369 results match your criteria: "National Health and Medical Research Council Clinical Trials Centre[Affiliation]"

Interindividual Variation in Low-Density Lipoprotein Cholesterol Level Reduction With Evolocumab: An Analysis of FOURIER Trial Data.

JAMA Cardiol

January 2019

Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Importance: Little is known about the heterogeneity in low-density lipoprotein cholesterol levels (LDL-C) lowering with proprotein convertase subtilisin kexin 9 (PCSK9) inhibitor medications.

Objective: To evaluate the interindividual variability in LDL-C reduction with the PCSK9 inhibitor drug evolocumab.

Design, Setting, And Participants: We examined the percentage change in LDL-C levels from baseline in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, a placebo-controlled randomized clinical trial of the PCSK9 inhibitor evolocumab in patients with stable atherosclerotic cardiovascular disease who were taking statin medications.

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Serum Free Methylated Glutathione S-transferase 1 DNA Levels, Survival, and Response to Docetaxel in Metastatic, Castration-resistant Prostate Cancer: Post Hoc Analyses of Data from a Phase 3 Trial.

Eur Urol

September 2019

Chris O'Brien Lifehouse, Sydney, Australia; Garvan Institute of Medical Research, Sydney, Australia; University of NSW, Sydney, Australia; University of Sydney, Sydney, Australia. Electronic address:

Background: Glutathione S-transferase 1 (GSTP1) expression is inactivated in >90% of all prostate cancers in association with aberrant DNA methylation. Detection of serum free methylated GSTP1 (mGSTP1) DNA is associated with overall survival (OS) and response to docetaxel in metastatic castration-resistant prostate cancer (mCRPC) in test and internal validation cohorts.

Objective: To assess the relationship between serum free mGSTP1 and treatment outcomes in SYNERGY, a phase 3 multicentre randomised trial testing the addition of custirsen to first-line chemotherapy with docetaxel in mCRPC.

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Background: The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer.

Patients And Methods: Patients were enrolled in an open-label, multicenter, phase II trial and randomly assigned to cetuximab 400 mg/m, then 250 mg/m cetuximab weekly, with or without irinotecan 180 mg/m every 2 weeks. The primary endpoint was 6-month progression-free survival; secondary endpoints were response rate, overall survival, toxicity, and quality of life.

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Background: Higher plasma fibroblast growth factor 21 (FGF21) levels predict incident cardiovascular events in type 2 diabetes patients. However, whether FGF21 levels predict cardiovascular events in statin-treated patients in the general population is unknown. We investigated whether FGF21 levels predict major cardiovascular event (MCVE) in the Treating to New Targets (TNT) trial participants.

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Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer.

N Engl J Med

November 2018

From the Department of Gynecologic Oncology and Reproductive Medicine, University of Texas M.D. Anderson Cancer Center, Houston (P.T.R., M.F., R.L.C.); the Department of Gynecologic Oncology, Instituto Nacional de Cancerología, Bogota, and Clínica de Oncología Astorga, Medellin - both in Colombia (R.P.); the Department of Gynecologic Surgery, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru (A.L.); the Department of Gynecologic Oncology, Barretos Cancer Hospital, Barretos (M.V.), the Department of Surgical Oncology, Erasto Gaertner Hospital, Curitiba (R.R.), and the Department of Gynecologic Oncology, Albert Einstein Hospital, São Paulo (M.T.) - all in Brazil; the Unit of Gynecologic Oncology Surgery, Department of Obstetrics and Gynecology, San Gerardo Hospital, Monza, Italy (A.B.); the Department of Gynecology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou (X.Y.), the Department of Obstetrics and Gynecology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou (Y.S.), and the Department of Gynecologic Oncology, Zhejiang Cancer Hospital, Hangzhou (T.Z.) - all in China; the Department of Gynecologic Oncology, Mater Health Services Brisbane, South Brisbane (N.C.), the National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney (K.P.R., V.G., R.A.), and the Queensland Centre for Gynaecological Cancer Research and the Faculty of Medicine, University of Queensland (V.B., A.O.), and the Department of Gynaecologic Oncology, Royal Brisbane and Women's Hospital (J.L.N.), Herston - all in Australia; and the Department of Gynecologic Oncology, Instituto Nacional de Cancerología, Mexico City (D.I.).

Background: There are limited data from retrospective studies regarding whether survival outcomes after laparoscopic or robot-assisted radical hysterectomy (minimally invasive surgery) are equivalent to those after open abdominal radical hysterectomy (open surgery) among women with early-stage cervical cancer.

Methods: In this trial involving patients with stage IA1 (lymphovascular invasion), IA2, or IB1 cervical cancer and a histologic subtype of squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, we randomly assigned patients to undergo minimally invasive surgery or open surgery. The primary outcome was the rate of disease-free survival at 4.

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A randomised controlled trial of an advance care planning intervention for patients with incurable cancer.

Br J Cancer

November 2018

Centre for Medical Psychology and Evidence-based Decision-making (CeMPED), School of Psychology and Department of Medicine, University of Sydney, Sydney, NSW, Australia.

Background: We modified and evaluated an advance care planning (ACP) intervention, which had been shown to improve compliance with patient's end of life (EoL) wishes, in a different patient population.

Methods: Patients with incurable cancer, and a Family Member (FM), were randomised one-to-one to usual care or usual care plus an ACP intervention, between April 2014 and January 2017. Oncologists and participants were non-blinded.

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Aim: To explore associations between weight and type/frequency of urinary incontinence (UI) in children presenting to a tertiary hospital incontinence clinic.

Methods: We retrospectively reviewed medical records of children who first attended the incontinence clinic at The Children's Hospital at Westmead between January 2004 and December 2014. A random sample of 1000 children was selected from 2022 patient records, and data were collected on weight, height, age, gender, UI parameters, bowel habits and medical history.

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Objective: The aim of the study was to determine the efficacy of laparoscopic rectal resection (Lap) versus open laparotomy and rectal resection (Open) for rectal cancer on locoregional recurrence (LRR) and disease-free survival (DFS) at 2 years.

Summary Background Data: Although a Lap approach to colon cancer surgery may offer similar oncological outcomes to Open with potentially less morbidity, this remains to be clearly established for the treatment of rectal cancer.

Methods: A randomized, multicenter noninferiority phase 3 trial of 475 patients with T1 to T3 rectal adenocarcinoma <15 cm from anal verge, given Lap or Open and followed for a minimum 2 years to assess LRR, DFS, and overall survival (OS).

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A Reduction in Inflammatory Macrophages May Contribute to Skin Cancer Chemoprevention by Nicotinamide.

J Invest Dermatol

February 2019

Dermatology, Sydney Cancer Centre, Bosch Institute, The University of Sydney and Royal Prince Alfred Hospital, Camperdown, Sydney, Australia; Melanoma Institute Australia, The University of Sydney, Sydney, Australia. Electronic address:

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Importance: An alternative option to maternal vaccination to prevent severe pertussis in infants is vaccination at birth. Data are needed on the immunogenicity and safety of a birth dose of monovalent acellular pertussis (aP) vaccine.

Objective: To compare IgG antibody responses to vaccine antigens at 6, 10, 24, and 32 weeks of age between newborn infants receiving the aP vaccine and hepatitis B vaccine (HBV) or HBV alone.

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Lowering the P Value Threshold.

JAMA

September 2018

National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.

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Background: Plasma lipidomic measures may enable improved prediction of cardiovascular outcomes in secondary prevention. The aim of this study is to determine the association of plasma lipidomic measurements with cardiovascular events and assess their potential to predict such events.

Methods: Plasma lipids (n = 342) were measured in a retrospective subcohort (n = 5,991) of the LIPID study.

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Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients.

N Engl J Med

September 2018

From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston (E.A.B., S.D.W., J.K., K.I., A.Q., M.P.B., C.T.R., M.S.S., B.M.S.); the Cardiovascular Division, University of Texas Southwestern Medical Center, Dallas (D.K.M.); the Section of Endocrinology, Yale School of Medicine, New Haven, CT (S.E.I.); the Department of Medicine, University of Minnesota, Minneapolis (C.L.F.); the Partners Clinical Research Centre, Nassau, Bahamas (C.B.); the Department of Cardiology, Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland (A.B.); Cardiolink Clinical Trials, Monterrey, Mexico (A.G.-C.); McMaster University, Brampton, ON (M.G.), and the Division of Endocrinology and Metabolism, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.) - both in Canada; MedStar Health Research Institute, Hyattsville, MD (N.J.W.); the Cardiology Department, Auckland City Hospital, Auckland, New Zealand (H.D.W.); Eisai, Woodcliff Lake, NJ (T.P., B.F., W.M., C.P., S.D.); National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney (A.C.K.); and the Translational Research Institute for Metabolism and Diabetes, Florida Hospital and the Sanford-Burnham Institute, Winter Park (S.R.S.).

Background: Lorcaserin, a selective serotonin 2C receptor agonist that modulates appetite, has proven efficacy for weight management in overweight or obese patients. The cardiovascular safety and efficacy of lorcaserin are undefined.

Methods: We randomly assigned 12,000 overweight or obese patients with atherosclerotic cardiovascular disease or multiple cardiovascular risk factors to receive either lorcaserin (10 mg twice daily) or placebo.

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Practical guide for identifying unmet clinical needs for biomarkers.

EJIFCC

July 2018

New South Wales Health Pathology, Department of Clinical Chemistry and Endocrinology, Prince of Wales Hospital and School of Medical Sciences, University of New South Wales, Australia.

The development and evaluation of novel biomarkers and testing strategies requires a close examination of existing clinical pathways, including mapping of current pathways and identifying areas of unmet need. This approach enables early recognition of analytical and clinical performance criteria to guide evaluation studies, in a cyclical and iterative manner, all the time keeping the clinical pathway and patient health outcomes as the key drivers in the process. The Test Evaluation Working Group of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM TE-WG) https://www.

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Background: The primary tumor side is emerging as a major prognostic factor for patients with metastatic colorectal cancer (mCRC). We examined the survival data from 2 randomized studies to determine whether the outcomes differ between patients with mCRC with right-sided primary (RSP) tumors and those with left-sided primary (LSP) tumors after selective internal radiation therapy (SIRT) plus mFOLFOX6 (folinic acid [leucovorin], 5-fluorouracil, oxaliplatin) chemotherapy, versus chemotherapy alone.

Patients And Methods: Separate and combined analyses were performed on the data from the SIRFLOX and FOXFIRE global trials, which compared chemotherapy plus SIRT with chemotherapy alone for patients with mCRC liver metastases.

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Background: Health system strengthening is needed to improve delivery of secondary prophylaxis against rheumatic heart disease.

Methods And Results: We undertook a stepped-wedge, randomized trial in northern Australia. Five pairs of Indigenous community clinics entered the study at 3-month steps.

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How proteins harness mechanical force to control function is a significant biological question. Here we describe a human cell surface receptor that couples ligand binding and force to trigger a chemical event which controls the adhesive properties of the receptor. Our studies of the secreted platelet oxidoreductase, ERp5, have revealed that it mediates release of fibrinogen from activated platelet αIIbβ3 integrin.

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Importance: A range of somatic driver alterations has been described in estrogen receptor-positive, HER2-negative (ER+/HER2-) early breast cancer (BC); however, the clinical relevance is unknown.

Objective: To investigate associations of driver alterations with prognosis and the role of PIK3CA mutations in prediction of benefit associated with endocrine therapy in postmenopausal patients with ER+/HER2- early BC treated with tamoxifen or letrozole.

Design, Setting, And Participants: The Breast International Group (BIG) 1-98 trial randomized 8010 postmenopausal patients with hormone receptor-positive, operable, invasive BC to monotherapy with letrozole, tamoxifen, or a sequential strategy for 5 years.

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Importance: Recent studies have shown that Friedewald underestimates low-density lipoprotein cholesterol (LDL-C) at lower levels, which could result in undertreatment of high-risk patients. A novel method (Martin/Hopkins) using a patient-specific conversion factor provides more accurate LDL-C levels. However, this method has not been tested in proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor-treated patients.

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Importance: There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen.

Objective: To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity.

Design, Setting, And Participants: Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation.

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Objectives: Lorcaserin, a selective serotonin 2C receptor agonist, is an effective pharmacologic weight-loss therapy that improves several cardiovascular risk factors. The long-term clinical cardiovascular and metabolic safety and efficacy in patients with elevated cardiovascular risk are unknown.

Research Design And Methods: CAMELLIA-TIMI 61 (NCT02019264) is a randomized, double-blind, placebo-controlled, multinational clinical trial designed to evaluate the safety and efficacy of lorcaserin with regard to major adverse cardiovascular events and progression to diabetes in overweight or obese patients at high cardiovascular risk.

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Background: Screening potential live kidney donors is an intense process for both candidates and the healthcare system. It is conventionally implemented using a standard generic protocol. Efficiencies in this process could potentially be achieved using personalized protocols that are optimized for a given candidate.

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