Challenges and recommendations for high quality research using electronic health records.

Harnessing Real World Data is vital to improve health care in the 21st Century. Data from Electronic Health Records (EHRs) are a rich source of patient centred data, including information on the patient's clinical condition, laboratory results, diagnoses and treatments. They thus reflect the true state of health systems. However, access and utilisation of EHR data for research presents specific challenges. We assert that using data from EHRs effectively is dependent on synergy between researchers, clinicians and health informaticians, and only this will allow state of the art methods to be used to answer urgent and vital questions for patient care. We propose that there needs to be a paradigm shift in the way this research is conducted - appreciating that the research process is iterative rather than linear. We also make specific recommendations for organisations, based on our experience of developing and using EHR data in trusted research environments.

Effects of platelets and platelet-derived material on the activated partial thromboplastin time (Cephotest) coagulation test.

OBJECTIVE: The Cephotest is an activated partial thromboplastin time (APTT) test used to measure the activity of the intrinsic pathway of coagulation. To perform this test, blood is usually centrifuged to obtain plasma that is almost without erythrocytes and leucocytes and with only a minimal amount of platelets. MATERIAL AND METHODS: In the present experiments blood was centrifuged at different speeds to produce either platelet-poor plasma (PPP) or platelet-rich plasma (PRP). PPP and PRP obtained from the same whole blood samples from each of several persons were tested in pairs using the standard Cephotest reagent to observe the consequences of Cephotest being performed on plasma containing platelets. The same procedure was used with a Cephotest reagent with a reduced concentration of phosphatidylserine. In succeeding experiments the PRP was preincubated with SFLLRN or Ca-ionophore to activate the platelets, a procedure also known to produce platelet-derived microparticles. PPP and PRP were compared by thrombin time and reptilase time tests to find out at which stage platelets might influence the Cephotest. RESULTS: The results showed that the platelets did influence Cephotest when using both the regular reagent and the phospholipid-reduced agent. When using the regular reagent, PRP showed a tendency towards a longer APTT than PPP. It is suggested that this was caused by platelets consuming some of the first traces of thrombin generated. CONCLUSIONS: When using the phospholipid-reduced reagent, PRP showed a shorter APTT than PPP, probably because the platelets contributed phosphatidylserine to the system. When the platelets were activated before testing, their effects on the tests were increased. Microparticles that formed during platelet activation may have contributed to these effects.

Total knee arthroplasty in Parkinson's disease.

Total knee arthroplasty in Parkinson's disease (PD) has been reported only twice in the literature. Parkinson's disease is considered a contra-indication for total knee replacement by some authors. We report on a 77-year-old man with PD who underwent total knee arthroplasty for severe degenerative joint disease. The patient had a somewhat prolonged but successful rehabilitation as an inpatient and continued to make gains following discharge. Currently he is an independent functional ambulator. Based on our experience with this patient, we recommend that patients with PD who maintain ambulatory function prior to surgery and are cognitively able to integrate new knowledge and follow commands should be considered candidates for total knee replacement if it is indicated. Our patient demonstrates, however, that even in patients suffering from mild PD the rehabilitation process may be significantly prolonged and more difficult than in patients without PD. Objective studies evaluating the role of pre-surgical rehabilitation are needed.

Age differences in immunity against wild and vaccine strains of poliovirus prior to the 1988 outbreak in Israel and response to booster immunization.

During the 1988 type 1 polio outbreak in Israel, most cases occurred in previously vaccinated subjects aged 11-30 years, suggesting a possible age-related immunity deficit against the wild virus responsible for the outbreak. We examined type 1 poliovirus neutralizing antibody titres against the Sabin strain, the standard wild strain (Mahoney), the wild strain responsible for the 1988 outbreak and a previous wild strain from the region, on frozen sera drawn prior to the mass vaccination campaign from subjects aged 6 to 40 years. Response to vaccination with oral poliovaccine (OPV) was examined in a subgroup aged 18-40 years. At all ages, the highest antibody titres prior to the outbreak were against the Sabin strain. Geometric mean titres (GMTs) against both the Sabin strain and the wild Mahoney strain were significantly higher in the age groups 6-7, 12-13 and 30-40 years compared with the 18-29-year-olds. For the other wild strains, the GMT for those aged 30-40 years was significantly and substantially higher than in the other age groups, followed by the 12-13- and 6-7-year-olds and lowest in those aged 18-29 years. Following vaccination with OPV in subgroups aged 18-29 and 30-40 years, GMTs against Sabin and all wild strains were similar to each other and in both age groups. These findings suggest that there was a relative immunity gap against the wild type 1 strains in the age group that lacked prior exposure to wild virus and had received the last OPV dose more than 17 years previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum pseudocholinesterase in state anxiety.

Levels of serum pseudocholinesterase in 14 medical students before and after oral examinations in psychiatry were compared. Blood samples were collected 1 hour before and 2 to 4 weeks after the oral examinations. Serum pseudocholinesterase was significantly higher in state anxiety than in relaxation. The relation between state anxiety and high levels of this enzyme was established. No significant difference was observed in pseudocholinesterase levels between students with physiologic anxiety symptoms and those without.

Antigenic determinants of high mobility group chromosomal proteins 1 and 2.

The antigenic determinants of nonhistone high mobility group chromosomal proteins 1 (HMG-1) and 2 (HMG-2) were studied with rabbit antisera elicited against HMG-1 and against HMG-2 and monoclonal antibodies elicited by HMG-1. The monoclonal antibodies did not distinguish between the two proteins, suggesting that they have specificity toward a shared determinant. Whereas anti-HMG-1 did not, anti-HMG-2 did distinguish between the proteins, suggesting that the anti-HMG-2 serum contains antibodies against peptides which differ between the proteins. Peptides were generated from HMG-1 and HMG-2 by controlled digestion with trypsin and pepsin. Analysis of the digests by ELISA and by sodium dodecyl sulfate electrophoresis followed by diazobenzyloxymethyl transfer, antibody binding and autoradiography revealed that most of the antibodies are against sequential determinants some of which are smaller than 3000 in molecular weight.

Effects of stimulating psychodynamically relevant unconscious fantasies on schizophrenic psychopathology.

This article reviews a series of studies investigating the relationship between various unconscious fantasies and manifest pathology in adult schizophrenics. The results support the view that the activation of specific fantasies can lead to both the exacerbation and amelioration of symptoms in schizophrenia. The theoretical and clinical implications of the experimental findings are discussed, and suggestions for further research are offered.

Integration site of polyoma virus DNA in the inducible LPT line of polyoma-transformed rat cells.

The structure of the polyoma virus (Py) integration site in the inducible LPT line of Py-transformed rat cells was determined by biochemical methods of gene mapping. LPT cell DNA was digested with various restriction enzymes. The digestion products were electrophoresed in agarose gels and transferred onto nitrocellulose sheets by Southern blotting. Fragments containing viral or cell DNA sequences, or both, were identified by hybridization with Py DNA or with a cloned flanking cell DNA probe. Cleavage of LPT DNA with enzymes that restrict the Py genome once generated linear Py DNA molecules and two fragments containing both cell and viral DNA sequences. Cleavage of LPT DNA with enzymes which do not restrict Py DNA generated series of fragments whose lengths were found to differ by increments of a whole Py genome; the smallest fragment in each series was found to be longer than the viral genome. These data indicate that LPT cultures contain Py insertions of various lengths integrated into the same chromosomal site in all the cells. The length heterogeneity of the viral insertions is due to the presence of 0, 1, 2, 3. . . Py genomes arranged in a direct tandem repeat within invariable sequences of viral DNA. Double-digestion experiments were also carried out with the above enzymes and with enzymes that cleave the Py genome at multiple sites. The data obtained in these experiments were used to construct a physical map of the integration site. This map showed that the early region of the virus remained intact even in the smallest insertion (which contains no whole duplicated genomes), whereas the late region was partially duplicated and split during integration. The smallest insertion is colinear with the Py physical map over a region including the entire Py genome and at least a part of the duplicated segment. This structure could give rise to nondefective circular viral DNA molecules by single homologous recombination events. Similar recombination events may occur at a higher frequency in the longer insertions, which include longer regions of homology, and may yield many more free viral genomes. The presence of these insertions in LPT cells could thus be one of the factors which account for the high inducibility of the LPT line.

The effects of stimulating symbiotic fantasies on manifest pathology in schizophrenics: a revised formulation.

This study was designed as a further investigation of the ameliorative effects of stimulating a symbiotic fantasy in schizophrenics. Fifty-four adult male schizophrenic subjects were each seen individually for three experimental sessions. In each session there was exposure to a neutral subliminal stimulus followed by a baseline assessment of thought disorder and behavioral pathology. This was followed by exposure to one of three critical stimuli: a) a neutral control stimulus; b) the stimulus "mommy and I are one," designed to activate a fantasy of symbiotic gratification, and found in past studies to lead to pathology reduction; and c) "mommy and I are two," designed as a test of the specificity of oneness fantasy in producing symptomatic improvement. Each subject was exposed to the three critical simuli by counterbalanced order. Assessments of pathology were repeated after exposure to the experimental stimuli and comparisons were made with baseline measures. Results were: a) the subliminal symbiotic stimulus produced improvement on one of the measures of pathology, replicating findings from previous studies; and b) unexpectedly, the "mommy and I are two" stimulus led to pathology reduction on both dependent measures and proved significantly more ameliorative than the oneness stimulus. Associations obtained from subjects on a post hoc basis, the relationship between responses of individual subjects to the two stimuli, and the way in which order of presentation of the critical stimuli affected results supported the view that the twoness message also gratified symbiotic wishes while simultaneously providing reassurance against dangers associated with boundary loss. Results were discussed with an eye toward sharpening and refining the formulation advanced in the past to account for the ameliorative effects of the "oneness" stimulus.

Pigmented villonodular tenosynovitis: a case report.

A case of pigmented villonodular tenosynovitis is described. The characteristics and clinical course are discussed and compared as to natural history, histopathology, pathophysiology, etiology, differential diagnosis, and treatment. The etiological factors of this entity are generally uncertain; however, this case may well be associated with a specific incident of trauma, eg., a puncture wound sustained from stepping on a nail.

A clinical application of subliminal psychodynamic activation. On the stimulation of symbiotic fantasies as an adjunct in the treatment of hospitalized schizophrenics.

This study attempted to utilize the subliminal psychodynamic activation method as an aid in the treatment of hospitalized schizophrenics. More specifically, we inbestigated whether the subliminal activation of a fantasy of symbiotic gratification would produce an increment in the degree of improvement that schizophrenics manifested as a result of hospitalization. Forty male patients were seen individually for three weekly sessions over a 6-week period for a fantasy expression task carried out by a psychology graduate student. Both at the beginning and at the end of each session and whenever during the session anxiety was in evidence, the patient was exposed to subliminal stimulation. The patients were divided into two groups equated for intelligence, pathology level, and other pertinent variables. For one group, the tachistoscopically presented stimulus consisted of MOMMY AND I ARE ONE, a verbal message which, in several prior studies, produced a significant reduction in ego impairment within a laboratory session. The other group served as a control, and their stimulus was PEOPLE ARE WALKING. The subjects in each group were subdivided in order to investigate the effects of two other interventions in addition to the subliminal symbiotic stimulation. One of these was aggressive expression consisting of an attempt to elicit specifically aggressive fantasies in the fantasy expression task. The other was self-focuing, designed to strengthen self-boundaries. All patients were blindly assessed for seven measures of ego impairment before and after the intervention period and for the number of rehospitalizations over a 9-month follow-up period. Of the three types of interventions impairment measures. For on of the variables, the symbiotic group showed significantly more improvement than the control group, while for two others the results approached significance. In addition, on an overall measure of ego impairment, there was significantly mor improvement for the symbiotic group than for the control patients.