Placental growth factor testing for suspected pre‐eclampsia: a cost‐effectiveness analysis

Objective To calculate the cost‐effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care. Design Cost‐effectiveness analysis. Setting Eleven maternity units participating in the PARROT stepped‐wedge cluster‐randomised controlled trial. Population Women presenting with suspected pre‐eclampsia between 20+0 and 36+6 weeks’ gestation. Methods Monte Carlo simulation utilising resource use data and maternal adverse outcomes. Main outcome measures Cost per maternal adverse outcome prevented. Results Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost‐saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost‐saving of UK£2,891,196 each year across the NHS in England. Conclusions Clinical care with PlGF testing is associated with the potential for cost‐savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre‐eclampsia. Tweetable abstract Placental growth factor testing for suspected pre‐eclampsia is cost‐saving and improves maternal outcomes

Can MR textural analysis improve the prediction of extracapsular nodal spread in patients with oral cavity cancer?

Objective: To explore the utility of MR texture analysis (MRTA) for detection of nodal extracapsular spread (ECS) in oral cavity squamous cell carcinoma (SCC). Methods: 115 patients with oral cavity SCC treated with surgery and adjuvant (chemo)radiotherapy were identified retrospectively. First-order texture parameters (entropy, skewness and kurtosis) were extracted from tumour and nodal regions of interest (ROIs) using proprietary software (TexRAD). Nodal MR features associated with ECS (flare sign, irregular capsular contour; local infiltration; nodal necrosis) were reviewed and agreed in consensus by two experienced radiologists. Diagnostic performance characteristics of MR features of ECS were compared with primary tumour and nodal MRTA prediction using histology as the gold standard. Receiver operating characteristic (ROC) and regression analyses were also performed. Results: Nodal entropy derived from contrast-enhanced T1-weighted images was significant in predicting ECS (p = 0.018). MR features had varying accuracy: flare sign (70%); irregular contour (71%); local infiltration (66%); and nodal necrosis (64%). Nodal entropy combined with irregular contour was the best predictor of ECS (p = 0.004, accuracy 79%). Conclusion: First-order nodal MRTA combined with imaging features may improve ECS prediction in oral cavity SCC

The future of social care funding: who pays?

With the UK population ageing, deciding upon a satisfactory and sustainable system for the funding of people’s long-term care (LTC) needs has long been a topic of political debate. Phase 1 of the Care Act 2014 (“the Act”) brought in some of the reforms recommended by the Dilnot Commission in 2011. However, the Government announced during 2015 that Phase 2 of “the Act” such as the introduction of a £72,000 cap on Local Authority care costs and a change in the means testing thresholds 1 would be deferred until 2020. In addition to this delay, the “freedom and choice” agenda for pensions has come into force. It is therefore timely that the potential market responses to help people pay for their care within the new pensions environment should be considered. In this paper, we analyse whether the proposed reforms meet the policy intention of protecting people from catastrophic care costs, whilst facilitating individual understanding of their potential care funding requirements. In particular, we review a number of financial products and ascertain the extent to which such products might help individuals to fund the LTC costs for which they would be responsible for meeting. We also produce case studies to demonstrate the complexities of the care funding system. Finally, we review the potential impact on incentives for individuals to save for care costs under the proposed new means testing thresholds and compare these with the current thresholds. We conclude that: ∙ Although it is still too early to understand exactly how individuals will respond to the pensions freedom and choice agenda, there are a number of financial products that might complement the new flexibilities and help people make provision for care costs. ∙ The new care funding system is complex making it difficult for people to understand their potential care costs. ∙ The current means testing system causes a disincentive to save. The new means testing thresholds provide a greater level of reward for savers than the existing thresholds and therefore may increase the level of saving for care; however, the new thresholds could still act as a barrier since disincentives still exist

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review

Background Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses. To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. Methods We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. Results Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. Conclusion There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect

Identification of a Novel ZIC3 Isoform and Mutation Screening in Patients with Heterotaxy and Congenital Heart Disease

Patients with heterotaxy have characteristic cardiovascular malformations, abnormal arrangement of their visceral organs, and midline patterning defects that result from abnormal left-right patterning during embryogenesis. Loss of function of the transcription factor ZIC3 causes X-linked heterotaxy and isolated congenital heart malformations and represents one of the few known monogenic causes of congenital heart disease. The birth incidence of heterotaxy-spectrum malformations is significantly higher in males, but our previous work indicated that mutations within ZIC3 did not account for the male over-representation. Therefore, cross species comparative sequence alignment was used to identify a putative novel fourth exon, and the existence of a novel alternatively spliced transcript was confirmed by amplification from murine embryonic RNA and subsequent sequencing. This transcript, termed Zic3-B, encompasses exons 1, 2, and 4 whereas Zic3-A encompasses exons 1, 2, and 3. The resulting protein isoforms are 466 and 456 amino acid residues respectively, sharing the first 407 residues. Importantly, the last two amino acids in the fifth zinc finger DNA binding domain are altered in the Zic3-B isoform, indicating a potential functional difference that was further evaluated by expression, subcellular localization, and transactivation analyses. The temporo-spatial expression pattern of Zic3-B overlaps with Zic3-A in vivo, and both isoforms are localized to the nucleus in vitro. Both isoforms can transcriptionally activate a Gli binding site reporter, but only ZIC3-A synergistically activates upon co-transfection with Gli3, suggesting that the isoforms are functionally distinct. Screening 109 familial and sporadic male heterotaxy cases did not identify pathogenic mutations in the newly identified fourth exon and larger studies are necessary to establish the importance of the novel isoform in human disease

Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. // Design: Multicenter, international, prospective cohort study. // Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. // Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. // Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality

Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial

Background. Continuous electronic fetal heart-rate monitoring is widely used during labour, and computerised interpretation could increase its usefulness. We aimed to establish whether the addition of decision-support software to assist in the interpretation of cardiotocographs affected the number of poor neonatal outcomes. Methods. In this unmasked randomised controlled trial, we recruited women in labour aged 16 years or older having continuous electronic fetal monitoring, with a singleton or twin pregnancy, and at 35 weeks’ gestation or more at 24 maternity units in the UK and Ireland. They were randomly assigned (1:1) to decision support with the INFANT system or no decision support via a computer-generated stratified block randomisation schedule. The primary outcomes were poor neonatal outcome (intrapartum stillbirth or early neonatal death excluding lethal congenital anomalies, or neonatal encephalopathy, admission to the neonatal unit within 24 h for ≥48 h with evidence of feeding difficulties, respiratory illness, or encephalopathy with evidence of compromise at birth), and developmental assessment at age 2 years in a subset of surviving children. Analyses were done by intention to treat. This trial is completed and is registered with the ISRCTN Registry, number 98680152. Findings. Between Jan 6, 2010, and Aug 31, 2013, 47062 women were randomly assigned (23515 in the decision-support group and 23547 in the no-decision-support group) and 46042 were analysed (22987 in the decision-support group and 23055 in the no-decision-support group). We noted no difference in the incidence of poor neonatal outcome between the groups—172 (0·7%) babies in the decision-support group compared with 171 (0·7%) babies in the no-decision-support group (adjusted risk ratio 1·01, 95% CI 0·82–1·25). At 2 years, no significant differences were noted in terms of developmental assessment. Interpretation. Use of computerised interpretation of cardiotocographs in women who have continuous electronic fetal monitoring in labour does not improve clinical outcomes for mothers or babies