Displaying publications 1 - 20 of 137 in total

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  1. Earnshaw VA, Jin H, Wickersham JA, Kamarulzaman A, John J, Lim SH, et al.
    AIDS Behav, 2016 Jan;20(1):98-106.
    PMID: 26324078 DOI: 10.1007/s10461-015-1168-x
    Men who have sex with men (MSM) living in countries with strong stigma toward MSM are vulnerable to HIV and experience significant barriers to HIV care. Research is needed to inform interventions to reduce stigma toward MSM in these countries, particularly among healthcare providers. A cross-sectional survey of 1158 medical and dental students was conducted at seven Malaysian universities in 2012. Multivariate analyses of variance suggest that students who had interpersonal contact with MSM were less prejudiced toward and had lower intentions to discriminate against MSM. Path analyses with bootstrapping suggest stereotypes and fear mediate associations between contact with prejudice and discrimination. Intervention strategies to reduce MSM stigma among healthcare providers in Malaysia and other countries with strong stigma toward MSM may include facilitating opportunities for direct, in-person or indirect, media-based prosocial contact between medical and dental students with MSM.
  2. Lim SH, Cheung DH, Guadamuz TE, Wei C, Koe S, Altice FL
    Drug Alcohol Depend, 2015 Jun 1;151:31-7.
    PMID: 25865907 DOI: 10.1016/j.drugalcdep.2015.02.040
    BACKGROUND: High prevalence of substance use among men who have sex with men (MSM) may drive the HIV epidemic in Malaysia but patterns of substance use among Malaysian MSM have not been examined. Our study investigated specific Malaysian MSM risk groups to determine the association between their substance use and sexual risk behaviors.
    METHODS: Data from Malaysian respondents (n=1235) in a large, multinational online survey of Asian MSM in 2010 were used to identify latent classes of substance use. Subsequent covariates were included in a joint model to predict class membership.
    RESULTS: The 3-class model was identified as the best fitting model, which included: (1) 'negligible substance use' for those reporting none or using any substance sparingly; (2) 'soft substance use' for those using poppers, ecstasy and drinking before sex; and (3) 'amphetamine-type stimulant (ATS) use' for those using stimulants (methamphetamine, ecstasy), erectile dysfunction drugs and recreational drug use before sex. Men in the 'ATS use' category were significantly less likely to not know their HIV status (AOR: 0.30, 95%CI: 0.14,0.66), more likely to have had more than 6 male sex partners (AOR: 4.83, 95% CI: 1.92-12.2), to have group sex (AOR:4.07, 95% CI: 2.31-7.15), to report inconsistent condom use (AOR:2.01, 95% CI: 1.12-3.60), to be HIV-infected (AOR:3.92, 95% CI: 1.63-8.42) and to have had any sexually transmitted infections (AOR:3.92, 95% CI:1.70, 9.08), compared to men in the 'negligible substance use' category.
    CONCLUSIONS: Our study identified subgroups of Malaysian MSM with distinct substance use patterns and HIV-related risk profiles, which provides implication for targeting HIV prevention in this subpopulation.
  3. Lim SH, Akbar M, Wickersham JA, Kamarulzaman A, Altice FL
    Int J Drug Policy, 2018 05;55:256-262.
    PMID: 29605540 DOI: 10.1016/j.drugpo.2018.02.019
    BACKGROUND: The intentional use of illicit drugs for sexual purposes (also known as 'chemsex') is well known within the MSM communities in Malaysia although research in this population is scarce primarily because both drug use and homosexuality are illegal and stigmatised in Malaysia.

    METHODS: From April to December 2014, interviews were conducted with twenty men (age range 21-43) living in Greater Kuala Lumpur who had sexual intercourse with other men in the past 6 months and who used illicit drugs at least monthly in the past 3 months. Fourteen men were recruited via gay social networking smartphone applications or websites while six were referred by the participants. Data were analsed using thematic analytic approach.

    FINDINGS: The average duration of illicit drug use was 6.4 years (range 1-21) and all participants were using methamphetamine ("ice" or crystal meth) with frequency of use ranged from daily to once a month. Participants came from diverse ethnic, economic, and occupational backgrounds. Most participants used an inhalation apparatus ("bong") to consume methamphetamine and injection was rare in the sample. The primary motivation of methamphetamine use was to increase sexual capacity, heighten sexual pleasure and enhance sexual exploration and adventurism. Socializing with friends ("chilling"), and increased energy for work were secondary motivations. Participants emphasized the need to control the use of methamphetamine and some have established rules to control the amount and duration of use and a minority of men have maintained condom use during anal sex while under the influence of methamphetamine. Participants who professed to be in control of their drug use characterized themselves as functional users regardless of the health and social consequences from continuing use. Overall, participants perceived themselves differently from the traditional opioid users and reported limited access to sexual health and substance use treatment services.

    CONCLUSION: There is a need to increase access to HIV prevention services such as PrEP and PEP, professional support, and substance abuse treatment for drug-using MSM. A more open and friendly environment towards drug-using MSM may help them access and engage with the health services.

  4. Ghani MA, Brown SE, Khan F, Wickersham JA, Lim SH, Dhaliwal SK, et al.
    Int J Drug Policy, 2015 Feb;26(2):175-82.
    PMID: 25577322 DOI: 10.1016/j.drugpo.2014.10.002
    BACKGROUND: In Malaysia, compulsory drug detention centres (CDDCs) hold suspected drug users for two years without adjudication. Acute detoxification without healthcare access has been documented. CDDCs are criticized globally due to ineffectiveness in treating addiction and human rights violations. In response, the Malaysian government began transitioning these facilities into voluntary drug treatment centres known as "Cure and Care" (C&C) centres that embrace a holistic treatment-based approach to drug addiction rehabilitation.

    METHODS: An explorative qualitative study was undertaken to explore patient perspectives and satisfaction regarding treatment and services at the new Cure and Care centre in Kota Bharu, Malaysia. A convenience sample of 20 patients was recruited to participate in semi-structured in-depth interviews. Content analysis was used to identify the salient themes.

    RESULTS: Patients identified methadone treatment, psychosocial programs, religious instruction, and recreational activities as important factors contributing to treatment success for addressing both health and addiction needs. Though many had previously been in a CDDC, adherence to treatment in the C&C centre was perceived to be facilitated by the degree of social support, the voluntary nature and the array of new programs available for selection.

    CONCLUSION: C&Cs represents a dramatic shift in the Malaysian government's approach to drug addiction. Our findings demonstrate positive patient experiences associated with the holistic treatment-based approach of these centres. This exploratory study provides additional evidence to document this ongoing policy transition and may guide continued expansion of new holistic drug treatment programs across the country.

  5. Khan F, Krishnan A, Ghani MA, Wickersham JA, Fu JJ, Lim SH, et al.
    Subst Use Misuse, 2018 01 28;53(2):249-259.
    PMID: 28635521 DOI: 10.1080/10826084.2016.1267217
    BACKGROUND: As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services.

    OBJECTIVES: We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan.

    METHODS: In June-July 2012, a cross-sectional convenience survey of 96 C&C inpatients and outpatients who entered treatment >30 days previously was conducted to assess drug use, criminal justice experience, medical co-morbidities, motivation for seeking treatment, and attitudes towards the C&C. Drug use was compared for the 30-day-period before C&C entry and the 30-day-period before the interview.

    RESULTS: Self-reported drug use levels decreased significantly among both inpatient and outpatient clients after enrolling in C&C treatment. Higher levels of past drug use, lower levels of social support, and more severe mental health issues were reported by participants who were previously imprisoned. Self-reported satisfaction with C&C treatment services was high. Conclusions/Importance: Preliminary evidence of reduced drug use and high levels of client satisfaction among C&C clients provide support for Malaysia's ongoing transition from compulsory drug detention centers (CDDCs) to these voluntary drug treatment centers. If C&C centers are successful, Malaysia plans to gradually transition away from CDDCs entirely.
  6. Earnshaw VA, Cox J, Wong PL, Saifi R, Walters S, Azwa I, et al.
    AIDS Behav, 2023 Jul;27(7):2055-2069.
    PMID: 36463390 DOI: 10.1007/s10461-022-03938-5
    Photovoice is an action-oriented qualitative method involving photography and story-telling. Although photovoice yields a powerful form of data that can be leveraged for research, intervention, and advocacy, it has arguably been underutilized within HIV research. Online, asynchronous photovoice methods represent a promising alternative to traditional in-person methods, yet their acceptability and feasibility with key populations and people living with HIV (PLWH) have yet to be explored. The current study describes the methods and evaluation of an online, asynchronous photovoice project conducted with 34 members of key populations and PLWH in Malaysia in 2021. A HIPAA-compliant website incorporating a series of instructional videos was created to facilitate participant engagement and data collection. Quantitative and qualitative indicators suggest that participants found the project to be highly acceptable and feasible. Online, asynchronous photovoice methods hold potential for increasing the scale of this powerful and versatile qualitative research method with key populations and PLWH.
  7. Ho WK, Tan MM, Mavaddat N, Tai MC, Mariapun S, Li J, et al.
    Nat Commun, 2020 07 31;11(1):3833.
    PMID: 32737321 DOI: 10.1038/s41467-020-17680-w
    Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.
  8. Lim SH, Mburu G, Bourne A, Pang J, Wickersham JA, Wei CKT, et al.
    PLoS One, 2017;12(9):e0182838.
    PMID: 28902857 DOI: 10.1371/journal.pone.0182838
    OBJECTIVE: We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia.

    METHODS: An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants' demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP.

    RESULTS: Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals.

    CONCLUSIONS: Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services.

  9. Lim SH, Brown SE, Shaw SA, Kamarulzaman A, Altice FL, Beyrer C
    J Homosex, 2020;67(1):104-126.
    PMID: 30307803 DOI: 10.1080/00918369.2018.1525946
    Malay-Muslim men who have sex with men (MSM) are marginalized and hidden in Malaysia, a predominantly Muslim country in southeast Asia. We explored the policy, network, community, and individual factors related to HIV infection among Malay-Muslim MSM through 26 in-depth interviews and one focus group discussion (n = 5) conducted in Kuala Lumpur and Kota Bharu between October 2013 and January 2014. As religion plays an important role in their lives, participants viewed homosexuality as a sin. Low risk perception and misconceptions about HIV/AIDS were common, and most participants expressed reluctance to consult a doctor unless they had symptoms. Additionally, buying condoms was embarrassing and anxiety-producing. Fear of discrimination by health care providers and community hindered participants from disclosing sexual behaviors and accessing health services. Homophobic comments and policies by the government and religious leaders were concerns of participants. A safe and enabling environment is needed to reduce HIV risks among Malay-Muslim MSM.
  10. Chong SCS, Hollingshead BM, Lim SH, Bourne A
    Glob Public Health, 2021 07;16(7):1014-1027.
    PMID: 32985388 DOI: 10.1080/17441692.2020.1822901
    The Malaysian government has committed to 'Fast Tracking the HIV Response' to achieve UNAIDS 2030 targets to end AIDS. The epidemic is concentrated among key populations and has shifted from people who inject drugs to HIV infection through sexual transmission among men who have sex with men, sex workers and transgender people. The aim of this scoping review was to examine social and behavioural research published since 2005 that can inform understanding of each stage of the 90:90:90 treatment cascade (as proposed by UNAIDS), including HIV risk behaviours and testing practices that precede entry. We found a concentration of studies related to predictors or correlates of HIV infections (mostly among men who have sex with men) and a shortfall in literature pertaining to sex workers or transgender people. While several studies examined factors associated with HIV testing, only one examined uptake of antiretroviral therapy and two explored issues of treatment adherence. No study examined broader care and support of people living with HIV. To scale-up effective programmes and apprise investment to achieve the ambitious targets set-out in the Malaysian National HIV/AIDS Strategic Plan, a combination of comprehensive strategic information and evidence generated through primary research is critical.
  11. Kwan P, Cabral-Lim L, D'Souza W, Jain S, Lee BI, Liao W, et al.
    Epilepsia, 2015 May;56(5):667-73.
    PMID: 25823580 DOI: 10.1111/epi.12957
    The Asia-Oceanian region is the most populous region in the world. Although there has been substantial economic development and improvement in health services in recent years, epilepsy remains generally an underrecognized and understudied condition. To help promote research in the region, the Commission on Asian and Oceanian Affairs (CAOA) of the International League Against Epilepsy (ILAE) appointed the Research Task Force (RTF) to facilitate the development of research priorities for the region. Research that focuses on issues that are unique or of particular importance in the Asia-Oceanian region is encouraged, and that captures the impact of the dynamic socioeconomic changes taking place in the region is emphasized. Based on these considerations, we propose research "dimensions" as priorities within the Asia-Oceanian region. These are studies (1) that would lead to fuller appreciation of the health burden of epilepsy, particularly the treatment gap; (2) that would lead to better understanding of the causes of epilepsy; (3) that would alleviate the psychosocial consequences of epilepsy; (4) that would develop better therapies and improved therapeutic outcomes; and (5) that would improve the research infrastructure.
  12. Tang RY, Lim SH, Lam JE, Nurasykin S, Eileen T, Chan YW
    Med J Malaysia, 2019 12;74(6):472-476.
    PMID: 31929471
    INTRODUCTION: Melioidosis is caused by Burkholderia pseudomallei, a gram-negative aerobic bacillus, found in the soil and surface water. Treating melioidosis has been a challenge in district hospitals due to high usage of broad spectrum antibiotics and prolonged hospitalisation. This study is to review the patients' demography, clinical presentations and microbiological data.

    METHODS: A 5-year retrospective study was carried out on patients admitted with culture positive for melioidosis from year 2013 to 2017 in Hospital Teluk Intan, Perak.

    RESULTS: There were a total of 46 confirmed cases of melioidosis. Majority of the patients were working in the agricultural and farming (28.6%), and factories (25.7%). Thirty-one patients had diabetes mellitus (71.1%). Presentations of patients with melioidosis included pneumonia (54.3%), skin and soft tissue infection (19.6%), deep abscesses (15.2%) and bone and joint infections (13%). An average of 5.8 days was needed to confirm the diagnosis of melioidosis via positive culture. However, only 39.4% of these patients were started on ceftazidime or carbapenem as the empirical therapy. The intensive care unit (ICU) admission rate for melioidosis was 46% and the mortality rate was 52%. Our microbial cultures showed good sensitivity towards cotrimoxazole (97.1%), ceftazidime (100%) and carbapenem (100%).

    CONCLUSION: Melioidosis carries high mortality rate, especially with lung involvement and bacteremia. Physicians should have high clinical suspicion for melioidosis cases to give appropriate antimelioidosis therapy early.

  13. Kuan JW, Su AT, Wong SP, Sim XY, Toh SG, Ong TC, et al.
    Transfus Apher Sci, 2015 Oct;53(2):196-204.
    PMID: 25910537 DOI: 10.1016/j.transci.2015.03.017
    There are few randomized trials comparing filgrastim and pegfilgrastim in peripheral blood stem cell mobilization (PBSCM). None of the trials studied the effects of the timing of pegfilgrastim administration on the outcomes of mobilization. We conducted a randomized triple blind control trial comparing the outcomes of filgrastim 5 µg/kg daily from day 3 onwards, 'early' pegfilgrastim 6 mg on day 3 and 'delayed' pegfilgrastim 6 mg on day 7 in cyclophosphamide PBSCM in patients with no previous history of mobilization. Peripheral blood (PB) CD34+ cell count was checked on day 8 and day 11 onward. Apheresis was started when PB CD34+ ≥ 10/µl from day 11 onward. The primary outcome was the successful mobilization rate, defined as cumulative collection of ≥2 × 10(6)/kg CD34+ cells in three or less apheresis. The secondary outcomes were the day of neutrophil and platelet engraftment post transplantation. There were 156 patients randomized and 134 patients' data analyzed. Pegfilgrastim 6 mg day 7 produced highest percentage of successful mobilization, 34 out of 48 (70.8%) analyzed patients, followed by daily filgrastim, 28 out of 44 (63.6%) and day 3 pegfilgrastim, 20 out of 42 (47.6%) (p = 0.075). Pegfilgrastim day 7 and daily filgrastim reported 1.48 (p = 0.014) and 1.49 (p = 0.013) times higher successful mobilization rate respectively as compared to pegfilgrastim day 3 after adjusting for disease, gender and exposure to myelotoxic agent. Multiple myeloma patients were three times more likely to achieve successful mobilization as compared to acute leukemia or lymphoma patients. Pegfilgrastim avoided the overshoot of white cells compared to filgrastim. There was no difference in the duration of both white cells and platelet recovery post transplantation between the three interventional arms.
  14. Yap YY, Law KB, Sathar J, Lau NS, Goh AS, Chew TK, et al.
    Exp Hematol Oncol, 2018;7:31.
    PMID: 30564475 DOI: 10.1186/s40164-018-0124-7
    Background: The evolution of molecular studies in myeloproliferative neoplasms (MPN) has enlightened us the understanding of this complex disease consisting of polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The epidemiology is well described in the western world but not in Asian countries like Malaysia.

    Materials and methods: This retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia.

    Results: A total of 1010 patients were registered over a period of 5 years. The mean age was 54 years with male predominance. The ethnic distribution revealed that Chinese had a relatively high weighted incidence proportion (43.2%), followed by Indian (23.8%), Malay (15.8%) and other ethnic groups (17.2%). The types of MPN reported were 40.4% of ET (n = 408), 38.1% of PV (n = 385), 9.2% of PMF (n = 93), 3.1% of hypereosinophilic syndrome (HES) (n = 31) and 7.9% of unclassifiable MPN (MPN-U) (n = 80). Splenomegaly was only palpable clinically in 32.2% of patients. The positive JAK2 V617F mutation was present in 644 patients with 46.6% in PV, 36.0% in ET, 9.0% in PMF, and 7.4% in MPN-U, and had significantly lower haemoglobin (p 

  15. Yap IK, Kho MT, Lim SH, Ismail NH, Yam WK, Chong CW
    Mol Biosyst, 2015 Jan;11(1):297-306.
    PMID: 25382376 DOI: 10.1039/c4mb00463a
    Understanding the basal gut bacterial community structure and the host metabolic composition is pivotal for the interpretation of laboratory treatments designed to answer questions pertinent to host-microbe interactions. In this study, we report for the first time the underlying gut microbiota and systemic metabolic composition in BALB/c mice during the acclimatisation period. Our results showed that stress levels were reduced in the first three days of the study when the animals were subjected to repetitive handling daily but the stress levels were increased when handling was carried out at lower frequencies (weekly). We also observed a strong influence of stress on the host metabolism and commensal compositional variability. In addition, temporal biological compartmental variations in the responses were observed. Based on these results, we suggest that consistency in the frequency and duration of laboratory handling is crucial in murine models to minimise the impact of stress levels on the commensal and host metabolism dynamics. Furthermore, caution is advised in consideration of the temporal delay effect when integrating metagenomics and metabonomics data across different biological matrices (i.e. faeces and urine).
  16. Voon SH, Kiew LV, Lee HB, Lim SH, Noordin MI, Kamkaew A, et al.
    Small, 2014 Dec 29;10(24):4993-5013.
    PMID: 25164105 DOI: 10.1002/smll.201401416
    Animal models, particularly rodents, are major translational models for evaluating novel anticancer therapeutics. In this review, different types of nanostructure-based photosensitizers that have advanced into the in vivo evaluation stage for the photodynamic therapy (PDT) of cancer are described. This article focuses on the in vivo efficacies of the nanostructures as delivery agents and as energy transducers for photosensitizers in animal models. These materials are useful in overcoming solubility issues, lack of tumor specificity, and access to tumors deep in healthy tissue. At the end of this article, the opportunities made possible by these multiplexed nanostructure-based systems are summarized, as well as the considerable challenges associated with obtaining regulatory approval for such materials. The following questions are also addressed: (1) Is there a pressing demand for more nanoparticle materials? (2) What is the prognosis for regulatory approval of nanoparticles to be used in the clinic?
  17. Kok ESK, Lim XJ, Chew SX, Ong SF, See LY, Lim SH, et al.
    BMC Oral Health, 2021 03 12;21(1):116.
    PMID: 33711992 DOI: 10.1186/s12903-021-01470-x
    BACKGROUND: Compare antimicrobial efficacy of a quarternary ammonium silane (QAS)/k21 as an intracanal medicament against E. faecalis and C. albicans biofilms formed on root dentin.

    METHODOLOGY: Dentin blocks were sterilized and E. faecalis and C. albicans microbial colonies were counted for colony-forming-units against 2%k21, 2%CHX and Ca(OH)2 medicaments. Biofilm colonies after 7 days on dentin were analysed using confocal laser scanning microscopy with live/dead bacterial viability staining. TEM was done to study dentin collagen matrix. Dentin discs from 3rd day and 7th day well plate was used for Raman spectra and observed under fluorescent-microscope. Docking studies were carried out on MMP-2 S1 binding-domain with k21.

    RESULTS: There was reduction of E. faecalis/C. albicans when k21, chlorhexidine and calcium hydroxide were used with highest percentage in 2%k21 treated specimens. 2%k21 showed dense and regular collagen network with intact cross-banding and decreased Raman intensity for 2%k21 on 3rd day. NaOCl + k21 showed least adherence, whereas saline groups showed highest adherence of E. faecalis and C. albicans to root-canal dentin. Alizarin red staining of hDPSCs revealed calcium deposition in all groups with significant difference seen amongst 2%k21 groups. MMP-2 ligand binding was seen accurately indicating possible target sites for k21 intervention.

    CONCLUSION: 2%k21 can be considered as alternative intracanal medicament.

  18. Breast Cancer Association Consortium, Mavaddat N, Dorling L, Carvalho S, Allen J, González-Neira A, et al.
    JAMA Oncol, 2022 Mar 01;8(3):e216744.
    PMID: 35084436 DOI: 10.1001/jamaoncol.2021.6744
    IMPORTANCE: Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction.

    OBJECTIVE: To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies.

    DESIGN, SETTING, AND PARTICIPANTS: The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991 and 2016. Sequencing and analysis took place between 2016 and 2021.

    EXPOSURES: Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53.

    MAIN OUTCOMES AND MEASURES: The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes.

    RESULTS: The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1 (11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)+ERBB2- high-grade subtype (OR, 4.99; 95% CI, 3.68-6.76). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32; 95% CI, 40.51-75.55). BRCA2 and PALB2 variants were also associated with triple-negative disease. TP53 variants were most strongly associated with HR+ERBB2+ and HR-ERBB2+ subtypes. Tumors occurring in pathogenic variant carriers were of higher grade. For most genes and subtypes, a decline in ORs was observed with increasing age. Together, the 9 genes were associated with 27.3% of all triple-negative tumors in women 40 years or younger.

    CONCLUSIONS AND RELEVANCE: The results of this case-control study suggest that variants in the 9 BC risk genes differ substantially in their associated pathology but are generally associated with triple-negative and/or high-grade disease. Knowing the age and tumor subtype distributions associated with individual BC genes can potentially aid guidelines for gene panel testing, risk prediction, and variant classification and guide targeted screening strategies.

  19. Tan HY, Yong YK, Lim SH, Ponnampalavanar S, Omar SF, Pang YK, et al.
    Sex Health, 2014 Dec;11(6):532-9.
    PMID: 25200957 DOI: 10.1071/SH14093
    Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication of antiretroviral therapy (ART) in countries with high rates of endemic TB, but data from South-East Asia are incomplete. Identification of prevalence, risk factors and treatment outcomes of TB-IRIS in Malaysia was sought.

    METHODS: A 3-year retrospective study was conducted among TB-HIV co-infected patients treated at the University of Malaya Medical Centre. Simple and adjusted logistic regressions were used to identify the predictors for TB-IRIS while Cox regression was used to assess the influence of TB-IRIS on long-term CD4 T-cell recovery.

    RESULTS: One hundred and fifty-three TB-HIV patients were enrolled, of whom 106 had received both anti-TB treatment (ATT) and ART. The median (IQR) baseline CD4 T-cell count was 52 cells μL(-1) (13-130 cells μL(-1)). Nine of 96 patients (9.4%) developed paradoxical TB-IRIS and eight developed unmasking TB-IRIS, at a median (IQR) time of 27 (12-64) and 19 (14-65) days, respectively. In adjusted logistic regression analysis, only disseminated TB was predictive of TB-IRIS [OR: 10.7 (95% CI: 1.2-94.3), P=0.032]. Mortality rates were similar for TB-IRIS (n=1, 5.9%) and non-TB-IRIS (n=5, 5.7%) patients and CD4 T-cell recovery post-ART was not different between the two groups (P=0.363).

    CONCLUSION: Disseminated TB was a strong independent predictor of TB-IRIS in Malaysian HIV-TB patients after commencing ART. This finding underscores the role of a high pathogen load in the pathogenesis of TB-IRIS; so interventions that reduce pathogen load before ART may benefit HIV patients with disseminated TB.

  20. Tan TL, Lim SH, Ruslan Mustapa M, Ganeswary R
    Med J Malaysia, 2020 11;75(6):742-744.
    PMID: 33219189
    Methicillin-resistant Staphylococcus aureus (MRSA) purulent pericarditis, characterised by frank pus collection or microscopic pyogenic effusion in the pericardium represents the most serious form of pericardial infection. The route of MRSA acquisition in pericardial abscess commonly occurs via the blood stream infection and it is more commonly observed among immunocompromised individuals. To date, diabetic foot ulcer infection rarely disseminates and becomes a nidus for pericardial infection. Herein, we report an unusual case of MRSA pericardial abscess in a 44-year-old man who presented at Hospital Seri Manjung, Malaysia with cardiac tamponade. Past medical history indicated that he was recently treated for infected diabetic foot ulcer with MRSA bacteraemia one week earlier. Despite adequate pericardial drainage and extended parenteral vancomycin therapy, this case ended in fatality on day 42 of admission due to nosocomial infection. It is hoped that this report serves to increase the vigilance among clinicians that diabetic foot ulcer infections have the potential to progress to pericardial abscess in the presence of MRSA bacteraemia, although they may appear seemingly innocuous at presentation. Systemic vancomycin must be instituted promptly when MRSA bacteraemia is confirmed in order to circumvent the propagation of MRSA.
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