Introduction
The aim of this study was to investigate the characteristics and outcome of systemic lupus erythematosus (SLE) among elderly-onset patients.
Methods
This study included 575 SLE patients ...managed at Cairo, Alexandria, and Helwan universities from August 2014 to 2018: of whom 49 (8.5%), 420 (73%), and 106 (18.4%) were elderly- (> 50 years), adult- (17–50 years), and juvenile- (≤ 16 years) onset patients, respectively. Cumulative characteristics were recorded. Disease activity at the last visit was investigated through the Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K), whereby lupus low disease activity (LLDA) was defined as a SLEDAI-2K score ≤ 4. The disease outcome was assessed through investigating disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)) and the prevalence of mortality. Quantitative and categorical data were compared using Kruskal–Wallis and Mann–Whitney tests, and chi-square (
χ
2
) test, respectively.
Results
Late-onset SLE (LSLE) patients demonstrated the lowest prevalence of constitutional and mucocutaneous manifestations (
p
< 0.001), serositis (
p
= 0.006), nephritis (
p
< 0.001), neuropsychiatric involvement (
p
< 0.001), and hypocomplementinemia (
p
< 0.001), but showed the highest prevalence of comorbidities and multimorbidity (comorbidities ≥ 2) (
p
< 0.001), and positive anti-ds DNA antibodies (
p
< 0.001). Elderly-onset patients demonstrated the lowest SLEDAI-2K and SDI scores, achieved LLDA the most (
p
< 0.001), and developed any damage (SDI ≥ 1) the least (
p
< 0.001). The prevalence of mortality was comparable across the three age groups (
p
= 0.6).
Conclusions
Late-onset SLE patients (8.5%) showed the lowest prevalence of major organ involvement and the highest prevalence of comorbidities, and demonstrated more favorable disease activity and damage indices.
Key Points
• The disease characteristics and outcome among LSLE patients are characterized by being controversial, with studies from the Middle East being limited. Our cohort constituted of 8.5% elderly-onset SLE patients—who were characterized by the lowest prevalence of major organ involvement and the lowest activity and damage indices—making the disease pattern more favorable in this age group, despite being characterized by the highest prevalence of comorbidities.
The study aimed to evaluate the association of demographic, clinical, and histopathologic characteristics with renal and disease outcomes. Persistent lack of partial or complete remission despite ...sequential induction therapy, chronic kidney disease (CKD) or endstage renal disease (ESRD), and/or mortality were determined as poor renal outcomes. Disease damage was investigated through the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI). Of 201 biopsy-proven lupus nephritis patients, a poor outcome was present in 56 (27.9%) patients, with nine (4.5%), 22 (10.9%), and 29 (14.4%) patients demonstrating lack of response, CKD, and ESRD, respectively, and the prevalence of mortality was 5.5% (11/201). The outcome was poor among males 29/201 (14.4%) P = 0.008; odds ratio (OR): 2.8; 95% confidence interval (CI): 1.2-6.4, yet comparable between adult- and juvenile-onset patients 80/201 (39.8%) (≤16 years) (P = 0.6; OR: 0.8; 95% CI: 0.4-1.6). Hypertension (P <0.001; OR: 6.3; 95% CI: 2.6-14.9), elevated creatinine (P <0.001; OR: 5.2; 95% CI: 2.6-10.3), and hematuria (P <0.001; OR: 3.7; 95% CI: 1.9-7.5) at presentation, and fibrinoid necrosis P <0.001; odds ratio (OR): 4.1; 95% confidence interval (CI): 2.1-8.1, wire loops (P = 0.006; OR: 2.4; 95% CI: 1.2-4.6), crescents (P <0.001; OR: 5.4 95% CI: 2.8-10.5), interstitial fibrosis (P = 0.001; OR: 2.7; 95% CI: 1.4-5.1), and acute vascular lesions (P = 0.004; OR: 3.6; 95% CI: 1.4-9.4) on biopsy were associated with a poor outcome. Chronic glomerular (P = 0.003) and acute vascular lesions (P <0.001), and a higher chronicity index (r = 0.1; P = 0.006) on biopsy, and frequent renal (r = 0.3; P <0.001) and extra-renal flares (r = 0.2; P <0.001) were associated with higher SDI scores. Among the studied renal and extra-renal parameters, independent predictors of higher disease damage solely included frequent renal flares (ᵝ= 1; P <0.001). To conclude, a poor renal outcome (27.9%) was associated with distinct features. Disease damage was associated with frequent renal flares.
Introduction/objectives
Despite its importance, adherence to treatment has not been sufficiently studied in Behçet’s disease (BD). The aim of this study was to evaluate medication adherence in BD ...using the Compliance Questionnaire of Rheumatology (CQR) and factors potentially affecting it.
Method
This cross-sectional study included 67 consecutive BD patients including 57 (85%) males with a mean age of 35.1 ± 9.27 years and mean disease duration of 129 ± 91 months. The cumulative clinical manifestations, the Behçet’s Disease Current Activity Form (BDCAF) score, and the Vasculitis Damage Index (VDI) were recorded. The CQR, Socioeconomic Status Questionnaire for Health Research in Egypt (SES), the Beliefs about Medication Questionnaire (BMQ), and the Short Form 36 (SF-36) quality of life assessment questionnaire were administered to the patients. Linear regression analysis was done to determine independent predictors of CQR.
Results
The mean BDCAF score was 3.27 ± 3.54 and the VDI was 3.36 ± 2.21. The mean CQR score was 69.2 ± 11.79. The CQR score varied significantly among different health sources (
p
= 0.02), with no relationship detected with other sociodemographic characteristics, nor with clinical characteristics or the SF-36. Among the investigated medications’ complexities, severity of side effects showed significantly different CQR scores (
p
= 0.004), and a weak positive correlation between medications’ numbers and the CQR was detected. Predictors for higher CQR scores included the necessity beliefs score of the BMQ (
β
= 1.1,
p
< 0.001); whereas, predictors for lower CQR scores were the harm and concern BMQ subscales ((
β
= − 1.5,
p
= 0.004) and (
β
= − 0.72,
p
= 0.032), respectively).
Conclusions
Beliefs about medications were the only predictor for adherence in our cohort.
•Assessment of physicochemical comparability of biosimilar trastuzumab products.•Stability indicating protocol comprised SE-HPLC & CEX-HPLC.•Effect of thermal and pH stress on trastuzumab biosimilars ...was investigated.•PCA & Cluster Analysis were utilized for the interpretation and correlation of results.•Variabilities in the degradation patterns of different biosimilars were noticed.
Biosimilar products present a growing opportunity to improve the global healthcare systems. The amount of accepted variability during the comparative assessments of biosimilar products introduces a significant challenge for both the biosimilar developers and the regulatory authorities. The aim of this study was to explore unsupervised machine learning tools as a mathematical aid for the interpretation and visualization of such comparability under control and stress conditions using data extracted from high throughput analytical techniques. For this purpose, a head-to-head analysis of the physicochemical characteristics of three Trastuzumab (TTZ) approved biosimilars and the originator product (Herceptin®) was performed. The studied quality attributes included the primary structure and identity by peptide mapping (PM) with reversed-phase chromatography-UV detection, size and charge profiles by stability-indicating size exclusion and cation exchange chromatography. Stress conditions involved pH and thermal stress. Principal component analysis (PCA) and two of the widely used cluster analysis tools, namely, K-means and Density-based Spatial Clustering of Applications with Noise (DBSCAN), were explored for clustering and feature representation of varied analytical datasets. It has been shown that the clustering patterns delineated by the used algorithms changed based on the included chromatographic profiles. The applied data analysis tools were found effective in revealing patterns of similarity and variability between i) intact and stressed as well as ii) originator and biosimilar samples.
Background
Transition of care means the process of educating and empowering adolescents and young adults to take an active role in their own healthcare, develop decision-making skills, and eventually ...transition from paediatric to adult healthcare providers. Most people do not switch doctors until they are young adults, but it can be beneficial to start preparing children earlier. We aimed to develop a specific toolkit tailored to paediatric and adult rheumatologists to assist them in transitioning of care of young people with juvenile onset rheumatic musculoskeletal diseases from the paediatric to adult rheumatology care.
Results
The expert panel was confined to an online survey (
n
= 18), all the experts completed the two rounds. At the conclusion of round 2, a total of 10 points were gathered. The range of respondents (ranks 7–9) who agreed with the recommendations was 88.9 to 100%. All 10 clinical standards identified by the scientific committee were written in the same way. Based on the answers to the structured key questions and the literature review, a structured template was developed presenting transition of care integrated pathway.
Conclusion
The developed rheumatology-specific guideline offers adolescents and young adults a focussed, multidisciplinary transition of care approach with equity of access, quality of care and flexibility and set up standards for transitional care for young adults with juvenile rheumatological diseases.
•Peptide mapping – principal component analysis for stability & biosimilarity assessment.•Forced degradation of recombinant human growth hormone.•Biosimilarity assessment of recombinant human growth ...hormone.•On-column digestion of recombinant human growth hormone.
Peptide mapping (PM) is a vital technique in biopharmaceutical industry. The fingerprint obtained helps to qualitatively confirm host stability as well as verify primary structure, purity and integrity of the target protein. Yet, in-solution digestion followed by tandem mass spectrometry is not suitable as a routine quality control test. It is time consuming and requires sophisticated, expensive instruments and highly skilled operators. In an attempt to enhance the fuctionality of PM and extract multi-dimentional data about various critical quality attributes and comparability of biosimilars, coupling of PM generated using immobilized trypsin followed by HPLC-UV to principal component analysis (PCA) is proposed. Recombinant human growth hormone (rhGH); was selected as a model biopharmaceutical since it is available in the market from different manufacturers and its PM is a well-established pharmacopoeial test. Samples of different rhGH biosimilars as well as degraded samples: deamidated and oxidized were subjected to trypsin digestion followed by RP-HPLC-UV analysis. PCA of the entire chromatograms of test and reference samples was then conducted. Comparison of the scores of samples and investigation of the loadings plots clearly indicated the applicability of PM-PCA for: i) identity testing, ii) biosimilarity assessment and iii) stability evaluation. Hotelling’s T2 and Q statistics were employed at 95% confidence level to measure the variation and to test the conformance of each sample to the PCA model, respectively. Coupling of PM to PCA provided a novel tool to identify peptide fragments responsible for variation between the test and reference samples as well as evaluation of the extent and relative significance of this variability. Transformation of conventional PM that is largely based on subjective visual comparison into an objective statiscally-guided analysis framework should provide a simple and economic tool to help both manufacturers and regulatory authorities in quality and biosimilarity assessment of biopharmaceuticals.
To evaluate the albumin-fibrinogen ratio (AFR) and C-reactive protein-albumin ratio (CAR) as inflammatory markers in rheumatoid arthritis (RA) and to investigate their association with disease ...activity correlating with musculoskeletal ultrasonographic findings.
A total of 125 cases of RA patients were consecutively enrolled in a multicenter cross-sectional study compared to 100 healthy controls, all subjects were investigated for fibrinogen, albumin, CRP, erythrocyte sedimentation rate, AFR, and CAR measurements. Patients' disease activity was assessed by disease activity score (DAS28-ESR), and they were subjected to high-frequency ultrasound both in greyscale and power Doppler.
RA patients had lower AFR and higher CAR than those in the control group (P < 0.001). A positive correlation was demonstrated between CAR and DAS score (r=0.589, P = 0.0001), whilst there was a precise negative correlation between AFR and DAS 28-ESR (r=-0.74, p<0.001). ROC curve analyses revealed fibrinogen showed the best sensitivity (92.1%) for the area under the curve of 0.928, at a criterion of 2.47, while AFR has an area under the curve of 0.826 with sensitivity and specificity (86.84% and 75%, respectively) at cut-off value 1.46. Actively diseased patients had elevated CAR than those in remission (P < 0.001). Patients with synovial thickening and bone erosions had lower AFR than those without, CAR was higher in patients with power doppler changes than those without (p=0.015).
Higher CAR and lower AFR were expressed in active RA than those in remission. CAR and AFR could be useful markers of ongoing inflammation and joint affection detected by musculoskeletal ultrasonography.
To study the visual disability predictors in Behçet's disease (BD).
A cross-sectional observational study including 54 patients. Sociodemographic and cumulative clinical characteristics were ...obtained. Ophthalmic examination focused on disease activity and degree of visual loss.
Presenting features included oral ulcers, orogenital ulcers, uveitis, and vascular involvement. Ocular involvement was also present in a majority of the cases 74.1%. The age at onset had no significant effect on diagnostic time lag (P = .9), unlike rural residency (P = .02). Laterality, ocular activity, and interventions significantly affected final visual acuity (P˂0.001). A diagnostic time lag ≥ 9 months significantly affected final visual acuity (P = .039).
BD is associated with considerable vision loss at a young age. Panuveitis, bilaterality, ocular activity, and interventions are significant predictors. A diagnostic time lag ≥ 9 months is associated with poor visual outcomes and is significantly associated with rural residency.
The nuclear receptor coactivator 5 (NCOA5) has been linked to several inflammatory disorders, including Behçet's disease (BD). We evaluated the expression of NCOA5 messenger RNA (mRNA) using ...real-time reverse transcription-polymerase chain reaction, and analyzed the rs2903908 T > C of NCOA5 using TaqMan allelic discrimination assay in 49 Egyptian BD patients and 50 controls. The NCOA5 mRNA levels were higher in patients compared to controls (p = .02), female patients compared to males (p = .037), and in patients with ocular involvement (p = .049). Non-CC genotype carriers had a higher frequency of articular manifestations compared with CC carriers (p = .047). Genotypes CC + CT were associated with reduced risk of cutaneous involvement (OR = 0.27, p = .04). CC carriers with active BD or cutaneous manifestations displayed significantly lower NCOA5 mRNA expression than TT carriers. Our results demonstrate that NCOA5 is linked to BD clinical findings and activity.
Objective
To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis.
Methodology
Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84 ...(41.8%) juvenile-onset (≤ 16 years)) were retrospectively reviewed. Data were analyzed through Kruskal–Wallis and Mann–Whitney, chi-square (
χ
2
) tests, and logistic regression.
Results
The median disease and follow-up durations were 36 (interquartile range (IQR) 24–70) and 24 (IQR 10–36) months, respectively. Fifty-eight (28.9%) patients had persistently idiopathic uveitis, and 143 (71.1%) were associated with rheumatic diseases, of whom uveitis heralded, coincided with, and succeeded the rheumatic manifestation(s) in 62/143 (43.4%), 37/143 (25.9%), and 44/143 (30.7%) patients, respectively. Established rheumatic diseases were Behçet’s disease (103/201 (51.2%)), juvenile idiopathic arthritis (13/201 (6.5%)), sarcoidosis (8/201 (4%)), seronegative spondyloarthropathy (7/201 (3.5%)), and Vogt-Koyanagi-Harada (7/201 (3.5%)), and other diagnoses were present in 5/201 (2.5%) patients. Patients with idiopathic uveitis were characterized by a juvenile-onset (
p
< 0.001), lower male predominance (
p
= 0.01), prevalent granulomatous (
p
< 0.001), and anterior (
p
= 0.001) uveitis. The median visual acuity at last visit was 0.3 (IQR 0.05–0.6). Visual loss was present in 45/201 (22.3%) patients (36/201 (17.9%) unilateral and 9/201 (4.4%) bilateral). Apart from a longer disease duration (
p
= 0.002), lower educational level (
p
= 0.03), and prevalent panuveitis (
p
< 0.001), visual loss was not associated with any other studied ocular or extra-ocular characteristics.
Conclusion
Behçet’s disease (51.2%) and idiopathic uveitis (28.9%) were the most prevalent causes of non-infectious uveitis in our study. Visual loss (22.3%) was associated with a longer disease duration, lower education level, and prevalent panuveitis.
Key Points
• Most common causes of uveitis referred to rheumatologists were Behçet’s disease and idiopathic uveitis.
• Several rheumatic diseases initially presented only with uveitis, more commonly in adult and male patients.
• Panuveitis was more frequent among patients with an established rheumatic disease, whereas granulomatous uveitis was uncommon.
• Longer disease duration and presence of panuveitis were independently associated with visual loss.
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