Frequency of delirium and subsyndromal delirium in an adult acute hospital population.

Background The frequency of full syndromal and subsyndromal delirium is understudied. Aims We conducted a point prevalence study in a general hospital. Method Possible delirium identified by testing for inattention was evaluated regarding delirium status (full/subsyndromal delirium) using categorical (Confusion Assessment Method (CAM), DSM-IV) and dimensional (Delirium Rating Scale-Revised-98 (DRS-R98) scores) methods. Results In total 162 of 311 patients (52%) screened positive for inattention. Delirium was diagnosed in 55 patients (17.7%) using DSM-IV, 52 (16.7%) using CAM and 58 (18.6%) using DRS-R98⩾12 with concordance for 38 (12.2%) individuals. Subsyndromal delirium was identified in 24 patients (7.7%) using a DRS-R98 score of 7-11 and 41 (13.2%) using 2/4 CAM criteria. Subsyndromal delirium with inattention (v. without) had greater disturbance of multiple delirium symptoms. Conclusions The point prevalence of delirium and subsyndromal delirium was 25%. There was modest concordance between DRS-R98, DSM-IV and CAM delirium diagnoses. Inattention should be central to subsyndromal delirium definitions.

Human platelet antigens - 2013.

To date, 33 human platelet alloantigens (HPAs) have been identified on six functionally important platelet glycoprotein (GP) complexes and have been implicated in alloimmune platelet disorders including foetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP) and multitransfusion platelet refractoriness (MPR). The greatest number of recognized HPA (20 of 33) resides on the GPIIb/IIIa complex, which serves as the receptor for ligands important in mediating haemostasis and inflammation. These include HPA-1a, the most commonly implicated HPA in FNAIT and PTP in Caucasian populations. Other platelet GP complexes, GPIb/V/IX, GPIa/IIa and CD109, express the remaining 13 HPAs. Of the recognized HPAs, 12 occur as six serologically and genetically defined biallelic 'systems' where the -a form designates the higher frequency allele and the -b form, the lower. Twenty-one other HPAs are low-frequency or rare antigens for which postulated higher frequency -a alleles have not yet been identified as antibody specificities. In addition to the HPA markers, platelets also express ABO and human leucocyte antigen (HLA) antigens; antibodies directed at the former are occasionally important in FNAIT, and to the latter, in MPR.

Patient Engagement with Online Portals and Online Radiology Results.

The purpose of this study was to examine patient portal enrollment and the usage with a specific focus on the utilization of on-line radiology reports by patients. Oracle SQL (Austin, TX, USA) queries were used to extract portal enrollment data over a 13-month period from March 1, 2017 through March 31, 2018 from the hospital system's EMR. Patient enrollment was collected as was patient information including basic demographics and utilization patterns. For enrolled patients, interaction within the portal with the "Radiology" work tab (RADTAB) was used as a surrogate for review of radiology results. As a comparator, interaction within the portal with the "Laboratory" work tab (LABTAB) was used as a surrogate for review of laboratory results. Statistical analysis on the data was performed using Chi-squared, Student's t-test, Logistic regression and multivariate analysis where appropriate. The population for analysis included 424,422 patients. Overall, 138,783 patients (32.7%) were enrolled in the portal. Patients enrolled in the portal were older (P < 0.0001), female (P < 0.0001) and Caucasian (P < 0.0001). Patients enrolled in the portal had higher levels of educational attainment (p < 0.0001), higher annual household income (P < 0.0001), and more outpatient clinic visits (P < 0.0001). The proportion of enrolled patients that interacted with the LABTAB (47.2%) was significantly higher than those that interacted with the RADTAB (27.1%) (P < 0.0001; Table 2). Patients that utilize the portal are more likely to utilize the Laboratory tab than the Radiology tab, and demographic differences do not account for this difference in usage. Further investigation is needed to better understand the reasons for the differing usage trends of Laboratory and Radiology tabs.

An Analysis of Internet Searches Performed on a Hospital System Homepage to Assess Search Patterns and Traffic Generated by Radiology-specific Terms.

OBJECTIVE: To understand the utilization of the search engine within our hospital system's homepage, stratifying the searches into physician specialty, procedures or therapies, patient conditions, and logistical queries, with a specific focus on radiology-specific terms as a baseline to guide future interventions. METHODS: The top 1000 most searched terms entered into the medical system's homepage between January 1, 2017 and February 28, 2018 were collected. Related or similar terms were combined for analysis. RESULTS: During the study period, there were 121,071 unique searches on the center's website, and the top 1000 most searched terms combined for 65,011 searches. The most searched category was logistical queries (n = 29,667), followed by searches for conditions (n = 14,033), specialties (n = 3083), and procedures or therapies (n = 2252). Within the top 1000 most searched terms, radiology-specific searches accounted for 96 searches. These terms were all mammography-related. CONCLUSION: Radiology as a specialty and radiology-specific terms were not frequently searched for by patients when compared with other specialties. Mammography-related terms were the only radiologic subspecialty items within the top 1000 search terms. Overall, patients searched more for conditions than they did for specialties or therapies. These findings could be a representation of the general public's lack of awareness regarding the specialty.

Objective comparison of errors and report length between structured and freeform abdominopelvic computed tomography reports.

PURPOSE: To objectively compare structured and freeform abdominopelvic CT reports based on the number and types of errors as well as report length. METHODS: 90 structured and 89 freeform reports from abdominopelvic CT scans with IV contrast obtained for the indication of abdominal pain were randomly selected for review. Each report was reviewed for errors, which were counted and categorized based on the type of error. The total number of words in each report was tallied. RESULTS: 105 total errors were found in the structured reports, compared to 157 total errors in freeform reports. There were 1.16 errors per structured report and 1.76 errors per freeform report (p < 0.001). 48% of structured reports contained at least one error, while 71% of freeform reports contained at least one error (p = 0.002). When a difference existed between the styles with regard to error categories, more errors were observed in freeform reports, with the exception of the duplicated period error where structured reports had more errors. No difference on the basis of average words per report existed, with 219.2 words per report for each reporting style. CONCLUSION: The use of structured reporting for abdominopelvic CT results in less errors in the report when compared to freeform reporting, potentially reducing clinically significant adverse outcomes in patient care. The report length on the basis of number of words per report is not different between the two reporting styles.

Detection and identification of platelet antibodies and antigens in the clinical laboratory.

As a result of the unique functional properties of platelets, more-robust methods were required for detection of antibodies raised against them. Immunofluorescence detection by flow cytometry, solid-phase red cell adherence, and antigen capture ELISAs are some of the current tests that have been developed to meet the challenges of platelet antibody detection and identification and antigen phenotyping. Recently developed protein liquid bead arrays are becoming the next-generation platelet antibody tests. Fueled by development of PCR and determination of the molecular basis of the PlA1 human platelet antigen (HPA), serologic platelet typing has now been replaced by genotyping of DNA. Allele-specific PCR, melting curve analysis, and 5'-nuclease assays are now evolving into more high-throughput molecular tests. Laboratory testing for the diagnosis of immune platelet disorders has advanced considerably from its humble beginnings.

Localization of human platelet autoantigens to the cysteine-rich region of glycoprotein IIIa.

The object of this study was to further localize autoantigenic structures on IIb-IIIa and, if possible, to precisely identify the epitopes recognized by human autoantibodies. In this paper, we identify a 50-kD chymotryptic fragment of IIIa that is recognized by a high percentage of human autoantibodies, typified by the prototype IgG autoantibody RA, which binds to IIIa on intact platelets as well as in an immunoblot assay under nonreduced conditions. Using an immunoblot assay, a carboxy-terminal region of this fragment (33 kD) that contains the cysteine-rich domains of IIIa was found to carry the epitope(s) recognized by the prototype autoantibody RA. The amino-terminal amino acid sequence of the reduced 33-kD fragment, the smallest fragment that retains the RA epitope, is XPSQQDEXSP, and that of the reduced 50-kD fragment is IVQVTFD. This indicates that the 33-kD fragment consists of approximately 175 amino acids beginning at residue 479 and extending at least through residues 636-654, while the 50-kD fragment spans the same region but begins at residue 427. It is apparent that the 33-kD fragment is generated from the 50-kD fragment by additional chymotryptic hydrolysis but remains associated because of the multiple disulfide bonds that are characteristic of this cysteine-rich domain. Sera from 48% of patients with chronic ITP and 2 of 8 patients with acute ITP contain antibodies that bind to the 50-kD fragment in an ELISA. Antibodies of the same specificity are also found in one-third of patients with either secondary immune thrombocytopenia or apparent non-immune thrombocytopenia. We conclude that the 50-kD cysteine-rich region of IIIa is a frequent target of autoantibodies in ITP, but that such antibodies may also be present in cases of thrombocytopenia that cannot be linked to an apparent autoimmune process.

An amino acid polymorphism within the RGD binding domain of platelet membrane glycoprotein IIIa is responsible for the formation of the Pena/Penb alloantigen system.

The human Pena/Penb alloantigen system represents a naturally occurring polymorphism of human platelet membrane glycoprotein (GP) IIIa, and has previously been implicated in the onset of two important clinical syndromes, neonatal alloimmune thrombocytopenic purpura and posttransfusion purpura. To investigate the molecular basis of the polymorphism underlying the Pen alloantigen system, we used the polymerase chain reaction to amplify platelet-derived GPIIIa mRNA transcripts. DNA sequence analysis of amplified GPIIIa cDNAs from nucleotides 161 to 1341 (encompassing amino acid residues 22-414) revealed a G526<==>A526 polymorphism that segregated precisely with Pen phenotype in twelve other individuals examined. This nucleotide substitution results in an Arg (CGA) to Gln (CAA) polymorphism at amino acid 143 of GPIIIa. Interestingly, this polymorphic residue is located within the putative RGD binding site (residues 109-171) of GPIIIa. Platelet aggregation patterns of a Penb/b individual, however, were nearly normal in response to all physiological agonists tested, indicating that this polymorphism does not grossly affect integrin function. Short synthetic peptides encompassing residue 143 were unable to mimic either the Pena or Penb antigenic determinants, suggesting that the Pen epitopes are dependent upon proper folding of the polypeptide chain. Finally, we constructed allele-specific recombinant forms of GPIIIa that differed only at amino acid residues 143. Whereas anti-Pena alloantibodies were able to recognize the Arg143 recombinant form of GPIIIa, anti-Penb antibodies were not. Conversely, anti-Penb alloantibodies were reactive only with the Gln143 isoform of the GPIIIa molecule. It thus appears that amino acid 143 of GPIIIa is not only associated with Pen phenotype, but specifically controls the formation and expression of the Pen alloantigenic determinants.

Metal-flavin complexation. A resonance Raman investigation.

Several groups have recently shown that high quality resonance Raman spectra can be obtained for flavin species in spite of their intense fluorescence. We are interested in obtaining the resonance Raman spectra of flavins in various chemical environments in order to determine whether the spectra are useful in probing the chemical interaction between flavins and protein in flavoenzymes. We have obtained the resonance Raman spectrum of a nonfluorescent Ag+ complex of FMN. Several large changes occur in the FMN resonance Raman spectrum upon Ag+ complexation; among these are changes in the 1580 cm-1 region of the FMN spectrum (assigned to nu C=N at N-5 and C-4a), the 1410 cm-1 region and the 1260 cm-1 region (associated with a vibration having some delta N-N-H character at N-3). Similar changes are observed in the same region of a Ru2+-FMN complex. Since these spectral changes occur in two metal flavin complexes with very different electronic spectra, they would seem to be due to vibrational changes induced by metal complexation at N-5 and the oxygen at C-4 of flavin rather than the details of the vibronic interactions which give rise to the resonance enhancement of the spectrum. A structure for the Ag+-FMN complex is suggested. This study has potential physiological significance, because it illustrates the possible role of resonance Raman spectroscopy as a tool for the determination of direct flavin metal interaction in dilute aqueous solution of metalloflavoproteins.

Guidelines for safe and effective use of NSAIDs in dogs.

NSAIDs are the most widely used analgesics in veterinary medicine, and all have some toxic potential. The most common adverse class effects are gastrointestinal, renal, hepatic, and coagulation disorders. When treating chronic pain associated with osteoarthritis, the effectiveness of NSAIDs can be enhanced by physical therapy, use of chondroprotective agents, certain adjunctive drugs, and diet and exercise to control weight. To treat acute perioperative pain, NSAIDs are more effective when used preemptively, in the context of balanced (multimodal) analgesia, and in well-hydrated patients with normal blood pressure and renal function. Screening and monitoring to identify high-risk candidates for NSAID treatment should include a physical examination and patient history, identification of preexisting diseases or conditions, obtaining baseline and periodic hematologic and clinical chemistry values, and ensuring that other NSAIDs or contraindicated drugs are not used concurrently. When switching a patient from one NSAID to another (when no side effects have been seen), a washout period of 5 to 7 days minimizes chances for adverse drug interactions. Informing clients of the potential adverse effects of NSAID therapy and signs of NSAID toxicity greatly increases the likelihood of safe use of this class of drugs.

Persistently negative HIV-1 antibody enzyme immunoassay screening results for patients with HIV-1 infection and AIDS: serologic, clinical, and virologic results. Seronegative AIDS Clinical Study Group.

OBJECTIVE: To describe persons with HIV infection and AIDS but with persistently negative HIV antibody enzyme immunoassay (EIA) results. DESIGN: Surveillance for persons meeting a case definition for HIV-1-seronegative AIDS. SETTING: United States and Canada. PATIENTS: A total of eight patients with seronegative AIDS identified from July 1995 through September 1997. MAIN OUTCOME MEASURES: Clinical history of HIV disease, history of HIV test results, and CD4 cell counts from medical record review; results of testing with a panel of EIA for antibodies to HIV-1, and HIV-1 p24 antigen; and viral subtype. RESULTS: Negative HIV EIA results occurred at CD4 cell counts of 0-230 x 10(6)/l, and at HIV RNA concentrations of 105,000-7,943,000 copies/ml. Using a panel of HIV EIA on sera from three patients, none of the HIV EIA detected infection with HIV-1, and signal-to-cut-off ratios were < or = 0.8 or all test kits evaluated. Sera from five patients showed weak reactivity in some HIV EIA, but were non-reactive in other HIV EIA. All patients were infected with HIV-1 subtype B. CONCLUSIONS: Rarely, results of EIA tests for antibodies to HIV-1 may be persistently negative in some HIV-1 subtype B-infected persons with AIDS. Physicians treating patients with illnesses or CD4 cell counts suggestive of HIV infection, but for whom results of HIV EIA are negative, should consider p24 antigen, nucleic acid amplification, or viral culture testing to document the presence of HIV.

Pathophysiology of platelet destruction in immune (idiopathic) thrombocytopenic purpura.

The mechanism of platelet destruction in immune (idiopathic) thrombocytopenic purpura (ITP) is thought to involve production of autoantibody to platelet surface antigens. Once coated with antibody, circulating platelets undergo sequestration via interaction with Fc receptors of macrophages in the reticuloendothelial system. A number of questions remain about the mechanism of platelet destruction in this disease: 1) What is the nature of the stimulus to the immune system that generates antiplatelet antibodies? 2) What is the role of interactions between T-helper lymphocytes and antigen-presenting cells in ITP? 3) What role, if any, is played by the targeting of single or multiple platelet surface glycoproteins by the autoimmune response? 4) Is the site of platelet destruction, intravascular or extravascular, or the state of activation of platelets important in the destruction of platelets?

Comparative molecular field analysis of anticoccidial triazines.

Comparative molecular field analysis (CoMFA) of 2-(substituted phenyl)-1,2,4-triazine-3,5(2H,4H)-diones (triazines henceforth) resulted in an excellent correlation of their anticoccidial potencies with their physical properties. Two items about this work are notable: (i) the biological data are from a whole animal infectious disease model; and (ii) for the best results CoMFA required columns of measured "lipophilicity" and "acidity" data in addition to the calculated data in the steric field and electrostatic field columns. CoMFA resulted in a quantitative description of the major steric and electrostatic field effects, and gave significant new insights to factors governing potency. The model was used to "predict" the potencies of diverse triazines not used in making the model itself.

Cluster significance analysis contrasted with three other quantitative structure-activity relationship methods.

Cluster significance analysis (CSA), a new statistical method to analyze structure-activity relationships in graphically displayed data, is contrasted with linear discriminant analysis, SIMCA, and the method of "relative odds". The data sets evaluated are as follows: antibacterial lasalocid derivatives, antimalarial naphthoquinones, and carcinogenic polycyclic aromatic hydrocarbons. CSA gives results comparable to these other methods, involves fewer assumptions, can be more reliable, and in general is easier to understand.

On the significance of clusters in the graphical display of structure-activity data.

A method is presented to evaluate the statistical significance of an apparently clustered group in the graphical display of structure-activity data. Two variations are described; each is implemented by means of a computer program. The first is applicable in situations with relatively small sets of compounds where a complete enumeration of all possible clusters can be accomplished reasonably on a high-speed electronic computer. The second is applicable in cases where such a calculation would be too time consuming. This latter variation uses random sampling of the set of all possible clusters. An application for each variation is given: for the smaller case a reevaluation of a study on aminotetralin and aminoindan monoamine oxidase inhibitors; for the larger case the discovery of some physical parameters that influence mutagenicity among some aminoacridine derivatives. It is proposed that this new technique be called cluster significance analysis (CSA).

Novel degradation products from the treatment of salinomycin and narasin with formic acid.

Salinomycin and narasin (4-methylsalinomycin) upon treatment with HCO2H furnish the known furanone fragment 3 and the complementary but rearranged fragments 1 and 2 respectively. The structure of 1 has been established by X-ray analysis. Upon being heated under reflux in PhMe, 1 undergoes the retrograde aldol reaction to furnish alpha, gamma-dimethyl-2-furanbutanal (4). The furan moiety of 1 is more resistant to electrophilic substitution than expected, but it can be acylated by highly reactive reagents such as (CF3CO)2O and AcOSO2Me. Compounds 1 and 2, the acetyl and trifluoracetyl derivatives of the former, and the reduction products thereof have no significant anticoccidial activity.

Linear discriminant and multiple regression analyses of anticoccidial triazines.

Quantitative structure-activity relationships among some anticoccidial 2-(substituted-phenyl)-1,2,4-triazine-3,5-(2H,4H)-diones were studied by multiple regression analysis (MRA, the Hansch approach) and by linear discriminant analysis (LDA). With MRA the potencies of these compounds are correlated with their reverse-phase HPLC retention times and their 1H NMR chemical shifts at the 6-position. While the coefficients of the variable terms are significant, the moderate R2 (0.56) of the correlating equation suggests that predictions made from this analysis are not likely to be accurate. LDA supports the idea that these descriptors are related to potency, but the discriminant function does not lead to good classification. However, when coupled with a graphic display of the results, LDA gives a more immediate sense of the synthetic direction to take when seeking highly potent analogues. It is apparent that other important but not yet identified factors also play a role in determining the potencies of these compounds.

Quantitative structure-activity relationships among macrolide antibacterial agents: in vitro and in vivo potency against Pasteurella multocida.

Quantitative structure-activity relationships have been found among macrolide antibacterial agents in their potencies against the bacterial pathogen Pasteurella multocida both in vitro and in mouse infections. To obtain these relationships we measured, among other things, the pK(a)'s and log P's of 15 known macrolides of diverse structures. Among these compounds, in vitro potency [log(1/MIC)] is a function of log P, log D, and CMR (R = 0.86). In vivo potency is a function of the higher pK(a), the HPLC chromatographic capacity factor log k', log(1/MIC) and pNF (R = 0.93). pNF is defined as the negative logarithm of the fraction of neutral drug molecules present in aqueous solution at pH 7.4. The same physical properties were determined for 14 macrolides not used in developing the original QSAR models. Using the in vivo model, we calculated the mouse protection potency ranges for these new compounds. Ten estimates agreed with those observed, three were lower by a half-order of magnitude, and one was calculated to be active in the range of 15-50 mg/kg, but in fact was not active at 50 mg/kg, the highest level tested. When these new compounds were combined with the original 15, and the QSAR's updated, the new equations for the in vitro and in vivo potencies were essentially the same as those originally found. Hence, the physical properties indicated above are major determinants of macrolide antibacterial potencies.

Repromicin derivatives with potent antibacterial activity against Pasteurella multocida.

Reductive amination of repromicin with polyfunctional amines has led to new macrolide antibacterial agents, some of which are highly potent against the Gram-negative pathogen Pasteurella multocida both in vitro and in a mouse infection model. A key element in this discovery was the recognition that among certain known macrolides increasing lipophilicity results in diminished in vivo activity. One repromicin derivative, 20-[N-[3-(dimethylamino)-propyl]-N-L-alanylamino]-20-deoxorepro micin (35), was selected for advanced evaluation. At 5 mg/kg, a single subcutaneous dose was found to control induced pasteurellosis in swine and induced respiratory disease in cattle.

Automated morphometric analysis of corneal endothelial cells.

This paper describes a feasibility study for computer image analysis of corneal endothelial specular micrographs. The analysis involved image enhancement, boundary detection of individual cells, and subsequent calculation of cell area, cell area distribution, cell perimeter, cell orientation, and cell diameter. Cell areas produced by automated analysis agreed well with manually measured cell areas from the same photomicrographs. The computer methods required little human guidance or correction, produced accurate results, and could be made to run fairly quickly with modest computing resources.