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In search of secreted protein biomarkers for the anti-inflammatory effect of beta2-adrenergic receptor agonists: application of DIGE technology in combination with multivariate and univariate data analysis tools.

Two-dimensional difference gel electrophoresis (DIGE) in combination with univariate (Student's t-test) and multivariate data analysis, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to study the anti-inflammatory effects of the beta(2)-adrenergic receptor (beta(2)-AR) agonist zilpaterol. U937 macrophages were exposed to the endotoxin lipopolysaccharide (LPS) to induce an inflammatory reaction, which was inhibited by the addition of zilpaterol (LZ). This inhibition was counteracted by addition of the beta(2)-AR antagonist propranolol (LZP). The extracellular proteome of the U937 cells induced by the three treatments were examined by DIGE. PCA was used as an explorative tool to investigate the clustering of the proteome dataset. Using this tool, the dataset obtained from cells treated with LPS and LZP were separated from those obtained from LZ treated cells. PLS-DA, a multivariate data analysis tool that also takes correlations between protein spots and class assignment into account, correctly classified the different extracellular proteomes and showed that many proteins were differentially expressed between the proteome of inflamed cells (LPS and LZP) and cells in which the inflammatory response was inhibited (LZ). The Student's t-test revealed 8 potential protein biomarkers, each of which was expressed at a similar level in the LPS and LZP treated cells, but differently expressed in the LZ treated cells. Two of the identified proteins, macrophage inflammatory protein-1beta (MIP-1beta) and macrophage inflammatory protein-1alpha (MIP-1alpha) are known secreted proteins. The inhibition of MIP-1beta by zilpaterol and the involvement of the beta(2)-AR and cAMP were confirmed using a specific immunoassay.

Adrenergic Agonists↗

Estimates of the discriminant ability of definitions of improvement for juvenile rheumatoid arthritis.

OBJECTIVE: To investigate the ability of various definitions of improvement to distinguish between patients with juvenile rheumatoid arthritis (JRA) treated with active drug from those given placebo in randomized trials. METHODS: A core set of 6 response (outcome) variables for use in JRA has been reported. These core variables were combined into a number of "definitions of improvement" for the purpose of classifying individual patients as either "clinically significantly improved" or "not improved." We used a large dataset from randomized controlled trials to test the discriminant ability (sensitivity to change) of the definitions. We calculated the proportion of patients classified as "improved" by each definition in each of the treatment and control groups. RESULTS: Effect sizes were weak in 4 of the treatment regimens used (D-penicillamine, hydroxychloroquine, auranofin, and very low dose methotrexate) and no definition discriminated well between drug and placebo treated groups. Definitions that required 20 to 30% improvement in 3 to 4 of the 6 core set variables showed statistically significant differences in the proportions of patients who were classified as improved in the group treated with low dose methotrexate (10 mg/m2 body surface area/wk) compared to placebo. A definition resembling the Paulus criteria used in adult RA trials (4 of 6 core set variables improved by > or = 20%) performed well, as did the definition selected previously as the best for JRA (3 of 6 core set variables improved by > or = 30%, not more than one worsening by > 30%). CONCLUSION: Definitions that require 20 to 30% improvement in 3 to 4 core outcome variables are sensitive to change and are able to clearly distinguish between treated and control groups when an effective drug is being tested. Further testing of their validity is under way.

Antirheumatic Agents↗

Statistical significance of hierarchical multi-body potentials based on Delaunay tessellation and their application in sequence-structure alignment.

Statistical potentials based on pairwise interactions between C alpha atoms are commonly used in protein threading/fold-recognition attempts. Inclusion of higher order interaction is a possible means of improving the specificity of these potentials. Delaunay tessellation of the C alpha-atom representation of protein structure has been suggested as a means of defining multi-body interactions. A large number of parameters are required to define all four-body interactions of 20 amino acid types (20(4) = 160,000). Assuming that residue order within a four-body contact is irrelevant reduces this to a manageable 8,855 parameters, using a nonredundant dataset of 608 protein structures. Three lines of evidence support the significance and utility of the four-body potential for sequence-structure matching. First, compared to the four-body model, all lower-order interaction models (three-body, two-body, one-body) are found statistically inadequate to explain the frequency distribution of residue contacts. Second, coherent patterns of interaction are seen in a graphic presentation of the four-body potential. Many patterns have plausible biophysical explanations and are consistent across sets of residues sharing certain properties (e.g., size, hydrophobicity, or charge). Third, the utility of the multi-body potential is tested on a test set of 12 same-length pairs of proteins of known structure for two protocols: Sequence-recognizes-structure, where a query sequence is threaded (without gap) through the native and a non-native structure; and structure-recognizes-sequence, where a query structure is threaded by its native and another non-native sequence. Using cross-validated training, protein sequences correctly recognized their native structure in all 24 cases. Conversely, structures recognized the native sequence in 23 of 24 cases. Further, the score differences between correct and decoy structures increased significantly using the three- or four-body potential compared to potentials of lower order.

Models, Chemical↗

Chemical testing strategies for predicting health hazards to children.

The United States Environmental Protection Agency has proposed the development of a Children's Health Test Program under the Toxic Substances Control Act. The Environmental Protection Agency's proposal for the children's health test battery has 12 different assays including general toxicity, genotoxicity, carcinogenicity, neurotoxicity, and developmental and reproductive toxicity. The current Environmental Protection Agency testing proposal is an "all or nothing" test battery. An alternative and preferable approach would be to use a science-based, tiered testing scheme. It is proposed that the Screening Information Dataset program, currently used by the Organization for Economic Co-operation and Development (OECD) for the Screening Information Dataset-High Production Volume test battery, or equivalent, be considered for the first step. Step 1 would include acute and repeat dose toxicity testing, developmental toxicity testing (first species OECD 414 or OECD 422), reproductive toxicity screening (OECD 415 or 422), and genetic toxicity testing. For this step, the rat would be the initial and only species tested unless the mouse was used for in vivo genetic toxicity. Step 2 of the proposed children's health test battery would include developmental testing (second species OECD 414) or special mode of action studies performed for those chemicals that proved to be developmental toxicants in Step 1. Those chemicals that tested positive as reproductive toxicants in Step 1 would be tested in a two-generation reproduction study (OECD 416) or a special mode of action study. Steps 1 and 2 provide information on whether oncogenicity or developmental neurotoxicity testing is useful. Step 3 would include chronic toxicity/oncogenicity testing for those chemicals that tested positive for genetic toxicity in Step 1, and positive for developmental concerns in Step 2. In this step, chemicals would also be tested for developmental neurotoxicity if they showed evidence of neuropathy, behavioral effects, or neurotoxic potential in earlier studies. This stepwise approach would conserve resources and answer scientific questions in a logical, orderly, timely, and cost-effective manner.

Animals↗

Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions.

OBJECTIVE: To investigate whether differences in antidepressant efficacy are moderated by an interaction of age and gender. METHODS: A pooled dataset from eight randomized, controlled trials of patients with major depressive disorder (MDD) was reanalyzed to compare remission rates following therapy with venlafaxine (n = 851), one of several selective serotonin reuptake inhibitors (SSRIs) (n = 748), or placebo (n = 446). Remission was defined as a final Hamilton Rating Scale for Depression (HAM-D) score < or =7. Pairwise comparisons were conducted using stepwise multiple logistic regression models with main effect and interaction terms for treatment, sex, and age (younger: <50; older: > or =50). Among older women, the impact of hormone replacement therapy (HRT) on remission rates also was examined. RESULTS: Remission rates on venlafaxine therapy were not affected by age, sex, or HRT use. Among women, but not men, there was a significant interaction reflecting poorer SSRI response in the older age group (Wald chi-square = 4.21, df = 1, p = 0.04); HRT appeared to eliminate this difference. Whereas the advantage in remission rates favoring venlafaxine was modest for men and younger women (6%-9%), the difference among older women not taking HRT was 23%. CONCLUSIONS: These findings provide further evidence that age, gender, and HRT moderate response to antidepressant medications.

Adult↗

Immunogenicity, safety, and predictors of response after a pneumococcal conjugate and pneumococcal polysaccharide vaccine series in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy.

BACKGROUND: The immunogenicity and safety of 2 doses of pneumococcal conjugate vaccine (PCV) and 1 dose of pneumococcal polysaccharide vaccine (PPV) were evaluated in human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). METHODS: Children 2 to <19 years, receiving stable HAART for > or =3-6 months, with HIV RNA PCR <30,000-60,000 copies/mL, received 2 doses of PCV and 1 dose of PPV at sequential 8-week intervals. Antibodies to pneumococcal serotypes (STs) 1 (PPV only) and 6B, 14, 19F, and 23F (PCV and PPV) were measured by ELISA. RESULTS: Two hundred sixty-three subjects were enrolled, of whom 225 met criteria for inclusion in the primary dataset. Antibody concentrations were low at entry, despite previous PPV in 75%. After vaccination, 76%-96% had concentrations > or =0.5 microg/mL and 62-88% > or =1.0 microg/mL to the 5 STs (geometric mean concentrations [GMCs] = 1.44-4.25 microg/mL). Incremental gains in antibody concentration occurred with each vaccine dose. Predictors of response included higher antibody concentration at entry, higher immune stratum (based on nadir CD4% before HAART and CD4% at screening), lower entry viral RNA, longer duration of the entry HAART regimen, and age <7 years. Response was more consistently related to screening CD4% than nadir CD4%. Seven percent had vaccine-related grade 3 events, most of which were local reactions. CONCLUSIONS: Two PCVs and 1 PPV were immunogenic and safe in HIV-infected children 2 to <19 years who were receiving HAART. Responses were suggestive of functional immune reconstitution. Immunologic status based on nadir and, especially, current CD4% and control of HIV viremia were independent determinants of response.

Adolescent↗

Responsiveness, effect size, and smallest detectable difference of Magnetic Resonance Imaging in knee osteoarthritis.

OBJECTIVE: The aim of this study was to determine the responsiveness, effect size (ES) and smallest detectable difference (SDD) of two Magnetic Resonance Imaging (MRI) measures for osteoarthritis (OA) of the knee: a whole-organ semiquantitative evaluation and cartilage volume. DESIGN: This analysis was performed on a dataset from a randomized, double-blind trial (Roche NI-15713) conducted in 1998 of a novel therapy in subjects with mild-moderate knee OA, with MRI at baseline and 6-month follow-up. The trial measurements included (1) cartilage volume measured using a proprietary software method; and (2) semiquantitative scoring of other parameters important for "whole organ" evaluation of OA knee joint pathology, using the Whole-Organ MRI Score (WORMS). The analysis initially examined the distributional characteristics of WORMS items, such as cartilage morphology. Standardized response mean (SRM), ES, and SDD between baseline and 6-month follow-up were then calculated in the whole group and the placebo group alone. RESULTS: In general, the differences were small and this was reflected in the small ESs and SRMs. There was also a suggestion of a treatment effect with reduction in differences between baseline and follow-up in the treatment group. CONCLUSION: Of the MRI semiquantitative measures, cartilage morphology, synovitis and osteophytes appeared to be responsive to change and the focus of repeat measures should highlight these articular features. In general, the ESs and SRMs were small.

Adult↗

Factors associated with patient involvement in surgical treatment decision making for breast cancer.

OBJECTIVE: To evaluate factors associated with women's reported level of involvement in breast cancer surgical treatment decision making, and the factors associated with the match between actual and preferred involvement in this decision. METHODS: Survey data from breast cancer patients in Detroit and Los Angeles was merged with surgeon data for an analytic dataset of 1101 patients and 277 surgeons. Decisional involvement and the match between actual and preferred amount of involvement were analyzed as three-level dependent variables using multinomial logistic regression controlling for clustering within surgeons. Independent variables included patient demographic and clinical factors, surgeon demographic and practice factors, cancer program designation, and two measures of patient-surgeon communication. RESULTS: We found variation in women's actual decisional involvement and match between actual and preferred involvement. Women with a surgeon-based or patient-based (versus shared) decision were significantly (p < or = 0.05) younger. Women who had too little decisional involvement (versus the right amount) were younger, while women with too much involvement had less education. Patient-surgeon communication variables were significantly associated with both involvement and match, and higher surgeon volume as associated with too little involvement. CONCLUSION: Patient factors and patient-surgeon communication influence women's perception of their involvement in breast cancer surgical treatment decision making. PRACTICE IMPLICATIONS: Decision tools are needed across surgeons and practice settings to elicit patients' preferences for involvement in treatment decisions for breast cancer.

Adult↗

Development and validation of a computerized South Asian Names and Group Recognition Algorithm (SANGRA) for use in British health-related studies.

BACKGROUND: Studies on ethnic variations in health have played an important role in aetiological and health services research. Most routine datasets, however, do not include information on ethnicity. South Asians, one of the largest minority ethnic groups in Britain, have distinctive names that also allow differentiation of the main sub-groups with their important differences in health-related exposures and disease risks. METHODS: A computerized name recognition algorithm (SANGRA) was developed incorporating directories of South Asian first names and surnames together with their religious and linguistic origin. SANGRA was validated using health-related data with self-ascribed information on ethnicity. RESULTS: SANGRA was successful in recognizing South Asian origin in reference datasets, with sensitivity of 89-96 per cent, specificity of 94-98 per cent, positive predictive value (PPV) of 80-89 per cent and negative predictive value (NPV) of 98-99 per cent. Religious origin was correctly assigned in the majority of cases: sensitivity, specificity and PPV were 94 per cent, 91 per cent and 90 per cent for Hindus; 90 per cent, 99 per cent and 98 per cent for Muslims; and 76 per cent, 99 per cent and 94 per cent for Sikhs. SANGRA correctly identified 76 per cent Gujerati and 70 per cent Punjabi names, although only 62 per cent of Gujerati names were sufficiently distinct to be allocated to the Gujerati-only category and only 53 per cent Punjabi names were allocated to the Punjabi-only category. However, specificity and PPV were high for both languages (respectively 97 per cent and 93 per cent for Gujerati, and 99 per cent and 97 per cent for Punjabi). CONCLUSIONS: SANGRA provides a practical and valid method of ascertaining South Asian origin by name and, to a lesser degree of accuracy, of differentiating between the main religious and linguistic subgroups living in Britain. This algorithm will be useful in health-related studies where information on self-ascribed ethnicity is not available or is of a limited nature.

Algorithms↗

Melanoma histopathology reporting: are we complying with the National Minimum Dataset?

BACKGROUND: The Royal College of Pathologists introduced the National Minimum Dataset (NMDS) for the histopathological reporting of cutaneous melanoma in February 2002. AIM: To determine if histological reporting of invasive primary cutaneous melanoma in the West Midlands region of the UK was compliant with the NMDS. METHODS: Reports were identified from March 2002 to March 2003 via the regional Cancer Intelligence Unit, and compared with the NMDS. If all items of the NMDS were adhered to, the report was considered compliant. If not compliant, the report was checked to see if it included selected clinical and staging parameters. RESULTS: 543 cases of invasive cutaneous melanoma were identified, but only 407 reports were analysed. 69/407 (17%) (95% CI 14% to 20%) reports were fully compliant with the NMDS. Of the non-complaint reports, 45/361 (12%) (95% CI 9% to 16%) reported all staging and clinically relevant parameters; 62/361 (17%) (95% CI 59% to 65%) reported all staging parameters. Breslow thickness was reported in all but one of the reports (99.7%), Clark's level was reported in 344/407 (85%), ulceration in 280/407 (69%), and microsatellites in 146/407 (36%). CONCLUSION: There was slow uptake of the NMDS in this region in the year following its introduction. Although major parameters required for staging were more consistently reported, ulceration and microsatellites were less frequently reported.

England↗

Linkage analysis of the GAW14 simulated dataset with microsatellite and single-nucleotide polymorphism markers in large pedigrees.

Recent studies have suggested that a high-density single nucleotide polymorphism (SNP) marker set could provide equivalent or even superior information compared with currently used microsatellite (STR) marker sets for gene mapping by linkage. The focus of this study was to compare results obtained from linkage analyses involving extended pedigrees with STR and single-nucleotide polymorphism (SNP) marker sets. We also wanted to compare the performance of current linkage programs in the presence of high marker density and extended pedigree structures. One replicate of the Genetic Analysis Workshop 14 (GAW14) simulated extended pedigrees (n = 50) from New York City was analyzed to identify the major gene D2. Four marker sets with varying information content and density on chromosome 3 (STR [7.5 cM]; SNP [3 cM, 1 cM, 0.3 cM]) were analyzed to detect two traits, the original affection status, and a redefined trait more closely correlated with D2. Multipoint parametric and nonparametric linkage analyses (NPL) were performed using programs GENEHUNTER, MERLIN, SIMWALK2, and S.A.G.E. SIBPAL. Our results suggested that the densest SNP map (0.3 cM) had the greatest power to detect linkage for the original trait (genetic heterogeneity), with the highest LOD score/NPL score and mapping precision. However, no significant improvement in linkage signals was observed with the densest SNP map compared with STR or SNP-1 cM maps for the redefined affection status (genetic homogeneity), possibly due to the extremely high information contents for all maps. Finally, our results suggested that each linkage program had limitations in handling the large, complex pedigrees as well as a high-density SNP marker set.

Chromosome Mapping↗

Access block in NSW hospitals, 1999-2001: does the definition matter?

OBJECTIVES: To estimate the magnitude of access block and its trend over time in New South Wales hospitals, using different definitions of access block, and to explore its association with clinical and non-clinical factors. DESIGN AND SETTING: An epidemiological study using the Emergency Department Information System datasets (1 January 1999 to 31 December 2001) from a sample of 55 NSW hospitals. MAIN OUTCOME MEASURES: Prevalence of access block measured by four different definitions; strength of association between access block, type of hospital, year of presentation, mode and time of arrival, triage category (an indicator of urgency), age and sex. RESULTS: Rates of access block (for all four definitions) increased between 1999 and 2001 by 1%-2% per year. There were increases across all regions of NSW, but urban regions in particular. Patients presenting to Principal Referral hospitals and those who arrived at night were more likely to experience access block. After adjusting for triage category and year of presentation, the mode of arrival, time of arrival, type of hospital, age and sex were significantly associated with access block. CONCLUSIONS: Access block continues to increase across NSW, whatever the definition used. We recommend that hospitals in NSW and Australia move to the use of one standard definition of access block, as our study suggests there is no significant additional information emerging from the use of multiple definitions.

Adolescent↗

Web-based research of lower urinary tract symptoms that affect quality of life in elderly Japanese men: analysis using a structural equation model.

OBJECTIVE: To investigate the distribution of lower urinary tract symptoms (LUTS) in elderly Japanese men, to clarify which variables contributed to medical care-seeking behaviour, and to construct a structural-equation model (SEM) to explain overall quality of life (QoL). SUBJECTS AND METHODS: A dataset was obtained from 662 Japanese men aged 50-79 years who participated in the programme by accessing a website via the Internet between 10.30 hours on 19 February 2003 and 10.30 hours on 24 February 2003. The participants were queried about their International Prostate Symptom Score (IPSS), bother, QoL index and medical care-seeking behaviour. RESULTS: Of the 662 participants, 314 reported intending to seek medical care for LUTS (intention group); the remaining 348 answered that they did not intend to see a doctor (no-intention group). The characteristic of weak stream had the strongest correlation with the QoL index, not only in the intention (r = 0.58) but also in the no-intention group (r = 0.48). Among several SEMs proposed, one that included a latent variable termed 'QoL sensitivity' was the most appropriate to explain overall QoL. In this model it was assumed that 'QoL sensitivity' was affected by other latent variables, termed the 'voiding symptom factors' and 'storage symptom factors', and affected the degree of bother related to each symptom. CONCLUSION: In Japanese men, voiding symptoms, especially weak stream, contributed to overall QoL for medical care-seeking behaviour. Differences in 'QoL sensitivity' among men may be one of the reasons why symptomatic severity is not always correlated with symptom-related bother.

Aged↗

Quantifying fractal dynamics of human respiration: age and gender effects.

We sought to quantify the fractal scaling properties of human respiratory dynamics and determine whether they are altered with healthy aging and gender. Continuous respiratory datasets (obtained by inductive plethysmography) were collected from 40 healthy adults (10 young men, 10 young women, 10 elderly men, and 10 elderly women) during 120 min of spontaneous breathing. The interbreath interval (IBI) time series were extracted by a new algorithm and fractal scaling exponents that quantify power-law correlations were computed using detrended fluctuation analysis. Under supine, resting, and spontaneous breathing conditions, both healthy young and elderly subjects had scaling exponents for the IBI time series that indicate long-range (fractal) correlations across multiple time scales. Furthermore, the scaling exponents (mean +/- SD) for the IBI time series were significantly (p < 0.03) lower (indicating decreased correlations) in the healthy elderly male (0.60 +/- 0.08) compared to the young male (0.68 +/- 0.07), young female (0.70 +/- 0.07), and elderly female (0.67 +/- 0.06) subjects. These results provide evidence for fractal organization in physiologic human breathing cycle dynamics, and for their degradation in elderly men. These findings may have implications for modeling integrated respiratory control mechanisms, quantifying their changes in aging or disease, and assessing the outcome of interventions aimed toward restoring normal physiologic respiratory dynamics.

Adult↗

Evaluation of methods for predicting the topology of beta-barrel outer membrane proteins and a consensus prediction method.

BACKGROUND: Prediction of the transmembrane strands and topology of beta-barrel outer membrane proteins is of interest in current bioinformatics research. Several methods have been applied so far for this task, utilizing different algorithmic techniques and a number of freely available predictors exist. The methods can be grossly divided to those based on Hidden Markov Models (HMMs), on Neural Networks (NNs) and on Support Vector Machines (SVMs). In this work, we compare the different available methods for topology prediction of beta-barrel outer membrane proteins. We evaluate their performance on a non-redundant dataset of 20 beta-barrel outer membrane proteins of gram-negative bacteria, with structures known at atomic resolution. Also, we describe, for the first time, an effective way to combine the individual predictors, at will, to a single consensus prediction method. RESULTS: We assess the statistical significance of the performance of each prediction scheme and conclude that Hidden Markov Model based methods, HMM-B2TMR, ProfTMB and PRED-TMBB, are currently the best predictors, according to either the per-residue accuracy, the segments overlap measure (SOV) or the total number of proteins with correctly predicted topologies in the test set. Furthermore, we show that the available predictors perform better when only transmembrane beta-barrel domains are used for prediction, rather than the precursor full-length sequences, even though the HMM-based predictors are not influenced significantly. The consensus prediction method performs significantly better than each individual available predictor, since it increases the accuracy up to 4% regarding SOV and up to 15% in correctly predicted topologies. CONCLUSIONS: The consensus prediction method described in this work, optimizes the predicted topology with a dynamic programming algorithm and is implemented in a web-based application freely available to non-commercial users at http://bioinformatics.biol.uoa.gr/ConBBPRED.

Algorithms↗

Variability of spirometry in chronic obstructive pulmonary disease: results from two clinical trials.

OBJECTIVE: Our goal is to determine short-term intraindividual biologic and measurement variability in spirometry of patients with a wide range of stable chronic obstructive pulmonary disease severity, using datasets from the National Emphysema Treatment Trial (NETT) and the Lung Health Study (LHS). This may be applied to determine criteria that can be used to assess a clinically meaningful change in spirometry. METHODS: A total of 5,886 participants from the LHS and 1,215 participants from the NETT performed prebronchodilator spirometry during two baseline sessions. We analyzed varying criteria for absolute and percent change of FEV(1) and FVC to determine which criterion was met by 90% of the participants. RESULTS: The mean +/- SD FEV(1) for the initial session was 2.64 +/- 0.60 L (75.1 +/- 8.8% predicted) for the LHS and 0.68 +/- 0.22 L (23.7 +/- 6.5% predicted) for the NETT. The mean +/- SD number of days between test sessions was 24.9 +/- 17.1 for the LHS and 85.7 +/- 21.7 for the NETT. As the degree of obstruction increased, the intersession percent difference of FEV(1) increased. However, the absolute difference between tests remained relatively constant despite the severity of obstruction (0.106 +/- 0.10 L). Over 90% of participants had an intersession FEV(1) difference of less than 225 ml irrespective of the severity of obstruction. CONCLUSIONS: Absolute changes in FEV(1) rather than percent change should be used to determine whether patients with chronic obstructive pulmonary disease have improved or worsened between test sessions.

Aged↗

Characteristics and study motivation of Danish dental students in a longitudinal perspective.

This survey encompasses 3 comparable datasets of newly admitted dental students in 1972 (n=236), 1982 (n=197), and 1994 (n=108). The objectives of the survey were to describe selected socio-demographic characteristics of dental students and to analyze possible changes over time as well as possible changes in the reasons reported by the students for choosing dentistry as a career, their motivations and their expectations concerning the study and the profession of dentistry. The results showed that the ratio of women to men remained unchanged at 6:4 in all 3 cohorts of students and that the students were increasingly recruited from the 2 upper social classes. The motives for choosing dentistry mainly included altruistic motives, the desire for varied work with the opportunity to put theory into practice, economic rewards, and the implicit social status. Compared to the 1972 students, those in 1994 placed greater emphasis on social status as a motive, on the opportunity to work in the biological and scientific field, and on the ready availability of work outside Denmark. The students in all 3 years had strong altruistic motives for choosing dentistry, and it would seem that this stable continuity in the cohort of dental students would ensure the continuous controlled development of dentistry in the new millennium.

Adolescent↗

Asking questions about medication: analysis of physician-patient interactions and physician perceptions.

OBJECTIVES: The purpose of this research was to examine physicians' and patients' question-asking about medications during medical encounters. METHODS: A dataset of 467 audiotapes and transcripts of outpatient visits, as well as postvisit interviews with chronic disease patients and their primary care physicians, was analyzed. RESULTS: All patients took at least one prescribed medication and were using an average of 3.9 continued medications. Physicians and patients spent an average of 3.94 minutes, or 20% of each medical visit, discussing medications. Physicians asked patients an average of 9.3 questions about medications during each medical visit. Physicians asked significantly more questions of non-white patients, lower-income patients, and patients using more continued medications. Almost half (47%) of the patients observed did not ask any medication questions at all even though they were currently taking at least one medication; for those patients who did ask questions, the average number asked was 2.4. Starting a new medication doubled a patient's likelihood of question-asking. Physicians perceive question-asking in a positive light; patients who asked questions about medication were rated by their physicians as more interested and assertive than patients who did not ask questions, but not any more irritated or angry. CONCLUSIONS: The findings of the study illustrate the importance of improving physicians' and patients' question-asking about medications in primary care settings so that potential problems with medications can be detected and avoided and patient compliance can be improved.

Adult↗