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Abstract Objective--To investigate whether an appropriate combination of maternal serum inhibin A, free β-human chorionic gonadotropin (free β-hCG), unconjugated estriol (u[E.sub.3]), and alpha-fetoprotein (AFP) may be an effective means of [...]

Abstract 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 [...]

Summary points To be a worthwhile screening test, a risk factor must be strongly associated with a disorder The strength of association between a risk factor and a disorder can [...]

EDITOR--Women who take folic acid when trying to conceive have been shown to have a lower risk of a pregnancy affected by neural tube defects.[1] The UK Department of Health [...]

Prenatal screening for Down syndrome can be performed using the first trimester Combined Test [nuchal translucency (NT), pregnancy-associated plasma protein A (PAPP-A), free β-human chorionic gonadotrophin (hCG) and maternal age] or the Integrated Test (for example, NT and PAPP-A in the first trimester and two or more serum markers in the second trimester, all with maternal age). We investigated the value of providing partial results when using the Combined Test or Integrated Test to identify women with a high enough risk of having an affected pregnancy based on NT and maternal age alone such that there would be little advantage in combining this information with data on the serum markers. We also assessed whether in programmes using the Integrated Test it is worthwhile reporting partial results based on risk using first trimester markers and not obtaining a second trimester blood sample. Published data based on 480 affected and 96 839 unaffected pregnancies were used for the present study. Using NT and age alone, about 0.14% of all women screened would have such a high risk that they would always remain screen-positive after the Combined Test and only 0.06% would remain screen-positive after the Integrated Test. Similarly, about 0.07% of all women screened who have a high risk based on NT, PAPP-A and age would remain screen-positive after the Integrated Test. These percentages are too small to justify reporting two risk estimates for all women, given the confusion this would generate. It is therefore not worthwhile reporting partial risk estimates in screening programmes using the Combined Test or Integrated Test. Copyright © 2001 John Wiley & Sons, Ltd.

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 β-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. Copyright © 2001 John Wiley & Sons, Ltd.

We aimed to determine the relationship between ruptured abdominal aortic aneurysm (AAA) and serum concentrations of lipids and apolipoproteins.

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. Copyright © 1999 John Wiley & Sons, Ltd.

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. Copyright © 1999 John Wiley & Sons, Ltd.

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. © 1998 John Wiley & Sons, Ltd.

Objective– To determine the feasibility of a randomised trial of ovarian cancer screening among women attending a breast cancer screening centre.Design– Randomised controlled trial of ovarian cancer screening using transvaginal ultrasonography as a primary screening test and colour Doppler imaging as a secondary screening test in the screened group and no intervention in the control group.Setting– Reading breast cancer screening centre (United Kingdom).Subjects– 8678 women, without a bilateral oophorectomy or hysterectomy, aged between SO and 64 attending for NHS breast cancer screening between September 1989 and February 1993.Main outcome measures– Uptake of ovarian cancer screening among eligible women and the screening false positive rate (considered as the referral rate to a gynaecologist for surgical intervention).Results −82% (7124/8678) of eligible women agreed to join the trial and were randomly allocated in equal numbers to each arm of the trial. 3280 women had an initial scan. The false positive rate after ultrasonography alone was 2·9% (86/2952), but this dropped to 0·5% after colour Doppler as a secondary screening test. One stage I primary ovarian cancer was detected at screening in a 58 year old women.Conclusions– A randomised trial of ovarian cancer screening using ultrasonography and colour Doppler imaging is feasible and acceptable among women attending a breast cancer screening centre. The results indicate that the expected odds of being affected given a positive result in the general population would be about 1:12. A full randomised trial of ovarian cancer screening with mortality as the end point is needed to assess whether screening reduces mortality from this disease. A multicentre European trial is currently in progress.

We aimed to determine how differences in the age at which women had their pregnancies influenced the expected detection and false‐positive rates of serum screening for Down's syndrome (i) between 1970 and 1993 in England and Wales, and (ii) between regions and districts of England and Wales in 1991. We applied published estimates of Down's syndrome screening to regional and district data on the age distribution of maternities and changes in the age distribution over time in England and Wales obtained from the Office of Population Censuses and Surveys. From 1970 to 1993 women, on average, became pregnant at an older age; the percentage of maternities among women aged 35 or more increased from 7 to 9·2 per cent. This was not a great enough change to have had a material effect on the performance of Down's syndrome screening. In 1991, the percentage of maternities among women aged 35 or more varied from 5 to 20 per cent among Health Districts, a difference that would influence the performance of screening; for example, using the triple test and a risk cut‐off of 1 in 250, the detection rates would have varied from about 55 to 70 per cent and the false‐positive rates from 4·4 to 8·8 per cent across different districts. The tendency for women to have their pregnancies at an older age would have had a negligible impact on the performance of serum screening for Down's syndrome, but differences in the age when women had their pregnancies in different parts of the country would lead to twice as many women being referred for amniocentesis in some districts than in others when offered the same method of serum screening and at the same risk cut‐off level. The results will have important implications for the local purchasers of Down's syndrome screening services. © 1997 John Wiley & Sons, Ltd.

Data on pregnancies with and without Down's syndrome between 10 and 14 weeks of pregnancy were used to determine the performance of combined ultrasound and biochemical markers in prenatal screening for Down's syndrome. We used three datasets: one published by Pandya et al. (1995) on nuchal translucency measurement in 86 Down's syndrome pregnancies; one published by Wald et al. (1996a) on free beta human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in 77 affected pregnancies and 385 unaffected pregnancies; and the third from Schuchter et al. on 561 unaffected pregnancies with nuchal translucency measurement. Combining the data from these three datasets showed that screening between 10 and 14 weeks by combining the serum markers with nuchal translucency measurement had a detection rate of 80 per cent for a 5 per cent false-positive rate, better than maternal age with two serum markers (62 per cent for 5 per cent) or maternal age with nuchal translucency measurement (63 per cent for 5 per cent). At this time in pregnancy, it appears that screening using the combined test is better than second-trimester serum screening (76 per cent for 5 per cent), though these estimates do not allow for any association between the markers and spontaneous fetal loss, an issue that needs to be clarified by further research. Meanwhile, these results provide a reasonable working estimate of screening performance using different combinations of these markers. © 1997 John Wiley & Sons, Ltd.

No Abstract

On 4 February 1993, the European Society of Mastology (EUSOMA) convened a meeting of experts in Paris to evaluate the current evidence on the value and hazards of breast cancer screening. The Committee consisted of individuals from different countries throughout Europe and from different disciplines. We summarise here the deliberations and conclusions of the Committee.

The concentrations of retinol and beta carotene were measured in serum samples taken from 113 women with cervical cancer, 32 with invasive and 81 with pre-invasive disease, and compared with those from 226 age-matched control women. There was little difference in serum retinol levels between women with cancer of the cervix, at any stage, and the control women, after adjusting for potential confounding factors. Serum beta carotene concentrations were likewise similar in women with invasive disease and the controls. However mean beta carotene levels were significantly reduced in women with pre-invasive disease compared to the controls (221.3 cf. 291.6 micrograms l-1, P less than 0.05). This reduction was more evident amongst women with a diagnosis of carcinoma-in-situ (mean 213.1 micrograms l-1 than amongst those with severe dysplasia (mean 228.7 micrograms l-1. There is a negative trend between beta carotene and risk of pre-invasive disease which is of borderline significance. These data have also been used to investigate the effects of smoking and oral contraceptive usage on the serum levels of retinol and beta carotene. Both habits tend to increase retinol and decrease beta carotene concentrations.

The detailed mortality and morbidity statistics on smoking tend to conceal the overall impact of the habit on health. About 3 million people die each year from smoking in economically developed countries, half of them before the age of 70. Cancers of eight sites are recognized as being caused by smoking--lung cancer almost entirely and the others (upper respiratory, bladder, pancreas, oesophagus, stomach, kidney, leukaemia) to a substantial extent. Six other potentially fatal diseases are also judged to be caused by smoking: respiratory heart disease, chronic obstructive lung disease, stroke, pneumonia, aortic aneurysm and ischaemic heart disease, the most common cause of death in economically developed countries. Non-fatal diseases, such as peripheral vascular disease, cataracts, hip fracture, and periodontal disease, which cause appreciable disability, cost and inconvenience are also caused by smoking. In pregnancy, smoking increases the risk of limb reduction defects, spontaneous abortion, ectopic pregnancy, and low birth weight. While there are some diseases for which smoking shows a protective effect, the 'benefits' of these are negligible in relation to the illness and premature mortality caused by smoking. About 20% of all deaths in developed countries are caused by smoking; an enormous human cost which can be completely avoided.

In a prospective study of 5,004 women in Guernsey, plasma samples were collected and stored. Retinol, beta-carotene and vitamin E levels were later measured in the samples from 39 women who subsequently developed breast cancer and from 78 controls who did not develop cancer. Plasma retinol levels were not related to the risk of breast cancer, mean levels among cases and controls being 485 micrograms l-1 and 479 micrograms l-1 respectively. Plasma vitamin E levels showed a clear association, low levels being associated with a significantly higher risk of cancer. The mean vitamin E levels among cases and controls were 4.7 mg l-1 and 6.0 mg l-1 respectively (P less than 0.025), and the risk of breast cancer in women with vitamin E levels in the lowest quintile was about 5-times higher than the risk for women with levels in the highest quintile (P less than 0.01). beta-carotene levels showed a tendency to be lower in women who developed cancer than in controls (36 micrograms l-1 among cases compared with 50 micrograms l-1 among controls) but the difference was not statistically significant.

An enzyme-linked immunosorbent assay (ELISA) was evaluated for serum alpha-fetoprotein determination in the antenatal screening for fetal open neural tube defects. The ELISA was used concurrently with an existing radioimmunoassay (RIA) method until serum specimens from 5000 pregnant women, between 15 and 20 weeks gestation, had been tested. The accuracy of the ELISA was similar to that of the RIA; the median AFP values by gestational week obtained with the ELISA were, on average, 2 KIU/L higher than the corresponding RIA values; the 10thand 90thpercentiles, in terms of multiples of the median (MoM), were very similar. The precision of the two methods was also similar. The ELISA method yielded 1·8% results from unaffected pregnancies above 2·5 MoM compared with 1·4% by RIA, a small but statistically significant difference (P=0·03). Both methods detected the same affected pregnancies identified during this period; five open neural tube defects, three with exomphalos and three intra-uterine deaths. The ELISA method was simple, required about one quarter less operator time than the RIA and enabled results to be generated in one day rather than the two days required by RIA. The ELISA method is a suitable alternative to RIA for routine use in screening for fetal neural tube defects.

England and Wales have shared in the dramatic decline in the prevalence of neural tube defects (NTDs) at birth. Reported rates of approximately 3.2 per 1000 births in the early 1970s have fallen to the current (1997) level of 0.1 per 1000, representing a 96 percent reduction (Fig. 1). The concurrent increase in terminations of NTD pregnancies is much too small to explain the drop in NTD births. There undoubtedly is some underreporting of terminations for NTDs, and this study was an attempt to estimate the extent of this effect. Data from 1976 to 1980 on reported terminations for CNS defects and NTD births were analyzed, assuming that the true number of NTD pregnancies during this time had either remained constant or changed by a constant amount each year. After adjusting for underreporting, the prevalence of NTD births and terminations in England and Wales in 1997 was 1.6 per 1000 births. It was estimated that 56 percent of NTD terminations were not reported as such.

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 pregnanceis 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. Copyright © 1999 John Wiley & Sons, Ltd.

To examine the Down's syndrome screening positive rate among in vitrofertilisation (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 β–human chorionic gonadotrophin (hCG) and total hCG were measured, 104 IVF pregnancies in which free α‐hCG was measured, and 39 IVF pregnancies in which inhibin A was measured. Median uE3levels were 6% lower (P= 0.003), median free β–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 uE3levels remain unexplained. In Down's syndrome screening in IVF pregnancies hCG and uE3values should be adjusted to avoid the high screen positive rate.

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. © 1998 John Wiley & Sons, Ltd.

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 α-hCG, free β-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.

Objectives— To evaluate the completeness of notifications of Down's syndrome live births and terminations to the Office for National Statistics (ONS) using data from the National Down Syndrome Cytogenetic Register (NDSCR). To examine the agreement of observed birth prevalence of Down's syndrome with the expected birth prevalence derived from published maternal age specific rates.Methods— The number of live births (adjusted to allow for the estimated under-ascertainment) and the number of terminations due to fetal Down's syndrome from NDSCR were compared with those figures reported to the ONS. Subsequently, using the NDSCR figures, the live birth prevalence of Down's syndrome that would have occurred in the absence of antenatal diagnosis and selective termination was calculated in England and Wales in the years 1990–1993. These figures were compared with those derived by applying published age specific prevalences to the maternal age distribution in England and Wales.Results— It is estimated that only 48% and 46% respectively of Down's syndrome live births and terminations of pregnancy were notified to ONS between 1990 and 1993. The annual expected birth prevalences of Down's syndrome obtained by applying maternal age specific prevalences to the maternal age distribution were in close agreement with observed rates from NDSCR.Conclusions— There is considerable underreporting of Down's syndrome births and terminations to ONS. The NDSCR data are more complete and therefore the effects of screening should be monitored using data from this source, or using estimates derived from the age specific rates of Down's syndrome.

Objective— To validate individual risk estimates in antenatal serum screening for Down's syndrome.Methods— Women screened for Down's syndrome using maternal serum a fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophs (hCG) with maternal age (the triple test) or AFP, uE3, free β subunit and free a subunit of hCG with maternal age (the quadruple test) were grouped according to their predicted risk of having an affected pregnancy. The mean predicted risk in each category was then compared with the observed prevalence based on the number of affected and unaffected pregnancies in each category.Subjects— About 100 000 pregnant women screened for Down's syndrome from 1989 to 1995.Results— There was close agreement between the predicted term risk and the prevalence at birth for both the triple test and the quadruple test. For example, with the quadruple test the predicted risk in the highest risk group was 1 in 3.3 and the prevalence was 1 in 2.6; in the lowest risk group these were 1 in 3000 and 1 in 2300 respectively.Conclusion— Risk estimates based on multiple marker screening for Down's syndrome are accurate. The technique used to demonstrate this is simple and offers a useful empirical check on screening performance.

Cigarette consumption and inhaling, assessed using carboxyhaemoglobin levels, were studied in 1786 men to investigate the importance of tar and nicotine as determinants of smoking habits. No prior warning was given that smoking habits would be studied. Neither nicotine nor tar yields materially influenced the number of cigarettes smoked a day. Both nicotine and tar yields were negatively associated with inhaling (p less than 0.001) but after allowing for either of the two yields the effect of the other on inhaling was no longer statistically significant. There was, therefore, no indication as to whether nicotine or tar was the more important determinant of smoking habit.

OBJECTIVE:s To determine the quantitative efficacy of different classes of blood pressure lowering drugs in preventing coronary heart disease (CHD) and stroke, and who should receive treatment. Design Meta-analysis. DATA SOURCE: Medline (1966-2007). STUDY SELECTION: Randomised trials of blood pressure lowering drugs recording CHD events and strokes. 108 trials studied differences in blood pressure between study drug and placebo (or control group not receiving the study drug) ("blood pressure difference trials"), and 46 trials compared drugs ("drug comparison trials"). Seven trials with three randomised groups fell into both categories. The results were interpreted in the context of those expected from the largest published meta-analysis of cohort studies, totalling 958 000 people. Participants 464 000 people defined into three mutually exclusive categories: participants with no history of vascular disease, a history of CHD, or a history of stroke. RESULTS: In the blood pressure difference trials β blockers had a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% confidence interval 22% to 34%) compared with 15% (11% to 19%) in trials of other drugs. The extra effect was limited to a few years after myocardial infarction, with a risk reduction of 31% compared with 13% in people with CHD with no recent infarct (P=0.04). In the other blood pressure difference trials (excluding CHD events in trials of β blockers in people with CHD), there was a 22% reduction in CHD events (17% to 27%) and a 41% (33% to 48%) reduction in stroke for a blood pressure reduction of 10 mm Hg systolic or 5 mm Hg diastolic, similar to the reductions of 25% (CHD) and 36% (stroke) expected for the same difference in blood pressure from the cohort study meta-analysis, indicating that the benefit is explained by blood pressure reduction itself. The five main classes of blood pressure lowering drugs (thiazides, β blockers, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers) were similarly effective (within a few percentage points) in preventing CHD events and strokes, with the exception that calcium channel blockers had a greater preventive effect on stroke (relative risk 0.92, 95% confidence interval 0.85 to 0.98). The percentage reductions in CHD events and stroke were similar in people with and without cardiovascular disease and regardless of blood pressure before treatment (down to 110 mm Hg systolic and 70 mm Hg diastolic). Combining our results with those from two other studies (the meta-analyses of blood pressure cohort studies and of trials determining the blood pressure lowering effects of drugs according to dose) showed that in people aged 60-69 with a diastolic blood pressure before treatment of 90 mm Hg, three drugs at half standard dose in combination reduced the risk of CHD by an estimated 46% and of stroke by 62%; one drug at standard dose had about half this effect. The present meta-analysis also showed that drugs other than calcium channel blockers (with the exception of non-cardioselective β blockers) reduced the incidence of heart failure by 24% (19% to 28%) and calcium channel blockers by 19% (6% to 31%). CONCLUSIONS: With the exception of the extra protective effect of β blockers given shortly after a myocardial infarction and the minor additional effect of calcium channel blockers in preventing stroke, all the classes of blood pressure lowering drugs have a similar effect in reducing CHD events and stroke for a given reduction in blood pressure so excluding material pleiotropic effects. The proportional reduction in cardiovascular disease events was the same or similar regardless of pretreatment blood pressure and the presence or absence of existing cardiovascular disease. Guidelines on the use of blood pressure lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure. Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some.

To determine the combination of drugs and vitamins, and their doses, for use in a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. The strategy was to simultaneously reduce four cardiovascular risk factors (low density lipoprotein cholesterol, blood pressure, serum homocysteine, and platelet function) regardless of pretreatment levels.

To determine by how much statins reduce serum concentrations of low density lipoprotein (LDL) cholesterol and incidence of ischaemic heart disease (IHD) events and stroke, according to drug, dose, and duration of treatment.

To determine the average reduction in blood pressure, prevalence of adverse effects, and reduction in risk of stroke and ischaemic heart disease events produced by the five main categories of blood pressure lowering drugs according to dose, singly and in combination.

No Abstract

Screening, whether in the first or second trimester, is an effective means of selecting women for chorionic-villus sampling or amniocentesis when Down syndrome is a possibility. At present, however, at least 5 percent of screened women have to undergo amniocentesis for 60 to 80 percent of affected fetuses to be detected. The present study was an effort to integrate measurements made during both trimesters to yield a single risk estimate. Data were taken from published studies of first-trimester screening (for serum pregnancy-associated plasma protein A in 77 affected and 383 unaffected pregnancies; for nuchal translucency on ultrasound in 326 affected and 95,476 unaffected pregnancies). In the second trimester, varying combinations of serum -fetoprotein (AFP), unconjugated estriol, human chorionic gonadotropin (hCG), and inhibin A tests were available for 77 affected and 385 unaffected pregnancies. The test regimens compared included the following 1) a double test, second-trimester measurements of serum AFP and hCG; 2) a triple test, second-trimester measurements of serum AFP, unconjugated estriol, and hCG; 3) a quadruple test, second-trimester measurements of the same parameters plus inhibin A; 4) a combined test, first-trimester measurements of pregnancy-associated plasma protein A, free subunit of hCG, and nuchal translucency; and 5) an integrated test, first-trimester tests of pregnancy-associated plasma protein A and nuchal translucency and second-trimester measurements of serum AFP, unconjugated estriol, hCG, and inhibin A.