A hierarchical cluster analysis for clinical profiling of tofacitinib treatment response in patients with rheumatoid arthritis.

Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12 weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA.

Validation and the associated factors of the Malay version of systemic lupus erythematosus-specific health-related quality of life questionnaires (SLEQoL and LupusQoL).

OBJECTIVES: To assess the reliability and validity of two disease-specific questionnaires that assess the quality of life (QoL) among patients with Systemic Lupus Erythematosus (SLE); SLEQoL and LupusQoL in Malay language. This study also identified the factors affecting each domain of the questionnaires. METHODS: This cross-sectional study was conducted from June 2021 until April 2022, and SLE patients were recruited to complete the SLEQoL, LupusQoL and Short Form Health Survey (SF-36) in Malay language. Disease activity were recorded using the modified SLE Disease Activity Index (M- SLEDAI) and British Isles Lupus Assessment Group 2004 (BILAG-2004) index. Presence of organ damage was determined using the SLICC Damage index. Cronbach's alpha was calculated to determine internal consistency while exploratory factor analysis was done to determine the construct validity. Concurrent validity was evaluated using correlation with SF-36. Multiple linear regression analysis was deployed to determine the factors affecting each domain of SLEQoL and LupusQoL. RESULTS: A total of 125 subjects were recruited. The Cronbach's α value for the Malay-SLEQoL (M-SLEQoL) and Malay-LupusQOL (M-LupusQoL) was 0.890 and 0.944 respectively. Exploratory factor analysis found formation of similar number of components with the original version of questionnaires and all items have good factor loading of >0.4. Both instruments also had good concurrent validity with SF-36. M-SLEQoL had good correlations with BILAG-2004 and M-SLEDAI scores. Musculoskeletal (MSK) involvement was independently associated with lower M-SLEQoL in physical function, activity and symptom domains. Meanwhile, MSK and NPSLE were associated with fatigue in M-LupusQoL. CONCLUSION: Both M-SLEQoL and M-LupusQoL are reliable and valid as disease -specific QoL instruments for Malaysian patients. The M-Lupus QoL has better discriminative validity compared to the M-SLEQoL. SLE patients with MSK involvement are at risk of poor QoL in multiple domains including physical function, activity, symptoms and fatigue.

Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study.

BACKGROUND: Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse. OBJECTIVE: The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results. METHODS: By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire. RESULTS: Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models. CONCLUSIONS: The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/31885.

A 3D Microfluidic ELISA for the Detection of Severe Dengue: Sensitivity Improvement and Vroman Effect Amelioration by EDC-NHS Surface Modification.

Serum is commonly used as a specimen in immunoassays but the presence of heterophilic antibodies can potentially interfere with the test results. Previously, we have developed a microfluidic device called: 3D Stack for enzyme-linked immunosorbent assay (ELISA). However, its evaluation was limited to detection from a single protein solution. Here, we investigated the sensitivity of the 3D Stack in detecting a severe dengue biomarker-soluble CD163 (sCD163)-within the serum matrix. To determine potential interactions with serum matrix, a spike-and-recovery assay was performed, using 3D Stacks with and without surface modification by an EDC-NHS (N-ethyl-N'-(3-(dimethylamino)propyl)carbodiimide/N-hydroxysuccinimide) coupling. Without surface modification, a reduced analyte recovery in proportion to serum concentration was observed because of the Vroman effect, which resulted in competitive displacement of coated capture antibodies by serum proteins with stronger binding affinities. However, EDC-NHS coupling prevented antibody desorption and improved the sensitivity. Subsequent comparison of sCD163 detection using a 3D Stack with EDC-NHS coupling and conventional ELISA in dengue patients' sera revealed a high correlation (R = 0.9298, p < 0.0001) between the two detection platforms. Bland-Altman analysis further revealed insignificant systematic error between the mean differences of the two methods. These data suggest the potentials of the 3D Stack for further development as a detection platform.