Substance use and sexual function in juvenile idiopathic arthritis

AbstractObjectiveTo evaluate alcohol/tobacco/illicit drug use and sexual function in adolescent juvenile idiopathic arthritis (JIA) and healthy controls.Methods174 adolescents with pediatric rheumatic diseases were selected. A cross-sectional study with 54 JIA patients and 35 controls included demographic/anthropometric data and puberty markers assessments, physician-conducted CRAFFT (car/relax/alone/forget/friends/trouble) screen tool for substance abuse/dependence high risk and a questionnaire that evaluated sexual function, bullying and alcohol/tobacco/illicit drug use. Clinical/laboratorial data and treatment were also assessed in JIA.ResultsThe median current age was similar between JIA patients and controls [15(10–19) vs. 15(12–18) years, p=0.506]. Frequencies of alcohol/tobacco/illicit drug use were high and similar in both JIA and controls (43% vs. 46%, p=0.829). However, age at alcohol onset was significantly higher in those with JIA [15(11–18) vs. 14(7–18) years, p=0.032], particularly in polyarticular onset (p=0.040). High risk for substance abuse/dependence (CRAFFT score≥2) was found in both groups (13% vs. 15%, p=1.000), likewise bullying (p=0.088). Further analysis of JIA patients regarding alcohol/tobacco/illicit drug use showed that the median current age [17(14–19) vs. 13(10–19)years, p<0.001] and education years [11(6–13) vs. 7(3–12)years, p<0.001] were significant higher in those that used substances. Sexual activity was significantly higher in the former group (48% vs. 7%, p<0.001). A positive correlation was evidenced between CRAFFT score and current age in JIA patients (p=0.032, r=+0.296).ConclusionA high risk for substance abuse/dependence was observed in both JIA and controls. JIA substance users were more likely to have sexual intercourse. Therefore, routine screening is suggested in all visits of JIA adolescents

Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0) and geometric mean titer (p = 0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7), seroconversion (68.1% vs. 65.2%, (p = 1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20), skin ulcers (p = 0.48), lupus-like cutaneous disease (p = 0.74), secondary Sjogren syndrome (p = 0.78), scleroderma-pattern in the nailfold capillaroscopy (p = 1.0), lymphopenia #1000/mm³ on two or more occasions (p = 1.0), hypergammaglobulinemia $1.6 g/d (p = 0.60), pulmonary hypertension (p = 1.0) and pulmonary fibrosis (p = 0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94), aldolase (p = 0.73), creatine phosphokinase (p = 0.40) and ribonucleoprotein antibody levels (p = 0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported. CONCLUSIONS: The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy

Intestinal microsporidiosis: a hidden risk in rheumatic disease patients undergoing anti-tumor necrosis factor therapy combined with disease-modifying anti-rheumatic drugs?

OBJECTIVE: Immunosuppressed patients are at risk of microsporidiosis, and this parasitosis has an increased rate of dissemination in this population. Our objective was to evaluate the presence of microsporidiosis and other intestinal parasites in rheumatic disease patients undergoing anti-tumor necrosis factor/disease-modifying anti-rheumatic drug treatment. METHODS: Ninety-eight patients (47 with rheumatoid arthritis, 31 with ankylosing spondylitis and 11 with psoriatic arthritis) and 92 healthy control patients were enrolled in the study. Three stool samples and cultures were collected from each subject. RESULTS: The frequency of microsporidia was significantly higher in rheumatic disease patients than in control subjects (36 vs. 4%, respectively; p<0.0001), as well as in those with rheumatic diseases (32 vs. 4%, respectively; p<0.0001), ankylosing spondylitis (45 vs. 4%, respectively; p<0.0001) and psoriatic arthritis (40 vs. 4%, respectively; p<0.0001), despite a similar social-economic class distribution in both the patient and control groups (p = 0.1153). Of note, concomitant fecal leukocytes were observed in the majority of the microsporidia-positive patients (79.5%). Approximately 80% of the patients had gastrointestinal symptoms, such as diarrhea (26%), abdominal pain (31%) and weight loss (5%), although the frequencies of these symptoms were comparable in patients with and without this infection (p&gt;0.05). Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis disease activity parameters were comparable in both groups (p&gt;0.05). The duration of anti-tumor necrosis factor/disease-modifying anti-rheumatic drugs and glucocorticoid use were also similar in both groups. CONCLUSION: We have documented that microsporidiosis with intestinal mucosa disruption is frequent in patients undergoing concomitant anti-tumor necrosis factor/disease-modifying anti-rheumatic drug therapy. Impaired host defenses due to the combination of the underlying disease and the immunosuppressive therapy is the most likely explanation for this finding, and this increased susceptibility reinforces the need for the investigation of microsporidia and implementation of treatment strategies in this population.FAPESPCNPQFederico FoundationWyet

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p&nbsp;=&nbsp;0.0001), GMT (21.3&nbsp;UA/mL vs. 67.7&nbsp;UA/mL, p&nbsp;&lt;&nbsp;0.001) and NAb- positivity (53.7% vs. 80.6%, p&nbsp;=&nbsp;0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p&nbsp;=&nbsp;0.015), mycophenolate mofetil (20% vs. 0%, p&nbsp;=&nbsp;0.037) and prednisone (60.0% vs. 28.6%, p&nbsp;=&nbsp;0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p&nbsp;=&nbsp;0.015) and IS (84.2% vs. 55.0%, p&nbsp;=&nbsp;0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR&nbsp;=&nbsp;0.2, 0,95% CI 0.05‒0.86, p&nbsp;=&nbsp;0.030) and with lower NAb positivity (OR&nbsp;=&nbsp;0.2, 0,95% CI 0.05‒0.88, p&nbsp;=&nbsp;0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p&nbsp;=&nbsp;0.074) and 32 CG (18.7%, p&nbsp;=&nbsp;0.041). For the NAb positivity, the 6-month decrease was not significant (p&nbsp;=&nbsp;0.114) whereas a major reduction occurred for CG (p&nbsp;&lt;&nbsp;0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p&nbsp;=&nbsp;0.023) and NAb-positivity (34.4%, p&nbsp;=&nbsp;0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698)

Physical activity: a strategy to improve antibody response to a SARS-CoV-2 vaccine booster dose in patients with autoimmune rheumatic diseases.

Physical activity associates with improved immunogenicity following a 2-dose schedule of CoronaVac (Sinovac's inactivated SARS-CoV-2 vaccine) in patients with autoimmune rheumatic diseases (ARD). This study evaluates whether physical activity impacts vaccine-induced antibody responses to a booster dose in this population. This was a phase-4 trial conducted in Sao Paulo, Brazil. Patients with ARD underwent a 3-dose schedule of CoronaVac. One month after the booster, we assessed seroconversion rates of anti-SARS-CoV-2 S1/S2 IgG, geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity. Physical activity was assessed through questionnaire. Physically active (n = 362) and inactive (n = 278) patients were comparable for most characteristics; however, physically active patients were younger (P<.01) and had a lower frequency of chronic inflammatory arthritis (P<.01). Adjusted models showed that physically active patients had -2 times odds of seroconversion rates (OR: 2.09; 95% confidence interval, 1.22 to 3.61), -22% greater geometric mean titers of anti-S1/S2 IgG (22.09%; 95% confidence interval, 3.91 to 65.60), and -7% greater neutralizing activity (6.76%; 95% confidence interval, 2.80 to 10.72) than inactive patients. Patients with ARD who are physically active have greater odds of experiencing better immunogenicity to a booster dose of CoronaVac. These results support the recommendation of physical activity to improve vaccination responses, particularly for immunocompromised individuals

No associations between physical activity and immunogenicity in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases prior to and after vaccination.

To investigate the association between physical activity and immunogenicity among SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases prior to and following a 2-dose schedule of CoronaVac (Sinovac inactivated vaccine). This was a prospective cohort study within an open-label, single-arm, phase 4 vaccination trial conducted in Sao Paulo, Brazil. In this substudy, only SARS-CoV-2 seropositive patients were included. Immunogenicity was assessed by seroconversion rates of total anti-SARS-CoV-2 S1/S2 immunoglobulin G (IgG), geometric mean titers of anti-S1/S2 IgG, frequency of positive neutralizing antibodies, and neutralizing activity before and after vaccination. Physical activity was assessed through a questionnaire. Model-based analyses were performed controlling for age (30 kg/m2), and use of prednisone, immunosuppressants, and biologics. A total of 180 seropositive autoimmune rheumatic disease patients were included. There was no association between physical activity and immunogenicity before and after vaccination. This study suggests that the positive association between physical activity and greater antibody responses seen in immunocompromised individuals following vaccination is overridden by previous SARS-CoV-2 infection, and does not extend to natural immunity

Emotional, hyperactivity and inattention problems in adolescents with immunocompromising chronic diseases during the COVID-19 pandemic

Objective: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. Methods: A cross-sectional study included&nbsp;343&nbsp;adolescents with immunocompromising diseases and 108&nbsp;healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). Results: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343&nbsp;[32%] vs.&nbsp;38/108 [35%], p&nbsp;=&nbsp;0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs.&nbsp;29/108 [27%], p&nbsp;=&nbsp;0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR&nbsp;=&nbsp;3.76]; 95%&nbsp;Confidence Interval (95%&nbsp;CI) 2.00‒7.05; p &lt; 0.001), poor sleep quality (OR&nbsp;=&nbsp;2.05; 95%&nbsp;CI&nbsp;1.08‒3.88; p&nbsp;=&nbsp;0.028) and intrafamilial violence during pandemic (OR&nbsp;=&nbsp;2.17; 95%&nbsp;CI&nbsp;1.12‒4.19; p&nbsp;=&nbsp;0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR&nbsp;=&nbsp;0.95; 95%&nbsp;CI&nbsp;0.93‒0.96; p &lt; 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR&nbsp;=&nbsp;0.97; 95%&nbsp;CI&nbsp;0.95‒0.99; p&nbsp;=&nbsp;0.010], changes in medical appointments during the pandemic (OR&nbsp;=&nbsp;0.39; 95%&nbsp;CI&nbsp;0.19-0.79; p&nbsp;=&nbsp;0.021), and reliable COVID-19 information (OR&nbsp;=&nbsp;0.35; 95%&nbsp;CI&nbsp;0.16‒0.77; p&nbsp;=&nbsp;0.026) remained inversely associated with abnormal HI scores. Conclusion: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics