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Joan K Morris

Publications and source records attributed to Joan K Morris.

16 recordsLinked to original sources
PubMed2006

Maternal age-specific fetal loss rates in Down syndrome pregnancies.

OBJECTIVES: Pregnancies affected by Down syndrome (DS) have a greater risk of spontaneous fetal loss than those that are unaffected. In this article, we investigate the relationship between maternal age and the risk of spontaneous fetal loss in DS pregnancies. METHODS: Fetal loss at different maternal ages were estimated by survival analysis using follow-up of 5177 prenatally diagnosed cases. The maternal age effect on loss rate was subsequently confirmed by a re-analysis of published comparisons of the maternal age-specific prevalence of DS at different gestational ages. RESULTS: The average fetal loss rate between the time of chorionic villus sampling (CVS) and term was 32% (95% CI: 26-38), increasing from 23% (95% CI: 16-31) for women aged 25 to 44% (33-56) for women aged 45. The average fetal loss rate between the time of amniocentesis and term was 25% (21-31), increasing from 19% (14-27) to 33% (26-45) across the same age range. CONCLUSION: The fetal loss rate in DS pregnancies increases with maternal age, and this has consequences when estimating the live birth prevalence of DS in the presence of prenatal diagnosis and termination, and when assessing the performance of prenatal screening techniques.

Aborted Fetus↗
PubMed2006

Cross-trimester marker ratios in prenatal screening for Down syndrome.

OBJECTIVE: To examine the performance of Integrated Down syndrome screening (first- and second-trimester measurements integrated into a single screening test) when ratios of the levels of the same serum markers measured in both these trimesters (cross-trimester ratios) are added as new screening markers. METHODS: Using data from Serum Urine and Ultrasound Screening Study (SURUSS), second-trimester concentrations (in multiples of the median, or MoM) of pregnancy associated plasma protein A (PAPP-A), alphafetoprotein (AFP), unconjugated oestriol (uE(3)), human chorionic gonadotrophin (hCG) (free beta and total), and inhibin-A were divided by the first-trimester concentration to obtain a cross-trimester (CT) ratio for each analyte in 74 Down syndrome and 492 unaffected pregnancies. We identified CT ratios that improved screening performance and then, using Monte Carlo simulations, estimated the efficacy and cost effectiveness of adding them to the Integrated and serum Integrated tests. RESULTS: All the median CT ratios differed significantly between Down syndrome and unaffected pregnancies. Setting the Integrated test to achieve a 90% detection rate, the false-positive rate (FPR) was 0.7% with CT ratios for PAPP-A, uE(3), inhibin-A, and total hCG compared with 2.2% without CT ratios, a reduction of about two-thirds. Using the serum Integrated test to achieve the same 90% detection rate and the first-trimester measurements made at 11 completed weeks of pregnancy, the corresponding FPRs were 2.4 and 8.1%, a similar proportional reduction. The AFP CT ratio had little effect on screening performance. Using CT ratios did not increase the cost per Down syndrome pregnancy detected. CONCLUSION: The addition of CT ratios to an Integrated test substantially improves the efficacy and safety of prenatal screening for Down syndrome. It is cost effective and could be usefully introduced into screening programmes.

Biomarkers↗
PubMed2006

Screening in early pregnancy for pre-eclampsia using Down syndrome quadruple test markers.

OBJECTIVES: To estimate the screening performance of early second-trimester prenatal serum markers for Down syndrome, in screening for the development of pre-eclampsia, and analyse the uncertainty over its screening performance. METHODS: A nested case-control study was carried out on 96 women with pre-eclampsia and 5 controls for each case from among the women attending three hospitals in London for their prenatal care. Record linkage between computerized obstetric and screening databases identified women with pre-eclampsia and unaffected control women. The stored frozen serum samples collected from these pregnancies between 15 and 22 weeks' gestation were retrieved and assayed for alpha-fetoprotein (AFP), unconjugated estriol (uE(3)), total human chorionic gonadotrophin (hCG), free beta-hCG and inhibin-A. RESULTS: Pre-eclampsia was identified from the computerized obstetric records and confirmed by examination of the medical notes. In the pregnancies that went on to develop pre-eclampsia, early second trimester inhibin-A and hCG values were significantly raised and uE(3) values were significantly lowered, while AFP values were not significantly altered. Using the Quadruple test markers (AFP, uE(3), hCG (total or free beta) and inhibin-A), an estimated 34% of pregnancies that developed pre-eclampsia were detected at a 5% false-positive rate. If all the women who had pre-eclampsia in a previous pregnancy (assuming a pre-eclampsia prevalence of 4%) are considered as screen positive and the serum test is applied to the remaining women, then around 42% of pre-eclamptic pregnancies would be detected at a 6.5% false-positive rate. Pre-eclampsia screening performance using the Quadruple test markers was materially better than that using the Triple test markers. CONCLUSION: Adding screening for pre-eclampsia to an existing Down syndrome screening programme using the Quadruple test markers is simple and worthwhile. It will detect over 40% of pregnancies with pre-eclampsia at an acceptable false-positive rate (about 6%) and with minimal additional costs.

Biomarkers↗
PubMed2006

Changes in maternal age in England and Wales--implications for Down syndrome.

The risk of having a pregnancy with Down syndrome increases with maternal age. The percentage of all births in England and Wales to mothers aged 35 and over increased from 9% in 1989 to 19% in 2003. A 51% increase in the numbers of pregnancies with Down syndrome has been observed over the same time period (from 954 to 1440). Due to improvements in antenatal screening for Down syndrome and the subsequent termination of affected pregnancies, the total number of births with Down syndrome decreased from 770 in 1989 to 609 in 2003. However the number of births with Down syndrome to women aged 35 and over increased from 186 in 1989 to 310 in 2003 because of the increasing number of pregnancies amongst these women.

Adolescent↗
PubMed2005

Headaches and the treatment of blood pressure: results from a meta-analysis of 94 randomized placebo-controlled trials with 24,000 participants.

BACKGROUND: Uncertainty exists over whether blood pressure-lowering drugs prevent headache. METHODS AND RESULTS: A meta-analysis was carried out of the 94 randomized placebo-controlled trials of 4 different classes of blood pressure-lowering drugs (thiazides, beta-blockers, ACE inhibitors, and angiotensin II receptor antagonists) in fixed doses in which data on headache were reported. There were 17,641 participants who were allocated blood pressure-lowering drugs and 6603 who were allocated placebo. Treatment lowered systolic and diastolic blood pressures by 9.4 and 5.5 mm Hg, respectively, on average. One third fewer people on average reported headache in the treated groups (8.0%) than the placebo groups (12.4%) (odds ratio, 0.67; 95% CI, 0.61 to 0.74; P<0.001). About 1 in 30 treated persons benefited by having headache prevented. The prevalence of headache was reduced (P<0.001) in trials of each of the 4 classes of drugs. CONCLUSIONS: Our results show that blood pressure-lowering drugs prevent a significant proportion of headaches. That this effect is seen with pharmacologically unrelated classes of drugs indicates that it is likely to be due to the reduction in blood pressure per se, the only recognized action that the drugs have in common. This in turn indicates that high blood pressure is a cause of headache, but this conclusion is not supported by observational studies of blood pressure and headache. The uncertainty over whether high blood pressure causes headache does not, however, detract from the practical benefits of the use of blood pressure-lowering drugs in preventing headaches and cardiovascular disease.

Antihypertensive Agents↗
PubMed2005

The efficacy of combining several risk factors as a screening test.

OBJECTIVE: To determine the quantitative effect on overall screening performance (detection rate for a given false-positive rate) of using several moderately strong, independent risk factors in combination as screening markers. SETTING: Theoretical statistical analysis. METHODS: For the purposes of this analysis, it was assumed that all risk factors were independent, had Gaussian distributions with the same standard deviation in affected and unaffected individuals and had the same screening performance. We determined the overall screening performance associated with using an increasing number of risk factors together, with each risk factor having a detection rate of 10%, 15% or 20% for a 5% false-positive rate. The overall screening performance was estimated as the detection rate for a 5% false-positive rate. RESULTS: Combining the risk factors increased the screening performance, but the gain in detection at a constant false-positive rate was relatively modest and diminished with the addition of each risk factor. Combining three risk factors, each with a 15% detection rate for a 5% false-positive rate, yields a 28% detection rate. Combining five risk factors increases the detection rate to 39%. If the individual risk factors have a detection rate of 10% for a 5% false-positive rate, it would require combining about 15 such risk factors to achieve a comparable overall detection rate (41%). CONCLUSION: It is intuitively thought that combining moderately strong risk factors can substantially improve screening performance. For example, most cardiovascular risk factors that may be used in screening for ischaemic heart disease events, such as serum cholesterol and blood pressure, have a relatively modest screening performance (about 15% detection rate for a 5% false-positive rate). It would require the combination of about 15 or 20 such risk factors to achieve detection rates of about 80% for a 5% false-positive rate. This is impractical, given the risk factors so far discovered, because there are too few risk factors and their associations with disease are too weak.

Biomarkers↗
PubMed2004

Mortality from hypertrophic cardiomyopathy in England and Wales: clinical and screening implications.

OBJECTIVES: Hypertrophic cardiomyopathy is considered a relatively common cause of death in the young. Screening for the disorder has been advocated, but its potential value cannot be assessed because the number of deaths in asymptomatic cases in the general population has not been investigated. We determined the annual number of deaths (and death rates) from hypertrophic cardiomyopathy in England and Wales according to age, sex and the presence or absence of symptoms so that an affected individual's risk of dying from the disorder and the implications of screening could be assessed. METHODS: Ascertainment of all deaths from hypertrophic cardiomyopathy over a 3-year period (1996-1998), using death certification data from the Office of National Statistics. Deaths in people without symptoms were identified from coroner's reports and correspondence with pathologists who conducted the necropsies. RESULTS: There were 184 deaths per year from hypertrophic cardiomyopathy in England and Wales (about 15% of all deaths from cardiomyopathy) of which one third (65) were in people without symptoms. Most (110) of the 184 deaths each year were in people over age 55. Under age 55 there were only 37 deaths each year in asymptomatic people, out of an estimated 60,000 people with the disorder in the population. Of the 37 deaths, 14 (20%) occurred in relation to physical activity and 2 after competitive sport. CONCLUSIONS: In young people without symptoms hypertrophic cardiomyopathy is fairly common (1 in 500) but it rarely causes death; the case-fatality rate is about 6 per 10,000 per year. Current risk estimates from the study of patients in tertiary referral centers or general hospital clinics (420 and 110 deaths per 10,000 per year, respectively) are not applicable to asymptomatic people in the general population; such people, if incidentally identified can be reassured of their low risk of death. Screening would not be worthwhile unless a satisfactory test becomes available that can detect those few cases likely to die.

Autopsy↗
PubMed2004

The dose-response relation between serum homocysteine and cardiovascular disease: implications for treatment and screening.

BACKGROUND: With the recognition that serum homocysteine may cause cardiovascular disease there is clinical interest in homocysteine measurement to guide treatment with folic acid. It is uncertain whether treatment is best directed at those with high homocysteine or those at high risk irrespective of initial homocysteine. DESIGN AND METHODS: Dose-response plots of the associations between serum homocysteine and ischaemic heart disease and deep vein thrombosis were determined from retrospective (case-control) studies (a meta-analysis of 12 age-matched studies) prospective studies and studies of the C677T MTHFR polymorphism (a comparison of risk in three genotypes in a meta-analysis of 72 studies). The value of serum homocysteine as a screening test was assessed from distributions of serum homocysteine in men who did and did not die from ischaemic heart disease in a large prospective study. RESULTS: There were straight-line relationships between serum homocysteine and disease events in the three types of study; a given decrease in homocysteine would produce a similar proportional risk reduction from any pre-treatment level. There was substantial overlap between the distributions of serum homocysteine in men who did and did not die of ischaemic heart disease, indicating poor screening performance; there was no serum homocysteine cut-off that concentrated the majority of disease events into a small minority of the population. CONCLUSION: Interventions to lower serum homocysteine, if judged to be worthwhile, should not be limited to people with a high homocysteine but should be offered to everyone at high risk, regardless of pre-treatment homocysteine.

Adult↗
PubMed2002

Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis.

OBJECTIVE: To assess whether the association of serum homocysteine concentration with ischaemic heart disease, deep vein thrombosis and pulmonary embolism, and stroke is causal and, if so, to quantify the effect of homocysteine reduction in preventing them. DESIGN: Meta-analyses of the above three diseases using (a) 72 studies in which the prevalence of a mutation in the MTHFR gene (which increases homocysteine) was determined in cases (n=16 849) and controls, and (b) 20 prospective studies (3820 participants) of serum homocysteine and disease risk. MAIN OUTCOME MEASURES: Odds ratios of the three diseases for a 5 micromol/l increase in serum homocysteine concentration. RESULTS: There were significant associations between homocysteine and the three diseases. The odds ratios for a 5 micromol/l increase in serum homocysteine were, for ischaemic heart disease, 1.42 (95% confidence interval 1.11 to 1.84) in the genetic studies and 1.32 (1.19 to 1.45) in the prospective studies; for deep vein thrombosis with or without pulmonary embolism, 1.60 (1.15 to 2.22) in the genetic studies (there were no prospective studies); and, for stroke, 1.65 (0.66 to 4.13) in the genetic studies and 1.59 (1.29 to 1.96) in the prospective studies. CONCLUSIONS: The genetic studies and the prospective studies do not share the same potential sources of error, but both yield similar highly significant results-strong evidence that the association between homocysteine and cardiovascular disease is causal. On this basis, lowering homocysteine concentrations by 3 micromol/l from current levels (achievable by increasing folic acid intake) would reduce the risk of ischaemic heart disease by 16% (11% to 20%), deep vein thrombosis by 25% (8% to 38%), and stroke by 24% (15% to 33%).

Cohort Studies↗
PubMed2002

Cardiovascular morbidity and mortality after orthotopic liver transplantation.

BACKGROUND: Hyperlipidemia and hypertension have been reported in liver allograft recipients and contribute to an increased risk of ischemic heart disease (IHD) after orthotopic liver transplantation (OLT). The aims of the study were (1) to determine the prevalence of risk factors for IHD in these patients and (2) to compare the observed incidence of cardiovascular events and related mortality in allograft recipients with a matched population. METHODS: One hundred ten consecutive adults (50 male) who attended for review after OLT (median follow-up 3.9 years; range 0.1-17.9) were assessed for cardiovascular risk factors using current blood pressure, diabetic status, and smoking history and measurements of total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations. Cardiovascular events and cardiovascular mortality data were collected from the prospective database of all adult liver allograft recipients and compared to matched data from myocardial infarction registries and Office for National Statistics data, respectively. RESULTS: Raised serum cholesterol (>5.0 mmol/L) was found in 48 (44%) patients (18 male), and systolic hypertension (>140 mmHg) was found in 69 (63%) patients (27 male). The relative risk of ischemic cardiac events was 3.07 (95% [confidence interval] CI, 1.98-4.53) and the relative risk for cardiovascular deaths was 2.56 (95% CI, 1.52-4.05) in allograft recipients compared to an age-matched population without transplants. CONCLUSIONS: Liver allograft recipients have a greater risk of cardiovascular deaths and ischemic events than an age- and sex-matched population. The prevalence of raised cholesterol concentrations in patients after OLT is similar to those in previous reports. Moderate hypertension and hyperlipidemia may be more detrimental in patients after OLT compared to non-transplant patients without these risk factors.

Adolescent↗