Assessment of hydroxychloroquine blood levels in Sjögren's disease patients: drug adherence and clinical associations.

Hydroxychloroquine (HCQ) has been used to treat Sjögren's disease (SjD) patients. However, there are no studies evaluating drug adherence through HCQ blood levels, pharmacy refill (PR) and medication adherence questionnaires. The relationship of HCQ blood levels with glandular/extraglandular disease parameters was also poorly assessed. This cross-sectional observational study included 74 adult SjD patients, who were receiving a stable HCQ dose (4-5.5 mg/kg/day, actual weight) for at least 3 months before study inclusion. HCQ blood levels were quantified by high-performance liquid chromatography coupled to mass spectrometry. Adherence was assessed by PR and Medida de Adesão aos Tratamentos (MAT) questionnaire. The following parameters were evaluated: Xerostomia Inventory, Ocular Surface Disease Index, EULAR (European League Against Rheumatism) Sjögren's Syndrome Disease Activity Index, EULAR Sjögren's Syndrome Patient Reported Index, Schirmer's I test and non-stimulated/stimulated salivary flow rates. HCQ blood levels were 775.3(25.0-2,568.6)ng/mL. Eleven patients (14.9%) had HCQ blood levels < 200ng/mL (non-adherent group); 11(14.9%), 200-499ng/mL (sub-therapeutic levels group); and 52(70.2%), ≥ 500ng/mL (adherent group). PR classified incorrectly all non-adherent/sub-therapeutic patients and 2/52(3.9%) adherent patients. Using MAT, the overall misclassification was 24/52(46.2%) in the adherent group, and were correctly identified 9/11(81.8%) patients in non-adherent and 7/11(63.6%) in sub-therapeutic groups. MAT sensitivity and specificity to identify non-adherent/sub-therapeutic patients were 72.7% and 53.9%, respectively. The three groups were comparable regarding glandular/extraglandular disease parameters (p > 0.05). The assessment of HCQ blood levels is a promising tool for evaluating drug adherence in SjD. This is particularly crucial as one-third of patients exhibited non-adherence/sub-therapeutic levels, and neither PR nor MAT reliably identified these patients.

Cross-cultural adaptation and initial validation of the Brazilian-Portuguese version of the pediatric automated neuropsychological assessment metrics.

Automated neuropsychiatric batteries have been used in research and clinical practice, including for chronic diseases, such as Systemic Lupus Erythematosus. The Pediatric Automated Neuropsychological Assessment Metrics battery (Ped-ANAM), originally developed for use in American-English speaking individuals, allows tracking of cognitive functions. It can be applied to people over 9 years old. The aim of this study was to translate and present initial validation data from the Ped-ANAM into Brazilian-Portuguese. We translated the battery according to Beaton's guidelines. Psychometric properties were tested, internal consistency was analyzed by Cronbach's alpha coefficient, test-retest reliability by the intraclass correlation coefficient (ICC). Further, we measured the test execution speed at both times as a temporal stability. Principal component analysis (PCA) was used for structural validity. Evidence of construct validity was assessed through assessment of the relationships with the Wechsler Intelligence Scales. All participants prior to the start of study related activities signed an informed consent form approved by the local ethics committee. A sample of 230 individuals [mean (range) of age: 23 (9 to 60) years; 65% females] was included; a subset of 51 individuals [mean (range) of age: 18 (9 to 57) years, 59% female] completed the Ped-ANAM twice to assess test-retest reliability, and another subset of 54 individuals [mean (range) of age: 20.4 (7 to 62) years; 67% female] completed the Wechsler Intelligence Scales for Children and Adult for assessment of the Ped-ANAM's construct validity. Our results suggest that the internal consistency of the Ped-ANAM (Cronbach's α = 0.890) and its subtest test-retest reliability were excellent (ICC: 0.59 to 0.94). There was no clustering in the Principal Components Analysis, suggestive of non-grouping of the evaluated variables. Construct validity assessment to the Wechsler Scales showed expected ranges of low to strong correlations (Spearman correlations: ρ = 0.40 to ρ = 0.69). We concluded that, based on the results of this study, a cross-culturally validated Brazilian-Portuguese version of the Ped-ANAM has been developed and it is a reliable tool for the screening cognitive function.

Segmental cardiac strain assessment by two-dimensional speckle-tracking echocardiography in surviving MIS-c patients: Correlations with myocardial flow reserve (MFR) by 13 N-ammonia PET-CT.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-c) is associated with severe cardiovascular impairment and eventually death. Pathophysiological mechanisms involved in myocardial injury were scarcely investigated, and cardiovascular outcomes are uncertain. Autopsy studies suggested that microvascular dysfunction may be relevant to LV impairment. OBJECTIVE: We aimed to evaluate segmental LV longitudinal strain by 2DST echocardiography and myocardial flow reserve (MFR) by 13 N-ammonia PET-CT, in six surviving MIS-c patients. METHODS: Each patient generated 34 LV segments for combined 2DST and MRF analysis. MFR was considered abnormal when <2, borderline when between 2 and 2.5 and normal when >2.5. RESULTS: From July 2020 to February 2021, six patients were admitted with MIS-c: three males, aged 9.3 (6.6-15.7) years. Time from admission to the follow-up visit was 6.05 (2-10.3) months. Although all patients were asymptomatic and LV EF was ≥55%, 43/102 (42.1%) LV segments showed MFR <2.5. There was a modest positive correlation between segmental peak systolic longitudinal strain and MFR: r = .36, p = .03 for basal segments; r = .41, p = .022 for mid segments; r = .42, p = .021 for apical segments. Median peak systolic longitudinal strain was different among MRF categories: 18% (12%-24%) for abnormal, 18.5% (11%-35%) for borderline, and 21% (12%-32%) for normal MFR (p = .006). CONCLUSION: We provided preliminary evidence that surviving MIS-c patients may present subclinical impairment of myocardial microcirculation. Segmental cardiac strain assessment 2DST seems useful for MIS-c cardiovascular follow-up, given its good correlation with 13 N-ammonia PET-CT derived MFR.

Epidemiology and management practices for childhood-onset systemic lupus erythematosus patients: a survey in Latin America.

To assess epidemiology and management practices of Latin America Pediatric Rheumatologists (LAPR) about childhood-onset systemic lupus erythematosus (cSLE). A cross-sectional study was performed in 288 LAPR PANLAR members based on online survey about cSLE practices. The response rate of web-based survey by LAPR was 170/288(59%) and the majority worked in university hospitals (63%). The ACR and/or SLICC classification criteria (99%) and disease activity tools (97%) were almost universally used by LAPR, whereas damage index (70%) and CHAQ (58%) instruments were less frequently used. Laboratory exams, diagnostic imaging, and biopsies were generally available (> 75%), however low availability for densitometry (66%). Drug access was excellent for the most common prescribed medications (> 75%), except for belimumab (11%). Emerging mosquito-borne diseases were also reported: dengue (20%), chikungunya (11%), and Zika (8%). Groups were further divided in two, according to the median number of cSLE patients followed by LAPR in the last year: groups A and B (≥ 25 and < 25, respectively). Frequencies of condom in combination with other contraceptive methods were significantly higher in group A than B (p = 0.01). The frequencies of reported pregnancy (p < 0.001) and non-adherence to therapy were significantly higher in group A (p = 0.023). Alcohol intake (p = 0.004) and illicit drug use (p = 0.007) were also reported more frequently by LAPR of group A in at least one cSLE patient. This first large web-based survey demonstrated an overall excellent access for diagnosis and therapy by LAPR, probably related to their high rate of practices in tertiary care of university hospitals. Adherence to therapy, pregnancy, and substance abuse was identified as major challenges in this population, particularly in larger centers.

Management considerations for childhood-onset systemic lupus erythematosus patients and implications on therapy.

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic inflammatory and autoimmune disease that may involve various organs and systems. This narrative review focuses on the recent evidence relating to cSLE management. The general management considerations of cSLE patients require the use of validated classification criteria, disease and health-related quality of life tools evaluation, as well as assessments of lupus nephritis biomarkers and cSLE quality indicators. The drug treatment for cSLE patients includes general supportive care and immunosuppressive therapy. Important implications on cSLE therapy are also updated such as infection, vaccination, infertility, pregnancy, contraception, dyslipidemia, physical activity, cancer, bone health, drug pharmacokinetics, adherence, academic outcomes, transition to adult care and cumulative organ damage.

Osteonecrose de mandíbula em pacientes com lúpus eritematoso sistêmico juvenil observada em exame de imagem / Osteonecrosis of the jaw on imaging exams of patients with juvenile systemic lupus erythematosus

OBJETIVO: O objetivo deste estudo foi avaliar alterações radiográficas da articulação temporomandibular (ATM) em pacientes com lúpus eritematoso sistêmico juvenil (LESJ) e controles. PACIENTE E MÉTODOS: Vinte e seis pacientes com LESJ e 28 controles foram avaliados com radiografia panorâmica da ATM. Tomografia computadorizada multislice (TCM) da ATM foi realizada naqueles que tiveram achatamento e/ou destruição dos côndilos mandibulares. Foram avaliados dados demográficos, índices de saúde bucal, manifestações clínicas, exames laboratoriais e tratamentos. RESULTADOS: Alterações radiográficas importantes compatíveis com osteonecrose de mandíbula e confirmadas pela TCM da ATM foram observadas em 2/26 (8 por cento) de LESJ versus 0 por cento do grupo controle (P = 0,22). Disfunção clínica leve e mobilidade alterada de ATM foram observadas em 67 por cento e 54 por cento, respectivamente. A idade de início, duração da doença e idade atual foram semelhantes nos pacientes com LESJ com e sem alterações radiográficas graves da ATM (9,3 versus 10,8 anos, P = 0,77; 3,3 versus 2 anos, P = 0,63; 12,6 versus 13,5 anos, P = 0,74; respectivamente). Assim como não foram evidenciadas diferenças estatísticas em ambos os grupos com relação a sexo, classe socioeconômica, índices de saúde bucal, manifestações clínicas, exames laboratoriais e tratamentos (P > 0,05). Esses dois pacientes com LESJ e osteonecrose de mandíbula tiveram curso crônico ativo da doença, utilizaram corticosteroides por um longo período e apresentaram disfunção clínica leve da ATM. Nenhum deles teve anticorpos antifosfolipídeos e não foram tratados previamente com bisfosfonatos. CONCLUSÕES: Osteonecrose de mandíbula com leve disfunção clínica da ATM foi observada em alguns pacientes, demonstrando a importância da avaliação odontológica durante o acompanhamento clínico.

OBJECTIVE: The objective of the present study was to evaluate radiographic changes of the temporomandibular joint (TMJ) in patients with juvenile systemic lupus erythematosus (JSLE) and a control group. PATIENTS AND METHODS: Panoramic radiographies of the TMJ of 26 JSLE patients and 28 healthy individuals were evaluated. Multislice computed tomography (MCT) was performed on those patients who presented flattening and/or destruction of mandibular condyles. Demographic data, oral health indices, clinical manifestations, laboratorial exams, and treatment were evaluated. RESULTS: Important radiographic changes consistent with osteonecrosis of the mandible, confirmed by MCT of the TMJ, were observed in 2/26 (8 percent) JSLE patients versus 0 percent in the control group (P = 0.22). Mild clinical dysfunction and abnormal TMJ mobility were observed in 67 percent and 54 percent of the patients, respectively. Age of onset, disease duration, and current age were similar in JSLE patients with and without severe radiographic changes of TMJ (9.3 versus 10.8 years, P = 0.77; 3.3 versus 2 years, P = 0.63; 12.6 versus 13.5 years, P = 0.74, respectively). Significant differences in gender, socioeconomical status, oral health indices, clinical manifestations, laboratorial exams, and treatment were not observed between both subgroups (P 0.05). Both JSLE patients with osteonecrosis of the mandible had active chronic disease, used corticosteroids for a prolonged period, and had mild TMJ dysfunction. Antiphospholipid antibodies were not observed in those two patients, and neither one had been treated with bisphosphonate. CONCLUSIONS: Osteonecrosis of the mandible with mild TMJ dysfunction was observed in some of the patients, demonstrating the importance of odontological assessment during clinical follow-up.

Quality of life and impact of the disease on primary caregivers of juvenile idiopathic arthritis patients.

OBJECTIVES: To evaluate the quality of life and the disease burden on primary caregivers of patients with juvenile idiopathic arthritis (JIA). METHODS: Seventy patients with JIA and their respective caregivers were enrolled in this study. Health, quality of life and psychological status were assessed by using the childhood health assessment questionnaire (CHAQ), the medical outcomes study 36-item short-form health survey (SF-36) and the psychiatric screening questionnaire (SRQ-20). Burden of disease on the caregivers was measured by the caregiver burden scale (CB Scale). RESULTS: Most caregivers were women (91.4%), married (76.6%), mothers (92.2%) and their average age was 37.2+/-8.8 years. Low education and socioeconomic state were observed in most of the caregivers. Psychoemotional disorders measured by the SRQ-20 were detected in 34.3% of the caregivers. Pain and mental health were the items in the SF-36 questionnaire most affected in these individuals. Mean score of global burden measured by the CB Scale was 1.6+/-0.3 (disappointment and environment had the lowest scores). The CB Scale was significantly correlated with the SRQ-20 (r=0.6), number of limited joints (r=0.3), number of visits (r=0.2), family income (r=-0.3) and mental health (r=-0.6), emotional aspects (r=-0.4), social aspects (r=-0.4), vitality (r=-0.5) and general health state of the SF-36 (r=-0.4). SRQ-20 was the most important determinant of CB Scale and of the components pain and mental health of the SF-36 questionnaire. CONCLUSIONS: Most of the disease burden on the caregivers depends upon emotional aspects rather than on the physical status of the patients.