific conditions related to menopause or menstrual health The evidence base included 10 systematic reviews covering: polycystic ovary syndrome (n=4), endometriosis (n=4) menopause (n=1), and menstruation (n=1). The reviews focused on prevalence (n=4), associations (n=4), and management (n=2). Recency of the evidence base ▪ The review included evidence available (from 2012, 2018, and 2021) up until September 2022. (Separate searches were conducted for different topics, with variable time limits due to the varying volume of research published in certain areas.) Summary of the evidence gaps ▪ There is a lack of primary and secondary research that explores communication between women and healthcare professionals (HCPs) within primary and secondary care settings. ▪ Secondary research evidence exists but there are gaps in the evidence base regarding access to services providing minor gynaecological procedures and pain management, or care for menstrual health and wellbeing, endometriosis, polycystic ovarian syndrome, menopause , heart conditions, autoimmune diseases, hypermobility spectrum disorders, myalgic encephalomyelitis, long COVID, fibromyalgia, skin conditions, or palliative and end of life care, which are priority areas identified by the Women’s Health Wales Coalition (2022). There are no active funding calls exploring these topics. ▪ Regarding endometriosis, there is a lack of review evidence regarding education and resources for HCPs and doctors to reduce diagnostic times and improve care . There is an evidence gap for primary research regarding information, support interventions and tools for women with endometriosis to help them manage their symptoms and improve their quality of life . ▪ A substantial amount of secondary evidence exists on menopause along with a plethora of research priorities around treatment and symptom management . It was beyond the scope of this REM to determine if any research had been conducted in these priority areas since the production of the guidelines and recommendations. Researchers in the field would like to see primary research conducted in the area of quality of life . ▪ There is a lack of research recommendations and review evidence that address mental health issues and specific issues that affect a women’s menstrual health such as adenomyosis, fibroids, heavy menstrual bleeding and premenstrual dysphoric disorder .

Lessons in Affect Regulation to Keep Stress and Pain UndeR control (LARKSPUR): Design of a randomized controlled trial to increase positive affect in middle-aged and older adults with fibromyalgia.

BACKGROUND: Fibromyalgia syndrome (FMS) is a leading cause of functional limitations and disability for which there is no cure. Positive psychological interventions for improving health have received increasing attention, but evidence of the feasibility, acceptability, and impact of such interventions in adult populations with FMS is limited. OBJECTIVES: To describe the rationale and design of a 5-week, online positive affect skills intervention, LARKSPUR: Lessons in Affect Regulation to Keep Stress and Pain UndeR control. METHODS: FMS participants (N = 90) will be randomized to one of two conditions: (1) LARKSPUR or (2) emotion reporting/attention control. LARKSPUR is an online multicomponent intervention that targets eight skills to help foster positive affect: (1) noticing positive events, (2) savoring positive events, (3) identifying personal strengths, (4) behavioral activation to set and work toward attainable goals, (5) mindfulness, (6) positive reappraisal, (7) gratitude, and (8) acts of kindness. The primary outcomes include feasibility (i.e., recruitment, retention, adherence) and acceptability (i.e., helpfulness, usability, satisfaction). Secondary outcomes include pain intensity and pain interference. SIGNIFICANCE: If feasibility and acceptability metrics are met and reductions in pain outcomes are achieved, we will undertake future efficacy and effectiveness trials of LARKSPUR among older adults with FMS. TRIAL REGISTRATION: NCT04869345.

Genetic Risk Factors for ME/CFS Identified using Combinatorial Analysis (preprint)

Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with the disease would begin to help to alleviate some of these issues for patients. Methods We applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case-control design with 1,000 cycles of fully random permutation. Results from this study were supported by a series of replication and cohort comparison experiments, including use of disjoint Verbal Interview CFS, post-viral fatigue syndrome and fibromyalgia cohorts also derived from UK Biobank, and results compared for overlap and reproducibility. Results Combinatorial analysis revealed 199 SNPs mapping to 14 genes, that were significantly associated with 91% of the cases in the ME/CFS population. These SNPs were found to stratify by shared cases into 15 clusters (communities) made up of 84 high-order combinations of between 3-5 SNPs. p -values for these communities range from 2.3 × 10 −10 to 1.6 × 10 −72 . Many of the genes identified are linked to the key cellular mechanisms hypothesized to underpin ME/CFS, including vulnerabilities to stress and/or infection, mitochondrial dysfunction, sleep disturbance and autoimmune development. We identified 3 of the critical SNPs replicated in the post-viral fatigue syndrome cohort and 2 SNPs replicated in the fibromyalgia cohort. We also noted similarities with genes associated with multiple sclerosis and long COVID, which share some symptoms and potentially a viral infection trigger with ME/CFS. Conclusions This study provides the first detailed genetic insights into the pathophysiological mechanisms underpinning ME/CFS and offers new approaches for better diagnosis and treatment of patients.

Prevalence of post-COVID-19 in patients with fibromyalgia: a comparative study with other inflammatory and autoimmune rheumatic diseases.

OBJECTIVES: To determine the prevalence and characteristics of post-COVID-19 (PC) in fibromyalgia (FM) patients. METHODS: Retrospective, multi-centric, observational study, comparing a group of FM patients (FM group) with another group of patients with other rheumatic diseases (RD group). COVID-19 diagnosis was established by positive polymerase chain reaction or antigen during acute infection or by positive antibodies thereafter. We considered PC diagnosis when symptoms remain after COVID-19. We collected the principal characteristics of COVID-19, the severity of fatigue, waking unrefreshed and cognitive impairment, and persistent symptoms. The American College of Rheumatology (ACR) criteria and the Combined Index of Severity in Fibromyalgia (ICAF) were collected in the FM group. RESULTS: RD group (n = 56) had more pneumonia (p = 0.001) and hospital admissions (p = 0.002), but the FM group (n = 78) had a higher number of symptoms (p = 0.002). The percentage of patients with PC was similar between groups (FM group 79.5%; RD group 66.1%, p = 0.081). FM group had more PC symptoms (p = 0.001), more impairment after COVID-19 (p = 0.002) and higher severity of fatigue, waking unrefreshed and cognitive impairment (p <  0.0001). Only loss of smell was more frequent in the FM group (p = 0.005). The FM group with PC (n = 29) showed more severity of the Combined Index of Severity in Fibromyalgia (ICAF) total score and physical factor after COVID-19, while emotional, coping factors and the ACR criteria did not change. CONCLUSIONS: The prevalence of PC in FM patients is similar to RD patients. In FM patients, the presence of PC does not appear to impact the severity of FM.

The relationship between COVID-19 and fibromyalgia syndrome: prevalence, pandemic effects, symptom mechanisms, and COVID-19 vaccines.

On March 11, 2020, the World Health Organization, realizing the level of spread worldwide and the severity of the condition, accepted coronavirus disease 19 (COVID-19) as a pandemic. Subsequently, quarantine conditions were implemented around the world, and these triggered particular results. Like all other individuals, fibromyalgia syndrome (FMS) patients were affected by these conditions. The stress load in pandemic conditions, difficulties in accessing healthcare services, changes in exercise compliance, variations in physiotherapy programs, and remote work conditions all had an impact on FMS patients. Although general expectations were negative, some FMS patients were able to manage the pandemic conditions and even turn them in their favor. This is thought to be due to this patient group having established strategies to cope with stress in the pre-pandemic period, and they had sufficient ability to adapt to changing situations. FMS-related symptoms occur in a subset of individuals following COVID-19. One of the factors is the increased psychological burden after COVID-19. There is evidence that neuroinflammatory pathways affect neuroplasticity in the central nervous system and trigger the onset of FMS-related symptoms. Among the probable mechanisms are alterations in inflammatory and anti-inflammatory pathways. Changes in the autonomic nervous system with the effect of SARS-CoV-2 may induce the emergence of FMS-related symptoms. FMS and COVID-19 can coexist, and FMS may create a tendency to vaccine hesitancy. Future studies should focus on elucidating FMS-related symptoms occurring post-COVID-19. There is a need to determine distinctions between the FMS clinical status that emerged following COVID-19 and the regular patient group in terms of diagnosis, treatment, and follow-up.

The impact of COVID-19 pandemic on mental and physical wellbeing in women with fibromyalgia: a longitudinal mixed-methods study.

OBJECTIVE: The COVID-19 pandemic has strongly influenced psychological and physical health worldwide. The aim of this study was to examine the impact of the pandemic on women with fibromyalgia. METHODS: This mixed methods pilot study explored measures of pain severity and interference, as well as pain catastrophizing and level of fibromyalgia impact among women with fibromyalgia before and during the COVID-19 pandemic in the USA. Fibromyalgia patients completed demographic, pain-related, and other validated psychosocial questionnaires prior to the onset of the COVID-19 pandemic, and then were re-assessed with those questionnaires, as well as a pandemic-related questionnaire assessing the impact of the pandemic on the patients' life, during the pandemic. RESULTS: When comparing data reported before the pandemic to data collected 3-6 months into the pandemic, women with fibromyalgia reported a general worsening of their pain and pain-related symptoms. During the pandemic, pain catastrophizing (p ≤ 0.05) and fibromyalgia impact (p ≤ 0.05) increased significantly compared to before the pandemic. The increase in pain catastrophizing scores was highly correlated with the impact of the pandemic on the participants' ability to cope with pain and on their mental health. Qualitative analysis corroborated the significant impact of the pandemic on patients' mental health, with the vast majority reporting a worsening of their mood. Other impacted domains included anxiety, level of activity and sleep. CONCLUSIONS: Collectively, the pandemic appears to have produced a substantive worsening of pain-related symptomatology among women with fibromyalgia, which should be addressed by targeted interventions.

Hyperbaric Oxygen for Treatment of Long COVID Syndrome (HOT-LoCO); Protocol for a Randomised, Placebo-Controlled, Double-Blind, Phase II Clinical Trial (preprint)

IntroductionLong COVID, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, post-exertional malaise, and cognitive dysfunction. There is currently no effective treatment, and the underlying mechanisms are unknown although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in Long COVID. This randomised placebo-controlled clinical trial will explore HBOT as a potential treatment for Long COVID. The primary objective is to evaluate if HBOT improves health related quality of life (HRQoL) for patients with Long COVID compared to placebo/sham. The main secondary objectives are to evaluate whether HBOT improves endothelial function, objective physical performance, and short term HRQoL. Methods and AnalysisA randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to Long COVID, with low HRQoL. Clinical data, HRQoL- questionnaires, blood samples, objective tests and activity meter data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over six weeks. Assessments for safety and efficacy will be performed at six, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND-36) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent Data Safety Monitoring Board. Ethics and DisseminationThe trial is approved by The Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Product Agency (5.1-2020-36673). Positive, negative, and inconclusive results will be published in peer-reviewed scientific journals with open access. Trial RegistrationNCT04842448. EudraCT: 2021-000764-30 Strengths and limitations of this trialStrengths O_LIRandomised placebo-controlled, double-blind, parallel groups, clinical trial in compliance with ICH-GCP C_LIO_LIEvaluation of safety and efficacy, including objective and explanatory endpoints C_LIO_LIIndependent Data Safety Monitoring Board (DSMB) C_LI Limitations O_LINew syndrome with unknown mechanisms C_LIO_LIPower calculation is based on similar syndromes C_LIO_LISelection bias as patients are enrolled from the same post-COVID clinic C_LI

Physical and mental impact of COVID-19 outbreak on fibromyalgia patients.

OBJECTIVES: Acute or chronic stress may trigger or aggravate symptoms of fibromyalgia (FM). We aimed to evaluate the physical and mental health of fibromyalgia patients during the COVID 19 outbreak and identify protective/risk factors. METHODS: An online survey was published in May 2020, following two months of lockdown due to the COVID 19 outbreak, including questionnaires regarding demographic characteristics, access to medical services, anxiety, depression, life approach, coping strategies, perception of social support, widespread pain index (WPI) and symptoms severity scale (SSS), insomnia severity index (ISI) and patient global assessment. RESULTS: Of the 233 patients included in the study, 98% were forced to discontinue complementary or alternative treatments during lockdown. Up to 30% of responders who had been treated with medical cannabis had to stop due to logistic difficulties and this was associated with significantly higher scores of WPI/SSS (p=0.024). Higher levels of anxiety and depression were significantly correlated with higher levels of pain, sleep disorders and subjective perception of deterioration (p=0.00). Higher scores of social support and positive life approach were correlated with less anxiety and depression (p<0.01), lower levels of pain (p<0.05) and less sleep disturbances (p<0.01). Avoidant coping style was strongly associated to higher levels of pain, sleep disturbances, anxiety, depression, and subjective perception of worsening (p<0.01). CONCLUSIONS: Fibromyalgia patients reported adverse mental and physical outcomes during the COVID-19 outbreak. Factors such as stopping current treatments may play a central role. Social support and a positive life approach appear to be protective.

A better but persistently low health status in women with fibromyalgia during the COVID-19 pandemic: a repeated cross-sectional data analysis.

Multiple overlapping and complementary theoretical arguments suggest that the COVID-19 pandemic could worsen health in fibromyalgia. The aim of this study was to determine mental and physical health in women with fibromyalgia before and during the pandemic. In a 3-sample, repeated cross-sectional design, we analyzed questionnaire data from Dutch women with fibromyalgia, collected in three independent samples: before the COVID-19 pandemic (2018; n = 142) and during the first acute (2020; n = 304) and prolonged (2021; n = 95) phases of the pandemic. Eight dimensions of mental and physical health were assessed using The RAND 36-Item Short Form Health Survey (RAND SF-36). Compared to norm group data, both before and during the pandemic, women with fibromyalgia showed high levels of fatigue and pain and low levels of general health, social functioning, physical functioning, role physical functioning (d > 1.2, very large effect sizes), role emotional functioning, and mental health (0.71 < d < 1.2, medium to large effect sizes). Contrary to theoretical expectation, levels at five health variables before vs. during the pandemic did not differ (p > 0.05), and levels of pain (p < 0.001), role physical functioning (p < 0.001), and physical functioning (p = 0.03) (0.014 ≤ pη2 ≤ 0.042, small effect sizes) reflected a healthier status during than before the pandemic. These findings indicate a somewhat better but persistently low health status in women with fibromyalgia during the pandemic. This suggests that the pandemic may include changed circumstances that are favorable for some women with fibromyalgia.