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1.
Clin Rheumatol ; 43(8): 2489-2501, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38922551

ABSTRACT

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.


Subject(s)
Arthritis, Rheumatoid , Piperidines , Pyrimidines , Humans , Piperidines/therapeutic use , Arthritis, Rheumatoid/drug therapy , Pyrimidines/therapeutic use , Male , Female , Middle Aged , Cluster Analysis , Adult , Treatment Outcome , Aged , Antirheumatic Agents/therapeutic use , Pyrroles/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Severity of Illness Index , Malaysia
2.
J Perinat Med ; 52(4): 385-391, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38511669

ABSTRACT

OBJECTIVES: To investigate factors associated with outcome of second twin during labour. METHODS: The study was a retrospective cohort study in a single tertiary centre in Malaysia from 2014 until 2018 involving all twin pregnancies delivered at or more than 24 weeks of gestation. RESULTS: Total of 409 twin pregnancies were included. Dichorionic twin comprises of 54.5 % (n=223) and 45.5 % (n=186) are monochorionic. Women with dichorionic pregnancies are significantly older (p<0.001), have more pre-existing medical disorders (p=0.011) and fetal structural anomalies (p=0.009). Monochorionic pregnancies are significantly more amongst Malay (p=0.01) and conceived spontaneously (p<0.001). There are significantly more fetuses both in cephalic presentation (p=0.026), birthweight discrepancy more than 20 % (p=0.038) and shorter mean inter-twin delivery duration (p=0.048) in monochorionic pregnancies. Second twin delivered with Apgar score <7 is significantly more in dichorionic pregnancies (p=0.006). The second twin is associated with lower birthweight, small for gestational age and arterial cord pH<7.25. Within the group of women who delivered both fetuses vaginally, there was significantly more second twins with intertwin delivery duration less than 30 min who were delivered vaginally without instrumentation (p=0.018). There was significantly more second twin with intertwin delivery duration of 30 min and more with arterial cord pH<7.25 (p=0.045). Those who delivered spontaneously had inter-twin delivery duration within 15-29 min. The outcome of second twin is not influenced by type of twin, gestational age at delivery, inter-twin delivery duration, mode of delivery and presentation at birth. CONCLUSIONS: The neonatal outcome for the second twin at birth is not influenced by type of twin, gestational age at delivery, inter-twin delivery duration, mode of delivery and presentation at birth in a cohort managed with non-active management of the second twin in Malaysia.


Subject(s)
Pregnancy Outcome , Pregnancy, Twin , Humans , Female , Pregnancy , Retrospective Studies , Malaysia/epidemiology , Pregnancy, Twin/statistics & numerical data , Adult , Infant, Newborn , Pregnancy Outcome/epidemiology , Tertiary Care Centers/statistics & numerical data , Birth Weight , Twins, Dizygotic
3.
J Pregnancy ; 2023: 8243058, 2023.
Article in English | MEDLINE | ID: mdl-37404975

ABSTRACT

This is a cross-sectional study comparing pregnancy outcomes between participants with 4 and 6 cm of cervical os dilatation at the diagnosis of the active phase of labour. It was conducted in a single tertiary centre involving low-risk singleton pregnancies at or beyond 37 weeks with spontaneous onset of labour. A total of 155 participants were recruited, 101 in group 1 (4 cm) and 54 in group 2 (6 cm). Both groups were similar in mean maternal age, mean gestational age at delivery, ethnicity, median haemoglobin level at delivery, body mass index, and parity. There were significantly more participants in group 1 who needed oxytocin augmentation (p < 0.001) for the longer mean duration (p = 0.015), use of analgesia (p < 0.001), and caesarean section rate (p = 0.002). None of the women had a postpartum haemorrhage or a third- or fourth-degree perineal tear, and none of the neonates required admission to the neonatal intensive care unit. There were significantly more nulliparas who had a caesarean section as compared to multiparas. A cervical os dilatation of 6 cm reduces the risk of caesarean section by 11% (95% CI, 0.01-0.9) and increases three times more the need for analgesia (AOR = 3.44, 95% CI, 1.2-9.4). In conclusion, the demarcation of the active phase of labour at a cervical os dilatation of 6 cm is feasible without an increase in maternal or neonatal complications.


Subject(s)
Labor, Obstetric , Pregnancy Outcome , Infant, Newborn , Pregnancy , Female , Humans , Cesarean Section , Cross-Sectional Studies , Dilatation
4.
BMC Pregnancy Childbirth ; 23(1): 221, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37005571

ABSTRACT

BACKGROUND: There is an increasing trend of Caesarean section rate in Malaysia. Limited evidence demonstrated the benefits of changing the demarcation of the active phase of labour. METHODS: This was a retrospective study of 3980 singletons, term pregnancy, spontaneous labouring women between 2015 and 2019 comparing outcomes between those with cervical dilation of 4 versus 6 cm at diagnosis of the active phase of labour. RESULTS: A total of 3403 (85.5%) women had cervical dilatation of 4 cm, and 577 (14.5%) at 6 cm upon diagnosis of the active phase of labour. Women in 4 cm group were significantly heavier at delivery (p = 0.015) but significantly more multiparous women were in 6 cm group (p < 0.001). There were significantly fewer women in the 6 cm group who needed oxytocin infusion (p < 0.001) and epidural analgesia (p < 0.001) with significantly lower caesarean section rate (p < 0.001) done for fetal distress and poor progress (p < 0.001 both). The mean duration from diagnosis of the active phase of labour until delivery was significantly shorter in the 6 cm group (p < 0.001) with lighter mean birth weight (p = 0.019) and fewer neonates with arterial cord pH < 7.20 (p = 0.047) requiring neonatal intensive care unit admissions (p = 0.01). Multiparity (AOR = 0.488, p < 0.001), oxytocin augmentation (AOR = 0.487, p < 0.001) and active phase of labour diagnosed at 6 cm (AOR = 0.337, p < 0.001) reduced the risk of caesarean delivery. Caesarean delivery increased the risk of neonatal intensive care admission by 27% (AOR = 1.73, p < 0.001). CONCLUSIONS: Active phase of labour at 6 cm cervical dilatation is associated with reduced primary caesarean delivery rate, labour intervention, shorter labour duration and fewer neonatal complications.


Subject(s)
Oxytocics , Oxytocin , Infant, Newborn , Pregnancy , Female , Humans , Male , Oxytocin/therapeutic use , Cesarean Section , Retrospective Studies , Labor Stage, First , Malaysia/epidemiology , Peripartum Period
5.
BMC Neurol ; 23(1): 117, 2023 Mar 22.
Article in English | MEDLINE | ID: mdl-36949469

ABSTRACT

BACKGROUND: There is a growing body of evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of autoimmune diseases. A recent systematic review reported that the new-onset autoimmune disorders during or after COVID-19 infection included inflammatory myopathies such as immune-mediated necrotizing myopathies. CASE PRESENTATION: We described a 60-year-old man diagnosed with COVID-19 infection and later presented with a two-week history of myalgia, progressive limb weakness, and dysphagia. He had a Creatinine Kinase (CK) level of more than 10,000 U/L, was strongly positive for anti-signal recognition particle (SRP) and anti-Ro52 antibody, and a muscle biopsy revealed a paucity-inflammation necrotizing myopathy with randomly distributed necrotic fibers, which was consistent with necrotizing autoimmune myositis (NAM). He responded well clinically and biochemically to intravenous immunoglobulin, steroids and immunosuppressant and he was able to resume to his baseline. CONCLUSION: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.


Subject(s)
Autoimmune Diseases , COVID-19 , Muscle, Skeletal , Myositis , COVID-19/blood , COVID-19/complications , COVID-19/pathology , Autoimmune Diseases/diagnosis , Autoimmune Diseases/drug therapy , Autoimmune Diseases/pathology , Autoimmune Diseases/virology , Necrosis , Myositis/diagnosis , Myositis/drug therapy , Myositis/immunology , Myositis/virology , Humans , Male , Middle Aged , Creatine Kinase/blood , Muscle, Skeletal/pathology , Myalgia/drug therapy , Myalgia/immunology , Myalgia/virology , Antibodies, Antinuclear/blood , Steroids/therapeutic use , Immunosuppressive Agents/therapeutic use , Treatment Outcome
6.
Biomedicines ; 11(2)2023 Feb 11.
Article in English | MEDLINE | ID: mdl-36831061

ABSTRACT

Breast carcinoma is the most common cancer of women in Malaysia. The most common sites of metastasis are the lung, liver, bone and brain. A 45-year-old lady was diagnosed with left invasive breast carcinoma stage IV (T4cN1M1) with axillary lymph nodes and lung metastasis. She was noted to have a cervical mass through imaging, and biopsy showed CIN III. Post chemotherapy, the patient underwent left simple mastectomy with examination under anaesthesia of the cervix, cystoscopy and staging. The cervical histopathological examination (HPE) showed squamous cell carcinoma, and clinical staging was 2A. The breast tissue HPE showed invasive carcinoma with triple receptors positivity. The patient was given tamoxifen and put on concurrent chemoradiotherapy (CCRT) for the cervical cancer. The management of each pathology of this patient involved a multi-disciplinary team that included surgeons, oncologists, gynaecologists, pathologists and radiologists. Due to the complexity of the case with two concurrent cancers, the gene expression profiles may help predict the patient's clinical outcome.

7.
Preprint in English | bioRxiv | ID: ppbiorxiv-520679

ABSTRACT

The sharing of COVID-19 sequences worldwide has allowed for comprehensive and real-time analyses of COVID-19 genomic diversity at regional levels. Temporal distribution of COVID-19 variants and lineages enables better infection control, surveillance, and facilitates policy making for public health. 417 sequences extracted from all COVID-19 cases in Negeri Sembilan of peninsular Malaysia from July 2021 until May 2022 were used for this study. Phylogenomics revealed a total of 20 circulating lineages, of which seven are still circulating. The majority (60.4%) of viruses in Negeri Sembilan are of GRA lineage with strong representation from the Malaysian lineage BA.1.1 (24.7%). A time series analysis showed a change in the dominating circulating lineage from AY.79 to BA.1.1, which correlated to the relaxing of lockdowns implemented by the Malaysian government. Several Malaysian sub-lineages (BA.2.40.1, BA.2.57 and BA.2.9) have emerged from April 2022 onwards. Evolutionary mutations of the sub-lineages also gave rise to novel single nucleotide polymorphisms (SNPs) in the spike proteins. Out of the 70 SNPs isolated from all samples, in silico prediction revealed five novel SNPs that could cause functional defects to the spike protein, which are S221L, L226S, V826L, C1240F and C1243F. Structural modelling of the V826L showed that the L826 possibly confers an increase in protein flexibility within the S2 region of S protein, which supports our in-silico predictions.

8.
Microbiol Resour Announc ; 11(11): e0083922, 2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36314917

ABSTRACT

Here, we report the draft genome sequence of a Candida parapsilosis clinical isolate (USM026) that was recovered from a blood sample from a patient who was treated for a catheter-related bloodstream infection (CRBSI). The draft genome is 12,839,916 bp in length, with 22,076,712 reads, 249 scaffolds, and 5,537 genes.

9.
Microbiol Resour Announc ; 11(11): e0084122, 2022 Nov 17.
Article in English | MEDLINE | ID: mdl-36301110

ABSTRACT

Here, we announce the draft genome sequence of a Candida parapsilosis clinical isolate (USM039K) recovered from a patient with catheter-related bloodstream infection (CRBSI). The genome size is 12,860,016 bp long, with 188 scaffolds, a G+C content of 38.65%, and 5,467 genes.

10.
Genes (Basel) ; 13(7)2022 07 20.
Article in English | MEDLINE | ID: mdl-35886067

ABSTRACT

Rheumatoid arthritis (RA) is a lifelong, debilitating disease which incredibly impacts a patient's quality of life if not treated to the optimal target. The clinical response of tocilizumab, an interleukin-6 (IL-6) inhibitor, is associated with several gene polymorphisms, particularly targeting the IL-6 pathway. This systematic review and meta-analysis seeks to investigate genetic biomarkers that predict the treatment outcome of tocilizumab therapy in RA patients. After evaluating the quality of retrieved records, five studies were chosen to carry out a quantitative synthesis involving 591 participants. We analysed genetic markers of IL-6R single nucleotide polymorphism (SNP)s rs12083537, rs2228145 and rs4329505, FCGR3A, CD69, GALNT18 and FCGR2A. A plausible finding based on meta-analysis revealed that RA patients with homozygous AA genotype for rs12083537 polymorphism of the IL-6R gene demonstrate a better response to TCZ treatment as opposed to homozygous and heterozygous patients with the G allele. Nonetheless, limitations in evaluating the available studies by meta-analysis include a lack of studies with dissimilarities in study design and outcome definitions, small sample sizes with low statistical power and heterogeneity of cohorts, a restricted the number of tested SNPs and small effects for the selected variants. Inconsistent finding remains as a great challenge to forge ahead towards personalised medicine for RA management.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Antibodies, Monoclonal, Humanized , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Genetic Markers , Humans , Interleukin-6/genetics , Polymorphism, Single Nucleotide , Quality of Life
11.
Rheumatol Int ; 42(9): 1629-1641, 2022 09.
Article in English | MEDLINE | ID: mdl-35661906

ABSTRACT

Anti-MDA5 (Melanoma differentiation-associated protein 5) myositis is a rare subtype of dermatomyositis (DM) characterized by distinct ulcerative, erythematous cutaneous lesions and a high risk of rapidly progressive interstitial lung disease (RP-ILD). It has been shown that SARS-CoV-2 (COVID-19) replicates rapidly in lung and skin epithelial cells, which is sensed by the cytosolic RNA-sensor MDA5. MDA5 then triggers type 1 interferon (IFN) production, and thus downstream inflammatory mediators (EMBO J 40(15):e107826, 2021); (J Virol, 2021, https://doi.org/10.1128/JVI.00862-21 ); (Cell Rep 34(2):108628, 2021); (Sci Rep 11(1):13638, 2021); (Trends Microbiol 27(1):75-85, 2019). It has also been shown that MDA5 is triggered by the mRNA COVID-19 vaccine with resultant activated dendritic cells (Nat Rev Immunol 21(4):195-197, 2021). Our literature review identified one reported case of MDA5-DM from the COVID-19 vaccine (Chest J, 2021, https://doi.org/10.1016/j.chest.2021.07.646 ). We present six additional cases of MDA5-DM that developed shortly after the administration of different kinds of COVID-19 vaccines. A review of other similar cases of myositis developing from the COVID-19 vaccine was also done. We aim to explore and discuss the evidence around recent speculations of a possible relation of MDA5-DM to COVID-19 infection and vaccine. The importance of vaccination during a worldwide pandemic should be maintained and our findings are not intended to discourage individuals from receiving the COVID-19 vaccine.


Subject(s)
COVID-19 Vaccines , COVID-19 , Dermatomyositis , Lung Diseases, Interstitial , Autoantibodies , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Dermatomyositis/etiology , Humans , Interferon-Induced Helicase, IFIH1 , Lung Diseases, Interstitial/etiology , SARS-CoV-2 , Vaccination
12.
Midwifery ; 105: 103238, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34968819

ABSTRACT

OBJECTIVE: to compare the effect of amniotomy with early vs delayed oxytocin infusion on successful vaginal delivery. DESIGN: randomised controlled trial of nulliparous women with spontaneous labour at term. SETTING: labour suite of a university teaching hospital in Kuala Lumpur, Malaysia. PARTICIPANTS: 240 women were included (120 randomised into two arms). INTERVENTIONS: the randomisation sequence was generated using a computer randomisation program in two blocks: oxytocin infused early following amniotomy; and oxytocin infused 2 h after amniotomy. MEASUREMENTS AND FINDINGS: labour duration, mode of delivery, oxytocin dosage used, uterine hyperstimulation, postpartum haemorrhage, Apgar score and admission to the neonatal intensive care unit were recorded. No differences in vaginal delivery rate (62.9% vs 70.9%; p = 0.248) and second-stage labour were found between the early and delayed oxytocin infusion groups (21.2 ± 18.3 min vs 25.5 ± 19.9 min; p = 0.220). The mean interval from amniotomy to vaginal delivery was significantly shorter for the early group (5.8 ± 1.7 h vs 7.0 ± 1.9 h; p = 0.001), and more women in the early group delivered during/before the planned review at 4 h after amniotomy (53.6% vs 10.6%; p<0.001). Maximum oxytocin usage was lower in the early group (5.6 ± 4.4 mL/hour vs 6.8 ± 5.3 mL/hour; p = 0.104). KEY CONCLUSIONS: early oxytocin augmentation following amniotomy could be employed in low-risk primigravida, given that it is associated with a shorter labour duration without jeopardising maternal or neonatal outcomes. IMPLICATIONS FOR PRACTICE: low-risk primigravida benefit from early oxytocin infusion following amniotomy, and this can be offered as an additional practice in labour room care.


Subject(s)
Oxytocics , Postpartum Hemorrhage , Amniotomy , Female , Humans , Labor Stage, Second , Labor, Induced , Oxytocin , Pregnancy
13.
Data Brief ; 39: 107640, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34901351

ABSTRACT

Escherichia coli strain INF32/16/A is a gram-negative bacteria which is an extended-spectrum beta-lactamases (ESBL). ESBL is an enzyme that is produced by bacteria to become resistant to existing antibiotic such as extended-spectrum penicillin, cephalosporins, and have been threatening the ability to treat an infection. Therefore, genome analysis will provide an insight of how this bacteria able to evolve and the information obtained will able to facilitate in designing new antibiotics. The genome of E. coli strain was sequenced using Illumina MiSeq and raw genome sequence have been submitted into NCBI SRA database (SRR15334628) under Bioproject accession number PRJNA726861.

14.
Med J Malaysia ; 76(6): 833-836, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34806669

ABSTRACT

OBJECTIVE: The aim of this study was to assess the prevalence of foetal anomaly diagnosed during a detailed ultrasonography amongst patients of advanced maternal age (AMA) and to identify the related anomalies in these age groups. METHOD: A retrospective observational study amongst AMA mothers was done in Universiti Kebangsaan Malaysia Medical Centre, a Malaysian teaching hospital. The data over a period of three years (January 2013 - December 2016) obtained from the Maternal Foetal Medicine clinic registry was analysed. AMA mothers with singleton pregnancy presenting for foetal structural anomaly scan was included. They were later subdivided into 2 groups (35-39 years and ≥ 40 years). The logistic regression analysis was used to analyse the association of the chromosomal anomalies and the age groups. RESULTS: In all 486 patients were recruited and 84 patients were identified with foetal anomaly (17.3%). There was no significant difference in the prevalence of foetal anomalies or significant association with a specific structural foetal anomaly identified (p>0.05). However, the number of followups for these patients are significantly higher (p<0.001). CONCLUSION: The prevalence of structural foetal anomalies identified in detailed ultrasonography was low in AMA mothers. Hence, referral criteria for detailed anomaly ultrasonography need to be re-looked.


Subject(s)
Maternal Age , Female , Humans , Malaysia/epidemiology , Pregnancy , Prevalence , Registries , Retrospective Studies
15.
BMC Pregnancy Childbirth ; 21(1): 368, 2021 May 10.
Article in English | MEDLINE | ID: mdl-33971828

ABSTRACT

BACKGROUND: Spontaneous preterm birth is a global issue that contributed to perinatal morbidities and mortalities worldwide. The study aimed to describe the experience at UKM Medical Center in managing women at high risk for spontaneous preterm birth using the Arabin pessary. METHODS: This is a retrospective observational study involving 58 pregnancies from 1st January 2013 to 31st December 2019. Inclusion criteria were previous mid-trimester miscarriage and/or preterm birth, previous cervical surgery or short cervical length on routine sonogram. The demographic data, characteristics of each pregnancy and details of outcomes and management were described. RESULTS: The majority of women were Malay with mean age and body mass index of 32.9 ± 4.2 years and 27.1 ± 6.3 kg/m2 respectively. The most frequent indications for Arabin pessary insertion were previous mid-trimester miscarriage (46.4%) and early preterm birth (17.2%). A total of 73.4% of these women had the pessary inserted electively at a mean cervical length of 31.6 ± 9.1 mm at median gestation of 15.0 weeks. They were managed as outpatient (56.9%), inpatient (24.1%) or mixed (19.0%) with combination of progestogen (81.0%) and 53.4% received antenatal corticosteroids. Spontaneous preterm birth at or more than 34 weeks gestation occurred in 74.1% with birthweight at or more than 2000 g (82.4%). Despite cervical funneling in 12 women (20.7%), 66.7% delivered at or later than 34 weeks gestation and 2 (16.7%) resulted in miscarriage. CONCLUSIONS: Insertion of the Arabin pessary is beneficial to prevent spontaneous preterm birth in pregnant women who are at high risk. In particular, early insertion and close monitoring allows the best possible outcomes. TRIAL REGISTRATION: This study was retrospectively registered with ClinicalTrials.gov ( NCT04638023 ) on 20/11/2020.


Subject(s)
Pessaries/statistics & numerical data , Premature Birth/prevention & control , Progestins/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Adult , Birth Weight , Cervical Length Measurement , Cervix Uteri/anatomy & histology , Combined Modality Therapy , Female , Humans , Malaysia , Pregnancy , Pregnancy Trimester, First , Premature Birth/epidemiology , Retrospective Studies , Risk Factors
16.
PLoS One ; 16(3): e0248845, 2021.
Article in English | MEDLINE | ID: mdl-33739994

ABSTRACT

Avascular necrosis of bone (AVN) is increasingly being recognized as a complication of SLE and causes significant disability due to pain and mobility limitations. We studied the prevalence and factors associated with avascular necrosis (AVN) in a multiethnic SLE cohort. SLE patients who visited the outpatient clinic from October 2017 to April 2019 were considered eligible. Their medical records were reviewed to identify patients who developed symptomatic AVN, as confirmed by either magnetic resonance imaging or plain radiography. Subsequently, their SLE disease characteristics and treatment were compared with the characteristics of patients who did not have AVN. Multivariable logistic regression analyses were performed to determine the independent factors associated with AVN among the multiethnic SLE cohort. A total of 390 patients were recruited, and the majority of them were females (92.6%); the patients were predominantly of Malay ethnicity (59.5%), followed by Chinese (35.9%) and Indian (4.6%). The prevalence of symptomatic AVN was 14.1%, and the mean age of AVN diagnosis was 37.6 ± 14.4 years. Both univariate and multivariable logistic regression analyses revealed that a longer disease duration, high LDL-C (low density lipoprotein cholesterol), positive anti-cardiolipin (aCL) IgG and anti-dsDNA results, a history of an oral prednisolone dose of more than 30 mg daily for at least 4 weeks and osteoporotic fractures were significantly associated with AVN. On the other hand, hydroxychloroquin (HCQ), mycophenolate mofetil (MMF) and bisphosphonate use were associated with a lower risk of AVN. No associations with ethnicity were found. In conclusion, several modifiable risk factors were found to be associated with AVN, and these factors may be used to identify patients who are at high risk of developing such complications. The potential protective effects of HCQ, MMF and bisphosphonates warrant additional studies.


Subject(s)
Ethnicity , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/epidemiology , Osteonecrosis/complications , Osteonecrosis/epidemiology , Adult , Cohort Studies , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Prevalence , Risk Factors , Young Adult
17.
Arthritis Res Ther ; 23(1): 46, 2021 01 30.
Article in English | MEDLINE | ID: mdl-33514426

ABSTRACT

BACKGROUND: Fine-mapping of human leukocyte antigen (HLA) region for rheumatoid arthritis (RA) risk factors has identified several HLA alleles and its corresponding amino acid residues as independent signals (i.e., HLA-A, HLA-B, HLA-DPB1, and HLA-DQA1 genes), in addition to the well-established genetic factor in HLA-DRB1 gene. However, this was mainly performed in the Caucasian and East Asian populations, and data from different Asian regions is less represented. We aimed to evaluate whether there are independent RA risk variants in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients from the multi-ethnic Malaysian population, using the fine-mapping of HLA region strategy. METHODS: We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region. RESULTS: We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30-5.49, PGWAS = 7.22 × 10-29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37-0.62, PGWAS = 2.58 × 10-08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09-0.30, PGWAS = 1.60 × 10-09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia. CONCLUSIONS: Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.


Subject(s)
Arthritis, Rheumatoid , Alleles , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/genetics , Autoantibodies/genetics , Case-Control Studies , Genetic Predisposition to Disease/genetics , HLA Antigens , HLA-DRB1 Chains/genetics , Humans
18.
Article in English | MEDLINE | ID: mdl-32987806

ABSTRACT

Gestational diabetes mellitus (GDM) is associated with maternal and neonatal complications. We aimed to evaluate the relationship between the abnormalities of the oral glucose tolerance test (OGTT) and adverse pregnancy outcomes. This was a retrospective study of GDM patients over a five-year period in a Malaysian tertiary center. The diagnosis of GDM was based on the National Institute for Health and Care Excellence (NICE) guideline. The data on patients' demographics, OGTT results, GDM treatment, and pregnancy outcomes were analyzed. A total of 1105 women were included in the final analysis. The percentage of women with isolated abnormal fasting glucose, isolated two-hour abnormality, and both abnormal values were 4.8%, 87.1%, and 8.1%, respectively. Women with both OGTT abnormalities had a higher risk of preeclampsia (odds ratio (OR) 4.73; 95% confidence interval (CI) 1.45-15.41) and neonatal hypoglycemia (OR 8.78; 95% CI 1.93-39.88). Isolated postprandial abnormality was associated with an 80% lesser risk of neonatal hypoglycemia (OR 0.19; 95% CI 0.04-0.87). Both isolated fasting and multiple OGTT abnormalities were associated with insulin therapy. Multiple OGTT abnormalities were a positive predictor of adverse pregnancy outcomes, while isolated postprandial abnormality was associated with a lesser risk of neonatal complication. Further prospective study is essential to validate these findings.


Subject(s)
Diabetes, Gestational , Glucose Tolerance Test , Adult , Blood Glucose , Cross-Sectional Studies , Diabetes, Gestational/epidemiology , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome/epidemiology , Prospective Studies , Retrospective Studies
19.
Hum Immunol ; 81(6): 263-264, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32312605

ABSTRACT

A total of 271 Southeast Asia Indians from Peninsular Malaysia were genotyped for HLA-A, -B, -C, -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, HLA-B and HLA-DQB1 was in Hardy-Weinberg proportions (HWEP) (p > 0.05). We observed significant deviation from the HWEP for HLA-A (p < 0.05), HLA-C (p < 0.01) and HLA-DRB1 (p < 0.01) loci. This genotype data is available in Allele Frequencies Network Database (AFND) Dos Santos et al. (2016).


Subject(s)
Ethnicity , Genotype , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-C Antigens/genetics , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Alleles , Asia, Southeastern , Asian People , Gene Frequency , Genetics, Population , Haplotypes , Humans , India/ethnology , Malaysia/epidemiology , Malaysia/ethnology
20.
Vaccine ; 38(9): 2183-2189, 2020 02 24.
Article in English | MEDLINE | ID: mdl-32001070

ABSTRACT

BACKGROUND: Vaccine hesitancy is a complex behaviour which involves various degrees of indecision about specific vaccines or vaccination uptake. Access to antenatal care had been associated with positive vaccine behavior. OBJECTIVE: To determine the prevalence of vaccine hesitancy towards childhood immunisation amongst urban pregnant mothers and the associated socio-demographic factors. METHODS: A cross-sectional study was conducted among 1081 women who received antenatal care at a teaching hospital in Kuala Lumpur. Vaccine hesitancy was assessed using the Parent Attitudes about Childhood Vaccines (PACV) Survey in both English and validated Malay versions. The sociodemographic data of the mothers and their partners, source of vaccine information and reasons for hesitancy were analysed. RESULTS: Eighty-six (8.0%) pregnant mothers were vaccine hesitant. Ethnicity, religion, number of children, educational level and employment status were significantly associated with vaccine hesitancy. Multivariable analysis showed that a low level of education was the most significant risk factor (p < 0.001), followed by religion (p = 0.03). Health professionals was the main source of information about vaccine. The non-vaccine hesitant women were more likely to seek information from health professionals, and health books and magazine. Fear of adverse side effects of vaccines was the predominant concern for all participants (58%) whilst fear of vaccination pain, preference for alternative medicine and lack of trust in the pharmaceutical industry were significant reasons given by the vaccine hesitant group. Partners' ethnicity, a low educational level and a low income were significantly associated with vaccine hesitancy amongst pregnant mothers. CONCLUSION: Prevalence of vaccine hesitancy amongst urban Malaysian pregnant women was relatively low. Muslim mothers are less likely to be vaccine hesitant. Educational level of mothers and their partners are the common determinant of vaccine hesitancy amongst antenatal mothers.


Subject(s)
Mothers , Patient Acceptance of Health Care/psychology , Pregnant Women/psychology , Vaccination/psychology , Vaccines , Child , Cross-Sectional Studies , Fear , Female , Health Knowledge, Attitudes, Practice , Humans , Malaysia , Pregnancy
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