Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness

OBJECTIVE: To determine the accuracy, acceptability and cost-effectiveness of polymerase chain reaction (PCR) and optical immunoassay (OIA) rapid tests for maternal group B streptococcal (GBS) colonisation at labour. DESIGN: A test accuracy study was used to determine the accuracy of rapid tests for GBS colonisation of women in labour. Acceptability of testing to participants was evaluated through a questionnaire administered after delivery, and acceptability to staff through focus groups. A decision-analytic model was constructed to assess the cost-effectiveness of various screening strategies. SETTING: Two large obstetric units in the UK. PARTICIPANTS: Women booked for delivery at the participating units other than those electing for a Caesarean delivery. INTERVENTIONS: Vaginal and rectal swabs were obtained at the onset of labour and the results of vaginal and rectal PCR and OIA (index) tests were compared with the reference standard of enriched culture of combined vaginal and rectal swabs. MAIN OUTCOME MEASURES: The accuracy of the index tests, the relative accuracies of tests on vaginal and rectal swabs and whether test accuracy varied according to the presence or absence of maternal risk factors. RESULTS: PCR was significantly more accurate than OIA for the detection of maternal GBS colonisation. Combined vaginal or rectal swab index tests were more sensitive than either test considered individually [combined swab sensitivity for PCR 84% (95% CI 79-88%); vaginal swab 58% (52-64%); rectal swab 71% (66-76%)]. The highest sensitivity for PCR came at the cost of lower specificity [combined specificity 87% (95% CI 85-89%); vaginal swab 92% (90-94%); rectal swab 92% (90-93%)]. The sensitivity and specificity of rapid tests varied according to the presence or absence of maternal risk factors, but not consistently. PCR results were determinants of neonatal GBS colonisation, but maternal risk factors were not. Overall levels of acceptability for rapid testing amongst participants were high. Vaginal swabs were more acceptable than rectal swabs. South Asian women were least likely to have participated in the study and were less happy with the sampling procedure and with the prospect of rapid testing as part of routine care. Midwives were generally positive towards rapid testing but had concerns that it might lead to overtreatment and unnecessary interference in births. Modelling analysis revealed that the most cost-effective strategy was to provide routine intravenous antibiotic prophylaxis (IAP) to all women without screening. Removing this strategy, which is unlikely to be acceptable to most women and midwives, resulted in screening, based on a culture test at 35-37 weeks' gestation, with the provision of antibiotics to all women who screened positive being most cost-effective, assuming that all women in premature labour would receive IAP. The results were sensitive to very small increases in costs and changes in other assumptions. Screening using a rapid test was not cost-effective based on its current sensitivity, specificity and cost. CONCLUSIONS: Neither rapid test was sufficiently accurate to recommend it for routine use in clinical practice. IAP directed by screening with enriched culture at 35-37 weeks' gestation is likely to be the most acceptable cost-effective strategy, although it is premature to suggest the implementation of this strategy at present.

Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc

Aqueous semi-solid polymeric gels, such as those based on hydroxyethylcellulose (HEC) and polyacrylic acid (e.g. Carbopol®), have a long history of use in vaginal drug delivery. However, despite their ubiquity, they often provide sub-optimal clinical performance, due to poor mucosal retention and limited solubility for poorly water-soluble actives. These issues are particularly pertinent for vaginal HIV microbicides, since many lead candidates are poorly water-soluble and where a major goal is the development of a coitally independent, once daily gel product. In this study, we report the use of a non-aqueous silicone elastomer gel for vaginal delivery of the HIV-1 entry inhibitor maraviroc. In vitro rheological, syringeability and retention studies demonstrated enhanced performance for silicone gels compared with a conventional aqueous HEC gel, while testing of the gels in the slug model confirmed a lack of mucosal irritancy. Pharmacokinetic studies following single dose vaginal administration of a maraviroc silicone gel in rhesus macaques showed higher and sustained MVC levels in vaginal fluid, vaginal tissue and plasma compared with a HEC gel containing the same maraviroc loading. The results demonstrate that non-aqueous silicone gels have potential as a formulation platform for coitally independent vaginal HIV microbicides.

The development of a testing procedure for dry friction brakes

A description of the background to testing friction materials for automotive brakes explains the need for a rapid, inexpensive means of assessing their behaviour in a way which is both accurate and meaningful. Various methods of controlling inertia dynamometers to simulate road vehicles are rejected in favour of programming by means of a commercially available XY plotter. Investigation of brake service conditions is used to set up test schedules, and a dynamometer programming unit built to enable service conditions on vehicles to be simulated on a full scale dynamometer. A technique is developed by which accelerated testing can be achieved without operating under overload conditions, saving time and cost without sacrificing validity. The development of programming by XY plotter is described, with a method of operating one XY plotter to programme the machine, monitor its own behaviour, and plot its own results in logical sequence. Commissioning trials are described and the generation of reproducible results in frictional behaviour and material durability is discussed. Teclmiques are developed to cross check the operation of the machine in retrospect, and retrospectively correct results in the event of malfunctions. Sensitivity errors in the measuring circuits are displayed between calibrations, whilst leaving the recorded results almost unaffected by error. Typical results of brake lining tests are used to demonstrate the range of performance parameters which can be studied by use of the machine. Successful test investigations completed on the machine are reported, including comments on behaviour of cast iron drums and discs. The machine shows that materials can repeat their complex friction/ temperature/speed/pressure relationships at a reproducibility of the order of +-0.003u and +~ 0.0002 in. thickness loss during wear tests. Discussion of practical and academic implications completes the report with recommendations for further work in both fields.

Rapid machine tool verification

This paper describes work carried out to develop methods of verifying that machine tools are capable of machining parts to within specification, immediately before carrying out critical material removal operations, and with negligible impact on process times. A review of machine tool calibration and verification technologies identified that current techniques were not suitable due to requirements for significant time and skilled human intervention. A 'solution toolkit' is presented consisting of a selection circular tests and artefact probing which are able to rapidly verify the kinematic errors and in some cases also dynamic errors for different types of machine tool, as well as supplementary methods for tool and spindle error detection. A novel artefact probing process is introduced which simplifies data processing so that the process can be readily automated using only the native machine tool controller. Laboratory testing and industrial case studies are described which demonstrate the effectiveness of this approach.

Can aberrometry provide rapid and reliable measures of subjective depth of focus following multifocal intraocular lens implantation?

Purpose: To determine whether the ‘through-focus’ aberrations of a multifocal and accommodative intraocular lens (IOL) implanted patient can be used to provide rapid and reliable measures of their subjective range of clear vision. Methods: Eyes that had been implanted with a concentric (n = 8), segmented (n = 10) or accommodating (n = 6) intraocular lenses (mean age 62.9 ± 8.9 years; range 46-79 years) for over a year underwent simultaneous monocular subjective (electronic logMAR test chart at 4m with letters randomised between presentations) and objective (Aston open-field aberrometer) defocus curve testing for levels of defocus between +1.50 to -5.00DS in -0.50DS steps, in a randomised order. Pupil size and ocular aberration (a combination of the patient’s and the defocus inducing lens aberrations) at each level of blur was measured by the aberrometer. Visual acuity was measured subjectively at each level of defocus to determine the traditional defocus curve. Objective acuity was predicted using image quality metrics. Results: The range of clear focus differed between the three IOL types (F=15.506, P=0.001) as well as between subjective and objective defocus curves (F=6.685, p=0.049). There was no statistically significant difference between subjective and objective defocus curves in the segmented or concentric ring MIOL group (P>0.05). However a difference was found between the two measures and the accommodating IOL group (P<0.001). Mean Delta logMAR (predicted minus measured logMAR) across all target vergences was -0.06 ± 0.19 logMAR. Predicted logMAR defocus curves for the multifocal IOLs did not show a near vision addition peak, unlike the subjective measurement of visual acuity. However, there was a strong positive correlation between measured and predicted logMAR for all three IOLs (Pearson’s correlation: P<0.001). Conclusions: Current subjective procedures are lengthy and do not enable important additional measures such as defocus curves under differently luminance or contrast levels to be assessed, which may limit our understanding of MIOL performance in real-world conditions. In general objective aberrometry measures correlated well with the subjective assessment indicating the relative robustness of this technique in evaluating post-operative success with segmented and concentric ring MIOL.