Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients

Background: Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam

Secchi disk measurements in turbid water

In the classical theory of the Secchi disk depth, diffuse sunlight falling on the disk is reflected back to the observer’s eye along the most direct route, as a beam. The disappearance depth, ZSD, of the disk is then expected to vary inversely with the sum of the beam and diffuse attenuation coefficients: c+KD. Observations presented here show that, in the most turbid waters sampled, the Secchi disk is visible at greater depths (by a factor of up to 4) than predicted by this theory. In these conditions, the disk appears blurry and it seems likely that some of the light reflected by the disk returns to the eye as diffuse light, photons being scattered one or more times on their journey from the disk surface to the observer. We have modified the theory of the Secchi disk in turbid water to allow for a mixture of beamed and diffuse light contributing to disk visibility. The modified theory corrects the under-estimate of Secchi depths in turbid waters and gives good agreement with observations over a wide range of turbidity. The insight gained allows a more informed interpretation of Secchi disk measurements in turbid water. Supplemental data files: https://doi.org/10.25773/z8qm-c77

Monte Carlo simulations: maximizing antibiotic pharmacokinetic data to optimize clinical practice for critically ill patients

Infections in critically ill patients continue to result in unacceptably high morbidity and mortality. Although few data exist for correlating antibiotic exposure with outcome, antibiotic dosing is likely to be highly important for maximizing resolution of infection in many patients. The practical and financial difficulties of performing pharmacokinetic (PK) studies in critically ill patients mean that analyses to maximize data such as Monte Carlo simulation (MCS) are highly valuable. MCS uses computer software to perform virtual clinical trials. The building blocks for MCS are: firstly, a robust population PK model from the patient population of interest; secondly, descriptors of the effect of covariates that influence the PK parameters; thirdly, description of the susceptibility of bacteria to the antibiotic and finally a PK/pharmacodynamic (PD) target associated with antibiotic efficacy. Probability of target attainment (PTA) outputs can then be generated that describe the proportion of patients that will achieve a pre-specified PD target for an MIC distribution. Such analyses can then inform dosing requirements, which can be used to have a high likelihood of achieving PK/PD targets for organisms with different MICs. In this issue of JAC, Zelenitsky et al. provide a very useful example of MCS for interpreting the optimal methods for dosing meropenem, piperacillin/tazobactam, cefepime and ceftobiprole in critically ill patients

Atom--Molecule Coherence in a Bose-Einstein Condensate

Coherent coupling between atoms and molecules in a Bose-Einstein condensate (BEC) has been observed. Oscillations between atomic and molecular states were excited by sudden changes in the magnetic field near a Feshbach resonance and persisted for many periods of the oscillation. The oscillation frequency was measured over a large range of magnetic fields and is in excellent quantitative agreement with the energy difference between the colliding atom threshold energy and the energy of the bound molecular state. This agreement indicates that we have created a quantum superposition of atoms and diatomic molecules, which are chemically different species.Comment: 7 pages, 6 figure

MDMA and brain activity during neurocognitive performance: An overview of neuroimaging studies with abstinent 'Ecstasy' users.

MDMA/Ecstasy has had a resurgence in popularity, with recent supplies comprising higher strength MDMA, potentially leading to increased drug-related harm. Neurocognitive problems have been widely reported in ecstasy users, equally some studies report null findings, and it remains unclear which factors underlie the development of neurocognitive impairments. This review covers the empirical research into brain activity during neurocognitive performance, using fMRI, fNIRS, and EEG. Our main conclusion is that chronic repeated use of recreational ecstasy can result in haemodynamic and electrophysiological changes that reflect recruitment of additional resources to perform cognitive tasks. Findings are consistent with serotonergic system changes, although whether this reflects neurotoxicity or neuroadaptation, cannot be answered from these data. There is a degree of heterogeneity in the methodologies and findings, limiting the strengths of current conclusions. Future research with functional neuroimaging paired with molecular imaging, genetics or pharmacological challenges of the serotonin system may help to decipher the link between serotonergic and cognitive changes in ecstasy users

Exome-wide association study of pancreatic cancer risk

We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10(-6); exome-wide statistical significance threshold P<2.5x10(-6)). Cases had more rare inactivating variants in DNA repair genes than controls, even after excluding 13 genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35, P=.045). At the suggestive threshold (P<.001), 6 genes were enriched for rare damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had associations with pancreatic cancer risk, based on the sequence-kernel association test. We confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic cancer and we also identified candidate pancreatic cancer genes. Large collaborations and novel approaches are needed to overcome the genetic heterogeneity of pancreatic cancer predisposition

Investigation of chlorine radical chemistry in the Eyjafjallajkull volcanic plume using observed depletions in non-methane hydrocarbons

As part of the effort to understand volcanic plume composition and chemistry during the eruption of the Icelandic volcano Eyjafjallajkull, the CARIBIC atmospheric observatory was deployed for three special science flights aboard a Lufthansa passenger aircraft. Measurements made during these flights included the collection of whole air samples, which were analyzed for non-methane hydrocarbons (NMHCs). Hydrocarbon concentrations in plume samples were found to be reduced to levels below background, with relative depletions characteristic of reaction with chlorine radicals (Cl). Recent observations of halogen oxides in volcanic plumes provide evidence for halogen radical chemistry, but quantitative data for free halogen radical concentrations in volcanic plumes were absent. Here we present the first observation-based calculations of Cl radical concentrations in volcanic plumes, estimated from observed NMHC depletions. Inferred Cl concentrations were between 1.3 × 10 and 6.6 × 10 Cl cm. The relationship between NMHC variability and local lifetimes was used to investigate the ratio between OH and Cl within the plume, with [OH]/[Cl] estimated to be ∼37. Copyright 2011 by the American Geophysical Union

A feasibility study of implementing grip strength measurement into routine hospital practice (GRImP): study protocol.

BACKGROUND: Handgrip strength is a non-invasive marker of muscle strength, and low grip strength in hospital inpatients is associated with poor healthcare outcomes including longer length of stay, increased functional limitations, and mortality. Measuring grip strength is simple and inexpensive. However, grip strength measurement is not routinely used in clinical practice. The aim of this study is to evaluate the feasibility of implementing grip strength measurement into routine clinical practice. METHODS/DESIGN: This feasibility study is a mixed methods design combining qualitative, quantitative, and economic elements and is based on the acute medical wards for older people in one hospital. The study consists of three phases: phase 1 will define current baseline practice for the identification of inpatients at high risk of poor healthcare outcomes, their nutrition, and mobility care through interviews and focus groups with staff as well as a review of patients' clinical records. Phase 2 will focus on the feasibility of developing and implementing a training programme using Normalisation Process Theory to enable nursing and medical staff to measure and interpret grip strength values. Following the training, grip strength will be measured routinely for older patients as part of admission procedures with the use of a care plan for those with low grip strength. Finally, phase 3 will evaluate the acceptability of grip strength measurement, its adoption, coverage, and basic costs using interviews and focus groups with staff and patients, and re-examination of clinical records. DISCUSSION: The results of this study will inform the translation of grip strength measurement from a research tool into clinical practice to improve the identification of older inpatients at risk of poor healthcare outcomes. TRIAL REGISTRATION: Clinicaltrials.gov NCTO2447445