Comorbid Ankylosing Spondylitis and Systemic Lupus Erythematosus: A Therapeutic Challenge.

Ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) are common rheumatologic ailments that cause multiorgan system disease. The incidence of lupus and AS in the same patient is rare and has seldom been described in the literature. Comorbid lupus and AS provide interesting diagnostic and therapeutic challenges. Here, we present a case of comorbid lupus and AS, discuss the diagnostic challenges in diagnosing these conditions, and put forth possible therapeutic interventions that may benefit similar patients.

Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen-Year Follow-up.

OBJECTIVE: Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. METHODS: We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. RESULTS: Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P = 0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. CONCLUSIONS: Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Acceptance and Attitude of Parents Regarding COVID-19 Vaccine for Children: A Cross-Sectional Study.

Background The coronavirus disease 2019 (COVID-19) pandemic has claimed millions of lives worldwide. India also launched a COVID-19 vaccination drive, and clinical trials for a pediatric COVID-19 vaccine are in development. Objectives The study aims to assess the acceptance and attitude of parents regarding the COVID-19 vaccine for children in India. The study also aims to find the association between selected demographic variables and acceptance and attitudes in parents regarding the COVID-19 vaccine for children. Materials and methods We conducted a cross-sectional descriptive study with 204 participants, and data were collected online using Google Forms. The study participants were parents of children aged two to 15 years. A self-structured tool was used to assess parents' acceptance regarding vaccinating their children, and a modified vaccination attitudes examination scale was used to assess parents' attitudes toward pediatric vaccination against COVID-19. We used IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, New York) to analyze the data. Demographic data were represented as frequency and percentage. Binary logistic regression analysis was used to determine the associations between sociodemographic data and parents' levels of acceptance and attitude. For all the data, p<0.05 was considered significant. Results The majority of the participants (85%) reported acceptance of the COVID-19 vaccine for children. More than 80% of parents agree that vaccines are essential to halt the COVID-19 pandemic and are mandatory for children. Most parents (62%) also believed that complementary medicine is better than vaccines for children. While most parents (95%) reported trusting the vaccine, but more than half (59%) reported concerns regarding the unknown future effects of the vaccine. Mothers (odds ratio (OR), 2.963; p=0.015) and parents of children who received routine vaccination (OR, 0.175; p=0.039) were willing to vaccinate their children when a COVID-19 vaccine became available. Mothers (OR, 3.294; p=0.002) and respondents whose family member or close relative suffered from COVID-19 (OR, 0.420; p=0.029) accepted the COVID-19 vaccine irrespective of the child's age. Study participants who had previously tested positive for COVID-19 (OR, 0.275; p=0.012) believed vaccines for children were necessary to halt the COVID-19 pandemic. Conclusion We sought to assess parents' acceptance and attitudes regarding the COVID-19 vaccine for children in India. According to our results, while parents have a high acceptance of a pediatric COVID-19 vaccine, they also have a few apprehensions. Therefore, for a successful mass vaccination drive among the pediatric age group, there should be rigorous communication regarding the vaccine and staunch health campaigns to create more awareness and acceptance toward the COVID-19 vaccine for children.

Effectiveness of Flippits and Virtual Reality Therapy on Pain and Anxiety Among Children Undergoing Painful Procedures.

Introduction Pain experienced by children during painful procedures may cause stress, fear, and anxiety. Currently, a number of interventions are used to reduce pain perception during medical procedures and distraction therapy is one of the most commonly used interventions. Method A randomized control trial was conducted among 105 children aged between three years and 12 years undergoing painful procedures such as intravenous cannulation, blood sampling, and injections to evaluate the effect of flippits and virtual reality therapy (VRT) on pain and anxiety. Through a computerized random approach, 35 samples were allotted to each group. Experimental group -1 received VRT, experimental group -2 received flippit (distraction card) therapy during painful procedures, and the control group received the conventional intervention. Standard tools were used to assess the pain and anxiety. Result Total 128 children were admitted to the ward and 23 were not included in the study for various reasons. Total 105 children undergone randomization to three groups, 35 in each group. All were analyzed for primary and secondary outcomes. After adjusting for confounding factors using multiple logistic regression, it was found that pain scores of VRT and flippit groups were less than the control group (aOR, 95% CI 0.635, 0.504-0.799, P = 0.000 and aOR, 95% CI 0.705, 0.572-0.868, P = 0.001, respectively) and no difference was observed between VRT and Flippit group (aOR, 95% CI; 0.901, 0.723 - 1.123, P 0.353). Flippit group perceived less intensity of pain compared to control group (aOR, 95% CI 0.542, 0.322-0.912, P = 0.021) and children received VRT perceived less intensity of pain than both control and flippit groups of children (aOR, 95% CI 0.258, 0.132-0.503, P = 0.000 and aOR, 95% CI 0.476, 0.252-0.900, respectively). Children received VRT and flippit therapy perceived less anxiety compared to control group (aOR, 95% CI 0.589, 0.348-0.999, P = 0.050 and aOR, 95% CI 0.385, 0.217-0.682, P = 0.001, respectively). But, there was no difference between VRT and flippit groups (aOR, 95% CI 1.532, 0.940-2.498, P = 0.087). Conclusion Flippit therapy and virtual reality therapy were better than conventional therapy in reducing the perception of anxiety and pain in children, aged three to 12 years, undergone painful procedures. Virtual reality therapy had an edge over flippit therapy in reducing the worst hurt.

COVID-19 and Major Organ Thromboembolism: Manifestations in Neurovascular and Cardiovascular Systems.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to cause multisystemic damage. We undertook a systematic literature review and comprehensive analysis of a total of 55 articles on arterial and venous thromboembolism in COVID-19 and articles on previous pandemics with respect to thromboembolism and compared the similarities and differences between them. The presence of thrombosis in multiple organ systems points to thromboembolism being an integral component in the pathogenesis of this disease. Thromboembolism is likely to be the main player in the morbidity and mortality of COVID -19 in which the pulmonary system is most severely affected. We also hypothesize that D-dimer values could be used as an early marker for prognostication of disease as it has been seen to be raised even in the pre-symptomatic stage. This further strengthens the notion that thromboembolism prevention is necessary. We also examined literature on the neurovascular and cardiovascular systems, as the manifestation of thromboembolic phenomenon in these two systems varied, suggesting different pathophysiology of damage. Further research into the role of thromboembolism in COVID-19 is important to advance the understanding of the virus, its effects and to tailor treatment accordingly to prevent further casualties from this pandemic.

An Evaluation of the Video Narrative Technique on the Self-Efficacy of Medication Understanding and Use Among Post-Stroke Patients: A Randomized-Controlled Trial.

INTRODUCTION: Self-efficacy is positively associated with medication understanding and use self-efficacy (MUSE) among post-stroke patients. It is also closely related to knowledge, belief, and perception, which vary among people from different socioeconomic backgrounds and cultures. As interventions using video and peer stories have emerged to be successful on behavior modification, this study aimed to explore the effectiveness of video narratives incorporated with Health Belief constructs on MUSE and its associated factors among patients with stroke at a local setting. METHODS: A randomized controlled trial (RCT) for 12 months was carried out on patients diagnosed with stroke at Hospital Kuala Lumpur, Malaysia. The RCT recruited up to 216 eligible patients who were requested to return for two more follow-ups within six months. Consented patients were randomized to either standard care or intervention with video narratives. The control of potential confounding factors was ensured, as well as unbiased treatment review with prescribed medications, only obtained onsite. RESULTS AND DISCUSSION: A repeated measure of MUSE mean score differences at T0 (baseline), T2 (6th month) and T4 (12th month) for antithrombotic, antihypertensive, and all medication categories indicated significant within and between groups differences in the intervention group (p<0.05). Moreover, this impact was reflected upon continuous blood pressure (BP) monitoring compared to the control group (F (1214) =5.23, p=0.023, ƞ2=0.024). Though BP measure differences were non-significant between the groups (p=0.552), repeated measure analysis displayed significant mean differences between intervention and control group on BP control over time (F (1.344, 287.55) =8.54, P<0.001, ƞ2=0.038). Similarly, the intervention's positive impact was also present with similar trends for knowledge, illness perception, and the belief about medicine. Though significant differences (p<0.05) of all outcome measures gradually decreased between T2 and T4 in the intervention group; nevertheless, these positive findings confirmed that personalized video narratives were able to motivate and influence MUSE and its associated factors among post-stroke patients. The significant improvement in medication-taking self-efficacy and the sustenance of BP monitoring habits among patients in the intervention group strengthened our conceptual framework's practicality.

Video Narratives Intervention Among Stroke Survivors: Feasibility and Acceptability Study of a Randomized Controlled Trial.

BACKGROUND: A large number of stroke survivors worldwide suffer from moderate to severe disability. In Malaysia, long-term uncontrolled stroke risk factors lead to unforeseen rates of recurrent stroke and a growing incidence of stroke occurrence across ages, predominantly among the elderly population. This situation has motivated research efforts focused on tapping into patient education, especially related to patient self-efficacy of understanding and taking medication appropriately. Video narratives integrated with health belief model constructs have demonstrated potential impacts as an aide to patient education efforts. OBJECTIVE: The aim of this study was to investigate the feasibility and acceptability of study procedures based on a randomized controlled trial protocol of a video narratives intervention among poststroke patients. We also aimed to obtain preliminary findings of video narratives related to medication understanding and use self-efficacy (MUSE) and blood pressure control. METHODS: A parallel group randomized controlled trial including a control group (without video viewing) and an intervention group (with video viewing) was conducted by researchers at a neurology outpatient clinic on poststroke patients (N=54). Baseline data included patients' sociodemographic characteristics, medical information, and all outcome measures. Measurements of MUSE and blood pressure following the trial were taken during a 3-month follow-up period. Feasibility of the trial was assessed based on recruitment and study completion rates along with patients' feedback on the burden of the study procedures and outcome measures. Acceptability of the trial was analyzed qualitatively. Statistical analysis was applied to ascertain the preliminary results of video narratives. RESULTS: The recruitment rate was 60 out of 117 patients (51.3%). Nevertheless, the dropout rate of 10% was within the acceptable range. Patients were aged between 21 and 74 years. Nearly 50 of the patients (>85%) had adequate health literacy and exposure to stroke education. Most of the patients (>80%) were diagnosed with ischemic stroke, whereby the majority had primary hypertension. The technicalities of randomization and patient approach were carried out with minimal challenge and adequate patient satisfaction. The video contents received good responses with respect to comprehension and simplicity. Moreover, an in-depth phone interview with 8 patients indicated that the video narratives were considered to be useful and inspiring. These findings paralleled the preliminary findings of significant improvement within groups in MUSE (P=.001) and systolic blood pressure control (P=.04). CONCLUSIONS: The queries and feedback from each phase in this study have been acknowledged and will be taken forward in the full trial. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12618000174280; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373554.

Neurosyphilis presenting as acute ischemic stroke.

Neurosyphilis is a broad term used to describe an infection caused by Treponema pallidum in the central nervous system. While this was a common cause of stroke in the 19th century, it saw a decline after the introduction of penicillin. However, in the recent past, there has been an increase in the incidence of syphilis, especially with HIV coinfection. Neurosyphilis results from an untreated primary syphilis. Neuropsychiatric disorder appears to be the commonest manifestation followed cerebrovascular accident, myelopathy, ocular disease and seizure. Known as the 'great imitator', this entity, however, may be easily missed if not for a high index of suspicion. This is especially so because of its similar presentation to other more common clinical conditions. We describe the case of a 39-year-old man displaying acute global aphasia and right-sided facial weakness in keeping with a left middle cerebral artery infarct. This was confirmed with computed tomography of the brain, and subsequently, further investigations revealed a diagnosis of neurosyphilis. The patient was treated with intravenous benzylpenicillin and recovered well with treatment.

Forme fruste anti-GQ1b-negative Miller Fischer syndrome masquerading as posterior circulation stroke.

Miller Fischer syndrome (MFS) is a variant of Guillain-Barré syndrome first described in 1956 and is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia. However, since its discovery, forme fruste and overlapping syndrome have been described. A forme fruste of MFS implies an attenuated form where not all of the clinical triad are present. In this report, a case of MFS is highlighted that was mistakenly treated as posterior circulation stroke, as well as the challenges faced in reaching the correct diagnosis and hence the appropriate treatment.

Exploring stroke survivors' self-efficacy in understanding and taking medication and determining associated factors: a cross-sectional study in a neurology clinic in Malaysia.

BACKGROUND AND AIM: Evidence-based prescribing practices for stroke-preventive medication have benefited stroke survivors; however, medication-nonadherence rates remain high. Medication understanding and use self-efficacy (MUSE) has shown great importance in medication-taking behavior, but its relationship with medication nonadherence in stroke-preventive regimens lacks exploration. The aim of this study was to determine the prevalence of MUSE and its association with nonadherence causes and other potential factors among stroke survivors in Malaysia. METHODS: This cross-sectional study was conducted among 282 stroke patients who provided informed consent and were in follow-up at the Neurology Outpatient Department of Hospital Kuala Lumpur, Malaysia. The study employed a data-collection form that gathered information on sociodemographics, clinical treatment, outcome measures on MUSE, and medication-nonadherence reasons. RESULTS: The prevalence of poor medication understanding and use self-efficacy among stroke patients was 46.5%, of which 29.1% had poor "learning about medication" self-efficacy, while 36.2% lacked self-efficacy in taking medication. Beliefs about medicine (74.02%) was the commonest reason for medication nonadherence, followed by medication-management issues (44.8%). In the multivariate model, independent variables significantly associated with MUSE were health literacy (AOR 0.2, 95% CI 0.069-0.581; P=0.003), medication-management issues (AOR 0.073, 95% CI 0.020-0.266; P<0.001), multiple-medication issues (AOR 0.28, 95% CI 0.085-0.925; P=0.037), beliefs about medicine (AOR 0.131, 95% CI 0.032-0.542; P=0.005), and forgetfulness/convenience issues (AOR 0.173, 95% CI 0.050-0.600; P=0.006). CONCLUSION: The relatively poor learning about medication and medication-taking self-efficacy in this study was highly associated with health literacy and modifiable behavioral issues related to nonadherence, such as medication management, beliefs about medicine, and forgetfulness/convenience. Further research ought to explore these underlying reasons using vigorous techniques to enhance medication understanding and use self-efficacy among stroke survivors to determine cause-effect relationships.

An Intervention to Promote Medication Understanding and Use Self-Efficacy: Design of Video Narratives for Aging Patients at Risk of Recurrent Stroke.

BACKGROUND: The debilitating effects of recurrent stroke among aging patients have urged researchers to explore medication adherence among these patients. Video narratives built upon Health Belief Model (HBM) constructs have displayed potential impact on medication adherence, adding an advantage to patient education efforts. However, its effect on medication understanding and use self-efficacy have not been tested. OBJECTIVE: The researchers believed that culturally sensitive video narratives, which catered to a specific niche, would reveal a personalized impact on medication adherence. Therefore, this study aimed to develop and validate video narratives for this purpose. METHODS: This study adapted the Delphi method to develop a consensus on the video scripts' contents based on learning outcomes and HBM constructs. The panel of experts comprised 8 members representing professional stroke disease experts and experienced poststroke patients in Malaysia. The Delphi method involved 3 rounds of discussions. Once the consensus among members was achieved, the researchers drafted the initial scripts in English, which were then back translated to the Malay language. A total of 10 bilingual patients, within the study's inclusion criteria, screened the scripts for comprehension. Subsequently, a neurologist and poststroke patient narrated the scripts in both languages as they were filmed, to add to the realism of the narratives. Then, the video narratives underwent a few cycles of editing after some feedback on video engagement by the bilingual patients. Few statistical analyses were applied to confirm the validity and reliability of the video narratives. RESULTS: Initially, the researchers proposed 8 learning outcomes and 9 questions based on HBM constructs for the video scripts' content. However, following Delphi rounds 1 to 3, a few statements were omitted and rephrased. The Kendall coefficient of concordance, W, was about 0.7 (P<.001) for both learning outcomes and questions which indicated good agreement between members. Each statement's Cronbach alpha was above .8 with SD values within a range below 1.5 that confirmed satisfactory content and construct validity. Approximately 75% (6/8) of members agreed that all chosen statements were relevant and suitable for video script content development. Similarly, more than 80% (8/10) of patients scored video engagement above average, intraclass correlation coefficient was above 0.7, whereas its Kendall W was about 0.7 with significance (P<.001), which indicated average agreement that the video narratives perceived realism. CONCLUSIONS: The Delphi method was proven to be helpful in conducting discussions systematically and providing precise content for the development of video narratives, whereas the Video Engagement Scale was an appropriate measurement of video realism and emotions, which the researchers believed could positively impact medication understanding and use self-efficacy among patients with stroke. A feasibility and acceptability study in an actual stroke care center is needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000174280; https://www.anzctr.org.au /Trial/Registration/TrialReview.aspx?id=373554&isReview=true.

Idiopathic CD4 lymphopenia in a case of disseminated cryptococcosis with brain, vertebral spine and reproductive organ involvement.

Cryptococcosis is an opportunistic fungal infection commonly seen in HIV cases. We present a case of disseminated cryptococcosis with multiple non-continuous infective foci in a non-HIV, non-transplant case.

Predictors of Hand Contracture in Early Systemic Sclerosis and the Effect on Function: A Prospective Study of the GENISOS Cohort.

OBJECTIVE: To identify baseline features that predict progression of hand contractures and to assess the effect of contractures on functional status in the prospective GENISOS cohort. METHODS: Rate of decline in hand extension, as an indicator of hand contracture, was the primary outcome. We assessed longitudinal hand extension measurements, modified Health Assessment Questionnaire (MHAQ) score, Medical Outcomes Study Short Form-36 (SF-36) physical function score, and demographic, clinical, and serological variables. Subjects with ≥ 2 hand measurements at least 6 months apart were included. RESULTS: A total of 1087 hand measurements for 219 patients were available over an average of 8.1 ± 4.8 years. Hand extension decreased on average by 0.11 cm/year. Antitopoisomerase I antibody (ATA) positivity and higher modified Rodnan Skin Score (mRSS) were predictive of faster decline in hand extension (p = 0.009 and p = 0.046, respectively). In a subgroup analysis of 62 patients with ≤ 2 years from SSc onset, ATA and diffuse disease type were associated with faster decline in hand extension; anticentromere positivity was associated with slower rate of decline. Although the rate of decline in patients with disease duration ≤ 2 years was numerically higher, the difference was not statistically significant. Hand extension continued to decline in a linear fashion over time and was inversely related to overall functional status. CONCLUSION: ATA was predictive of contracture development in both early disease (≤ 2 yrs) and in the overall cohort. Hand extension declined linearly over time and was inversely associated with MHAQ and SF-36 scores. ATA positivity and higher baseline mRSS were predictive of faster decline in hand extension.

The Needs and Barriers of Medication-Taking Self-Efficacy Among Poststroke Patients: Qualitative Study.

BACKGROUND: Stroke is one of the top 10 leading diseases worldwide, with high mortality and morbidity rates. There is an incomplete understanding of the various types of self-efficacy involved in the prevention of recurrent stroke, and one of them is medication-taking self-efficacy. OBJECTIVE: This study aimed to explore the fundamental needs and barriers of medication-taking self-efficacy in poststroke patients in Malaysia. METHODS: We performed in-depth individual interviews with poststroke patients (N=10) from the Outpatient Neurology Clinic, Hospital Kuala Lumpur. All interviews were transcribed verbatim, and an inductive thematic analysis was performed on the data collected from the interviews. RESULTS: Two key themes were identified: (1) self-efficacy in taking the effort to understand stroke and its preventative treatment for recurrent stroke and (2) self-efficacy in taking prescribed medication to prevent stroke. Patients needed to be proactive in seeking reliable information about stroke and the perceived benefits of preventative treatment for stroke. The discussion was focused on eliciting the needs and barriers related to medication-taking self-efficacy. Patients needed to develop independence and self-reliance to overcome barriers such as dependency and low motivation. External factors such as limited information resources, low perceived severity, poor social environment, and poor communication add to the challenges of poststroke patients to improve their self-efficacy of managing their medications. CONCLUSIONS: The study identified potential key findings related to the needs of patients in a localized setting, which are also related to several health behavioral concepts and constructs, indicating the importance of overcoming barriers to improve the quality of life in poststroke patients. We anticipate that the results will be taken into consideration for future personalized patient education interventions.

The effectiveness of culturally tailored video narratives on medication understanding and use self-efficacy among stroke patients: A randomized controlled trial study protocol.

INTRODUCTION: A substantial number of the world's population appears to end with moderate to severe long-term disability after stroke. Persistent uncontrolled stroke risk factor leads to unpredicted recurrent stroke event. The increasing prevalence of stroke across ages in Malaysia has led to the adaptation of medication therapy adherence clinic (MTAC) framework. The stroke care unit has limited patient education resources especially for patients with medication understanding and use self-efficacy. Nevertheless, only a handful of studies have probed into the effectiveness of video narrative at stroke care centers. METHOD: This is a behavioral randomized controlled trial of patient education intervention with video narratives for patients with stroke lacking medication understanding and use self-efficacy. The study will recruit up to 200 eligible stroke patients at the neurology tertiary outpatient clinic, whereby they will be requested to return for follow-up approximately 3 months once for up to 12 months. Consenting patients will be randomized to either standard patient education care or intervention with video narratives. The researchers will ensure control of potential confounding factors, as well as unbiased treatment review with prescribed medications only obtained onsite. RESULTS: The primary analysis outcomes will reflect the variances in medication understanding and use self-efficacy scores, as well as the associated factors, such as retention of knowledge, belief and perception changes, whereas stroke risk factor control, for example, self-monitoring and quality of life, will be the secondary outcomes. DISCUSSION AND CONCLUSION: The study should be able to determine if video narrative can induce a positive behavioral change towards stroke risk factor control via enhanced medication understanding and use self-efficacy. This intervention is innovative as it combines health belief, motivation, and role model concept to trigger self-efficacy in maintaining healthy behaviors and better disease management. TRIAL REGISTRATION: ACTRN (12618000174280).

Linkage disequilibrium between polymorphisms of ABCB1 and ABCC2 to predict the treatment outcome of Malaysians with complex partial seizures on treatment with carbamazepine mono-therapy at the Kuala Lumpur Hospital.

PURPOSE: Carbamazepine (CBZ) is used as the first line of treatment of Complex Partial Seizures (CPS) in the Epilepsy Clinic, Neurology Department of Kuala Lumpur Hospital (KLH). More than 30% of the patients remain drug resistant to CBZ mono-therapy. CBZ is transported by the P-glycoprotein (P-gp). The P-gp encoded by the ABCB1 and ABCC2 genes are expressed in drug resistant patients with epilepsy. A few studies have shown significant association between CBZ resistant epilepsy and Linkage Disequilibrium (LD) with adjacent polymorphisms of these genes. Our study is aimed at determining the correlation between patients' response to CBZ mono-therapy to Single Nucleotide Polymorphisms G2677T and C3435T of the ABCB1 gene as well as G1249A and -24C>T of the ABCC2 gene. METHOD: 314 patients with CPS were recruited from the Neurology Department of the KLH based on stringent inclusion and exclusion criteria, of whom 152 were responders and the other 162 were non-responders. DNA was extracted from their blood samples and Taqman technology for allelic discrimination was performed. Results were described as genotype frequencies. The SHEsis analysis platform was used to calculate linkage disequilibrium index and infer haplotype frequencies. Haploview was used to do permutation test to obtain a corrected p-value. RESULTS: Resistance to treatment with CBZ mono-therapy was significantly associated with the 2677TT and the 3435TT genotypes while it was not significantly associated with the G1249A and -24C>T polymorphisms. The GCGC haplotype combination of the 2677G>T, 3435C>T, 1249G>A and -24C>T respectively was found to be extremely significant (p = 1.10e-20) with good drug response to CBZ mono-therapy. CONCLUSION: Linkage disequilibrium between the 2677G>T, 3435C>T, 1249G>A and -24C>T SNPs may be used as a reliable screening marker to determine the treatment outcome of CBZ mono-therapy with CPS irrespective of race or gender.

Clinical profile and HLA-DRB1 genotype of late onset multiple sclerosis in Western Australia.

We aimed to characterize the clinical profile and human leukocyte antigen (HLA)-DRB1 genotype of patients with late onset multiple sclerosis (LOMS) in Western Australia. The clinical features, laboratory studies and HLA-DRB1 alleles were analysed in patients with multiple sclerosis (MS) with onset over 50years of age and compared with 100 patients with early onset MS (EOMS). Of a cohort of 829 patients with MS, 73 (8.8%) presented at over 50years of age, including 14 (1.7%) over 60years. Patients with LOMS had a lower female to male ratio, more frequent initial motor dysfunction, less frequent sensory symptoms and optic neuritis, a more frequent primary-progressive course and shorter time to reach Extended Disability Status Scale (EDSS) scores of 3.0 and 6.0. More LOMS patients were initially misdiagnosed compared to patients with EOMS. HLA-DRB1 *1501 was strongly associated with both LOMS and EOMS compared to the Control subjects, while HLA-DRB1 *0801 was over-represented in patients with LOMS. We concluded that patients with LOMS have a different clinical profile when compared to those with EOMS. Carriers of HLA-DRB1 *0801 may be more prone to develop MS at a later age.

Presence of CSF oligoclonal bands (OCB) is associated with the HLA-DRB1 genotype in a West Australian multiple sclerosis cohort.

High-resolution HLA-DRB1 genotyping was performed in 97 OCB-positive and 68 OCB-negative cases with demyelinating disease to determine the influence of HLA-DRB1 alleles on the presence of OCB in a West Australian multiple sclerosis (MS) cohort. Carriage of the HLA-DRB1*1501 allele was associated with both OCB-positive and OCB-negative MS compared with controls, but more strongly with the OCB-positive group, and increased the likelihood of having OCB 2.1-fold with evidence of a dominant dose-effect. The HLA-DRB1*0301 allele was negatively correlated with OCB, with all homozygotes OCB-negative, suggesting a possible recessive protective effect of HLA-DRB1*0301. There was no significant correlation between OCB and the DRB1*04 alleles which have been associated with OCB-negative MS in previous Swedish and Japanese studies. Evidence of allelic interactions was found with HLA-DRB1*1501/*1301 heterozygotes having a reduced frequency of OCB and HLA-DRB1*0301/*0401 heterozygotes all being OCB-negative. These findings confirm the strong association between HLA-DRB1*1501 and OCB which has been found in other populations but indicate that the influence of other HLA-DRB1 alleles varies in different populations. Our study is the first to show that HLA-DRB1 allele interactions and dose-effects influence the frequency of OCB.

Modifying effects of HLA-DRB1 allele interactions on age at onset of multiple sclerosis in Western Australia.

The contribution of genetic factors to the age at onset in multiple sclerosis is poorly understood. Our objective was to investigate the disease modifying effects of HLA-DRB1 alleles and allele interactions on age at onset of multiple sclerosis. High-resolution four-digit HLA-DRB1 genotyping was performed in a cohort of 461 multiple sclerosis patients from the Perth Demyelinating Diseases Database. Carriage of the HLA-DRB1*1501 risk allele was not significantly associated with age at onset but HLA-DRB1*0801 was associated with a later onset of the disease. The HLA-DRB1*0401 allele was associated with a reduced age at onset when combined with DRB1*1501 but may delay age at onset when combined with DRB1*0801. These findings indicate that epistatic interactions at the HLA-DRB1 locus have significant modifying effects on age at onset of multiple sclerosis and demonstrate the value of high-resolution genotyping in detecting such associations.