DVPI measurements between 10 and 13 weeks' gestation in 66 Down's syndrome and 7184 unaffected pregnancies were collected from women attending the Hospital Clinic, Barcelona, for antenatal care from 1999 to 2007 and combined with the Serum Urine and Ultrasound Screening Study (SURUSS) data to model screening performance, safety and cost-effectiveness of the screening tests with and without DVPI.

The median DVPI multiple of the normal median in Down's syndrome pregnancies was 1.55 (95% CI 1.36–1.73). As a single screening marker without using maternal age, DVPI has a 62% detection rate for a 5% false-positive rate. At a 90% detection rate (first trimester measurements at 11 weeks' gestation) the addition of DVPI reduced the false-positive rate of the Combined test from 8.5% to 4.6% and the Integrated test from 2.0% to 1.1%, with a corresponding reduction in fetal losses from diagnostic procedures. There was no material loss of cost-effectiveness.

Addition of DVPI measurements to the Combined and Integrated tests substantially improves the efficacy and safety of antenatal Down's syndrome screening.

Umbilical cord blood total thyroxin (CB-TT4) was measured. In samples with low T4 concentrations, an additional measurement of cord blood thyroid-stimulating hormone was made.

A total of 96,015 newborn infants were screened in the period January 1990–December 2007. Twenty-six cases of primary congenital hypothyroidism, six cases of transient hypothyroidism and 13 cases of central hypothyroidism were detected. This method of screening resulted in 100% sensitivity and 98% specificity (95% CI 84–100, and 95% CI 98–98.2, respectively). However, there was a high mean recall rate of 1.9%.

The use of CB-TT4 is a valid screening strategy for primary congenital hypothyroidism. It meets the metabolic screening demands of early discharge policy and guarantees screening all newborns delivered in the hospital.

Participants invited for screening in 12 of the 14 study centres in the UK FS Trial.

A postal survey following FS screening assessed bowel cancer worry, psychological distress, generalized anxiety, bowel symptoms, general practitioner (GP) visits, positive emotional consequences of screening, and reassurance among people with no polyps (n = 26,573), lower-risk polyps removed at FS (n = 7401) and higher-risk polyps who underwent colonoscopy and were either assigned to colonoscopic surveillance (n = 1543) or discharged (n = 183). A sub-sample (n = 6389) also completed a questionnaire prior to screening attendance that measured bowel cancer worry, generalized anxiety, bowel symptoms and GP visits, making it possible to examine longitudinal changes in this group.

People offered surveillance reported lower psychological distress and anxiety than those with either no polyps or lower-risk polyps. The surveillance group also reported more positive emotional benefits of screening than the other outcome groups. Post-screening bowel cancer worry and bowel symptoms were higher in people assigned to surveillance, but both declined over time, reaching levels observed in either one or both of the other two groups found to have polyps, suggesting these results were a consequence of polyp detection rather than surveillance per se. Few differences were observed between the group assigned surveillance and the group discharged following colonoscopy.

The results of the current study are broadly reassuring and indicate that referral for colonoscopic surveillance is not associated with adverse psychological consequences.

Two regions with different screening practices and performance.

620,145 subsequent screens (1996–2002) performed in women aged 50–69 and 1280 interval cancers were analysed. Various definitions and quantification methods for interval cancers were compared.

ICR for one year follow-up were lower in Norway compared with NC both when the rate was based on all screens (0.54 versus 1.29 per 1000 screens), negative final assessments (0.54 versus 1.29 per 1000 screens), and negative screening assessments (0.53 versus 1.28 per 1000 screens). The rate of ductal carcinoma in situ was significantly lower in Norway than in NC for cases diagnosed in both the first and second year after screening. The distributions of histopathological tumour size and lymph node involvement in invasive cases did not differ between the two regions for interval cancers diagnosed during the first year after screening. In contrast, in the second year after screening, tumour characteristics remained stable in Norway but became prognostically more favorable in NC.

Even when applying a common set of definitions of interval cancer, the ICR was lower in Norway than in NC. Different definitions of interval cancer did not influence the ICR within Norway or NC. Organization of screening and screening performance might be major contributors to the differences in ICR between Norway and NC.

We compared the association between breast density and tumour size for 1007 screen-detected and 341 interval cancers diagnosed in an Australian mammographic screening programme between 1994 and 1996, for three semi-automated continuous measures of breast density: per cent density, dense area and dense area adjusted for non-dense area.

After adjustment for age, hormone therapy use, family history of breast cancer and mode of detection (screen-detected or interval cancers), all measures of breast density shared a similar positive and significant association with tumour size. For example, tumours increased in size with dense area from an estimated mean 2.2 mm larger in the second quintile (β = 2.2; 95% CI 0.4–3.9, P < 0.001) to mean 6.6 mm larger in the highest decile of dense area (β = 6.6; 95% CI 4.4–8.9, P < 0.001), when compared with first quintile of breast density.

Of the breast density measures assessed, either dense area or per cent density are suitable measures for identifying women who might benefit from more intensive mammographic screening or alternative screening strategies.

To assess the screening performance of carotid artery intima-media thickness (IMT) and carotid plaque in the identification of individuals with CHD.

Meta-analysis of case-control and cohort studies, reporting carotid IMT or plaque in individuals with and without CHD. Screening performance (detection rates [DRs] for specified false-positive rates [FPRs]) was assessed from the relative Gaussian distributions of IMT among individuals with and without CHD and from the proportion of affected and unaffected individuals with plaque.

Eighteen studies, involving 2920 individuals with CHD (mean age range 46–73 years) and 41,941 without (aged 44–73 years) were included in the meta-analysis. For plaque the DR was 62% for an FPR of 30%; likelihood ratio (2.1 [95% CI 1.6–2.4]). For IMT, the DR was 65% for the same 30% FPR (IMT cut-off ≥0.82 mm); likelihood ratio 2.2 (1.9–2.5). The results were similar in case-control and cohort studies.

Neither carotid plaque nor IMT has a CHD screening performance that is sufficiently discriminatory between affected and unaffected individuals to be a worthwhile screening test.

To assess the increase in screening performance of combining carotid IMT and plaque compared with each measurement alone in the identification of individuals with CHD.

Ultrasound examination of left and right carotid arteries was performed on 100 individuals (median age 57), 55 with a history of CHD (unstable angina or myocardial infarction) and 45 without. IMT measurements were taken from the common carotid artery and plaque was identified above, at and below the carotid bifurcation. Associations between IMT and plaque were determined using logistic regression, and screening performance was assessed from the distributions of IMT and plaque among cases and controls.

At a false-positive rate of 5%, IMT (cut-off >0.75 mm) identified 30% (95% CI 14–58) of affected individuals. There was an increase in the detection rate of 8 percentage points (1–33%) using IMT and plaque combined compared with IMT alone. As the false-positive increased, the difference in the detection rate increased, up to a maximum of 20 percentage points (5–38%) at a false-positive rate of 20%. The comparison of IMT and plaque combined with plaque alone could only be estimated for the false-positive rate observed using plaque alone (18%); at this point the detection rate was 72% for plaque and 75% for plaque and IMT combined, an increase of 3 percentage points (0–4%).

In screening for CHD, combining carotid IMT measurement with plaque assessment is better than using either measurement alone, but the improvement in discrimination is not sufficient to make carotid ultrasound screening for CHD worthwhile.

A tertiary medical centre in West Virginia.

We retrospectively reviewed 342 obstetric patients with quad screen data from a single clinic. The quad screen included maternal serum levels of alphafetoprotein (AFP), human chorionic gonadotrophin (hCG), uncongjugated oestriol (uE₃), and inhibin A. The risk of APO was compared between patients with at least one abnormal marker versus no abnormal markers and ≥2 abnormal markers versus <2 abnormal markers. Abnormal markers were determined by cut-off values produced by Receiver Operator Characteristic (ROC) curves and the FASTER trial. Unadjusted and adjusted effects were estimated using logistic regression analysis.

The risk of having an APO increased significantly for patients with abnormal markers by about three-fold using ROC and two-fold using FASTER trial thresholds.

The quad screen shows value in predicting risk of APO in high-risk patients.

From July 2005–July 2006, a random sample of 18–55-year-old English-speaking patients being treated for sub-critical injury or illness at a northeastern US ED were interviewed on their history of HIV testing. Logistic regression models were created to compare patients by their history of being tested for HIV according to their demography. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated.

Of 2107 patients surveyed who were not known to be HIV-infected, the median age was 32 years; 54% were male, 71% were white, and 45% were single/never married; 49% had private health-care insurance and 45% had never been tested for HIV. Of the 946 never previously tested for HIV, 56.1% did not consider themselves at risk for HIV. In multivariable logistic regression analyses, those less likely to have been HIV tested were male (OR: 1.32 [1.37–2.73]), white (OR: 1.93 [1.37–2.73]), married (OR: 1.53 [1.12–2.08]), and had private health-care insurance (OR: 2.10 [1.69–2.61]). There was a U-shaped relationship between age and history of being tested for HIV; younger and older patients were less likely to have been tested. History of HIV testing and years of formal education were not related.

Almost half of ED patients surveyed had never been tested for HIV. Certain demographic groups are being missed though HIV diagnostic testing and screening programmes in other settings. These groups could potentially be reached through universal screening.

Two values per rating were added to the league tables: the best-case scenario and the worst-case scenario. True performance will lie somewhere between these two values. The method is illustrated using data from the Dutch breast cancer screening programme.

By focusing on one performance indicator and one confounder, it was possible to show shifts in the rating order of breast cancer screening units and thus expose the uncertainty about the true performance of each screening unit.

The worst-case and best-case scenario ratings demonstrated the uncertainty within the ratings of a league table. League tables should therefore only be used with great caution and after providing the public with sufficient information.

The study population of the W-E Trial of mammography screening was included in the first (W and E county) and the second (E-county) OVC summary of all Swedish randomized mammography screening trials. The OVC and the W-E Trial used different criteria for case definition and causes of death determination.

A Review Committee compared the original data files from W and E county and the first and second OVC. The reason for a discrepancy was determined individually for all non-concordant cases or breast cancer deaths.

Of the 2615 cases included by the W-E Trial or the OVC, there were 478 (18%) disagreements. Of the disagreements 82% were due to inclusion/exclusion criteria, and 18% to disagreement with respect to cause of death or vital status at ascertainment. For E-County, the OVC inclusion rules and register based determination of cause of death (second OVC) rather than individual case review (W-E Trial and 1st OVC) resulted in a reduction of the estimate of the effect of screening, but for W-County the difference between the original trial and the OVC was modest.

The conclusion that invitation to mammography screening reduces breast cancer mortality remains robust. Disagreements were mainly due to study design issues, while disagreements about cause of death were a minority. When secondary research does not adhere to the protocols of the primary research projects, the consequences of such design differences should be investigated and reported. Register linkage of trials can add follow-up information. The precision of trials with modest size is enhanced by individual monitoring of case status and outcome status such as determination of cause of death.

Persistent non-attenders were identified in routine screening lists. Phone contact was attempted or a home visit was made. If the case was not resolved, a second appointment was made and further phone calls and home visits were attempted.

Of 548 persistent non-attenders identified, 228 (42%) declined screening, 171 (31%) attended, 72 (13%) had moved away or died, 11 (2%) were recently screened or under care for other conditions. Sixty-six cases (12%) remained unresolved. Fourteen women opted to be permanently withdrawn from the National Health Service Breast Screening Programme (NHSBSP). Twenty-four women had a negative experience of breast cancer screening (defaulted, recalled for assessment, recalled for technical reasons). No malignancies were found. A total of 1375 phone calls and 230 home visits were attempted. Uptake would have been 62.2% if none of the persistent non-attenders included in the initiative had attended for screening. With the initiative, uptake of breast cancer screening was increased to 65.3%.

Phone calls and home visits resulted in only a moderate increase in breast cancer screening uptake. The initiative encouraged nervous attenders who were reassured about the screening process. However, more women declined screening than were screened and the initiative made it easier for women to request to be permanently withdrawn from the NHSBSP.

This population-based cohort study followed a total of 5,469,581 women from Taiwan, who were 30 years old or older in 2001 and covered the period January 2001 to December 2003. Of the total study population, 184,701 individuals were women with disability. Gynecologist-obstetrician/general practitioner to female population ratio was used as an indicator of physician availability. Multiple logistical regression models were used.

After adjusting for age, socioeconomic status, racial group, residence area and physician availability, women with severe disability (OR = 0.38; 95% CI: 0.38, 0.39) were the least likely to undergo Pap smear testing. Women with moderate disability (OR = 0.59; 95% CI: 0.58, 0.60) and mild disability (OR = 0.88; 95% CI: 0.86, 0.89) were also significantly less likely to undergo a routine test than women without disability. Women residing in the areas with the greatest physician availability (OR = 0.93; 95% CI: 0.93, 0.94) were significantly less likely to undergo a Pap test than those in the areas with the lowest level of resource availability. The disparity in routine screening between women with and without disability remained across the different levels of physician availability.

In Taiwan, women with disability were found to be at higher risk of lower compliance than women without disability. The gap between women with and without disability persisted across different levels of physician availability.

Interview data from a sample of 16,574 Norwegian women, aged 18–45, in 2004–2005, was compared with information from the population-based cytology register. Crude validity in the self-reports with respect to ever/never having taken a Pap smear was summarized. The validity of the reported interval since last Pap smear was assessed by a smoothed distribution of the reported interval, stratified by the registered interval. Characteristics of influence on validity were identified by logistic regression for true positives (sensitivity and positive predictive value), true negatives (specificity and negative predictive value) and for more than one year discrepancy in time since last Pap smear, between reported and registered interval.

Overall validity was summarized by: concordance = 0.9, sensitivity = 0.97, positive predictive value = 0.92, specificity = 0.55, negative predictive value = 0.78 and report-to-records ratio = 1.51. The variance in the reported interval increased proportionally with the registered interval, and women tended to underestimate the interval (telescoping). Age and registered number of years since last Pap smear had the strongest influence on ever/never and time interval validity, respectively.

Estimated screening rates, based on self-reporting without organized screening, are biased. Telescoping leads to increased risk for developing invasive disease, because women will postpone their next Pap smear.

Between 2002 and 2005, 1514 men aged 50–69 years were identified with prostate cancer following community-based PSA testing as part of the ProtecT study. In the same period, 2021 men aged 50–69 years with clinically diagnosed prostate cancer were registered at a population-based cancer registry in the East of England. Using logistic regression analysis and controlling for age, the odds ratio (OR) for advanced stage (TNM stage T3 and above) prostate cancer among the PSA-detected group was compared with the clinically diagnosed tumours. The evidence that stage shift differs by Gleason score was assessed using the likelihood ratio test for interaction.

Advanced stage disease among the PSA-detected cancers was less common than among the clinically detected cancers (OR = 0.47, 95% CI 0.39–0.56). PSA-detected tumours had a substantial shift to earlier-stage disease where the Gleason score was <7 (OR = 0.52; 95% CI 0.36–0.77, P < 0.001) but showed no such shift where the Gleason score was 7 or more (OR = 0.84; 95% CI 0.66–1.07, P = 0.1). There was evidence of interaction between detection mode and Gleason score (P = 0.03).

The observed stage shift could be partially explained by length bias or overdiagnosis. These findings may have implications on understanding pathways of prostate cancer progression and on identifying potential targets for screening, pending further investigation of complexities of associations between PSA testing, Gleason score, and stage.

North Thames region of England (including large parts of inner London).

Maternally acquired rubella IgG antibody levels were measured in 18882 newborn screening blood spot samples. Latent class regression finite mixture models were used to classify samples as seronegative to rubella. Data on maternal country of birth were available through linkage to birth registration data.

An estimated 2.7% (95% CI 2.4%–3.0%) of newly delivered women in North Thames were found to be seronegative. Mothers born abroad, particularly in Sub-Saharan Africa and South Asia, were more likely to be seronegative than UK-born mothers, with adjusted odds ratios of 4.2 (95% CI 3.1–5.6) and 5.0 (3.8–6.5), respectively. Mothers under 20 years were more likely to be seronegative than those aged 30 to 34.

Our findings highlight the need for vaccination to be targeted specifically at migrant women and their families to ensure that they are protected from rubella in pregnancy and its serious consequences.

In 256 primarily diagnosed CH patients identified through the neonatal screening programme from May 2002 to February 2005, treatment was discontinued for 4 weeks and T4 and thyroid stimulating hormone (TSH) were measured. Permanent or transient CH was determined from the results of the thyroid function tests and the radiologic findings. Patients with TSH levels >6 (mIU/l) were diagnosed with permanent CH.

Results were available from 204 patients, of whom 122 patients were diagnosed with permanent CH (59.8%) (prevalence 1:748 births), and 82 with transient hypothyroidism (prevalence 1:1114). Permanent CH was associated with higher initial TSH levels than transient hypothyroidism (P < 0.05). The most common aetiology of CH was dyshormonogenesis.

The rates of both permanent and transient CH in our study were higher than the comparable worldwide rates. The transient group had low T4 levels, suggesting that iodine contamination should be investigated. The aetiology of CH was also different from that recorded in many other studies.

The study sample consisted of all infants born at a single academic paediatric hospital between February 1998 and February 2002.

There were 16,007 infants screened using ALGO automated auditory brainstem response. Eighteen of the infants who failed the screen in one ear but passed in the other ear were found to have permanent hearing loss, and had their subsequent clinical course and audiologic management analysed. The final audiologic outcome after four years in both the pass and fail ear were examined.

One group of unilateral referrals (n = 6) had obvious anatomic reasons for the ear failing the screen (canal atresia/stenosis). There were five patients in which the ear that passed the screen was later found on more extensive audiologic evaluation to have significant hearing loss. Review of recent literature was also completed to examine the methods by which unilateral screening referrals are commonly reported and whether or not this affected follow-up diagnostic evaluation.

Infants who pass one ear and refer one ear on neonatal hearing screening still need to have thorough and prompt evaluations. In many cases, the ear that passed can be found to have significant hearing loss.

We reviewed the clinical database of an ED HIV screening programme at a large, urban, teaching hospital in the United States from 2003–2007. Data were analyzed descriptively. The main outcome measure was the rate of positive test results computed with either the visit or the patient as the unit of analysis.

HIV testing was provided at 9629 visits, representing 8450 unique patients. For patient-level analysis, the proportion of patients found to be positive was 0.91%. For visit-level analysis, the proportion of tests with positive results was 0.83%. Of the 910 patients with repeat testing, 7 (0.77%) were identified as positive at a repeat test. The median time between tests was 383 days (range 1–1742).

Results changed little regardless of whether unique patients or unique visits were used as the unit of analysis. Any differences in positive rates were mitigated by the contribution of repeat testing to the identification of newly infected patients. Given these findings, and the difficulty of tracking repeat testing over time, visit-level analysis are appropriate for comparing programme outcomes when detailed modeling of epidemiology, cost, and/or outcomes is not required.

We performed a cross-sectional study of 327 first-degree relatives of hospitalized patients aged higher than 40 years, divided into Group A (151 relatives of colorectal cancer patients) and Group B (176 relatives of non-cancer patients) at the University Hospital of the Canary Islands, Spain. All were personally briefed by a surgeon, aided by a colorectal cancer pamphlet, and encouraged to accept screening colonoscopy with sedation.

Willingness to undergo colonoscopy screening was greater in Group A (66.9%) than in Group B (29.0%); (odds ratio: 11.1; 95% confidence interval = 4.27 to 29.14; P < 0.001). Pre-briefing awareness of screening colonoscopy was also significantly higher in Group A (76.8% vs. 33.5%; P < 0.001), the main source of information being a close relative with colorectal cancer.

Being a close relative of a colorectal cancer patient is positively related with willingness to undergo colonoscopy screening in this study. This cross-sectional study outlines a strategy for increasing the level of willingness to undergo colorectal cancer screening in a group of people at risk.

Since 1989, women aged 40–74 years (n = 55,000) have been invited to biennial screening by the NMSP, Norrbotten county, Sweden.

Data on 1047 invasive breast cancers from six screening rounds of the NMSP (1989–2002) were collected. We estimated the invasive interval cancer rates, rate ratios and the episode sensitivity using the detection and incidence methods. A linear Poisson-model was used to analyse association between interval cancer incidence and sensitivity.

768 screen-detected and 279 interval cancer cases were identified. The rate ratio of interval cancer decreased with age. The 50–59 year age group showed the highest rate ratio (RR = 0.52, 95% CI 0.41–0.65) and the 70–74 year age group the lowest (RR = 0.23, 95% CI 0.15–0.36). The rate ratios for the early (0–12 months) and late (13–24 months) interval cancers were similar (RR = 0.18, 95% CI 0.15–0.22 and 0.20, 95% CI 0.17–0.24). There was a significantly lower interval cancer incidence in the prevalence round as compared with the incidence rounds. According to the detection method the episode sensitivity increased with age from 57% in the age group 40–49 years to 84% in the age group 70–74 years. The corresponding figures for the incidence method were 50% and 77%, respectively.

Our study showed an interval cancer incidence of 38% and the episode sensitivity of 62–73%, depending on the method of calculation. Our results are of clinically acceptable level and concert with the reference values of the European guidelines.

Projections of incidence and mortality of colorectal cancer in England, and the policy that has been adopted for screening in England (biennial at ages 60–69 from 2007, then 60–74 in 2010).

The results are based on the output of a simulation model that has been used to examine cost-effectiveness of screening policy options, with two scenarios regarding compliance with screening; both assume that 20% of the population will never attend for screening, but attendance of those who do is modelled either as a random 60% or 80%, at each screening round.

The decrease in mortality rates expected 20 years after introducing screening is 13–17% in men and 12–15% in women (depending on the attendance levels). The model predicts an initial rise in incidence, followed (after six to seven years) by a fall, so that there is little net change in the number of cases detected over a 20-year period.

Percentage changes in mortality seem modest, but the projected saving in terms of numbers of lives is not negligible – 1800–2400 per year by 2025 in England (equivalent numbers are 2200–2700 in all over the UK). Newer screening modalities may improve on these projected results.

Florence district residents aged 50–70 were invited to undergo one-time I-FOBT every two years. Full colonoscopy was recommended for FOBT-positive subjects. Direct cost analysis was carried out separately for the first and repeat screening. All relevant resources consumed by the programme were calculated.

Among 25,428 or 62,369 subjects invited to the first or repeat screening, respectively, the corresponding participation rate was 47.8% or 52.3%, and the positivity rate was 4.4% and 3.3%. Corresponding detection rates and positive predictive values for cancer and advanced adenoma were 11.3% or 8.9% and 32.4% or 32.8%, respectively. The assessment phase accounted for the major cost, as compared with recruitment and screening. All cost indicators were slightly higher in the first screening compared with repeat screening. Cost per cancer and advanced adenoma detected was similar in the first or repeat screening. A higher than observed participation rate would have substantially reduced screening cost.

Analysis of I-FOBT-organized population-based screening cost demonstrates lower cost at repeat compared with first screening and provides reference for decision-making in screening implementation.

Data were obtained for women participating in the Screening Mammography Programme of British Columbia (SMPBC) for 1988–2005. The SMPBC changed its policy for women aged 50–79 years from annual to biennial mammography in 1997, but retained an annual recommendation for women aged 40–49 years.

Breast cancer outcomes were compared for women participating in the programme before and after 1997 for two groups: ages 40–49 and 50–79 years.

There were data on 658,151 women. Comparing pre-1997 and post-1997, the median interscreen interval increased by 11.1 months in women 50–79 but by only 0.3 months in women aged 40–49. Excluding those detected at initial screen, 6291 breast cancers were identified. Comparing pre-1997 and post-1997: the relative rates (RR) of screen detected cancer increased in women aged 40–49 (RR = 1.32) and the rate of invasive cancers ≥20 mm at diagnosis decreased (RR = 0.83); the rate of cancers with axillary node involvement increased in women aged 50–79 (RR = 1.23). Cancer survival improved after 1997 for women diagnosed at ages 40–49 (hazard ratio = 0.62), but was unchanged for women aged 50–79. Breast cancer mortality rates did not change between the periods in either age group.

The proximal cancer outcomes considered (staging and survival) improved in women aged 40–49 but this was offset in women aged 50–79 associated with the change in screen frequency. These changes did not result in alterations in breast cancer mortality rates in either age group.

Systematic review of the literature and meta-analysis of prevalence and proportion data. The review was confined to studies reporting on NECs in smears from postmenopausal women or women aged 40+.

A total of 22 relevant primary studies were identified from 1970 to 2007. The overall summary estimate for the prevalence of NECs in smears from postmenopausal women or women aged 40+ in all screening smears was 0.4% (95% CI 0.2–0.7%); this was 0.3% (95% CI 0.1–0.5%) and 0.9% (95% CI 0.5–1.4%) for conventional and LBC smears, respectively; P = 0.003 for difference. The overall estimate for the proportion of NECs associated with significant endometrial pathology was 7% (95% CI 4–10%); this was 11% (95% CI 8–14%) and 2% (95% CI 1–2%) for conventional and LBC smears, respectively; P < 0.001 for difference. In women with significant endometrial pathology, the presence of NECs in followed-up women was associated with abnormal uterine bleeding in 79% (95% CI 68–87%) of cases.

Compared with conventional cytology, LBC may be associated with a higher prevalence of NECs but these are less likely to be associated with endometrial pathology. This finding might be explained by more consistent use of sampling instruments for LBC with better access to the endocervical canal or alternatively by changes over time, broadly coincident with the introduction of LBC, in the population in which NECs are reported. In followed-up women with NECs, most endometrial pathology is accompanied by symptoms, implying that a relatively smaller number of additional cases are identified through follow-up of asymptomatic women.

Based on the autofluorescence of protoporphyrin, we used an automatic image acquisition platform for examining fluorocytes in peripheral blood with minimal sample preparation. The image acquisition is easy-to-use under automated operations of excitation, focusing, detection and data analysis. Quality image and semi-quantitative fluorescence measurement of fluorocytes can be generated in a single step. For high-throughput analysis, the platform can image more than 200 96-well micro-plates, i.e. 19200 samples, in approximately 10 hours. Importantly, the reagent cost of analysis is negligible.

In this pilot study, three EPP patients were diagnosed and 4000 normal individuals were screened for EPP by this method. Our results showed that the method can distinguish the overt case and asymptomatic carriers. It gives reliable evidence for rapid EPP screening.

This automated imaging system provides multiple advantages that improve the traditional fresh blood film method as a more effective diagnostic tool and facilitates population screening for EPP. As fluorocytes are present in the umbilical cord blood of EPP patients, this high-throughput method can be potentially used for newborn screening of EPP.

The difference in the median multiple of the median (MoM) values in smokers compared to non-smokers was determined for NT, PAPP-A and free β-hCG in 12,517 unaffected pregnancies that had routine first trimester Combined test screening. These results were then included in a meta-analysis of published studies and the effect of adjusting for smoking on screening performance of the Combined test was estimated.

The results using the routine screening data were similar to the summary estimates from the meta-analysis of all studies. The results from the meta-analysis were; median MoM in smokers compared to non-smokers: 1.06 NT (95% confidence interval 1.03 to 1.10), 0.81 PAPP-A (0.80 to 0.83) and 0.94 free β-hCG (0.89 to 0.99). The effect of adjusting for smoking on the Combined test is small, with an estimated less than half percentage point increase in the detection rate (the proportion of affected pregnancies with a positive result) for a 3% false-positive rate (the proportion of unaffected pregnancies with a positive result) and less than 0.2 percentage point decrease in the false-positive rate for an 85% detection rate.

Adjusting first trimester screening markers for smoking has a minimal favourable effect on screening performance, but it is simple to implement and this paper provides the adjustment factors needed if a decision is made to make such an adjustment.