BACKGROUND: In singleton pregnancies, studies investigating cellfree DNA in maternal blood have consistently reported high detection rate and low false-positive rate for the 3 common fetal trisomies (trisomies 21, 18, and 13). The potential advantages of noninvasive prenatal testing in twin pregnancies are even greater than in singletons, in particular lower need for invasive testing and consequent fetal loss rate. However, several organizations do not recommend cell-free DNA in twin pregnancies and call for larger prospective studies. OBJECTIVE: In response to this, we undertook a large prospective multicenter study to establish the screening performance of cell-free DNA for the 3 common trisomies in twin pregnancies. Moreover, we combined our data with that reported in published studies to obtain the best estimate of screening performance. STUDY DESIGN: This was a prospective multicenter blinded study evaluating the screening performance of cell-free DNA in maternal plasma for the detection of fetal trisomies in twin pregnancies. The study took place in 6 fetal medicine centers in England, United Kingdom. The primary outcome was the screening performance and test failure rate of cell-free DNA using next generation sequencing (the IONA test). Maternal blood was taken at the time of (or after) a conventional screening test. Data were collected at enrolment, at any relevant invasive testing throughout pregnancy, and after delivery until the time of hospital discharge. Prospective detailed outcome ascertainment was undertaken on all newborns. The study was undertaken and reported according to the Standards for Reporting of Diagnostic Accuracy Studies. A pooled analysis was also undertaken using our data and those in the studies identified by a literature search (MEDLINE, Embase, CENTRAL, Cochrane Library, and ClinicalTrials.gov) on June 6, 2020. RESULTS: A total of 1003 women with twin pregnancies were recruited, and complete data with follow-up and reference data were available for 961 (95.8%); 276 were monochorionic and 685 were dichorionic. The failure rate was 0.31%. The mean fetal fraction was 12.2% (range, 3%e36%); all 9 samples with a 3% fetal fraction provided a valid result. There were no false-positive or false-negative results for trisomy 21 or trisomy 13, whereas there was 1 false-negative and 1 false-positive result for trisomy 18. The IONA test had a detection rate of 100% for trisomy 21 (n¼13; 95% confidence interval, 75e100), 0% for trisomy 18 (n¼1; 95% confidence interval, 0e98), and 100% for trisomy 13 (n¼1; 95% confidence interval, 3e100). The corresponding false-positive rates were 0% (95% confidence interval, 0e0.39), 0.10% (95% confidence interval, 0e0.58), and 0% (95% confidence interval, 0e0.39), respectively. By combining data from our study with the 11 studies identified by literature search, the detection rate for trisomy 21 was 95% (n¼74; 95% confidence interval, 90e99) and the false-positive rate was 0.09% (n¼5598; 95% confidence interval, 0.03e0.19). The corresponding values for tri...
Functional ambulation categories (0-5) were recorded on 105 patients on the first and last days of a day hospital physiotherapy programme. Walking speed was measured in patients capable of walking without physical support from another person (functional ambulation categories 3-5). Patients attended for a median of 10 therapy days. Ambulation categories improved in 26 patients, deteriorated in three patients and there was no change in 76 patients. Mean walking speed, measured in 61 patients who did not change walking aid, increased from 0.38 to 0.44 metres per second (p = 0.003). Forty-three patients who did not show improvement in functional ambulation category had an increase in mean walking speed from 0.37 to 0.43 metres per second (p = 0.015). Both measurements are valuable, complementary and suitable for routine use in day hospital practice. Together they provide a basis for assess ing effectiveness of therapy.
National guidance on these issues was found to be contentious and implementation was variable. Wide consultation with stakeholders is needed prior to the publication of revised guidance.
SummaryInformation about patients in ambulance service records has been linked to that in the patients' hospital records in an attempt to make the most efficient use of a special ambulance service for patients suspected of having heart attacks. During one week 248 emergency (999) calls for an ambulance were made by the public in the city of Nottingham. The quality of information given to the ambulance centre was poor, and all four patients eventually found to have had a myocardial infarction were described as having collapsed. A further study of patients who were also described as having collapsed has led to a system which allows an ambulance controller to send a "coronary ambulance" only in answer to those emergency calls where there is a reasonable possibility that the patient has had a heart attack.
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