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N J Wald

Publications and source records attributed to N J Wald.

At least 55 records · Page 3Linked to original sources
PubMed2001

Repeat testing in antenatal screening for Down syndrome using dimeric inhibin-A in combination with other maternal serum markers.

The effect on screening performance of collecting a second fresh blood sample in antenatal screening for Down syndrome has been previously reported for the commonly used double and triple tests. Recently, dimeric inhibin-A has been used with the triple test (together constituting the quadruple test) in several centres and here we assess the effect of repeat testing using inhibin-A. Routine repeat testing using the quadruple test did not yield a material increase in performance compared with having no repeat testing. For a 5% false-positive rate the increase in detection rate was only about 3-5 percentage points; a modest increase which is probably not worthwhile in the light of the extra cost and delay.

Biomarkers↗
PubMed2001

Inaccurate estimation of risk in second trimester serum screening for Down syndrome among women who have already had first trimester screening.

Problems can arise in prenatal screening for Down syndrome when tests are performed in the first and second trimester and some women who have a negative first trimester test have a second trimester serum test. The second test result does not usually take account of the previous one being negative. Even if it does, it is often inaccurate. Using published data the extent of the error was examined. The age-specific risk of an affected pregnancy in such women will be lower than if no first trimester test had been performed. The distributions of the screening markers in affected and unaffected pregnancies will be different from those in unscreened women. If the appropriate age-specific risk and marker distributions are not used, error will arise. For example, a 35-year-old woman with nuchal translucency (NT), pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotrophin (hCG) levels at the normal median would have a risk of 1 in 6500. If she then had the Triple Test with alpha-fetoprotein (AFP), unconjugated oestriol, and hCG levels of 0.7, 0.7 and 1.5 multiples of the median (MoM), respectively, her risk, ignoring the previous result, would be overestimated (1 in 95 compared with the correct estimate of 1 in 705). If the previous result was included, but the age-specific risk and second trimester marker distributions were not revised, her risk would be underestimated (1 in 820). If the correct age-specific risk and screening marker distributions were used, risk estimates would be accurate, but two tests would be less efficient than integrating all the screening information into a single test. The practice of offering second trimester serum screening to women who have already been screened is best avoided.

Adult↗
PubMed2000

Chlamydia pneumoniae infection and mortality from ischaemic heart disease: large prospective study.

OBJECTIVE: To determine whether there is an independent association between infection with Chlamydia pneumoniae and ischaemic heart disease. DESIGN: Prospective study using a nested case-control design. SETTING: Medical centre in London run by BUPA, a private medical organisation. PARTICIPANTS: 21 520 professional men aged 35-64 who attended for a medical examination in London between 1975 and 1982. MAIN OUTCOME MEASURE: Death from ischaemic heart disease. RESULTS: The distributions of concentrations of IgG and IgA antibodies to C pneumoniae were similar in the 647 men who subsequently died of ischaemic heart disease and in 1294 age matched controls who did not. There was no material association with heart disease irrespective of the cut-off point chosen to define seropositivity. At a cut-off point that defines 15% of controls as positive, for example, the odds ratios were 1.26 (95% confidence interval 0.95 to 1.68) for IgG and 1.09 (0.82 to 1.43) for IgA. CONCLUSIONS: No material association was found between infection with C pneumoniae and ischaemic heart disease. The size and prospective design of the study and the socioeconomic homogeneity of the cohort minimise both random and systematic error.

Adult↗
PubMed2000

Advances in antenatal screening for Down syndrome.

Antenatal screening for Down Syndrome using maternal age alone is no longer an adequate standard of care. Screening in the early second trimester of pregnancy (between 15 and 20 weeks of pregnancy) using the quadruple test can identify 76% of affected pregnancies with a 5% false-positive rate. Screening in the first trimester of pregnancy (between 10 and 13 weeks of pregnancy) is possible using two biochemical markers (PAPP-A and free beta-hCG) together with an ultrasound marker nuchal translucency measurement; using these three markers together with maternal age can identify 85% of affected pregnancies, with a 5% false-positive rate. While there is debate over issues involved in choosing between first and second trimester screening, the most effective screening test for Down Syndrome is the integrated test based on the integration of the first trimester and the second trimester markers. This has a 94% detection rate for a 5% false-positive rate. If the false-positive rate were set at 1%, the detection rate would be 85%. No other screening test for Down Syndrome can detect such a high proportion of affected pregnancies with such a low false-positive rate.

Biomarkers↗
PubMed2000

An investigation into why two-view mammography is better than one-view in breast cancer screening.

AIM: To determine why two-view mammography in screening for breast cancer is more effective than using a single medio-lateral oblique view. MATERIALS AND METHODS: In the United Kingdom Coordinating Committee on Cancer Research randomized trial of one- vs two-view mammography in breast cancer screening the oblique view was assessed by one radiologist and two views (oblique and cranio-caudal) assessed by another. For the present study the mammographic films were retrieved from the screening centres and assessed by three consultant radiologists. Mammographic films were available from 110 women; 87 had their breast cancer detected by both one and two views and in 23 it was missed by one view but detected using two views. Outcome measures were breast size, location and size of the cancer, mammographic features, presence of microcalcification and overall radiological assessment. RESULTS: Although 23 cancers were missed in the original trial when one view was used, only two were not visible on the oblique view. Cancers missed using a single oblique view (and only detected if the cranio-caudal view was available with the oblique) tended to be smaller by about 4 mm (P = 0.05), centrally located in the breast (P = 0.16), not spiculated or round, (P </= 0. 001) and lacked microcalcification (P = 0.15). Breast size and breast radiographic density were not significantly associated with breast cancer detection. CONCLUSIONS: The results provide the basis for the observation that two-view mammographic screening is more effective than one-view mammographic screening.Hackshaw, A. (2000). Clinical Radiology55, 454-458.

Breast Neoplasms↗
PubMed2000

Adding free to total prostate-specific antigen levels in trials of prostate cancer screening.

We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to alpha-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials.

Case-Control Studies↗
PubMed2000

Assay precision of serum alpha fetoprotein in antenatal screening for neural tube defects and Down's syndrome.

OBJECTIVES: To assess the impact of current serum alpha fetoprotein (AFP) assays on the performance of screening for open neural tube defects and Down's syndrome. METHODS: Maternal serum samples, collected between weeks 15 and 22 from 470 singleton pregnancies without neural tube defects or Down's syndrome, were assayed for AFP using an automated fluorometric immunoassay. The samples had been assayed for AFP using an in house radioimmunoassay with a lower precision ten years before. The variance of AFP using the radioimmunoassay was compared with that using the current fluorometric assay and then used to estimate the detection rates and false positive rates for neural tube defect and Down's syndrome screening. RESULTS: Current serum AFP assays are more precise. Using a cut off level of 2.5 multiples of the median, the false positive rate in screening for anencephaly and open spina bifida was 0.8% with the new assay compared with 2% using the previous assay. When screening for Down's syndrome, the false positive rate is reduced by about one percentage point without loss of detection. CONCLUSION: Improvements in the precision of maternal serum AFP measurement have led to small but useful improvements in screening for open neural tube defects and Down's syndrome. Published estimates of screening performance using such modern assays can be revised accordingly.

Anencephaly↗
PubMed1999

Down's syndrome screening in the UK in 1998.

The extent of antenatal screening for Down's syndrome with serum or ultrasound markers has increased over the past decade. We here present a survey of screening in the UK in 1998 and compare the results with similar surveys from 1991 and 1994.

Adult↗
PubMed1999

Integrated screening for Down's syndrome based on tests performed during the first and second trimesters.

BACKGROUND: Both first-trimester screening and second-trimester screening for Down's syndrome are effective means of selecting women for chorionic-villus sampling or amniocentesis, but there is uncertainty about which screening method should be used in practice. We propose a new screening method in which measurements obtained during both trimesters are integrated to provide a single estimate of a woman's risk of having a pregnancy affected by Down's syndrome. METHODS: We used data from published studies of various screening methods employed during the first and second trimesters. The first-trimester screening consisted of measurement of serum pregnancy-associated plasma protein A in 77 pregnancies affected by Down's syndrome and 383 unaffected pregnancies and measurements of nuchal translucency obtained by ultrasonography in 326 affected and 95,476 unaffected pregnancies. The second-trimester tests were various combinations of measurements of serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin A in 77 affected and 385 unaffected pregnancies. RESULTS: When we used a risk of 1 in 120 or greater as the cutoff to define a positive result on the integrated screening test, the rate of detection of Down's syndrome was 85 percent, with a false positive rate of 0.9 percent. To achieve the same rate of detection, current screening tests would have higher false positive rates (5 to 22 percent). If the integrated test were to replace the triple test (measurements of serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin), currently used with a 5 percent false positive rate, for screening during the second trimester, the detection rate would be higher 85 percent vs. 69 percent), with a reduction of four fifths in the number of invasive diagnostic procedures and consequent losses of normal fetuses. CONCLUSIONS: The integrated test detects more cases of Down's syndrome with a much lower false positive rate than the best currently available test.

Adolescent↗
PubMed1999

Serum markers for Down's syndrome in women who have had in vitro fertilisation: implications for antenatal screening.

To examine the Down's syndrome screening positive rate among in vitro fertilisation (IVF) pregnancies, we measured second trimester serum marker levels in singleton IVF pregnancies (cases) and in five non-IVF pregnancies (controls) matched to each case for gestational age, age of mother, and duration of storage of the serum sample. There were 151 IVF pregnancies in which alpha fetoprotein, unconjugated oestriol (uE3), free beta-human chorionic gonadotrophin (hCG) and total hCG were measured, 104 IVF pregnancies in which free alpha-hCG was measured, and 39 IVF pregnancies in which inhibin A was measured. Median uE3 levels were 6% lower (P = 0.003), median free beta-hCG 9% higher (P = 0.024), and median total hCG 14% higher (P = 0.026) in IVF pregnancies compared with controls. The screen positive rate in the IVF pregnancies (28%) was about twice as high as that in controls (17%). High hCG levels may be explained by progesterone remaining high in IVF pregnancies. The low uE3 levels remain unexplained. In Down's syndrome screening in IVF pregnancies hCG and uE3 values should be adjusted to avoid the high screen positive rate.

Biomarkers↗