Displaying publications 41 - 60 of 60 in total

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  1. Munusamy T, Karuppiah R, Bahuri NFA, Sockalingam S, Cham CY, Waran V
    World Neurosurg, 2021 01;145:e53-e60.
    PMID: 32956888 DOI: 10.1016/j.wneu.2020.09.076
    OBJECTIVE: The coronavirus disease 2019 pandemic poses major risks to health care workers in neurocritical care. Recommendations are in place to limit medical personnel attending to the neurosurgical patient as a protective measure and to conserve personal protective equipment. However, the complexity of the neurosurgical patient proves to be a challenge and an opportunity for innovation. The goal of our study was to determine if telemedicine delivered through smart glasses was feasible and effective in an alternative method of conducting ward round on neurocritical care patients during the pandemic.

    METHODS: A random pair of neurosurgery resident and specialist conducted consecutive virtual and physical ward rounds on neurocritical patients. A virtual ward round was first conducted remotely by a specialist who received real-time audiovisual information from a resident wearing smart glasses integrated with telemedicine. Subsequently, a physical ward round was performed together by the resident and specialist on the same patient. The management plans of both ward rounds were compared, and the intrarater reliability was measured. On study completion a qualitative survey was performed.

    RESULTS: Ten paired ward rounds were performed on 103 neurocritical care patients with excellent overall intrarater reliability. Nine out of 10 showed good to excellent internal consistency, and 1 showed acceptable internal consistency. Qualitative analysis indicated wide user acceptance and high satisfaction rate with the alternative method.

    CONCLUSIONS: Virtual ward rounds using telemedicine via smart glasses on neurosurgical patients in critical care were feasible, effective, and widely accepted as an alternative to physical ward rounds during the coronavirus disease 2019 pandemic.

  2. Lee YH, Baharuddin NA, Chan SW, Rahman MT, Bartold PM, Sockalingam S, et al.
    Clin Oral Investig, 2021 Mar;25(3):1441-1450.
    PMID: 32656595 DOI: 10.1007/s00784-020-03452-9
    OBJECTIVES: It has been proposed that citrullination and carbamylation occur in the inflamed periodontium and could be the plausible mechanisms for the generation of antigens involved in the development and progression of RA. The purpose of this study was to determine the presence and location of citrullinated and carbamylated proteins in the gingival tissues and compare their abundance in periodontitis (PD) patients with or without RA.

    MATERIALS AND METHODS: Gingival tissue samples of healthy (n = 5), PD with RA (n = 5) and PD without RA (n = 5) were collected. Specimens were formalin fixed, paraffin embedded and sectioned at 4 μm. The tissue sections were analysed for the presence of citrullinated and carbamylated proteins by immunohistochemistry. Semi-quantitative analysis was performed to quantify and compare the protein abundance between groups.

    RESULTS: The number of cells containing citrullinated and carbamylated proteins with higher intensity was markedly increased in gingival tissues from PD with or without RA in comparison with healthy controls.

    CONCLUSION: Inflamed gingival tissue is a potential source of citrullinated and carbamylated proteins other than synovial tissues. The extent to which the local accumulation of these proteins contributes to the pathogenesis of RA needs further elucidation.

    CLINICAL RELEVANCE: If PD is a potential source of post-translationally modified proteins, untreated PD should not be taken lightly in the context of RA. Hence, addressing gingival inflammation should be viewed as an important preventive measure in the general population not only for the progression of periodontal disease but also reducing the risk of developing extra-oral comorbidities.

  3. Lew PH, Rahman MT, Safii SH, Baharuddin NA, Bartold PM, Sockalingam S, et al.
    BMC Oral Health, 2021 07 20;21(1):360.
    PMID: 34284769 DOI: 10.1186/s12903-021-01712-y
    BACKGROUND: Previous studies have reported conflicting findings between serum anti-citrullinated protein antibodies (ACPA) levels in rheumatoid arthritis (RA) participants with and without periodontitis (Pd). This study aimed to analyse possible correlations between serum ACPA levels and clinical parameters in Pd and RA participants.

    METHODS: Full mouth periodontal examination (probing pocket depth, clinical attachment levels, gingival bleeding index, visual plaque index) was conducted and serum samples obtained from 80 participants comprising RA, Pd, both RA and Pd (RAPd) and healthy individuals (HC). Erythrocyte sedimentation rates (ESR) and periodontal inflamed surface area (PISA) were obtained. Serum samples were analysed for ACPA quantification using enzyme-linked immunosorbent assay (ELISA).

    RESULTS: Median levels (IU/mL) of ACPA (interquartile range, IQR) in RAPd, RA, Pd and HC groups were 118.58(274.51), 102.02(252.89), 78.48(132.6) and 51.67(91.31) respectively. ACPA levels were significantly higher in RAPd and RA as compared to HC group (p  RA > Pd > HC. However, lack of any significant correlation between the serum ACPA levels with the clinical Pd and RA parameters warrants further studies to investigate the causal link between RA and Pd for such a trend. Further studies involving more inflammatory biomarkers might be useful to establish the causal link between Pd in the development and progression of RA or vice versa.

  4. Chopra A, Lin HY, Navarra SV, Saeed MA, Sockalingam S, Thongpooswan S, et al.
    Int J Rheum Dis, 2021 Sep;24(9):1106-1111.
    PMID: 34375036 DOI: 10.1111/1756-185X.14185
    Rheumatoid arthritis (RA) is a major health burden in Asia Pacific affecting the quality of life of patients and consuming healthcare resources. According to recent estimates from the World Health Organization-International League Against Rheumatism-Community Oriented Program for Control of Rheumatic Diseases, prevalence is around 0.3%-0.5%. Management guidelines have helped to improve treatment across this diverse region. To gain better insight into current real-world management applications in view of these guidelines, virtual meetings were conducted in mid-2020 to explore perspectives of rheumatologists and patients, as well as discuss the impact of coronavirus disease 2019 on RA management. Patients and rheumatologists from Hong Kong, Malaysia, Singapore, the Philippines, Thailand, India, Pakistan, and Taiwan were included, representing a diverse mix of healthcare systems, wealth, ethnicity and culture. Despite many countries having prospered in recent years, similar challenges in RA diagnosis and treatment were identified. The daily impact and patient experience of RA were also similar across countries, marked by "silent" pain and disability, and universal misunderstanding of the disease. Late diagnosis and treatment, and barriers to access to appropriate treatment, remain problematic. The experience shared by Taiwan offers a glimmer of hope, however, wherein patient advocacy groups have succeeded in being included in policy-making decisions and securing access to advanced treatment. Real-world solutions that pay heed to the unique local needs and diversity of Asia Pacific are required to improve RA management, which will take time. In the interim, help can be sought from the trained, non-rheumatologist community to reduce some of the disease burden.
  5. Kandane-Rathnayake R, Louthrenoo W, Golder V, Luo SF, Wu YJ, Lateef A, et al.
    Rheumatology (Oxford), 2021 Nov 03;60(11):5185-5193.
    PMID: 33693676 DOI: 10.1093/rheumatology/keab217
    OBJECTIVE: The prevalence and associations of leucopenia in SLE remain incompletely understood. We evaluated associations of disease activity and medication use with leucopenia (lymphopenia and neutropenia) in a multinational, prospectively followed SLE cohort.

    METHODS: Data from the Asia Pacific Lupus Collaboration cohort, in which disease activity and medications were prospectively captured from 2013 to 2018, were used. Predictors of lymphopenia (lymphocyte count <0.8 × 109/l) and neutropenia (neutrophil count <1.5 × 109/l) were examined using multiple failure, time-dependent survival analyses.

    RESULTS: Data from 2330 patients and 18 287 visits were analysed. One thousand and eighteen patients (43.7%) had at least one episode of leucopenia; 867 patients (37.2%) had lymphopenia, observed in 3065 (16.8%) visits, and 292 (12.5%) patients had neutropenia, in 622 (3.4%) visits. After multivariable analyses, lymphopenia was associated with overall disease activity, ESR, serology, prednisolone, AZA, MTX, tacrolimus, CYC and rituximab use. MTX and ciclosporin were negatively associated with neutropenia. Lupus low disease activity state was negatively associated with both lymphopenia and neutropenia.

    CONCLUSION: Both lymphopenia and neutropenia were common in SLE patients but were differentially associated with disease and treatment variables. Lymphopenia and neutropenia should be considered independently in studies in SLE.

  6. Kandane-Rathnayake R, Louthrenoo W, Luo SF, Wu YJ, Chen YH, Golder V, et al.
    Arthritis Care Res (Hoboken), 2022 Dec;74(12):2033-2041.
    PMID: 34197023 DOI: 10.1002/acr.24740
    OBJECTIVE: Evidence for the utility of medications in settings lacking randomized trial data can come from studies of treatment persistence. The present study was undertaken to examine patterns of medication use in systemic lupus erythematosus (SLE) using data from a large multicenter longitudinal cohort.

    METHODS: Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLE Disease Activity Index 2000 [SLEDAI-2K]) and medication details, captured at every visit from 2013-2018, were used. Medications were categorized as glucocorticoids (GCs), antimalarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time-to-discontinuation of medications, stratified by SLE disease activity.

    RESULTS: Data from 19,804 visits of 2,860 patients were analyzed. Eight medication categories were observed: no treatment; GC, AM, or IS only; GC plus AM; GC plus IS; AM plus IS; and GC plus AM plus IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits); single agents were used in 21% of visits, and biologics in only 3%. Time-to-discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with a time-adjusted mean SLEDAI-2K score of ≥10 had lower discontinuation of GCs and higher discontinuation of IS.

    CONCLUSION: Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.

  7. Kandane-Rathnayake R, Golder V, Louthrenoo W, Chen YH, Cho J, Lateef A, et al.
    Lancet Rheumatol, 2022 Dec;4(12):e822-e830.
    PMID: 38261390 DOI: 10.1016/S2665-9913(22)00304-6
    BACKGROUND: Treat-to-target goals for patients with systemic lupus erythematosus (SLE) have been validated to protect against organ damage and to improve quality of life. We aimed to investigate the association between lupus low disease activity state (LLDAS) and remission and risk of mortality in patients with SLE. We hypothesised that LLDAS has a protective association with mortality risk.

    METHODS: In this prospective, multinational, longitudinal cohort study, we used data from patients with SLE in the Asia Pacific Lupus Collaboration cohort collected between May 1, 2013, and Dec 31, 2020. Eligible patients were adults (aged ≥18 years) who met either the 1997 American College of Rheumatology modified classification criteria for SLE or the 2012 Systemic Lupus International Collaborating Clinics classification criteria. The primary outcome was all-cause mortality, and LLDAS, remission, and variations of remission with lower glucocorticoid thresholds were the primary exposure variables. Survival analyses were used to examine longitudinal associations between these endpoints and risk of mortality. This study is registered with ClinicalTrials.gov, NCT03138941.

    FINDINGS: Among a total of 4106 patients in the cohort, 3811 (92·8%) patients were included in the final analysis (median follow-up 2·8 years [IQR 1·0-5·3]; 3509 [92·1%] women and 302 [7·9%] men), of whom 80 died during the observation period (crude mortality rate 6·4 deaths per 1000 person-years). LLDAS was attained at least once in 43 (53·8%) of 80 participants who died and in 3035 (81·3%) of 3731 participants who were alive at the end of the study (p<0·0001); 22 (27·5%) participants who died versus 1966 (52·7%) who were alive at the end of the study attained LLDAS for at least 50% of observed time (p<0·0001). Remission was attained by 32 (40·0%) of 80 who died and in 2403 (64·4%) of 3731 participants who were alive at the end of the study (p<0·0001); 14 (17·5%) participants who died versus 1389 (37·2%) who were alive at the end of the study attained remission for at least 50% of observed time (p<0·0001). LLDAS for at least 50% of observed time (adjusted hazard ratio 0·51 [95% CI 0·31-0·85]; p=0·010) and remission for at least 50% of observed time (0·52 [0·29-0·93]; p=0·027) were associated with reduced risk of mortality. Modifying the remission glucocorticoid threshold (<5·0 mg/day prednisolone) was more protective against mortality than current remission definitions (0·31 [0·12-0·77]; p=0·012), and glucocorticoid-free remission was the most protective (0·13 [0·02-0·96]; p=0·046).

    INTERPRETATION: LLDAS significantly reduced the risk of mortality in patients with SLE. Remission did not further reduce the risk of mortality compared with LLDAS, unless lower glucocorticoid thresholds were used.

    FUNDING: The Asia-Pacific Lupus Collaboration received funding from Janssen, Bristol Myers Squibb, Eli Lilly, and UCB for this study.

  8. Connelly K, Kandane-Rathnayake R, Hoi A, Louthrenoo W, Hamijoyo L, Cho J, et al.
    Lancet Rheumatol, 2022 Dec;4(12):e831-e841.
    PMID: 38261391 DOI: 10.1016/S2665-9913(22)00307-1
    BACKGROUND: The selection and categorisation of laboratory tests in disease activity measures used within systemic lupus erythematosus (SLE) trial endpoints lack strong evidence. We aimed to determine whether longitudinal improvements in routinely measured laboratory tests are associated with measures of clinical improvement in patients with baseline active SLE.

    METHODS: We included patients from a multicentre longitudinal cohort (recruited between May 1, 2013, and Dec 31, 2019) with active SLE (SLEDAI-2K ≥6) coinciding with an abnormality in at least one of 13 routine laboratory tests, at a visit designated as baseline. At 12 months, we analysed associations between thresholds of improvement in individual laboratory test results, measured as continuous variables, and five clinical outcomes using logistic regression. Primary outcomes were damage accrual and lupus low disease activity state (LLDAS), and secondary outcomes were modified SLE responder index (mSRI), physician global assessment (PGA) improvement of at least 0·3, and flare.

    FINDINGS: We included 1525 patients (1415 [93%] women and 110 [7%] men, 1328 [87%] Asian ethnicity) in separate subsets for each laboratory test. The strongest associations with LLDAS and damage protection were seen with improvements in proteinuria (complete response: adjusted odds ratio [OR] 62·48, 95% CI 18·79-208·31 for LLDAS, OR 0·22, 95% CI 0·10-0·49 for damage accrual), albumin (complete response: adjusted OR 6·46, 95% CI 2·20-18·98 for LLDAS, OR 0·42, 95% CI 0·20-1·22 for damage accrual), haemoglobin (complete response: adjusted OR 1·97, 95% CI 1·09-3·53 for LLDAS, OR 0·33, 95% CI 0·15-0·71 for damage accrual), erythrocyte sedimentation rate (complete response: adjusted OR 1·71, 95% CI 1·10-2·67 for LLDAS, OR 0·53, 95% CI 0·30-0·94 for damage accrual), and platelets (complete response: adjusted OR 4·82, 95% CI 1·54-15·07 for LLDAS, OR 0·49, 95% CI 0·20-1·19 for damage accrual). Improvement in serological tests were mainly associated with PGA and mSRI. White cell and lymphocyte count improvements were least predictive.

    INTERPRETATION: Improvements in several routine laboratory tests correspond with clinical outcomes in SLE over 12 months. Tests with the strongest associations were discrepant with laboratory tests included in current trial endpoints, and associations were observed across a range of improvement thresholds including incomplete resolution. These findings suggest the need to revise the use of laboratory test results in SLE trial endpoints.

    FUNDING: Abbvie.

  9. Connelly K, Kandane-Rathnayake R, Hoi A, Louthrenoo W, Hamijoyo L, Luo SF, et al.
    Arthritis Rheumatol, 2023 Mar;75(3):401-410.
    PMID: 36122172 DOI: 10.1002/art.42350
    OBJECTIVE: In trials of systemic lupus erythematosus (SLE), the SLE Responder Index (SRI) is the most commonly used primary efficacy end point but has limited validation against long-term outcomes. We aimed to investigate associations of attainment of a modified version of the SRI (mSRI) with key clinical outcomes in SLE patients with up to 5 years of follow-up.

    METHODS: We used data from a large multicenter, longitudinal SLE cohort in which patients received standard of care. The first visit with active disease (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6) was designated as baseline, and mSRI attainment (defined as a reduction in SLEDAI-2K ≥4 points with no worsening in physician global assessment ≥0.3 points) was determined at annual intervals from baseline up to 5 years. Associations between mSRI attainment and outcomes including disease activity, glucocorticoid dose, flare, damage accrual, Lupus Low Disease Activity State (LLDAS), and remission were studied.

    RESULTS: We included 2,060 patients, with a median baseline SLEDAI-2K score of 8. An mSRI response was attained by 56% of patients at 1 year, with similar responder rates seen at subsequent annual time points. Compared to nonresponders, mSRI responders had significantly lower disease activity and prednisolone dose and higher proportions of LLDAS and remission attainment at each year, and less damage accrual at years 2 and 3. Furthermore, mSRI responder status at 1 year predicted clinical benefit at subsequent years across most outcomes, including damage accrual (odds ratio [OR] range 0.58-0.69, P 

  10. Tan BH, Sockalingam S, Ganesan D
    Br J Neurosurg, 2023 Jun 22.
    PMID: 37345453 DOI: 10.1080/02688697.2023.2225611
    OBJECTIVES: Posterior cervical foraminotomy is a surgical procedure used to treat unilateral cervical radiculopathy. It provides direct decompression of the nerve root without the necessity of fusion while maintaining cervical mobility. With the advancement in image-guidance technology and minimal access techniques, intra-operative CT has provided a safer, more accurate instrumentation placement with less radiation exposure to operative staff and provides better anatomical visualization quality compared to traditional intra-operative imaging techniques. This case series aims to address the applications of advanced image guidance in posterior cervical foraminotomy and describe the nuances.

    METHOD: A technical report on a series of seven cases on intraoperative CT navigation for posterior cervical foraminotomy surgery. Posterior cervical foraminotomy was performed in all patients under CT guided navigation system without an image intensifier. In one case after the foraminotomy, the extruded disc was carefully removed by gentle retraction.

    RESULT: From 1 January 2020 to 31 December 2021, a total of seven patients with nine cervical foraminotomy procedures were performed using the aid of CT-guided navigation. The series comprised five women and two men whose mean age was 50.6 years. In all cases, the radiculopathy symptoms were diminished significantly. There were no cases of instability on the dynamic cervical radiograph. There were no complications during the surgical procedure.

    CONCLUSION: The navigation also allows the surgeon to localise the index level accurately and appraise the adequacy of the intended decompression in three planes of the CT scan image. The ability to perform accurate spine navigation would be the precursor for robotic spinal surgery.

  11. Lee JK, Abbas AA, Cheah TE, Simanjuntak RN, Sockalingam S, Roohi S
    J Orthop Res, 2023 Sep;41(9):1916-1924.
    PMID: 36924071 DOI: 10.1002/jor.25549
    Osteoarthritis (OA) contributes to significant medical and socioeconomic burden in many populations. Its prevalence is expected to rise continuously owing to the combined effects of aging and increase in risk factors, including obesity, physical inactivity, and joint injuries. Pain is a hallmark presentation of OA. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended by many international guidelines as an early treatment option of the management of osteoarthritic pain. However, the use of topical NSAIDs remains low in Malaysia and appears not to be a preferred agent in managing OA pain by prescribers. There is also limited guidance from local medical bodies on the use of topical NSAIDs to manage OA pain. This consensus recommendation is intended to serve as a practical guide for healthcare practitioners on the use of topical NSAIDs in the management of OA pain. Eight statements and recommendations were finalized covering the areas of OA burden, topical NSAIDs formulations, safety and efficacy of topical NSAIDs, and patient education. Robust evidence is available to support the efficacy and safety of topical NSAIDs, with its benefits further strengthened by ease of use and access. Taking these into consideration, we recommend that healthcare practitioners advocate for the early use of topical NSAIDs over oral NSAIDs for mild-to-moderate OA pain, while engaging in a shared decision-making process with patients for optimal clinical outcomes.
  12. Tan BC, Mahyuddin A, Sockalingam SNMP, Zakaria ASI
    BMC Complement Med Ther, 2023 Sep 20;23(1):331.
    PMID: 37730579 DOI: 10.1186/s12906-023-04163-w
    BACKGROUND: The downfall of formocresol as a pulpotomy medicament highlights the importance of cytotoxic evaluation and the establishment of a safe concentration of dental material prior to its usage in the oral cavity. Uncaria gambir is an herbal plant that possesses antimicrobial, anti-inflammatory and antioxidant properties, suggesting its potential as an alternative medicament for pulpotomy. However, there are not many studies published on its cytotoxicity, with some using non-standardised techniques and reported variable outcomes. Here, we investigated the concentration and time-dependent toxicity of Uncaria gambir extract towards the M3CT3-E1 cell line and compared it with the gold standard pulpotomy medicament: mineral trioxide aggregate (MTA).

    METHODS: Uncaria gambir extracts at concentrations ranging from 1000 to 7.8 µg/ml and MTA eluates at 4- and 48 h setting times were prepared. 10% dimethyl sulfoxide (DMSO) and culture media were used as positive and negative controls respectively. Cell viability on days 1, 2, 3 and 7 was analysed using Alamar Blue and Live and Dead Cell assay. Any morphological cellular changes were evaluated using transmission electron microscopes (TEM). Data were analysed using a two-way mixed Analysis of Variance (ANOVA).

    RESULTS: The interaction between the concentration and exposure time on the fluorescence intensity of Uncaria gambir extract and MTA 48 h was found to be statistically significant (p < 0.001). No cytotoxic effects on the cells were exerted by both MTA 48 h and Uncaria gambir extract at a concentration below 500 µg/mL. TEM analysis and Live and Dead Cell assay for both materials were comparable to the negative control. No significant differences in fluorescent intensity were observed between Uncaria gambir extract at 500 µg/mL and MTA 48 h (p > 0.05).

    CONCLUSION: Uncaria gambir extracts at a maximum concentration of 500 μg/mL are non-cytotoxic over time and are comparable to the MTA.

  13. Chandraseharan P, Sockalingam SNM, Shafiei Z, Zakaria ASI, Mahyuddin A, Rahman MA
    J Contemp Dent Pract, 2023 Oct 01;24(10):779-786.
    PMID: 38152911 DOI: 10.5005/jp-journals-10024-3581
    AIMS AND BACKGROUND: This study evaluates the antimicrobial activities of commercially available 5% apple cider vinegar (ACV) against Enterococcus faecalis, Streptococcus mutans, and Lactobacillus casei. Materials and methods: Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were conducted using the broth microdilution method. Sodium hypochlorite (NaOCl) of 5.25% was used as a positive control, and comparisons were also made with acetic acid (AA) as the main ingredient in ACV. The three test bacteria treated with the most effective ACV dilution were visualized under a transmission electron microscope (TEM) for structural changes.

    RESULTS: Minimal inhibitory concentration was determined at 0.625% of the concentration of ACV against S. mutans and E. faecalis and 1.25% of the concentration of ACV against L. casei with two-fold serial dilutions. A concentration of 5 × 10-1% with 10-fold serial dilutions was found to be the MIC value for all three bacteria. No significant differences were found when compared with the positive control (NaOCl) (p = 0.182, p = 0.171, and p = 0.234), respectively, for two-fold serial dilutions and (p = 1.000, p = 0.658, and p = 0.110), respectively for 10-fold serial dilutions. MBC was observed to be 5% ACV for both E. faecalis and S. mutans. However, positive microbial growth was observed on the agar plate when cultured with L. casei. An independent sample t-test showed no significant differences (p > 0.05) in the antimicrobial activities between 5% ACV and 5% pure AA. TEM revealed cell wall and cytoplasmic membrane disruptions on all three bacteria at MIC value.

    CONCLUSION: Apple cider vinegar has antimicrobial activities against Enterococcus faecalis, Streptococcus mutans, and Lactobacillus casei at their respective MIC values.

    CLINICAL SIGNIFICANCE: Apple cider vinegar can be an alternative antimicrobial dental pulp disinfectant to sodium hypochlorite. Apple cider vinegar can be used safely, especially in children's dental pulp therapy and deep caries management, when adequate tooth isolation is not readily achievable. Thus, adverse reactions commonly associated with other frequently used chemical disinfectants can be avoided.

  14. Cho J, Shen L, Huq M, Kandane-Rathnayake R, Golder V, Louthrenoo W, et al.
    Lancet Rheumatol, 2023 Oct;5(10):e584-e593.
    PMID: 38251484 DOI: 10.1016/S2665-9913(23)00209-6
    BACKGROUND: Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission.

    METHODS: This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission.

    FINDINGS: Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare.

    INTERPRETATION: Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months.

    FUNDING: AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB.

  15. Kuppusamy E, Ratnasingam MD, Yazid F, Rosli TI, Ali AM, Sockalingam SNMP, et al.
    J Int Soc Prev Community Dent, 2023;13(2):133-140.
    PMID: 37223451 DOI: 10.4103/jispcd.JISPCD_213_22
    OBJECTIVES: This study aims to explore the information-seeking behavior patterns of parents with children receiving treatment for early childhood caries (ECC).

    MATERIALS AND METHODS: Semistructured in-depth interviews were conducted with 20 parents of children with ECC. A topic guide was developed, focusing on questions relating to (i) the timing of their seeking information on ECC, (ii) the types of EEC information they seek, and (iii) the resources used to seek information. The interviews were audio-recorded and transcribed verbatim. Thematic analysis was performed, whereby the data were coded and categorized into themes and subthemes.

    RESULTS: Four main themes were identified: the immediacy of seeking information, perceived information need, use of resources, and barriers to seeking information. Parents either sought information immediately after detecting changes to the appearance of their child's teeth, with some being aware of the changes after signs and symptoms developed. The types of information parents usually sought covered the disease, its prevention, and management. Common sources of information were friends, family, the internet, and healthcare professionals. Barriers to seeking information discussed by parents were lack of time as well as insufficiency and inaccuracy of the information they received.

    CONCLUSION: This study highlighted the need for comprehensive, tailored early education on ECC for parents using reliable information sources. There is also a need to empower other nondental healthcare professionals to provide oral healthcare education for parents.

  16. Yeo AL, Kandane-Rathnayake R, Koelmeyer R, Golder V, Louthrenoo W, Chen YH, et al.
    Rheumatology (Oxford), 2024 Feb 01;63(2):525-533.
    PMID: 37208196 DOI: 10.1093/rheumatology/kead231
    OBJECTIVE: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive.

    METHODS: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare.

    RESULTS: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P 3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009).

    CONCLUSION: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.

  17. Katsumata Y, Inoue E, Harigai M, Cho J, Louthrenoo W, Hoi A, et al.
    Ann Rheum Dis, 2024 Feb 29.
    PMID: 38423757 DOI: 10.1136/ard-2023-225369
    OBJECTIVES: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE).

    METHODS: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred.

    RESULTS: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day.

    CONCLUSIONS: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.

  18. Ng YM, Sockalingam SNM, Shafiei Z, Zakaria ASI, Mahyuddin A, Rahman MA
    J Contemp Dent Pract, 2024 Mar 19;25(3):260-266.
    PMID: 38690700 DOI: 10.5005/jp-journals-10024-3645
    AIM AND BACKGROUND: This study aimed to explore the potential synergistic interaction of virgin coconut oil (VCO) and virgin olive oil (VOO) mixture against Streptococcus sanguinis, Streptococcus mutans, and Lactobacillus casei in a single and mixture species through the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), antiadherence, and antibiofilm activities.

    MATERIALS AND METHODS: The broth microdilution technique was used to individually determine the MIC of both oils and an oil mixture (in the ratio of 1:1) in a 96-well microtiter plate. As for the MBC, the subcultured method was used. The fractional inhibitory concentration index (ΣFIC) was determined to identify the interaction types between both oils. The oil mixture at its MIC was then tested on its antibiofilm and antiadherence effect.

    RESULTS: The MIC of the oil mixture against the tested microbiota was 50-100%. The oil mixture was bactericidal at 100% concentration for all the mentioned microbes except S. mutans. The ΣFIC value was 2 to 4, indicating that the VCO and VOO acted additively against the microbiota. Meanwhile, the oil mixture at MIC (50% for S. sanguinis and L. casei; 100% for S. mutans and mixture species) exhibited antiadherence and antibiofilm activity toward the microbiota in mixture species.

    CONCLUSION: The oil mixture possesses antibacterial, antibiofilm, and antiadherence properties toward the tested microbiota, mainly at 50-100% concentration of oil mixture. There was no synergistic interaction found between VCO and VOO.

    CLINICAL SIGNIFICANCE: Children and individuals with special care may benefit from using the oil mixture, primarily to regulate the biofilm formation and colonization of the bacteria. Furthermore, the oil mixture is natural and nontoxic compared to chemical-based oral healthcare products. How to cite this article: Ng YM, Sockalingam SNMP, Shafiei Z, et al. Biological Activities of Virgin Coconut and Virgin Olive Oil Mixture against Oral Primary Colonizers: An In Vitro Study. J Contemp Dent Pract 2024;25(3):260-266.

  19. Golder V, Kandane-Rathnayake R, Louthrenoo W, Chen YH, Cho J, Lateef A, et al.
    J Rheumatol, 2024 May 01.
    PMID: 38490668 DOI: 10.3899/jrheum.2023-0900
    OBJECTIVE: To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE).

    METHODS: Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare.

    RESULTS: Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up.

    CONCLUSION: LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).

  20. de Luca Montes RA, Huq M, Godfrey T, Oon S, Calderone A, Kandane-Rathnayake R, et al.
    Adv Rheumatol, 2024 May 08;64(1):38.
    PMID: 38720354 DOI: 10.1186/s42358-024-00366-y
    BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.

    METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.

    RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.

    CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

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