Pro Con debates in clinical medicine Infection prevention and control in cystic fibrosis: one size fits all? The argument against

As awareness of the risks of cross infection has increased, infection prevention and control measures have become more draconian. Infection control measures can have a profound effect of the organisation and delivery of CF services and on the lives of people with CF outside the hospital. However, the consequences of inadequate infection control measures may be the permanent acquisition of a chronic infection which is virtually untreatable. Recommendations for infection prevention and control therefore must protect patients but should also be evidence-based and proportionate. This article will review the literature, juxtaposing evidence and popular practice

Do current clinical trials in cystic fibrosis match the priorities of patients and clinicans? A systematic review

There are many uncertainties regarding Cystic Fibrosis (CF) treatment. Recently, the first James Lind Alliance (JLA) Priority Setting Partnership (PSP) in CF was completed, bringing clinicians, patients and carers together to identify the Top 10 research priorities. Here we investigate how well the current clinical trials landscape reflects these priorities. Trials in CF were identified through searches of research databases (Pubmed, ANZCTR, EU clinical trials register, ClinicalTrials.gov and ISRCTN). Trials meeting inclusion criteria of registered intervention studies in CF published between 01.012016 and 11.09.2017 were matched to the Top 10 priorities. We identified 259 trials, with 193 fulfilling the inclusion criteria. Only 63 (33%) of these matched one or more of the JLA priorities showing that current clinical trials poorly reflect the JLA Top 10. By increasing awareness of the Top 10 priorities, it is hoped that this will fuel future research in areas important to the CF community

Habitat-specific distinctions in estuarine denitrification affect both ecosystem function and services

Resource limitation controls the base of food webs in many aquatic ecosystems. In coastal ecosystems, nitrogen (N) has been found to be the predominant limiting factor for primary producers. Due to the important role nitrogen plays in determining ecosystem function, understanding the processes that modulate its availability is critical. Shallow-water estuarine systems are highly heterogeneous. In temperate estuaries, multiple habitat types can exist in close proximity to one another, their distribution controlled primarily by physical energy, tidal elevation and geomorphology. Distinctions between these habitats such as rates of primary productivity and sediment characteristics likely affect material processing. We used membrane inlet mass spectrometry to measure changes in N2 flux (referred to here as denitrification) in multiple shallow-water estuarine habitats through an annual cycle. We found significantly higher rates of denitrification (DNF) in structured habitats such as submerged aquatic vegetation, salt marshes and oyster reefs than in intertidal and subtidal flats. Seasonal patterns were also observed, with higher DNF rates occurring in the warmer seasons. Additionally, there was an interaction between habitat type and season that we attributed to the seasonal patterns of enhanced productivity in individual habitat types. There was a strong correlation between denitrification and sediment oxygen demand (SOD) in all habitats and all seasons, suggesting the potential to utilize SOD to predict DNF. Denitrification efficiency was also higher in the structured habitats than in the flats. Nitrogen removal by these habitats was found to be an important contributor to estuarine ecosystem function. The ecosystem service of DNF in each habitat was evaluated in US dollars using rates from a regional nutrient-offset market to determine the cost to replace N through management efforts. Habitat-specific values of N removal ranged from approximately three thousand U.S. dollars per acre per year in the submerged aquatic vegetation to approximately four hundred U.S. dollars per acre per year in the subtidal flat. Because of the link between habitat type and processes such as DNF, changes in habitat area and distribution will have consequences for both ecosystem function and the delivery of ecosystem services

Biological activity exceeds biogenic structure in influencing sediment nitrogen cycling in experimental oyster reefs

Oysters are estuarine ecosystem engineers, in that their physical structure and biological function affect ecosystem processes such as organic matter and nutrient cycling. Oysters deliver material to the sediments through biodeposition and sedimentation caused by modification of flow around the reef. We conducted an experiment to distinguish between biotic effects and physical structure of oyster reefs on sediment nitrogen cycling. Experimental reefs consisting of live oysters, oyster shells alone and mudflats (controls) were sampled for a period of 4 wk for sediment organic matter, C and N content and fluxes of nitrogen (NH4+, NOX and N2) and oxygen (O2). We hypothesized that the biological activity of the oyster would deposit more, higher quality organic matter compared to deposition from flow modification alone, thus facilitating denitrification and having a larger impact on sediment nitrogen cycling. Compared to the controls, the live oyster experimental reefs increased sediment denitrification by 61% and the shell experimental reefs showed a 24% increase. The live oyster experimental reef also had the largest O2 demand and NH4+ production. Reef structure likely increased organic matter deposition, but the higher quality and larger quantity of organic matter associated with live oysters increased denitrification and microbial respiration. This experiment shows that the ecosystem service of nitrogen removal provided by oysters is primarily driven by the biological function of the oysters and secondarily from the physical structure of the reef. Our increased understanding of how oysters engineer ecosystems and modify nutrient cycling can help guide future oyster restoration efforts

The pharmacokinetics and toxicity of morning vs. evening tobramycin dosing for pulmonary exacerbations of cystic fibrosis:A randomised comparison

AbstractBackgroundCircadian variation in renal toxicity of aminoglycosides has been demonstrated in animal and human studies. People with CF are frequently prescribed aminoglycosides. Altered pharmacokinetics of aminoglycosides are predictive of toxicity.AimTo investigate whether the time of day of aminoglycoside administration modulates renal excretion of tobramycin and toxicity in children with CF. To determine whether circadian rhythms are disrupted in children with CF during hospital admission.MethodsChildren (age 5–18years) with CF scheduled for tobramycin therapy were randomly allocated to receive tobramycin at 0800 or 2000h. Serum tobramycin levels were drawn at 1h and between 3.5 and 5h post-infusion between days 5 and 9 of therapy. Melatonin levels were measured serially at intervals from 1800h in the evening until 1200h on the next day. Circadian rhythm was categorised as normal when dim light melatonin onset was demonstrated between 1800 and 2200h and/or peak melatonin levels were observed during the night. Weight and spirometry were measured at the start and end of the therapy. Urinary biomarkers of kidney toxicity (KIM1, NAG, NGAL, IL-18 and CysC) were assayed at the start and end of the course of tobramycin.ResultsEighteen children were recruited to the study. There were no differences in renal clearance between the morning and evening groups. The increase in urinary KIM-1 was greater in the evening dosage group compared to the morning group (mean difference, 0.73ng/mg; 95% CI, 0.14 to 1.32; p=0.018). There were no differences in the other urinary biomarkers. There was normal circadian rhythm in 7/11 participants (64%).ConclusionsRenal elimination of tobramycin was not affected by the time of day of administration. Urinary KIM-1 raises the possibility of greater nephrotoxicity with evening administration. Four children showed disturbed circadian rhythm and high melatonin levels (ClinicalTrials.gov NCT01207245)

Consumption rates vary based on the presence and type of oyster structure: A seasonal and latitudinal comparison

As oyster reefs continue to decline worldwide, interest has turned to restoration and aquaculture as ways to sustain the services derived from these ecologically and economically valuable habitats. While biogenic oyster reefs support a variety of ecological functions, it remains unclear whether aquaculture and its associated infrastructure can provide equivalent levels of functioning. Here, we compare consumption rates by fish and invertebrate predators, a key indicator of energy transfer between trophic levels, between reef and aquaculture habitats for the Eastern oyster (Crassostrea virginica) in the Western Atlantic. We deployed a standardized dried squid prey item (‘Squidpops’) in three different structured settings: biogenic oyster reefs, on-bottom aquaculture, and off-bottom aquaculture. For each habitat treatment, we also implemented an adjacent control in nearby bare (unstructured) sediment. These assays were repeated across three seasons at twelve locations spanning 900 km of coastline. We found that consumption rates were contingent on the presence and type of structure: they were highest near off-bottom floating bags, and the difference between structured habitats and unstructured controls was also greatest for this treatment. Moreover, at large temporal and spatial scales, consumption rates increased with increasing temperature, and independently declined with increasing latitude. Our study revealed that certain types of aquaculture support comparable or greater consumption rates than natural reefs, suggesting an important role for this novel structured habitat in maintaining coastal food webs

Saltwater Intrusion Modifies Microbial Community Structure and Decreases Denitrification in Tidal Freshwater Marshes

Environmental changes can alter the interactions between biotic and abiotic ecosystem components in tidal wetlands and therefore impact important ecosystem functions. The objective of this study was to determine how saltwater intrusion affects wetland nutrient biogeochemistry, with a specific focus on the soil microbial communities and physicochemical parameters that control nitrate removal. Our work took place in a tidal freshwater marsh in South Carolina, USA, where a 3.5-year saltwater intrusion experiment increased porewater salinities from freshwater to oligohaline levels. We measured rates of denitrification, soil oxygen demand, and dissimilatory nitrate reduction to ammonium (DNRA) and used molecular genetic techniques to assess the abundance and community structure of soil microbes. In soils exposed to elevated salinities, rates of denitrification were reduced by about 70% due to changes in the soil physicochemical environment (higher salinity, higher carbon:nitrogen ratio) and shifts in the community composition of denitrifiers. Saltwater intrusion also affected the microbial community responsible for DNRA, increasing the abundance of genes associated with this process and shifting microbial community composition. Though rates of DNRA were below detection, the microbial community response may be a precursor to increased rates of DNRA with continued saltwater intrusion. Overall, saltwater intrusion reduces the ability of tidal freshwater marshes to convert reactive nitrogen to dinitrogen gas and therefore negatively affects their water quality functions. Continued study of the interrelationships between biotic communities, the abiotic environment, and biogeochemical transformations will lead to a better understanding of how the progressive replacement of tidal freshwater marshes with brackish analogues will affect the overall functioning of the coastal landscape

A systematic review to identify how the current clinical trials landscape reflects the James Lind Alliance top 10 research priorities for cystic fibrosis

This is a protocol to describe the methodology for a systematic review of clinical trials registries to identify intervention trials in the treatment of CF and map them to priorities for CF research

A systematic review to identify how the current clinical trials landscape reflects the James Lind Alliance top 10 research priorities for cystic fibrosis

This is a protocol to describe the methodology for a systematic review of clinical trials registries to identify intervention trials in the treatment of CF and map them to priorities for CF research