Antenatal Screening for Down Syndrome Using Serum Placental Growth Factor with the Combined, Quadruple, Serum Integrated and Integrated Tests

PMCID: PMC3463523This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Incorporating DNA Sequencing into Current Prenatal Screening Practice for Down's Syndrome

PMCID: PMC3604109This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Prevention of Neural Tube Defects: A Cross-Sectional Study of the Uptake of Folic Acid Supplementation in Nearly Half a Million Women

BACKGROUND: Taking folic acid supplements before pregnancy to reduce the risk of a neural tube defect (NTD) is especially important in countries without universal folic acid fortification. The extent of folic acid supplementation among women who had antenatal screening for Down's syndrome and NTDs at the Wolfson Institute of Preventive Medicine, London between 1999 and 2012 was assessed. METHODS AND FINDINGS: 466,860 women screened provided details on folic acid supplementation. The proportion of women who took folic acid supplements before pregnancy was determined according to year and characteristics of the women. The proportion of women taking folic acid supplements before pregnancy declined from 35% (95% CI 34%-35%) in 1999-2001 to 31% (30%-31%) in 2011-2012. 6% (5%-6%) of women aged under 20 took folic acid supplements before pregnancy compared with 40% of women aged between 35 and 39. Non-Caucasian women were less likely to take folic acid supplements before pregnancy than Caucasian women; Afro-Caribbean 17% (16%-17%), Oriental 25% (24%-25%) and South Asian 20% (20%-21%) compared with 35% (35%-35%) for Caucasian women. 51% (48%-55%) of women who previously had an NTD pregnancy took folic acid supplements before the current pregnancy. CONCLUSIONS: The policy of folic acid supplementation is failing and has led to health inequalities. This study demonstrates the need to fortify flour and other cereal grain with folic acid in all countries of the world

Metformin to reduce metabolic complications and inflammation in patients on systemic glucocorticoid therapy: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial

Background: An urgent need to reduce the metabolic side-effects of glucocorticoid overexposure has been recognised, as glucocorticoid excess can lead to Cushing's syndrome, which is associated with high morbidity. We aimed to evaluate the potential of metformin to reverse such effects while sparing the anti-inflammatory benefits of glucocorticoids.  Methods: We did a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial involving four hospitals in the UK. Patients without diabetes were eligible if they were between the ages of 18 and 75 years with an inflammatory disease treated with continuous prednisolone (≥20 mg/day for ≥4 weeks and remaining on ≥10 mg/day for the subsequent 12 weeks, or its cumulative dose-equivalent). Eligible patients were randomly allocated (1:1) to either the metformin or placebo groups, using a computer-generated randomisation table stratified according to age and BMI. Metformin and placebo were administered orally for 12 weeks in escalating doses: 850 mg/day for the first 5 days, 850 mg twice a day for the next 5 days, and 850 mg three times a day subsequently. The primary outcome was the between-group difference in visceral-to-subcutaneous fat area ratio over 12 weeks, assessed by CT. Secondary outcomes included changes in metabolic, bone, cardiovascular, and inflammatory parameters over 12 weeks. Our analysis followed a modified intention-to-treat principle for the primary outcome. This study is registered with ClinicalTrials.gov, NCT01319994.  Findings: Between July 17, 2012, and Jan 14, 2014, 849 patients were assessed for study eligibility, of which 53 were randomly assigned to receive either metformin (n=26) or placebo (n=27) for 12 weeks. 19 patients in the metformin group and 21 in the placebo group were eligible for the primary outcome analysis. Both groups received an equivalent cumulative dose of glucocorticoids (1860 mg prednisolone-equivalent [IQR 1060–2810] in the metformin group vs 1770 mg [1020–2356] in the placebo group); p=0·76). No change in the visceral-to-subcutaneous fat area ratio between the treatment groups was observed (0·11, 95% CI −0·02 to 0·24; p=0·09), but patients in the metformin group lost truncal subcutaneous fat compared with the placebo group (−3835 mm 2, 95% CI −6781 to −888; p=0·01). Improvements in markers of carbohydrate, lipid, liver, and bone metabolism were observed in the metformin group compared with the placebo group. Additionally, those in the metformin group had improved fibrinolysis, carotid intima–media thickness, inflammatory parameters, and clinical markers of disease activity. The frequency of pneumonia (one event in the metformin group vs seven in the placebo group; p=0·01), overall rate of moderate-to-severe infections (two vs 11; p=0·001), and all-cause hospital admissions due to adverse events (one vs nine; p=0·001) were lower in the metformin group than in the placebo group. Patients in the metformin group had more events of diarrhoea than the placebo group (18 events vs eight; p=0·01).  Interpretation: No significant changes in the visceral-to-subcutaneous fat area ratio between the treatment groups were observed; however, metformin administration did improve some of the metabolic profile and clinical outcomes for glucocorticoid-treated patients with inflammatory disease, which warrants further investigation.  Funding: Barts Charity and Merck Serono

Randomised Trial of Text Messaging on Adherence to Cardiovascular Preventive Treatment (INTERACT Trial)

BACKGROUND: About one third of patients prescribed blood pressure or lipid-lowering drugs for the prevention of coronary heart disease and stroke do not take their medication as prescribed. We conducted a randomized trial to evaluate text messaging as a means of improving adherence to cardiovascular disease preventive treatment. METHODS: 303 patients taking blood pressure and/or lipid-lowering medications were randomly assigned to being sent text messages (Text group, 151) or not being sent them (No text group, 152). Texts were sent daily for 2 weeks, alternate days for 2 weeks and weekly thereafter for 22 weeks (6 months overall), using an automated computer programme. Patients were asked to respond on whether they had taken their medication, whether the text reminded them to do so if they had forgotten, and if they had not taken their medication to determine if there was a reason for not doing so. At 6 months, use of medication was assessed. RESULTS: Two patients were lost to follow-up, providing data on 301 for analysis. In the No text group 38/151 (25%) took less than 80% of the prescribed regimen (ie. stopped medication completely or took it on fewer than 22 of the last 28 days of follow-up) compared to 14/150 patients (9%) in the Text group - an improvement in adherence affecting 16 per 100 patients (95% CI 7 to 24), p<0.001. The texts reminded 98/151 patients (65%) to take medication on at least one occasion and lead to 20/151 (13%) who stopped taking medication because of concern over efficacy or side-effects, resuming treatment. CONCLUSIONS: In patients taking blood pressure or lipid-lowering treatment for the prevention of cardiovascular disease, text messaging improved medication adherence compared with no text messaging. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74757601

Subtle motor disturbances in PREDICT-PD participants

PREDICT-PD has been funded by Parkinson’'s UK (reference F1201)

COVID‐19 Vaccine Response in People with Multiple Sclerosis

ObjectiveThe purpose of this study was to investigate the effect of disease modifying therapies on immune response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines in people with multiple sclerosis (MS).MethodsFour hundred seventy-three people with MS provided one or more dried blood spot samples. Information about coronavirus disease 2019 (COVID-19) and vaccine history, medical, and drug history were extracted from questionnaires and medical records. Dried blood spots were eluted and tested for antibodies to SARS-CoV-2. Antibody titers were partitioned into tertiles with people on no disease modifying therapy as a reference. We calculated the odds ratio of seroconversion (univariate logistic regression) and compared quantitative vaccine response (Kruskal Wallis) following the SARS-CoV-2 vaccine according to disease modifying therapy. We used regression modeling to explore the effect of vaccine timing, treatment duration, age, vaccine type, and lymphocyte count on vaccine response.ResultsCompared to no disease modifying therapy, the use of anti-CD20 monoclonal antibodies (odds ratio = 0.03, 95% confidence interval [CI] = 0.01–0.06, p [less than] 0.001) and fingolimod (odds ratio = 0.04; 95% CI = 0.01–0.12) were associated with lower seroconversion following the SARS-CoV-2 vaccine. All other drugs did not differ significantly from the untreated cohort. Both time since last anti-CD20 treatment and total time on treatment were significantly associated with the response to the vaccination. The vaccine type significantly predicted seroconversion, but not in those on anti-CD20 medications. Preliminary data on cellular T-cell immunity showed 40% of seronegative subjects had measurable anti-SARS-CoV-2 T cell responses.InterpretationSome disease modifying therapies convey risk of attenuated serological response to SARS-CoV-2 vaccination in people with MS. We provide recommendations for the practical management of this patient group. ANN NEUROL 202

Child-parent screening for familial hypercholesterolaemia: screening strategy based on a meta-analysis

Objective To develop a population screening strategy for familial hypercholesterolaemia

Screening performance of reflex DNA tests with the Integrated test according to percentage of women having reflex DNA test (Integrated test risk cut-off 1 in 50).

<p>Screening performance of reflex DNA tests with the Integrated test according to percentage of women having reflex DNA test (Integrated test risk cut-off 1 in 50).</p

Illustration of the cost per woman screened according to the cost of the DNA test, expressed as a multiple of the cost of an Integrated test, and the proportion of women who have a DNA test (i.e. positive based on a the first trimester stage of the Integrated test, 75% of the cost of the Integrated test incurred in the first trimester).

<p>Illustration of the cost per woman screened according to the cost of the DNA test, expressed as a multiple of the cost of an Integrated test, and the proportion of women who have a DNA test (i.e. positive based on a the first trimester stage of the Integrated test, 75% of the cost of the Integrated test incurred in the first trimester).</p