Displaying publications 61 - 80 of 101 in total

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  1. Sng JH, Ali AB, Lee SC, Zahar D, Wong JE, Blake V, et al.
    J Med Genet, 2003 Oct;40(10):e117.
    PMID: 14569140
    Matched MeSH terms: Age of Onset
  2. Sulaiman FN, Wong KK, Ahmad WAW, Ghazali WSW
    Medicine (Baltimore), 2019 Mar;98(12):e14945.
    PMID: 30896663 DOI: 10.1097/MD.0000000000014945
    Rheumatoid arthritis (RA) is a chronic debilitating inflammatory disease affecting mainly the joint, surrounding tissue and other extra-articular structures in the body. RA can lead to destruction of bone and cartilage which may cause severe disability and it is characterized by the presence of serum rheumatoid factor (RF). The anti-cyclic citrullinate peptide (anti-CCP) antibody is another serum biomarker used in RA diagnosis with higher sensitivity and specificity.In this cross-sectional study with retrospective record review, 159 established RA patients from Hospital Universiti Sains Malaysia (HUSM) were recruited. Enzyme-linked immunosorbent assays (ELISAs) for serum RF and anti-CCP were performed. Our goal was to evaluate the significance of anti-CCP antibody in predicting the disease activity and progression in terms of radiological and extra-articular manifestations upon diagnosis.Of the 159 RA patients included in this study, mean age was 48.3 years old and majority (n = 134; 84.3%) were female. A total of 83 (52.2%) and 99 (62.3%) patients had anti-CCP antibody and RF, respectively. Mean Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (ESR) (DAS28-ESR) score for all patients was 4.74 (medium and high disease activity). Fifty-eight (36.5%) patients had radiological defects and 49 (30.8%) patients had extra-articular involvement manifested by rheumatoid nodule, pulmonary involvement, and anemia.In terms of anti-CCP antibody association with clinical and laboratory parameters, a significant co-occurrence of RF and anti-CCP antibody (P = .002) was observed. Anti-CCP antibody was significantly associated with radiological defects in which majority of patients with such defects (n = 40/58; 68.9%) were positive for anti-CCP antibody (P = .001). However, there was no significant difference between mean and classes of disease activity score and extra-articular manifestations between different anti-CCP antibody groups. In addition, extra-articular manifestations were not associated with high disease activity upon RA diagnosisThere was a significant association between anti-CCP antibody positivity and positive RF. Radiological defects were the sole clinical parameter significantly associated with anti-CCP antibody positivity, indicating that patients positive for anti-CCP antibody should be routinely monitored for radiological defects and their onset.
    Matched MeSH terms: Age of Onset
  3. Courage C, Oliver KL, Park EJ, Cameron JM, Grabińska KA, Muona M, et al.
    Am J Hum Genet, 2021 04 01;108(4):722-738.
    PMID: 33798445 DOI: 10.1016/j.ajhg.2021.03.013
    Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function. We performed whole-exome sequencing (WES) in 84 (78 unrelated) unsolved PME-affected individuals, with or without additional family members, to discover novel causes. We identified likely disease-causing variants in 24 out of 78 (31%) unrelated individuals, despite previous genetic analyses. The diagnostic yield was significantly higher for individuals studied as trios or families (14/28) versus singletons (10/50) (OR = 3.9, p value = 0.01, Fisher's exact test). The 24 likely solved cases of PME involved 18 genes. First, we found and functionally validated five heterozygous variants in NUS1 and DHDDS and a homozygous variant in ALG10, with no previous disease associations. All three genes are involved in dolichol-dependent protein glycosylation, a pathway not previously implicated in PME. Second, we independently validate SEMA6B as a dominant PME gene in two unrelated individuals. Third, in five families, we identified variants in established PME genes; three with intronic or copy-number changes (CLN6, GBA, NEU1) and two very rare causes (ASAH1, CERS1). Fourth, we found a group of genes usually associated with developmental and epileptic encephalopathies, but here, remarkably, presenting as PME, with or without prior developmental delay. Our systematic analysis of these cases suggests that the small residuum of unsolved cases will most likely be a collection of very rare, genetically heterogeneous etiologies.
    Matched MeSH terms: Age of Onset
  4. Bauer M, Glenn T, Alda M, Aleksandrovich MA, Andreassen OA, Angelopoulos E, et al.
    Acta Psychiatr Scand, 2017 Dec;136(6):571-582.
    PMID: 28722128 DOI: 10.1111/acps.12772
    OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder.

    METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density.

    RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001).

    CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

    Matched MeSH terms: Age of Onset
  5. Loo CH, Tan WC, Tang JJ, Khor YH, Manikam MT, Low DE, et al.
    Int J Dermatol, 2018 Dec;57(12):1454-1463.
    PMID: 30182482 DOI: 10.1111/ijd.14210
    BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disorder of follicular occlusion, resulting in abscesses with tunnel formation and severe scarring. Our objectives were to identify the clinical patterns and the prevalence of metabolic syndrome (MetS) among our HS patients and to determine the role of ultrasonography in the clinical assessment of HS.

    METHODS: This was a cross-sectional study carried out from September 2016 to August 2017 at three tertiary hospitals in Northern Peninsular Malaysia.

    RESULTS: A total of 62 patients were recruited, 83.9% of whom were male. The mean age was 29.2 with the median age of onset at 18 years old. The median duration of delay in diagnosis was 3 years. A quarter of them had positive family history. Nearly three-quarters were overweight and obese. About 12/62 (19.4%) had MetS, and it was comparable to healthy controls (15/62, 24.2%). HS patients had a significant higher risk of low-high-density lipoprotein (HDL) and obesity. Based on Hurley staging, 15/62 (24.2%) were in stage I, 38/62 (61.3%) and 9/62 (14.5%) in stages II and III, respectively. However, sonographic scoring showed 50% had severe stage of disease, and 56.9% of the patients had subclinical lesions. There was only a fair agreement between ultrasonography and Hurley staging of disease severity (k = 0.25; P = 0.004).

    CONCLUSION: There was a male preponderance among HS patients in Northern Peninsular Malaysia with early age of onset and more severe disease. Only one-fifth had MetS, but they had significantly higher risks of obesity and low HDL. Ultrasonography examination was useful to detect subclinical lesions and providing a better understanding on disease severity.

    Matched MeSH terms: Age of Onset
  6. Bauer M, Glenn T, Alda M, Andreassen OA, Angelopoulos E, Ardau R, et al.
    J Psychiatr Res, 2019 06;113:1-9.
    PMID: 30878786 DOI: 10.1016/j.jpsychires.2019.03.001
    In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p 
    Matched MeSH terms: Age of Onset
  7. Wan Nazaimoon WM, Faridah I, Singaraveloo M, Ismail IS, Wan Mohamad WB, Letchuman R, et al.
    Diabetes Res Clin Pract, 1999 Jan;43(1):59-66.
    PMID: 10199589 DOI: 10.1016/s0168-8227(98)00108-9
    This study determined the prevalence of glutamic acid decarboxylase antibodies (GAD Ab) in a group of 926 young Malaysian diabetics of three ethnic groups, Malay, Chinese, and Indian. Patients were clinically diagnosed to be Type 1 or Type 2 before the age of 40 years. The overall GAD Ab positivity was 17.4% (161/926), significantly higher in the Type 1 than the Type 2 diabetics (35.5%, 116/329 vs. 7.5%, 45/597, P=0.0001). Compared to GAD Ab negative patients, seropositive diabetics were diagnosed at younger age (21.2+/-0.9 vs. 27.4+/-0.3 y, P=0.0001), had lower fasting (289+/-27.4 vs. 640+/-17.6 pmol/l, P=0.0001) and post-glucagon C-peptide levels (527+/-51.8 vs. 1030+/-28.9 pmol/l, P=0.0001). There were no racial differences in the prevalence of GAD Ab; of the total Type 1, 30.8, 36.4, and 39.4% were Malay, Chinese, and Indian diabetics, respectively and of the total Type 2, 8.8, 8.2, and 4.4% were Malay, Chinese, and Indian diabetics respectively. There was a curvilinear relationship between GAD Ab and the post-glucagon C-peptide levels, suggesting that GAD Ab do play a role in the beta-cells destruction and could be an important immune marker for the LADA group. This study reconfirmed previous reports that the autoimmune mechanisms in the Type 1 Asian diabetics are indeed different from the Caucasians, and further investigations should be carried out to explain the differences.
    Matched MeSH terms: Age of Onset
  8. Gururaj A, Sztriha L, Hertecant J, Eapen V
    J Psychosom Res, 2006 Sep;61(3):343-7.
    PMID: 16938512
    This study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable seizures in children in the Al Ain Medical District in the United Arab Emirates.
    Matched MeSH terms: Age of Onset
  9. Johnson N, Dudbridge F, Orr N, Gibson L, Jones ME, Schoemaker MJ, et al.
    Breast Cancer Res, 2014 May 26;16(3):R51.
    PMID: 24887515 DOI: 10.1186/bcr3662
    INTRODUCTION: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.

    METHODS: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.

    RESULTS: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29).

    CONCLUSIONS: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

    Matched MeSH terms: Age of Onset
  10. Salehi MH, Houshmand M, Aryani O, Kamalidehghan B, Khalili E
    Iran Biomed J, 2014;18(1):28-33.
    PMID: 24375160
    BACKGROUND: Friedreich ataxia (FRDA) is an autosomal recessive disorder caused by guanine-adenine-adenine (GAA) triplet expansions in the FXN gene. Its product, frataxin, which severely reduces in FRDA patients, leads to oxidative damage in mitochondria. The purpose of this study was to evaluate the triple nucleotide repeated expansions in Iranian FRDA patients and to elucidate distinguishable FRDA clinical differences in these patients.

    METHODS: A number of 22 Iranian patients (8 females and 14 males) from 16 unrelated families were studied. DNA was extracted from the peripheral blood of patients. The frequency and length of (GAA)n repeats in intron 1 of the FXN gene were analyzed using long-range PCR. In this study, the clinical criteria of FRDA in our patients and the variability in their clinical signs were also demonstrated.

    RESULTS: An inverse relationship was observed between GAA repeat size and the age of onset. Although some distinguishable clinical features (such as limb ataxia and lower limb areflexia) were found in our patients, 90-95% of them had extensor plantar response and dysarthria. The results showed only one positive diabetes patient and also different effects on eye movement abnormality among our patients.

    CONCLUSION: The onset age of symptoms showed a significant inverse correlation with allele size in our patients (P>0.05). Based on comparisons of the clinical data of all patients, clinical presentation of FRDA in Iranian patients did not differ significantly from other FRDA patients previously reported.

    Matched MeSH terms: Age of Onset
  11. Cheng YC, Stanne TM, Giese AK, Ho WK, Traylor M, Amouyel P, et al.
    Stroke, 2016 Feb;47(2):307-16.
    PMID: 26732560 DOI: 10.1161/STROKEAHA.115.011328
    BACKGROUND AND PURPOSE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years.

    METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls.

    RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2.

    CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.

    Matched MeSH terms: Age of Onset
  12. Wolf NI, Toro C, Kister I, Latif KA, Leventer R, Pizzino A, et al.
    Neurology, 2015 Jan 20;84(3):226-30.
    PMID: 25527264 DOI: 10.1212/WNL.0000000000001157
    To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset.
    Matched MeSH terms: Age of Onset
  13. Norsa'adah B, Zainab J, Knight A
    PMID: 23972031 DOI: 10.1186/1477-7525-11-143
    Epilepsy, a chronic disorder of brain characterised by a predisposition to generate epileptic seizures, has an effect on the psychosocial well-being of sufferers. Measuring the quality of life (QOL) of people with epilepsy (PWE) is increasingly recognized as an important component of clinical management. QOL measures differ between countries and there is limited information regarding PWE in Malaysia. The aim of this study was to determine the health related QOL and its relationship with the presence of seizures in PWE at a Malaysian tertiary referral center.
    Matched MeSH terms: Age of Onset
  14. Robson N, Bond A, Wolff K
    Prev Med, 2013;57 Suppl:S8-10.
    PMID: 23624111 DOI: 10.1016/j.ypmed.2013.04.010
    OBJECTIVES: There is evidence that smoking behaviour differs by ethnicity. This study aims to compare smoking behaviour characteristics between Caucasian and Malay smokers.
    METHODS: A cross sectional survey, involving 175 smokers attending smoking cessation clinics at the Institute of Psychiatry, London, United Kingdom and University Malaya, Kuala Lumpur, Malaysia between May 2005 and February 2007. Data on demographics, smoking history, nicotine dependence and smoking behaviour were collected.
    RESULTS: All participants were males, mean age 30.7 ± 10.3 years. Caucasians initiated smoking significantly earlier (mean age 14.8 ± 2.8 years) (p = 0.001) and smoked regularly significantly earlier (mean age 17.3 ± 3.5) (p = 0.003) than Malays (mean starting age 16.9 ± 4.4 years and mean age regular use 19.5 ± 4.5 years), respectively. Caucasians smoked less for social integration than Malays (p = 0.03) but smoked more for regulation of negative affect than Malays (p = 0.008) and smoked more for hedonism than Malays (p < 0.001).
    CONCLUSION: Malays smoke as a means of socially integrating. This has important public health implications. Social reasons and the social environment play a role in smoking uptake, smoking maintenance and smoking cessation and this should be borne in mind for strategies planning to promote smoking cessation.
    KEYWORDS: Behaviour; Caucasian; Character; Cigarette; Malay; Nicotine; Smoking
    Matched MeSH terms: Age of Onset
  15. Karen-Ng LP, Marhazlinda J, Rahman ZA, Yang YH, Jalil N, Cheong SC, et al.
    Asian Pac J Cancer Prev, 2011;12(5):1161-6.
    PMID: 21875259
    Dietary isothiocyanates (ITCs) found in cruciferous vegetables (Brassica spp.) has been reported to reduce cancer risk by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). This case-control study was aimed at determining associations between dietary ITCs, GSTs polymorphisms and risk habits (cigarette smoking, alcohol drinking and betel-quid chewing) with oral cancer in 115 cases and 116 controls. Information on dietary ITC intake from cruciferous vegetables was collected via a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood lymphocytes were obtained for genotyping of GSTM1, GSTT1 and GSTP1 using PCR multiplex and PCR-RFLP. Chi-square and logistic regression were performed to determine the association of ITC and GSTs polymorphism and risk of oral cancer. When dietary ITC was categorized into high (greater than/equal to median) and low (less than median) intake, there was no significant difference between cases and control group. Logistic regression yielding odd ratios resulted in no significant association between dietary ITC intake, GSTM1, GSTT1 or GSTP1 genotypes with oral cancer risk overall. However, GSTP1 wild-type genotype was associated with later disease onset in women above 55 years of age (p= 0.017). Among the men above 45 years of age, there was clinical significant difference of 17 years in the age of onset of oral cancer between GSTP1 wild-type + low ITC intake and GSTP1 polymorphism + high ITC intake (p= 0.001). Similar conditions were also seen among men above 45 years of age with risk habits like drinking and chewing as the earlier disease onset associated with GSTP1 polymorphism and high ITC intake (p< 0.001). This study suggests that combination effects between dietary ITCs, GSTP1 polymorphism and risk habits may be associated with the risk of oral cancer and modulate the age of disease onset.
    Matched MeSH terms: Age of Onset
  16. Naidu R, Har YC, Taib NA
    APMIS, 2011 Jul;119(7):460-7.
    PMID: 21635553 DOI: 10.1111/j.1600-0463.2011.02753.x
    In the present study, we evaluated the association between the TP53BP1 Glu353Asp and T-885G polymorphisms and breast cancer risk as well as with the clinicopathological characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using PCR-RFLP method in a hospital-based Malaysian population. Breast cancer risk was not observed among women who were heterozygous (OR(adj) = 0.887; 95% CI, 0.632-1.245) or homozygous (OR(adj) = 1.083; 95% CI, 0.595-1.969) for Asp allele, and those carriers of Asp allele (OR(adj) = 0.979; 95% CI, 0.771-1.243). Similarly, women who were TG heterozygotes (OR(adj) = 1.181; 95% CI, 0.842-1.658) or GG homozygotes (OR(adj) = 1.362; 95% CI, 0.746-2.486) and carriers of G allele (OR(adj) = 1.147; 95% CI, 0.903-1.458) were not associated with increased risk of breast cancer. Asp allele genotype was significantly associated with ER negativity (p = 0.0015) and poorly differentiated tumours (p = 0.008), but G allele genotype was not associated with the clinicopathological characteristics. In conclusion, Glu353Asp and T-885G polymorphic variants might not have an influence on breast cancer risk, thus might not be potential candidates for cancer susceptibility. Glu353Asp variant might be associated with tumour aggressiveness as defined by its association with ER negativity and poorly differentiated tumours.
    Matched MeSH terms: Age of Onset
  17. Goh KJ, Tian S, Shahrizaila N, Ng CW, Tan CT
    Amyotroph Lateral Scler, 2011 Mar;12(2):124-9.
    PMID: 21039118 DOI: 10.3109/17482968.2010.527986
    Our objective was to determine the survival and prognostic factors of motor neuron disease (MND) in a multi-ethnic cohort of Malaysian patients. All patients seen at a university medical centre between January 2000 and December 2009 had their case records reviewed for demographic, clinical and follow-up data. Mortality data, if unavailable from records, were obtained by telephone interview of relatives or from the national mortality registry. Of the 73 patients, 64.4% were Chinese, 19.2% Malays and 16.4% Indians. Male: female ratio was 1.43: 1. Mean age at onset was 51.5 + 11.3 years. Onset was spinal in 75.3% and bulbar in 24.7% of the patients; 94.5% were ALS and 5.5% were progressive muscular atrophy (PMA). Overall median survival was 44.9 + 5.8 months. Ethnic Indians had shorter interval from symptom onset to diagnosis and shorter median survival compared to non-Indians. On Cox proportional hazards analysis, poor prognostic factors were bulbar onset, shorter interval from symptom onset to diagnosis and worse functional score at presentation. In conclusion, age of onset and median survival duration are similar to previous reports in Asians. Clinical features and prognostic factors are similar to other populations. In our cohort, ethnic Indians had more rapid disease course accounting for their shorter survival.
    Matched MeSH terms: Age of Onset
  18. Vicknasingam B, Narayanan S, Navaratnam V
    AIDS Care, 2009 Aug;21(8):984-91.
    PMID: 20024754 DOI: 10.1080/09540120802657530
    Despite the growing HIV threat among injecting drug users (IDUs) in Malaysia, there is a dearth of information on their HIV risk behaviour. This study focused on identifying specific risk behaviours that distinguished HIV positive IDUs from those who were not. For the first time, data on IDUs not in treatment were obtained through a cross-sectional survey of 526 subjects recruited from five selected cities across peninsular Malaysia. A structured questionnaire and face-to-face interviews were utilised to collect detailed information on their drug use practices and sexual behaviours. On-site serological testing determined their HIV and hepatitis C status. The findings indicated that ethnic Malays, who are also Muslims, form the majority of IDUs not in treatment. Bivariate analysis identified six risk factors associated with HIV seropositivity: being 44 years or younger; not holding a regular job; initiating drug use at age 23 or younger; being a morphine user; sharing injecting equipment and having multiple-sex partners. However, only the last two remained significant in multivariate analysis. That sharing contaminated injecting equipment is a significant risk factor strongly justifies the widening of the pilot needle and syringe exchange programme initiated hesitantly in late 2005 as a reaction to the worsening HIV/AIDS situation. Condom use, though not independently significant, remains important because consistent and wider use could neutralise the second risk factor--having multiple-sex partners. The finding that injecting drug use is increasingly occurring in groups underscores the need for outreach programmes that emphasise safe injecting practices in group settings. In addition, counsellors should endeavour to convince drug users to enter treatment since being in treatment appears to reduce risk behaviours. Finally, conservative Muslim unease about harm reduction must be assuaged quickly since Malay Muslims form the majority of IDUs not in treatment.
    Matched MeSH terms: Age of Onset
  19. Lim SL, Lim AK, Mumtaz M, Hussein E, Wan Bebakar WM, Khir AS
    Thyroid, 2008 Dec;18(12):1297-301.
    PMID: 19012471 DOI: 10.1089/thy.2008.0044
    The prevalence of thyroid-associated ophthalmopathy (TAO) has been reported to be lower in several Asian populations than in Caucasians. The risk factors for TAO that have been demonstrated in Caucasians have not been studied in Asian populations. The aim of this study, therefore, was to determine the prevalence, risk factors, and clinical features of TAO in a cohort of multiethnic Malaysian patients with Graves' disease (GD).
    Matched MeSH terms: Age of Onset
  20. Cross-Disorder Group of the Psychiatric Genomics Consortium
    Lancet, 2013 Apr 20;381(9875):1371-9.
    PMID: 23453885 DOI: 10.1016/S0140-6736(12)62129-1
    BACKGROUND: Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specific variants underlying genetic effects shared between the five disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia.

    METHODS: We analysed genome-wide single-nucleotide polymorphism (SNP) data for the five disorders in 33,332 cases and 27,888 controls of European ancestory. To characterise allelic effects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fitting model of relations between genotype and phenotype. We examined cross-disorder effects of genome-wide significant loci previously identified for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such effects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the five disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples.

    FINDINGS: SNPs at four loci surpassed the cutoff for genome-wide significance (p<5×10(-8)) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported effects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specificity. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all five disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers.

    INTERPRETATION: Our findings show that specific SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic effects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause.

    FUNDING: National Institute of Mental Health.

    Matched MeSH terms: Age of Onset
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