The rate of brain abnormalities on in utero MRI studies in fetuses with normal ultrasound examinations of the brain and calculation of indicators of diagnostic performance

AIM To estimate the rate of unexpected brain abnormalities detected by in utero magnetic resonance imaging (iuMRI) in fetuses without abnormalities at ultrasonography (USS). MATERIALS AND METHODS A prospective cohort study of pregnant women whose fetus had no structural brain (or body) abnormalities recognised on antenatal ultrasonography. Women were recruited from 12 centres across the UK and underwent iuMRI at 18 gestational weeks or more in the [blinded for review]. The imaging studies were reviewed by an experienced neuroradiologist. The positive and negative predictive values of both USS and iuMRI have been calculated by combining the results of this study with the results from the main [blinded for review] study. RESULTS One hundred and ninety-eight pregnant women were recruited and underwent iuMRI of 205 fetuses. Brain abnormalities were shown on iuMRI in two fetuses that were not recognised on USS (one case of a focal cortical abnormality and one case of mild ventriculomegaly). The negative predictive value for USS was 99.5% and 100% for iuMRI. CONCLUSIONS To the authors' knowledge, this is the first study comparing USS and iuMRI in low-risk pregnancies. USS has a comparatively high rule-out for fetal brain abnormalities and should remain the screening tool of choice

Time trends in breast cancer survival: experience in a single centre, 1975-89.

The aim of this retrospective cohort study was to investigate whether survival of patients with breast cancer has changed over the period 1975-89. A total of 2604 women diagnosed as having invasive breast cancer at a clinical oncology unit in London were followed up for between 5 and 20 years. Patients were divided into four groups according to menstrual status (pre or post) and the staging of cancer (operable or inoperable). For each group, survival from diagnosis was compared between three consecutive 5-year cohorts, both with and without adjustments made for relevant prognostic factors. No temporal patterns were found in patients with inoperable cancer, in whom the survival rate was consistently low. Of women with operable cancers, differences were seen only among post-menopausal women, for whom the best survival patterns were seen in patients diagnosed between 1985-89. This is probably due to tamoxifen being commonly prescribed as adjuvant treatment for this cohort of patients. We cannot explain an apparently worse survival in the group of patients presenting in the early 1980s compared with that observed in the late 1970s

UK-based, multisite, prospective cohort study of small bowel obstruction in acute surgical services: National Audit of Small Bowel Obstruction (NASBO) protocol

Introduction Small bowel obstruction (SBO) is a common indication for emergency laparotomy in the UK, which is associated with a 90-day mortality rate of 13%. There are currently no UK clinical guidelines for the management of this condition. The aim of this multicentre prospective cohort study is to describe the burden, variation in management and associated outcomes of SBO in the UK adult population. Methods and analysis UK hospitals providing emergency general surgery are eligible to participate. This study has three components: (1) a clinical preference questionnaire to be completed by consultants providing emergency general surgical care to assesses preferences in diagnostics and therapeutic approaches, including laparoscopy and nutritional interventions; (2) site resource profile questionnaire to indicate ease of access to diagnostic services, operating theatres, nutritional support teams and postoperative support including intensive care; (3) prospective cohort study of all cases of SBO admitted during an 8-week period at participating trusts. Data on diagnostics, operative and nutritional interventions, and in-hospital mortality and morbidity will be captured, followed by data validation. Ethics and dissemination This will be conducted as a national audit of practice in conjunction with trainee research collaboratives, with support from patient representatives, surgeons, anaesthetists, gastroenterologists and a clinical trials unit. Site-specific reports will be provided to each participant site as well as an overall report to be disseminated through specialist societies. Results will be published in a formal project report endorsed by stakeholders, and in peer-reviewed scientific reports. Key findings will be debated at a focused national meeting with a view to quality improvement initiatives

Accuracy of in-utero MRI to detect fetal brain abnormalities and prognosticate developmental outcome : postnatal follow-up of the MERIDIAN cohort

Background In utero MRI (iuMRI) detects fetal brain abnormalities more accurately than ultrasonography and provides additional clinical information in around half of pregnancies. We aimed to study whether postnatal neuroimaging after age 6 months changes the diagnostic accuracy of iuMRI and its ability to predict developmental outcome. Methods Families enrolled in the MERIDIAN study whose child survived to age 3 years were invited to have a case note review and assessment of developmental outcome with the Bayley Scales of Infant and Toddler Development, the Ages and Stages Questionnaire, or both. A paediatric neuroradiologist, masked to the iuMRI results, reviewed the postnatal neuroimaging if the clinical report differed from iuMRI findings. Diagnostic accuracy was recalculated. A paediatric neurologist and neonatologist categorised participants' development as normal, at risk, or abnormal, and the ability of iuMRI and ultrasonography to predict developmental outcome were assessed. Findings 210 participants had case note review, of whom 81 (39%) had additional investigations after age 6 months. The diagnostic accuracy of iuMRI remained higher than ultrasonography (proportion of correct cases was 529 [92%] of 574 vs 387 [67%] of 574; absolute difference 25%, 95% CI 21 to 29; p<0·0001). Developmental outcome data were analysed in 156 participants, and 111 (71%) were categorised as normal or at risk. Of these 111 participants, prognosis was normal or favourable for 56 (51%) using ultrasonography and for 76 (69%) using iuMRI (difference in specificity 18%, 95% CI 7 to 29; p=0·0008). No statistically significant difference was seen in infants with abnormal outcome (difference in sensitivity 4%, 95% CI −10 to 19; p=0·73). Interpretation iuMRI remains the optimal tool to identify fetal brain abnormalities. It is less accurate when used to predict developmental outcome, although better than ultrasonography for identifying children with normal outcome. Further work is needed to determine how the prognostic abilities of iuMRI can be improved. Funding National Institute for Health Research Health Technology Assessment programme

A rapid review indicated higher recruitment rates in treatment trials than in prevention trials

Objectives To test the hypothesis that the percentage of patients screened that randomize differs between prevention and therapy trials. Study Design and Setting Rapid review of randomized controlled trials (RCTs) identified through published systematic reviews in August 2013. Individually randomized, parallel group controlled RCTs were eligible if they evaluated metformin monotherapy or exercise for the prevention or treatment of type 2 diabetes. Numbers of patients screened and randomized were extracted by a single reviewer. Percentages were calculated for each study for those randomized: as a function of those approached, screened, and eligible. Percentages (95% confidence intervals) from each individual study were weighted according to the denominator and pooled rates calculated. Statistical heterogeneity was assessed using I2. Results The percentage of those screened who subsequently randomized was 6.2% (6.0%, 6.4%; 3 studies, I2 = 100.0%) for metformin prevention trials; 50.7% (49.9%, 51.4%; 21 studies, I2 = 99.6%) for metformin treatment trials; 4.8% (4.7%, 4.8%; 14 studies, I2 = 99.9%) for exercise prevention trials; and 43.3% (42.6%, 43.9%; 28 studies, I2 = 99.8%) for exercise treatment trials. Conclusion This study provides qualified support for the hypothesis that prevention trials recruit a smaller proportion of those screened than treatment trials. Statistical heterogeneity associated with pooled estimates and other study limitations is discussed. Keywords Prevention; Treatment; RCTs; Recruitment rates; Exercise; Screening failures; Consent rates; Eligibilit

Should we perform in utero MRI on a fetus at increased risk of a brain abnormality if ultrasonography is normal or shows non-specific findings?

There are a number of reasons why a pregnant woman might be considered to have an increased risk of carrying a fetus with a brain abnormality, but they fall broadly into two groups. First, there may be a relevant family history usually, but not always, when a fetus/child from a previous pregnancy has a developmental brain abnormality and a clinical geneticist judges that there is a risk of recurrence. Second, there may be findings in their current pregnancy that increases the risk of the fetus either having a developmental brain abnormality or accruing acquired brain pathology. Antenatal ultrasonography remains the mainstay of fetal screening and anomaly scanning, but there is now persuasive evidence that in utero magnetic resonance imaging should have an important supporting role. This is important, as more accurate and more certain diagnoses are central to providing parents with accurate information about the likely clinical outcome. In pregnancies at increased risk of brain abnormalities, it is also important to provide the best quality information that the fetal brain is normal to provide reassurance to parents. In this paper, we review the proposition that in utero magnetic resonance imaging should be used in pregnancies at increased risk of brain abnormalities, even if the consultant-led ultrasound examination is normal or showed non-specific findings only

A randomised trial found online questionnaires supplemented by postal reminders generated a cost-effective and generalisable sample, but don't forget the reminders.

OBJECTIVE: To compare the response rates, data completeness and representativeness of survey data produced by online and postal surveys. STUDY DESIGN AND SETTING: A randomised trial nested within a cohort study in Yorkshire, United Kingdom. Participants were randomised to receive either an electronic (online) survey questionnaire with paper reminder (N=2982), or paper questionnaire with electronic reminder (N=2855). RESULTS: Response rates were similar for electronic contact and postal contacts (50.9% versus 49.7%, difference = 1.2%, 95% confidence interval -1.3% to 3.8%). The characteristics of those responding to the two groups were similar. Participants nevertheless demonstrated an overwhelming preference for postal questionnaires, with the majority responding by post in both groups. CONCLUSION: Online survey questionnaire systems need to be supplemented with a postal reminder to achieve acceptable uptake, but doing so provides a similar response rate and case mix when compared to postal questionnaires alone. For large surveys, online survey systems may be cost saving

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammatio

Use of MRI in the diagnosis of fetal brain abnormalities in utero (MERIDIAN): a multicentre, prospective cohort study.

BACKGROUND: In-utero MRI (iuMRI) has shown promise as an adjunct to ultrasound but the comparative diagnostic performance has been poorly defined. We aimed to assess whether the diagnostic accuracy and confidence of the prenatal diagnosis of fetal brain abnormalities is improved with iuMRI and assess the clinical impact and patient acceptability of iuMRI. METHODS: We did a multicentre, prospective, cohort study in the UK, at 16 fetal medicine centres, of pregnant women aged 16 years or older whose fetus had a brain abnormality detected by ultrasound at a gestational age of 18 weeks or more, had no contraindications to iuMRI, and consented to enter the study. Women carrying a fetus suspected of having a brain anomaly on ultrasound had iuMRI done within 14 days of ultrasound. The findings were reviewed by two independent panels and used to estimate diagnostic accuracy and confidence by comparison with outcome diagnoses. Changes in diagnosis, prognosis, and clinical management brought about by iuMRI and patient acceptability were assessed. FINDINGS: Participants were recruited between July 29, 2011, and Aug 31, 2014. The cohort was subdivided by gestation into the 18 weeks to less than 24 weeks fetus cohort (n=369) and into the 24 weeks or older fetus cohort (n=201). Diagnostic accuracy was improved by 23% (95% CI 18-27) in the 18 weeks to less than 24 weeks group and 29% (23-36) in the 24 weeks and older group (p<0·0001 for both groups). The overall diagnostic accuracy was 68% for ultrasound and 93% for iuMRI (difference 25%, 95% CI 21-29). Dominant diagnoses were reported with high confidence on ultrasound in 465 (82%) of 570 cases compared with 544 (95%) of 570 cases on iuMRI. IuMRI provided additional diagnostic information in 387 (49%) of 783 cases, changed prognostic information in at least 157 (20%), and led to changes in clinical management in more than one in three cases. IuMRI also had high patient acceptability with at least 95% of women saying they would have an iuMRI study if a future pregnancy were complicated by a fetal brain abnormality. INTERPRETATION: iuMRI improves diagnostic accuracy and confidence for fetal brain anomalies and leads to management changes in a high proportion of cases. This finding, along with the high patient acceptability, leads us to propose that any fetus with a suspected brain abnormality on ultrasound should have iuMRI to better inform counselling and management decisions. FUNDING: National Institute for Health Research Health Technology Assessment programme