Temporal changes in the incidence and predictors of severe hypoglycaemia in type 2 diabetes: The Fremantle Diabetes Study.

Aim: To determine the incidence of severe hypoglycaemia and its predictors in community-based patients with type 2 diabetes studied between 2008 and 2013 compared with those in a cohort of patients with type 2 diabetes from the same geographical area assessed a decade earlier.

Methods: We studied 1551 participants (mean age 65.7 years, 51.

The relationship between intensification of blood glucose-lowering therapies, health status and quality of life in type 2 diabetes: The Fremantle Diabetes Study Phase II.

Aims: To determine whether therapeutic intensification in type 2 diabetes influences health status and quality of life (QoL).

Methods: We studied 930 participants in the longitudinal observational Fremantle Diabetes Study Phase II (mean age 65.3 years, 53.

Temporal changes in glycaemic thresholds for treatment intensification in type 2 diabetes in an urban Australian setting: the Fremantle Diabetes Study.

Background: Pharmacotherapy and supportive care for diabetes in Australia are improving, with potential beneficial effects on therapeutic procrastination.

Aim: To determine whether glycaemic thresholds for therapeutic intensification in type 2 diabetes changed over the 15 years between phases of the community-based Fremantle Diabetes Study (FDS).

Methods: We studied 531 Phase 1 participants (mean age 62.

Relationship between depression and diabetes in pregnancy: A systematic review.

Aim: To systematically review the literature on women with both diabetes in pregnancy (DIP) and depression during or after pregnancy.

Methods: In this systematic literature review, PubMed/MEDLINE and EMBASE were searched (13 November 2015) using terms for diabetes (type 1, type 2, or gestational), depression, and pregnancy (no language or date restrictions). Publications that reported on women who had both DIP (any type) and depression or depressive symptoms before, during, or within one year after pregnancy were considered for inclusion.

Pemetrexed Continuation Maintenance in Patients with Nonsquamous Non-small Cell Lung Cancer: Review of Two East Asian Trials in Reference to PARAMOUNT.

Purpose: A recent phase III study (PARAMOUNT) demonstrated that pemetrexed continuation maintenance therapy is a new treatment paradigm for advanced nonsquamous non-small cell lung cancer (NSCLC). The majority of patients enrolled in PARAMOUNT were Caucasian (94%). We reviewed efficacy and safety data from two clinical trials, which enrolled East Asian (EA) patients, to supplement data from PARAMOUNT on pemetrexed continuation maintenance therapy in patients with nonsquamous NSCLC.

Efficacy and safety of pemetrexed/cisplatin versus gemcitabine/cisplatin as first-line treatment in Chinese patients with advanced nonsquamous non-small cell lung cancer.

Objectives: Retrospective subgroup analysis in JMDB study indicates that the between-arm differences in overall survival (OS) in the East Asian subgroup were consistent with those observed in the entire JMDB study population. This bridging study (JMIL) further evaluated the efficacy and safety of first-line pemetrexed/cisplatin (PC) versus gemcitabine/cisplatin (GC) in Chinese patients with nonsquamous non-small cell lung cancer (NSCLC). The primary endpoint of this local registration trial was designed to compare OS in the combined dataset, consisting of Chinese patients in JMIL and 1252 nonsquamous patients in JMDB.

First-line pemetrexed plus cisplatin followed by gefitinib maintenance therapy versus gefitinib monotherapy in East Asian patients with locally advanced or metastatic non-squamous non-small cell lung cancer: a randomised, phase 3 trial.

Background: In the Iressa Pan-ASia Study (IPASS), gefitinib claimed improved progression-free survival (PFS) versus carboplatin-paclitaxel in clinically selected lung cancer patients. The primary objective of this study was to assess the PFS of pemetrexed-cisplatin (PC) followed by gefitinib maintenance versus gefitinib monotherapy in an IPASS-like population.

Methods: In this open-label, randomised, phase 3 trial, eligible patients were ⩾18 years, chemonaïve, East Asian, light ex-smokers/never-smokers with advanced non-squamous non-small cell lung cancer, an Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and unknown epidermal growth factor receptor (EGFR) mutation status who enrolled at 12 sites in Asia.

Elderly subset analysis of randomized phase III study comparing pemetrexed plus carboplatin with docetaxel plus carboplatin as first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer.

Background: Many physicians consider platinum-doublet chemotherapy inappropriate for elderly patients, regardless of their medical fitness.

Objective: This was a retrospective subgroup analysis of data from a multicenter, randomized, phase III clinical trial evaluating pemetrexed + carboplatin versus docetaxel + carboplatin in elderly chemo-naive patients with advanced, nonsquamous non-small cell lung cancer (NSCLC).

Methods: Data from elderly patients (aged ≥65 years and ≥70 years) were evaluated using the same statistical methods as those used in patients aged <70 years and qualified intent-to-treat (Q-ITT) populations.

Biostatistics primer: what a clinician ought to know--prognostic and predictive factors.

Several prognostic factors in oncology have been established over the years, such as performance status, tumor size, and disease stage. The identification of prognostic and predictive factors is becoming increasingly important in medical research, particularly as scientific discoveries have led to better understanding of diseases and genetics, resulting in tailored therapy. Advances in drug discovery and better understanding of the mechanism of action, may also identify factors that may be prognostic and/or predictive.

A phase 2 study of sequential neoadjuvant chemotherapy with gemcitabine and doxorubicin followed by gemcitabine and cisplatin in patients with large or locally advanced operable breast cancer: results from long-term follow-up.

Background: Neoadjuvant chemotherapy (NACT) is being increasingly used for patients with large-size operable breast cancer. This phase 2 study of sequential NACT with gemcitabine and doxorubicin (Gem + Dox) followed by gemcitabine and cisplatin (Gem + Cis) was conducted in women with large or locally advanced breast cancer. The objectives were to evaluate the pathological complete response (pCR) rate, toxicity, pathological and genetic markers predicting response, the proportion of patients undergoing breast conservation surgery, progression-free survival (PFS) and overall survival (OS) after 5 years, and time to treatment failure (TtTF).

Smoking history as a predictive factor of treatment response in advanced non-small-cell lung cancer: a systematic review.

Recent trials in patients with advanced non-small-cell lung cancer (NSCLC) suggest that nonsmokers may benefit more from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy than will smokers. The aim of this systematic review was to assess smoking history as a predictive factor for treatment outcomes in patients with NSCLC. Relevant published literature was identified through systematic searches of databases (MEDLINE, EMBASE, Cochrane Library), oncology and thoracic journals, and abstracts from major oncology conferences using prespecified criteria.

A randomized phase 3 trial comparing pemetrexed/carboplatin and docetaxel/carboplatin as first-line treatment for advanced, nonsquamous non-small cell lung cancer.

Introduction: This study compared survival without toxicity in patients with advanced, nonsquamous non-small cell lung cancer who were treated with first-line pemetrexed/carboplatin or docetaxel/carboplatin.

Methods: This multicenter, open-label, parallel-group, phase 3 trial comprised patients randomized (1:1) to pemetrexed/carboplatin (n = 128) or docetaxel/carboplatin (n = 132). Patients received treatment on day 1 of each 21-day cycle (maximum of six cycles).

Histology as a treatment effect modifier in advanced non-small cell lung cancer: a systematic review of the evidence.

Background And Objective: We conducted a systematic review of prospective, randomized, controlled trials (RCT) to examine whether histology had a treatment modifying effect (TME) on the efficacy outcomes of chemotherapeutic agents in patients with advanced (stage IIIB-IV) non-small cell lung cancer (NSCLC).

Methods: Potentially pertinent publications were reviewed in full to determine if there was any TME by histology for overall survival (OS), progression-free survival (PFS) or treatment response rate (TRR).

Results: Data from three pemetrexed RCT, comparing (i) pemetrexed versus docetaxel, (ii) pemetrexed and cisplatin versus gemcitabine and cisplatin, and (iii) pemetrexed versus placebo, showed a statistically significant TME by histology for OS and PFS.

Biostatistics primer: what a clinician ought to know: hazard ratios.

Hazard ratios (HRs) are used commonly to report results from randomized clinical trials in oncology. However, they remain one of the most perplexing concepts for clinicians. A good understanding of HRs is needed to effectively interpret the medical literature to make important treatment decisions.

Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix.

Purpose: To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.

Patients And Methods: Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2) weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m(2) on day 1, plus gemcitabine, 1,000 mg/m(2) on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A).

A systematic review of the interobserver variability for histology in the differentiation between squamous and nonsquamous non-small cell lung cancer.

Introduction: The importance of identifying non-small cell lung cancer (NSCLC) histologic subtype has increased recently because of the development of target-specific chemotherapeutic agents. This systematic review was undertaken to examine the interobserver variability for histology in differentiating between subtypes of NSCLC, specifically the ability to differentiate squamous from nonsquamous histology.

Methods: A systematic literature search was undertaken to identify studies that evaluated the reproducibility of histologic diagnosis by pathologists in their reporting of NSCLC subtypes.

Biostatistics primer: what a clinician ought to know: subgroup analyses.

Large randomized phase III prospective studies continue to redefine the standard of therapy in medical practice. Often when studies do not meet the primary endpoint, it is common to explore possible benefits in specific subgroups of patients. In addition, these analyses may also be done, even in the case of a positive trial to find subsets of patients where the therapy is especially effective or ineffective.

Degree-of-spread artefact in the New South Wales Central Cancer Registry.

Objective: To describe a data artefact in degree-of-spread at first presentation in the New South Wales Central Cancer Registry (NSW CCR), the only Australian cancer registry that records degree-of-spread data for all solid tumours.

Method: Trends in the proportions of cancer cases diagnosed annually over 1972-2004 by degree-of-spread categories of localised, regional, distant and unknown were calculated for each major cancer type.

Results: Excepting breast cancer and melanoma, the proportion of localised cancer cases reported from 1993-1998 was approximately 5% lower than expected, and was mirrored by an artefactual increase in unknown degree-of-spread cases.

Evolutionary relationships and protein domain architecture in an expanded calpain superfamily in kinetoplastid parasites.

Employing whole-genome analysis we have characterized a large family of genes coding for calpain-related proteins in three kinetoplastid parasites. We have defined a total of 18 calpain-like sequences in Trypanosoma brucei, 27 in Leishmania major, and 24 in Trypanosoma cruzi. Sequence characterization revealed a well-conserved protease domain in most proteins, although residues critical for catalytic activity were frequently altered.