Achieving quality primary care data: a description of the Canadian Primary Care Sentinel Surveillance Network data capture, extraction, and processing in Alberta.

INTRODUCTION: Electronic medical record (EMR) databases have become increasingly popular for secondary purposes, such as health research. The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) is the first and only pan-Canadian primary care EMR data repository, with de-identified health information for almost two million Canadians. Comprehensive and freely available documentation describing the data 'lifecycle' is important for assessing potential data quality issues and appropriate interpretation of research findings. Here, we describe the flow and transformation of CPCSSN data in the province of Alberta. APPROACH: In Alberta, the data originate from 54 publicly-funded primary care settings, including one community pediatric clinic, with 318 providers contributing de-identified EMR data for 410,951 patients (as of December 2018). Data extraction methods have been developed for five different EMR systems, and include both backend and automated frontend extractions. The raw EMR data are transformed according to specific rules, including trimming implausible values, converting values and free text to standard terminologies or classification systems, and structuring the data into a common CPCSSN format. Following local data extraction and processing, the data are transferred to a central repository and made available for research and disease surveillance. CONCLUSION: This paper aims to provide important contextual information to future CPCSSN data users.

A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4.

S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional targets of S100A4 via Toll-like receptor 4 (TLR4)/nuclear factor-κB signaling. SAA proteins stimulated the transcription of RANTES (regulated upon activation normal T-cell expressed and presumably secreted), G-CSF (granulocyte-colony-stimulating factor) and MMP2 (matrix metalloproteinase 2), MMP3, MMP9 and MMP13. We have also shown for the first time that SAA stimulate their own transcription as well as that of proinflammatory S100A8 and S100A9 proteins. Moreover, they strongly enhanced tumor cell adhesion to fibronectin, and stimulated migration and invasion of human and mouse tumor cells. Intravenously injected S100A4 protein induced expression of SAA proteins and cytokines in an organ-specific manner. In a breast cancer animal model, ectopic expression of SAA1 or SAA3 in tumor cells potently promoted widespread metastasis formation accompanied by a massive infiltration of immune cells. Furthermore, coordinate expression of S100A4 and SAA in tumor samples from colorectal carcinoma patients significantly correlated with reduced overall survival. These data show that SAA proteins are effectors for the metastasis-promoting functions of S100A4, and serve as a link between inflammation and tumor progression.

The special deterrent effects of a jail sanction on first-time drunk drivers: a quasi-experimental study.

This study examines the special deterrent effects of alternative sanctions on first-time offenders convicted of driving while intoxicated (DWI). It uses a quasi-experimental design based on the fact that in Hennepin County, Minnesota, some judges did not comply with the judicial policy that mandated a two-day jail sentence for all first-time DWI offenders. Data were collected on all drunk driving cases adjudicated by two judges during an 11-month period. One judge was known to sentence few first offenders to jail; the other was reputed to sentence virtually all first offenders to jail. Of the 383 offenders sentenced by the two judges, 60 were, reconvicted within the 23-month follow-up period. Using judge as an indirect measure of the jail sanction, we found no statistically significant difference in the recidivism rates of persons sentenced by the "jail" and "no jail" judges. Nor did the sanction have a direct effect. After statistically controlling for offender characteristics and prior traffic record, there was no significant difference between those sentenced to a fine (large or small) with no jail and those who were given a two-day jail sentence plus a small fine. Thus, a two-day jail stay is found to be no more effective in deterring subsequent drunk driving by convicted first offenders than an alternative monetary sanction.

Discrimination of three parallel pathways of lactate transport in the human erythrocyte membrane by inhibitors and kinetic properties.

The transmembrane movements of lactate and other monocarboxylate anions in mammalian erythrocytes have been claimed, by virtue of their sensitivity to SH-reagents, to involve a transfer system different from the classical anion system (Deuticke, B., Rickert, I. and Beyer, E. (1978) Biochim. Biophys. Acta 507, 137-155). Inhibition of monocarboxylate transfer by SH-reagents, however, was incomplete to an extent varying for different monocarboxylates. The transport component insensitive to SH-reagents has now been shown to involve (a) the classical anion-exchange system, as demonstrated by sensitivity to specific disulfonate inhibitors, and (b) nonionic diffusion, as indicated by the characteristic pH- and concentration dependency of this component and its stimulation by aliphatic alcohols. Under physiological conditions about 90% of total lactate movement proceed via the specific system, 5% via the classical anion-transfer system, 5% by nonionic diffusion. These three components of lactate exchange differ in their activation energies. The specific lactate system mediates net fluxes almost as fast as exchange fluxes, in marked contrast to the classical anion-exchange system which mediated halide exchange much faster than halide net movements. The underlying mechanism, for maintenance of electroneutrality, is an OH- -antiport or an H+ -symport as indicated by the particular response of lactate net fluxes to changes of intra- or extracellular pH.

Influence of enzymatic phospholipid cleavage on the permeability of the erythrocyte membrane: III. Discrimination between the causal role of split products and of lecithin removal.

Cleavage of 55% of the lecithin in intact human erythrocytes by phospholipase A2 (bee venom) markedly inhibits the mediated transport of L-lactate (via the monocarboxylate carrier) and of L-arabinose (via the monosaccharide carrier), while the major anion exchange system (probed by oxalate) and diffusion via the lipid domain (probed by erythritol) remain essentially unaltered. the causal role of the split products, unsaturated fatty acids and saturated lysolecithin, and of lecithin removal were now studied by sequential extraction of split products with serum albumin and by their controlled insertion into normal membranes. Careful choice of the albumin-to-cell ration allowed the extraction of more than 95% or the fatty acids and up to 80% of the lysolecithin without hemolysis. Extraction of fatty acids abolished inhibition of lactate and arabinose transfer, but induced inhibition of anion exchange and translipid permeation. Subsequent extraction of lysolecithin produced no further effects except on lactate transfer, which was inhibited. Exogenous oleic and linoleic acid, at intramembrane concentrations equal to those produced by phospholipase A2, inhibit lactate and arabinose transfer, while accelerating oxalate and erythritol movements, in agreement with effects of endogenous fatty acids. Exogenous lysolecithin inhibits all mediated transfer processes but does not alter translipid permeation. This pattern differs from that obtained for endogenous lysolecithin. The action of exogenous lysolecithin can be suppressed by loading of the cells with cholesterol. Insertion of exogenous lysolecithin into cells depleted of endogenous lysolecithin does not restore the functional state before depletion, indicating that exogenous and endogenous lysolecithin may act differently.

Dual effect of membrane cholesterol on simple and mediated transport processes in human erythrocytes.

The influence of cholesterol on simple and facilitated transport processes across the membrane of intact human erythrocytes was studied after graded depletion or enrichment of membrane cholesterol by incubation of the cells in phospholipid or phospholipid/cholesterol suspensions. 1. The carrier-mediated transfer of L-lactate and of L-arabinose proved to be enhanced in this effect. In contrast, the self-exchange of SO4(2-), mediated by the inorganic anion-exchange system, and the simple diffusion of erythritol via the lipid phase of the membrane are inhibited by cholesterol. 2. Reversibility of these two opposite effects of cholesterol was demonstrated by measurements on cells depleted again after cholesterol enrichment and enriched again after previous depletion. 3. Certain phospholipids used for preparing the lipid dispersions that are required for cholesterol variation have effects on permeability of their own, due, for example, to traces of contaminants. A discrimination of such artifacts due, for example, to traces of contaminants. A discrimination of such artifacts from the effects of cholesterol is only possible by demonstrating reversibility. 4. The opposite effects of cholesterol on various facilitated transfer processes, which have a correlation in the opposite effects of other modifications of the membrane lipid phase (Deuticke, B., Grunze, M. and Haest, C.W.M. (1979) Alfred Benzon Symposium 14, Munksgaard, Copenhagen, in the press), are indicative of different types of lipid-protein interaction in the erythrocyte membrane.