Evidence-based rules from family practice to inform family practice; The learning healthcare system case study on urinary tract infections

Background: Analysis of encounter data relevant to the diagnostic process sourced from routine electronic medical record (EMR) databases represents a classic example of the concept of a learning healthcare system (LHS). By collecting International Classification of Primary Care (ICPC) coded EMR data as part of the Transition Project from Dutch and Maltese databases (using the EMR TransHIS), data mining algorithms can empirically quantify the relationships of all presenting reasons for encounter (RfEs) and recorded diagnostic outcomes. We have specifically looked at new episodes of care (EoC) for two urinary system infections: simple urinary tract infection (UTI, ICPC code: U71) and pyelonephritis (ICPC code: U70). Methods: Participating family doctors (FDs) recorded details of all their patient contacts in an EoC structure using the ICPC, including RfEs presented by the patient, and the FDs' diagnostic labels. The relationships between RfEs and episode titles were studied using probabilistic and data mining methods as part of the TRANSFoRm project. Results: The Dutch data indicated that the presence of RfE's "Cystitis/Urinary Tract Infection", "Dysuria", "Fear of UTI", "Urinary frequency/urgency", "Haematuria", "Urine symptom/complaint, other" are all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract Infection". The Maltese data indicated that the presence of RfE's "Dysuria", "Urinary frequency/urgency", "Haematuria" are all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract Infection". The Dutch data indicated that the presence of RfE's "Flank/axilla symptom/complaint", "Dysuria", "Fever", "Cystitis/Urinary Tract Infection", "Abdominal pain/cramps general" are all strong, reliable, predictors for the diagnosis "Pyelonephritis". The Maltese data set did not present any clinically and statistically significant predictors for pyelonephritis. Conclusions: We describe clinically and statistically significant diagnostic associations observed between UTIs and pyelonephritis presenting as a new problem in family practice, and all associated RfEs, and demonstrate that the significant diagnostic cues obtained are consistent with the literature. We conclude that it is possible to generate clinically meaningful diagnostic evidence from electronic sources of patient data

Freshly Formed Dust in the Cassiopeia A Supernova Remnant as Revealed by the Spitzer Space Telescope

We performed Spitzer Infrared Spectrograph mapping observations covering nearly the entire extent of the Cassiopeia A supernova remnant (SNR), producing mid-infrared (5.5-35 micron) spectra every 5-10". Gas lines of Ar, Ne, O, Si, S and Fe, and dust continua were strong for most positions. We identify three distinct ejecta dust populations based on their continuum shapes. The dominant dust continuum shape exhibits a strong peak at 21 micron. A line-free map of 21 micron-peak dust made from the 19-23 micron range closely resembles the [Ar II], [O IV], and [Ne II] ejecta-line maps implying that dust is freshly formed in the ejecta. Spectral fitting implies the presence of SiO2, Mg protosilicates, and FeO grains in these regions. The second dust type exhibits a rising continuum up to 21 micron and then flattens thereafter. This ``weak 21 micron'' dust is likely composed of Al2O3 and C grains. The third dust continuum shape is featureless with a gently rising spectrum and is likely composed of MgSiO3 and either Al2O3 or Fe grains. Using the least massive composition for each of the three dust classes yields a total mass of 0.02 Msun. Using the most-massive composition yields a total mass of 0.054 Msun. The primary uncertainty in the total dust mass stems from the selection of the dust composition necessary for fitting the featureless dust as well as 70 micron flux. The freshly formed dust mass derived from Cas A is sufficient from SNe to explain the lower limit on the dust masses in high redshift galaxies.Comment: 8 figures: Accepted for the publication in Ap

Time Variability in the X-ray Nebula Powered by Pulsar B1509-58

We use new and archival Chandra and ROSAT data to study the time variability of the X-ray emission from the pulsar wind nebula (PWN) powered by PSR B1509-58 on timescales of one week to twelve years. There is variability in the size, number, and brightness of compact knots appearing within 20" of the pulsar, with at least one knot showing a possible outflow velocity of ~0.6c (assuming a distance to the source of 5.2 kpc). The transient nature of these knots may indicate that they are produced by turbulence in the flows surrounding the pulsar. A previously identified prominent jet extending 12 pc to the southeast of the pulsar increased in brightness by 30% over 9 years; apparent outflow of material along this jet is observed with a velocity of ~0.5c. However, outflow alone cannot account for the changes in the jet on such short timescales. Magnetohydrodynamic sausage or kink instabilities are feasible explanations for the jet variability with timescale of ~1.3-2 years. An arc structure, located 30"-45" north of the pulsar, shows transverse structural variations and appears to have moved inward with a velocity of ~0.03c over three years. The overall structure and brightness of the diffuse PWN exterior to this arc and excluding the jet has remained the same over the twelve year span. The photon indices of the diffuse PWN and possibly the jet steepen with increasing radius, likely indicating synchrotron cooling at X-ray energies.Comment: accepted to ApJ, 14 pages, 8 figure

Temperature-Dependent Magnetoelectric Effect from First Principles

We show that nonrelativistic exchange interactions and spin fluctuations can give rise to a linear magnetoelectric effect in collinear antiferromagnets at elevated temperatures that can exceed relativistic magnetoelectric responses by more than 1 order of magnitude. We show how symmetry arguments, ab initio methods, and Monte Carlo simulations can be combined to calculate temperature-dependent magnetoelectric susceptibilities entirely from first principles. The application of our method to Cr2O3 gives quantitative agreement with experiment.

Cassiopeia A: dust factory revealed via submillimetre polarimetry

If Type-II supernovae - the evolutionary end points of short-lived, massive stars - produce a significant quantity of dust (>0.1 M_sun) then they can explain the rest-frame far-infrared emission seen in galaxies and quasars in the first Gyr of the Universe. Submillimetre observations of the Galactic supernova remnant, Cas A, provided the first observational evidence for the formation of significant quantities of dust in Type-II supernovae. In this paper we present new data which show that the submm emission from Cas A is polarised at a level significantly higher than that of its synchrotron emission. The orientation is consistent with that of the magnetic field in Cas A, implying that the polarised submm emission is associated with the remnant. No known mechanism would vary the synchrotron polarisation in this way and so we attribute the excess polarised submm flux to cold dust within the remnant, providing fresh evidence that cosmic dust can form rapidly. This is supported by the presence of both polarised and unpolarised dust emission in the north of the remnant, where there is no contamination from foreground molecular clouds. The inferred dust polarisation fraction is unprecedented (f_pol ~ 30%) which, coupled with the brief timescale available for grain alignment (<300 yr), suggests that supernova dust differs from that seen in other Galactic sources (where f_pol=2-7%), or that a highly efficient grain alignment process must operate in the environment of a supernova remnant.Comment: In press at MNRAS, 10 pages, print in colou

Lithium-to-calcium ratios in Modern, Cenozoic, and Paleozoic articulate brachiopod shells

Li/Ca ratios in modern brachiopod shells generally correlate inversely with growth temperature, ranging from ∼20 µmol/mol at 30°C to ∼50 µmol/mol at 0°C with no apparent interspecific offsets. Causes of the temperature effect on Li/Ca ratios are not yet understood. Cenozoic brachiopod Li/Ca ratios average ∼30 µmol/mol, similar to the average observed in modern brachiopods. Relatively constant Li/Ca ratios for Eocene to Pleistocene nonluminescent brachiopod shells, consistent with previous observations of Cenozoic planktonic foraminifera, support the conclusion of little variation in Cenozoic seawater Li/Ca. Nonluminescent portions of Permian and Carboniferous brachiopods have Li/Ca ratios substantially lower (generally <10 µmol/mol) than modern, Cenozoic, or Devonian samples. Mass balance considerations, constrained by δ18O of brachiopods, suggest that low Li concentrations in Permo-Carboniferous seawater could be the result of a lower flux of dissolved Li from the continents and/or a higher flux of Li from seawater to clastic marine sediments. Nonluminescent Devonian brachiopods from a single hand specimen have Li/Ca ratios around 70% of the modern average. These Li/Ca ratios can be explained by either somewhat higher temperature with constant seawater Li/Ca, somewhat lower seawater Li/Ca at constant temperature, or a combination of slightly elevated temperature and slightly lower seawater Li/Ca

Competition between phasic and asynchronous release for recovered synaptic vesicles at developing hippocampal autaptic synapses

Developing hippocampal neurons in microisland culture undergo rapid and extensive transmitter release-dependent depression of evoked (phasic) excitatory synaptic activity in response to 1 sec trains of 20 Hz stimulation. Although evoked phasic release was attenuated by repeated stimuli, asynchronous (miniature like) release continued at a high rate equivalent to approximately 2.8 readily releasable pools (RRPs) of quanta/sec. Asynchronous release reflected the recovery and immediate release of quanta because it was resistant to sucrose-induced depletion of the RRP. Asynchronous and phasic release appeared to compete for a common limited supply of release-ready quanta because agents that block asynchronous release, such as EGTA-AM, led to enhanced steady-state phasic release, whereas prolongation of the asynchronous release time course by LiCl delayed recovery of phasic release from depression. Modeling suggested that the resistance of asynchronous release to depression was associated with its ability to out-compete phasic release for recovered quanta attributable to its relatively low release rate (up to 0.04/msec per vesicle) stimulated by bulk intracellular Ca2+ concentration ([Ca2+]i) that could function over prolonged intervals between successive stimuli. Although phasic release was associated with a considerably higher peak rate of release (0.4/msec per vesicle), the [Ca2+]i microdomains that trigger it are brief (1 msec), and with asynchronous release present, relatively few quanta can accumulate within the RRP to be available for phasic release. We conclude that despite depression of phasic release during train stimulation, transmission can be maintained at a near-maximal rate by switching to an asynchronous mode that takes advantage of a bulk presynaptic [Ca2+]i

Improving specialist drug prescribing in primary care using task and error analysis: an observational study

Background Electronic prescribing has benefited from computerised clinical decision support systems (CDSSs); however, no published studies have evaluated the potential for a CDSS to support GPs in prescribing specialist drugs. Aim To identify potential weaknesses and errors in the existing process of prescribing specialist drugs that could be addressed in the development of a CDSS. Design and setting Semi-structured interviews with key informants followed by an observational study involving GPs in the UK. Method Twelve key informants were interviewed to investigate the use of CDSSs in the UK. Nine GPs were observed while performing case scenarios depicting requests from hospitals or patients to prescribe a specialist drug. Activity diagrams, hierarchical task analysis, and systematic human error reduction and prediction approach analyses were performed. Results The current process of prescribing specialist drugs by GPs is prone to error. Errors of omission due to lack of information were the most common errors, which could potentially result in a GP prescribing a specialist drug that should only be prescribed in hospitals, or prescribing a specialist drug without reference to a shared care protocol. Half of all possible errors in the prescribing process had a high probability of occurrence. Conclusion A CDSS supporting GPs during the process of prescribing specialist drugs is needed. This could, first, support the decision making of whether or not to undertake prescribing, and, second, provide drug-specific parameters linked to shared care protocols, which could reduce the errors identified and increase patient safety

Improving specialist drug prescribing in primary care using task and error analysis: an observational study

BACKGROUND: Electronic prescribing has benefited from computerised clinical decision support systems (CDSSs); however, no published studies have evaluated the potential for a CDSS to support GPs in prescribing specialist drugs. AIM: To identify potential weaknesses and errors in the existing process of prescribing specialist drugs that could be addressed in the development of a CDSS. DESIGN AND SETTING: Semi-structured interviews with key informants followed by an observational study involving GPs in the UK. METHOD: Twelve key informants were interviewed to investigate the use of CDSSs in the UK. Nine GPs were observed while performing case scenarios depicting requests from hospitals or patients to prescribe a specialist drug. Activity diagrams, hierarchical task analysis, and systematic human error reduction and prediction approach analyses were performed. RESULTS: The current process of prescribing specialist drugs by GPs is prone to error. Errors of omission due to lack of information were the most common errors, which could potentially result in a GP prescribing a specialist drug that should only be prescribed in hospitals, or prescribing a specialist drug without reference to a shared care protocol. Half of all possible errors in the prescribing process had a high probability of occurrence. CONCLUSION: A CDSS supporting GPs during the process of prescribing specialist drugs is needed. This could, first, support the decision making of whether or not to undertake prescribing, and, second, provide drug-specific parameters linked to shared care protocols, which could reduce the errors identified and increase patient safety

Alvimopan for the Management of Postoperative Ileus After Bowel Resection: Characterization of Clinical Benefit by Pooled Responder Analysis

BACKGROUND: A pooled post hoc responder analysis was performed to assess the clinical benefit of alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist, for the management of postoperative ileus after bowel resection. METHODS: Adult patients who underwent laparotomy for bowel resection scheduled for opioid-based intravenous patient-controlled analgesia received oral alvimopan or placebo preoperatively and twice daily postoperatively until hospital discharge or for 7 postoperative days. The proportion of responders and numbers needed to treat (NNT) were examined on postoperative days (POD) 3-8 for GI-2 recovery (first bowel movement, toleration of solid food) and hospital discharge order (DCO) written. RESULTS: Alvimopan significantly increased the proportion of patients with GI-2 recovery and DCO written by each POD (P \u3c 0.001 for all). More patients who received alvimopan achieved GI-2 recovery on or before POD 5 (alvimopan, 80%; placebo, 66%) and DCO written before POD 7 (alvimopan, 87%; placebo, 72%), with corresponding NNTs equal to 7. CONCLUSIONS: On each POD analyzed, alvimopan significantly increased the proportion of patients who achieved GI-2 recovery and DCO written versus placebo and was associated with relatively low NNTs. The results of these analyses provide additional characterization and support for the overall clinical benefit of alvimopan in patients undergoing bowel resection