Features and frequency of use of electronic health records in primary care across 20 countries: a cross-sectional study.

OBJECTIVES: Variation exists in the capabilities of electronic healthcare records (EHRs) systems and the frequency of their use by primary care physicians (PCPs) from different settings. We aimed to examine the factors associated with everyday EHRs use by PCPs, characterise the EHRs features available to PCPs, and to identify the impact of practice settings on feature availability. STUDY DESIGN: Cross-sectional study. METHODS: PCPs from 20 countries completed cross-sectional online survey between June and September 2020. Responses which reported frequency of EHRs use were retained. Associations between everyday EHRs use and PCP and practice factors (country, urbanicity, and digital maturity) were explored using multivariable logistic regression analyses. The effect of practice factors on the variation in availability of ten EHRs features was estimated using Cramer's V. RESULTS: Responses from 1520 out of 1605 PCPs surveyed (94·7%) were retained. Everyday EHRs use was reported by 91·2% of PCPs. Everyday EHRs use was associated with PCPs working >28 h per week, having more years of experience using EHRs, country of employment, and higher digital maturity. EHRs features concerning entering, and retrieving data were available to most PCPs. Few PCPs reported having access to tools for 'interactive patient education' (37·3%) or 'home monitoring and self-testing of chronic conditions' (34·3%). Country of practice was associated with availability of all EHRs features (Cramer's V range: 0·2-0·6), particularly with availability of tools enabling patient EHRs access (Cramer's V: 0·6, P < 0.0001). Greater feature availability of EHRs features was observed with greater digital maturity. CONCLUSIONS: EHRs features intended for patient use were uncommon across countries and levels of digital maturity. Systems-level research is necessary to identify the country-specific barriers impeding the implementation of EHRs features in primary care, particularly of EHRs features enabling patient interaction with EHRs, to develop strategies to improve systems-wide EHRs use.

Which positive factors determine the GP satisfaction in clinical practice? A systematic literature review.

BACKGROUND: Looking at what makes General Practitioners (GPs) happy in their profession, may be important in increasing the GP workforce in the future. The European General Practice Research Network (EGPRN) created a research team (eight national groups) in order to clarify the factors involved in GP job satisfaction throughout Europe. The first step of this study was a literature review to explore how the satisfaction of GPs had been studied before. The research question was "Which factors are related to GP satisfaction in Clinical Practice?" METHODS: Systematic literature review according to the PRISMA statement. The databases searched were Pubmed, Embase and Cochrane. All articles were identified, screened and included by two separate research teams, according to inclusion or exclusion criteria. Then, a qualitative appraisal was undertaken. Next, a thematic analysis process was undertaken to capture any issue relevant to the research question. RESULTS: The number of records screened was 458. One hundred four were eligible. Finally, 17 articles were included. The data revealed 13 subthemes, which were grouped into three major themes for GP satisfaction. First there were general profession-related themes, applicable to many professions. A second group of issues related specifically to a GP setting. Finally, a third group was related to professional life and personal issues. CONCLUSIONS: A number of factors leading to GP job satisfaction, exist in literature They should be used by policy makers within Europe to increase the GP workforce. The research team needs to undertake qualitative studies to confirm or enhance those results.

Ex vivo characterization of human atherosclerotic iliac plaque components using cryo-imaging.

We characterized atherosclerotic plaque components with a novel cryo-imaging system in lieu of standard histological methods commonly used for imaging validation and research endpoints. We aim to accurately identify plaque tissue types from fresh cadaver specimens rapidly (less than 5 h) in three dimensions for large specimens (up to 4 cm vessel segments). A single-blind validation study was designed to determine sensitivity, specificity and inter-rater agreement (Fleiss' Kappa) of cryo-imaging tissue types with histology as the gold standard. Six naïve human raters identified 344 tissue type samples in 36 cryo-image sets after being trained. Tissue type sensitivities are as follows: greater than 90% for adventitia, media-related, smooth muscle cell ingrowth, external elastic lamina, internal elastic lamina, fibrosis, dense calcification and haemorrhage; greater than 80% for lipid and light calcification; and greater than 50% for cholesterol clefts. Specificities were greater than 95% for all tissue types. The results demonstrate convincingly that cryo-imaging can be used to accurately identify most tissue types. If the cryo-imaging data are entered into visualization software, three-dimensional renderings of the plaque can be generated to visualize and quantify plaque components.

Influenza surveillance during winter 1997-1998 in Israel.

BACKGROUND: Each winter influenza activity is a major cause of morbidity and mortality both in Israel and worldwide. OBJECTIVES: To identify the influenza viruses active in Israel during the winter season and to assess the extent of influenza morbidity. METHODS: Information was collected on a population of 18,684 individuals enrolled in two community clinics in central Israel. It included the total number of visits for acute respiratory infection--including influenza and influenza-like illness (ARI/flu-like)--during a 20 week surveillance period (23 November 1997 to 27 March 1998) and the percent of influenza virus isolates in nasopharyngeal specimens from a sample of patients with ARI/flu-like collected on a weekly basis during the same period. RESULTS: A total of 5,947 visits for ARI/flu-like were recorded among 18,684 enrolled patients in two community clinics (18.1%). The progressive increase in the number of visits for ARI/flu-like reached a peak on week 2/98 with 597 visits and a rate of 31.95 visits per 1,000 population. After this, a decrease to the initial values was evident by week 12/98. Most affected patients were in the age groups 5-14 and 65 years and over, with a rate of 733.5 and 605.3 visits per 1,000 population, respectively. Influenza virus was isolated from 92 of the 426 nasopharyngeal specimens (21.6%). The most commonly detected strain was A/Sydney/5/97 (H3N2) like (77.2%). The peak rate of isolates was recorded at the beginning of January (01/98). CONCLUSIONS: A/Sydney/5/97 (H3N2) like-strain was the dominant influenza virus. Its presence did not prevent the simultaneous activity of influenza A/H1N1 virus. The dynamic of the clinical disease as expressed by the weekly visit rate for ARI/flu-like was similar to the temporal pattern of the virological findings. The extent of morbidity suggests moderate epidemic activity.

A primer on lower extremity outcome measurement instruments.

Tracing the roots of lower extremity outcome scales is an interesting and somewhat bemusing journey. A large number of different grading methods can be found with limited reliability and/or validity testing. The usefulness of these instruments in the assessment of patient outcomes after lower extremity interventions is worrisome. This article focuses on the most commonly used scales and demonstrates an alarming and incestuous pattern of cross-validation with moderate to weak associations between potentially unreliable and crudely validated original instruments.

The role of antibiotics in the management of elective and post-traumatic hand surgery.

The use of prophylactic antibiotics in elective and emergency hand surgery is an unsettled issue. Although their benefit in general surgical cases and certain orthopedic cases is well established, the lower infection rates in elective and emergency hand surgery have made attempts to prove the efficacy of prophylaxis more difficult. Valid arguments can be made for the use of antibiotics in human and animal bites. Prophylactic antibiotic use is efficacious in the following scenarios: (1) soft-tissue reconstructive procedures with large flaps, (2) total elbow or wrist implant arthroplasty, (3) procedures of long duration, and (4) complex open hand trauma with wound contamination and extensive soft-tissue and bony injury. Antibiotic prophylaxis does not appear warranted in clean, elective procedures lasting fewer than 2 hours. The duration of antibiotic use should be as short as possible to minimize complications and the development of bacterial resistance. The selection of a particular antibiotic regimen remains the surgeon's choice, but many inexpensive and relatively safe antibiotic agents are available. Although uncommon, potentially serious hazards exist with the use of antibiotics. Definitive guidelines on the use of antibiotics in hand surgery are not available; hand surgeons should apply basic principles of prophylaxis and be aware of the existing controversies.

Role of cytokines in periodontal diseases.

The known actions of cytokines suggest that these molecules hold a great potential for modulating the host immune response and enhancing tissue regeneration. These molecules would be useful in controlling the adverse effects of the host immune response and/or augmenting the regenerative potential of cytokines. Once the technology is optimized, it may be possible for dentists to apply cytokine therapy to resolve periodontal infections. Such therapeutic measures hold promise not only in the resolution of periodontal infections, but also in the treatment of other diseases of the oral cavity.

Measurement of vertebral cortical integrity during pedicle exploration for intrapedicular fixation.

STUDY DESIGN: This study determined the predictive ability of electrical impedance measurement in detecting cortical perforation in a porcine model of pedicular exploration. OBJECTIVE: This study tested the hypothesis that a large decrease in electrical impedance would occur as a result of perforation of the vertebral cortex by the pedicle probe. SUMMARY OF BACKGROUND DATA: The resistivity of cortical bone has been reported to be 25 to 100 times greater than that of soft tissues. METHODS: A total of 42 pedicles of the lumbar spines of six swine were explored using the instrumented pedicle probes. RESULTS: Using a 1 microAmp 30-Hz current source, measurement of electrical impedance predicted cortical rupture with a sensitivity, specificity, and accuracy of 95%. Maximum applied voltages of 2.8 mV did not result in myogenic stimulus. CONCLUSIONS: Electrical impedance measurement provides an accurate real-time measurement of cortical perforation. This technique is adapted readily for use with pedicular screws and screw tape. Further investigation to determine the clinical use of this technique is recommended.

Importance of severity of coronary artery disease for the tolerance to normovolemic hemodilution. Comparison of single-vessel versus multivessel stenoses in a canine model.

The response of global cardiovascular and regional myocardial function (as seen with sonomicrometry) to continuous, progressive hemodilution (Dextran 70) was compared in dogs with proximal circumflex coronary artery stenosis and dogs with proximal circumflex coronary artery and proximal left anterior descending artery stenoses. Hemodilution-induced failure, defined as greater than 50% loss in function or death of the animal, was determined for systolic shortening in the circumflex coronary artery and left anterior descending artery territories, mean arterial pressure, and maximum left ventricular rate of pressure rise. Time to failure was compared between groups by log-rank tests. Systolic shortening of the circumflex coronary artery failed at a similar median time point in both groups (30 minutes in the group with single-vessel stenosis and hemodilution versus 40 minutes in the group with multivessel stenosis and hemodilution). Systolic shortening of the left anterior descending artery (80 versus 50 minutes), mean arterial pressure (70 versus 50 minutes), and maximum left ventricular rate of pressure rise (70 versus 40 minutes), however, failed significantly later (p < 0.01) in animals with single circumflex coronary artery stenosis. A marked increase (+50%) in systolic shortening of the left anterior descending artery was observed during hemodilution only in the circumflex coronary artery stenosis group. The better hemodilution tolerance in the circumflex coronary artery stenosis group may be explained by the compensatory increase in myocardial contractile function in non-coronary flow-compromised myocardium, which seems to be crucial for global cardiovascular stability during hemodilution in the presence of coronary stenoses.

The importance of screening edentulous patients for oral cancer.

A study of the dental status of 947 patients with oral cancer was conducted to determine how dentists might gain better access to patients in whom this disease develops. This access could lead to earlier diagnosis and thereby improve the prognosis. Dental profiles revealed that 68% of the patients were partially or totally edentulous, 14% had neglected teeth, and the remaining 18% had intact dentitions. The mean age of patients was 61.7 years. Efforts should be made to promote the recall of edentulous patients. This may facilitate an earlier discovery of many oral cancers.

Iodophenylarsine oxide and arsenical affinity chromatography: new probes for dithiol proteins. Application to tubulins and to components of the insulin receptor-glucose transporter signal transduction pathway.

In our studies of the effects of the trivalent arsenical phenylarsine oxide on insulin-dependent hexose uptake in 3T3-L1 adipocytes, we needed direct methods to study arsenical-protein interactions. In this report, we describe two such new tools. The first is the radiolabeled covalent affinity reagent 4-[125I]iodophenylarsine oxide. This compound has effects on 3T3-L1 adipocytes similar to those of phenylarsine oxide both with respect to effects of hexose uptake and the accumulation of pp15, a phosphotyrosine-containing putative mediator of insulin action. Iodophenylarsine oxide labels numerous proteins in intact cells in a concentration-dependent, but apparently insulin-independent fashion. The second tool is trivalent arsenical affinity chromatography, which we use to show novel direct interactions between trivalent arsenicals and several proteins from 3T3-L1 adipocytes including the insulin-responsive glucose transporter GLUT4, the insulin proreceptor, and both the alpha and beta subunits of tubulin. The non-insulin-dependent glucose transporter GLUT1, the mature insulin receptor, and the fatty acid-binding protein 422(aP2) do not show strong interactions with arsenical resin. These results provide a new chemical approach to the study of both insulin-dependent hexose transport and tubulin function.

Painless intussusception. Giving conservative treatment another chance.

Treatment options for intussusception in children range from reduction by barium enema to surgical intervention. The authors describe a case in which a conservative option--a fifth attempt to reduce an ileocolic intussusception by barium enema, this time using general anesthesia--successfully resolved the problem.

Excitatory amino acid immunoreactivity in vestibulo-ocular neurons in gerbils.

Retrogradely labeled vestibulo-ocular neurons (VOR) that also stain with antibodies for the excitatory amino acid neurotransmitters glutamate (GLU-LI) or aspartate (ASP-LI) were studied. VOR neurons that contained GLU-LI or ASP-LI label were identified in the medial (MVN) and superior (SVN) vestibular nuclei, and cell group Y. More than half of the VOR cells in MVN were also GLU-LI positive, but less than half of the VOR cells in SVN were double labeled.

Phosphotyrosyl turnover in insulin signaling. Characterization of two membrane-bound pp15 protein tyrosine phosphatases from 3T3-L1 adipocytes.

It was shown previously that 422 (aP2) protein, a 15-kDa fatty acid binding protein, is phosphorylated on Tyr19 both in vitro by the insulin receptor tyrosine kinase and in intact 3T3-L1 adipocytes treated with insulin and phenylarsine oxide (PAO). Phospho-422(aP2) protein (pp15) accumulates in cells treated with insulin and PAO because the arsenical blocks turnover of the phosphoryl group of pp15. These findings suggest that a PAO-sensitive enzyme mediates turnover of the pp15 tyrosine phosphoryl group. We have purified and characterized two membrane protein tyrosine phosphatases (PTPases) from 3T3-L1 adipocytes that catalyze hydrolysis of phospho-Tyr19 of authentic pp15. These enzymes, designated PTPases HA1 and HA2, were purified approximately 20,000-fold and approximately 15,000-fold, respectively, and shown to differ markedly in their sensitivity to both vanadate and phosphotyrosine. Both enzymes are inhibited by PAO and accordingly can be labeled with 4-[125I]iodo-PAO. By this method, it was demonstrated that PTPases HA1 and HA2 have molecular masses of approximately 60 kDa and approximately 38 kDa, respectively. Both enzymes exhibit substrate preference for pp15 when compared with other phosphotyrosine-containing protein substrates. Proteins containing phosphoserine and phosphothreonine do not serve as substrates for the enzymes. The pp15 PTPase HA2 is expressed both in 3T3-L1 preadipocytes and adipocytes, whereas pp15 PTPase HA1 is expressed only in 3T3-L1 adipocytes.

Insulin receptor tyrosine kinase-catalyzed phosphorylation of 422(aP2) protein. Substrate activation by long-chain fatty acid.

It was established previously that the 15-kDa protein phosphorylated in 3T3-L1 adipocytes treated with insulin and phenylarsine oxide is O-phospho-Tyr19 422(aP2) protein, a fatty acid-binding protein. To assess its capacity to serve as substrate of the insulin receptor tyrosine kinase in vitro, native 422(aP2) protein was isolated from 3T3-L1 adipocytes and purified to homogeneity. Receptor-catalyzed phosphorylation of 422(aP2) protein on Tyr19 was markedly activated when long-chain fatty acid, e.g. oleic acid, is bound to the protein. Fatty acid had no effect on autophosphorylation of the insulin receptor by its intrinsic tyrosine kinase. Both saturated (C14, C16, and C18) and unsaturated (all cis-delta 9 C16, -delta 9 C18, and -delta 9,12 C18, -delta 9,12,15 C18, and -delta 5,8,11,14 C20) fatty acids caused substrate activation. The Km for 422(aP2) protein was greatly reduced (from 170 to 3 microM) by oleic acid with little or no effect on Vmax. Upon binding fatty acid to 422(aP2) protein the susceptibility of Tyr19 and Tyr128 to iodination by the lactoperoxidase method increased greatly. These results indicate that upon binding fatty acid, 422(aP2) protein undergoes a conformational change whereby Tyr19, which lies within a consensus-type sequence for tyrosine kinase substrates, becomes accessible for phosphorylation by the insulin receptor tyrosine kinase and to iodination by lactoperoxidase.

Insulin-receptor tyrosine kinase and glucose transport.

We identified the earliest events in autophosphorylation of the insulin receptor after insulin addition. Insulin-stimulated autophosphorylation at specific sites in the tyrosine kinase domain of the receptor's beta-subunit is correlated kinetically with activation of kinase-catalyzed phosphorylation of a model substrate (reduced and carboxyamidomethylated lysozyme; RCAM-lysozyme). To identify these sites, the deduced amino acid sequence of the 3T3-L1 adipocyte insulin receptor of the mouse was determined. Insulin-induced activation of substrate phosphorylation was shown to require autophosphorylation of three neighboring tyrosines (Tyr1148, Tyr1152, and Tyr1153) in the mouse receptor. A search for cellular substrates of the receptor kinase revealed that insulin causes accumulation of a 15,000-Mr phosphorylated (on tyrosine) cytosolic protein (pp15) in 3T3-L1 adipocytes treated with oxophenylarsine (PAO). PAO blocks turnover of the phosphoryl group of pp15, causing its accumulation, and thereby appears to interrupt signal transmission from the receptor to the glucose-transport system. Two membrane-bound protein phosphotyrosine phosphatases that are inhibited by PAO and are apparently responsible for the turnover of the pp15 phosphoryl group have been purified from 3T3-L1 adipocytes and characterized. These and other results support the hypothesis that turnover of the phosphoryl group of pp15, a product of insulin-receptor tyrosine kinase action, couples signal transmission to the glucose-transport system. [32P]pp15 was purified to homogeneity from 3T3-L1 adipocytes. Amino acid and radiochemical sequence analysis of the purified tryptic [32P]phosphopeptide revealed that pp15 is the phosphorylation product of 422(aP2) protein, a 15,000-Mr adipocyte protein whose cDNA we previously cloned and sequenced. 422(aP2) protein was found to bind fatty acids. When exposed to a free fatty acid, notably oleic acid, 422(aP2) protein becomes an excellent substrate of the isolated insulin-receptor tyrosine kinase. Compelling evidence indicates that on binding fatty acid, 422(aP2) protein undergoes a conformational change whereby Tyr19 becomes accessible to the receptor tyrosine kinase and undergoes O-phosphorylation. Adipose tissue and skeletal and heart muscle, which exhibit insulin-stimulated glucose uptake, express a specific insulin-responsive glucose transporter. A cDNA (GT2) that encodes this protein was isolated from a mouse 3T3-L1 adipocyte library and sequenced. We also isolated and characterized the corresponding mouse gene GLUT4. DNase I footprinting with nuclear extracts from 3T3-L1 cells revealed that a differentiation-specific nuclear factor binds to the GLUT4 promoter. The purified transcription factor C/EBP binds at the same position.(ABSTRACT TRUNCATED AT 400 WORDS)

Lysophosphatidylcholine metabolism to 1,2-diacylglycerol in lymphoblasts: involvement of a phosphatidylcholine-hydrolyzing phospholipase C.

We have previously described the chemoattraction of lymphoblasts by lysophosphatidylcholine [Hoffman, R. D., et al. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 3285-3289]. In studying the mechanism of chemoattraction it was found that lysophosphatidylcholine was metabolized to 1,2-diacylglycerol by the lymphoblastic cell line 6C3HED. One route of metabolism involves the acylation of lysophosphatidylcholine to phosphatidylcholine with subsequent hydrolysis to 1,2-diacylglycerol and phosphocholine by the action of phospholipase C. The increase in cellular 1,2-diacylglycerol was established by metabolic experiments using [14C]glycerol-labeled lysophosphatidylcholine and by mass measurements of 1,2-diacylglycerol. The presence of a phosphatidylcholine-hydrolyzing phospholipase C was confirmed in 6C3HED cell homogenates. In intact cells, lysophosphatidylcholine induced a pattern of protein phosphorylation similar to those of 1,2-dioctanoylglycerol and phorbol 12-myristate 13-acetate, two known activators of protein kinase C. This pathway of lysophosphatidylcholine metabolism, which involves a phosphatidylcholine-hydrolyzing phospholipase C, may be important in the activation of protein kinase C independent of inositol phospholipid hydrolysis.

Identification of phosphorylated 422(aP2) protein as pp15, the 15-kilodalton target of the insulin receptor tyrosine kinase in 3T3-L1 adipocytes.

[32P]pp15, the [32P]phosphorylated form of a specific cytosolic substrate of the insulin receptor tyrosine kinase, was purified to homogeneity from mouse 3T3-L1 adipocytes incubated with 32Pi. Evidence presented here and previously indicates that pp15 contains a single phosphotyrosine residue. Alkylated [32P]pp15 was subjected to limited digestion with trypsin, after which three incompletely digested tryptic [32P]phosphopeptides were purified for analysis. Amino acid and radiochemical sequence analysis of the [32P]phosphopeptides revealed that pp15 is the phosphorylation product of 422(aP2) protein, a 15-kDa adipocyte protein previously sequenced in this laboratory from the corresponding cDNA.

Leukocyte chemoattraction by 1,2-diacylglycerol.

Previous reports have demonstrated the hydrolysis of inositol phospholipids in polymorphonuclear leukocytes (PMN) in response to chemoattractants and in lymphocytes in response to the mitogen phytohemagglutinin. We investigated the role of 1,2-diacylglycerol, one of the products of receptor-linked phosphatidylinositol hydrolysis, in mediating the migratory response of leukocytes. In an under-agarose migration system, we found 1,2-dioctanoylglycerol to be a strong chemoattractant for human PMN, 6C3HED (a mouse thymic lymphoma), and Jurkat (a human T-cell leukemia). By using a modified Boyden chamber assay, the migratory response of PMN to 1,2-dioctanoylglycerol was determined to be primarily chemotactic. Analysis of structural analogs indicated that both the position and number of acyl chains are important in determining chemoattractant activity. These studies demonstrate that exogenous 1,2-diacylglycerol can stimulate the directed migration of leukocytes. They further suggest that the formation of 1,2-diacylglycerol following receptor-mediated stimulation may represent a common step in the migratory responses of myeloid and lymphoid cells.