Clinical usefulness of brief screening tool for activating weight management discussions in primary cARE (AWARE) : a nationwide mixed methods pilot study

Objective The Edmonton Obesity Staging System (EOSS) is based on weight related health complications among individuals with overweight and obesity requiring clinical intervention. We aimed to assess the clinical usefulness of a new screening tool based on the EOSS for activating weight management discussions in general practice. Methods We enrolled five General Practitioners (GPs) and 25 of their patients located nationwide in metropolitan areas of Australia to test the feasibility, acceptability, and accuracy of the new ‘EOSS-2 Risk Tool’, using cross-sectional and qualitative study designs. Diagnostic accuracy of the tool for the presence of EOSS ≥2 criteria was based on clinical information collected prospectively. To assess feasibility and applicability, we explored the views of GP and patient participants by thematic analysis of transcribed verbatim and de-identified data collected by semi-structured telephone interviews. Results Nineteen (76%) patients were aged ≥45 years, five (20%) were male, and 20 (80%) were classified with obesity. All 25 patients screened positive for EOSS ≥2 criteria by the tool. Interviews with patients continued until data saturation was reached resulting in a total of 23 interviews. Our thematic analysis revealed five themes: GP recognition of obesity as a health priority (GPs expressed strong interest in and understanding of its importance as a health priority); obesity stigma (GPs reported the tool helped them initiate health based and non-judgmental conversations with their patients); patient health literacy (GPs and patients reported increased awareness and understanding of weight related health risks), patient motivation for self-management (GPs and patients reported the tool helped focus on self-management of weight related complications), and applicability and scalability (GPs stated it was easy to use, relevant to a range of their patient groups, and scalable if integrated into existing patient management systems). Conclusion The EOSS-2 Risk Tool is potentially clinically useful for activating weight management discussions in general practice. Further research is required to assess feasibility and applicability

Understanding the confluence of injury and obesity in a Grade 2 obesity and above population

Objective: Obesity and injury are major inter-related public health challenges. The objective of this study was to explore the perceptions of injury in people with severe obesity. Methods: A cross-sectional design was employed to capture injury perception and lifestyle habits via questionnaires. Weight (kg) and height (m) were measured by clinicians for patients attending a weight loss group program. Univariate, chi-square, ANOVA and ordinal regression analyses were undertaken. Results: There were 292 participants (67.1% female), mean age 49.3 years and Body Mass Index 47.2 kg/m2 (range 30.7–91.9 kg/m2). Concern about having an injury was found in 83%, and 74.2% thought that weight would increase the likelihood of injury. A greater concern of being injured at baseline was associated with less weight loss at eight weeks (F=3.567; p=0.03). Depression, anxiety and sleepiness score were higher in those who reported greater ‘Concern about having an injury’. Conclusions: People with obesity fear injury and falling, which limits their willingness to exercise. Anxiety symptoms appear to exacerbate this connection. Implications for public health: In individuals with obesity, anxiety, sleepiness and depression are associated with a fear of being injured. Addressing fear and reducing anxiety may decrease barriers to participating in physical activity

Development and internal validation of the Edmonton Obesity Staging System-2 Risk screening Tool (EOSS-2 Risk Tool) for weight-related health complications : a case-control study in a representative sample of Australian adults with overweight and obesity

Objective Excess weight and related health complications remain under diagnosed and poorly treated in general practice. We aimed to develop and validate a brief screening tool for determining the presence of unknown clinically significant weight-related health complications for potential application in general practice. Design We considered 14 self-reported candidate predictors of clinically significant weight-related health complications according to the Edmonton Obesity Staging System (EOSS score of ≥2) and developed models using multivariate logistic regression across training and test data sets. The final model was chosen based on the area under the receiver operating characteristic curve and the Hosmer-Lemeshow statistic; and validated using sensitivity, specificity and positive predictive value. Setting and participants We analysed cross-sectional data from the Australian Health Survey 2011–2013 sample aged between 18 and 65 years (n=7518) with at least overweight and obesity. Results An EOSS≥2 classification was present in 78% of the sample. Of 14 candidate risk factors, 6 (family history of diabetes, hypertension, high sugar in blood/urine, high cholesterol and self-reported bodily pain and disability) were automatically included based on definitional or obvious correlational criteria. Three variables were retained in the final multivariate model (age, self-assessed health and history of depression/anxiety). The EOSS-2 Risk Tool (index test) classified 89% of those at ‘extremely high risk’ (≥25 points), 67% of those at ‘very high risk’ (7–24 points) and 42% of those at ‘high risk’ (<7 points) of meeting diagnostic criteria for EOSS≥2 (reference). Conclusion The EOSS-2 Risk Tool is a simple, safe and accurate screening tool for diagnostic criteria for clinically significant weight-related complications for potential application in general practice. Research to determine the feasibility and applicability of the EOSS-2 Risk Tool for improving weight management approaches in general practice is warranted

The golden native drone fly (Eristalinus punctulatus) is an effective hybrid carrot pollinator that lives within Australian crop agroecosystems

1. Native insect flower visitors can be important contributors to crop pollination, yet little is known of their pollination abilities and the resources (habitat) they need to be supported within crop agroecosystems. 2. Here, we compared the abundance and pollination abilities of the golden drone fly (Eristalinus punctulatus) to the European honey bee (Apis mellifera) in hybrid carrot crop fields known to produce variable seed yields in regional New South Wales, Australia. We further observed the egg-laying behaviours of female golden drone flies at a commercial berry orchard to provide insight into the habitat needs of this species. 3. In hybrid carrot crop fields, golden drone flies were far less abundant flower visitors than European honey bees" however, these flies deposited more carrot pollen grains on average (8.21±3.04SE) onto carrot flowers than European honey bees (3.45±1.06SE). Both insects also deposited pollen onto a similar number of carrot flowers (pollinated) per visit (about 2 out of 18). 4. Golden drone flies were observed laying eggs within masses of discarded red raspberry plant roots and soil (root balls) at a commercial berry orchard. The natural habitat utilised by these flies, as well as their egg-laying behaviours, were described for the first time. 5. Our results indicate that golden drone flies are effective pollinators of hybrid carrot crop plants. The habitat that these flies utilised to lay eggs (discarded plants and water) is cheap and commonly found in crop agroecosystems. Therefore, we recommend placing this low-cost habitat within, or nearby, crop fields as a potential management practice to support the lifecycle needs of golden drone flies and other non-bee pollinators

Tsukushi Modulates Xnr2, FGF and BMP Signaling: Regulation of Xenopus Germ Layer Formation

Cell-cell communication is essential in tissue patterning. In early amphibian development, mesoderm is formed in the blastula-stage embryo through inductive interactions in which vegetal cells act on overlying equatorial cells. Members of the TGF-beta family such as activin B, Vg1, derrière and Xenopus nodal-related proteins (Xnrs) are candidate mesoderm inducing factors, with further activity to induce endoderm of the vegetal region. TGF-beta-like ligands, including BMP, are also responsible for patterning of germ layers. In addition, FGF signaling is essential for mesoderm formation whereas FGF signal inhibition has been implicated in endoderm induction. Clearly, several signaling pathways are coordinated to produce an appropriate developmental output; although intracellular crosstalk is known to integrate multiple pathways, relatively little is known about extracellular coordination

Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

We thank the Peggy and Charles Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, for funding, who received an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103639 for the use of the Histology and Immunohistochemistry Core for providing immunohistochemistry and photographic services. This work was also supported by Oklahoma State University, Center of Veterinary Health Science (Support Grant AE-1-50060 to P.C.S.), the Musella Foundation (R.A.T.), and the Childhood Brain Tumor Foundation (R.A.T.).Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals (Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05), as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients.Yeshttp://www.plosone.org/static/editorial#pee

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Transient diabetes insipidus in a post-partum woman with pre-eclampsia associated with residual placental vasopressinase activity

This case illustrates the exceedingly rare phenomenon of transient diabetes insipidus, in association with pre-eclampsia, occurring in the post-partum period following an in vitro fertilisation pregnancy, in an otherwise well 48-year-old lady. Diabetes insipidus can manifest during pregnancy, induced by increased vasopressinase activity secreted by placental trophoblasts and usually manifests in the third trimester. This presentation elucidates not only the intricate balance between the physiology of pregnancy and hormonal homeostasis, but also the importance of post-partum care as the physiological changes of pregnancy still hold pathological potential in the weeks immediately following delivery