So what I'm stressed? A qualitative study examininga caregivers' reactions to emerging biomarkers of stress.

Background: Caregivers of adults with cancer often report significant distress yet remain difficult to engage in supportive services. While the field of Psychosomatic Medicine has continued to identify important markers of physiologic stress, and demonstrated disruption in these markers in caregiver populations, no research has investigated whether biomarker information on caregivers' reaction to stress could impact their willingness to address their ongoing distress. Methods: Here, we report on a qualitative study (N = 17) in which we conducted individual interviews with cancer caregivers to explore their key attitudes towards, and subjective experience of, mock stress biomarker data. A total of 17 caregivers of patients (M age = 56.1 years; SD = 12.3) with primarily metastatic brain tumors (glioblastoma) were interviewed regarding four commercially available biomarkers (telomere length; hair cortisol, activity levels and heart rate variability). Once presented with information about stress biomarkers, caregivers were asked to discuss their subjective reaction as if it was their own data as well as their motivation and willingness to seek support after receiving such information. We identified and extracted relevant themes. Results: Analysis utilizing the framework method revealed four emerging themes. The first theme described caregivers' ability to manage stress and willingness to engage with supportive services. Second, caregivers generally accepted the biomarker data but preferred it to be presented in a specific way. The third theme demonstrated that for some, biomarker data may actually increase their subjective distress (e.g., whether or not something could be done to improve their mental state). The last theme described how biomarkers were generally received as meaningful motivators that could increase caregivers' willingness to engage with supportive services. Conclusions: In addition to the more general identified theme of CG's willingness to engage with additional support, we gained insights into caregivers' reaction to the stress biomarkers presented. Findings will set the stage for the utility of stress biomarker information and whether it influences cancer caregivers' willingness to address their distress and motivation to engage in supportive services.

Dispensary personnel's views and experiences regarding oncologic cannabis and the counsel they offer adults with cancer.

BACKGROUND: A minority of oncologists feel qualified to advise adults with cancer on issues pertaining to medicinal cannabis. Adults with cancer frequently access medicinal cannabis information from non-medical sources such as cannabis dispensaries. We explored dispensary personnel's views and experiences regarding oncologic cannabis and the counsel they extend individuals with cancer. METHODS: Snowball sampling in this qualitative study facilitated recruitment across 13 states (N = 26). Semi-structured phone interviews ceased with thematic saturation. A multi-stage thematic analysis combined inductive and deductive codes. RESULTS: Of the 26 dispensary personnel interviewed, 54% identified as female and 19% as non-white. Median age was 40 years. A consensus emerged among participants concerning the botanical's efficacy for cancer-related symptoms; less so regarding its antineoplastic potential. Principles for serving those with cancer included provision of client-centered, symptom-based, and trial-and-error approaches. Non-inhalation modes of administration were generally recommended. No consensus was reached as to whether delta-9-tetrahydrocannabinal (THC)- or cannabidiol-predominant products were preferable in this population. Challenges in oncologic advising included successfully identifying individuals with cancer at the dispensary counter, financial toxicity, the special treatment required for the THC-naïve, and operating in the absence of standardized guidelines. CONCLUSIONS: These informed assertions suggest that members of the oncologic community should grapple with the extent to which they feel comfortable with both the nature and degree of counsel adults with cancer receive through dispensaries.

COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data.

OBJECTIVES: To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). METHODS: ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. RESULTS: 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62-8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02-5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33-24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02-0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41-53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03-0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02-0.76; p = 0.02) remained at final model as protective factor. CONCLUSIONS: Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

High levels of immunosuppression are related to unfavourable outcomes in hospitalised patients with rheumatic diseases and COVID-19: first results of ReumaCoV Brasil registry.

OBJECTIVES: To evaluate risk factors associated with unfavourable outcomes: emergency care, hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death in patients with immune-mediated rheumatic disease (IMRD) and COVID-19. METHODS: Analysis of the first 8 weeks of observational multicentre prospective cohort study (ReumaCoV Brasil register). Patients with IMRD and COVID-19 according to the Ministry of Health criteria were classified as eligible for the study. RESULTS: 334 participants were enrolled, a majority of them women, with a median age of 45 years; systemic lupus erythematosus (32.9%) was the most frequent IMRD. Emergency care was required in 160 patients, 33.0% were hospitalised, 15.0% were admitted to the ICU and 10.5% underwent mechanical ventilation; 28 patients (8.4%) died. In the multivariate adjustment model for emergency care, diabetes (prevalence ratio, PR 1.38; 95% CI 1.11 to 1.73; p=0.004), kidney disease (PR 1.36; 95% CI 1.05 to 1.77; p=0.020), oral glucocorticoids (GC) (PR 1.49; 95% CI 1.21 to 1.85; p<0.001) and pulse therapy with methylprednisolone (PR 1.38; 95% CI 1.14 to 1.67; p=0.001) remained significant; for hospitalisation, age >50 years (PR 1.89; 95% CI 1.26 to 2.85; p=0.002), no use of tumour necrosis factor inhibitor (TNFi) (PR 2.51;95% CI 1.16 to 5.45; p=0.004) and methylprednisolone pulse therapy (PR 2.50; 95% CI 1.59 to 3.92; p<0.001); for ICU admission, oral GC (PR 2.24; 95% CI 1.36 to 3.71; p<0.001) and pulse therapy with methylprednisolone (PR 1.65; 95% CI 1.00 to 2.68; p<0.043); the two variables associated with death were pulse therapy with methylprednisolone or cyclophosphamide (PR 2.86; 95% CI 1.59 to 5.14; p<0.018). CONCLUSIONS: Age >50 years and immunosuppression with GC and cyclophosphamide were associated with unfavourable outcomes of COVID-19. Treatment with TNFi may have been protective, perhaps leading to the COVID-19 inflammatory process.

Cachexia in patients with rheumatoid arthritis: a cohort study.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that leads to altered body composition. The loss of lean mass with a preservation or increase in fat mass has been termed rheumatoid cachexia (RC), to contrast with classic cachexia, which is characterized by severe weight loss. There are limited data on the prevalence and progression of cachexia in RA over time, as well as on associated factors. Our aim was to determine the prevalence of cachexia and to determine associations with potential factors. METHODS: This prospective cohort study recruited consecutively patients diagnosed with RA and followed for 1 year. The assessments were performed: clinical features, body composition, and physical function. RC and classic cachexia were assessed by several established diagnostic criteria. The pairwise Student's t test, Chi-square test, and GEE were performed (accepted at p ≤ 0.05). RESULTS: Of 90 patients recruited, 81 completed the study. Most patients were women (88.9%), and the mean age was 56.5 ± 7.3 years. At baseline, the median DAS28-CRP was 3.0 (IQR, 1.0-3.0), 13.3-30.0% of the included patients had RC, while none met criteria for classic cachexia. The prevalence of cachexia did not change after 12 months. Disease activity status and treatment with biologic disease-modifying antirheumatic drugs were significantly associated with changes on body composition and physical function (p < 0.05). CONCLUSIONS: In this cohort, RC was common, while classic cachexia was absent. Disease activity and use of biologic therapies were associated with changes on body composition and physical function, underscoring the importance of aiming for remission when treating RA.

Ultrasound Assessment of Disease Activity Prevents Disease-Modifying Antirheumatic Drug (DMARD) Escalation and May Reduce DMARD-Related Direct Costs in Rheumatoid Arthritis With Fibromyalgia: An Exploratory Study.

OBJECTIVES: as an objective measure, ultrasound (US) could prevent rheumatoid arthritis (RA) overtreatment induced by concomitant fibromyalgia (FM). Our goal was to study how patients with RA and FM who underwent a US examination differed from those without a US examination in terms of overall disease-modifying antirheumatic drug (DMARD) escalation and biologic DMARD-related direct costs. METHODS: Patients with RA and FM were seen between 2011 and 2017. In cases of 28-joint Disease Activity Score (DAS28) overestimation, patients were referred to undergo a US examination. The US group underwent a US examination to confirm disease activity, and the DAS28 group had disease activity assessment based solely on the DAS28. RESULTS: Of 230 patients with RA, 22 women with RA and FM (DAS28 group, n = 9; and US group, n = 13) were seen in 316 visits (115.68 patient-years). The DMARD treatment was escalated in 27.1% of visits in the DAS28 group versus 17.3% in the US group (P = .046). The relative risk of DMARD escalation in the DAS28 group compared to the US group was 1.57 (95% confidence interval, 1.01-2.43). In sum total, US$240,784.52 were spent on biologics throughout the entire study period. Basing biologic DMARD prescriptions on US results could save an average of US$405.66 per patient-year. CONCLUSIONS: In this real-life study of patients with RA and FM, a US examination was associated with less DMARD escalation and could reduce biologic DMARD direct costs. Specifically, synovitis as scored by power Doppler US could be useful as a treatment target for RA in patients with DAS28 overestimation due to FM, but further studies are necessary.

Incidence of tuberculosis in patients receiving anti-TNF therapy for rheumatic diseases: a systematic review.

INTRODUCTION: The TNF inhibitors were the first immunobiologicals used to treat rheumatic diseases, but their use is associated with an increased risk of tuberculosis. The primary objective is to estimate the incidence of tuberculosis in patients with rheumatic diseases exposed to anti-TNF therapy. The secondary objectives are to evaluate the incidence of tuberculosis by region and subgroups of diseases, to review the presentation of tuberculosis in these patients, and to assess the time elapsed between onset of anti-TNF therapy and development of active granulomatous disease. METHODS: A systematic review of the literature was conducted in MEDLINE, the Cochrane Library, and LILACS. The primary endpoint was described as incidence and secondary outcomes, through subgroup analyses and comparisons of means. RESULTS: We included 52 observational studies. Among the exposed patients, 947 cases of tuberculosis were documented (62.2% pulmonary), with a cumulative incidence of 9.62 cases per 1000 patients exposed. TB incidence across different continents was distributed as follows: South America, 11.75 cases/1000 patients exposed; North America, 4.34 cases/1000 patients exposed; Europe, 6.28 cases/1000 patients exposed; and Asia, 13.47 cases/1000 patients exposed. There were no significant differences in TB incidence among the described diseases. The mean time elapsed from start of anti-TNF therapy until the endpoint was 18.05 months. CONCLUSION: The incidence of TB in patients with rheumatic diseases exposed TNF inhibitor considering all countries was 9.62 cases per 1000 patients exposed. TB incidence was higher in South America and Asia compared with North America and Europe. Most cases occurred in the first XX months of use, and the pulmonary form predominated.Key Points• Higher incidence of tuberculosis in patients exposed to anti-TNF compared with the general population.• Higher incidence of TB in countries of South America and Asia compared with North America and Europe.

Incidence of tuberculosis infection in spondyloarthritis patients treated with biological and conventional disease-modifying anti-rheumatic drugs in an endemic area

Introduction: Registries of spondyloarthritis (SpA) patients' follow-up provided evidence that tumor necrosis factor inhibitors (TNFi) increase the incidence of active tuberculosis infection (TB). However, most of these registries are from low burden TB areas. Few studies evaluated the safety of biologic agents in TB endemic areas. This study compares the TB incidence rate (TB IR) in anti-TNF-naïve and anti-TNF-experienced subjects with SpA in a high TB incidence setting.Methods: In this retrospective cohort study, medical records from patients attending a SpA clinic during 13 years (2004 to 2016) in a university hospital were reviewed. The TB IR was calculated and expressed as number of events per 105 patients/year; the incidence rate ratio (IRR) associated with the use of TNFi was calculated.Results: A total of 277 patients, 173 anti-TNF-naïve and 104 anti-TNF-experienced subjects, were evaluated; 35.7% (N = 35) of patients who were prescribed an anti-TNF drug were diagnosed with latent tuberculosis infection (LTBI). Total follow-up time (person-years) was 1667.8 for anti-TNF-naïve and 394.9 for anti-TNF-experienced patients. TB IR (95% CI) was 299.8 (37.4-562.2) for anti-TNF naïve and 1012.9 (25.3-2000.5) for anti-TNF experienced subjects. The IRR associated with the use of TNFi was 10.4 (2.3- 47.9).Conclusions: In this high TB incidence setting, SpA patients exposed to anti-TNF therapy had a higher incidence of TB compared to anti-TNF-naïve subjects, although the TB incidence in the control group was significant.(AU)

Treating psoriatic arthritis to target: discordance between physicians and patients' assessment, non-adherence, and restricted access to drugs precluded therapy escalation in a real-world cohort.

The treat-to-target strategy (T2T) was associated with better outcomes in psoriatic arthritis (PsA) compared to standard care in clinical trials. This study aimed to analyze factors precluding treatment optimization in a T2T strategy conducted in a real-world cohort of PsA patients. A retrospective cross-sectional study nested in a cohort was conducted. Medical records of patients ≥ 18 years old, fulfilling CASPAR criteria and with at least one visit in the PsA clinic, were reviewed. Demographic data, current medication, and minimal disease activity (MDA) criteria were recorded. Reasons for the non-escalation of therapy in patients who were not classified as MDA were reported as absolute and relative frequencies. In the 8-month period, 131 visits (corresponding to 74 patients) were conducted. The MDA criteria were available in 113 visits (86.3%) and patients were classified as MDA in 31.0% of the visits (N = 35/113). Although in 69.0% of the visits patients were not in MDA, (N = 78/113), therapy was adjusted in only 42.3% (N = 33/78). Reasons precluding treatment escalation in non-MDA subjects were physician's impression of remission (57.7%, N = 26), non-adherence to previous prescription (17.8%, N = 8), restricted access to drugs (17.8%, N = 8), adverse events (11.1%, N = 5), poor understanding of medication instructions (6.7%, N = 3), patient's refusal to escalate therapy (4.4%, N = 2), and recent change in therapy (2.2%, N = 1). Discordance between the physician's clinical evaluation and the MDA criteria, non-adherence to prescription, and poor access to drugs were the main factors precluding escalation of therapy in a T2T strategy in a real-world PsA cohort.

High prevalence of obesity in rheumatoid arthritis patients: association with disease activity, hypertension, dyslipidemia and diabetes, a multi-center study

Abstract Introduction: Rheumatoid arthritis (RA) is a well-documented independent risk factor for cardiovascular disease. Obesity may provide an additional link between inflammation and accelerated atherosclerosis in RA. Objective: To evaluate the association between obesity and disease parameters and cardiovascular risk factors in RA patients. Method: Cross-sectional study of a cohort of RA patients from three Brazilian teaching hospitals. Information on demographics, clinical parameters and the presence of cardiovascular risk factors was collected. Blood pressure, weight, height and waist circumference (WC) were measured during the first consultation. Laboratory data were retrieved from medical records. Obesity was defined according to the NCEP/ATPIII and IDF guidelines. The prevalence of obesity was determined cross-sectionally. Disease activity was evaluated using the DAS28 system (remission < 2.6; low 2.6—3.1; moderate 3.2-5.0; high >5.1). Results: The sample consisted of 791 RA patients aged 54.7 ± 12.0 years, of whom 86.9% were women and 59.9% were Caucasian. The mean disease duration was 12.8 ± 8.9 years. Three quarters were rheumatoid factor-positive, the mean body mass index (BMI) was 27.1 ±4.9, and the mean WC was 93.5 ± 12.5 cm. The observed risk factors included dyslipidemia (34.3%), type-2 diabetes (15%), hypertension (49.2%) and family history of premature cardiovascular disease (16.5%). BMI-defined obesity was highly prevalent (26.9%) and associated with age, hypertension and dyslipidemia. Increased WC was associated with diabetes, hypertension, dyslipidemia and disease activity. Conclusion: Obesity was highly prevalent in RA patients and associated with disease activity.

Long-term outcomes of treat-to-target strategy in established rheumatoid arthritis: a daily practice prospective cohort study.

To examine disease activity and physical function after implementation of treat-to-target (T2T) strategy in patients with established rheumatoid arthritis (RA) over a long-term period. Patients with RA were started on a T2T strategy in 2005 and followed through 2014. Patients were seen every 3-4 months until remission/low disease activity was achieved and every 6 months thereafter. Disease activity was measured by the DAS28 and CDAI, and physical function by the HAQ-DI. Results were presented as all observed data, without imputation for missing values. Changes in disease activity and physical function were evaluated by generalized estimating equations (GEE). Two hundred and twenty-nine patients were included, with a mean (SD) disease duration of 10.6 (7.4) years. Significant improvements were seen in both composite scores during the follow-up period, as demonstrated by DAS28 (ß coefficient = 0.19; 95% CI = 0.16-0.21; p < 0.01) and by CDAI (ß coefficient = 1.59; 95% CI = 1.84-1.34; p < 0.01). Physical function also improved, as demonstrated by HAQ-DI (ß coefficient = 0.03; 95% CI = 0.02-0.04; p < 0.01). Biological therapy was associated with improvement in disease activity and in physical function. Leflunomide was only associated with improvement in physical function. Clinically meaningful reductions of DAS28, CDAI and HAQ-DI were observed in patients with established rheumatoid arthritis from 2005 to 2014. Implementation of new therapeutic options, in the scenario of T2T strategy, was associated with improvement in disease activity and physical function.