Search

BackgroundThis phase 1 clinical trial was conducted to determine the safety, maximum-tolerated dose (MTD), and pharmacokinetics of imatinib, bevacizumab, and metronomic cyclophosphamide in patients with advanced colorectal cancer (CRC).MethodsPatients with refractory stage IV CRC were treated with bevacizumab 5 mg kg(-1) i.v. every 2 weeks (fixed dose) plus oral cyclophosphamide q.d. and imatinib q.d. or b.i.d. in 28-day cycles with 3+3 dose escalation. Response was assessed every two cycles. Pharmacokinetics of imatinib and cyclophosphamide and circulating tumour, endothelial, and immune cell subsets were measured.ResultsThirty-five patients were enrolled. Maximum-tolerated doses were cyclophosphamide 50 mg q.d., imatinib 400 mg q.d., and bevacizumab 5 mg kg(-1) i.v. every 2 weeks. Dose-limiting toxicities (DLTs) included nausea/vomiting, neutropaenia, hyponatraemia, fistula, and haematuria. The DLT window required expansion to 42 days (1.5 cycles) to capture delayed toxicities. Imatinib exposure increased insignificantly after adding cyclophosphamide. Seven patients (20%) experienced stable disease for >6 months. Circulating tumour, endothelial, or immune cells were not associated with progression-free survival.ConclusionThe combination of metronomic cyclophosphamide, imatinib, and bevacizumab is safe and tolerable without significant drug interactions. A subset of patients experienced prolonged stable disease independent of dose level.

Rotator cuff related shoulder pain (RCRSP) is a common and disabling shoulder condition and surgical management is becoming more common. The rates and costs of surgical interventions have been on the rise. Understanding decision-making related to surgery and providing adequate information to people with RCRSP may improve patient-centred care and potentially reduce rates of surgery. To explore the decision-making processors of people who have undertaken surgery for RCRSP. An in-depth thematic analysis. Interviews were conducted with patients from Melbourne who had had surgical management for RCRSP. Data were analysed using an inductive thematic approach. Fifteen participants were recruited. Six key themes emerged: (1) Needing to get it done: "It was necessary to remedy the dire situation"; (2) Non-surgical treatment experience:" I knew that I'd done all I could"; (3) Mechanical problem:" Physio's not going to repair a torn tendon"; (4) Trust in medical professionals "If they told me that I needed to swallow a thousand spiders, I would have done it."; (5) Varied information sources "Dr Google played a big part in it"; (6) Organisational barriers "It was absolutely useless, my insurance." Surgery appears to be commonly precipitated by unremitted severe symptoms and failed non-surgical treatment. While there was strong trust in highly trained surgeons, decision to undergo surgery also drew on questionable pathoanatomical beliefs and instances of inadequate patient information about treatment choices and risks that may be addressed by adopting a more patient-centred care approach. Understanding decision-making related to surgery and providing adequate information to people with rotator cuff related shoulder pain may improve patient-centred care. Surgery appears to be commonly precipitated by unremitted severe symptoms and failed non-surgical treatment. Decision to undergo surgery sometimes drew on questionable pathoanatomical beliefs. There was strong trust in highly trained surgeons but there were instances of inadequate patient information about treatment choices and risks. [ABSTRACT FROM AUTHOR]

Context: Early sown, annual ryegrass pastures and winter crops provide a high-quality feed for livestock and also have a high water content during autumn and early winter compared with typical temperate pastures. Aim: We hypothesised that beef cattle grazing annual ryegrass or forage oats would not need additional access to drinking water to maintain their intake and growth. Methods: In Experiment 1, 48 weaned, castrated male Hereford calves with liveweight 154 kg (±6.7 kg; s.d.) grazed Italian ryegrass at a daily allowance of 4.5 kg dry matter (DM)/100 kg liveweight in two treatments including with or without access to drinking water. In Experiment 2, 60 Hereford steers with liveweight 382 kg (±20.6 kg; s.d.) were offered a daily allowance of 5 kg DM/100 kg liveweight of forage oats in a 2 × 2 factorial design either with or without access to drinking water and with or without sorghum grain silage supplemented at 1% of liveweight. The experiments were analysed as a completely randomised design, with individual pasture plots as the experimental unit. Key results: Daily growth rates of calves in the two treatments were similar (P > 0.05); however, calves with access to drinking water consumed 60% more water than did the calves without drinking water (P < 0.001). Access to drinking water had no effect (P > 0.05) on the daily growth rate of steers (P > 0.05); however, the daily growth rate of supplemented steers was 9% higher than that of the unsupplemented steers (P < 0.05). Total water intake was affected by access to drinking water (P < 0.005) but not access to supplementation (P > 0.05). Conclusions: Both calves and steers derived no production benefits by having access to drinking water when grazing actively growing annual ryegrass pasture or forage oats. Nevertheless, livestock should be monitored closely so that appropriate interventions can be made if there are changes in the pasture availability or weather. Implications: Grazing early sown winter forages by livestock can help circumvent the autumn–winter feed gap and these forages can be utilised more cost-effectively by not having to provide drinking water when the DM content is low. In temperate environments, there is often insufficient forage during autumn and early winter to meet the requirements of cattle, but at the same time farmers often have forage available as winter cereal crops. One reason for not grazing such crops is the lack of water points in the cropped paddocks. However, we demonstrate that cattle can perform adequately without access to drinking water when grazing actively growing annual ryegrass or winter cereal crops. This allows the feed gap to be diminished without farmers needing to provide infrastructure for drinking water, that can be costly. [ABSTRACT FROM AUTHOR]

Presents two hypothetical dialogues, one intended to illustrate some of the problems parents encounter when they confer with teachers, the other to illustrate a successful parent teacher conference. (Author/SJL)

Proper performance monitoring of cows on pasturebased diets is crucial to inform nutritional recommendations that minimize undesirable effects of high ruminant CH4 emissions into the environment. The prediction of linkages between rumination patterns, methane emissions, and correlated production traits of cows in a pasture-based automatic milking system was tested. A previous 10-d baseline measurement of rumination activity by acoustic methodology of 156 Holstein-Friesian cows was used for frequency analysis of rumination time and identification of 2 treatment groups (n = 37 cows/group) represented by cows with consistently high (HR; 75th rumination percentile = 617.55 ± 81.37 min/d) or low (LR; 25th rumination percentile = 356.65 ± 72.67 min/d) rumination. The HR and LR cows were paired by nearest parity, days in milk, body weight (BW), and previous 10-d milk production, and within pairs randomly assigned to 1 of 2 experimental groups managed on a voluntary milking system with diets consisting of at least 75% pasture, plus concentrates. Animal traits, including rumination time, mass flux of CH4 (QCH4) and carbon dioxide (QCO2), milk production, and estimated dry matter intake according to individual QCO2 fluxes over a 22-d period were analyzed with repeated measure mixed models for a completely randomized design, structural equation modeling, and nonlinear regression. High rumination and methane was seen in older and heavier cows that had greater estimated dry matter intake and milk production. A consistent difference in rumination time and QCH4 across days was detected between HR and LR, even after adjustment for metabolic BW. Estimated dry matter intake had direct positive effects on rumination and QCH4, but no independent direct effect of rumination on QCH4 was detected. The LR cows produced more QCH4/milk, associated with lower milk, BW, concentrate intake, and greater activity at pasture. A typical dilution of maintenance effect on QCH4/milk was detected as a consequence of increasing milk yield and similar significant reduction of QCO2/ milk. The results raise challenging questions regarding the rumination patterning of grazing dairy cows and alternatives to reduce ruminant methane emissions in grazing dairy cows. [ABSTRACT FROM AUTHOR]