The influence of task environment and health literacy on the quality of parent-reported ADHD data.

OBJECTIVES: To determine 1) the extent to which paper-based and computer-based environments influence the sufficiency of parents' report of child behaviors and the accuracy of data on current medications, and 2) the impact of parents' health literacy on the quality of information produced. METHODS: We completed a randomized controlled trial of data entry tasks with parents of children with Attention Deficit Hyperactivity Disorder (ADHD). Parents completed the NICHQ Vanderbilt ADHD screen and a report of current ADHD medications on paper or using a computer application designed to facilitate data entry. Literacy was assessed by the Test of Functional Health Literacy in Adults (TOFHLA). Primary outcomes included sufficient data to screen for ADHD subtypes and accurate report of total daily dose of prescribed ADHD medications. RESULTS: Of 271 parents screened, 194/271 were eligible and 182 were randomized. Data from 180 parents were analyzed. 5.6% parents had inadequate/marginal TOFHLA scores. Using the computer, parents provided more sufficient and accurate data compared to paper (sufficiency for ADHD screening, paper vs. computer: 87.8% vs. 93.3%, P = 0.20; accuracy of medication report: 14.3% vs. 69.4%; p<0.0001). Parents with adequate literacy had increased odds of reporting sufficient and accurate data (sufficiency for ADHD screening: OR 8.0, 95% CI 2.0-32.1; accuracy of medication report: OR 4.4, 95% CI 0.5-37.4). In adjusted models, the computer task environment remained a significant predictor of accurate medication report (OR 18.7, 95% CI 7.5-46.9). CONCLUSIONS: Structured, computer-based data entry by parents may improve the quality of specific types of information needed for ADHD care. Health literacy affects parents' ability to share valid information.

Getting the data right: information accuracy in pediatric emergency medicine.

OBJECTIVES: (1) To identify the extent to which information provided by parents in the pediatric emergency department (ED) can drive the assessment and categorization of data on allergies to medications, and (2) to identify errors related to the capture and documentation of allergy data at specific process level steps during ED care. METHODS: An observational study was conducted in a pediatric ED, combining direct observation at triage, a structured verbal interview with parents to ascertain a full allergy history related to medications, and chart abstraction. A comparative standard for the allergy history was established using parents' interview responses and existing guidelines for allergy. Errors associated with ED information management of allergy data were evaluated at five steps: (1) triage assessment, (2) treating physician's discussion with parent, (3) treating nurse's discussion with parent, (4) use of an allergy bracelet, and (5) documentation of allergy history on medication order sheets. RESULTS: 256 parent-child dyads were observed at triage; 211/256 parents (82.4%) completed the structured verbal interview that served as the basis for the comparative standard (CS). Parents reported a total of 59 medications as possible allergies; 56 (94.9%) were categorized as allergy or not based on the CS. Twenty eight of 48 patient cases were true allergies by guideline based assessment. Sensitivity of triage for detecting true medication allergy was 74.1% (95% confidence interval (CI) 53.7 to 88.9). Specificity of triage personnel for correctly determining that no allergy existed was 93.2% (95% CI 88.5 to 96.5). Physician and nursing care had performance gaps related to medication allergy in 10-25% of cases. CONCLUSIONS: There are significant gaps in the quality of information management regarding medication allergies in the pediatric ED.

Optimal data entry by patients: effects of interface structure and design.

UNLABELLED: Direct electronic acquisition of data from patients possesses accuracy and diagnostic value. The mechanics of how best to capture historical information from patients using electronic interfaces are not well studied. We undertook an iterative usability experiment to answer 2 questions: 1) How can maximal electronic data input from a patient be achieved, and 2) Do varying structures for data entry promote differential documentation of specified data elements? METHODS: A series of four trials comprised the testing cycle. Unstructured text entry, directed text entry, and closed ended questions were tested in combination against outcomes of word count, time to task completion, and user preferences. Covariates of interest included participants' technologic experience and ergonomic experience with keyboards, as well as self-report of educational status, literacy, and primary language. RESULTS: Participants clearly preferred the order of initial closed-ended questions followed by unstructured text entry, and this ordering was not associated with decrements in word count or increase in time. When compared to unstructured text entry, directed text entry provided higher documentation of data for past medical history and questions which parents wished to discuss with the clinician. A closed-end question structure, when compared to directed text entry, provided higher capture of parents' questions for discussion. CONCLUSIONS: Optimal design of an electronic interview for the capture of medical histories will benefit from a mixed structure of directed text entry and closed-ended questions. For historical or clinically relevant items where maximal capture of data is desired, a structure with closed-ended questions would be preferred.

Evolution of Asian monsoons and phased uplift of the Himalaya-Tibetan plateau since Late Miocene times.

The climates of Asia are affected significantly by the extent and height of the Himalayan mountains and the Tibetan plateau. Uplift of this region began about 50 Myr ago, and further significant increases in altitude of the Tibetan plateau are thought to have occurred about 10-8 Myr ago, or more recently. However, the climatic consequences of this uplift remain unclear. Here we use records of aeolian sediments from China and marine sediments from the Indian and North Pacific oceans to identify three stages of evolution of Asian climates: first, enhanced aridity in the Asian interior and onset of the Indian and east Asian monsoons, about 9-8 Myr ago; next, continued intensification of the east Asian summer and winter monsoons, together with increased dust transport to the North Pacific Ocean, about 3.6-2.6 Myr ago; and last, increased variability and possible weakening of the Indian and east Asian summer monsoons and continued strengthening of the east Asian winter monsoon since about 2.6 Myr ago. The results of a numerical climate-model experiment, using idealized stepwise increases of mountain-plateau elevation, support the argument that the stages in evolution of Asian monsoons are linked to phases of Himalaya-Tibetan plateau uplift and to Northern Hemisphere glaciation.

Patients as experts: a collaborative performance support system.

Performance support systems that provide decision support and encourage quality improvement historically focus on physicians as the expert to the exclusion of an active role for patients. This paper outlines an argument for the development of a collaborative expert system in the acute care setting that emphasizes a key role for patients. Patients are not just seekers of information; they remain capable of sharing and integrating their knowledge and expertise actively in an electronically-supported care process. Collaborative use of information technology emerges as a novel variation of consumer informatics. I will define specific domains of expertise for patients and place the proposed collaborative expert system within the framework of Wagner's view of idealized collaborative care for chronic illness. Basic architecture for a patient-inclusive system is proposed with additional detail provided for a patient-level interface targeting pediatric asthma. The benefits of the electronically-supported collaboration include the activation of patients in the information-sharing process, enhanced decision support, a patient-focused needs assessment, and improved communication and partnership between patients and providers.

Drug release from film-coated chlorpheniramine maleate nonpareil beads: effect of water-soluble polymer, coating level, and soluble core material.

The purpose of this research was to use a new drug release model to study the effects of formulation parameters on drug release from a film-coated chlorpheniramine (CPM) nonpareil system. The film-coated CPM nonpareils were prepared by using a fluid bed apparatus. A hydroxylpropylmethylcellulose (HPMC) solution was blended with an aqueous ethylcellulose dispersion (Surelease) to adjust the permeability of the film. The apparent permeability of samples was obtained from dissolution data using a previously reported drug release equation. The apparent permeability was plotted versus the film coating level or the HPMC concentration in the film. When the natural logarithm of the apparent permeability versus coating level was graphed, a biphasic plot was observed in the group without HPMC in the film, showing the occurrence of a critical coating level. It was suggested that a mechanically formed porous film (due to an incomplete coating) could change to a nonporous film after the bead was completely coated. However, in the group that contained 12% HPMC in the film, the critical coating level was not observed. A porous film, formed by the leaching out of the water-soluble polymer, would not change to a nonporous film even after the bead is completely coated. Through a mathematical derivation, the decrease of apparent permeability versus coating level was related to the reduction of the total hole area. The apparent permeability was found to increase with the HPMC concentration. After a critical concentration was reached, the further addition of HPMC into the film caused a rapid increase in apparent permeability. The critical HPMC concentration was related to a minimum domain formation concentration (MDFC). A rapid increase of the drug release was observed when the dissolution profile of a sample made from a regular sugar nonpareil core (soluble) was compared with the sample made from a precoated nonpareil core (insoluble), which suggests that the drug release can be enhanced by the dissolution of the core. A minimum concentration of the HPMC was required to effectively modify permeability of the film. The critical coating level and critical concentration of HPMC can be determined from the apparent permeability plot using a previously published equation. The dissolution of a soluble core can greatly enhance the release of the drug from the nonpareil system.

Parents as direct contributors to the medical record: validation of their electronic input.

STUDY OBJECTIVES: We assessed the validity and completeness of data in the past medical history (PMH) obtained electronically from parents and examined effects of the human-computer interface and sociodemographic variables on electronic parental report. METHODS: We compared parents' electronic report of PMH data with a criterion standard, structured face-to-face interview by a pediatrician blinded to the electronic data. The electronic medical record interface enabled parents to provide 5 elements of the PMH: birth status, allergies, current medications, immunization status, and previous hospitalizations. The setting was the emergency department waiting room in an academic, urban children's hospital; parents of infants up to 12 months old participated. Outcome measures were validity of the PMH data obtained using the electronic medical record interface and odds of having an invalid or incomplete response using the electronic medical record interface. RESULTS: One hundred parents were enrolled (69.4% of eligible subjects). Study subjects did not differ from nonenrollees on demographic variables and visit characteristics. The validity of the electronic medical record interface data was high across the PMH elements (94% to 99%). Two demographic features predicted invalid response: parental primary language other than English or Spanish (odds ratio [OR] 11.4, 95% confidence interval CI 1.7 to 76.3), and Asian ethnicity (OR 14. 6, 95% CI 1.2 to 182.4). Incomplete responses were predicted by limited previous experience with computers; computer-naive subjects had an eightfold increased odds of skipping a question (OR 7.9, 95% CI 1.8 to 34.6). CONCLUSION: Parents are accurate independent reporters of their infants' general PMH using the electronic medical record interface. Their participation in care may be enhanced by allowing them to contribute medical information directly to the electronic medical record.

Data quality and the electronic medical record: a role for direct parental data entry.

INTRODUCTION: The paper and electronic medical record (EMR) have evolved with little scientific inquiry into what effect the informant (clinician or patient) has on the validity of the recorded information. We have previously reported on an electronic interview program that facilitated parents' direct reporting of past medical history data. We sought to define additional data elements that parents could report electronically and to compare parents' electronically entered data to that charted by physicians using the current EMR system. METHODS: A convenience sample of parents was recruited to enter data on history of present illness (HPI) and review of systems (ROS) elements using an electronic interview. Data from the electronic parental interview and information abstracted from the physician EMR were compared to data derived from a face-to-face criterion standard interview. Validity, sensitivity and specificity of each mode of data entry were calculated. RESULTS: 100 of 140 eligible parents (71.4%) participated. Validity of information from the electronic interview was comparable to that charted by emergency physicians for HPI regarding fever and ROS questions. Sensitivity of parents' electronic interview was superior to physicians' charting for ROS elements specific to hydration status. CONCLUSIONS: Improved sensitivity for detection of historical risk factors for illness can be achieved by augmenting the pediatric EMR with a section for direct parental direct data input. Direct parental data input to the EMR should be considered to improve the quality of documentation for medical histories.

Depression screening in adolescents with somatic complaints presenting to the emergency department.

STUDY OBJECTIVE: To determine the frequency of documented depression screening for adolescents presenting with somatic chief complaints to a pediatric emergency department. METHODS: We conducted a retrospective chart review of 408 consecutive patients aged 11 to 17 years who presented to the ED with a chief complaint of chest pain, abdominal pain, headache, weakness/fatigue, dizziness/fainting, or hyperventilation. RESULTS: Documentation of depression screening was noted in 4.2% of cases (17 of 408). For patients charts listing both a somatic chief complaint and a similar nonspecific discharge diagnosis, the documentation rate for depression screening rose to 7.5%. No change in screening documentation was noted for chronically ill patients. We did detect a significant difference in screening frequency between black adolescents and adolescents of all other races (P = .021). CONCLUSION: Our findings demonstrate an extremely low frequency of documentation of depression screening in adolescents with somatic complaints presenting to the ED. Documentation of screening in black patients was still low but was performed at a significantly higher rate. These results indicate a need for education on the adolescent at risk for depression and suicide in the acute care setting.

Oligomerization of NTRC at the glnA enhancer is required for transcriptional activation.

To activate transcription of the glnA gene, the dimeric NTRC protein (nitrogen regulatory protein C) of enteric bacteria binds to an enhancer located approximately 100 bp upstream of the promoter. The enhancer is composed of two binding sites for NTRC that are three turns of the DNA helix apart. One role of the enhancer is to tether NTRC in high local concentration near the promoter to allow for its frequent interaction with sigma 54 holoenzyme by DNA looping. We have found that a second role of the enhancer is to ensure oligomerization of NTRC into a complex of at least two dimers that is required for transcriptional activation. Formation of this complex is greatly facilitated by a protein-protein interaction between NTRC dimers that is increased when the protein is phosphorylated.

Tensile properties of free films cast from aqueous ethylcellulose dispersions.

Free films of two commercially available formulations of aqueous ethylcellulose dispersion differing only in plasticizer content (Sure-lease/E-7-7050 without silica and E-7-7060 containing dibutyl sebacate and glyceryl tricaprylate/caprate as plasticizers, respectively) were cast and coalesced at temperatures ranging between 30 and 70 degrees C. Mechanical properties of these films were measured using tensile stress analysis. Three mechanical parameters, namely, tensile strength, work of failure, and elastic modulus, were computed from the load-time profiles of these films. The results showed that the tensile strength and elastic modulus values of the films cast from both formulations increased with the corresponding increase in coalescence temperature up to 60 degrees C, beyond which no significant differences were observed. In the case of work of failure, however, the difference between the two formulations was observed above 60 degrees C. The films cast from Surelease/E-7-7050 formulation without silica (dibutyl sebacate as the plasticizer) were relatively softer than those from Surelease/E-7-7060 formulation (glyceryl tricaprylate/caprate as the plasticizer). At coalescence temperatures above 50 degrees C, the films cast from both formulations exhibited temperature-dependent plastic deformation.

Aqueous ethylcellulose dispersion of ethylcellulose. I. Evaluation of coating process variables.

Formulation and process variables play an important role in the film-forming properties of coating polymers. Three selected independent coating process variables, namely, percent solids content in the coating polymeric dispersion, inlet-air temperature, and spray rate of the polymeric dispersion, were investigated in this study to determine their effect on the performance characteristics of tablets coated with a plasticized aqueous ethylcellulose dispersion (Sure-lease) in a fluid-bed equipment. Response surface methodology (RSM) was utilized to study the complex relationship between these process variables and selected response variables. Three response variables were considered, namely, rate of drug release from the "untreated" coated tablets and the "thermal-treated" coated tablets and microindentation hardness of the untreated coated tablets. A 12-point factorial experimental design was utilized, and three-dimensional (3-D) response surface plots were generated using a second-order polynomial model. The model provided information needed to predict optimal process conditions. Drug release from the coated tablets followed zero-order kinetics. Inlet-air temperature was found to be the most critical process variable for all the three response variables studied. A correlation was observed between the drug release rate and the microindentation hardness of the applied polymeric coat in the case of untreated coated tablets. The 3-D response surface plots indicated that lower rates of drug release from the coated tablets may be obtained by using high inlet-air temperature and low spray rate of the polymeric dispersion during coating.

Role of integration host factor in stimulating transcription from the sigma 54-dependent nifH promoter.

In a wide variety of nitrogen-fixing organisms among the Purple Bacteria (large division of Gram-negative bacteria) the nitrogen fixation (nif) operons are transcribed by an alternative holoenzyme form of RNA polymerase, sigma 54-holoenzyme. Transcription depends on the activator protein NIFA (nitrogen fixation protein A), which catalyzes isomerization of closed complexes between this polymerase and a promoter to transcriptionally productive open complexes. NIFA-mediated activation of transcription from the nifH promoter of Klebsiella pneumoniae is greatly stimulated by the integration host factor IHF, which binds to a site between the upstream binding site for NIFA and the promoter, and bends the DNA. IHF fails to stimulate activation of transcription from this promoter by another activator of sigma 54-holoenzyme, NTRC (nitrogen regulatory protein C), which lacks a specific binding site in the nifH promoter region. As predicted, if the IHF-induced bend facilitates interaction between NIFA and sigma 54-holoenzyme, substitution of an NTRC-binding site for the NIFA-binding site allowed IHF to stimulate NTRC-mediated activation of transcription from the nifH promoter. The stimulation was of the same order of magnitude as that for NIFA in the native configuration of the promoter-regulatory region (up to 20-fold). With purified NTRC and the substitution construct we could demonstrate that stimulation by IHF in a purified transcription system was comparable to that in a crude coupled transcription-translation system, indicating that the stimulation in the crude system could be accounted for by IHF. The IHF stimulation was observed on linear as well as supercoiled templates, indicating that the geometric requirements are relatively simple. We have attempted to visualize the arrangement of proteins on DNA fragments carrying the nifH promoter-regulatory region of K. pneumoniae by electron microscopy. IHF stimulated NIFA-mediated activation of transcription from the nifH and nifD promoters of Bradyrhizobium japonicum and less so from the nifH promoters of Rhizobium meliloti and Thiobacillus ferrooxidans, consistent with previous observations that stimulation is greatest at promoters that are weak binding sites for sigma 54-holoenzyme in closed complexes.

Androgen responsiveness of the murine beta-glucuronidase gene is associated with nuclease hypersensitivity, protein binding, and haplotype-specific sequence diversity within intron 9.

The tissue specificity and genetic variability of the murine beta-glucuronidase (GUS) response to androgen provide useful markers for identifying elements which underlie this responsiveness. While GUS is expressed constitutively in all examined cell types, kidney epithelial cells uniquely exhibit a manyfold yet slow rise in GUS mRNA and enzyme levels when stimulated by androgens. Three major phenotypes of this androgen response have been described among inbred strains of mice: (i) a strong response in strains of the Gusa haplotype, (ii) a reduced response in strains of the Gusb and Gush haplotypes, and (iii) no response, as observed in Gusor mice. These response variants define a cis-active element(s) which is tightly linked to the GUS structural gene. Nuclease hypersensitivity scans of kidney chromatin within and surrounding the structural gene revealed an androgen-inducible hypersensitive site in intron 9 of the gene in Gusa but not in Gusor mice. When a radiolabeled fragment of Gusa DNA containing this hypersensitive site was incubated with kidney nuclear extracts and then subjected to gel electrophoresis, two shifted bands were observed whose levels were dramatically higher in extracts of androgen-treated than in those of untreated Gusa mice. The shifted bands reflect binding of a kidney-specific factor(s) to a 57-bp region of complex dyad symmetry in Gusa and Gusor mice which is partially deleted in Gusb and Gush mice. This binding site is located approximately 130 bp downstream of a glucocorticoid response element sequence motif which is totally deleted in [Gus]or mice. Taken together, our results suggest that the androgen responsiveness of GUS in murine kidney epithelial cells is controlled by elements within the proximal end of intron 9 of the GUS structural gene.

An evaluation of the properties of enteric coating polymers: measurement of glass transition temperature.

When submitted to X-ray crystallography, two enteric coating polymers, cellulose acetate phthalate and polyvinyl acetate phthalate, were found to be essentially amorphous in structure. Values for the glass transition temperature, Tg, of each polymer have been obtained using both a surface microindentation technique and differential scanning calorimetry. The effect on this parameter of an increasing concentration of a plasticizer, diethyl phthalate, has also been determined. Measured values for Tg have been compared with predicted values obtained using a suitable mixture-rule model: the surface microindentation technique values were closer to the predicted.

The permeability of enteric coatings and the dissolution rates of coated tablets.

The effect of an increasing concentration of plasticizer and pigment on the permeability to both water vapour and simulated gastric juice of cellulose acetate phthalate and polyvinyl acetate phthalate has been evaluated. There were significant differences between the permeability coefficients of each polymer, particularly with regard to water vapour. The presence of additives within the film coatings had a greater effect on the properties of cellulose acetate phthalate than those of polyvinyl acetate phthalate. Suitable formulations of each polymer were used to enteric coat 325 mg aspirin tablets, which were subsequently subjected to both the Disintegration Test for Enteric Coated Tablets B.P. and a dissolution procedure to monitor the release of drug in simulated gastric juice and simulated intestinal fluid. Both polymers demonstrated their suitability for producing enteric coatings. However, polyvinyl acetate phthalate yielded a faster release of aspirin in simulated intestinal fluid than did cellulose acetate phthalate.