Health technology assessment (HTA) agencies are considering adopting a lifecycle approach to assessments to address uncertainties in the evidence base at launch and to revisit the clinical and economic value of therapies in a dynamic clinical landscape. For reassessments of therapies post launch, HTA agencies are looking to real-world evidence (RWE) to enhance the clinical and economic evidence base, though challenges and concerns in using RWE in decision-making exists. Stakeholders are embarking on demonstration projects to address the challenges and concerns and to further define when and how RWE can be used in HTA decision making. The Institute for Clinical and Economic Review piloted a 24-month observational RWE reassessment. Key learnings from this pilot include identifying the benefits and challenges with using RWE in reassessments and considerations on prioritizing and selecting topics relevant for RWE updates.

Increased substitution of marine ingredients by terrestrial plant products in aquafeeds has been proven to be suitable for Atlantic salmon farming. However, a reduction in n-3 long-chain PUFA is a consequence of this substitution. In contrast, relatively little attention has been paid to the effects of fishmeal and oil substitution on levels of micronutrients such as Se, considering fish are major sources of this mineral for human consumers. To evaluate the effects of dietary marine ingredient substitution on tissue Se distribution and the expression of Se metabolism and antioxidant enzyme genes, Atlantic salmons were fed three feeds based on commercial formulations with increasing levels of plant proteins (PP) and vegetable oil. Lipid content in flesh did not vary at any sampling point, but it was higher in the liver of 1 kg of fish fed higher PP. Fatty acid content reflected dietary input and was related to oxidation levels (thiobarbituric acid-reactive substances). Liver had the highest Se levels, followed by head kidney, whereas the lowest contents were found in brain and gill. The Se concentration of flesh decreased considerably with high levels of substitution, reducing the added value of fish consumption. Only the brain showed significant differences in glutathione peroxidase, transfer RNA selenocysteine 1-associated protein 1b and superoxide dismutase expression, whereas no significant regulation of Se-related genes was found in liver. Although Se levels in the diets satisfied the essential requirements of salmon, high PP levels led to a reduction in the supply of this essential micronutrient.

The effects of varying dietary digestible protein (DP) and digestible energy (DE) content on performance, nutrient retention efficiency and the de novo lipogenesis of DP origin were examined in triplicate groups of gilthead sea bream (Sparus aurata), fed nine extruded experimental diets. In order to trace the metabolic fate of dietary protein, 1·8 % fishmeal was replaced with isotope-labelled whole protein (>98 % 13C). The experiment was divided into a growth period lasting 89 d, growing fish from approximately 140 to 350 g, followed by a 3 d period feeding isotope-enriched diets. Isotope ratio MS was applied to quantify the 13C enrichment of whole-body lipid from dietary DP. Between 18·6 and 22·4 % of the carbon derived from protein was recovered in the lipid fraction of the fish, and between 21·6 and 30·3 % of the total lipid deposited could be attributed to dietary protein. DP retention was significantly improved by reductions in dietary DP:DE ratio, while the opposite was true for apparent digestible lipid retention. Both overall DE retention and whole-body proximate composition of whole fish were largely unaffected by dietary treatments, while feed conversion ratios were significantly improved with increasing dietary energy density. The present study suggests that gilthead sea bream efficiently utilises dietary nutrients over a wide range of DP:DE ratios and energy densities. In addition, they appear to endeavour a certain body energy status rather than maximising growth, which in the present trial was apparent from inherently high de novo lipogenesis originating from DP.

The effects of replacing a digestible energy source from fat (fish oil) with carbohydrate (wheat starch) on performance, glycogenesis and de novo lipogenesis was examined in triplicate groups of juvenile gilthead sea bream (Sparus aurata), fed four extruded experimental diets. In order to trace the metabolic fate of dietary starch, 0·7 % wheat starch was replaced with isotope-labelled starch (>98 % 13C). Fish were fed the experimental diets for three consecutive 10 d periods, and isotope ratio MS was applied to quantify 13C enrichment of liver and whole-body glycogen and lipid pools over the three feeding periods. Glycogenesis originating from dietary starch accounted for up to 68·8 and 38·8 % of the liver and whole-body glycogen pools, respectively, while up to 16·7 % of the liver lipid could be attributed to dietary starch. Between 5 and 8 % of dietary starch carbon was recovered in whole-body lipid, and estimated deposition rates of de novo synthesised lipid originating from starch ranged from 18·7 to 123·7 mg/kg biomass per d. Dietary treatments did not significantly affect growth, feed performance or body composition of the fish, while the hepatosomatic index and glycogen content of whole fish and livers correlated directly with dietary starch inclusion level. The study suggests that gilthead sea bream efficiently synthesises glycogen from both dietary starch and endogenous sources. In contrast, lipogenesis from carbon derived from starch seems to play a minor role in overall lipid synthesis and deposition under the specified experimental conditions.

Pectinmethylesterase (PME) activity was found in the salivary glands of nymphs and adults of a leaf-footed bug, Leptoglossus occidentalis Heidemann. Puncture wounds in cone scales resulting from PME activity in the saliva of these bugs were seen by staining with a 0.05% aqueous solution of ruthenium red. This staining technique can be used to estimate feeding damage by L. occidentalis on cones of western white pine (Pinus monticola Dougl.), sugar pine (P. lambertiana Dougl.), and Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco).