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  1. Zambahari R, Kwok OH, Javier S, Mak KH, Piyamitr S, Tri Ho HQ, et al.
    Int J Clin Pract, 2007 Mar;61(3):473-81.
    PMID: 17313616
    Several therapeutic approaches have been developed to improve the outcome among patients with acute coronary syndrome (ACS). However, treatment with antithrombotic therapies such as oral glycoprotein IIb/IIIa inhibitors has been limited by the lack of efficacy and excess bleeding complications. As the publication of the landmark study Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE), the clinical benefit of early and intermediate-term use of combined antiplatelet agents--clopidogrel plus aspirin--in non-ST-segment elevation myocardial infarction (NSTEMI) patients became evident. Pretreatment and intermediate-term therapy with clopidogrel in NSTEMI ACS patients undergoing percutaneous coronary intervention (PCI) was further supported by the PCI-CURE trial. Recently, the results of two major trials Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28, Clopidogrel and Metoprolol in Myocardial Infarction Trial established the pivotal role of clopidogrel in the other spectrum of ACS-STEMI. Coupled with the results from previous multicentre trials, these two studies provide a guide for the early and long-term use of clopidogrel in the whole spectrum of ACS. A review summarising the results of the recent clinical trials and a discussion on its implications for the clinical management of ACS is presented.
  2. Liu Y, Uemura H, Ye D, Lee JY, Chiong E, Pu YS, et al.
    Prostate Int, 2019 Sep;7(3):108-113.
    PMID: 31485435 DOI: 10.1016/j.prnil.2018.12.001
    Background: The incidence of prostate cancer (PC) in Asian countries is increasing for reasons that are not clear. Data describing how PC is diagnosed and treated are fragmented across Asia, with marked intercountry and intracountry differences in outcome and knowledge gaps in clinical diagnostic and treatment practices. To address these knowledge gaps, we have established a PC disease registry with the aim of providing a comprehensive picture of PC diagnosis, prognosis, treatment and outcome, population characteristics, and comorbidities in real-world clinical practice in Asia.

    Methods: This is a multinational, multicenter, longitudinal, and observational registry of PC patients presenting to participating tertiary-care hospitals in eight Asian countries (www.clinicaltrials.gov NCT02546908. Registry Identifier: NOPRODPCR4001). Approximately 3500-4000 eligible patients with existing or newly diagnosed high-risk localized PC (cohort 1), nonmetastatic biochemically recurrent PC (cohort 2), or metastatic PC (cohort 3) will be consecutively enrolled and followed-up for 5 years. An enrollment cap of 600 patients each will be applied to cohorts 1 and 2. Disease status is collected at enrollment, and outcome variables captured at 3-monthly intervals include diagnostic/staging, treatments including reason for change, laboratory results, comorbidities, and concomitant medications. Treatments and survival outcomes will be captured real time until study end. Patient-reported quality-of-life will be measured every 6 months, and medical resource utilization summarized at study end. Data analysis will include exploratory analyses of potential associations between multiple risk factors and socioeconomic variables with disease progression and evaluation of various treatments for PC including novel therapies on clinical outcome and health-related quality-of-life outcomes.

    Results: 3636 men with PC were enrolled until July 2018; 416 in cohort 1, 399 in cohort 2 and 2821 in cohort 3.

    Discussion: A total of 3636 patients were enrolled until July 2018. The prospective disease registry will provide comprehensive and wide-ranging real-world information on how PC is diagnosed and treated in Asia. Such information can be used to inform policy development for best practice and direct clinical study design evaluating new treatments.

  3. Mak WY, Mak OS, Lee CK, Tang W, Leung WK, Wong MTL, et al.
    J Crohns Colitis, 2018 Nov 28;12(12):1392-1398.
    PMID: 30165543 DOI: 10.1093/ecco-jcc/jjy120
    Background: The presence of perianal fistulas in Crohn's disease [CD] denotes increased disease aggressiveness. We studied the epidemiology and clinical outcomes of perianal CD [PCD] using the Hong Kong territory-wide IBD Registry [HKIBDR].

    Methods: Consecutive patients with PCD were identified from the HKIBDR, and disease characteristics, treatments, and outcomes were analysed. The risks for medical and surgical therapies were assessed using Kaplan-Meier analysis.

    Results: Among 981 patients with CD with 10530 patient-years of follow-up, 283 [28.8%] had perianal involvement, of which 120 [42.4%] were as first presentation. The mean age at diagnosis of PCD was 29.1 years, and 78.8% were male. The median follow-up duration was 106 months (interquartile range [IQR]: 65-161 months]. Perianal fistula [84.8%] and perianal abscess [52.7%] were the two commonest forms. Male, younger age at diagnosis of CD, and penetrating phenotypes were associated with development of PCD in multivariate analysis. Of 242 patients with fistulizing PCD, 70 [29.2%] required ≥5 courses of antibiotics, and 98 [40.5%] had ≥2 surgical procedures. Nine patients required defunctioning surgery and 4 required proctectomy. Eighty-four patients [34.7%] received biologics. Cumulative probabilities for use of biologics were 4.7%, 5.8%, and 8.6% at 12 months, 36 months, and 96 months, respectively, while the probabilities for surgery were 67.2%, 71.6%, and 77.7%, respectively. Five mortalities were recorded, including 2 cases of anal cancer, 2 CD-related complications, and one case of pneumonia.

    Conclusion: Over 40% of CD patients presented with perianal disease at diagnosis. Patients with PCD had poor outcome, with young age of onset, multiple antibiotic use, and repeated surgery.

  4. Machiela MJ, Hofmann JN, Carreras-Torres R, Brown KM, Johansson M, Wang Z, et al.
    Eur Urol, 2017 Nov;72(5):747-754.
    PMID: 28797570 DOI: 10.1016/j.eururo.2017.07.015
    BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.

    OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.

    DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.

    RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).

    CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.

    PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

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