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  1. Sukkar L, Talbot B, Jun M, Dempsey E, Walker R, Hooi L, et al.
    Can J Kidney Health Dis, 2019;6:2054358119879896.
    PMID: 31662874 DOI: 10.1177/2054358119879896
    Background: There are limited studies on the effects of statins on outcomes in the moderate chronic kidney disease (CKD) population and their trajectory to end-stage kidney disease.

    Objective: To examine the long-term effects of lipid-lowering therapy on all-cause mortality, cardiovascular morbidity, CKD progression, and socioeconomic well-being in Australian, New Zealand, and Malaysian SHARP (Study of Heart and Renal Protection) trial participants-a randomized controlled trial of a combination of simvastatin and ezetimibe, compared with placebo, for the reduction of cardiovascular events in moderate to severe CKD.

    Design: Protocol for an extended prospective observational follow-up.

    Setting: Australian, New Zealand, and Malaysian participating centers in patients with advanced CKD.

    Patients: All SHARP trial participants alive at the final study visit.

    Measurements: Primary outcomes were measured by participant self-report and verified by hospital administrative data. In addition, secondary outcomes were measured using a validated study questionnaire of health-related quality of life, a 56-item economic survey.

    Methods: Participants were followed up with alternating face-to-face visits and telephone calls on a 6-monthly basis until 5 years following their final SHARP Study visit. In addition, there were 6-monthly follow-up telephone calls in between these visits. Data linkage to health registries in Australia, New Zealand, and Malaysia was also performed.

    Results: The SHARP-Extended Review (SHARP-ER) cohort comprised 1136 SHARP participants with a median of 4.6 years of follow-up. Compared with all SHARP participants who originally participated in the Australian, New Zealand, and Malaysian regions, the SHARP-ER participants were younger (57.2 [48.3-66.4] vs 60.5 [50.3-70.7] years) with a lower proportion of men (61.5% vs 62.8%). There were a lower proportion of participants with hypertension (83.7% vs 85.0%) and diabetes (20.0% vs 23.5%).

    Limitations: As a long-term follow-up study, the surviving cohort of SHARP-ER is a selected group of the original study participants, which may limit the generalizability of the findings.

    Conclusion: The SHARP-ER study will contribute important evidence on the long-term outcomes of cholesterol-lowering therapy in patients with advanced CKD with a total of 10 years of follow-up. Novel analyses of the socioeconomic impact of CKD over time will guide resource allocation.

    Trial Registration: The SHARP trial was registered at ClinicalTrials.gov NCT00125593 and ISRCTN 54137607.

  2. Duncan CJ, Mohamad SM, Young DF, Skelton AJ, Leahy TR, Munday DC, et al.
    Sci Transl Med, 2015 Sep 30;7(307):307ra154.
    PMID: 26424569 DOI: 10.1126/scitranslmed.aac4227
    Type I interferon (IFN-α/β) is a fundamental antiviral defense mechanism. Mouse models have been pivotal to understanding the role of IFN-α/β in immunity, although validation of these findings in humans has been limited. We investigated a previously healthy child with fatal encephalitis after inoculation of the live attenuated measles, mumps, and rubella (MMR) vaccine. By targeted resequencing, we identified a homozygous mutation in the high-affinity IFN-α/β receptor (IFNAR2) in the proband, as well as a newborn sibling, that rendered cells unresponsive to IFN-α/β. Reconstitution of the proband's cells with wild-type IFNAR2 restored IFN-α/β responsiveness and control of IFN-attenuated viruses. Despite the severe outcome of systemic live vaccine challenge, the proband had previously shown no evidence of heightened susceptibility to respiratory viral pathogens. The phenotype of IFNAR2 deficiency, together with similar findings in STAT2-deficient patients, supports an essential but narrow role for IFN-α/β in human antiviral immunity.
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