A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same drug

Litter quality and its response to water level drawdown in boreal peatlands at plant species and community level

Changes in the structure of plant communities may have much more impact on ecosystem carbon (C) cycling than any phenotypic responses to environmental changes. We studied these impacts via the response of plant litter quality, at the level of species and community, to persistent water-level (WL) drawdown in peatlands. We studied three sites with different nutrient regimes, and water-level manipulations at two time scales. The parameters used to characterize litter quality included extractable substances, cellulose, holocellulose, composition of hemicellulose (neutral sugars, uronic acids), Klason lignin, CuO oxidation phenolic products, and concentrations of C and several nutrients. The litters formed four chemically distinct groups: non-graminoid foliar litters, graminoids, mosses and woody litters. Direct effects of WL drawdown on litter quality at the species level were overruled by indirect effects via changes in litter type composition. The pristine conditions were characterized by Sphagnum moss and graminoid litters. Short-term (years) responses of the litter inputs to WL drawdown were small. In longterm (decades), total litter inputs increased, due to increased tree litter inputs. Simultaneously, the litter type composition and its chemical quality at the community level greatly changed. The changes that we documented will strongly affect soil properties and C cycle of peatlands.Peer reviewe

Linking Diet, Behavior, and Bioenergetics of a Migratory Waterbird to Evaluate Response to Wintering Ground Conditions

Rivers in semi-arid regions are highly sensitive and pressured yet can support diverse assemblages of species. In central New Mexico, the Rio Grande (River) is the lifeblood of the Middle Rio Grande Valley (MRGV), a semi-arid region which maintains large urban and agricultural centers and is also the principal wintering area for the Rocky Mountain Population of greater sandhill cranes (Antigone canadensis tabida). Human-induced environmental change has transformed the MRGV and habitat availability prompting concerns for the population. To address these concerns, I investigated dietary and behavioral responses of sandhill cranes to the collection of features that function as winter habitat. In Chapter 1, I demonstrated a novel application of stable isotopes to evaluate dietary reliance of sandhill cranes on corn subsidies provisioned by natural resource agencies, estimated rates of carbon isotope incorporation in tissues of sandhill cranes, and estimated tissue-derived winter arrival dates of sandhill cranes. I found subsidized corn was the primary dietary component of sandhill cranes, rates of carbon isotope incorporation in sandhill crane tissues differed predictably by metabolic activity, and estimated tissue-derived arrival dates on wintering grounds approximated actual arrival dates. In Chapter 2, I advanced a hierarchical Bayesian framework for overcoming challenges and improving analysis of behavioral data frequently generated in animal behavior studies and used behavioral observations of sandhill cranes as a case study. In Chapter 3, I estimated energetic and temporal availability of corn subsidies and seasonal energy requirements of sandhill cranes. I found seasonal energetic requirements of the population are likely satisfied by corn subsides but not without strategic planning. In Chapter 4, I examined how current landscape and riverine configuration influenced patterns of diel habitat selection by sandhill cranes. Sandhill cranes avoided sources of anthropogenic disturbance, relied heavily on managed public land resources, and selected roosting locations in the Rio Grande with a wider channel, interspersion of sandbars and shallow water, and low channel bank vegetation. My research suggests sandhill cranes have coped with alterations that have led to current conditions in the MRGV, however, habitat-related resources will need to be managed adaptively as drivers of environmental change will undoubtedly influence future circumstances