Looking at fibromyalgia differently - An observational study of the meaning and consequences of fibromyalgia as a dimensional disorder.

OBJECTIVE: Despite data showing that fibromyalgia can be represented as a dimensional disorder, almost all assessments treat fibromyalgia as a dichotomous categorial disorder; and research shows that agreement between community diagnosis of fibromyalgia and fibromyalgia criteria is poor. We investigated the validity of FM as a discrete disorder by exploring the relationships of categorical fibromyalgia, the polysymptomatic distress (PSD) scale, and clinical variables. METHODS: In a databank of 33,972 rheumatic disease patients, we studied the categorical diagnosis of fibromyalgia, the PSD scale separately and divided into severity groups, measures of widespread pain, as well as somatic syndrome questionnaires like the Patient Health Questionnaire-15 (PHQ-15), and clinical pain, global, HAQ disability and quality of life scales (EQ-5D). RESULTS: Clinical and demographic variables became more abnormal with increasing PSD score groups, indicating substantial increase in symptoms and pain. The changes across PSD categories were linear and large. When we compared FM- (PSD 8-11) with FM+ (PSD 12-18) patients we found considerable overlap in scores for pain, HAQ disability, patient global, PHQ-15, psychological status, and other variables. Somatic symptom scores were highly correlated with PSD (r=0.718). There was no evidence of a differential pain effect that was present in FM+ but not FM- subjects. CONCLUSION: Fibromyalgia is more accurately considered a dimensional than a dichotomous disorder. There is vast variability among fibromyalgia positive and negative cases that is governed by the strong and linear relationships between the dimensional PSD scale and clinical variables. The PSD scale provides measurements of the fibromyalgia dimension that support and enlighten categorical fibromyalgia and are an effective tool to measure clinical status and changes. Whatever the mechanism of the pain and symptom increase in fibromyalgia, it appears to operate over the entire fibromyalgia symptom dimension, not just in those with categorical fibromyalgia.

The measurement of fibromyalgia severity: converting scores between the FIQR, the PSD and the FASmod.

OBJECTIVES: The revised Fibromyalgia Impact Questionnaire (FIQR) is a widely used fibromyalgia severity assessment tool that was introduced in 2009 prior to the publication of the American College of Rheumatology (ACR) preliminary fibromyalgia criteria in 2010 and its revision in 2016. In 2020, the modified Fibromyalgia Assessment Scale (FASmod) was published. The Polysymptomatic Distress scale (PSD) of the fibromyalgia criteria and FASmod include assessments of pain location severity and can be used for diagnosis as well as in non-fibromyalgia patients. The aim of this study is to provide equations for the conversion of the FIQR scores to PSD and FASmod as an aid to understanding and sharing fibromyalgia severity information. METHODS: 3089 patients with fibromyalgia, diagnosed according to the ACR 2010/2011 criteria and belonging to the Italian Fibromyalgia Registry completed FIQR, FASmod and PSD questionnaires. Pearson's correlation coefficient was used to test the correlations between indices. The least square regression approach was used to produce predictive equations for each scale based on the remaining scales. RESULTS: FIQR was correlated with PSD (r=0.714) and FASmod (r=0.801); PSD and FASmod showed the highest correlation (r=0.897), expected since they assess the same constructs. Predictive equations showing a linear model were effective in producing mean cohort values, but individual predictions deviated substantially, precluding prediction in the individual patient. CONCLUSIONS: Conversion equations that allow for interconversion of multiple scales fibromyalgia severity assessment scales are produced. These can be useful in obtaining mean values for cohorts but are not accurate enough for use in individual patients.

Increase in Cannabis Use Among Adults With Rheumatic Diseases: Results From a 2014-2019 United States Observational Study.

OBJECTIVE: Despite advances in treatments and outcomes among patients with rheumatic diseases, there is an unmet need in pain management. Cannabis has emerged as a potential opioid-sparing alternative, with arthritic pain as a commonly cited reason for medicinal cannabis use. However, little is known, and we set out to understand patterns of cannabis use in a US-wide rheumatic disease population. METHODS: The study included participants in FORWARD, The National Databank for Rheumatic Diseases. Participants were asked in 2014 and 2019 about their past and current cannabis use. Demographic characteristics, patient-reported outcomes, medications, comorbidities, and diagnoses were compared between cannabis users and non-users with t-tests, chi-square tests, logistic regression, and geographic assessment. RESULTS: Among 11,006 respondents, cannabis use increased from 6.3% in 2014 to 18.4% in 2019, with the greatest prevalence of use in states where cannabis use was legalized. Most users (74% and 62% in 2014 and 2019, respectively) reported that cannabis was effective in the relief of arthritis symptoms. Cannabis users were more likely to be taking weak opioids (odds ratio 1.2 [95% confidence interval 1.0, 1.5], P = 0.03), to have a history of smoking tobacco (odds ratio 1.7 [95% confidence interval 1.5, 2.1], P < 0.001), and had worse measures on all assessed patient-reported outcomes. CONCLUSION: Reported cannabis use in this cohort increased significantly between 2014 and 2019. Characteristics of users suggest that those who try cannabis are feeling worse symptomatically, and their pain management needs may not be adequately addressed by other therapies. The association between cannabis, opioids, and patient-reported outcomes highlight areas for future work.

Fibromyalgia revisited: do latent class analyses of symptom profiles in the general population confirm 2016 fibromyalgia diagnostic criteria?

OBJECTIVES: The definition of the 2016 diagnostic criteria of fibromyalgia (FM) syndrome and of FM severities was based on studies with clinical samples. We tested if somatic symptom profiles consistent with the symptom pattern of the FM 2016 diagnostic criteria and of severities of FM can be found in the general population. METHODS: Somatic symptom burden was measured by the Somatic Symptom Scale - 8 in 2,531 persons aged ≥14 years representative for the general German population. We used latent class analysis of SSS-8 items to identify somatic symptom profiles. The profiles were described by their association with age, gender, self-reported disabling somatic disease, psychological symptom burden, illness worries and self-perceived health. RESULTS: We identified five somatic symptom profiles. The majority of the population (40.9%) had a profile characterised by the absence of bothering symptoms. 5.9% had a profile defined by "considerable bothering" back and extremities pains, fatigue and sleep problems. This symptom profile was associated with older age, self-reported somatic diseases, psychological symptom burden and fair to poor general health. 63.2% of persons meeting FM 2016 criteria belonged to this profile. 17.8% of the sample were characterized by little perturbation by multiple somatic symptoms and good to fair general health. 36.8% of persons meeting FM 2016 criteria belonged to this profile. CONCLUSIONS: Two somatic symptom profiles consistent with the 2016 FM diagnostic criteria were identified in the general German population. These symptom profiles differed in somatic and psychological symptom burden and general health supporting the distinction of FM severities.

The relation of fibromyalgia and fibromyalgia symptoms to self-reported seizures.

OBJECTIVE: Several epidemiological and clinical reports associate fibromyalgia (FM) with seizure disorders, and clinical studies associate FM diagnosis with psychogenic non-epileptic seizures. However, these associations rely on self-reports of being diagnosed with FM or unstandardized clinical diagnosis in combination with small samples. We investigated the association of FM and self-reported seizures using a large rheumatic disease databank and the current established self-reported, symptom-based FM diagnostic criteria. METHODS: We selected a random observation from 11,378 subjects with rheumatoid arthritis (RA), 2,390 (21.0%) of whom satisfied 2016 revised criteria for FM. Patients were inquired about the presence of any kind of seizures in the previous 6 months, anti-epileptic medications, and patient-reported symptoms and outcomes. RESULTS: Seizures were reported by 89 RA patients who met FM criteria (FM+) and by 97 patients who did not (FM-), resulting in an age- and sex-adjusted seizure prevalence of 3.74 (95% CI 2.95 to 4.53) per 100 FM+ subjects and 1.08 (95% CI 0.87 to 1.30) in FM- subjects. The seizure odds ratio of FM+ to FM- cases was 3.54 (95% CI 2.65 to 4.74). Seizures were associated to a very similar degree with symptom reporting (somatic symptom count and comorbidity index) as to FM diagnosis variables. RA patients reporting seizures also reported worse pain, quality of life, and functional status. Seizure patients treated with anti-seizure medication had worse outcomes and more comorbidities than seizure patients with no seizure drugs. CONCLUSIONS: We found a significant and similar association of both FM diagnostic variables and FM-related symptom variables, including the number of symptoms and comorbidities, with self-reported seizures in people with RA. The observed association was similar to those found in previous studies of symptoms variables and seizures and does not suggest a unique role for fibromyalgia diagnosis. Rather, it suggests that multi-symptom comorbidity is linked to seizures in a complex and not yet clearly understood way. As the current study relied on self-reported seizures and was not able to distinguish between epileptic and psychogenic nonepileptic seizures, future studies are needed to replicate the findings using both validated FM criteria assessments and clinically verified diagnoses of epileptic and psychogenic seizures.

Subjective Cognitive Dysfunction in Patients With and Without Fibromyalgia: Prevalence, Predictors, Correlates, and Consequences.

BACKGROUND: Subjective cognitive dysfunction (SCD) is common in fibromyalgia (FM), where it has been called 'fibrofog.' But its predictors and correlates are not well understood, including the extent to which SCD is present in fibromyalgia and non-fibromyalgia clinical populations. In addition, there are no studies available concerning SCD and fibromyalgia in the general population. We investigated these issues in a longitudinal rheumatic disease research databank and two cross-sectional general population studies. METHODS: 11,150 unselected patients with rheumatoid arthritis completed an assessment of FM and cognitive severity (CS) status using the full 0-3 fibromyalgia 2016 criteria assessment. In addition, CS was dummy coded as present/absent (CS+). Assessments of SCD and fibromyalgia prevalence were available in two German general population studies. RESULTS: Fibromyalgia was present (FM+) in 2,493 (21.7%) of clinical subjects and absent (FM-) in 9,017 (78.3%) by FM 2016 criteria. Cognitive severity was present in 1,304 (52.3%) of those with fibromyalgia and 1,009 (11.2%) of non-fibromyalgia subjects (FM-). In two general population studies, 42.0% to 52.3% of those with fibromyalgia were CS+ as were 1.4% to 5.5% of FM- subjects. Patients with CS+ had more abnormal scores for every measure of rheumatoid arthritis (RA) severity, fibromyalgia severity, and general health. The presence of CS+ was strongly related to somatic and non-somatic symptoms scores and less strongly to pain variables. The best predictor of CS+ in the clinic and the general population was the symptom severity scale (SSS), a criterion of fibromyalgia. CONCLUSIONS: Persons with SCD have high counts of somatic and psychological symptoms. Subjective cognitive dysfunction is best predicted by a simple symptoms score, and not by pain extent scores. Although SCD is called fibrofog in patients with FM, 43.6% of CS+ cases occurred in FM- subjects. Fibromyalgia and CS are correlated but appear to be different parts of a symptom severity continuum. 'Fibrofog' as a phenomenon linked only to fibromyalgia is a misnomer because it can be identified in many non-fibromyalgia patients as well.

The Evolution of Fibromyalgia, Its Concepts, and Criteria.

Fibromyalgia developed in the 1950s from a substrate of difficult to explain regional and widespread pain mixed with symptoms of psychosocial distress. Controversies regarding psychological issues were common. Multiple criteria arose to define the disorder, but each identified a different set of patients. The identification of widespread pain as a criterion changed the nature of the disorder by effectively eliminating regional pain as a component condition. The easy-to-measure and relatively reliable widespread pain criterion then came to define the disorder. In the primary care community, diagnostic criteria were largely ignored, and a substantial fraction of diagnosed patients with lower pain scores, particularly women and those with high non-pain symptom scores, were diagnosed. Non-pain symptoms were added back to the fibromyalgia definition and criteria in 2010. Recognition grew that fibromyalgia fit the description of a functional somatic disorder. The idea of fibromyalgia as a primary pain disorder with a neurobiological basis contended with fibromyalgia as a broader biopsychosocial disorder. It is increasingly recognized that fibromyalgia represents a dimensional, non-binary condition and that features of fibromyalgia extend to persons who do not satisfy the criteria. Severity assessments are now available but rarely used. The course of fibromyalgia is not well studied, and improvement and remission criteria have not been successfully defined. The future of fibromyalgia as a discrete disorder remains uncertain as features of fibromyalgia are increasingly observed in patients with multiple different medical conditions.

Modified 2016 American College of Rheumatology Fibromyalgia Criteria, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy, and the Prevalence of Fibromyalgia.

OBJECTIVE: To study the prevalence of fibromyalgia (FM) in the general population according to a 2016 modification of the American College of Rheumatology criteria (FM 2016) and the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society pain taxonomy criteria (AAPT), and to compare diagnostic and clinical variables between the criteria sets. METHODS: We studied 2,531 randomly selected subjects from the German general population in 2019. Pain regions from the Michigan Body Map were fitted to the FM 2016 and the AAPT criteria, and criteria symptom items were derived from validated questionnaires assessing somatic and psychological symptom burden and disability. We determined FM criteria prevalence and criteria-related scales including widespread and multisite pain (MSP) and symptom scales, and measured symptom burden and disability. RESULTS: According to the FM 2016 criteria, the prevalence of FM was 3.4% (n = 75 subjects; 95% confidence interval [95% CI] 2.7, 4.3) compared with 5.7% (n = 130 subjects; 95% CI 4.8, 6.8) for the AAPT criteria; κ = 0.65. Compared with AAPT-positive subjects, FM 2016-positive subjects had higher MSP, Widespread Pain Index score, Polysymptomatic Distress Scale scores, Symptom Severity Scores, and psychological symptom burden. Physician-diagnosed FM was reported by 1.1% of the subjects. Of these, 44.0% met the FM 2016 criteria, and 47.5% met the AAPT criteria. CONCLUSION: The prevalence of FM in the German general population is 73% greater using the AAPT criteria than the FM 2016 criteria. The AAPT criteria select individuals with less symptom severity and fewer pain sites. The FM 2016 criteria, but not the AAPT criteria, provide a general severity measure for FM.

Petrochemical wastewater and produced water: Treatment technology and resource recovery.

Petrochemical wastewater and produced water from oil and gas operations typically contain an array of organic and inorganic contaminants. The complexity of the wastewater, stringent environmental regulations, and the need for sustainable solutions have driven many research efforts in studying and developing advanced technology or combined treatment processes. On the other hand, the wastewater itself can be resources for water, energy, and other valuable product if appropriate technology is developed to recover them in a cost-effective fashion. The research advances in wastewater treatment and resource recovery technology are reviewed and summarized. For petrochemical wastewater, progresses were made in advanced oxidation, biological processes, and recovery of energy and water from wastewater. For produced water, many efforts were focused on membrane processes, combined systems, and biological treatment. PRACTITIONER POINTS: Significant progress continued to be made on petrochemical wastewater and produced water treatment. Recent technological advances in various treatment processes were summarized. Technologies focusing on resource recovery (e.g., water or energy) were presented.

Prevalence and overlap of somatic symptom disorder, bodily distress syndrome and fibromyalgia syndrome in the German general population: A cross sectional study.

OBJECTIVE: To study the prevalence and clinical characteristics of Somatic Symptom Disorder (SSD), Bodily Distress Syndrome (BDS) and fibromyalgia syndrome (FMS) and their overlap in the general German population. METHODS: A cross-sectional nationally representative population survey was performed. 2531 participants (mean age 48.8 ±â€¯17.85 years, 53.3% women) completed the Somatic Symptom Scale SSS-8, the Bodily Distress Syndrome (BDS) 25 checklist, the Whiteley Index 7 (WI-7), the self-administered comorbidity questionnaire and the Michigan Body Map. Case definitions of SSD, BDS and FMS were assigned using established criteria. RESULTS: 4.5% of participants met the criteria of SSD (SSS - 8 at least one item "bothered very much" and WI- 7 total score ≥ 1). 9.6% met the criteria of single-organ BDS and 1.3% of multi-organ BDS. Prevalence of FMS according to 2016 criteria was 3.4%. 82.3% of FMS cases met any BDS criteria.28.1% of FMS cases satisfied SSD criteria. 28.8% of any BDS cases met the criteria of SSD. 75.1% of SSD cases met the criteria of any BDS. FMS cases reported the highest amount of somatic and psychological symptom burden and health anxieties. There were no differences in age and gender between any BDS and SSD cases. SSD cases reported worse general health and more fibromyalgia-related variables than any BDS cases. CONCLUSIONS: In the general population, there is a substantial overlap between FMS and BDS, but not of FMS and SSD, and not of SSD and any BDS. Case definitions of the three disorders partially captured different groups in the general population.

All-cause and cause-specific mortality in persons with fibromyalgia and widespread pain: An observational study in 35,248 persons with rheumatoid arthritis, non-inflammatory rheumatic disorders and clinical fibromyalgia.

PURPOSE: Studies of the relation of fibromyalgia (FM) and widespread pain (WSP) to mortality have differed as to the presence or absence of an association and the extent of cause-specific mortality. However, no studies have investigated which definitions of FM and WSP associate with mortality, nor of FM mortality in other diseases. We investigated these issues and the meaning of mortality in patients with FM. METHODS: We used Cox regression to study 35,248 rheumatic disease patients with up to 16 years of mortality follow-up in all patients and separately in those with diagnoses of rheumatoid arthritis (RA) (N = 26,458), non-inflammatory rheumatic disorders (NIRMD) (N = 5,167) and clinically diagnosed FM (N = 3,659). We applied 2016 FM criteria and other FM and WSP criteria to models adjusted for age and sex as well as to models that included a full range of covariates, including comorbid disease and functional status. We estimated the degree of explained of variance (R2) as a measure of predictive ability. RESULTS: We found positive associations between al`l definitions of FM and WSP and all-cause mortality, with relative risks (RR)s ranging from 1.19 (95%CI 1.15-1.24) for American College of Rheumatology (ACR) 1990 WSP to 1.38 (1.31-1.46) in age and sex adjusted revised 2016 criteria (FM 2016). However, in full covariate models the FM 2016 RR reduced further to 1.15 (1.09-1.22). The association with mortality was noted with RA (1.52 (1.43-1.61)), NIRMD (1.43 (1.24-1.66)) and clinical FM (1.41 (1.14-1.75) - where 37% of FM diagnosed patients did not satisfy FM 2016 criteria. In the all-patient analyses, the age and sex explained variation (R2) was 0.255, increasing to 0.264 (4.4%) when FM 2016 criteria were added, and to 0.378 in a full covariate model. Death causes related to FM 2016 status included accidents, 1.45 (1.11-1.91); diabetes 1.78 (1.16-2,71); suicide, 3.01 (1.55-5.84) and hypertensive related disorders, 3.01 (1.55-5.84). Cancer deaths were less common 0.77 (0.68-0.88). CONCLUSIONS: FM is weakly associated with mortality within all criteria definitions of FM and WSP examined (3.4% of explained variance), and across all diseases (RA, NIRMD, clinical FM) equally. Clinical and criteria-defined FM had different mortality outcomes. We found no evidence for a positive association of cancer and FM or WSP.

The Relation of Physical Comorbidity and Multimorbidity to Fibromyalgia, Widespread Pain, and Fibromyalgia-related Variables.

OBJECTIVE: To investigate the relation of physical (non-psychological) comorbidity and multimorbidity to quantitative measures of fibromyalgia (FM) and musculoskeletal pain. METHODS: We studied 12,215 patients in a research databank with quantitative measures of FM-related variables (FMV) that included binary determinations of FM and widespread pain (WSP), and constituent variables of FM diagnosis that included the WSP index (WPI), the symptom severity score (SSS), and the polysymptomatic distress scale (PSD). We assessed self-reported comorbid conditions and covariates that included age, sex, body mass index, hypertension, smoking history, and total household income. We used nearest-neighbor matching and regression adjustment treatment effects models to measure the effect of comorbidities on FMV. RESULTS: We found a positive association between FMV and the probability of having each comorbid condition. Patients with ≥ 1 comorbidities had PSD, WPI, and SSS increases of 3.0 (95% CI 2.7-3.3), 1.8 (95% CI 1.6-2.0), and 1.2 (95% CI 1.1-1.3) units, respectively, and an increase in FM prevalence from 20.4% to 32.6%. As the number of comorbid conditions present increased from 1 to 4 or more, PSD, WPI, SSS, and FM percent increased stepwise. For patients with ≥ 4 conditions, the predicted prevalence of FM was 55.2%. CONCLUSION: FM and FMV are associated with an increase in the number of comorbidities, and the association can be measured quantitatively. However, the association of WSP and FM may be an effect of definitions of WSP and FM, because comorbidity increases are also present with subsyndromal levels of both conditions.

The Problematic Nature of Fibromyalgia Diagnosis in the Community.

BACKGROUND: Recently, some studies suggested that clinical diagnosis of fibromyalgia is inaccurate and does not reflect current definitions. However, this hypothesis has not been tested. We examined whether fibromyalgia was accurately diagnosed in the community. METHODS: We surveyed 3276 primary care patients to determine current fibromyalgia status by criteria (CritFM). We also determined whether the patients had a physician's diagnosis of fibromyalgia (MDFM) and the level of symptom severity as measured by the polysymptomatic distress scale (PSD). RESULTS: The prevalence of MDFM and CritFM was 6.1% (95% confidence interval [CI] 5.3%, 6.9%) and 5.5% (95% CI 4.8%, 6.3%), respectively. However, only 32.2% with MDFM met 2016 criteria (CritFM), and only 35.4% with CritFM also had MDFM. The kappa statistic for diagnostic agreement was 0.296 (minimal agreement). The mean PSD score was 12.4 and 18.4 in MDFM and CritFM, respectively. The odds ratio for being a woman compared with being a man was 3.2 for MDFM versus 1.9 for CritFM, P = 0.023. Of the patients with MDFM, 68.3% received specific fibromyalgia pharmacotherapy. CONCLUSIONS: There is little agreement between MDFM and CritFM. Only one-third of MDFM satisfy fibromyalgia criteria, and only one-third of patients who meet the criteria have a clinical diagnosis of fibromyalgia. Physician diagnosis is biased and more likely in women. Fibromyalgia treatment is common in MDFM (70.7%). Overall, MDFM appears subjective and unrelated to fibromyalgia criteria. There appears to be no common definition of fibromyalgia in the community.

Risk of Serious Infection in Patients With Rheumatoid Arthritis Treated With Biologic Versus Nonbiologic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: The objective of this study is to examine the risk of serious infections (SIs) associated with biological disease-modifying antirheumatic drugs (bDMARDs) compared with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis (RA). METHODS: We studied patients with RA who initiated bDMARDs or csDMARDs from 2001 to 2016 in FORWARD-The National Databank for Rheumatic Diseases. Disease-modifying antirheumatic drugs (DMARDs) were categorized into three groups: (1) csDMARDs (bDMARD-naïve; reference), (2) tumor necrosis factor α inhibitors (TNFis), and (3) non-TNFi biologics (abatacept, rituximab, tocilizumab, and anakinra). SIs were defined as those requiring intravenous antibiotics or hospitalization or those resulting in death. We calculated the propensity score (PS), which reflected the probability of receiving a specific DMARD group, and estimated the hazard ratio (HR) (with the 95% confidence interval [CI]) for SI from multivariable Cox models, adjusting for PS and time-varying confounders. RESULTS: A total of 694 (5.9%) first SIs were identified in 11 623 patients with RA during 27 552 patient-years of follow-up. The SI incidence rate per 1000 patient-years was 22.4 (95% CI 19.2-26.1) for csDMARDs, 26.9 (95% CI 24.5-29.6) for TNFis, and 23.3 (95% CI 19.0-28.5) for non-TNFi bDMARDs. Adjusted HRs for SIs were 1.33 (95% CI 1.05-1.68) for TNFis and 1.48 (95% CI 1.02-2.16) for non-TNFi bDMARDs, compared with csDMARDs. The SI risk with non-TNFi bDMARDs versus TNFis was not different. Other risk factors for SI were older age, higher comorbidity burden (particularly pulmonary disease), higher weighted cumulative prednisone dose, disability and disease activity, and number of prior csDMARD failures. CONCLUSION: TNFis and non-TNFi bDMARDs were associated with an increased SI risk compared with csDMARDs in RA, even after accounting for risk-associated patient characteristics.