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  1. Bruni C, Raja J, Denton CP, Matucci-Cerinic M
    Autoimmun Rev, 2015 Dec;14(12):1111-5.
    PMID: 26235995 DOI: 10.1016/j.autrev.2015.07.016
    Systemic sclerosis is a chronic multi-organ autoimmune disease, leading to important clinical and psychological implications. Among organ complications, sexual dysfunction is a major issue for both male and female gender, with high prevalence and great impact on quality of life, although frequently not addressed by both clinicians and patients. While erectile dysfunction is the most common cause of sexual problems in males, genital tract and general physical changes are major contributors to sexual impairment in females. This review presents current state of the art on this topic, discussing published data on presentation, evaluation and therapeutic options.
  2. Amjad RJ, Sahar MR, Dousti MR, Ghoshal SK, Jamaludin MN
    Opt Express, 2013 Jun 17;21(12):14282-90.
    PMID: 23787617 DOI: 10.1364/OE.21.014282
    We report significant enhancements in Er(3+) luminescence as well as in Raman intensity in silver nanoparticles embedded zinc-tellurite glass. Surface enhanced Raman scattering effect is highlighted for the first time in tellurite glass containing silver NPs resulting in an enhanced Raman signal (~10 times). SAED manifest the growth of Ag(0) nanoparticles along the (111) and (200) crystallographic planes having average diameter in the range 14-36 nm. Surface plasmon resonance bands are observed in the range 484-551 nm. Furthermore, four prominent photoluminescence bands undergo significant enhancements up to 3 times. The enhancement is majorly attributed to the local field effect of silver NPs.
  3. Gopal K, Thevarajah M, Ng CM, Raja J
    Int J Rheum Dis, 2019 May;22(5):834-841.
    PMID: 30729713 DOI: 10.1111/1756-185X.13484
    AIM: Vitamin D3 or 25(OH)D3 may have a potential role in rheumatoid arthritis (RA) pathogenesis by inhibiting the expression of pro-inflammatory cytokines including interleukin-6 (IL-6). The aim of this study is to determine the clinical factors of vitamin D deficiency in multi-ethnic Malaysian RA patients and its association with disease activity, functional disability and serum IL-6 levels.

    METHOD: One hundred RA patients and 50 healthy controls, sex- and age-matched, were recruited. Disease Activity Score of 28 joints and Health Assessment Questionnaire scores were assessed. Baseline serum 25(OH)D3 and IL-6 were measured in all subjects. RA patients who were vitamin D deficient were given loading doses of vitamin D3 and repeated assessments were done.

    RESULTS: Vitamin D deficiency (<50 nmol/L) was found in 63% of RA patients and 76% of healthy controls. Chinese RA patients and healthy controls had significantly more sufficient 25(OH)D3 levels compared to Malays and Indians (P 

  4. Raja J, Balaikerisnan T, Ramanaidu LP, Goh KJ
    Int J Rheum Dis, 2021 Mar;24(3):347-354.
    PMID: 33432774 DOI: 10.1111/1756-185X.14042
    AIM: The reported prevalence of peripheral neuropathy in systemic sclerosis (SSc) is variable between 0.01% to 28%, probably due to differences in sample size, study design and population. Our aim is to determine the prevalence of large fiber peripheral neuropathy in SSc and to identify any contributing factors.

    METHOD: A prospective cross-sectional study of 60 SSc patients were evaluated for large fiber neuropathy using the modified clinical Total Neuropathy Score (cTNS) and nerve conduction study (NCS) of the upper and lower limbs. A combination of clinical (cTNS score ≥ 2) and NCS criteria (≥2 abnormal nerves including 1 sural [symmetrical polyneuropathy] and NCS abnormalities consistent with individual nerves/nerve roots [focal neuropathy]) was used to diagnose peripheral neuropathy.

    RESULTS: The majority had limited cutaneous subset (75%). Mean age was 55.73 (SD ± 13.04) years and mean disease duration was 8.61 (SD ± 8.09) years. Twenty-two (36.7%) had combined clinical and NCS criteria for peripheral neuropathy, 14 (23.3%) with symmetrical polyneuropathy and 8 (13.3%) with focal neuropathy. Symmetrical polyneuropathy patients had significantly lower hemoglobin levels (11.2 vs. 12.35 g/L; P = .047). Serum vitamin B12 levels were normal, therefore excluding vitamin B12 deficiency. No other associations were found for both polyneuropathy and focal neuropathy with demography, co-morbid diseases and SSc disease factors such as Raynaud's phenomenon and modified Rodnan skin score.

    CONCLUSION: Large fiber neuropathy is common in SSc patients, which could contribute to non-lethal burden in SSc with sensory loss and muscle weakness. Apart from lower hemoglobin in polyneuropathy, there were no associations with disease-specific features or co-morbid diseases.

  5. Fong SY, Raja J, Wong KT, Goh KJ
    Rheumatol Int, 2021 02;41(2):355-360.
    PMID: 32488429 DOI: 10.1007/s00296-020-04610-8
    Asymptomatic electrophysiological peripheral neuropathy is described in systemic lupus erythematosus (SLE) patients. To determine if SLE could have an even earlier effect on peripheral nerve function even before the development of electrophysiological abnormalities, we compared nerve conduction studies (NCS) of SLE patients without electrophysiological or clinical peripheral neuropathy with healthy controls. Consecutive SLE patients without clinical neuropathy (or other known causes of neuropathy) underwent sensory and motor NCS of all four limbs. Results of 61 patients without electrophysiological criteria of neuropathy were compared with age- and gender-matched controls. Although still within the laboratory's range of normal values, significant differences were found in several NCS parameters between patients and controls. SLE patients had lower amplitudes for ulnar, fibular, and tibial compound muscle action potentials (CMAP) and sural sensory nerve action potentials (SNAP); slower conduction velocities for median, ulnar, and fibular motor nerves, and median, ulnar and sural sensory nerves. SLE patients also had longer minimum F-wave latencies for median, ulnar, fibular, and tibial nerves. H reflexes were more often absent in patients. Correlations were found between the number of disease relapses and motor conduction velocities of the fibular and tibial nerves. SLE may have early effect on peripheral nerve function in patients even before they develop electrophysiological or clinical neuropathy.
  6. Raja J, Ng CT, Sujau I, Chin KF, Sockalingam S
    Clin Exp Rheumatol, 2016 Sep-Oct;34 Suppl 100(5):115-121.
    PMID: 26843456
    OBJECTIVES: To evaluate the associations between objectively measured gastroesophageal involvement using high-resolution manometry and 24- hour impedance-pH study, and clinical presentations in systemic sclerosis (SSc) patients.
    METHODS: This cross-sectional study was conducted in University of Malaya Medical Centre (UMMC) with 31 consecutive SSc patients recruited into this study. Clinical symptoms of gastroesophageal involvement, high-resolution impedance-manometry and 24-hour impedance-pH monitoring were assessed. Their associations with serological features and other organ involvement were evaluated.
    RESULTS: Twenty-five (80.6%) patients had gastroesophageal reflux disease (GORD) symptoms, mainly heartburn (45.1%), regurgitation (32.2%) and dysphagia (29%). Using manometry, oesophageal dysmotility was detected in 24 (88.9%) patients, while hypotensive lower oesophageal sphincter (LOS) was observed in 17 (63%) patients. 21 (84%) patients had GORD based on pH study. Hypotensive LOS was significantly associated with presence of digital ulcers. The main gastroesophageal symptoms were absent in majority of the SSc patients including in those with severe gastroesophageal manifestations demonstrating failed peristalsis >75%, hypotensive LOS, Demeester score >200 and acid reflux >200 per day. Demeester score >200 is associated with severity of GORD symptoms. Demeester score >200 was also associated with restrictive lung pattern (p=0.001). Significant association between GORD severity (daily number of acid reflux episodes >200) and pulmonary fibrosis was seen (p=0.030).
    CONCLUSIONS: The presence and severity of gastroesophageal symptoms may not accurately reflect the seriousness of oesophageal involvement. GORD severity is associated with presence of restrictive lung pattern and pulmonary fibrosis. Oesophageal manometry and 24-hour pH study should be considered more frequently in the assessment of SSc patients.
  7. Raja J, Nihtyanova SI, Murray CD, Denton CP, Ong VH
    Rheumatology (Oxford), 2016 Jan;55(1):115-9.
    PMID: 26320139 DOI: 10.1093/rheumatology/kev318
    OBJECTIVE: IVIG is known to confer significant benefit in rheumatologic conditions, including inflammatory myopathy. This study aimed to assess the efficacy of IVIG across different aspects of internal organ involvement in refractory active SSc, particularly the gastrointestinal (GI) system.
    METHODS: SSc patients with overlap polymyositis who remained active and unresponsive to conventional disease-modifying agents and who subsequently received IVIG were identified. GI symptoms were assessed using validated questionnaires. The Medical Research Council Sum Score for muscle strength and modified Rodnan skin score (mRSS) were assessed. Serial measurements were undertaken at baseline prior to the first IVIG treatment and post-treatment in the most recent assessment.
    RESULTS: Fifteen SSc patients were consecutively recruited into this observational study. The mean duration of IVIG treatment was 2.3 years, with treatment frequency ranging from every 6 weeks to 4 months. Compared with baseline, there was a significant reduction in gastro-oesophageal reflux frequency and intensity mean scores (P = 0.006 and P = 0.013, respectively). Significant improvement in the Gastrointestinal Tract (GIT) 2.0 score from a baseline mean score of 1.07 (s.d. 0.67) to 0.60 (0.46) (P = 0.002) was observed. There was regression in the markers of muscle disease with a reduction in the mean (s.d.) Medical Research Council sum score and the median creatine kinase level (P = 0.001 and P = 0.025, respectively). Significant amelioration of the mean basal modified Rodnan skin score from 21.5 (s.d. 13.8) to 10 (10.6) (P = 0.005) was observed.
    CONCLUSION: IVIG may be a helpful adjunctive therapy in the amelioration of some key clinical aspects in refractory SSc. Sustained benefit from IVIG suggests a specific immunomodulatory effect on those with established SSc GI complications.
    Study site: Royal Free Hospital, United Kingdom
  8. Raman L, Yahya F, Ng CM, Sockalingam S, Ramasamy K, Ratnam R, et al.
    Lupus, 2020 Dec;29(14):1885-1891.
    PMID: 33040647 DOI: 10.1177/0961203320962848
    BACKGROUND: Hospital admissions and re-admissions in lupus patients are common occurrences that can lead to poor prognosis.

    OBJECTIVES: We evaluated the leading causes of all-cause hospitalizations and their predictive factors in the Malaysian multi-ethnic SLE patients.

    METHODS: This is a retrospective study involving 300 SLE patients. Demographic data and details of hospitalizations from the year 1988 until 2019 were reviewed. Baseline and latest disease activity (SLEDAI-2 K) and SLICC/ACR damage index (SDI) scores were evaluated. To be eligible for this study, their SLE diagnosis and disease duration was at least one year; this is to ensure that the baseline disease damages were measured at least after 6 months of diagnosis and subsequent disease damage indexes were captured.

    RESULTS: Majority were of Chinese ethnicity 150 (50%). The cohort's median age was 48 (18-82) years and median disease duration was 13 (1-52) years. 133 (44.3%) had SDI score of ≥1 at baseline (early damage). 69 (23%) had developed new organ damage during this study period.There were 222 (74%) patients ever hospitalized from this cohort. The main cause of hospitalization was lupus flare which included concurrent infection (n = 415 admissions, 46%), followed by elective admissions for procedures and others (n = 284 admissions, 31.5%). Admissions for treatment and disease related complications were 13.8%. 8.7% of admissions were due to infections alone. Median length of stay for SLE-related cause admissions was longer compared to non-SLE related causes. Jointly predictive factors for hospitalization were anti-phospholipid syndrome (OR 5.82), anti-Smith (OR 6.30), anti-SSA (OR 3.37), serositis (OR 14.56), neurological (OR 5.52) and high baseline SDI (OR 1.74), all p 

  9. Lee HJ, Pok LSL, Ng CM, Yahya F, Sockalingam S, Tee YC, et al.
    Int J Rheum Dis, 2020 Aug;23(8):1088-1093.
    PMID: 32597545 DOI: 10.1111/1756-185X.13897
    INTRODUCTION: Fatigue is an important yet infrequently evaluated component in patients with rheumatoid arthritis (RA) and may have a major impact on quality of life.

    OBJECTIVES: To evaluate fatigue, identify factors associated with fatigue and assess the effect of fatigue on health-related quality of life (HRQoL) in a multi-ethnic cohort of RA patients.

    METHODS: A cross-sectional study was performed in patients who fulfilled European League Against Rheumatism/ American College of Rheumatology 2010 criteria for RA. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire was used to assess fatigue. Potential factors for fatigue were categorized into RA-related (gender, seropositivity [rheumatoid factor and/or anti-citrullinated protein antibody], disease duration, visual analog scale pain score, Disease Activity Score of 28 joints - erythrocyte sedimentation rate [DAS28-ESR], ESR, hemoglobin level, functional disability [Health Assessment Questionnaire - Disability Index, HAQ-DI score], EQ-5D-3L, concomitant prednisolone use and number of conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] used) and non-RA-related (age, body mass index, ethnicity and number of co-morbidities).

    RESULTS: A total of 214 patients (86.9% female) were included; the median age was 62 (25-91) years and 67.3% were seropositive. Seventy-six (33.5%) patients had moderate disease activity, 12 (5.6%) had high disease activity and 152 (71%) patients had mild difficulties to moderate disability HAQ-DI scores. Median of total FACIT-F score was 113.2 (36.3-160.0). Joint factors of younger age, longer disease duration, higher HAQ score (increased functional disability), and lower EQ-5D (poorer HRQoL) were significantly associated with higher levels of fatigue (all P 

  10. Mat S, Jaafar MH, Sockalingam S, Raja J, Kamaruzzaman SB, Chin AV, et al.
    Int J Rheum Dis, 2018 May;21(5):930-936.
    PMID: 29611292 DOI: 10.1111/1756-185X.13279
    AIM: To determine the association between vitamin D and knee pain among participants of the Malaysian Elders Longitudinal Research (MELoR) study.

    METHOD: This was a cross-sectional study from the MELoR study consisting of a representative group of 1011 community-dwelling older persons (57% female), mean age 86.5 (54-94) years; 313 were Malays, 367 Chinese and 330 Indians. Participants were asked if they had knee pain. Levels of serum 25-hydroxy cholecalciferol (25-[OH]D), an indicator of vitamin D status, were measured using routine laboratory techniques.

    RESULTS: In unadjusted analysis, presence of knee pain was significantly associated with vitamin D deficiency (odds ratio [OR] 1.42; 95% confidence interval (CI) 1.08-1.85, P 0.011). Vitamin D levels were significantly associated with ethnicity differences where Malays (OR 7.08; 95% CI 4.94-10.15) and Indians (OR 6.10; 95% CI 4.28-9.71) have lower levels of vitamin D compared to Chinese. Subsequent multivariate analysis revealed that the association between vitamin D deficiency and knee pain was confounded by ethnic differences.

    CONCLUSION: A previous study suggested that vitamin D deficiency was associated with knee pain. This relationship was reproduced in our study, but we further established that the association was explained by ethnic variations. As vitamin D status is dependent on skin tone, diet and sunlight exposure, which are all effected by ethnicity, future studies are now required to determine whether a true relationship exists between vitamin D and knee pain.
  11. Mat S, Jaafar MH, Ng CT, Sockalingam S, Raja J, Kamaruzzaman SB, et al.
    PLoS One, 2019;14(11):e0225075.
    PMID: 31751378 DOI: 10.1371/journal.pone.0225075
    Knee pain is often underreported, underestimated and undertreated. This study was conducted to estimate the prevalence, burden and further identify socioeconomic factors influencing ethnic differences in knee pain and symptoms of OA among older adults aged 55 years and over in Greater Kuala Lumpur (the capital city of Malaysia). The sample for the Malaysian Elders Longitudinal Research (MELoR) was selected using stratified random sampling, by age and ethnicity from the electoral rolls of three parliamentary constituencies. Information on knee pain was available in 1226 participants, mean age (SD) 68.96 (1.57) years (409 Malay, 416 Chinese, 401 Indian). The crude and weighted prevalence of knee pain and self-reported knee OA symptoms were 33.3% and 30.8% respectively. There were significant ethnic differences in knee pain (crude prevalence: Malays 44.6%, Chinese 23.5% and Indians 31.9%, p<0.001). The presence of two or more non-communicable diseases (NCD) attenuated the increased risk of knee pain among the ethnic Indians compared to the ethnic Chinese. The prevalence of knee pain remained significantly higher among the ethnic Malays after adjustment for confounders. While the prevalence of knee pain in our older population appears similar to that reported in other published studies in Asia, the higher prevalence among the ethnic Malays has not previously been reported. Further research to determine potential genetic susceptibility to knee pain among the ethnic Malays is recommended.
  12. Trabelsi K, Ammar A, Masmoudi L, Boukhris O, Chtourou H, Bouaziz B, et al.
    Biol Sport, 2021 Oct;38(4):495-506.
    PMID: 34937958 DOI: 10.5114/biolsport.2021.101605
    Symptoms of psychological distress and disorder have been widely reported in people under quarantine during the COVID-19 pandemic; in addition to severe disruption of peoples' daily activity and sleep patterns. This study investigates the association between physical-activity levels and sleep patterns in quarantined individuals. An international Google online survey was launched in April 6th, 2020 for 12-weeks. Forty-one research organizations from Europe, North-Africa, Western-Asia, and the Americas promoted the survey through their networks to the general society, which was made available in 14 languages. The survey was presented in a differential format with questions related to responses "before" and "during" the confinement period. Participants responded to the Pittsburgh Sleep Quality Index (PSQI) questionnaire and the short form of the International Physical Activity Questionnaire. 5056 replies (59.4% female), from Europe (46.4%), Western-Asia (25.4%), America (14.8%) and North-Africa (13.3%) were analysed. The COVID-19 home confinement led to impaired sleep quality, as evidenced by the increase in the global PSQI score (4.37 ± 2.71 before home confinement vs. 5.32 ± 3.23 during home confinement) (p < 0.001). The frequency of individuals experiencing a good sleep decreased from 61% (n = 3063) before home confinement to 48% (n = 2405) during home confinement with highly active individuals experienced better sleep quality (p < 0.001) in both conditions. Time spent engaged in all physical-activity and the metabolic equivalent of task in each physical-activity category (i.e., vigorous, moderate, walking) decreased significantly during COVID-19 home confinement (p < 0.001). The number of hours of daily-sitting increased by ~2 hours/days during home confinement (p < 0.001). COVID-19 home confinement resulted in significantly negative alterations in sleep patterns and physical-activity levels. To maintain health during home confinement, physical-activity promotion and sleep hygiene education and support are strongly warranted.
  13. Trabelsi K, Ammar A, Masmoudi L, Boukhris O, Chtourou H, Bouaziz B, et al.
    PMID: 33921852 DOI: 10.3390/ijerph18084329
    BACKGROUND: The COVID-19 lockdown could engender disruption to lifestyle behaviors, thus impairing mental wellbeing in the general population. This study investigated whether sociodemographic variables, changes in physical activity, and sleep quality from pre- to during lockdown were predictors of change in mental wellbeing in quarantined older adults.

    METHODS: A 12-week international online survey was launched in 14 languages on 6 April 2020. Forty-one research institutions from Europe, Western-Asia, North-Africa, and the Americas, promoted the survey. The survey was presented in a differential format with questions related to responses "pre" and "during" the lockdown period. Participants responded to the Short Warwick-Edinburgh Mental Wellbeing Scale, the Pittsburgh Sleep Quality Index (PSQI) questionnaire, and the short form of the International Physical Activity Questionnaire.

    RESULTS: Replies from older adults (aged >55 years, n = 517), mainly from Europe (50.1%), Western-Asia (6.8%), America (30%), and North-Africa (9.3%) were analyzed. The COVID-19 lockdown led to significantly decreased mental wellbeing, sleep quality, and total physical activity energy expenditure levels (all p < 0.001). Regression analysis showed that the change in total PSQI score and total physical activity energy expenditure (F(2, 514) = 66.41 p < 0.001) were significant predictors of the decrease in mental wellbeing from pre- to during lockdown (p < 0.001, R2: 0.20).

    CONCLUSION: COVID-19 lockdown deleteriously affected physical activity and sleep patterns. Furthermore, change in the total PSQI score and total physical activity energy expenditure were significant predictors for the decrease in mental wellbeing.

  14. Ammar A, Chtourou H, Boukhris O, Trabelsi K, Masmoudi L, Brach M, et al.
    Int J Environ Res Public Health, 2020 Aug 27;17(17).
    PMID: 32867287 DOI: 10.3390/ijerph17176237
    Public health recommendations and governmental measures during the new coronavirus disease (COVID-19) pandemic have enforced numerous restrictions on daily living including social distancing, isolation, and home confinement. While these measures are imperative to mitigate spreading of COVID-19, the impact of these restrictions on psychosocial health is undefined. Therefore, an international online survey was launched in April 2020 to elucidate the behavioral and lifestyle consequences of COVID-19 restrictions. This report presents the preliminary results from more than one thousand responders on social participation and life satisfaction.

    METHODS: Thirty-five research organizations from Europe, North-Africa, Western Asia, and the Americas promoted the survey through their networks to the general society, in 7 languages (English, German, French, Arabic, Spanish, Portuguese, and Slovenian). Questions were presented in a differential format with questions related to responses "before" and "during" confinement conditions.

    RESULTS: 1047 participations (54% women) from Asia (36%), Africa (40%), Europe (21%), and others (3%) were included in the analysis. Findings revealed psychosocial strain during the enforced COVID-19 home confinement. Large decreases (p < 0.001) in the amount of social activity through family (-58%), friends/neighbors (-44.9%), or entertainment (-46.7%) were triggered by the enforced confinement. These negative effects on social participation were also associated with lower life satisfaction (-30.5%) during the confinement period. Conversely, the social contact score through digital technologies significantly increased (p < 0.001) during the confinement period with more individuals (+24.8%) being socially connected through digital technology.

    CONCLUSION: These preliminary findings elucidate the risk of psychosocial strain during the early COVID-19 home confinement period in 2020. Therefore, in order to mitigate the negative psychosocial effects of home confinement, implementation of national strategies focused on promoting social inclusion through a technology-based solution is strongly suggested.

  15. Ammar A, Mueller P, Trabelsi K, Chtourou H, Boukhris O, Masmoudi L, et al.
    PLoS One, 2020;15(11):e0240204.
    PMID: 33152030 DOI: 10.1371/journal.pone.0240204
    BACKGROUND: Public health recommendations and government measures during the COVID-19 pandemic have enforced restrictions on daily-living. While these measures are imperative to abate the spreading of COVID-19, the impact of these restrictions on mental health and emotional wellbeing is undefined. Therefore, an international online survey (ECLB-COVID19) was launched on April 6, 2020 in seven languages to elucidate the impact of COVID-19 restrictions on mental health and emotional wellbeing.

    METHODS: The ECLB-COVID19 electronic survey was designed by a steering group of multidisciplinary scientists, following a structured review of the literature. The survey was uploaded and shared on the Google online-survey-platform and was promoted by thirty-five research organizations from Europe, North-Africa, Western-Asia and the Americas. All participants were asked for their mental wellbeing (SWEMWS) and depressive symptoms (SMFQ) with regard to "during" and "before" home confinement.

    RESULTS: Analysis was conducted on the first 1047 replies (54% women) from Asia (36%), Africa (40%), Europe (21%) and other (3%). The COVID-19 home confinement had a negative effect on both mental-wellbeing and on mood and feelings. Specifically, a significant decrease (p < .001 and Δ% = 9.4%) in total score of the SWEMWS questionnaire was noted. More individuals (+12.89%) reported a low mental wellbeing "during" compared to "before" home confinement. Furthermore, results from the mood and feelings questionnaire showed a significant increase by 44.9% (p < .001) in SMFQ total score with more people (+10%) showing depressive symptoms "during" compared to "before" home confinement.

    CONCLUSION: The ECLB-COVID19 survey revealed an increased psychosocial strain triggered by the home confinement. To mitigate this high risk of mental disorders and to foster an Active and Healthy Confinement Lifestyle (AHCL), a crisis-oriented interdisciplinary intervention is urgently needed.

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