Comparison of placental growth factor and fetal flow Doppler ultrasonography to identify fetal adverse outcomes in women with hypertensive disorders of pregnancy: an observational study.

BACKGROUND: Hypertensive disorders of pregnancy and intrauterine growth restriction (IUGR) are leading causes of maternal and perinatal morbidity and mortality. Failure to detect intrauterine growth restriction in women at high risk has been highlighted as a significant avoidable cause of serious fetal outcome. In this observational study we compare fetal flow using Doppler ultrasonography with a new test for placental growth factor (PlGF) to predict fetal adverse events. METHODS: Eighty-nine women with hypertensive disorders of pregnancy (24 with chronic hypertension, 17 with gestational hypertension, 12 with HELLP syndrome, 19 with preeclampsia and 17 with superimposed preeclampsia) were enrolled. A single maternal blood sample to measure free PlGF (Alere Triage) taken before 35 weeks of pregnancy was compared to the last Doppler ultrasound measurement of fetal flow before delivery. PlGF was classified as normal (PlGF>/=100 pg/ml), low (12<PlGF<100) or very low (PlGF</=12 pg/ml). A positive test for abnormal fetal flow was defined as either signs of centralisation of the fetal circulation or diastolic block or reverse flow in the umbilical artery or descending aorta; this was a criterion for delivery. Fetal outcomes were intrauterine growth restriction and birth before 37 weeks of pregnancy. RESULTS: In total 61/89 women had a preterm birth and 22 infants had IUGR. Of those who delivered preterm, 20/20 women with abnormal fetal flow and 36/41 (87.8%) women with normal fetal flow had low or very low PlGF. Of those infants with IUGR, 22/22 had low or very low maternal PlGF and 10/22 had abnormal fetal flow. CONCLUSIONS: PlGF may provide useful information before 35th gestational week to identify fetuses requiring urgent delivery, and those at risk of later adverse outcomes not identified by fetal flow Doppler ultrasonography

Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne

Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne. Two natural history cohorts were studied including 168 longitudinal samples belonging to 66 patients. We further studied 1536 samples obtained from 3 independent clinical trials with drisapersen, an antisense oligonucleotide targeting exon 51: an open label study including 12 patients; a phase 3 randomized, double blind, placebo controlled study involving 186 patients; an open label extension study performed after the phase 3. Analysis of natural history cohorts showed elevated MMP-9 levels in patients and a significant increase over time in longitudinal samples. MMP-9 decreased in parallel to clinical stabilization in the 12 patients involved in the open label study. The phase 3 study and subsequent extension study clarified that the decrease in MMP-9 levels was not predictive of treatment response. These data do not support the inclusion of serum MMP-9 as predictive biomarker for DMD patients

Periodic assessment of plasma sFlt-1 and PlGF concentrations and its association with placental morphometry in gestational hypertension (GH) - a prospective follow-up study.

BACKGROUND: Hypertensive disorders in pregnancy contributes to about 12% of maternal deaths in Malaysia and similarly worldwide. Early detection and adequate management are preventable strategies. Biochemical markers of abnormal angiogenesis would be more specific in early detection than routine blood pressure and proteinuria measurements. The aim of this study was to estimate maternal plasma PlGF and sFlt-1 levels in pregnant women with gestational hypertension at three intervals of pregnancy and correlate these biomarker levels with placental morphometry. METHODS: Venous blood samples (antepartum, intrapartum and post partum periods) were drawn to estimate for sFlt-1 and PlGF levels while placental tissue samples were examined for placental morphometry. RESULTS: PlGF levels were lower in gestational hypertension (GH) compared to normotensive during antepartum and intrapartum period, whereas sFlt-1 levels were elevated in GH at antepartum, intrapartum and postpartum intervals during pregnancy. An inverse relationship between these two biomarkers was observed through correlation analysis. PlGF levels were inversely correlated with total villous surface area of the placental periphery (TCsa-C) and villous capillarization (VC-C) of the placental periphery. CONCLUSION: We established periodic values of for sFlt-1 and PlGF levels for the first time in an ethnically diverse Malaysian setting. We suggest the development of GH in women is related to defective capillarization. In demonstrating periodic changes, this study suggest the possibility of developing GH and other long term health complications as a result of prolonged exposure to sFlt-1. The correlation between PlGF levels and morphometric findings also support possible capillarization defect

The Multiple Mini-Interview (MMI) for student selection in health professions training - a systematic review.

BACKGROUND: The Multiple Mini-Interview (MMI) has been used increasingly for selection of students to health professions programmes. OBJECTIVES: This paper reports on the evidence base for the feasibility, acceptability, reliability and validity of the MMI. DATA SOURCES: CINAHL and MEDLINE STUDY ELIGIBILITY CRITERIA: All studies testing the MMI on applicants to health professions training. STUDY APPRAISAL AND SYNTHESIS METHODS: Each paper was appraised by two reviewers. Narrative summary findings on feasibility, acceptability, reliability and validity are presented. RESULTS: Of the 64 citations identified, 30 were selected for review. The modal MMI consisted of 10 stations, each lasting eight minutes and assessed by one interviewer. The MMI was feasible, i.e. did not require more examiners, did not cost more, and interviews were completed over a short period of time. It was acceptable, i.e. fair, transparent, free from gender, cultural and socio-economic bias, and did not favour applicants with previous coaching. Its reliability was reported to be moderate to high, with Cronbach's alpha = 0.69-0.98 and G = 0.55-0.72. MMI scores did not correlate to traditional admission tools scores, were not associated with pre-entry academic qualifications, were the best predictor for OSCE performance and statistically predictive of subsequent performance at medical council examinations. CONCLUSIONS: The MMI is reliable, acceptable and feasible. The evidence base for its validity against future medical council exams is growing with reports from longitudinal investigations. However, further research is needed for its acceptability in different cultural context and validity against future clinical behaviours

The Multiple Mini-Interview (MMI) for student selection in health professions training - a systematic review.

BACKGROUND: The Multiple Mini-Interview (MMI) has been used increasingly for selection of students to health professions programmes. OBJECTIVES: This paper reports on the evidence base for the feasibility, acceptability, reliability and validity of the MMI. DATA SOURCES: CINAHL and MEDLINE STUDY ELIGIBILITY CRITERIA: All studies testing the MMI on applicants to health professions training. STUDY APPRAISAL AND SYNTHESIS METHODS: Each paper was appraised by two reviewers. Narrative summary findings on feasibility, acceptability, reliability and validity are presented. RESULTS: Of the 64 citations identified, 30 were selected for review. The modal MMI consisted of 10 stations, each lasting eight minutes and assessed by one interviewer. The MMI was feasible, i.e. did not require more examiners, did not cost more, and interviews were completed over a short period of time. It was acceptable, i.e. fair, transparent, free from gender, cultural and socio-economic bias, and did not favour applicants with previous coaching. Its reliability was reported to be moderate to high, with Cronbach's alpha = 0.69-0.98 and G = 0.55-0.72. MMI scores did not correlate to traditional admission tools scores, were not associated with pre-entry academic qualifications, were the best predictor for OSCE performance and statistically predictive of subsequent performance at medical council examinations. CONCLUSIONS: The MMI is reliable, acceptable and feasible. The evidence base for its validity against future medical council exams is growing with reports from longitudinal investigations. However, further research is needed for its acceptability in different cultural context and validity against future clinical behaviours

Promoting inclusivity in health professions education publishing

A taskforce established by Medical Education asks readers to engage in discussion about how the journal and field can do better to ensure that health professional education publishing is inclusive of diverse knowledge and perspectives