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The IBIS project: data collection in London. Improved Monitoring for Brain Dysfunction during Intensive Care and Surgery.

The primary aim of the Improved Monitoring for Brain Dysfunction during Intensive Care and Surgery (IBIS) project was to create a unique and comprehensively annotated data library (DL) of multiple physiological, including neurophysiological, signals. Data collection was undertaken in Kuopio, Finland and London, UK, and comparable protocols were used at all the sites. In London, 43 patients were recruited at the Royal Brompton Hospital, followed by nine at St. Bartholomew's Hospital, all of whom underwent cardiac or combined cardiac and carotid artery surgery. Thirty-seven patients underwent a single operation, while 15 underwent two procedures. The protocols and equipment used, problems specific to the electrically hostile environment and preliminary results are described, including those of clinical interest. The DL is being used for the development of clinically applicable neurophysiological monitoring tools.

Adult↗

G-protein-coupled receptor affinity prediction based on the use of a profiling dataset: QSAR design, synthesis, and experimental validation.

A QSAR model accounting for "average" G-protein-coupled receptor (GPCR) binding was built from a large set of experimental standardized binding data (1939 compounds systematically tested over 40 different GPCRs) and applied to the design of a library of "GPCR-predicted" compounds. Three hundred and sixty of these compounds were randomly selected and tested in 21 GPCR binding assays. Positives were defined by their ability to inhibit by more than 70% the binding of reference compounds at 10 microM. A 5.5-fold enrichment in positives was observed when comparing the "GPCR-predicted" compounds with 600 randomly selected compounds predicted as "non-GPCR" from a general collection. The model was efficient in predicting strongest binders, since enrichment was greater for higher cutoffs. Significant enrichment was also observed for peptidic GPCRs and receptors not included to develop the QSAR model, suggesting the usefulness of the model to design ligands binding with newly identified GPCRs, including orphan ones.

Combinatorial Chemistry Techniques↗

Evaluation of an imaging platform during the development of a FRET protease assay.

Synthetic peptide substrates labeled with a fluorescent donor and quenching moiety flanking an enzyme cleavage site provide a reliable method for monitoring enzyme activity. The dye pair Mca/Dnp has been widely used for this purpose, but poor solubility characteristics, combined with fluorescence emission in the region of the spectrum associated with interference from biologicals and library compounds, can limit the usefulness of Mca/Dnp substrates in a high-throughput screening (HTS) environment. Peptide Mca-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH(2) is a matrix-metalloproteinase 3 (MMP-3) enzyme substrate that the authors have labeled with a CyDye pair, Cy3/Cy5Q. The Mca/Dnp- and CyDye-labeled substrates were compared during the development of an MMP-3 inhibitor assay. The results obtained showed that although the peptide substrates behaved similarly throughout the development of the MMP-3 assay, during a test screen of 934 compounds randomly selected from a collection of more than 70000 compounds, the CyDye substrate was considerably more reliable. Screen Z factor values of 0.84 and 0.15 were obtained using the CyDye and Mca/Dnp peptides respectively, and the authors found that although < 1% of the test compounds were auto-fluorescent at Cy3 wavelengths, > 10% could not be screened using the Mca/Dnp substrate because of compound auto-fluorescence and interference. During this study, the authors used a PMT-based fluorescence plate reader and at the same time evaluated a charged couple device (CCD)-based imaging platform specifically optimized for use with CyDye reagents. The imaging platform gave improved read accuracy and faster plate processing times compared with the PMT reader. Overall, the results presented here highlight the potential benefit of employing the red-shifted CyDye reagents and imaging technology during the development and execution of HTS protease screens.

Fluorescence↗

A novel muscle LIM-only protein is generated from the paxillin gene locus in Drosophila.

Paxillin is a protein containing four LIM domains, and functions in integrin signaling. We report here that two transcripts are generated from the paxillin gene locus in Drosophila; one encodes a protein homolog of the vertebrate Paxillin (DPxn37), and the other a protein with only three LIM domains, partly encoded by its own specific exon (PDLP). At the myotendinous junctions of Drosophila embryos where integrins play important roles, both DPxn37 and PDLP are highly expressed with different patterns; DPxn37 is predominantly concentrated at the center of the junctions, whereas PDLP is highly enriched at neighboring sides of the junction centers, primarily expressed in the mesodermal myotubes. Northern blot analysis revealed that DPxn37 is ubiquitously expressed throughout the life cycle, whereas PDLP expression exhibits a biphasic pattern during development, largely concomitant with muscle generation and remodeling. Our results collectively reveal that a unique system exists in Drosophila for the generation of a novel type of LIM-only protein, highly expressed in the embryonic musculature, largely utilizing the Paxillin LIM domains.

3T3 Cells↗

Interfacing U.S. census map files with statistical graphics software: application and use in epidemiology.

In 1990, the United States Bureau of the Census released detailed geographic map files known as TIGER/Line (Topologically Integrated Geographic Encoding and Referencing). The TIGER files, accessible through purchase or federal repository libraries, contain 24 billion characters of data describing various geographic features including coastlines, hydrography, transportation networks, political boundaries, etc. for the entire United States. Many of these physical features are of potential interest in epidemiological case studies. Unfortunately, the TIGER data base only provides raw alphanumeric data; no utility software, graphical or otherwise, is included. Recently, the S statistical software package has been extended to include a map display function. The map function augments S's high-level approach towards statistical analysis and graphical display of data. Coupling this statistical software with the map data base developed for U.S. Census data collection will facilitate epidemiological research. We discuss the technical background necessary to utilize the TIGER data base for mapping with S. Two types of S maps, segment-based and polygon-based, are discussed along with methods to construct them from TIGER data. Polygon-based maps are useful for displaying regional statistical data, such as disease rates or incidence at the census tract level. Segment-based maps are easier to assemble and are appropriate when the data are not regionalized. Census tract data of AIDS incidence in San Francisco and lung cancer case locations relative to petrochemical refinery sites in Contra Costa County are used to illustrate the methods and potential uses of interfacing the TIGER data base with S.

Acquired Immunodeficiency Syndrome↗

A one-bead, one-stock solution approach to chemical genetics: part 2.

BACKGROUND: Chemical genetics provides a systematic means to study biology using small molecules to effect spatial and temporal control over protein function. As complementary approaches, phenotypic and proteomic screens of structurally diverse and complex small molecules may yield not only interesting individual probes of biological function, but also global information about small molecule collections and the interactions of their members with biological systems. RESULTS: We report a general high-throughput method for converting high-capacity beads into arrayed stock solutions amenable to both phenotypic and proteomic assays. Polystyrene beads from diversity-oriented syntheses were arrayed individually into wells. Bound compounds were cleaved, eluted, and resuspended to generate 'mother plates' of stock solutions. The second phase of development of our technology platform includes optimized cleavage and elution conditions, a novel bead arraying method, and robotic distribution of stock solutions of small molecules into 'daughter plates' for direct use in chemical genetic assays. This library formatting strategy enables what we refer to as annotation screening, in which every member of a library is annotated with biological assay data. This phase was validated by arraying and screening 708 members of an encoded 4320-member library of structurally diverse and complex dihydropyrancarboxamides. CONCLUSIONS: Our 'one-bead, multiple-stock solution' library formatting strategy is a central element of a technology platform aimed at advancing chemical genetics. Annotation screening provides a means for biology to inform chemistry, complementary to the way that chemistry can inform biology in conventional ('investigator-initiated') small molecule screens.

Bromodeoxyuridine↗

Screening drugs for metabolic stability using pulsed ultrafiltration mass spectrometry.

A pulsed ultrafiltration-mass spectrometric screening method has been developed to evaluate the metabolic stability of drugs. Pooled human liver microsomes containing cytochrome P450 enzymes were trapped by an ultrafiltration membrane in a stirred flow-through chamber, and eight beta-blocker drugs including acebutolol, alprenolol, atenolol, metoprolol, oxprenolol, pindolol, propranolol, and timolol were flow-injected through the chamber along with the cofactor NADPH. The ultrafiltrate was collected, concentrated and analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS-MS) in order to quantitate the unmetabolized fraction of each drug. The metabolic stability of each beta-blocker was determined based on the difference between the corresponding LC-MS-MS peak areas of an experimental incubation and a control without NADPH. A flow-through incubation method, pulsed ultrafiltration metabolic screening minimizes the potential for product feed back inhibition of cytochrome P450 enzymes. The importance of this phenomenon was illustrated by the observation that the metabolic stability of the set of beta-blocker drugs measured using pulsed ultrafiltration more closely resembled the in vivo stability than that determined using a conventional batch incubation with microsomes or an incubation with human hepatocytes. Since a mixture of compounds was analyzed, the relative metabolic stability of each compound could be assessed by comparison to the other compounds in the incubation. This approach might be particularly useful for the ranking of a directed library of drug leads with respect to metabolic stability and then the selection of lead compounds for further drug development.

Adrenergic beta-Antagonists↗

A CD-ROM database product for oncology.

This article discusses the development of a vertically oriented CD-ROM database product in the medical subdiscipline of oncology. Called OncoDisc, the CD-ROM is mastered by ISG. It contains three major information collections: (1) PDQ (a system of a series of files and a set of relationships; the user accesses the data through those relationships); (2) Cancerlit (the research literature that underlies the treatment information contained in PDQ), and (3) full-text articles. SearchLITE, the retrieval system, is written in C language and has been implemented on the the DEC VAX family and the IBM PC/XT and PC/AT. The disc provides a personal library of oncology information for immediate local use by the health professional; it requires no subscription to an online service, no telecommunications, and no online search charges.

Clinical Protocols↗

Split--pool synthesis of 1,3-dioxanes leading to arrayed stock solutions of single compounds sufficient for multiple phenotypic and protein-binding assays.

Diversity-oriented organic synthesis offers the promise of advancing chemical genetics, where small molecules are used to explore biology. While the split--pool synthetic method is theoretically the most effective approach for the production of large collections of small molecules, it has not been widely adopted due to numerous technical and analytical hurdles. We have developed a split--pool synthesis leading to an array of stock solutions of single 1,3-dioxanes. The quantities of compounds are sufficient for hundreds of phenotypic and protein-binding assays. The average concentration of these stock solutions derived from a single synthesis bead was determined to be 5.4 mM in 5 microL of DMSO. A mass spectrometric strategy to identify the structure of molecules from a split--pool synthesis was shown to be highly accurate. Individual members of the 1,3-dioxane library have activity in a variety of phenotypic and protein-binding assays. The procedure developed in this study allows many assays to be performed with compounds derived from individual synthesis beads. The synthetic compounds identified in these assays should serve as useful probes of cellular and organismal processes.

Animals↗

A library of Arabidopsis 35S-cDNA lines for identifying novel mutants.

We have developed a system to over-express or co-suppress random cDNAs in Arabidopsis thaliana upon Agrobacterium tumefaciens-mediated transformation. We constructed a binary vector containing a novel Arabidopsis cDNA library driven by the cauliflower mosaic virus (CaMV) 35S promoter. The vector, 35SpBARN, offers in terra selection with glufosinate ammonium (BASTA) and the ability to identify the cDNA insert using PCR with flanking primers. We introduced this overexpression library into Arabidopsis and selected over 30,000 transformants. A random sample of 50 T1 plants was analyzed to determine the quality of the cDNA library in planta. About 90% of T1 plants in the collection have inserts, the average insert size is ca. 1.1 kb, and ca. 43% of these inserts appear to encode full-length proteins. T1 plants were screened for visible abnormalities, and one mutant, V5, was chosen for further study. This mutant displays a pale green phenotype, and its transgene contains a partial petH cDNA encoding chloroplast ferredoxin-NADP+ reductase (EC 1.18.1.2). This construct co-suppresses the endogenous petH transcript. We recapitulated the mutant phenotype by expressing either the full-length or truncated petH cDNA from the CaMV 35S promoter in wild-type Arabidopsis. Our results indicate that co-suppressing endogenous genes can cause dominant phenotypes as expected. As we have also used the 35SpBARN vector to successfully over-express other transcripts in planta, we predict that this system will be generally useful for identifying genes that yield phenotypes upon over-expression as well.

Arabidopsis↗

ArrayTrack--supporting toxicogenomic research at the U.S. Food and Drug Administration National Center for Toxicological Research.

The mapping of the human genome and the determination of corresponding gene functions, pathways, and biological mechanisms are driving the emergence of the new research fields of toxicogenomics and systems toxicology. Many technological advances such as microarrays are enabling this paradigm shift that indicates an unprecedented advancement in the methods of understanding the expression of toxicity at the molecular level. At the National Center for Toxicological Research (NCTR) of the U.S. Food and Drug Administration, core facilities for genomic, proteomic, and metabonomic technologies have been established that use standardized experimental procedures to support centerwide toxicogenomic research. Collectively, these facilities are continuously producing an unprecedented volume of data. NCTR plans to develop a toxicoinformatics integrated system (TIS) for the purpose of fully integrating genomic, proteomic, and metabonomic data with the data in public repositories as well as conventional (Italic)in vitro(/Italic) and (Italic)in vivo(/Italic) toxicology data. The TIS will enable data curation in accordance with standard ontology and provide or interface a rich collection of tools for data analysis and knowledge mining. In this article the design, practical issues, and functions of the TIS are discussed through presenting its prototype version, ArrayTrack, for the management and analysis of DNA microarray data. ArrayTrack is logically constructed of three linked components: a) a library (LIB) that mirrors critical data in public databases; b) a database (MicroarrayDB) that stores microarray experiment information that is Minimal Information About a Microarray Experiment (MIAME) compliant; and c) tools (TOOL) that operate on experimental and public data for knowledge discovery. Using ArrayTrack, we can select an analysis method from the TOOL and apply the method to selected microarray data stored in the MicroarrayDB; the analysis results can be linked directly to gene information in the LIB.

Databases, Factual↗

Impact of the Pacific Southwest Regional Medical Library Service on hospital library development.

A study was designed to evaluate the progress of hospital libraries within Region 7 since the Pacific Southwest Regional Medical Library Services (PSRMLS) began in 1969. Library progress was defined as an increase in extent and types of services and resources offered. The study assessed the impact of Regional Medical Library programs on hospital libraries and compared resources and services reported in 1969, 1971, and 1984. The 1984 data were also measured against a set of core library services and resources that should be provided by a full-service hospital library. In addition to assessing the quality of PSRMLS programs and their effect on Region 7 hospital libraries, the study documented extensive growth in staffing, collection size, and services. PSRMLS programs were highly rated by the respondents, who also indicated that participation in PSRMLS programs improved specific library resources and services.

Arizona↗

Physiotherapy treatment approaches for the recovery of postural control and lower limb function following stroke.

BACKGROUND: There are a number of different approaches to physiotherapy treatment following stroke. Central to these are approaches based on 'neurophysiological' principles, 'motor learning' principles and 'orthopaedic' principles. OBJECTIVES: To determine if there is a difference in the recovery of postural control and lower limb function in patients with stroke if physiotherapy treatment is based on orthopaedic or neurophysiological or motor learning principles, or on a mixture of these treatment principles. SEARCH STRATEGY: This review drew on the search strategy developed by the Stroke Group as a whole. Relevant trials were identified in the Stroke Group Trials Register of Controlled Trials which was last searched in May 2001. We also searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4 1999), MEDLINE (1966-1999), EMBASE (1980-1999) and CINAHL (1982-1999) and contacted experts and researchers with an interest in stroke. SELECTION CRITERIA: Studies - randomised or quasi-randomised controlled trials. Participants - adults with a clinical diagnosis of stroke. Interventions - physiotherapy treatment approaches aimed at promoting the recovery of postural control and lower limb function. Outcomes - measures of disability, motor impairment or participation. DATA COLLECTION AND ANALYSIS: Two independent reviewers categorised the identified trials according to the inclusion/exclusion criteria, documented the methodological quality and extracted the data. MAIN RESULTS: Eleven trials were included in the review, three of which were included in two comparisons. Four trials compared a neurophysiological approach with another approach; four trials compared a motor learning approach with another approach; four studies compared a mixed approach with another approach; two trials reported comparisons of sub-groups of the same approach. A large number of heterogeneous outcome measures were used, limiting the comparison of trial results. No one type of approach had a significantly better outcome than any other type of approach. REVIEWER'S CONCLUSIONS: There is insufficient evidence to conclude that any one physiotherapy treatment approach is more effective than another in promoting the recovery of postural control or lower limb function.

Adult↗

Organisational infrastructures to promote evidence based nursing practice.

BACKGROUND: The purpose of this systematic review is to determine to what extent organisational infrastructures are effective in promoting the implementation of high quality research evidence on the effectiveness of nursing interventions. OBJECTIVES: To identify and summarize rigorous evaluations of organisational infrastructure developments aimed at promoting evidence based nursing practice. SEARCH STRATEGY: We searched: The Cochrane Library, MEDLINE, EMBASE, CINAHL, SIGLE, HEALTHLINE, National Research Register, Nuffield Database of Health Outcomes, NIH Databases up to August 2002. We hand searched the Journal of Advanced Nursing, Applied Nursing Research and Journal of Nursing Administration (to 1999), and checked the reference lists of articles obtained. We contacted experts in the field and relevant Internet groups. SELECTION CRITERIA: Randomized controlled trials, controlled clinical trials and interrupted times series studies of an entire or identified component of an organisational infrastructure development aimed at promoting effective nursing interventions. The participants were health care organisations comprising nurses, midwives and health visitors in hospital and community settings. DATA COLLECTION AND ANALYSIS: All identified papers were screened independently for relevance, design and outcome by two reviewers. MAIN RESULTS: No studies were sufficiently rigorous to be included in this systematic review. Seven case study evaluations were identified but excluded from the review because of poor design and lack of controls. REVIEWER'S CONCLUSIONS: 1. There are no clear implications for practice.2. Several conceptual models on organisational processes to promote evidence based practice have been described in published papers, and a number of organisational infrastructural interventions have been described in published papers. None have been evaluated properly. The next step in this field should be to conduct well planned evaluations of well planned interventions. 3. Interrupted and Complex Interrupted Times Series (ITS and CITS) designs should be adopted as a useful alternative to randomized controlled trials where such trials would be impractical. The health service cost of any infrastructure developments should be assessed in any evaluation. If possible, patient outcomes should be measured directly.

Efficiency, Organizational↗

Garlic for preventing pre-eclampsia and its complications.

BACKGROUND: The suggestion that garlic may lower blood pressure, inhibit platelet aggregation, and reduce oxidative stress has led to the hypothesis that it may have a role in preventing pre-eclampsia and its complications. OBJECTIVES: To assess the effects of garlic on prevention of pre-eclampsia and its complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 2), and EMBASE (1974 to April 2005). SELECTION CRITERIA: Studies were included if they were randomised trials evaluating the effects of garlic on prevention of pre-eclampsia and its complications. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Data were entered on Review Manager software for analysis, and double checked for accuracy. MAIN RESULTS: One trial (100 women) of uncertain quality compared garlic with placebo. Another study was excluded as 29% of women were lost to follow up. There was no clear difference between the garlic and control groups in the risk of developing gestational hypertension (relative risk (RR) 0.50, 95% confidence interval (CI) 0.25 to 1.00) or pre-eclampsia (RR 0.78, 95% CI 0.31 to 1.93). Women allocated garlic were more likely to report odour than those allocated placebo (RR 8.50, 95% CI 2.07 to 34.88), but there were no significant differences in other reported side-effects. The only other outcomes reported were caesarean section (RR 1.35, 95% CI 0.93 to 1.95), and perinatal mortality. There were no perinatal deaths in the study. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend increased garlic intake for preventing pre-eclampsia and its complications. Although garlic is associated with odour, other more serious side-effects have not been reported. Further large randomised trials evaluating the effects of garlic are needed before any recommendations can be made to guide clinical practice.

Female↗

An efficient strategy for large-scale high-throughput transposon-mediated sequencing of cDNA clones.

We describe an efficient high-throughput method for accurate DNA sequencing of entire cDNA clones. Developed as part of our involvement in the Mammalian Gene Collection full-length cDNA sequencing initiative, the method has been used and refined in our laboratory since September 2000. Amenable to large scale projects, we have used the method to generate >7 Mb of accurate sequence from 3695 candidate full-length cDNAs. Sequencing is accomplished through the insertion of Mu transposon into cDNAs, followed by sequencing reactions primed with Mu-specific sequencing primers. Transposon insertion reactions are not performed with individual cDNAs but rather on pools of up to 96 clones. This pooling strategy reduces the number of transposon insertion sequencing libraries that would otherwise be required, reducing the costs and enhancing the efficiency of the transposon library construction procedure. Sequences generated using transposon-specific sequencing primers are assembled to yield the full-length cDNA sequence, with sequence editing and other sequence finishing activities performed as required to resolve sequence ambiguities. Although analysis of the many thousands (22 785) of sequenced Mu transposon insertion events revealed a weak sequence preference for Mu insertion, we observed insertion of the Mu transposon into 1015 of the possible 1024 5mer candidate insertion sites.

Bacteriophage mu↗

A quarter-long exercise that introduces general education students to neurophysiology and scientific writing.

Providing large numbers of general education students with an introduction to science is a challenge. To meet this challenge, a quarter-long neurophysiology project was developed for use in an introductory biology course. The primary goals of this multistep project were to introduce students to the scientific method, scientific writing, on-line scientific bibliographic databases, and the scientific literature, while improving their academic literacy skills. Students began by collecting data on their own circadian rhythms in autonomic, motor, and cognitive function, reliably demonstrating the predicted circadian changes in heart rate, eye-hand coordination, and adding speed. Students wrote a journal-style article using pooled class data. Students were prepared to write the paper by several methods that were designed to improve academic language skills, including a library training exercise, "modeling" of the writing assignment, and drafting of subsections of the paper. This multistep neurophysiology project represents a significant commitment of time by both students and instructors, but produces a valuable finished product and ideally gives introductory students a positive first experience with science.

Circadian Rhythm↗

Intravenous oxytocin alone for cervical ripening and induction of labour.

BACKGROUND: Oxytocin is the commonest induction agent used worldwide. It has been used alone, in combination with amniotomy or following cervical ripening with other pharmacological or non-pharmacological methods. Prior to the introduction of prostaglandin agents oxytocin was used as a cervical ripening agent as well. In developed countries oxytocin alone is more commonly used in the presence of ruptured membranes whether spontaneous or artificial. In developing countries where the incidence of HIV is high, delaying amniotomy in labour reduces vertical transmission rates and hence the use of oxytocin with intact membranes warrants further investigation. This review will address the use of oxytocin alone for induction of labour. Amniotomy alone or oxytocin with amniotomy for induction of labour has been reviewed elsewhere in the Cochrane Library. Trials which consider concomitant administration of oxytocin and amniotomy will not be considered. This is one of a series of reviews of methods of cervical ripening and labour induction using a standardised methodology. OBJECTIVES: To determine the effects of oxytocin alone for third trimester cervical ripening or induction of labour in comparison with other methods of induction of labour or placebo/no treatment. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group Trials Register, the Cochrane Controlled Trials Register and bibliographies of relevant papers. Last searched: May 2001. SELECTION CRITERIA: The criteria for inclusion included the following: (1) clinical trials comparing vaginal prostaglandins used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods; (2) random allocation to the treatment or control group; (3) adequate allocation concealment; (4) violations of allocated management not sufficient to materially affect conclusions; (5) clinically meaningful outcome measures reported; (6) data available for analysis according to the random allocation; (7) missing data insufficient to materially affect the conclusions. DATA COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. The initial data extraction was done centrally, and incorporated into a series of primary reviews arranged by methods of induction of labour, following a standardised methodology. The data is to be extracted from the primary reviews into a series of secondary reviews, arranged by category of woman. MAIN RESULTS: In total, 110 trials were considered; 52 have been excluded and 58 included examining a total of 11,129 women. Comparing oxytocin alone with expectant management: Oxytocin alone reduced the rate of unsuccessful vaginal delivery within 24 hours when compared with expectant management (8.3% versus 54%, relative risk (RR) 0.16, 95% confidence interval (CI) 0.10,0.25) but the caesarean section rate was increased (10.4% versus 8.9%, RR 1.17, 95% CI 1.01,1.36). This increase in caesarean section rate was not apparent in the subgroup analyses. Women were less likely to be unsatisfied with induction rather than expectant management, in the one trial reporting this outcome (5.5% versus 13.7%, RR 0.43, 95% CI 0.33, 0.56). Comparing oxytocin alone with vaginal prostaglandins: Oxytocin alone was associated with an increase in unsuccessful vaginal delivery within 24 hours (52% versus 28%, RR 1.85, 95% CI 1.41, 2.43), irrespective of membrane status, but there was no difference in caesarean section rates (11.4% versus 10%, RR 1.12, 95% CI 0.95, 1.33). Comparing oxytocin alone with intracervical prostaglandins: Oxytocin alone was associated with an increase in unsuccessful vaginal delivery within 24 hours when compared with intracervical PGE2 (51% versus 35%, RR 1.49, 95% CI 1.12,1.99). For all women with an unfavourable cervix regardless of membrane status, the caesarean section rates were increased (19.0% versus 13.1%, RR 1.42, 95% CI 1.11, 1.82). REVIEWER'S CONCLUSIONS: Overall, comparison of oxytocin alone with either intravaginal or intracervical PGE2 reveals that the prostaglandin agents probably overall have more benefits than oxytocin alone. The amount of information relating to specific clinical subgroups is limited, especially with respect to women with intact membranes. Comparison of oxytocin alone to vaginal PGE2 in women with ruptured membranes reveals that both interventions are probably equally efficacious with each having some advantages and disadvantages over the others. With respect to current practice in women with ruptured membranes induction can be recommended by either method and in women with intact membranes there is insufficient information to make firm recommendations.

Cervical Ripening↗