Search PubMed⌕ Search

Biomedical subjects

N J Wald

Publications and source records attributed to N J Wald.

At least 73 records · Page 4Linked to original sources
PubMed1999

The importance of age in screening for cancer.

OBJECTIVE: To derive a rational method of selecting the age range over which screening tests for cancer should be offered (that is, over which they would be most effective in saving life). MAIN OUTCOME MEASURE: The number of person-years of life that are lost through deaths occurring at each year of age from each of six cancers. RESULTS: For each cancer the number of years of life lost to age 80, plotted against age at death, showed a rise followed by a fall. The peak indicates the age at which deaths from the cancer result in most years of life lost. Special screening tests, such as mammography for breast cancer, will be most effective in saving life shortly before that age. The peak (as a five year age span) occurs at age 55-59 for breast cancer (189 years of life lost per 10,000 women per year), 70-74 for prostate cancer (114), 65-69 for colorectal cancer (96), 55-59 for ovarian cancer (61), 50-54 for cervical cancer (47), and 45-50 for melanoma (8). The precise interval by which special screening tests should precede the peak age is not critical; five years would be appropriate. Given current evidence on the efficacy of cancer screening, if it were stipulated that screening could only be performed when at least 50 years of life were to be gained per 10,000 persons screened, only mammography for breast cancer would be conducted, between the ages of 50 and 59. If the stipulation was 25 or more years of life gained mammography would be offered to women aged 40-69 and cervical smears to women aged 35-59. With only 10 or more years of life gained (unlikely to be worthwhile) mammography would be extended to women aged 30-74, cervical smears to 25-69, and faecal occult blood testing for colorectal cancer offered to those aged 45-74. Extending cervical cancer screening to age 69 would save more years of life than the present policy of screening women aged 20-29. Extending breast cancer screening to the age of 74 would be more effective than cervical screening at any age. CONCLUSIONS: Determining the number of years of life lost through deaths from a particular cancer at each age is useful in public health screening policy, both in selecting the age range over which special screening tests of proven efficacy should be offered and in quantitatively comparing the value of screening for different cancers.

Adolescent↗
PubMed1999

Quantifying the decline in the birth prevalence of neural tube defects in England and Wales.

In England and Wales there has been a large decline in the birth prevalence of neural tube defects (NTDs) from the early 1970s (reported rates of about 3.2 per 1000 births) to the present (0.1 per 1000 births in 1997). The reported number of terminations of NTD pregnancies increased from 0.02 per 1000 in 1970 to 0.66 per 1000 in 1997, much too small an increase to explain the decline in NTD births. Some underreporting of NTD terminations is recognised. We estimated its extent using 1976-80 data on reported central nervous system (CNS) defect terminations and NTD births in an analysis in which the true total number of NTD pregnancies during this short period was assumed to have either remained constant or else to have been changing by a constant amount per year. The estimate was that 56% of NTD terminations were not reported as such and this fitted the data well. In 1997 the estimated birth prevalence of NTDs was 0.14 per 1000 births, a fall of 96% since 1970. This 96% was apportioned as 40% due to antenatal screening and termination of pregnancy and 56% due to a decline in incidence. Over the period 1970-97 there was an increase in dietary folate, and this will have at least in part caused the decline in incidence of NTDs.

Abortion, Induced↗
PubMed1999

The target plot: a new way of displaying the performance of a screening test.

OBJECTIVES: To produce a graphical method to represent the performance of a screening test that illustrates the prevalence of the disorder being screened for, as well as its discriminatory potential. CONCEPT: A target plot was constructed in which the risk of the disorder is represented by a series of concentric circles of constant risk (isorisks) equivalent to specified false positive rates, with the highest risk in the centre and lower risks spreading outwards towards the circumference. Dots were drawn to represent cases of the disorder; these were of a size such that their total area as a proportion of the area of the whole target plot equalled the prevalence of the disorder in the screened population. The discriminatory power of the test was seen as the clustering of dots around the centre or bull's eye of the target. The detection rate could be estimated as the proportion of dots which fell within the isorisk corresponding to a specified false positive rate. APPLICATION: The target plot was applied to second trimester antenatal screening for Down's syndrome using different combinations of screening markers, and also to screening for ischaemic heart disease using protein components of cholesterol (apolipoproteins A I and B and Lp(a) lipoprotein), systolic blood pressure, and smoking status. DISCUSSION: The efficacy of the different methods of screening for Down's syndrome is readily apparent using the target plot, as is the poorer performance of screening for ischaemic heart disease. CONCLUSIONS: The target plot is a simple and quantitative way of displaying the performance of a screening test that may be useful in teaching and educational material.

Audiovisual Aids↗
PubMed1999

Fetal loss in Down syndrome pregnancies.

It is recognized that pregnancies with Down syndrome are liable to end in spontaneous fetal loss. It is important to determine the magnitude of this effect so that it can be taken into account when assessing the results of antenatal screening programmes for Down syndrome. Failure to do so will tend to overestimate the detection rate in intervention studies in which the screening results are used to identify women for a diagnostic test and the offer of a termination of pregnancy if indicated. We present new data on the spontaneous fetal loss in Down syndrome pregnancies from the National Down Syndrome Cytogenetic Register (1989-1996). We compare our results with published results of other studies on the subject to obtain a summary estimate. We exclude one study from the meta analysis due to incorrect methodology resulting in an overestimate of fetal loss. Based on the combined data (i) between the time of chorionic villus sampling and term an estimated 43 per cent (95 per cent CI: 31-54 per cent) of pregnancies ended in a miscarriage or still birth, (ii) between the time of amniocentesis and term an estimated 23 per cent (95 per cent CI: 19 28 per cent) of pregnancies ended in a miscarriage or still birth, and (iii) 12 per cent (95 per cent CI: 2-23 per cent) of births were stillborn or resulted in a neonatal death.

Abortion, Spontaneous↗
PubMed1999

SP1 in pregnancies with Down syndrome in the first trimester of pregnancy. International Prenatal Screening Research Group.

We conducted a study to determine the value of serum pregnancy-specific beta-1-glycoprotein (Schwangerschafts protein 1, SP1) as an antenatal screening test for Down syndrome in the first trimester. Serum samples collected from women at 8 to 14 weeks of pregnancy, immediately prior to having a chorionic villus sampling procedure on account of advanced maternal age, were retrieved from 96 women with Down syndrome pregnancies (cases) and from 480 women with unaffected pregnancies (controls). Cases and controls were ascertained at 21 obstetric centres in nine countries. Each case was matched with five controls for maternal age (same five-year age groups), duration of storage of the serum sample (same calendar year) and gestational age (usually the same week of pregnancy). The levels of SP1 were lower in pregnancies associated with Down syndrome: the median level was 0.86 multiples of the median level in the controls (95 per cent confidence interval 0.76 to 0.97). This difference, though statistically significant, was not large enough for SP1 to be a useful marker in screening, at least from 10 weeks onwards where most of our data lie.

Biomarkers↗
PubMed1999

Maternal serum prostate-specific antigen and Down syndrome in the first and second trimesters of pregnancy. International Prenatal Screening Research Group.

It has been suggested that high levels of maternal serum prostate-specific (PSA) may be associated with fetal Down syndrome. We retrieved stored blood samples from 102 singleton Down syndrome pregnancies at 8-14 weeks' gestation and 99 at 15-22 weeks' gestation, together with samples from five unaffected singleton control pregnancies matched for gestational age. PSA was measured using an ultrasensitive assay. Contrary to earlier reports, PSA levels were similar in affected and unaffected pregnancies in both the first and second trimester of pregnancy; 1.1 and 0.9 multiple of the normal median, respectively, in affected pregnancies. There was no indication that PSA would be a useful screening marker.

Down Syndrome↗
PubMed1998

Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention.

BACKGROUND: Results from prospective studies of serum homocysteine levels and ischemic heart disease (IHD) are inconclusive. We carried out a further prospective study to help clarify the position. METHODS: In the British United Provident Association (BUPA) prospective study of 21,520 men aged 35 to 64 years, we measured homocysteine levels in stored serum samples and analyzed data from 229 men without a history of IHD at study entry who subsequently died of IHD and 1126 age-matched control subjects (nested case-control design). RESULTS: Serum homocysteine levels were significantly higher in men who died of IHD than in men who did not (mean, 13.1 vs 11.8 micromol/L; P<.001). The risk of IHD among men in the highest quartile of serum homocysteine levels was 3.7 times (or 2.9 times after adjusting for other risk factors) the risk among men in the lowest quartile (95% confidence interval [CI], 1.8-4.7). There was a continuous dose-response relationship, with risk increasing by 41% (95% CI, 20%-65%) for each 5-micromol/L increase in the serum homocysteine level. After adjustment for apolipoprotein B levels and blood pressure, this estimate was 33% (95% CI, 22%-59%). In a meta-analysis of the retrospective studies of homocysteine level and myocardial infarction, the age-adjusted association was stronger: an 84% (95% CI, 52%-123%) increase in risk for a 5-micromol/L increase in the homocysteine level, possibly because the participants were younger; the relationship between serum homocysteine level and IHD seems to be stronger in younger persons than in older persons. CONCLUSIONS: Our positive results help resolve the uncertainty that resulted from previous prospective studies. The epidemiological, genetic, and animal evidence together indicate that the association between serum homocysteine level and IHD is likely to be causal. A general increase in consumption of the vitamin folic acid (which reduces serum homocysteine levels) would, therefore, be expected to reduce mortality from IHD.

Adult↗
PubMed1998

Screening for Down syndrome at 14 weeks of pregnancy.

To investigate whether statistical parameters used in Down syndrome screening between 15 and 22 weeks of pregnancy can be used at 14 weeks, we assayed alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, and inhibin-A in 16 pregnancies with Down syndrome in the 14th week of pregnancy and expressed values in multiples of the normal median. The median and standard deviation values for these 16 pregnancies were not materially different from those published for 15-22 weeks. It is reasonable, therefore, to offer Down syndrome screening using these markers starting at 14 completed weeks of pregnancy instead of 15 weeks. It needs to be recognized, however, that serum AFP measurement for neural tube defect screening is less effective at this time than between 16 and 18 weeks of pregnancy.

Chorionic Gonadotropin↗
PubMed1998

The pattern of maternal serum inhibin-A concentrations in the second trimester of pregnancy.

Maternal serum inhibin-A concentration is a useful marker in prenatal screening for Down syndrome in the second trimester. We measured inhibin-A concentrations in 4304 pregnancies without Down syndrome between 14 and 22 weeks of pregnancy to determine the median values according to gestational age. There was a U-shaped pattern of inhibin-A concentration against gestational age with a minimum concentration at 17 weeks and 1 day (120 days). We suggest that screening centres use a quadratic equation when estimating their normal median inhibin-A level, constraining the shape of the curve and fixing the lower point of the curve to occur at 120 days, but allowing its position in relation to the vertical inhibin-A axis to be set according to the local data. This approach will systematically allow for the changing inhibin-A concentration without introducing the instability of deriving a fresh quadratic equation for each screening centre and each time a centre's medians are revised.

Biomarkers↗
PubMed1998

Serum triglyceride: a possible risk factor for ruptured abdominal aortic aneurysm.

BACKGROUND: We aimed to determine the relationship between ruptured abdominal aortic aneurysm (AAA) and serum concentrations of lipids and apolipoproteins. METHODS: A cohort of 21 520 men, aged 35-64 years, was recruited from men attending the British United Provident Association (BUPA) clinic in London for a routine medical examination in 1975-1982. Smoking habits, weight, height and blood pressure were recorded at entry. Lipids and apolipoproteins were measured in stored serum samples from the 30 men who subsequently died of ruptured AAA and 150 matched controls. RESULTS: Triglyceride was strongly related to risk of ruptured AAA. In univariate analyses the risk in men on the 90th centile of the distribution relative to the risk in men on the 10th (RO10-90) was 12 (95% confidence interval [CI] : 3.8-37) for triglyceride, 5.5 (95% CI: 1.8-17) for apolipoprotein B (apoB) (the protein component of low density lipoprotein [LDL]), 0.15 (95% CI : 0.04-0.56) for apo A1 (the protein component of high density lipoprotein [HDL]), 3.7 (95% CI: 1.4-9.4) for body mass index and 3.0 (95% CI: 1.1-8.5) for systolic blood pressure. Lipoprotein (a) (Lp(a)) was not a significant risk factor (RO10-90 = 1.6, 95% CI: 0.6-3.0). In multivariate analysis triglyceride retained its strong association. CONCLUSION: Triglyceride appears to be a strong risk factor for ruptured AAA, although further studies are required to clarify this. If this and other associations are cause and effect, then changing the distribution of risk factors in the population (by many people stopping smoking and adopting a lower saturated fat diet and by lowering blood pressure) could achieve an important reduction in mortality from ruptured AAA.

Adult↗
PubMed1998

Alternative methods of maternal weight adjustment in maternal serum screening for Down syndrome and neural tube defects.

Serum markers used in screening for Down syndrome and neural tube defects are often adjusted to take account of the effect of maternal weight on the marker levels. The standard adjustment procedure is based on a linear relationship between the marker concentration, expressed as the log of the multiple of the median (MOM), and maternal weight on a linear scale. It has been proposed that maternal weight adjustment may be better performed using a linear relationship between marker concentration expressed in MOM and the reciprocal of maternal weight. In a dataset of 8905 singleton pregnancies in white women without Down syndrome or neural tube defects we compared the two methods of weight adjustment and found that both were satisfactory and neither had an obvious advantage over the other. In the analysis it was noticed that hCG levels in very heavy women (> 120 kg) were higher than expected from the decreasing linear trend with maternal weight--a result that was statistically highly significant (p < 0.01) but for which we have no explanation. In screening it will have virtually no effect because the finding was restricted to only the 0.3 per cent of the heaviest women.

Biomarkers↗