Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review.

BACKGROUND: Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. METHOD: A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. RESULTS: Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. CONCLUSION: Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review

Abstract Background Increased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis. Method A retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol. Results Of the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min-max) SLEDAI-2 K scores were 9 (0-38), median (min-max) SLICC/ACR-DI (SDI) score were 1 (1-5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma. Conclusion Estimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus.

INTRODUCTION: Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. OBJECTIVE: To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. METHODS: 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. RESULTS: JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 (p = 0.713), as well as between patients with and without current use of prednisone (p = 0.420), azathioprine (p = 1.0), mycophenolate mofetil (p = 0.185), and methotrexate (p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups (p > 0.05). CONCLUSION: This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www. CLINICALTRIALS: gov , NCT03540823).

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years.

OBJECTIVES: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. METHODS: A cross-sectional study including a sample of adolescents' autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59). RESULTS: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018). CONCLUSION: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

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 343 adolescents with immunocompromising diseases and 108 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 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00‒7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08‒3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12‒4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93‒0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95‒0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16‒0.77; p = 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.

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years

Abstract Objectives: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. Methods: A cross-sectional study including a sample of adolescents' autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59). Results: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018). Conclusion: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

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

Abstract 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 343 adolescents with immunocompromising diseases and 108 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 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00-7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08-3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12-4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93-0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95-0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16-0.77; p = 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.

Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus

Abstract Introduction Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature. Objective To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE. Methods 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/ INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated. Results JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 ( p = 0.713), as well as between patients with and without current use of prednisone ( p = 0.420), azathioprine ( p = 1.0), mycophenolate mofetil ( p = 0.185), and methotrexate ( p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups ( p > 0.05). Conclusion This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www.clinicaltrials.gov , NCT03540823).

Yellow fever vaccination in Brazil: Short-term safety and immunogenicity in juvenile autoimmune rheumatic diseases.

Yellow fever vaccine (YFV) is a live attenuated vaccine usually contraindicated for juvenile autoimmune rheumatic disease (JARD) patients. During the recent epidemic in Sao Paulo-Brazil, YFV was indicated for patients under low immunosuppression. Thirty JARD patients with inactive diseases undergoing low immunosuppression and 30 healthy controls (HC) were vaccinated with a fractional dose 17DD YFV (∼5495 IU) and evaluated 30 days later. JARD patients and controls had comparable median age (12.4 vs. 12 years, p = 0.250). Disease parameters remained stable 30 days after 17DD YFV (p > 0.05) and only mild adverse events were reported in both groups (p > 0.05). JARD and HC had similar seroprotection [93% vs. 100%;p = 0.49], seroconversion rates [96% vs. 100%;p = 0.489], and GMT [1249 vs.1293;p = 0.821]. Both groups had similar white-blood-cells kinetics with transient decreases in lymphocytes at D5 and neutrophils at D10, followed by full recovery at D30 (P < 0.05). In conclusion, 17DD YFV was safe and immunogenic in JARD. This study may contribute to recommendations for patients living/travelling to endemic areas.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine.

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.

Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial.

BACKGROUND: The Butantan Institute has manufactured a lyophilised tetravalent live-attenuated dengue vaccine Butantan-DV, which is analogous to the US National Institutes of Health (NIH) TV003 admixture. We aimed to assess the safety and immunogenicity of Butantan-DV. METHODS: We did a two-step, double-blind, randomised placebo-controlled phase 2 trial at two clinical sites in São Paulo, Brazil. We recruited healthy volunteers aged 18-59 years; pregnant women, individuals with a history of neurological, heart, lung, liver or kidney disease, diabetes, cancer, or autoimmune diseases, and individuals with HIV or hepatitis C were excluded. Step A was designed as a small bridge-study between Butantan-DV and TV003 in DENV-naive participants. In step A, we planned to randomly assign 50 dengue virus (DENV)-naive individuals to receive two doses of Butantan-DV, TV003, or placebo, given 6 months apart. In step B, we planned to randomly assign 250 participants (DENV-naive and DENV-exposed) to receive one dose of Butantan-DV or placebo. Participants were randomly assigned, by computer-generated block randomisation (block sizes of five); participants in step A were randomly assigned (2:2:1) to receive Butantan-DV, TV003, or placebo and participants in step B were randomly assigned (4:1) to receive Butantan-DV or placebo. Participants and study staff were unaware of treatment allocation. The primary safety outcome was the frequency of solicited and unsolicited local and systemic adverse reactions within 21 days of the first vaccination, analysed by intention to treat. The primary immunogenicity outcome was seroconversion rates of the DENV-1-4 serotypes measured 91 days after the first vaccination, analysed in the per-protocol population, which included all participants in step A, and all participants included in step B who completed all study visits with serology sample collection. This trial is registered with ClinicalTrials.gov, NCT01696422. FINDINGS: Between Nov 5, 2013, and Sept 21, 2015, 300 individuals were enrolled and randomly assigned: 155 (52%) DENV-naive participants and 145 (48%) DENV-exposed participants. Of the 155 DENV-naive participants, 97 (63%) received Butantan-DV, 17 (11%) received TV003, and 41 (27%) received placebo. Of the 145 DENV-exposed participants, 113 (78%) received Butantan-DV, three (2%) received TV003, and 29 (20%) received placebo. Butantan-DV and TV003 were both immunogenic, well-tolerated, and no serious adverse reactions were observed. In step A, rash was the most frequent adverse event (16 [845] of 19 participants in the Butantan-DV group and 13 [76%] of 17 participants in the TV003 group). Viraemia was similar between the Butantan-DV and TV003 groups. Of the 85 DENV-naive participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis and thus were included in the per-protocol analysis population, 74 (87%) achieved seroconversion to DENV-1, 78 (92%) to DENV-2, 65 (76%) to DENV-3, and 76 (89%) to DENV-4. Of the 101 DENV-exposed participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis, 82 (81%) achieved seroconversion to DENV-1, 79 (78%) to DENV-2, 83 (82%) to DENV-3, and 78 (77%) to DENV-4. INTERPRETATION: Butantan-DV and TV003 were safe and induced robust, balanced neutralising antibody responses against the four DENV serotypes. Efficacy evaluation of the Butantan-DV vaccine is ongoing. FUNDING: Intramural Research Program US NIH National Institute of Allergy and Infectious Diseases, Brazilian National Bank for Economic and Social Development, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Fundação Butantan.

Lower genital tract infections in young female juvenile idiopathic arthritis patients.

BACKGROUND: To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. METHODS: After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. RESULTS: The mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p = 0.206) and biological agent use (p = 0.238) were similar in both JIA groups. CONCLUSIONS: To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.

Sexual function in female juvenile idiopathic arthritis patients.

OBJECTIVE: To evaluate sexual function female adolescents and young adults with juvenile idiopathic arthritis (JIA) and healthy controls. METHODS: After exclusion, 21 female adolescent and young JIA patients and 25 healthy controls were selected for this study. Sexual function was assessed by the Sexual Quotient Questionnaire for Females (SQQ-F) score, which is a validated tool and adapted for Brazilian Portuguese language. Demographic data, JIA clinical/laboratory parameters and treatment were also assessed. RESULTS: The median current age [26.5 (17-38.1) vs. 29.3 (19.7-35.8) years, p = 0.700)] as well as age at the first sexual activity [18 (14-30) vs. 17 (10-24) years, p = 0.158] were similar in JIA patients and healthy controls. The median of SQQ-F score was alike in both groups [75.9 (50-92) vs. 78.2 (58-94), p = 0.529], as well as frequencies of sexual dysfunction (14% vs. 12%, p = 1.000). The frequencies of all sexual domains (desire/sexual fantasies, desire/interest, arousal/foreplay, arousal/lubrication, arousal/in tune with partner, penetration/relaxation, pain/penetration, desire/involvement, orgasm and general satisfaction scores) were similar in JIA patients and healthy controls (p > 0.05). CONCLUSIONS: To our knowledge, this was the first study using a validated sexual score in a chronic arthritis population suggesting a low frequency of overall sexual dysfunction in young JIA patients. Future multicenter studies with a large sample will be necessary to confirm this finding.

Lower genital tract infections in young female juvenile idiopathic arthritis patients

Abstract Background: To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. Methods: After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. Results: The mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p =0.206) and biological agent use (p =0.238) were similar in both JIA groups. Conclusions: To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.