Reduced Immune Response to Inactivated Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine in a Cohort of Immunocompromised Patients in Chile.

BACKGROUND: Inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been widely implemented in low- and middle-income countries. However, immunogenicity in immunocompromised patients has not been established. Herein, we aimed to evaluate immune response to CoronaVac vaccine in these patients. METHODS: This prospective cohort study included 193 participants with 5 different immunocompromising conditions and 67 controls, receiving 2 doses of CoronaVac 8-12 weeks before enrollment. The study was conducted between May and August 2021, at Red de Salud UC-CHRISTUS, Santiago, Chile. Neutralizing antibody (NAb) positivity, total anti-SARS-CoV-2 immunoglobulin G antibody (TAb) concentrations, and T-cell responses were determined. RESULTS: NAb positivity and median neutralizing activity were 83.1% and 51.2% for the control group versus 20.6% and 5.7% (both P < .001) in the solid organ transplant group, 41.5% and 19.2% (both P < .0001) in the autoimmune rheumatic diseases group, 43.3% (P < .001) and 21.4% (P<.01 or P = .001) in the cancer with solid tumors group, 45.5% and 28.7% (both P < .001) in the human immunodeficiency virus (HIV) infection group, 64.3% and 56.6% (both differences not significant) in the hematopoietic stem cell transplant group, respectively. TAb seropositivity was also lower for the solid organ transplant (20.6%; P < .0001), rheumatic diseases (61%; P < .001), and HIV groups (70.9%; P = .003), compared with the control group (92.3%). On the other hand, the number of interferon γ spot-forming T cells specific for SARS-CoV-2 tended to be lower in all immunocompromising conditions but did not differ significantly between groups. CONCLUSIONS: Diverse immunocompromising conditions markedly reduce the humoral response to CoronaVac vaccine. These findings suggest that a boosting vaccination strategy should be considered in these vulnerable patients. CLINICAL TRIALS REGISTRATION: NCT04888793.

Are Cannabis, Cannabis-Derived Products, and Synthetic Cannabinoids a Therapeutic Tool for Rheumatoid Arthritis? A Friendly Summary of the Body of Evidence.

BACKGROUND: Symptom management in rheumatoid arthritis (RA) remains a complex challenge. Widespread use of cannabis-based medicines for a myriad of symptoms has fostered rheumatology patients' interest. However, their safety and efficacy in RA remain unclear. OBJECTIVE: The aim of this study was to perform a structured summary of the body of evidence in order to determine whether cannabis, cannabis-derived products, and synthetic cannabinoids are an effective treatment for rheumatoid arthritis. METHODS: An electronic search in Epistemonikos database was performed to identify systematic reviews and their primary studies that addressed our clinical question. The body of evidence was collected in a pivot table in Epistemonikos. Information and data from the primary studies were extracted from the identified reviews. Finally, extracted data were reanalyzed, and a summary of findings table was generated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Twenty-six systematic reviews were identified which included in total only 1 randomized trial assessing our clinical question. CONCLUSIONS: Cannabis, cannabis-derived products and synthetic cannabinoids may slightly reduce disease activity in patients with RA. Its use may result in little to no difference in pain reduction and may slightly increase nervous system adverse events. The evidence is very uncertain about the effect of cannabis, cannabis-derived products, and synthetic cannabinoids on serious adverse events risk.

Chronic Musculoskeletal Pain and Chronic Widespread Pain in Chile: Prevalence Study Performed as Part of the National Health Survey.

OBJECTIVES: Chronic musculoskeletal pain (CMP) causes significant health loss worldwide. Given that cultural factors may affect pain processing, it is key to have more information regarding CMP epidemiology in Latin America. In this study, we aimed to determine the prevalence of CMP and chronic widespread pain (CWP) in Chile. METHODS: This was a cross-sectional survey study. We used data recollected in the 2016-2017 Chilean National Health Survey, a nationwide household survey. Our study population included subjects older than 14 years living in urban and rural Chile. We defined CMP as nontraumatic pain with a duration of longer than 3 months. Chronic widespread pain was defined by the presence of CMP in 5 body regions. The association between CMP and CWP and potential risk factors was investigated through univariate and multivariate logistic regression models. RESULTS: After excluding subjects with missing information our final sample constituted 4045 subjects. Chronic musculoskeletal pain was present in 21.8% (95% confidence interval, 19.6%-24.1%) and CWP in 4.2% (95% confidence interval, 3.3%-5.1%). Significant risk factors in multivariate analysis were older age, female sex, lower educational level, and depressive symptoms. Factors associated with a reduced risk of CMP were not being married and moderate alcohol consumption. CONCLUSIONS: One of 5 Chilean people has chronic pain, and 1 of 20 has CWP. Data regarding alcohol and pain have been controversial in previous studies; therefore, this decreased risk in moderate consumers should be further explored. Chronic widespread pain shared risk factors and protective factors with CMP but with a higher magnitude of association.

Psychometric Properties of the Fibromyalgia Survey Questionnaire in Chilean Women With Fibromyalgia.

OBJECTIVE: The aim of this study was to evaluate the psychometric properties of the Chilean version of the Fibromyalgia Survey Questionnaire (FSQ). METHODS: Women with fibromyalgia (FM; n = 214), women with rheumatoid arthritis (RA; n = 97), and women without chronic pain (being followed by Gynecology, G; n = 117) from the Red de Salud UC CHRISTUS (Santiago, Chile) participated. Women with FM completed the FSQ, Fibromyalgia Impact Questionnaire (Revised Version), Numerical Pain Rating Scale, Pain Catastrophizing Scale, Pain Vigilance and Awareness Questionnaire, Patient Health Questionnaire 15, and Short-Form Health Survey. Two weeks later, they completed the FSQ again by phone (n = 120). RESULTS: The FSQ total scale showed excellent to good internal consistency at T1 (α = 0.91, ω = 0.91) and T2 (α = 0.78, ω = 0.78), and good test-retest reliability (intraclass correlation coefficient, 0.79; 95% confidence interval [CI], 0.72-0.85). It showed medium to large correlations with the other measures. Discriminant analysis between the FM group and the control group (RA and G) revealed that the FSQ total scale reached a classification accuracy of 81.3%. Receiver operating characteristic curve (adjusted area under the curve, 0.88; 95% CI, 0.85-0.92) showed that the best FSQ cutoff was 17, resulting in sensitivity of 89% (95% CI, 0.84-0.93) and specificity of 75% (95% CI, 0.69-0.80). Considering the FM diagnosis performed by a rheumatologist as the criterion standard, sensitivity and specificity of the modified 2010 American College of Rheumatology preliminary criteria for FM were 92.8% (95% CI, 0.88-0.96) and 63.4% (95% CI, 0.57-0.70), respectively. CONCLUSIONS: The Chilean version of the FSQ presents good psychometric properties and is a useful tool in clinical settings to assist in FM diagnosis and symptom assessment. A cutoff score of 17 or higher seems to be the most appropriate for Chilean population.

Evaluation of the Health Assessment Questionnaire Disability Index in Chilean patients with rheumatoid arthritis.

BACKGROUND: The Health Assessment Questionnaire Disability Index (HAQDI) is one of the main instruments used to evaluate functional status in rheumatoid arthritis (RA). AIM: To assess the reliability and validity of the Spanish version of HAQDI in Chilean RA population. MATERIALS AND METHODS: The questionnaire was applied to 98 patients with RA aged 44 ± 12 years (90% women). Reliability was assessed using Cronbach's alpha statistic for internal consistency. Construct validity was assessed by comparing total HAQDI value and eight HAQDI domains with multiple parameters of disease activity. Discriminant validity was evaluated by classifying disease activity in low, medium or high and evaluating HAQDI value in each category. Floor and ceiling effects were evaluated. To assess construct validity, principal components analysis was performed using varimax rotation. RESULTS: There were no issues in the comprehensibility of the questionnaire. Mean HAQDI score was 1.57 ± 0.66. Standardized Cronbach's Alpha was 0.883. Correlations between Chilean HAQ domains had a p value less than 0.001, and values ranged from 0.317 to 0.597. Activity parameters, DAS 28 and CDAI were significantly correlated with HAQDI domains. Mean HAQDI values were 0.98 ± 0.59,1.45 ± 0.57, and 1.90 ± 0.56 for mild, moderate and severe disease activity. A principal components analysis identified two factors that accounted for 70.0% of total variability. CONCLUSIONS: This study shows that the Spanish version of HAQDI is reliable and valid and can be used in Chilean patients with RA.

Methotrexate dosage as a source of bias in biological trials in rheumatoid arthritis: a systematic review.

OBJECTIVES: To evaluate if optimal dose of either oral or injectable regimens of methotrexate (MTX) of 25 mg/week was used in the comparator arms of studies comparing biologic drugs with MTX in rheumatoid arthritis (RA). METHODS: A systematic literature search was carried out in MEDLINE, EMBASE and the Cochrane Library databases for randomised controlled trials comparing biologics with MTX in RA. A systematic review was performed among studies that met predefined criteria focusing on assessment of dose of MTX used in the comparator arm. Study authors were contacted when necessary. Study quality was assessed. RESULTS: A total of 3276 references were identified and 13 trials were included. We obtained maximal dose and regimen for all. The maximal dose of MTX used in the comparator arm of the trials was no more than 20 mg/week in any trial and for all but one trial, MTX was given orally and not by injection. The trial that used an injectable form reached a maximum of 15 mg/week. CONCLUSIONS: A suboptimal dose of MTX was used in biological clinical trials performed in RA, particularly regarding route of administration. This may have biased findings in favour of biological agents.

The effect on treatment response of fibromyalgic symptoms in early rheumatoid arthritis patients: results from the ESPOIR cohort.

OBJECTIVE: To evaluate whether patients with RA who belong to the spectrum of fibromyalgic RA (FRA) have an impaired response to treatment measured by traditional activity scores. METHODS: Patients from the ESPOIR cohort were analysed. This prospective cohort included 813 patients with early arthritis not initially receiving DMARDs. Among the 697 patients who met RA classification criteria, we studied two groups, one with and the other without FRA. The following endpoints were compared at 6, 12 and 18 months using a mixed linear regression model: 28-joint DAS (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and HAQ. In addition, attainment of low disease activity (LDA; DAS28 <3.2) and remission (DAS28 <2.6, SDAI <3.3, CDAI <2.8) at these time points was analysed. RESULTS: Patients with FRA (n = 120) had higher DAS28, SDAI, CDAI and HAQ scores than patients with RA and no fibromyalgic characteristics (n = 548). DAS28 and other DASs started out higher in subjects with FRA, and while they improved to a similar extent to in the isolated RA group, they remained consistently higher among FRA patients. Achievement of LDA and remission was significantly less likely in subjects with FRA. CONCLUSION: Patients with FRA and RA will have a similar response to treatment according to the decrease in indexes of disease activity, but may miss the target of remission or LDA.

Chronic pain in Chile: first prevalence report of noncancer chronic pain, fibromyalgia, and neuropathic pain and its associated factors.

ABSTRACT: Although we know chronic pain (CP) affects approximately 30% of people in developed countries, data from Latin America are scarce. Moreover, prevalence of specific CP conditions, such as chronic noncancer pain (CNCP), fibromyalgia (FM), and neuropathic pain (NP), is unknown. To estimate them in Chile, we prospectively enrolled 1945 participants (61.4% women and 38.6% men), aged 38 to 74 years, from an agricultural town who answered a Pain Questionnaire, the Fibromyalgia Survey Questionnaire, and Douleur Neuropathique 4 (DN4) to identify CNCP, FM, and NP, respectively. The estimated prevalence of CNCP was 34.7% (95% CI 32.6; 36.8), with an average duration of 32.3 months (SD ± 56.3), producing deep impairments in daily activities, sleep, and mood. We estimated a prevalence of 3.3% for FM (95% CI 2.5; 4.1) and 12% for NP (95% CI 10.6; 13.4). Female sex, fewer school years, and depressive symptoms were associated with FM and NP, whereas diabetes was only associated with NP. We standardized the results from our sample against the whole Chilean population and found no significant difference to our crude estimates. This is in line with studies from developed countries, highlighting the idea that despite genetic and environmental differences, the conditions that confer risk to CNCP remain stable.

Latin American Genes: The Great Forgotten in Rheumatoid Arthritis.

The successful implementation of personalized medicine will rely on the integration of information obtained at the level of populations with the specific biological, genetic, and clinical characteristics of an individual. However, because genome-wide association studies tend to focus on populations of European descent, there is a wide gap to bridge between Caucasian and non-Caucasian populations before personalized medicine can be fully implemented, and rheumatoid arthritis (RA) is not an exception. In this review, we discuss advances in our understanding of genetic determinants of RA risk among global populations, with a focus on the Latin American population. Geographically restricted genetic diversity may have important implications for health and disease that will remain unknown until genetic association studies have been extended to include Latin American and other currently under-represented ancestries. The next few years will witness many breakthroughs in personalized medicine, including applications for common diseases and risk stratification instruments for targeted prevention/intervention strategies. Not all of these applications may be extrapolated from the Caucasian experience to Latin American or other under-represented populations.

The Genetics of Spondyloarthritis.

The term spondyloarthritis (SpA) encompasses a group of chronic inflammatory diseases with common features in terms of clinical presentation and genetic predisposition. SpA is characterized by inflammation of the spine and peripheral joints, and is also be associated with extra-articular inflammatory manifestations such as psoriasis, uveitis, or inflammatory bowel disease (IBD). The etiology of SpA is not completely understood, but it is known to have a strong genetic component dominated by the human leukocyte antigen (HLA)-B27. In the last few years, our understanding of genetic susceptibility to SpA, particularly ankylosing spondylitis (AS), has greatly improved thanks to the findings derived from powered genome-wide association studies (GWAS) based on single nucleotide polymorphism (SNP) arrays. These studies have identified many candidate genes, therefore providing new potential directions in the exploration of disease mechanisms, especially with regard to the key role of the immune system in the pathogenesis of SpA. SpA is a complex disease where genetic variability, environmental factors, and random events interact to trigger pathological pathways. The aim of this review is to summarize current findings on the genetics of SpA, some of which might help to study new treatment approaches.

The Prevalence of Rheumatoid Arthritis in Chile: A Nationwide Study Performed as Part of the National Health Survey.

OBJECTIVE: Genetic and environmental backgrounds influence the development of rheumatoid arthritis (RA). In Latin America, epidemiologic data are scarce. We aimed to determine the prevalence of RA in Chile in a population-based study. METHODS: The National Health Survey was a cross-sectional household survey with a stratified multistage probability sample of 6233 participants performed between August 2016 and March 2017. A screening instrument for RA was applied to a random sample of 3847 subjects > 30 years old. Positive screening was defined by at least 1 of the following: 2 swollen joints for at least 4 consecutive weeks (past/present), and/or a diagnosis of arthritis in the past. Individuals with positive screening had rheumatoid factor, anticitrullinated protein antibodies, and C-reactive protein measured, as well as clinical examination performed by a rheumatologist. Self-report of doctor-diagnosed RA was also performed. RESULTS: The screening questionnaire was applied to 2998 subjects. A positive screening was found for 783 (22.1%). Among subjects with positive screening, 493 (66%) had a clinical evaluation performed by a rheumatologist. Using the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria, prevalence was 0.6% (95% CI 0.3-1.2). Prevalence was higher in women, and 3.3% of subjects self-reported having RA. CONCLUSION: According to this national population-based study, RA prevalence in Chile is 0.6% (0.3-1.2), a value similar to what has been found in developed countries and slightly lower than some Latin American countries. Self-reporting leads to overestimating RA.

Effects of Mediterranean diet on the treatment of rheumatoid arthritis. / Efectos de la dieta mediterránea en el tratamiento de la artritis reumatoide.

INTRODUCTION: It has been suggested that environmental and lifestyle factors might contribute to the severity and progression of inflammation in rheumatoid arthritis. An intervention generating high interest due to its supposed anti-inflammatory properties is the Mediterranean diet. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified seven systematic reviews including four primary studies, of which only one corresponded to a randomized trial. We concluded Mediterranean diet may make little or no difference in pain or disease activity and may slightly increase weight in rheumatoid arthritis patients, but the certainty of the evidence is low. On the other hand, it was not possible to clearly establish whether Mediterranean diet has any effect on functionality, morning stiffness or quality of life as the certainty of the existing evidence has been assessed as very low.

INTRODUCCIÓN: Se ha planteado que factores ambientales y relacionados con el estilo de vida pueden contribuir a la severidad y progresión de la inflamación en la artritis reumatoide. Una intervención que genera un alto interés, debido a sus supuestas propiedades antiinflamatorias es la dieta mediterránea. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos siete revisiones sistemáticas que en conjunto incluyeron cuatro estudios primarios, de los cuales sólo uno corresponde a un ensayo aleatorizado. Concluimos que la dieta mediterránea podría hacer poca o nula diferencia en el dolor articular o actividad de la enfermedad, y aumentar levemente el peso en pacientes con artritis reumatoide, pero la certeza de la evidencia es baja. Por otra parte, no es posible establecer con claridad si la dieta mediterránea tiene algún efecto sobre la funcionalidad, rigidez matinal o calidad de vida, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

Efficacy and safety of biological agents in the older rheumatoid arthritis patients compared to Young: A systematic review and meta-analysis.

OBJECTIVE: Biologic anti-rheumatic drugs are used with less frequency among older patients compared to young patients. This population is less represented in studies performed to evaluate the efficacy and safety of this drugs. We aimed to assess the efficacy and safety of biological agents between the older RA patients compared to young. METHODS: A comprehensive, systematic search was conducted in major indexing databases using key terms for RA and each biological agent. The review process was completed by 2 investigators. Both randomized controlled trials and observational studies of at least 6-month duration conducted in adult RA patients were included. Outcomes of interest were clinical efficacy and safety. Effect-estimates were pooled using random-effects modeling if 4 or more studies used the same scale and time-frame for measuring outcomes. RESULTS: 24 studies (16 focusing on anti-TNF agents) representing 63,705 patients (24% were older) were included. Older RA patients had worse baseline RA disease activity, longer disease duration at the time of enrollment in the trial (14.4 ±â€¯3.6 vs. 10.9 ±â€¯3.6 years; p < 0.001) and higher steroid use (73.2 vs. 64.7%, p < 0.001) than younger. 5 out of 6 studies assessing anti-TNF agents showed worse efficacy outcomes in older patients. The pooled OR of infection and ADRs with anti-TNF agents in older compared to young RA patients was OR 1.59 (95% CI: 1.45-1.76) and 1.40 (95% CI: 1.23-1.61) respectively. CONCLUSIONS: Older patients had worse safety and efficacy with biological agents but also had worse baseline disease activity. There was significant heterogeneity in reporting outcomes and very limited studies in biological agents other than anti-TNF drugs.

Comparison of oral versus parenteral methotrexate in the treatment of rheumatoid arthritis: A meta-analysis.

OBJECTIVE: Studies suggest that parenteral MTX may be more efficacious than the oral form at equivalent doses for the treatment of rheumatoid arthritis. We carried out a meta-analysis to compare the efficacy of oral versus parenteral MTX in RA. METHODS: PubMed, Web of Science and Embase were systematically searched from inception to June 8th 2017 and reviewed following PRISMA 2009 guidelines, by two independent reviewers. To be included, trials had to study adults with RA randomized to the same dose of either oral or parenteral MTX. The primary endpoint was ACR20 at 6 months. Intention-to-treat analysis results were used when possible. Data from direct comparisons between oral and parenteral methotrexate quantitatively analyzed using maximum likelihood random effects meta-analysis. Relative treatment effects were generated as an odds ratio [OR] (OR>1 indicated a benefit for parenteral therapy). RESULTS: The search yielded 357 papers or abstracts. After review of titles or abstracts and full text papers, we found 4 that met inclusion criteria with 703 patients randomized. Dose of MTX started at 15mg/week and increased up to 25mg/week. The summary OR for achieving ACR20 using parenteral vs. oral MTX was 3.02 (95% CI 1.41, 6.46), with no significant difference in the risk for all adverse events. CONCLUSION: Parenteral MTX therapy had significantly higher odds than oral MTX of achieving reduction in disease activity. We propose that parenteral MTX is more effective than weekly oral MTX; its widespread use may lead to better control of disease and a decrease in demand for biologic agents.

Effect of nitric oxide on Dengue virus replication in Aedes aegypti and Anopheles albimanus.

UNLABELLED: Dengue virus (DENV) is transmitted to humans by Aedes sp. mosquitoes. Little is known about the cellular and molecular interactions between the virus and the mosquito. The identification of resistance mechanisms could provide insight for the development of control strategies based on genetic manipulation. OBJECTIVE: To determine the effect of nitric oxide (NO) donors/inhibitors on DENV replication in Aedes aegypti and Anopheles albimanus. MATERIALS AND METHODS: Ae. aegypti and An. albimanus were fed with a blood suspension supplemented with DENV and donors/inhibitors of NO; DENV replication was assessed by immunofluorescence, RT-PCR and qRT-PCR parallel to NO measurement by means of the Griess reaction. RESULTS: DENV replicates at 3x10(6) genome copies/day/mosquito in Aedes. In comparison, no evidence of virus genome accumulation was detected when 2 mM sodium nitroprusside, a NO donor, were added to the infected blood meal. DENV did not replicate in Anopheles unless 1 mM L-N(G)-nitroarginine methyl ester, a NO synthesis inhibitor, was added to the infected blood meal, although the absolute viral load was significantly lower than in Aedes. CONCLUSIONS: As in humans, NO participates in the control of the virus load in mosquitoes. However, other mechanisms could also be involved in virus resistance in Anopheles.

The efficacy of adding group behavioral activation to usual care in patients with fibromyalgia and major depression: design and protocol for a randomized clinical trial.

BACKGROUND: Fibromyalgia and major depression frequently co-occur. Patients with both conditions have a worse prognosis and higher disability, and their treatment options are scarce. Behavioral activation (BA) may be an especially useful intervention for these patients, as it targets mechanisms of action that seem to be common to both disorders. Nevertheless, its efficacy has not been examined in people with both conditions. We describe the design and rationale of a randomized clinical trial aimed to evaluate the efficacy of adding BA (applied in groups) to usual care in order to reduce the severity of depressive symptoms (primary outcome) among Chilean women with fibromyalgia and major depression (N = 90). Pain intensity, fibromyalgia impact, pain catastrophizing and hypervigilance, physical health symptoms, environmental reward, and BA will be evaluated as secondary outcomes. METHODS: Women will be randomized to an experimental arm (n = 45) which will receive usual care (UC) for fibromyalgia with comorbid depression plus BA; and a comparison arm, which will receive only UC for fibromyalgia with comorbid depression (n = 45). Outcome assessment will take place at four time points: (1) at baseline, (2) when the experimental arm is under treatment (between sessions 6 and 7), (3) immediately after the experimental arm complete the treatment, and (4) at a 3-month follow-up. The following instruments will be used: Chilean version of the Patient Health Questionnaire-9 (PHQ-9), Composed Pain Intensity Index, Fibromyalgia Impact Questionnaire Revised (FIQ-R), Pain Catastrophizing Scale (PCS), Pain Vigilance and Awareness Questionnaire (PVAQ), Patient Health Questionnaire (PHQ-15), Reward Probability Index (RPI), and the Activation subscale of the Behavioral Activation for Depression Scale (BADS). DISCUSSION: We expect that, after treatment, the group receiving BA should experience greater reductions in the primary and secondary outcomes than the group receiving only UC. These reductions should be both statistically and clinically significant and will be maintained at follow-up. This study will contribute to facilitate the integrated treatment of fibromyalgia and depression. TRIAL REGISTRATION: ClinicalTrials.gov under the name "Testing Interventions for Patients with Fibromyalgia and Depression," Identifier: NCT03207828 . Registered on 5 July 2017 (last update posted 21 September 2017).