ABSTRACT
BACKGROUND: Chronic kidney disease (CKD) causes a significant health burden in Australia, and up to 50% of Australians with CKD remain undiagnosed. AIMS: To estimate the 5-year risk for CKD from general practice (GP) clinical records and to investigate the spatial variation and hot spots of CKD risk in an Australian community. METHOD: A cross-sectional study was designed using de-identified GP clinical data recorded from 2010 to 2015. A total of 16 GP participated in this study from West Adelaide, Australia. We used health records of 36 565 patients aged 35-74 years, with no prior history of CKD. The 5-year estimated CKD risk was calculated using the QKidney algorithm. Individuals' risk score was aggregated to Statistical Area Level 1 to predict the community CKD risk. A spatial hotspot analysis was applied to identify the communities with greater risk. RESULTS: The mean estimated 5-year risk for CKD in the sample population was 0.95% (0.93-0.97). Overall, 2.4% of the study population was at high risk of CKD. Significant hot spots and cold spots of CKD risk were identified within the study region. Hot spots were associated with lower socioeconomic status. CONCLUSIONS: This study demonstrated a new approach to explore the spatial variation of CKD risk at a community level, and implementation of a risk prediction model into a clinical setting may aid in early detection and increase disease awareness in regions of unmet CKD care.
Subject(s)
General Practice , Renal Insufficiency, Chronic , Australia/epidemiology , Cross-Sectional Studies , Humans , Policy , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiologyABSTRACT
Activators of the pyruvate kinase M2 (PKM2) are currently attracting significant interest as potential anticancer therapies. They may achieve a novel antiproliferation response in cancer cells through modulation of the classic 'Warburg effect' characteristic of aberrant metabolism. In this Letter, we describe the optimization of a weakly active screening hit to a structurally novel series of small molecule 3-(trifluoromethyl)-1H-pyrazole-5-carboxamides as potent PKM2 activators.
Subject(s)
Carrier Proteins/metabolism , Drug Discovery/methods , Membrane Proteins/metabolism , Pyrazoles/chemistry , Pyrazoles/metabolism , Thyroid Hormones/metabolism , Carrier Proteins/agonists , Enzyme Activation/drug effects , Enzyme Activation/physiology , Humans , Isoenzymes/metabolism , Membrane Proteins/agonists , Pyrazoles/pharmacology , Structure-Activity Relationship , Thyroid Hormones/agonists , Thyroid Hormone-Binding ProteinsABSTRACT
Inactivation of the M2 form of pyruvate kinase (PKM2) in cancer cells is associated with increased tumorigenicity. To test the hypothesis that tumor growth may be inhibited through the PKM2 pathway, we generated a series of small-molecule PKM2 activators. The compounds exhibited low nanomolar activity in both biochemical and cell-based PKM2 activity assays. These compounds did not affect the growth of cancer cell lines under normal conditions in vitro, but strongly inhibited the proliferation of multiple lung cancer cell lines when serine was absent from the cell culture media. In addition, PKM2 activators inhibited the growth of an aggressive lung adenocarcinoma xenograft. These findings show that PKM2 activation by small molecules influences the growth of cancer cells in vitro and in vivo, and suggest that such compounds may augment cancer therapies.
Subject(s)
Benzylamines/pharmacology , Carrier Proteins/agonists , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Membrane Proteins/agonists , Pyrazoles/pharmacology , Thyroid Hormones/agonists , Animals , Benzylamines/chemistry , Carrier Proteins/chemistry , Carrier Proteins/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Female , Humans , Lung Neoplasms/drug therapy , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Mice , Models, Molecular , Molecular Conformation , Protein Binding , Pyrazoles/chemistry , Thyroid Hormones/chemistry , Thyroid Hormones/metabolism , Tumor Burden/drug effects , Xenograft Model Antitumor Assays , Thyroid Hormone-Binding ProteinsABSTRACT
This prospective observational study aimed to assess the feasibility of adapting peritoneal hyperdistention to 25 mmHg during laparoscopy in an Australian hospital environment. A total of 1150 consecutive diagnostic or operative laparoscopies were performed. All cases were monitored for early detection of untoward physiological changes. All patients had Veress needle insufflation with distension to 25 mmHg prior to insertion of the primary trocar. No patients experienced any surgical entry complications or adverse clinical effects noted during anaesthetic. The aim of the current study is to assess the feasibility and safety of increasing the peritoneal insufflation pressure to 25 mmHg for primary trocar insertion.
Subject(s)
Laparoscopy/methods , Surgical Instruments , Abdomen/physiopathology , Abdomen/surgery , Australia , Humans , Intraoperative Care , Intraoperative Complications , Laparoscopy/adverse effects , Monitoring, Physiologic , Pressure , Prospective Studies , Reproducibility of ResultsABSTRACT
OBJECTIVE: The purpose of this study was to assess the level of skill of laparoscopic surgeons in electrosurgery. DESIGN: Subjects were asked to complete a practical diathermy station and a written test of electrosurgical knowledge. SETTING: Tests were held in teaching and non-teaching hospitals. SAMPLE: Twenty specialists in obstetrics and gynaecology were randomly selected and tested on the Monash University gynaecological laparoscopic pelvi-trainer. Twelve candidates were consultants with 9-28 years of practice in operative laparoscopy, and 8 were registrars with up to six years of practice in operative laparoscopy. Seven consultants and one registrar were from rural Australia, and three consultants were from New Zealand. METHODS: Candidates were marked with checklist criteria resulting in a pass/fail score, as well as a weighted scoring system. We retested 11 candidates one year later with the same stations. MAIN OUTCOME MEASURES: No improvement in electrosurgery skill in one year of obstetric and gynaecological practice. RESULTS: No candidate successfully completed the written electrosurgery station in the initial test. A slight improvement in the pass rate to 18% was observed in the second test. The pass rate of the diathermy station dropped from 50% to 36% in the second test. CONCLUSION: The study found ignorance of electrosurgery/diathermy among gynaecological surgeons. One year later, skills were no better.
Subject(s)
Clinical Competence/standards , Diathermy/standards , Electrosurgery/standards , Gynecology/standards , Obstetrics/standards , Educational Status , Female , Humans , New Zealand , Prospective StudiesABSTRACT
IMPLICATIONS: Clonidine, an alpha(2)-adrenergic agonist, is used to minimize withdrawal symptoms related to ultra-rapid opioid detoxification procedures. These preliminary data suggest that clonidine possesses dose-related antidiarrheal activity.
