Generation of systemic lupus erythematosus-specific induced pluripotent stem cells from urine

Systemic lupus erythematosus (SLE) is the prototype of complex autoimmune diseases characterized by the production of autoantibodies which results in widespread immunologic abnormalities and immune complex formation. The underlying etiology remains largely unknown. When progressing toward kidney failure, it is becoming a serious public health problem. Kidney transplantation is a feasible therapy, but significant limitations were existed, including shortage of donor organs and lack of funding. To find an alternative proposal for kidney replacement, the induced pluripotent stem cells (iPSCs) technology was adopted. We identified typical SLE patients. Lentiviral transduction of OCT4, SOX2, KLF4, and c-MYC, under feeder conditions, resulted in reprogramming of urine-derived renal tubular cells. We investigated the viability of iPSCs generation from patients with SLE by identification of totipotency and pluripotency. SLE patient renal tubular cells–derived iPSCs exhibited properties of human embryonic stem cells, including morphology, growth properties, alkaline phosphatase, expression of pluripotency, genes and surface markers, and teratoma formation. We demonstrated that generation of SLE-specific iPSCs from urine was not only the first time worldwide, but was feasible and efficient. IPSCs from SLE would provide convenient model to study disease pathogenesis, drugs screening, and gene therapy.     

Development and initial validation of a self‐assessed lupus organ damage instrument

Objective

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is a validated instrument for assessing organ damage in systemic lupus erythematosus (SLE). Trained physicians must complete it, thus limiting utility where this is impossible.

Methods

We developed and pilot tested a self‐assessed organ damage instrument, the Lupus Damage Index Questionnaire (LDIQ), in 37 SLE subjects and 7 physicians. After refinement, 569 English‐speaking SLE subjects and 14 rheumatologists from 11 international SLE clinics participated in validation. Subjects and physicians completed the instruments separately. We calculated sensitivity, specificity, Spearman's correlations, and agreement using the SDI as the gold standard. Six hundred five SLE participants in the community‐based National Data Bank for Rheumatic Diseases (NDB) study completed the LDIQ and we assessed correlations with outcome and disability measures.

Results

The mean LDIQ score was 3.3 (range 0–16) and the mean SDI score was 1.5 (range 0–9). The LDIQ had a moderately high correlation with the SDI (Spearman's r = 0.50, P < 0.001). Specificities of individual LDIQ items were >80%, except for neuropathy. Sensitivities were variable and lowest for damage, with <1% prevalence. Agreement between the SDI and LDIQ was >85% for all but neuropathy, reduced renal function, deforming arthritis, and alopecia. In the NDB, the LDIQ correlated well with the comorbidity index (r = 0.45), the Short Form 36 physical component scale (r = 0.43), the Medical Research Council dyspnea scale (r = 0.40), disability (r = 0.37), and the Systemic Lupus Erythematosus Activity Questionnaire score (r = 0.37).

Conclusion

The metric properties of the LDIQ are good compared with the SDI. It has construct validity and correlations with health assessments similar to the SDI. The LDIQ should allow expansion of SLE research. Its ultimate value will be determined in longitudinal studies.     

BMI, disease activity, and health-related quality-of-life in systemic lupus erythematosus

The aim of this study was to examine the independent and interactive associations among body mass index (BMI), disease activity, on health-related quality-of-life (HRQoL) in Chinese patients with systemic lupus erythematosus (SLE). Three hundred eighty-four patients with SLE were recruited in this study. The investigations were conducted by the Short Form-36 (MOS SF-36) questionnaire. Disease activity was assessed by the SLE disease activity index (SLEDAI). The regression analyses were used to identify independent and interactive associations that were associated with the PCS and MCS. The presence of psychological morbidity was associated with all the scores from SF-36. In multivariable analyses, The physical (PCS) and mental (MCS) component summary scores of MOS SF-36 were negative correlation with BMI and SLEDAI; BMI was independently associated with PCS and MCS but not with disease activity. However, the interactive association of BMI and SLEDAI on HRQoL was negligible. An increased BMI and SLEDAI are independently associated with quality-of-life in patients with SLE. Optimizing weight merits investigation to see if it can significantly improve the HRQoL of SLE patients.     

Development,piloting and validation of the Recommending Cardiac Rehabilitation (ReCaRe) instrument

BackgroundHealth practitioners’ values, attitudes and beliefs largely determine their referrals to cardiac rehabilitation (CR).ObjectiveTo develop and test the Recommending Cardiac Rehabilitation scale (ReCaRe), designed to assess health professionals attitudes, values and beliefs to CR referral.MethodsReCaRe was appraised for: content validity (Delphi method, expert panel); interpretability and face validity (interview, health professionals); factor structure and internal consistency (survey, health professionals); and test-retest reliability (survey, health professionals). Normative scores were collated.ResultsReCaRe initially comprised 75 items. Initially, a Content Validity Index (CVI) was calculated for ratings of item relevance (CVI range; 0.27–1.0), which resulted in the removal of 19 items. After preliminary validation and psychometric testing, 34 items were factor-analysed (n = 24) providing a 17-item, four-factor scale: perceived severity and susceptibility (α = 0.93, κ = 0.37); perceived service accessibility (α = 0.91, κ = 0.67); perceived benefit (α = 0.97, κ = 0.47); perceived barriers and attitudes (α = 0.82, κ = 0.49). ReCaRe normative scores (n = 75) are reported.ConclusionsThis psychometric analysis found ReCaRe to demonstrate good face validity, internal consistency and fair to substantial test-retest reliability. The next step is to validate these initial findings on a larger sample size to confirm whether ReCaRe can enable identification of factors impacting CR referral.     

Development and validation of a self-administered systemic sclerosis questionnaire (SySQ).

OBJECTIVE: To develop a self-administered systemic sclerosis questionnaire (SySQ) covering condition-specific functional limitation and symptoms. METHODS An initial item pool was generated by open patient interviews. A preliminary questionnaire was devised using 62 systemic sclerosis (SSc; scleroderma) patients. Factor analysis was used for further selection and grouping of items into distinct scales. The retrieved scales were tested for internal consistency and test-retest reliability. Spearman's rank correlation and Wilcoxon's rank sum test were used to examine hypothesized associations of the SySQ with various clinical and laboratory features. RESULTS: Altogether 32 SySQ items were selected and aggregated into 12 scales addressing 'pain', 'stiffness', 'coldness', 'complex functions', 'strength of hands', 'rising', 'walking', shortness of breath', 'upper airway symptoms', 'eating', 'swallowing' and 'heartburn/regurgitation'. Internal consistency ranged from 0.93 ('complex functions') to 0.73 ('heartburn/regurgitation'); Spearman's correlation coefficient for test retest reliability ranged from 0.93 to 0.73 (P < 0.001). While the scales were associated with corresponding functional impairments, there was generally less association with morphological impairments. CONCLUSION: The SySQ is a valid and reliable condition-specific measure in patients with SSc. Individually applicable scales cover a wide spectrum of general and organ-specific SSc symptoms and functional limitation. After further validation with respect to its ability to measure change, it may be used in clinical, health services and epidemiological research.     

Development and psychometric evaluation of a diabetes-specific quality-of-life (D-QOL) scale

Aims

The aims of this study were to develop a diabetes-specific quality-of-life (D-QOL) scale and to determine its psychometric properties.

Methods

An initial pool of items was generated based on a conceptual construct and attributes of health-related quality of life. The items were reviewed by experts, and a pilot test was conducted. A content-validated preliminary D-QOL scale was verified for use with psychometric tests on 402 patients who were recruited from 3 hospitals in Korea. The data were analyzed using exploratory and confirmatory factor analyses, Cronbach's alpha, generalizability coefficients, ANOVA, and Pearson's correlations.

Results

From exploratory analyses, a total of sixteen items clustered four factors were extracted. The four-factor structure was supported by confirmatory factor analysis. Concurrent validity was established with the 36-item Short-Form Health Survey. As hypothesized, the D-QOL scores were worse in severely or moderately depressed patients than in those who were either less depressed or not depressed, implying satisfactory known-groups validity. The reliability of the D-QOL scale was supported by Cronbach's alpha and generalizability coefficients.

Conclusions

The D-QOL scale is a simple and brief scale, the use of which is feasible in practice. It demonstrated excellent psychometric properties, and so may also be used in clinical research.     

Illness intrusiveness explains race-related quality-of-life differences among women with systemic lupus erythematosus

Our objective was to investigate whether quality of life in systemic lupus erythematosus (SLE) differs across ethnoracial groups and to identify factors that may explain race-related differences. Self-administered questionnaire data from 335 White, 40 Black, and 30 Asian women with SLE were obtained from a multi-center database. Measures assessed illness intrusiveness, psychological well-being, depressive symptoms, musculoskeletal pain, and learned helplessness. Extent of SLE disease activity was indexed by self-reported functional-system involvement. Educational attainment was indicated by number of years in school. Principal-components analysis reduced the four psychosocial measures to a single factor score. This represented psychosocial well-being In path analysis. Psychosocial well-being differed significantly across the three groups, with Whites reporting the highest, and Blacks the lowest, levels. Path analysis indicated that illness intrusiveness accounted for this race-related difference. Although disease activity was significantly associated with psychosocial well-being, it did not differ across ethnoracial groups. Illness intrusiveness and educational attainment emerged as independent mediators of the race-related difference in psychosocial well-being. We conclude that race-related quality-of-life differences exist among women with SLE and are mediated independently by illness intrusiveness and educational attainment.     

Dehydroepiandrosterone (DHEA) and systemic lupus erythematosus

Objective:

This study was performed to evaluate in vivo and in vitro dataon the effects of the adrenal steroid dehydroepiandrosterone (DHEA) with emphasis on its potential use in the treatment of systemic lupus erythematosus (SLE).

Methods:

The literature dealing with DHEA was reviewed.

Results:

Initially, research on DHEA focused on effects of DHEA in relation to obesity. Over the past decade, research stimulated by associations between the physiological decline in DHEA and aging, cardiovascular disease, changes in metabolism, brain function, and immune senescense have generated insight into the many effects that DHEA or its metabolites may have. In SLE a role for sex hormones in both the etiopathogenesis and disease activity is recognized. In SLE, as in aging, low DHEA levels are frequently found, especially with corticosteroid treatment.

Conclusions:

Research data in the elderly, on both hormonal and immunologiceffects, suggest that DHEA may become an adjunctive treatment for SLE patients.     

Lues and lupus: syphilis mimicking systemic lupus erythematosus (SLE)

Malar rash and photosensitivity are common findings in systemic lupus erythematosus (SLE). However, a number of inflammatory, dermatologic, infectious or drug-induced conditions may mimic cutaneous findings of SLE. These typically include seborrheic dermatitis, contact dermatitis, rosacea, polymorphous light eruption, syphilis and dermatomyositis sine myositis. Herein we describe a patient with fever, malar rash, alopecia, photosensitivity, arthralgias and lymphadenopathy who was subsequently diagnosed with secondary syphilis. In this case report we review clinical and histopathological findings in the differential diagnosis of malar rash and photosensitivity and discuss the overlapping features of syphilis and SLE.     

The Chinese version of the SLEQOL is a reliable assessment of health-related quality of life in Han Chinese patients with systemic lupus erythematosus

To assess the health-related quality of life (HRQOL) of Han Chinese people with systemic lupus erythematosus (SLE) using a Chinese version of the Systemic Lupus Erythematosus-Specific Quality of Life Questionnaire (SLEQOL-C) and explore the factors influencing HRQOL of people with SLE. Participants were Han Chinese people with SLE. The SLEQOL-C and 36-item Short Form Health Survey (SF-36) were used to estimate the HRQOL. Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Participant factors included age, gender, educational background, disease duration, erythrocyte sedimentation rate (ESR), and complement C3 and C4 levels. The results showed that higher SLEQQL-C scores correlated with lower SF-36 both measures are essential for HRQQL prediction. The SLEQOL-C scores were correlated with educational level,age, FACIT-F score, SLEDAI score, and ESR, which suggests that poor educational background, old-age, and increased fatigue, disease activity, and ESR might represent poor HRQOL. Although disease duration did not significantly correlate with the scores on the SLEQOL-C; those whose disease duration was 12–24 months had higher SLEQOL-C summary scores and physical functioning, symptoms, and treatment subscale scores than did those whose duration was less than 6 months. The FACIT-F score, education level, age, disease duration, SLEDAI score, and ESR contributed to SLEQOL-C scores. The SLEQOL-C is reliable for assessing HRQOL of Han Chinese people with SLE. Fatigue, educational level, age, disease duration, ESR, and disease activity mainly influenced HRQOL of SLE patients.     

Development and preliminary validation of a children's arthritis self-efficacy scale

OBJECTIVE: To develop a valid and reliable measure of arthritis self-efficacy for use with school-age children with juvenile idiopathic arthritis (JIA). METHODS: Construction of the 11-item Children's Arthritis Self-Efficacy Scale (CASE) was based on an existing body of knowledge and the results of focus groups with children, their parents, and health professionals. Data for validation of the CASE were collected by self-administered questionnaires completed by 89 children and 151 caregivers. RESULTS: Analyses revealed a 3-factor structure relating to self-efficacy for managing symptoms, emotional consequences, and activities, explaining 76.5% of the total variance. The CASE demonstrated high internal consistency, concurrent validity, and construct validity. CONCLUSION: Preliminary findings suggest that the CASE is worthy of further psychometric testing and may have the potential to help delineate variations in adjustment among children with JIA.     

Development and validation of a needs-based quality of life instrument for osteoarthritis

OBJECTIVE: To develop and validate a disease-specific quality of life (QOL) measure for osteoarthritis (OA), the OAQoL, using the needs-based conceptual model. METHODS: In the first phase of this study, in-depth, semistructured interviews were conducted with 44 OA patients to explore the issues associated with impact of OA and to derive items for a draft OAQoL questionnaire. In phase 2, 17 OA patients were interviewed on the relevance, clarity, and ease of completion of the measure in structured interviews. In phase 3, the draft questionnaire was mailed to 635 patients to test the psychometric properties of the questionnaire using Rasch analysis. Test-retest assessment of the revised questionnaire was performed in phase 4 by mailing the questionnaire to an additional 201 participants, with a second questionnaire repeated 2 weeks later. RESULTS: A 38-item draft measure was devised during phase 1 and mailed in phase 2. Rasch analysis of the draft questionnaire (n = 259) indicated initial misfit, which was rectified with the removal of 13 problematic items (chi(2)[75] = 83.602, P = 0.232). For the test-retest assessment (n = 60), 3 additional items were removed, leaving a 22-item OAQoL that demonstrated good fit to the Rasch model (chi(2)[44] = 44.559, P = 0.533) with excellent test-retest correlation (rho = 0.925, P < 0.001; z = -0.06, P = 0.995). CONCLUSION: The OAQoL is a simple and easy to use 22-item unidimensional questionnaire developed specifically to assess the impact of OA on QOL. The measure has been developed as a true patient-based questionnaire and demonstrates good psychometric properties, including test-retest reliability.     

Immunoadsorption (IAS) for systemic lupus erythematosus

Immunoadsorption (IAS) is used as a rescue therapy in severely ill SLE patients who are refractory to conventional therapies. This extracorporeal method aims at the rapid and extensive removal of pathogenic immunocomplexes (ICs) and (auto-)antibodies (Abs). Although past data have shown short- to mid-term efficacy and biocompatibility of IAS in (renal) SLE, it is still an experimental and rather expensive procedure - and evidence from randomized controlled trials (RCTs) is lacking. Nevertheless, IAS is successfully used in life-threatening situations because of its fast mode of action and its acceptable safety profile.