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A comparison of two ambulatory blood pressure monitors, the Del Mar Avionics Pressurometer IV and the Spacelabs 90202.

The purpose of this study was to evaluate the accuracy of two noninvasive ambulatory blood pressure (BP) monitors, the new Del Mar Avionics Pressurometer IV (PIV) and the second generation Spacelabs 90202. Two sets of comparisons were made between two trained observers and the monitors on 17 normotensive and 28 hypertensive subjects. The result of the first comparison showed that the average difference between observers and the PIV was 1.2/-2.2 mm Hg for systolic and diastolic BP. Comparisons of both monitors to the observers showed differences of 0.9/1.0 mm Hg for the PIV and 0.3/0.8 mm Hg for the 90202 (systolic/diastolic). Correlations between the average observer reading and the monitors over both sets of comparisons ranged from 0.90 (diastolic 90202 vs observer) to 0.98 (systolic PIV vs observer). The percentage of readings within 5 mm Hg between observer and monitor over all comparisons ranged from a low of 68% (90202, systolic and diastolic) to a high of 83% (PIV, diastolic). In general, both devices are satisfactory and reliable machines for ambulatory BP monitoring, but each has a slightly different bias compared to auscultatory readings.

Adult↗

LASSAP, a LArge Scale Sequence compArison Package.

MOTIVATION: This paper presents LASSAP, a new software package for sequence comparison. LASSAP is a programmable, high-performance system designed to raise current limitations of sequence comparison programs in order to fit the needs of large-scale analysis. LASSAP provides an API (Application Programming Interface) allowing the integration of any generic pairwise-based algorithm. RESULTS: Whatever pairwise algorithm is used in LASSAP, it shares with all other algorithms numerous enhancements such as: (i) intra- and inter-databank comparisons; (ii) computational requests (selections and computations are achieved on the fly); (iii) frame translations on queries and databanks; (iv) structured results allowing easy and powerful post-analysis; (v) performance improvements by parallelization and the driving of specialized hardware. LASSAP currently implements all major sequence comparison algorithms (Fasta, Blast, Smith/Waterman), and other string matching and pattern matching algorithms. LASSAP is both an integrated software for end-users and a framework allowing the integration and the combination of new algorithms. LASSAP is used in different projects such as the building of PRODOM, the exhaustive comparison of yeast sequences, and the subfragments matching problem of TREMBL.

Algorithms↗

Measurement of the effectiveness of transitive sequence comparison, through a third 'intermediate' sequence.

MOTIVATION: Transitive sequence matching expands the scope of sequence comparison by re-running the results of a given query against the databank as a new query. This sometimes results in the initial query sequence (Q) being related to a final match (M) indirectly, through a third, 'intermediate' sequence (Q --> I --> M ). This approach has often been suggested as providing greater sensitivity in sequence comparison; however, it has not yet been possible to gauge its improvement precisely. RESULTS: Here, this improvement is comprehensively measured by seeing what fraction of the known structural relationships transitive sequence matching can uncover beyond that found by normal pairwise comparison (i.e. direct linkage). The structural relationships are taken from a well-characterized test set, the scop classification of protein structure. Specifically, 2055 known structural similarities (called 'pairs') between distantly related proteins constitute the basic test set. To make the measurement of transitive matching properly, special data sets, called 'baseline sets', are derived from this. They consist of pairs of sequences that have a clear structural relationship that cannot be found by normal sequence comparison (i.e. they cannot be directly linked). Specifically, using standard sequence comparison protocols (FASTA with an e-value cut-off of 0. 001), it is found that the baseline set consists of 1742 pairs. A third intermediate sequence can link 86 of these indirectly (5%), where this third sequence is drawn from the entire, current universe of protein sequences. The number of false positives is minimal. Furthermore, when one considers only the relationships within the test set that correspond to a close structural alignment, the coverage increases considerably. In particular, 862 of the baseline set pairs fit to better than 2.6 A RMS, and transitive matching can find 62 of these (9%). AVAILABILITY: All the test data, including precise similarity values calculated from structural alignment, are available in tabular format over the Web from http://bioinfo.mbb. yale.edu/align. CONTACT: Mark.Gerstein@yale.edu

Amino Acid Sequence↗

ACT: the Artemis Comparison Tool.

The Artemis Comparison Tool (ACT) allows an interactive visualisation of comparisons between complete genome sequences and associated annotations. The comparison data can be generated with several different programs; BLASTN, TBLASTX or Mummer comparisons between genomic DNA sequences, or orthologue tables generated by reciprocal FASTA comparison between protein sets. It is possible to identify regions of similarity, insertions and rearrangements at any level from the whole genome to base-pair differences. ACT uses Artemis components to display the sequences and so inherits powerful searching and analysis tools. ACT is part of the Artemis distribution and is similarly open source, written in Java and can run on any Java enabled platform, including UNIX, Macintosh and Windows.

Algorithms↗

A comparison of somatic mutational spectra in healthy study populations from Russia, Sweden and USA.

A comparison of mutation spectra at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene of peripheral blood T-lymphocytes may provide an insight into the aetiology of somatic mutation contributing to carcinogenesis and other diseases. To increase the knowledge of mutation spectra in healthy people, we have analysed HPRT mutant T-cells of 50 healthy Russians originally recruited as controls in a study involving Chernobyl clean-up workers [I.M. Jones, H.Galick, P.Kato et al. (2002) Radiat. Res., 158, 424-442]. Reverse transcriptase-polymerase chain reactions and DNA sequencing identified 161 independent mutations among 176 thioguanine-resistant mutants. Forty mutations affected splicing mechanisms and 27 deletions or insertions of 1-60 nt were identified. Ninety-four single base substitutions were identified, including 62 different mutations at 55 different nucleotide positions, of which 19 had not been reported previously in human T-cells. Comparison of this base substitution spectrum with mutation spectra in a USA [K.J.Burkhart-Schultz, C.L. Thompson and I.M. Jones (1996) Carcinogenesis, 17, 1871-1883] and two Swedish populations [A.Podlutsky, A.-M.Osterholm, S.-M.Hou, A. Hofmaier and B. Lambert (1998) Carcinogenesis, 19, 557-566; A.Podlutsky, S.M.Hou, F.Nyberg, G. Pershagen and B. Lambert (1999) Mutat. Res., 431, 325-39] revealed similarity in the type, frequency and distribution of mutations in the four spectra, consistent with aetiologies inherent in human metabolism. There were 15-19 identical mutations in the three pairwise comparisons of Russian with USA and Swedish spectra. Intriguingly, there were 21 mutations unique to the Russian spectrum, and comparison by the Monte Carlo method of W.T. Adams and T.R. Skopek [(1987) J. Mol. Biol., 194, 391-396] indicated that the Russian spectrum was different from both Swedish spectra (P = 0.007, 0.002), but not different from the USA spectrum (P = 0.07) when Bonferroni correction for multiple comparisons was made (P < 0.008 required for significance). Age and smoking did not account for these differences. Other factors causing mutational differences need to be explored.

Adult↗

The efficacy of a population-based comparison group in cross-sectional occupational health studies.

The availability and the choice of appropriate comparison groups are essential for valid occupational epidemiologic studies. Too often, however, adequate comparison groups cannot easily be found within a workplace environment or extracted from the general population. An evaluation of the efficacy of using a pool of comparison subjects from the health and Nutrition Examination Survey (HANES) was performed on data gathered by the National Institute for Occupational Safety and Health in 1979. Comparison groups from the HANES pool were derived for 246 workers at four different commercial/industrial facilities in the Niagara Falls, New York, area and the comparability between the groups was assessed for several demographic, behavioural, and biomedical variables. The HANES groups exhibited a high degree of comparability with regard to most variables, excluding ancestry. The HANES pool may serve as a useful source of subjects to allow for the comparison of disease rates where occupational exposure is the key distinguishing feature between groups.

Adult↗

Use of observational databases to evaluate the effectiveness of antiretroviral therapy for HIV infection: comparison of cohort studies with randomized trials. EuroSIDA, the French Hospital Database on HIV and the Swiss HIV Cohort Study Groups.

OBJECTIVES: It is important to assess the extent of bias when comparing the clinical efficacy of antiretroviral regimens in observational databases because, with the current lack of planned large trials, such analyses may represent the only means of assessing the risk of serious clinical events associated with new regimens. We aimed to compare the results from observational databases with those from randomized trials. METHODS: Three treatment comparisons from randomized trials [Delta, AIDS Clinical Trials Group (ACTG) 175, Community Programs for Clinical Research on AIDS (CPCRA) 007 and ACTC 320] were mimicked in cohorts: (i) zidovudine monotherapy versus combination regimens of two nucleoside analogues; (ii) zidovudine combined with either didanosine or zalcitabine; and (iii) a dual combination versus a triple regimen including a protease inhibitor. Data for over 10 000 patients from the French Hospital Database on HIV, the EuroSIDA study and the Swiss HIV cohort study were analysed for each of the comparisons. Progression to AIDS disease or death was analysed in Cox models, adjusting for baseline differences, and results compared with randomized trials. RESULTS: For comparison (i) the adjusted relative risk estimates from cohorts were between 0.61 and 0.84, favouring combinations over monotherapy, compared with 0.57 to 0.63 for trials. For comparison (ii) relative risk estimates from cohorts ranged from 0.81 to 1.01 compared with 0.77 to 0.92 for trials. For comparison (iii), two of the cohorts showed similar results to the ACTG 320 trial but one indicated a higher risk of progression on triple therapy [relative risk 1.20, 95% confidence interval (CI) 1.01-1.441, in direct contrast to the trial result (relative risk 0.50, 95% CI 0.33-0.76). CONCLUSION: Serious biases can be present when comparing outcomes from the use of antiretroviral regimens in observational studies. However, such bias is not inevitable and careful interpretation of the results from several observational studies considered together is likely to be informative, guiding the design of new trials.

Anti-HIV Agents↗

A comparison of ICRP Publication 30 lung model-based predictions with measured bioassay data for airborne natural UO2 exposure.

In this paper a comparison is made between the build-up of U thorax burdens and the predicted total lung (lung and lymph) burden, based on the lung model provided in ICRP Publication 30 for a group of 29 atomic radiation workers at a Canadian fuel fabrication facility. A similar comparison is made between the predicted ratio of the total lung burden to urinary excretion and the ratio obtained from bioassay data. The study period for the comparison is 5 y. The inhalation input for the lung model calculations was derived from air-sampling data and the choice of particle size activity median aerodynamic diameter (AMAD) was guided by particle size measurements made at representative work locations. The pulmonary clearance half-times studied were 100, 250 and 500 d. For the purpose of this comparison, averaged exposure and averaged bioassay data for the group were used. This comparison indicates that for the conditions of this facility, the assumption of a 500-d pulmonary clearance half-time and a particle size of 1 micron (AMAD) may be too conservative. It is suggested that measurements of air concentrations and particle size used as input parameters for the ICRP Publication 30 lung model may be used to calculate bioassay parameters which may then be tested against bioassay data obtained as part of an operational health physics program, thereby giving a useful step towards defining a derived air concentration value for U in the workplace.

Air Pollutants↗

Impact of comparison group on cohort dose response regression: an example using risk estimation in atomic-bomb survivors.

Cohort-based dose-response analyses can be biased if based on a comparison group that is not comparable to the exposed persons with respect to uncontrolled factors related to disease incidence or mortality. When data exist over a range of doses including the very low dose region, internal regression standardized analyses based on the regression intercept derived from the exposed subcohort alone can provide risk estimates that are not subject to such comparison-group bias. In the Life Span Study cohort of atomic-bomb survivors, persons with dose estimates of zero comprise a broader geographic distribution than that of persons with non-zero dose estimates. Because there is geographic variation in mortality rates, the zero-dose persons might bias background rate estimates thereby affecting inference about radiation risk. This is illustrated using mortality due to all causes. Restricting the comparison group to certain geographically defined subcohorts resulted in as much as a 6% increase or 8% decrease in the risk estimate. This bias can be corrected using an SMR-type estimate in the regression model, allowing retention of the comparison group in the analysis if it is needed for stability or precision in estimating age, time, and sex effects. Consideration of heterogeneity in comparison groups is particularly important in dose-response studies focused on low doses at which the response may be comparable in magnitude to such heterogeneity.

Age Factors↗

Are productivity and cost-effectiveness comparisons between in-house clinical engineering departments possible or useful?

Inter-institutional comparisons of productivity and cost-effectiveness can be a valuable source of feedback to the in-house biomedical or clinical engineering services manager. But for such comparisons to be valid, all institutions must use the same criteria. As yet, there are no standard definitions for such criteria and, in most cases, the necessary data are not kept. Therefore, reliable comparisons are not possible. It is possible, however, to keep data on the variety of tasks common to all clinical engineering departments that can then be compared inter-institutionally. As task comparisons become more common, "norms" will evolve that can become standards for the profession. From there, it is a realizable step to standards that permit comparison of productivity and cost-effectiveness. A national organization, like the American Hospital Association could help by including clinical engineering data as part of their annual hospitals survey.

Biomedical Engineering↗

Meta-analysis and indirect comparisons of levetiracetam with other second-generation antiepileptic drugs in partial epilepsy.

Few comparative clinical trials of newer antiepileptic drugs (AEDs) in patients with refractory partial epilepsy are available. Therefore, meta-analysis is a widely used and useful method for comparing them. Despite the limitations of indirect comparisons, and recognizing that these drugs were tested at different doses, such comparisons can be helpful to physicians making practical treatment decisions. The purposes of this study were to present newer meta-analysis results for add-on levetiracetam compared with placebo and to estimate its efficacy and tolerability compared with other new AEDs (gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and zonisamide) in a meta-analysis using methods for making indirect comparisons. Randomized placebo-controlled clinical trials of add-on therapy with levetiracetam, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and zonisamide in patients with refractory partial epilepsy were identified in the Cochrane Library 2002. A fixed-effects model was used to estimate Mantel-Haenszel odds ratios for the responder rate (efficacy measure) and withdrawal rate (mainly tolerability measure) of levetiracetam and other new AEDs versus placebo. Because no head-to-head clinical trials comparing these new AEDs exist, adjusted indirect comparisons were then made between levetiracetam and each other AED using the meta-analysis results. At the doses tested, levetiracetam was more effective in terms of responder rate than gabapentin (odds ratio 2.64 with 95% CI 1.51-4.63) and lamotrigine (odds ratio 1.86 with 95% CI 1.04-3.34) and equally well tolerated. Levetiracetam had a significantly lower withdrawal rate than topiramate (odds ratio 0.52 with 95% CI 0.29-0.93) and oxcarbazepine (odds ratio 0.55 with 95% CI 0.33-0.92), with comparable efficacy. Although levetiracetam did not differ significantly from the other AEDs, numerical trends favoring levetiracetam were obtained in response rate and in withdrawal rate (tiagabine, zonisamide). Indirect comparisons based on meta-analysis suggest that add-on therapy with levetiracetam has a favorable responder and/or withdrawal rate relative to several AEDs in patients with partial epilepsy with doses used in clinical trials. These meta-analyses give only short-term efficacy and safety data. Comparative clinical trials and long-term studies of these agents are needed to confirm these findings.

Anticonvulsants↗

Finite width model sequence comparison.

Sequence comparison is a widely used computational technique in modern molecular biology. In spite of the frequent use of sequence comparisons, the important problem of assigning statistical significance to a given degree of similarity is still outstanding. Analytical approaches to filling this gap usually make use of an approximation that neglects certain correlations in the disorder underlying the sequence comparison algorithm. Here, we use the longest common subsequence problem, a prototype sequence comparison problem, to analytically establish that this approximation does make a difference to certain sequence comparison statistics. In the course of establishing this difference we develop a method that can systematically deal with these disorder correlations.

Algorithms↗

Dose-response in direct comparisons of different doses of aspirin, ibuprofen and paracetamol (acetaminophen) in analgesic studies.

AIMS: Establishing the dose-response relationship for clinically useful doses of aspirin, ibuprofen and paracetamol has been difficult. Indirect comparison from meta-analysis is compromised by too little information at some doses. METHODS: A systematic review of randomized, double-blind trials in acute pain comparing different doses of aspirin, ibuprofen and paracetamol was therefore undertaken. RESULTS: Fifty trials were found. Numerical superiority of higher over lower dose was found by the original authors in 37/50 trials (74%) and statistical superiority in 11/50 (22%). Twenty-eight trials had design, quality and data reporting characteristics to allow pooling of common doses; in 3/28 (11%) of the individual trials our calculations showed statistical superiority of higher over lower dose. Pooled comparison of 1000/1200 mg aspirin over 500/600 mg was statistically superior, with a number-needed-to-treat (NNT) for higher over lower dose of 16 (8 to > 100). Pooled comparison of 400 mg ibuprofen over 200 mg was statistically superior, with an NNT for higher over lower dose of 10 (6-23). Pooled comparison of 1000 mg paracetamol over 500 mg was statistically superior, with an NNT for higher over lower dose of 9 (6-20). CONCLUSIONS: Use of trials making direct comparison of two different doses of target drugs revealed the underlying dose-response curve for clinical analgesia.

Acetaminophen↗

Skin tolerability and efficacy of combination therapy with hydrogen peroxide stabilized cream and adapalene gel in comparison with benzoyl peroxide cream and adapalene gel in common acne. A randomized, investigator-masked, controlled trial.

BACKGROUND: Combination therapy with antiseptics such as benzoyl peroxide (BP) and topical retinoids is widely used as first-line treatment for acne vulgaris (AV). However, these combinations could have a suboptimal skin tolerability. Recently, a new formulation of hydrogen peroxide (HP) 1% in stabilized cream (Crystacide; Mipharm, Milan, Italy) became available. A previous clinical study has shown that HP cream monotherapy presents a better skin tolerability in comparison with BP in patients with mild AV. OBJECTIVES: To evaluate the tolerability and the efficacy of combination therapy with HP cream and adapalene 0.1% gel in comparison with the combination of BP 4% cream and adapalene 0.1% gel in the treatment of mild to moderate AV. METHODS: In a randomized, investigator-blinded trial, 52 patients (mean +/- SD age 25 +/- 6 years; 19 men and 33 women) with AV were randomly assigned to HP cream and adapalene gel (group HP + A) or to BP cream and adapalene gel (group BP + A), for eight consecutive weeks. Efficacy was assessed by total (TL), inflammatory (IL) and noninflammatory (NL) lesion counts performed at baseline and weeks 4 and 8. Tolerability was assessed by evaluating skin erythema, burning and dryness at weeks 4 and 8. RESULTS: All patients completed the study. At baseline, the mean +/- SD numbers of TL, IL and NL were 44 +/- 9, 25 +/- 7 and 19 +/- 6 in group HP + A and 40 +/- 9, 21 +/- 7 and 19 +/- 9 in group BP + A, respectively. At the end of the treatment period, TL, IL and NL were reduced by 93%, 92% and 95%, respectively, in group HP + A and by 88%, 86% and 90%, respectively, in group BP + A. A significantly (P = 0.0025) greater reduction in NL was observed in group HP + A in comparison with group BP + A. Tolerability was significantly better in group HP + A in comparison with group BP + A (P = 0.02). Skin dryness and burning sensation were more frequent in group BP + A. CONCLUSIONS: The combination of adapalene and HP cream is an effective topical treatment regimen in mild to moderate AV. This combination has shown a better tolerability profile in comparison with the combination of BP and adapalene.

Acne Vulgaris↗

The standard primipara as a basis for inter-unit comparisons of maternity care.

OBJECTIVE: To assess the suitability of the standard primipara (a subset of the obstetric population that has relatively low risk or intervention and of adverse outcome) for making inter-unit comparisons of indicators of the process and outcome of maternity care. DESIGN: Inter-unit comparison of 10 indicators of obstetric intervention and adverse outcome derived from routinely collected computerised data held on the St Mary's Maternity Information System. SETTING: Fifteen maternity units in the former North West Thames Region. PARTICIPANTS: 15,463 primiparae who were delivered in 1992. MAIN OUTCOME MEASURES: Proportion of primiparae within the standard definition; degree to which standard primiparae are associated with lower rates of intervention and adverse outcome, as compared to other primiparae. RESULTS: Within the database, 42.6% of all primiparae were found to be standard, with rates varying between units from 25.9% to 57.7%. As expected, the standard primiparous woman is at less risk of intervention or adverse outcome than other primiparae. All but one component variable of the standard definition is a significant risk factor for at least four of the 10 indicators. Statistically significant differences in indicator rates are seen between standard and nonstandard primiparae within units. Within the standard group, significant differences in rates of intervention and adverse outcome are seen between units. Units with relatively high levels of intervention within the higher risk nonstandard group also have relatively high levels of intervention within the standard group. CONCLUSIONS: Use of the standard primipara, rather than the whole obstetric population, as the basis for inter-unit comparisons of maternity care will control for the substantial difference in case mix seen in different units, thereby increasing the validity of those comparisons. The technique has the additional benefit of clarifying the relationship between everyday clinical decision making and a unit's performance in comparative indicator reports. The approach must be combined with a separate study of the other groups in the case mix, such as multiparae and high risk primiparae. Additional nonoverlapping groups, homogeneous in terms of risk factors, should be defined and used to extend the basis on which comparisons may be made.

Adult↗

Evaluation of how age modifies the risk for Parkinson's disease, based on stratified comparisons of descriptive data.

This is a study of selected information on incidence and prevalence of Parkinson's disease (PD), mortality from Parkinsonism, and levodopa use (LDU). The concept of effect modification (EM) by age (EMA), a variation across age of incidence or odds ratios, was here extended to comparisons of prevalences, mortalities and drug use, and mathematically defined following a reported model. Age-specific EM from comparisons of empirical data was measured and combined with figures for calendar time and the annual infant mortality rates (IMRs) in the population of each observation, using linear regression analysis. Statistically significant associations of EM at ages 70-79 and 80+ were found: with IMR from prevalence comparisons; and with IMR and calendar time in comparisons of proportionate mortalities in longitudinal observations. A similar age-specific pattern of associations was observed with time from incidence in Rochester. The observations for LDU and PD incidence in Iceland and Turku, Finland, fitted well the age-specific regression lines of the IMRs with the age-specific EM components from prevalence data. We concluded that there is a universal age-specific pattern of variation of epidemiological characteristics of PD related to calendar time, and to local factors represented by the IMR. Moreover, this change can be perceived from different parameters under certain conditions. Comparisons of survey, death-records, and LDU data when used for generation of causal hypotheses for PD require that EMA be taken into account.

Age Factors↗

Social comparison as a mediator between health problems and subjective health evaluations.

The role of social comparison in mediating the relation between 'objective' health status and subjective health evaluations was examined. In a random population sample (N = 361) it was shown that health problems were related to psychological distress, which in turn induced a downward comparison process. This downward comparison resulted in a perception of being better off than others in a similar situation (relative evaluation). While both health problems and psychological distress had strong direct effects on general health evaluations, relative evaluations explained further significant variance. In addition, it was found that although women reported more psychological and physical problems than men, they engaged more often in downward comparison and consistently felt more than men did that their health was better than that of most others. No gender differences in general health evaluations were found. Interestingly, social comparison had a stronger impact on the general subjective well-being of women than of men.

Adolescent↗

Comparison of sonar discrimination: dolphin and an artificial neural network.

The capability of an echolocating dolphin to discriminate differences in the wall thickness of cylinders (3.81 cm o.d. and 12.7 cm length) was determined by Au and Pawloski [J. Comp. Physiol. A 170, 41-47 (1992)]. The dolphin was required to discriminate a standard target from comparison targets of differing wall thicknesses. Performance varied from 96% to 56% correct depending on the wall thickness of the comparison targets. The 75% correct threshold was determined to be wall thickness differences of -0.23 mm for comparison targets with thinner walls and +0.27 mm for comparison targets with thicker walls than the standard. The dolphin performance was unchanged in the presence of artificial broadband masking noise until the echo-energy-to-noise ratio fell below approximately 15 dB. A counterpropagation artificial neural network was used to examine broadband echo features from the same cylinders. Features of the echoes were determined by passing them through a filter bank of constant-Q filters. Echo features of the standard and each comparison target were analyzed in pairs by a neural network having two output nodes. Twenty echoes per target were used in the training set and 30 additional echoes per target were used in the test set. For the noise free condition, the network performed at a comparable level to the dolphin for Q values between 4 and 5. In the presence of noise, Q values between 7 and 8 were needed before the network could perform at a comparable level to the dolphin for echo-energy-to-noise ratios of 10 and 15 dB.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗