ObjectiveTo assess the impact of home telemonitoring on health service use and quality of life in patients with severe chronic lung disease.DesignRandomised crossover trial with 6 months of standard best practice clinical care (control group) and 6 months with the addition of telemonitoring.Participants68 patients with chronic lung disease (38 with COPD; 30 with chronic respiratory failure due to other causes), who had a hospital admission for an exacerbation within 6 months of randomisation and either used long-term oxygen therapy or had an arterial oxygen saturation (SpO2) of <90% on air during the previous admission. Individuals received telemonitoring (second-generation system) via broadband link to a hospital-based care team.Outcome measuresPrimary outcome measure was time to first hospital admission for an acute exacerbation. Secondary outcome measures were hospital admissions, general practitioner (GP) consultations and home visits by nurses, quality of life measured by EuroQol-5D and hospital anxiety and depression (HAD) scale, and self-efficacy score (Stanford).ResultsMedian (IQR) number of days to first admission showed no difference between the two groups—77 (114) telemonitoring, 77.5 (61) control (p=0.189). Hospital admission rate at 6 months increased (0.63 telemonitoring vs 0.32 control p=0.026). Home visits increased during telemonitoring; GP consultations were unchanged. Self-efficacy fell, while HAD depression score improved marginally during telemonitoring.ConclusionsTelemonitoring added to standard care did not alter time to next acute hospital admission, increased hospital admissions and home visits overall, and did not improve quality of life in chronic respiratory patients.Trial registration numberNCT02180919 (ClinicalTrials.gov).

Objectives To determine whether the dose of inhaled corticosteroids can be stepped down in patients with chronic stable asthma while maintaining control. Design One year, randomised controlled, double blind, parallel group trial. Setting General practices throughout western and central Scotland. Participants 259 adult patients with asthma receiving regular treatment with inhaled corticosteroids at high dose (mean dose 1430 g beclomethasone dipropionate). Interventions Participants were allocated to receive either no alteration to their dose of inhaled corticosteroid (control) or a 50% reduction in their dose if they met criteria for stable asthma (stepdown). Main outcome measuresComparison of asthma exacerbation rates, asthma related visits to general practice and hospital, health status measures, and corticosteroid dosage between the two groups. Results The proportions of subjects with asthma exacerbations were not significantly different (stepdown 31%, control 26%, P=0.354). Similarly, the numbers of visits to general practice or hospital and the disease specific and generic measures of health status over the one year period were not significantly different. On average the stepdown group received 348 g (95% confidence interval 202 g to 494 g) of beclomethasone dipropionate less per day than the controls (a difference of 25%), with no difference in the annual dose of oral corticosteroids between the two treatment regimens. Conclusions By adopting a stepdown approach to the use of inhaled steroids at high doses in asthma a reduction in the dose can be achieved without compromising asthma control.

We evaluated the potential for gossypol intoxication and resulting effects of feeding large amounts of cottonseed meal to dairy cows in early lactation. Twenty-four Holstein cows were grouped by age, prior production, and days postpartum and randomly assigned to one of three diets. After 14-day standardization cows individually were fed a blended corn-corn silage ration supplemented with screw-pressed cottonseed meal, direct solvent extracted cottonseed meal, or soybean meal during a 14-wk comparison. Packed cell volume, copper in plasma, activities of transaminases, and gross composition of milk were not affected by ration. Hemoglobin was depressed, and total protein of plasma was elevated by the 9th wk in cows fed the solvent meal. Erythrocyte fragility was detected in those cows by the 7th wk and appeared later in cows fed the pressed meal. Gossypol was identified and quantitated in plasma and liver but was not detected in erythrocytes or milk from cows fed cottonseed meal. Elevated ambient temperatures precipitated increased respiration rates in the cows fed solvent meal. Physiological changes and gossypol in tissues of cows suggest that intoxication is possible in mature ruminants consuming cottonseed meal containing high free gossypol.

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TPS9119 Background: The toxicity profile of the third-generation EGFR-tyrosine kinase inhibitor (TKI) osimertinib makes it an attractive backbone for combination with other targeted agents, possibly overcoming acquired resistance mechanisms. Combination with a MET-inhibitor is an intuitive approach as MET-amplification was identified as the most common mechanism of resistance to osimertinib in preliminary ctDNA data from the Phase III FLAURA (15% of pts) and AURA3 (19% of pts) studies. Savolitinib (AZD6094, HMPL-504, volitinib) is an oral, potent and highly selective MET-TKI that had an acceptable safety profile when combined with osimertinib in the Phase Ib TATTON study, providing the basis for this Phase II SAVANNAH study (NCT03778229). Other mechanisms of acquired resistance to osimertinib, including secondary EGFR mutations (e.g. C797S), RAS/RAF activation, and oncogenic gene fusions, provide additional opportunities for developing osimertinib-based combinations. Methods: Eligible pts will have histologically/cytologically confirmed EGFR-mutant NSCLC, and MET+ disease by central FISH, central IHC, or local NGS (retrospectively confirmed by central FISH/IHC). Pts must have documented radiological progression following 1–3 lines of prior therapy (must include osimertinib). Pts will receive osimertinib 80 mg plus weight-based dosing with savolitinib 300 or 600 mg PO QD, in 28-day cycles. The primary objective is efficacy (RECIST 1.1) by overall response rate (ORR) in pts who are MET+ by central FISH. Secondary endpoints include: ORR ( MET+ by central IHC and all pts); progression-free survival, overall survival, duration of response, percent change in tumor size, HRQoL, and EGFR mutation ctDNA clearance ( MET+ by central FISH, central IHC, and all pts); safety, and pharmacokinetics (all pts). Based on the TATTON study, we anticipate enrolling ~172 MET+ pts to include ≥117 pts with MET+ disease by central FISH. Enrolment began in Q1 2019. Ongoing development of complementary trials targeting other osimertinib resistance mechanisms will also be discussed. Clinical trial information: NCT03778229.

With 32 lactating Holstein cows we evaluated physiological effects of gossypol and cyclopropenoid fatty acids in diets containing 18.5% whole cottonseed (dry matter) based on corn, corn silage, and soybean meal. All cows consumed a control diet for the first 2 wk of lactation and then were assigned to either control or whole cottonseed diet for the remainder of their lactation. Milk production, milk fat and protein percentages, and daily dry matter intake were measured. Dry matter intakes were less for cows consuming the whole cottonseed diet, but net energy intake was similar for all diets. Milk fat from cows consuming whole cottonseed contained detectable concentrations of cyclopropene fatty acids. Total lipid in plasma, total serum cholesterol, serum gossypol, and apparent liver gossypol concentrations were greater in cows fed whole cottonseed. Gossypol and cyclopropenoid fatty acids appeared to be absorbed from the gut of cows fed whole cottonseed. Small amounts of gossypol in serum and liver tissue and small amounts of cyclopropene fatty acids in adipose tissue lipids and milk fat indicate a need to elucidate the significance of these physiologically active compounds in the human diet and their biological effects on lactating dairy cows.

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