High-dose Omega-3 Alters Serum Magnesium and Calcium Levels and Affects Fibromyalgia Symptoms: A Randomized, Double-blind, Placebo-Control Study.

OBJECTIVE: The aim of this study is to investigate the effect of a high oral dose of omega- 3 on serum magnesium (Mg) and calcium (Ca) levels and their effects on clinical measures of pain threshold. METHODS: One hundred twenty patients were recruited and randomized 1:1 to omega-3 or placebo and blinded to their treatment group. At baseline and after 8 weeks of treatment, the Widespread Pain Index (WPI), the Symptom Severity Scale (SSS), the Visual Analogue Scale (VAS), and the FM Impact Questionnaire (FIQ) were completed. In addition, serum was taken for Ca and Mg analysis at the same time point. RESULTS: The WPI, SSS, VAS, and FIQ scores improved significantly in the omega-3 group compared to the placebo group (P < 0.001). Serum Ca levels correlated negatively with WPI (r = - 0.308), SSS (r = -0.28), VAS (r = -0.311), and FIQ (r= -0.348) scores (P < 0.001) after 8 weeks of treatment. Serum Mg levels were negatively correlated with SSS (r = -0.212) and VAS (r = -0.231) scores after 8 weeks of treatment. The difference between serum Ca levels before and after 8 weeks of omega-3 treatment and serum Mg levels increased significantly compared to 8 weeks of placebo treatment. CONCLUSION: The results of this study showed that a high dose of omega-3 could have a positive effect on the relief of FM pain, which could be due to an increase in serum Mg and Ca levels.

Effects of transcranial magnetic stimulation on sleep quality in fibromyalgia: A double-blind randomized clinical trial.

OBJECTIVES: The aim of the current study was to assess the therapeutic impact of repeated low frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex (rDLPFC) on sleep problems in patients with fibromyalgia. METHODS: Forty two patients with fibromyalgia who had sleep difficulties were randomly assigned to receive either real or sham rTMS treatment. Patients received 20 treatment sessions (5 sessions per week) in which 1200 rTMS pulses were applied over the rDLPFC using a frequency of 1 Hz and an intensity of 120 % of the resting motor threshold. All participants were evaluated at baseline, and then 1 month and 3 months after treatment using the Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), Medical Outcomes Study Sleep Scale (MOS-SS) and polysomnography (PSG). RESULTS: There were significant time (pre, 1month, and 3 months)X group (real versus sham group) interactions in all 3 clinical rating scales; FIQ (Df = 1.425, F = 237.645, P = 0.001), PSQI (Df = 2, F = 64.005, P = 0.001), MOS-SS (Df = 2, F = 28.938, P = 0.001) due to the fact that the real group improved significantly more over time than the sham group. Similarly, the real group improved more on the PSG parameters than the sham group. The effect sizes were large both in the rating scales and PSG, indicating a substantial clinical improvement. Correlation as an exploratory analysis between the changes (pre - post 3 months) in MOS-SS and PLMs index (/h) showed significant negative correlation (r = -0.643, P = 0.002). CONCLUSIONS: 20 sessions of LF-rTMS over rDLPFC can improve sleep quality in both subjective (PSQI and MOSS) as well as objective (PSG) rating scales.

Identification of texture MRI brain abnormalities on Fibromyalgia syndrome using interpretable machine learning models.

To provide objective diagnostic markers for fibromyalgia symptoms (FMS) diagnosis, we have created interpretable extreme gradient boosting (XGBoost) models using radiomics to aid in the diagnosis of chronic pain (CP) and to develop nomogram models for diagnosing subgroups of FMS. A group of 54 patients with CP and 71 healthy controls was randomly separated into training and validation groups, using a 7:3 ratio. Radiomics features were extracted from grey-matter and white-matter in the filtered mwp0* image. The Mann-Whitney U test, Spearman's rank correlation test, and least absolute shrinkage and selection operator (LASSO) were utilized to select features. An XGBoost model was created based on these features, and Shapley Additive exPlanations (SHAP) was used for personalization and visual interpretation. A nomogram was developed for the diagnosis of FMS subgroups, utilizing radiomics scores and clinical predictors. The efficacy of the nomogram was evaluated using the area under the receiver operating characteristic curve, while decision curve analysis was employed to evaluate its clinical efficacy. The XGBoost model displays stability in the training validation group, indicating lower overfitting of CP model. The nomogram model combined with the rad-score has a greater ability to distinguish between typical and sub-clinical than the clinical factor model alone. We developed and validated a CP diagnosis model by XGBoost and realized model visualization through SHAP. The rad-score obtained by machine learning was used to build a nomogram model that combines clinical scales to distinguish patients with typical and sub-clinical fibromyalgia.

Prevalence and characteristics of fibromyalgia according to three fibromyalgia diagnostic criteria: A secondary analysis study.

Objective: The purpose of this study was to explore the prevalence of fibromyalgia (FM) according to different diagnostic criteria in a clinical sample and to explore the clinical characteristics in cases and non-cases by the diagnostic criteria used. Methods: A sample of 182 participants, both positive (n = 120) and negative (n = 62) FM individuals according to a clinical, pragmatic classification was used. Their characteristics were explored according to three different FM diagnostic criteria, i.e., the American College of Rheumatology (ACR) 1990, ACR 2016, and APS Pain Taxonomy (AAPT), respectively. Thus, impact of FM (FIQ), symptoms of anxiety and depression (HADS), tender point (TP) counts, and mechanical pressure sensitivity (in kPa) were compared in cases versus non-cases depending on diagnostic criteria of FM used. Descriptive analyses used chi-square statistic for categorical variables and non-parametric Mann-Whitney U tests for continuous variables. Results: From the clinical positive FM sample (n = 120), n = 99, 108, and 110 persons were diagnosed positive according to the ACR 1990, ACR 2016, and AAPT FM diagnostic criteria, respectively. All these three diagnostic tools discriminated FM positively from diagnostic FM non-cases when measuring TP-counts, mechanical pressures, and most FIQ-items, but they varied for anxiety and depression. Conclusion: The prevalence of FM differed somewhat with the use of ACR 1990, ACR 2016, and the AAPT as diagnostic tools. The anxiety and depression symptoms differed significantly between cases and non-cases using some but not all the diagnostic criteria. Regarding other FM symptoms, e.g., TPs and most FIQ items, all diagnostic criteria contrasted case from non-case.

Disruptive compensatory mechanisms in fibromyalgia syndrome and their association with pharmacological agents.

Fibromyalgia syndrome (FMS) is a chronic disorder characterized commonly by widespread musculoskeletal pain and fatigue, predominantly affecting women, with its complexity often leading to underdiagnosis and complicating treatment effectiveness. Transcranial magnetic stimulation (TMS) metrics are potential markers to optimize FMS treatments; however, evidence is limited. Our study aimed to explore the relationship between cortical excitability and inhibition, assessed through TMS markers, and clinical characteristics in patients with FMS. This presented cross-sectional study employed baseline data from a clinical trial with 108 FMS patients, mostly female (88.8%), and mean age of 47.3 years old (SD = 12.06). Our analysis showed that decreased short-intracortical inhibition (SICI) was associated with gabapentinoids use, nicotine history, and increased fatigue levels, suggesting its connection with compensatory mechanisms for non-painful FMS features. Increased motor intracortical facilitation (ICF) was linked with greater pain severity and shorter FMS duration, implying its relationship with a reorganization of sensorimotor pathways due to chronic pain. Additionally, higher resting motor threshold (rMT) was associated with less effective pain modulation (lower conditioned pain modulation [CPM]), indicating a disruption of pain compensatory mechanism. Given the role of SICI in indexing homeostatic brain mechanisms and its association with fatigue, a hallmark characteristic of FMS-induced behavioral changes, these results suggest that FMS likely has a deleterious effect on brain inhibitory function, thus providing a potential novel insight for FMS mechanisms. In addition, it seems that this compensatory mechanism's disruption is enhanced by pharmacological agents such as gabapentioids and nicotine.

Effects of Tryptophan and Physical Exercise on the Modulation of Mechanical Hypersensitivity in a Fibromyalgia-like Model in Female Rats.

Though the mechanisms are not fully understood, tryptophan (Trp) and physical exercise seem to regulate mechanical hypersensitivity in fibromyalgia. Here, we tested the impact of Trp supplementation and continuous low-intensity aerobic exercise on the modulation of mechanical hypersensitivity in a fibromyalgia-like model induced by acid saline in female rats. Twelve-month-old female Wistar rats were randomly divided into groups: [control (n = 6); acid saline (n = 6); acid saline + exercise (n = 6); acid saline + Trp (n = 6); and acid saline + exercise + Trp (n = 6)]. Hypersensitivity was caused using two intramuscular jabs of acid saline (20 µL; pH 4.0; right gastrocnemius), 3 days apart. The tryptophan-supplemented diet contained 7.6 g/hg of Trp. The three-week exercise consisted of progressive (30-45 min) treadmill running at 50 to 60% intensity, five times (Monday to Friday) per week. We found that acid saline induced contralateral mechanical hypersensitivity without changing the levels of Trp, serotonin (5-HT), and kynurenine (KYN) in the brain. Hypersensitivity was reduced by exercise (~150%), Trp (~67%), and its combination (~160%). The Trp supplementation increased the levels of Trp and KYN in the brain, and the activity of indoleamine 2,3-dioxygenase (IDO), and decreased the ratio 5-HT:KYN. Exercise did not impact the assessed metabolites. Combining the treatments reduced neither hypersensitivity nor the levels of serotonin and Trp in the brain. In conclusion, mechanical hypersensitivity induced by acid saline in a fibromyalgia-like model in female rats is modulated by Trp supplementation, which increases IDO activity and leads to improved Trp metabolism via the KYN pathway. In contrast, physical exercise does not affect mechanical hypersensitivity through brain Trp metabolism via either the KYN or serotonin pathways. Because this is a short study, generalizing its findings warrants caution.

Environmental pollution impact on the severity of some rheumatic diseases: a comparative analytical study on inflammatory and non-inflammatory samples.

OBJECTIVE: Environmental pollution of heavy metals is increasingly a problem and has become of great concern due to the adverse effects it causes worldwide. Heavy metal exposure has been implicated in health problems, including fibromyalgia and rheumatoid arthritis. We aim to evaluate the rule of chronic heavy metals toxicity on the induction of vitamin D3 (VD) deficiency and parathyroid hormone (PTH) disturbances in an inflammatory disease like rheumatoid arthritis (RA) and non-inflammatory disease like fibromyalgia syndrome (FMS). METHODS: This comparative analytical study was conducted on sixty adults (age ≥ 18 years). Participants were divided into three groups. Group I: twenty patients diagnosed with RA according to the specific ACR/EULAR criteria for RA. Group II: twenty patients diagnosed with FMS according to the specific 2010 (ACR) criteria for FMS. Group III: twenty healthy adults. All patients and controls were subjected to routine laboratory tests as well as the measurement of PTH, VD and estimation of serum levels of lead, cadmium, and chromium. RESULTS: VD was significantly inversely correlated to PTH, lead, cadmium, chromium, and activity scores in the RA and FMS groups. Lead, Cadmium and Chromium had a significant independent risk on the VD level in RA patients, while lead had a significant independent risk on the VD level in FMS patients. CONCLUSION: Heavy metals may affect VD synthesis, leading to hypovitaminosis D and secondary hyperparathyroidism in RA and FMS patients. Heavy metals play a key role in the pathogenesis of RA, FMS, and their disease activity.

Long COVID: a new disease?

The definition of quaternary prevention as the set of interventions that avoids or mitigates the consequences of unnecessary or excessive activity of medical interventionism and the health system. The definition of a new disease is a complex process that involves the identification, characterization and description of a medical condition that has not been previously recognized or documented. Since mid-2020, the term chronic COVID/long COVID has been used to describe the presence of signs and symptoms after an acute SARS-CoV-2 infection, with multiple terminologies and definitions in international literature. Post-infectious syndromes, myalgia encephalomyelitis and fibromyalgia, are some of the diseases that have similarities with chronic COVID. This article presents an analysis relating the concepts of new disease and quaternary prevention with chronic COVID and other diseases described in the literature.

Se define prevención cuaternaria como el conjunto de intervenciones que evita o atenúa las consecuencias de la actividad innecesaria o excesiva del intervencionismo médico y del sistema sanitario. La definición de una nueva enfermedad es un proceso complejo que involucra la identificación, caracterización y descripción de un cuadro clínico que no ha sido previamente reconocida o documentada. Desde mediados del año 2020 se utiliza el término COVID crónico/long COVID para describir la presencia de signos y síntomas luego de una infección aguda por SARS-CoV-2, con múltiples terminologías y definiciones en la literatura internacional. Los síndromes posinfecciosos, la encefalomielitis mialgia y la fibromialgia, son algunas de las enfermedades que tienen similitudes con el COVID crónico. En este artículo se presenta un análisis relacionando los conceptos de nueva enfermedad y prevención cuaternaria con el COVID crónico y otras enfermedades descritas en la literatura.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis.

Background: Chronic pain is common and costly. Antidepressants are prescribed to reduce pain. However, there has not been a network meta-analysis examining all antidepressants across all chronic pain conditions, so effectiveness and safety for most antidepressants for pain conditions remain unknown. Objective: To assess the efficacy and safety of antidepressants for chronic pain (except headache) in adults. Our primary outcomes were as follows: substantial pain relief (50%), pain intensity, mood and adverse events. Our secondary outcomes were as follows: moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change, serious adverse events and withdrawal. Design: This was a systematic review with a network meta-analysis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, AMED and PsycINFO databases for randomised controlled trials of antidepressants for chronic pain conditions up until 4 January 2022. The review was registered in PROSPERO (CRD42020171855), and the protocol was published in the Cochrane Library (https://doi.org/10.1002/14651858.CD014682). Setting: We analysed trials from all settings. Participants: We included trials in which participants had chronic pain, defined as longer than 3 months, from any condition excluding headache. Interventions: We included all antidepressants. Main outcome measures: Our primary outcome was substantial pain relief, defined as a reduction ˃ 50%. We also measured pain intensity, mood and adverse events. Secondary measures included moderate pain relief (above 30% reduction), physical function, sleep, quality of life, Global Impression of Change, serious adverse events, and withdrawal from trial. Results: We identified 176 studies with a total of 28,664 participants. Most studies were placebo-controlled (n = 83) and parallel armed (n = 141). The most common pain conditions examined were fibromyalgia (59 studies), neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of randomised controlled trials was 10 weeks. Most studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. Standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that for duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Limitations: The evidence for antidepressants other than duloxetine is poor. For duloxetine, it is not clear whether the effect applies to groups with both pain and low mood, since these groups were excluded from trials. There is also insufficient evidence on long-term outcomes and on adverse effects. Conclusions: There is only reliable evidence for duloxetine in the treatment of chronic pain. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Data for all other antidepressants were of low certainty. However, the findings should not be read as an encouragement to prescribe antidepressants where other non-pharmacological intervention could be equally effective, especially in the absence of good evidence on side effects and safety. Future work: There is a need for large, methodologically sound trials testing the effectiveness of antidepressants for chronic pain. These trials should examine long-term outcomes (> 6 months) and include people with low mood. There should also be better reporting of adverse events, tolerance of drugs, and long-term compliance. Study registration: This study is registered as PROSPERO CRD42020171855. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128782) and is published in full in Health Technology Assessment; Vol. 28, No. 62. See the NIHR Funding and Awards website for further award information.

Chronic pain is pain that lasts for more than 3 months. Over one-third of people across the world experience chronic pain. This often has a detrimental impact on people's mood, disability and well-being. Antidepressants are often prescribed to reduce pain, but we are not sure which antidepressants work best for different types of pain, or whether they are safe. We wanted to find out whether antidepressants were effective and safe for management of chronic pain. We searched for studies that had compared any antidepressant with any other treatment for any type of chronic pain (except headache). We compared all the treatments against each other using a statistical method called network meta-analysis. This method allows us to rank the treatments in order of best to worst for each outcome. We found 176 studies that included a total of 28,664 people with chronic pain. Most of the studies (83/176) compared an antidepressant with a placebo (which looks like the real medicine but does not have any medicine in it). The evidence from our analysis suggests that: Duloxetine is the antidepressant that we have the most confidence in. It was the best antidepressant for reducing pain and improving physical function. A standard dose of duloxetine was equally as effective for reducing pain as a high dose of duloxetine. Milnacipran was also effective at reducing pain, but we are not as confident in this result as in the one for duloxetine because there were fewer studies with fewer people involved. Aside from duloxetine and milnacipran, we do not have confidence in the results from any other antidepressant included in this review, and even for duloxetine and milnacipran, we do not know the long-term effects. It is important to recognise that the lack of evidence for the majority of antidepressants in this review does not necessarily equal a lack of benefit. Rather, this means that the large, high-quality trials required for us to be certain of an antidepressant's effectiveness have not been undertaken. Altogether, although duloxetine and milnacipran are effective, the results of this review should not be read as an encouragement to prescribe antidepressants where other non-pharmacological intervention could be equally effective, especially in the absence of good evidence on side effects and safety. These conclusions were informed by our patient and public involvement group.

Bidirectional Two-Sample Mendelian Randomization Analysis Reveals Causal Associations Between Modifiable Risk Factors and Fibromyalgia.

Introduction: This study aims to investigate the potential causal effects of modifiable risk factors on Fibromyalgia (FM). Methods: Genetic variants associated with 34 exposure factors were obtained from Genome-wide association studies (GWAS). Summary statistics for FM were acquired from the FinnGen consortium. Bidirectional Mendelian randomization (MR) analysis was conducted between all exposures and outcomes. The inverse-variance weighted (IVW) method was employed as the primary estimation technique. Heterogeneity and pleiotropy were assessed using MR-PRESSO global test, the weighted median, Cochran's Q statistic and MR-Egger. Results: Depression (OR=2.087, 95% CI: 1.466-2.971), alcohol consumption (OR=1.489, 95% CI: 1.094-2.028), body fat percentage (OR=1.524, 95% CI: 1.153-2.013) and body mass index (BMI) (OR=1.542, 95% CI: 1.271-1.872) were associated with an increased risk of FM among genetically susceptible individuals. Conversely, higher education level (OR=0.404, 95% CI: 0.297-0.549), longer years of education (OR=0.489, 95% CI: 0.290-0.825) and higher household income (OR=0.328, 95% CI: 0.215-0.502) were protective against FM. Additionally, rheumatoid arthritis (OR=1.138, 95% CI: 1.061-1.221) and ankylosing spondylitis (OR=1.079, 95% CI: 1.021-1.140) were identified as important risk factors for FM. Conclusion: This MR study unveiled a complex causal relationship between modifiable risk factors and FM. Psychosocial factors significantly increase the odds of FM, while obesity and some autoimmune diseases that frequently coexist with FM demonstrate causal associations. Additionally, lifestyle habits such as alcohol consumption are causally related to FM. Further investigation is needed to determine whether risk factors contribute to the pathogenesis of FM through mechanisms involving central sensitization, inflammatory, and hyperalgesia. This study enhances our understanding of the factors that drive FM onset and progression, offering valuable insights for future targeted prevention and treatment strategies.

Behavioral Changes and Long-Term Cortical Thickness Alterations in Women with Fibromyalgia.

OBJECTIVES: The purpose of this study was to examine long-term brain and behavioral changes in patients with fibromyalgia (FM) compared to healthy individuals. METHODS: Data from 33 female volunteers with FM and 33 healthy controls women paired by age and school degree were used to analyze the cortical thickness from high-resolution T1-weighted magnetic resonance imaging (MRI) obtained through a 3T-MRI scanner. Additionally, the Toronto Alexithymia Scale, the Positive and Negative Affect Scale, the emotion regulation questionnaire (ERQ), and the Hamilton Depression and Anxiety rating scales were used to evaluate the behavioral changes. RESULTS: The findings indicate significant cortical structure differences in the right cerebral hemisphere between groups in the insular anterior cortex precentral and postcentral gyrus (P < .001). The FM group scored higher for alexithymia (P < .01), negative affect (P < .01), anxiety (P < .01), and depression (P < .01) symptoms, on the other hand, scored lower for positive affect (P < .01). No differences were found on the left cerebral hemisphere. Furthermore, there was a negative correlation between the right insular anterior cortex and Toronto Alexithymia Scale (P < .001). CONCLUSION: This study showed long-term brain and behavioral changes in patients with FM, suggesting notable neurophysiological alterations associated with this chronic pain condition. It provides new insights into how FM may affect brain health and potential biomarkers for the condition.

Nociplastic Pain: A Critical Paradigm for Multidisciplinary Recognition and Management.

Our understanding of chronic pain has evolved significantly, shifting from a focus on peripheral damage to recognizing the central mechanisms underlying pain perception. This perspective article explores the concept of nociplastic pain, a term introduced by the International Association for the Study of Pain (IASP) in 2017, which describes pain arising from altered pain modulation within the central nervous system, without clear evidence of tissue damage or inflammation. The historical progression from fibrositis to fibromyalgia, and now to nociplastic pain, underscores the complexity of chronic pain syndromes and the need for a multidisciplinary approach to management. Nociplastic pain is characterized by central sensitization, leading to heightened pain sensitivity and often accompanied by comorbidities such as fatigue, sleep disturbances, and cognitive difficulties. Advances in neuroimaging have revealed altered connectivity within key brain networks, such as the default mode and salience networks, in patients with nociplastic pain, providing insights into the neural underpinnings of this condition. The article also addresses controversies surrounding the role of small fiber neuropathy and autonomic dysfunction in nociplastic pain, highlighting the ongoing debates in the field. The practical importance of recognizing nociplastic pain across various medical disciplines-including primary care, orthopedics, neurology, psychiatry, and rheumatology-is emphasized, with recommendations for integrating this knowledge into clinical practice. Emerging therapies, such as neurofeedback, hyperbaric oxygen therapy, and neuromodulation, offer new avenues for treatment, particularly for patients who do not respond to conventional approaches. The article calls for continued research into the mechanisms of nociplastic pain, the development of reliable diagnostic tools, and the exploration of novel therapeutic strategies to improve patient outcomes. The recognition and management of nociplastic pain are crucial for advancing the care of patients with chronic pain, necessitating interdisciplinary collaboration and a patient-centered approach.

Patient-Reported Outcomes of Depression and Fibromyalgia Symptoms Do Not Predict Non-Inflammatory versus Inflammatory Diagnoses at Initial Rheumatology Consultation.

OBJECTIVE: The objective of this study was to assess the potential value of patient-reported outcomes (PROs) of depression, fibromyalgia symptoms, and pain in predicting non-inflammatory vs. inflammatory diagnoses in rheumatology patients. METHODS: This retrospective, single-center study evaluated electronic health record (EHR) data from adults who were seen for their first rheumatology consultation and subsequently received a diagnosis of an inflammatory (e.g., rheumatoid arthritis or spondyloarthritis) or non-inflammatory (e.g., osteoarthritis or fibromyalgia) condition. The PROs evaluated included depressive symptoms (Patient Health Questionnaire-2 [PHQ-2]), fibromyalgia symptom severity (FM SS), and pain. RESULTS: A total of 3669 patients were evaluated, including patients with (n = 984; 26.82%) and without (n = 2685; 73.18%) inflammatory rheumatologic disease, of whom 141 (3.8%) had fibromyalgia. The non-inflammatory subgroup reported higher FM SS scores, and the inflammatory subgroup had higher pain and inflammatory markers. Bivariate models based on PHQ-2 and FM SS had a very low specificity (0.3%) for predicting non-inflammatory conditions, resulting in the misclassification of >99% of inflammatory cases. Adding pain, inflammatory markers, and other relevant EHR variables increased specificity but still resulted in a high level of misclassification. CONCLUSIONS: The PROs evaluated in this study are not suitable for predicting non-inflammatory vs. inflammatory rheumatologic disease, even when combined with other EHR variables.

Understanding Non-Pharmacological Treatments for Fibromyalgia Functional and Well-Being Status: The Role of Literacy.

BACKGROUND/OBJECTIVES: Fibromyalgia (FM) affects up to 5% of the global population and is a leading cause of significant social and economic consequences. Higher health literacy leads to better understanding of treatment plans, improved self-care, and adherence to recommendations, enhancing overall quality of life. This study aims to determine whether different aspects of the disease are influenced by patients' education level and literacy when applying the same therapy and to assess how patients' perceptions of therapy outcomes vary over time based on their educational level. METHODS: This study involved 140 fibromyalgia (FM) patients diagnosed using the 2016 ACR criteria, with 128 completing the study. Participants attended three visits over 28 weeks and were stratified into four groups based on educational level: Group 1-secondary school or less; Group 2-high school graduates; Group 3-college graduates; Group 4-university graduates. Patients were assigned to groups (n = 32, 32, 30, and 34, respectively) after the initial evaluation (T0). The treatment was assessed (T1) and followed up three months later (T2) to evaluate changes in functional status and quality of life. All patients underwent the same rehabilitation program, cognitive therapy, and kinesiotherapy. RESULTS: Significant differences in disease impact on the patient's life (FIQ total score) were observed between groups from the initial evaluation (p = 0.000). The overall FIQ score was notably affected by non-pharmacological therapy in patients with higher education. These differences continued to be significant even three months after the treatment ended (p = 0.000). Functional limitations were evident from the start (p = 0.000) and improved significantly post-treatment in patients with higher education (p = 0.000). However, subjective evaluations of disease impact (assessed by the first item of FIQ) did not consistently align with objective findings (hand grip strength). Functional limitations did not significantly differ in subjective evaluations (F1Q1) across educational levels (p = 0.045), and inverse correlations were noted between functional status and SF-12 well-being components. CONCLUSIONS: This study underscores that higher education enhances fibromyalgia management and functional outcomes, particularly when combined with non-pharmacological therapies. However, subjective perceptions may not always align with objective improvements, indicating that factors beyond education, such as personal and external influences, also impact disease management. Thus, improving health literacy through educational interventions could further benefit FM patients' quality of life.

Adapted Low-FODMAP Diet in IBS Patients with and without Fibromyalgia: Long-Term Adherence and Outcomes.

BACKGROUND/OBJECTIVES: A low-FODMAPs Diet (LFD) is considered a "second line" dietary strategy for irritable bowel syndrome (IBS) but, after a period of strict restriction of all FODMAP foods, it has to be adapted and tailored to each patient (AdLFD). Fibromyalgia often coexists with IBS in up to 65% of cases. Our aims were to evaluate if comorbid fibromyalgia influenced the long-term clinical outcomes and adherence to an AdLFD in IBS patients. METHODS: IBS patients with or without fibromyalgia who had started an AdLFD were enrolled. Patients had been evaluated before starting the LFD (T0). After a mean follow-up of 62.5 ± 22.7 months (T1), they were re-evaluated using questionnaires on disease severity, bowel habits, psychological status, and adherence to AdLFD. RESULTS: In total, 51 IBS patients entered the study. Nineteen of them had comorbid fibromyalgia. Thirty patients reported a reduction in symptom severity at T1 in comparison with T0. Despite some slight differences in single IBS Symptom Severity Score items, comorbid fibromyalgia did not influence the IBS-SSS total score at T1. Patients with comorbid fibromyalgia showed a higher Hospital Anxiety and Depression Scale (HADS) score at baseline. A total of 44 patients showed good long-term adherence to the AdLFD. All patients improved their HADS score and had long-term adherence to the AdLFD. CONCLUSIONS: Comorbid fibromyalgia showed only a slight influence on long-term outcomes of an AdLFD on IBS symptoms, without affecting the relief of global symptoms. No influence on long-term adherence to AdLFD was detected. Hence, this approach can be taken into account in fibromyalgia patients for a nonpharmacological management of IBS symptoms. However, multicentric studies on larger samples would be welcome in the future.

High body mass index disrupts the homeostatic effects of pain inhibitory control in the symptomatology of patients with fibromyalgia.

This study examines the influence of body mass index (BMI) on the relationship between quantitative sensory testing (QST) measures and clinical characteristics in fibromyalgia syndrome (FMS). Utilizing BMI as a categorical covariate (≥25 or ≥30kg/m²) in associations between QST metrics (Pain-60, conditioned pain modulation [CPM], and temporal summation of pain [TSP]) and FMS clinical features, we explored BMI's role as both a confounder (change-in-estimate criterion - change equal or higher than 10%) and effect modifier (interaction term). Significant interactions revealed overweight/obese BMI as a modifier in the relationship between CPM and both depression and symptom impact, with a homeostatic relationship between better clinical profile and pain inhibitory response observed solely in the normal weight group. Similar results were found for Pain-60 and depression. Additionally, BMI ≥30kg/m² modified TSP's effect on pain, demonstrating lower pain with increased TSP, exclusively in the non-obese group. This study highlights the significant role of BMI in moderating the relationships of important pain inhibitory control processes and pain intensity, depression, and the overall impact of FMS symptoms. Our results suggest that high BMI states disrupt the homeostatic effects of pain inhibition, reducing its salutogenic response in FMS participants. We discuss the mechanistic and therapeutic implications of targeting BMI in FMS clinical trials and the potential impact of this important relationship. PERSPECTIVE: This investigation highlights the disruptive influence of high BMI on pain inhibitory control in fibromyalgia, unbalancing clinical symptoms such as pain and depression. It underscores the necessity of integrating BMI considerations into therapeutic approaches to enhance pain management and patient outcomes.

Does practice make perfect? Functional connectivity of the salience network and somatosensory network predicts response to mind-body treatments for fibromyalgia.

Background: Mind-body treatments can improve coping mechanisms to deal with pain, improve the quality of life of patients with fibromyalgia syndrome (FMS), and reduce perceived pain in some cases. However, responses to these treatments are highly variable, the mechanisms underpinning them remain unclear, and reliable predictors of treatment response are lacking. We employed resting-state blood oxygen level-dependent (rsBOLD) functional magnetic resonance imaging (fMRI) to examine changes in brain functional connectivity (FC) following mind-body treatment that may relate to and predict pain relief. Methods: We recruited patients with FMS who underwent either mindfulness-based stress reduction (MBSR; n = 18) or a psychoeducational program (FibroQoL; n = 22) and a treatment-as-usual FMS group (TAU; n = 18). We collected rsBOLD data, alongside subjective pain, anxiety, depression, and catastrophizing measures prior to and following treatments. We examined behavioral changes and FC changes in the salience network (SN) and sensorimotor network (SMN) and performed regression analyses to identify predictors for treatment response. Results: The MBSR and FibroQoL groups experienced significant reductions in pain catastrophizing. After treatment, the FC of the sensorimotor cortex with the rest of the SMN became significantly reduced in the MBSR group compared to the TAU group. The FC between the SN and the SMN at baseline was negatively correlated with pain reductions following MBSR but positively correlated with pain reductions in the FibroQoL group. These results yielded large to very large effect sizes. Following MBSR, only for those patients with lower baseline SMN-SN FC, minutes of mindfulness practice were positively associated with clinical improvement (small to medium effect size). Conclusions: Different mind-body treatments are underpinned by discrete brain networks. Measures of the functional interplay between SN and SMN have the potential as predictors of mind-body treatment response in patients with FMS.

Exploring the psychopathological profile of fibromyalgia: insights from the personality assessment inventory and its association with disease impact.

Background: Fibromyalgia (FM) is a complex rheumatic disorder characterized by chronic nociplastic pain and central sensitization. Psychopathological conditions can influence FM symptoms, which worsen their condition. However, not all patients with FM have psychopathological disorders, indicating a heterogeneous population. Objective: To investigate the psychopathological profile and personality disorders in patients with FM and its relationship impact on this disease. Methods: An observational and cross-sectional comparative study was conducted with a sample of 90 women, mean age 48.7 years (SD = 8.12), from Hospital del Mar, Barcelona. The Personality Assessment Inventory (PAI) and the Fibromyalgia Impact Questionnaire (FIQ) were used for assessment. Results: FM patients predominantly exhibited psychopathological profiles resembling affective disorders (37.7%) and Cluster C personality disorders (58.8%). The severity of FM's impact was related to affective disorder symptoms, hypervigilance, derealization, somatization, and Cluster B personality disorder (emotional instability). Different rheumatic symptoms correlated with specific psychopathological patterns. Increased somatic symptoms on the FIQ were related to an unstable and dependent personality, while heightened emotional symptoms on the FIQ were associated with avoidance, borderline traits, and passive-aggressive reactions. Conclusion: Recognizing psychopathological aspects is crucial for managing FM. The PAI is a valuable tool for establishing its psychopathological multidimensional profile, which predominantly shows an affective spectrum conditions and comorbid Cluster C personality disorder, exacerbating the disease's impact.

Mood states and well-being of spouses of fibromyalgia patients: a systematic review and meta-analysis.

Background: We carried out a systematic review of the medical literature on potential effects of caregiving on the health and well being of spouses of Fibromyalgia (FM) patients and pooled the results in a meta-analysis. Methods: The review is comprised of original studies that examined the mood states and well-being of husbands/wives, or long-term intimate partners, of FM patients. The authors searched the PubMed, Scopus, APA PsycNet and Web of Science databases using the key words "fibromyalgia and spouses," "fibromyalgia and partners," and "fibromyalgia and husbands." Of 570 papers that were initially identified using the search words, 18 papers were considered eligible. We used the Joanna Briggs Institute Critical Appraisal Checklist (JBICAC) and Critical Appraisal Skills Program (CASP) tools to assess the risk of bias in the analytical cross-sectional and qualitative studies, respectively. Results: The overall score in mood states was significantly higher among spouses of FM patients than among spouses of individuals without FM (SMD [95% CI] = 0.52 [0.30; 0.74]). The strongest evidence was found for depression, SMD [95% CI] = 0.68 [0.33; 1.03]. The overall standardized score of quality of life was significantly lower among spouses of FM patients, SMD [95% CI] = -0.59 [-0.79; -0.38], with significant differences in physical function and role, emotional role, and mental health subscales. Limitation: Limitation of this review is the scant number of studies that addressed several health domains, which made it impossible to carry out meta-analyses in these domains. Conclusion: Spouses of FM patients show the emotional and physical consequences of caregiving, and impaired quality of life. Addressing these problems can prevent deterioration of their health and improve their quality of life.

Cushing's Syndrome Masquerading as Fibromyalgia: A Case Series.

Three young female patients with a history of generalized body pain were diagnosed with fibromyalgia. They visited several specialities which related patients' symptoms to their previous diagnosis of fibromyalgia and were treated symptomatically. These patients developed a multitude of clinical features including fractures, hypertension, abnormal weight gain, proximal myopathic pain and bruising. They were seen by rheumatologists whose assessment was that their clinical features were not entirely due to fibromyalgia and suspected that patients have a possible underlying endocrine cause. Patients were referred to an endocrinologist for further tests with suspicion of Cushing's syndrome. Laboratory tests and imaging confirmed a diagnosis of Cushing's syndrome. Two of them had adrenal adenoma and one had iatrogenic corticosteroid use. These cases emphasize the need for thorough clinical evaluation for patients who are thought to have fibromyalgia. Fibromyalgia is a diagnosis of exclusion.