Displaying publications 1 - 20 of 97 in total

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  1. Zanaruddin SN, Saleh A, Yang YH, Hamid S, Mustafa WM, Khairul Bariah AA, et al.
    Hum Pathol, 2013 Mar;44(3):417-26.
    PMID: 23026198 DOI: 10.1016/j.humpath.2012.06.007
    The presence of lymph node (LN) metastasis significantly affects the survival of patients with oral squamous cell carcinoma (OSCC). Successful detection and removal of positive LNs are crucial in the treatment of this disease. Current evaluation methods still have their limitations in detecting the presence of tumor cells in the LNs, where up to a third of clinically diagnosed metastasis-negative (N0) patients actually have metastasis-positive LNs in the neck. We developed a molecular signature in the primary tumor that could predict LN metastasis in OSCC. A total of 211 cores from 55 individuals were included in the study. Eleven proteins were evaluated using immunohistochemical analysis in a tissue microarray. Of the 11 biomarkers evaluated using receiver operating curve analysis, epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2/neu), laminin, gamma 2 (LAMC2), and ras homolog family member C (RHOC) were found to be significantly associated with the presence of LN metastasis. Unsupervised hierarchical clustering-demonstrated expression patterns of these 4 proteins could be used to differentiate specimens that have positive LN metastasis from those that are negative for LN metastasis. Collectively, EGFR, HER-2/neu, LAMC2, and RHOC have a specificity of 87.5% and a sensitivity of 70%, with a prognostic accuracy of 83.4% for LN metastasis. We also demonstrated that the LN signature could independently predict disease-specific survival (P = .036). The 4-protein LN signature validated in an independent set of samples strongly suggests that it could reliably distinguish patients with LN metastasis from those who were metastasis-free and therefore could be a prognostic tool for the management of patients with OSCC.
    Matched MeSH terms: Kaplan-Meier Estimate
  2. Yusoff FM, Kajikawa M, Matsui S, Hashimoto H, Kishimoto S, Maruhashi T, et al.
    Sci Rep, 2019 05 22;9(1):7711.
    PMID: 31118440 DOI: 10.1038/s41598-019-44176-5
    Critical limb ischemia (CLI) is associated with a high risk of limb amputation. It has been shown that cell therapy is safe and has beneficial effects on ischemic clinical symptoms in patients with CLI. The aim of this study was to further investigate the outcomes of intramuscular injection of autologous bone-marrow mononuclear cells (BM-MNCs) in a long-term follow-up period in atherosclerotic peripheral arterial disease (PAD) patients who have no optional therapy. This study was a retrospective and observational study that was carried out to evaluate long-term clinical outcomes in 42 lower limbs of 30 patients with atherosclerotic PAD who underwent BM-MNC implantation. The median follow-up period was 9.25 (range, 6-16) years. The overall amputation-free rates were 73.0% at 5 years after BM-MNC implantation and 70.4% at 10 years in patients with atherosclerotic PAD. The overall amputation-free rates at 5 years and at 10 years after implantation of BM-MNCs were significantly higher in atherosclerotic PAD patients than in internal controls and historical controls. There were no significant differences in amputation rates between the internal control group and historical control group. The rate of overall survival was not significantly different between the BM-MNC implantation group and the historical control group. Implantation of autologous BM-MNCs is feasible for a long-term follow-up period in patients with CLI who have no optional therapy.
    Matched MeSH terms: Kaplan-Meier Estimate
  3. Yee HA, Loh HS, Ng CG
    Int J Psychiatry Clin Pract, 2013 Oct;17(4):292-7.
    PMID: 23170840 DOI: 10.3109/13651501.2012.752012
    To determine the prevalence of alcohol-use disorder and associated correlates amongst bipolar patients in a university hospital in Malaysia.
    Matched MeSH terms: Kaplan-Meier Estimate
  4. Yakubu ML, Yusop Z, Yusof F
    ScientificWorldJournal, 2014;2014:361703.
    PMID: 25126597 DOI: 10.1155/2014/361703
    This paper presents the modelled raindrop size parameters in Skudai region of the Johor Bahru, western Malaysia. Presently, there is no model to forecast the characteristics of DSD in Malaysia, and this has an underpinning implication on wet weather pollution predictions. The climate of Skudai exhibits local variability in regional scale. This study established five different parametric expressions describing the rain rate of Skudai; these models are idiosyncratic to the climate of the region. Sophisticated equipment that converts sound to a relevant raindrop diameter is often too expensive and its cost sometimes overrides its attractiveness. In this study, a physical low-cost method was used to record the DSD of the study area. The Kaplan-Meier method was used to test the aptness of the data to exponential and lognormal distributions, which were subsequently used to formulate the parameterisation of the distributions. This research abrogates the concept of exclusive occurrence of convective storm in tropical regions and presented a new insight into their concurrence appearance.
    Matched MeSH terms: Kaplan-Meier Estimate
  5. Yakub MA, Dillon J, Krishna Moorthy PS, Pau KK, Nordin MN
    Eur J Cardiothorac Surg, 2013 Oct;44(4):673-81.
    PMID: 23447474 DOI: 10.1093/ejcts/ezt093
    Contemporary experience with mitral valve (MV) repair in the rheumatic population is limited. We aimed to examine the long-term outcomes of rheumatic MV repair, to identify the predictors of durability and to compare the repair for rheumatic and degenerative MVs.
    Matched MeSH terms: Kaplan-Meier Estimate
  6. Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al.
    Ann Oncol, 2015 Sep;26(9):1883-1889.
    PMID: 26105600 DOI: 10.1093/annonc/mdv270
    BACKGROUND: The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

    PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.

    RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.

    CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

    Matched MeSH terms: Kaplan-Meier Estimate
  7. Wu YL, Lee V, Liam CK, Lu S, Park K, Srimuninnimit V, et al.
    Lung Cancer, 2018 12;126:1-8.
    PMID: 30527172 DOI: 10.1016/j.lungcan.2018.10.004
    OBJECTIVE: Patients with advanced non-small-cell lung cancer (NSCLC) with an adenocarcinoma component are recommended to undergo epidermal growth factor receptor (EGFR) mutation testing when being considered for EGFR targeted therapy. We conducted an exploratory analysis to inform the clinical utility of EGFR mutation testing in blood cell-free DNA using the cobas®EGFR Mutation Test v2.

    MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.

    RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.

    CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.

    Matched MeSH terms: Kaplan-Meier Estimate
  8. Wong KK, Gascoyne DM, Soilleux EJ, Lyne L, Spearman H, Roncador G, et al.
    Oncotarget, 2016 Aug 16;7(33):52940-52956.
    PMID: 27224915 DOI: 10.18632/oncotarget.9507
    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL.
    Matched MeSH terms: Kaplan-Meier Estimate
  9. Wong KK, Ch'ng ES, Loo SK, Husin A, Muruzabal MA, Møller MB, et al.
    Exp Mol Pathol, 2015 Dec;99(3):537-45.
    PMID: 26341140 DOI: 10.1016/j.yexmp.2015.08.019
    Huntingtin-interacting protein 1-related (HIP1R) is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. We have previously shown that low HIP1R protein expression was associated with poorer survival in diffuse large B-cell lymphoma (DLBCL) patients from Denmark treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In this multicenter study, we extend these findings and validate the prognostic and subtyping utility of HIP1R expression at both transcript and protein level. Using data mining on three independent transcriptomic datasets of DLBCL, HIP1R transcript was preferentially expressed in germinal center B-cell (GCB)-like DLBCL subtype (P<0.01 in all three datasets), and lower expression was correlated with worse overall survival (OS; P<0.01) and progression-free survival (PFS; P<0.05) in a microarray-profiled DLBCL dataset. At the protein level examined by immunohistochemistry, HIP1R expression at 30% cut-off was associated with GCB-DLBCL molecular subtype (P=0.0004; n=42), and predictive of OS (P=0.0006) and PFS (P=0.0230) in de novo DLBCL patients treated with R-CHOP (n=73). Cases with high FOXP1 and low HIP1R expression frequency (FOXP1(hi)/HIP1R(lo) phenotype) exhibited poorer OS (P=0.0038) and PFS (P=0.0134). Multivariate analysis showed that HIP1R<30% or FOXP1(hi)/HIP1R(lo) subgroup of patients exhibited inferior OS and PFS (P<0.05) independently of the International Prognostic Index. We conclude that HIP1R expression is strongly indicative of survival when utilized on its own or in combination with FOXP1, and the molecule is potentially applicable for subtyping of DLBCL cases.
    Matched MeSH terms: Kaplan-Meier Estimate
  10. Wong HY, Wong PL, Bador MK, Chong ML, Shenoi S, Rozanova J, et al.
    J Acquir Immune Defic Syndr, 2023 May 01;93(1):64-72.
    PMID: 36716735 DOI: 10.1097/QAI.0000000000003169
    BACKGROUND: In resource-limited settings, HIV-related services are often targeted to younger key populations, although increasing reports have found that adults ≥50 years now account for among the highest increase in new HIV diagnosis. We assessed the proportion of new HIV infections among older adults (≥50 years) and compared their sociodemographics, risk behaviors, and HIV-related outcomes to newly diagnosed younger adults (<50 years).

    METHODS: This retrospective analysis included all new HIV diagnosis from 2016 to 2019 at the University of Malaya Medical Centre, Malaysia. Trends of HIV diagnosis was assessed using join point regression analysis, and characteristics between the older and younger adults were compared using χ 2 test or Mann-Whitney U test. Kaplan-Meier analysis and log-rank test were used to compare the survival probability in both age groups.

    RESULTS: From a total of 594 new HIV diagnosis between 2016 and 2019, 11.5% (N = 68) were among older adults with an annual percent increase of 5.50%. Older adults were more likely ethnic Indians ( P < 0.001), acquired HIV through heterosexual contact ( P = 0.001), had late presentation to care ( P = 0.003), and multimorbidity ( P < 0.001). Immunological responses after 12 months on antiretroviral therapy were comparable in both the groups. Older adults had a higher probability of death compared with younger adults (adjusted hazard ratio 1.81, 95% confidence interval: 1.02 to 3.23, P = 0.043) after adjusting for sex, mode of HIV transmission, late presentation to care, antiretroviral therapy initiation, and multimorbidity.

    CONCLUSION: Older adults diagnosed with HIV were associated with late care presentation and increased mortality. There is an urgent need to enhance uptake of HIV testing and linkage to care among older individuals in our setting.

    Matched MeSH terms: Kaplan-Meier Estimate
  11. Wong FY, Yip CS, Chua ET
    World J Surg, 2012 Feb;36(2):287-94.
    PMID: 22105650 DOI: 10.1007/s00268-011-1353-7
    BACKGROUND: We investigated the implications of HER2 amplification in Asian women with small, node-negative breast cancer in low- and middle-income countries (LMCs).
    METHODS: We reviewed the charts patients treated between 1989 and 2009 with breast conservation therapy for node-negative breast cancers measuring ≤ 2 cm. Disease-free survival (DFS), ipsilateral breast tumor recurrence (IBTR), distant disease-free survival (DDFS), and overall survival (OS) rates were estimated using the Kaplan-Meier method and were compared by the log-rank test. Potential covariates-age, tumor grade, hormone receptor status--were analyzed by multivariate analysis.
    RESULTS: A total of 519 patients were studied including 204 (39%) and 315 (61%) patients diagnosed with pT1ab and pT1c tumors, respectively. Median follow-up was 57 months. HER2 amplification was found in 17.1% of all patients and in 16.7% patients with pT1ab tumors. Among patients with T1ab tumors, 73.0 and 9.3% underwent adjuvant hormonal and chemotherapy, respectively; 3 of 34 T1ab patients with HER2-amplified tumors received trastuzumab. HER2 amplification was associated with poorer 5-year DFS (83.7% vs. 95.5%, P < 0.0001), DDFS (87.5% vs. 97.9%, P < 0.0001), and IBTR (8.6% vs. 2.1%, P < 0.0001) rates in patients with pT1 tumors. Multivariate analysis showed that HER2 amplification remained a significant negative prognostic factor for DFS [hazard ratio (HR) 4.1, 95% confidence interval (CI) 2.1-7.8, P < 0.0001], DDFS (HR 6.3, 95% CI 2.4-17.0, P < 0.0001), and IBTR (HR 4.5, 95% CI 2.0-10.0, P < 0.0001) rates. In the pT1ab subgroup, univariate analysis showed that HER2 amplification prognosticated for DFS (85.1% vs. 95.7%, P = 0.022) and IBTR (14.9% vs. 3.5%, P = 0.004) rates but not for the OS (100% vs. 99.2%, P = 0.487) rate. Similar results were obtained after excluding patients given trastuzumab.
    CONCLUSIONS: The decision to use trastuzumab in HER2-amplified pT1ab tumors must balance their poor outcome against intrinsic financial limitations in LMCs. Patient selection criteria needs fine-tuning, and resource-sensitive regimens must be explored.
    Matched MeSH terms: Kaplan-Meier Estimate
  12. Windecker S, Latib A, Kedhi E, Kirtane AJ, Kandzari DE, Mehran R, et al.
    N Engl J Med, 2020 03 26;382(13):1208-1218.
    PMID: 32050061 DOI: 10.1056/NEJMoa1910021
    BACKGROUND: Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited.

    METHODS: In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus-coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority.

    RESULTS: A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drug-coated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P = 0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P = 0.007 for noninferiority).

    CONCLUSIONS: Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.).

    Matched MeSH terms: Kaplan-Meier Estimate
  13. Wickersham JA, Zahari MM, Azar MM, Kamarulzaman A, Altice FL
    Drug Alcohol Depend, 2013 Sep 1;132(1-2):378-82.
    PMID: 23414931 DOI: 10.1016/j.drugalcdep.2013.01.005
    To evaluate the impact of methadone dose on post-release retention in treatment among HIV-infected prisoners initiating methadone maintenance treatment (MMT) within prison.
    Matched MeSH terms: Kaplan-Meier Estimate
  14. Wan NurHazirah Wan Ahmad Kamil, Zuraiza Mohamad Zaini, Anand Ramanathan, Thomas Abraham, Rosnah Mohd Zain
    MyJurnal
    Introduction: Oral squamous cell carcinoma (OSCC) is a major health problem worldwide. The overall survival rate remains at 50% despite numerous studies and various treatment modalities in OSCC. The presence of lymph node metastasis in OSCC is well established as an independent prognostic factor. This present study aims to investigate the association of four tumour antigens; FJX-1, GNα12, IFITM3 and MAGED4B with the sociodemographic and clinicopathological parameters of OSCC. The potential use of these markers as a prognostic indicator of patient sur-vival and lymph node metastasis in OSCC was explored. Methods: 35 cases of OSCC with available formalin-fixed paraffin-embedded (FFPE) specimens involving the tongue, buccal mucosa, gingiva, alveolus and floor of mouth were evaluated by immunohistochemistry for FJX-1, GNA12, IFITM3 and MAGED4B expression. Assessment of the expression of these tumour antigens was based on the cellular sub-site, intensity and percentage of staining in the OSCC samples. Results: The expression of all four tumour markers were expressed in all samples (n=35) but none statistically associated with any clinicopathological or socio-demographic parameters. Survival analysis using Kaplan-Meier test showed high expression of GNA12, IFITM3 and MAGED4B individually with poor prognosis in OSCC patients. A combination of markers, GNA12 and MAGED4B demonstrated a significant association with pa-tient survival in OSCC (p=0.014). Multivariate analysis after adjustment for selected socio-demographic factors (age, gender, risk habits and sub-sites of the oral cavity) revealed that high expression of both MAGED4B and GNA12 remained as an independent prognostic factor for poor prognosis in OSCC (HRR =5.231, 95% CI 1.601,17.084; p=0.006). Conclusion: We concluded that high combined expression of both marker (Gα12 and mAGED4B) might be used as an independent prognostic indicator in OSCC.
    Matched MeSH terms: Kaplan-Meier Estimate
  15. WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al.
    N Engl J Med, 2021 Feb 11;384(6):497-511.
    PMID: 33264556 DOI: 10.1056/NEJMoa2023184
    BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19).

    METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.

    RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.

    CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

    Matched MeSH terms: Kaplan-Meier Estimate
  16. Vasaikar S, Tsipras G, Landázuri N, Costa H, Wilhelmi V, Scicluna P, et al.
    BMC Cancer, 2018 02 06;18(1):154.
    PMID: 29409474 DOI: 10.1186/s12885-018-4012-7
    BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor with median survival of 12-15 months. Owing to uncertainty in clinical outcome, additional prognostic marker(s) apart from existing markers are needed. Since overexpression of endothelin B receptor (ETBR) has been demonstrated in gliomas, we aimed to test whether ETBR is a useful prognostic marker in GBM and examine if the clinically available endothelin receptor antagonists (ERA) could be useful in the disease treatment.

    METHODS: Data from The Cancer Genome Atlas and the Gene Expression Omnibus database were analyzed to assess ETBR expression. For survival analysis, glioblastoma samples from 25 Swedish patients were immunostained for ETBR, and the findings were correlated with clinical history. The druggability of ETBR was assessed by protein-protein interaction network analysis. ERAs were analyzed for toxicity in in vitro assays with GBM and breast cancer cells.

    RESULTS: By bioinformatics analysis, ETBR was found to be upregulated in glioblastoma patients, and its expression levels were correlated with reduced survival. ETBR interacts with key proteins involved in cancer pathogenesis, suggesting it as a druggable target. In vitro viability assays showed that ERAs may hold promise to treat glioblastoma and breast cancer.

    CONCLUSIONS: ETBR is overexpressed in glioblastoma and other cancers and may be a prognostic marker in glioblastoma. ERAs may be useful for treating cancer patients.

    Matched MeSH terms: Kaplan-Meier Estimate
  17. Urban P, Meredith IT, Abizaid A, Pocock SJ, Carrié D, Naber C, et al.
    N Engl J Med, 2015 Nov 19;373(21):2038-47.
    PMID: 26466021 DOI: 10.1056/NEJMoa1503943
    BACKGROUND: Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month.
    METHODS: In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual antiplatelet therapy. The primary safety end point, tested for both noninferiority and superiority, was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target-lesion revascularization.
    RESULTS: We enrolled 2466 patients. At 390 days, the primary safety end point had occurred in 112 patients (9.4%) in the drug-coated-stent group and in 154 patients (12.9%) in the bare-metal-stent group (risk difference, -3.6 percentage points; 95% confidence interval [CI], -6.1 to -1.0; hazard ratio, 0.71; 95% CI, 0.56 to 0.91; P<0.001 for noninferiority and P=0.005 for superiority). During the same time period, clinically driven target-lesion revascularization was needed in 59 patients (5.1%) in the drug-coated-stent group and in 113 patients (9.8%) in the bare-metal-stent group (risk difference, -4.8 percentage points; 95% CI, -6.9 to -2.6; hazard ratio, 0.50; 95% CI, 0.37 to 0.69; P<0.001).
    CONCLUSIONS: Among patients at high risk for bleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet therapy. (Funded by Biosensors Europe; LEADERS FREE ClinicalTrials.gov number, NCT01623180.).
    Matched MeSH terms: Kaplan-Meier Estimate
  18. Tromp J, Tay WT, Ouwerkerk W, Teng TK, Yap J, MacDonald MR, et al.
    PLoS Med, 2018 03;15(3):e1002541.
    PMID: 29584721 DOI: 10.1371/journal.pmed.1002541
    BACKGROUND: Comorbidities are common in patients with heart failure (HF) and complicate treatment and outcomes. We identified patterns of multimorbidity in Asian patients with HF and their association with patients' quality of life (QoL) and health outcomes.

    METHODS AND FINDINGS: We used data on 6,480 patients with chronic HF (1,204 with preserved ejection fraction) enrolled between 1 October 2012 and 6 October 2016 in the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry. The ASIAN-HF registry is a prospective cohort study, with patients prospectively enrolled from in- and outpatient clinics from 11 Asian regions (Hong Kong, Taiwan, China, Japan, Korea, India, Malaysia, Thailand, Singapore, Indonesia, and Philippines). Latent class analysis was used to identify patterns of multimorbidity. The primary outcome was defined as a composite of all-cause mortality or HF hospitalization within 1 year. To assess differences in QoL, we used the Kansas City Cardiomyopathy Questionnaire. We identified 5 distinct multimorbidity groups: elderly/atrial fibrillation (AF) (N = 1,048; oldest, more AF), metabolic (N = 1,129; obesity, diabetes, hypertension), young (N = 1,759; youngest, low comorbidity rates, non-ischemic etiology), ischemic (N = 1,261; ischemic etiology), and lean diabetic (N = 1,283; diabetic, hypertensive, low prevalence of obesity, high prevalence of chronic kidney disease). Patients in the lean diabetic group had the worst QoL, more severe signs and symptoms of HF, and the highest rate of the primary combined outcome within 1 year (29% versus 11% in the young group) (p for all <0.001). Adjusting for confounders (demographics, New York Heart Association class, and medication) the lean diabetic (hazard ratio [HR] 1.79, 95% CI 1.46-2.22), elderly/AF (HR 1.57, 95% CI 1.26-1.96), ischemic (HR 1.51, 95% CI 1.22-1.88), and metabolic (HR 1.28, 95% CI 1.02-1.60) groups had higher rates of the primary combined outcome compared to the young group. Potential limitations include site selection and participation bias.

    CONCLUSIONS: Among Asian patients with HF, comorbidities naturally clustered in 5 distinct patterns, each differentially impacting patients' QoL and health outcomes. These data underscore the importance of studying multimorbidity in HF and the need for more comprehensive approaches in phenotyping patients with HF and multimorbidity.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT01633398.
    Matched MeSH terms: Kaplan-Meier Estimate
  19. Teh LK, Mohamed NI, Salleh MZ, Rohaizak M, Shahrun NS, Saladina JJ, et al.
    AAPS J, 2012 Mar;14(1):52-9.
    PMID: 22183189 DOI: 10.1208/s12248-011-9313-6
    CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.
    Matched MeSH terms: Kaplan-Meier Estimate
  20. Teh CL, Ling GR
    Lupus, 2013 Jan;22(1):106-11.
    PMID: 23112253 DOI: 10.1177/0961203312465780
    Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can be life threatening and fatal if left untreated. Causes and prognostic indicators of death in SLE have been well studied in developed countries but lacking in developing countries. We aimed to investigate the causes of mortality in hospitalized patients with SLE and determine the prognostic indicators of mortality during hospitalization in our center. All SLE patients who were admitted to Sarawak General Hospital from January 1, 2006 to December 31, 2010, were followed up in a prospective study using a standard protocol. Demographic data, clinical features, disease activities and damage indices were collected. Logistic regression and Cox regression analysis were used to determine the prognostic indicators of mortality in our patients. There were a total of 251 patients in our study, with the female to male ratio 10 to 1. Our study patients were of multiethnic origins. They had a mean age of 30.5 ± 12.2 years and a mean duration of illness of 36.5 ± 51.6 months. The main involvements were hematologic (73.3%), renal (70.9%) and mucocutaneous (67.3%). There were 26 deaths (10.4%), with the main causes being: infection and flare (50%), infection alone (19%), flare alone (19%) and others (12%). Independent predictors of mortality in our cohort of SLE patients were the presence of both infection and flare of disease (hazard ratio (HR) 5.56) and high damage indices at the time of admission (HR 1.91). Infection and flare were the main causes of death in hospitalized Asian patients with SLE. The presence of infection with flare and high damage indices at the time of admission were independent prognostic indicators of mortality.
    Matched MeSH terms: Kaplan-Meier Estimate
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