Antenatal screening for Down's syndrome relies on the use of multiple markers in combination. Markers that are highly correlated can cause statistical instability. We used the maximum variance inflation factor (VIFmax) to determine whether a screening test using multiple markers was robust to imprecision in the estimation of the marker distribution parameters.
The VIFmax for a specified screening test was calculated from the correlations between markers in Down's syndrome pregnancies for six tests: integrated and serum integrated tests without repeat measurements, both tests with repeat measurements across trimesters analysed in the standard way, and both tests with repeat measurements analysed as cross-trimester (CT) marker ratios. The screening performance of each test using published parameter values, in terms of the false-negative rates for a 3% false-positive rate (FN3), were calculated for simulated populations with medians 0.2 standard deviations (SD) higher or lower than the published values (to reflect imprecision in parameter estimation) for pregnancy-associated plasma protein A and unconjugated oestriol in affected pregnancies. For each test, the VIFmax value was compared with the coefficient of variation of the FN3 (FN3 CV). An independent set of 27 Down's syndrome pregnancies was used to determine how many had meaningless low risks (<1 in 10,000) with each test.
Tests with VIFmax values greater than 5 had FN3CV values over 50%, but those with VIFmax values less than 5 had FN3 CV values less than 21%. The numbers of Down's syndrome pregnancies with meaningless low risk estimates in the independent set were 18 (64%) in tests with VIFmax values ≥5 and none for those with values <5.
VIFmax values of 5 or more suggest instability. The tests using CT marker ratios were stable (VIFmax < 3), but the tests using repeat measurements in the standard manner were not (VIFmax > 5).
To determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Isfahan, the central state of Iran.
From February to March 2006, a total of 2501 samples were screened for the quantitative measurement of G6PD activity by enzymatic colorimetric assay by a commercial kit (GAMMA, Belgium). The neonates were referred from 17 delivery units to the Isfahan neonatal screening center at 3–7 days after birth. Any neonate with a value < 6.4 U/gHb was considered G6PD deficient.
Of the 2501 newborns (1307 males, 1194 females) screened, 79 neonates were found to have G6PD deficiency (67 males, 12 females). The overall incidence of G6PD deficiency was 3.2%. Frequency in male population was 5.1 % (67 out of 1307 male neonates) and in female population was 1% (12 out of 1194 female neonates).The female:male ratio was 1:5.5 (P = 0.0001). The mean enzyme activity in deficient patients was 3.22 ± 1.8 U/gHb (male deficient group; 3.17 ± 1.74 U/gHb, female deficient group; 3.49 ± 2.17 U/gHb, P = 0.58).
Routine neonatal screening in Isfahan, Iran with a relatively high prevalence of G6PD deficiency is justified and meets the World Health Organization recommendation.
To evaluate the screening performance of 6/6 and 6/12 vision cut-offs with an illiterate E-chart implemented by a public health nurse to test children for ocular abnormalities and uncorrected refractive error. The gold standard diagnosis is an eye examination performed by an ophthalmologist.
A cross-sectional population-based study was conducted among 2113 students' ages 6–7 and 13–14 years old in 70 Northern District Israeli schools.
Students were tested by nurses and ophthalmologists. A nurse examination was carried out using the illiterate E-chart for vision measurement. The medical examination included vision history, clinical eye examination, vision and retinoscopy testing. The Physician's evaluation of whether students needed a referral for diagnostic procedures, treatment and/or follow-up was recorded. Screening test's performance was determined using ophthalmologist's decision regarding referral as the gold standard. Detection rate (DR), false-positive rate (FPR), odds affected positive result (OAPR), positive predictive value (PPV) and negative predictive value (NPV) were estimated overall and by students' demographic characteristics.
For vision >6/6 cut-off in at least one eye (eyes tested separately): DR – 71.9% (95% CI 65.8–78.7%), FPR – 22.8% (95% CI 17.9–28.9%), OAPR – 0.98:1 (95% CI 0.84:1–1.15:1), PPV – 52.7% (95% CI 45.4–61.2%), NPV – 90.9% (95% CI 88.7–93.1%). For 6/12 vision cut-off, namely vision 6/12 or worse in both eyes (tested separately): DR – 58.6 (95% CI 51.8–66.4%), FPR – 15.2% (95% CI 10.9–21.1%), OAPR – 1.13:1 (95% CI 0.94:1–1.35:1), PPV – 61.1% (95% CI 52.9–70.6%), NPV – 87.6% (95% CI 84.9–90.4%).
Vision-screening test performance measures are mild. It is suggested to change vision cut-off level that denotes vision abnormality from current policy of vision not equal 6/6 in both eyes (tested separately) to vision 6/12 or worse in both eyes (tested separately). This change will result in reduction of FPR from 22% to 15%, concomitant with an increase in false-negative rate from 28% to 41%. Students may be equally screened by either a senior or a less experienced nurse.
To analyse the relationship between the false-positive/false-negative predictive value (FPPV/FNPV) of the HIV-antibody (HIV-Ab) test and prevalence in different Chinese population groups.
HIV prevalence among different population groups was obtained by a screening survey of blood donors and the national HIV/AIDS surveillance programme in China. Given the sensitivity and specificity of a test kit and the prevalence of HIV infection, the estimated values of FPPV/FNPV were calculated using Bayes' formula. The actual value of FPPV of blood donors was obtained by screening 1,195,286 blood donors.
This study indicates that the FPPV of HIV-Ab enzyme-linked immunosorbent assay (ELISA) assays varies widely in different Chinese populations: about 99.5% in the blood donor population, but only 3.2% in the injecting-drug users in high-risk areas. In 1,195,286 sera specimens from the blood donors, 2439 specimens were HIV-Ab positive by third ELISA, and 11 HIV cases were confirmed by Western blot. The HIV prevalence of the blood donor population in this survey was 0.0009% (11/1,195,286), but the HIV-Ab positive rate of third ELISA is 0.2% (2439/1,195,286) and 222 times higher than the prevalence.
Evaluation of HIV prevalence through the HIV-Ab positive rate by third ELISA will significantly overestimate the true prevalence in a low-prevalence population. Individual HIV-infection status should be taken into consideration when analysing the results of HIV-Ab tests in a population with low infection.
Previous studies have not assessed whether evidence-based information about the outcomes of colorectal cancer screening increases informed choice among people from a range of socioeconomic backgrounds nor have they assessed whether this can be administered away from a health-care provider.
Randomized controlled trial in six primary care locations. Three hundred and fourteen people aged 50–74 years received a self-administered decision aid (DA) booklet about outcomes of biennial faecal occult blood testing (FOBT) screening or government consumer guidelines (G).
Significantly more DA recipients (20.9%) were ‘informed’ compared with G recipients (5.8%) (P = 0.0001, OR 4.32; 95% CI 2.49 to 7.52); the DA did not affect values clarity (61.9% clear after DA versus 59.1% after G) nor screening decisions overall (87.3% would screen after DA versus 90.5% after G). Test uptake at one month was uniformly low (5.2% DA versus 6.6% G); mostly due to being ‘too busy’. DA recipients were more likely to make decisions ‘integrating’ knowledge with values (10.4% DA versus 1.5% G). Decisions not to screen were equally uncommon in both groups but more likely to be uninformed in G (P = 0.03). More DA recipients from all education levels were ‘informed’ (P = 0.02), particularly in lower education (50.0% DA versus 17.8% G) and university-educated groups (79.4% DA versus 32.1% G).
Detailed absolute risk and benefit information about FOBT screening can be effectively used at home by people to increase informed choice. The DA was effective in people with lower education levels.
Unique Protocol ID 211705 ClinicalTrials.gov ID NCT 00148226.
Mean sojourn time (MST) and screening test sensitivity (STS), is usually estimated by Markov models using incidence data from the first screening round and the interval between screening examinations. However, several screening programmes do not have full registration of cancers submerging after screening, and increased use of opportunistic screening over time can raise questions regarding the quality of interval cancer registration.
Based on the earlier used Markov model, formulas for expected number of cases given time since former screening activity was developed. Using questionnaire data for 336,533 women in the Norwegian Breast Cancer Screening Programme (NBCSP), mean square regression estimates of MST and STS were calculated.
In contrast to the previously used method, the new approach gave satisfactory model fit. MST was estimated to 5.6 years for women aged 50–59 years, and 6.9 years for women aged 60–69 years, and STS was estimated to 55% and 60%, respectively. Attempts to add separate parameters for breast cancer incidence without screening, or previous STS, resulted in wide confidence intervals if estimated separately, and non-identifiably if combined.
Previously published results of long MST and low screen test sensitivity were confirmed with the new approach. Questionnaire data on time since previous screening can be used to estimate MST and STS, but the approach is sensitive to relaxing the assumptions regarding the expected breast cancer incidence without screening and constant STS over time.
To examine sociodemographic predictors of self-reported screening attendance, intention to accept human papillomavirus (HPV) testing and willingness to accept vaccination for a daughter under 16.
Home-based, computer-assisted interviews with a population representative sample of British women.
Participants were selected using random probability sampling of the Postcode Address File, 994 women aged 25–64 were included in these analyses. Women reported their attendance at cervical screening and intention to accept an HPV test. A subsample of those with a daughter under 16 years (n = 296) reported their willingness to accept HPV vaccination for their daughter.
Screening attendance was associated with education level (odds ratio [OR] = 1.66, confidence interval [95% CI]: 1.07–2.56) and being married (OR = 2.04, 95% CI: 1.37–3.03). Acceptance of HPV testing was predicted by regular attendance for cervical screening (OR = 1.58, 95% CI: 1.03–2.42) and being from a white background (OR = 2.20, 95% CI: 1.18–4.13). Daughter's age was the only predictor of HPV vaccine acceptance, with mothers whose youngest daughter was 13–16 years old being the most likely to accept vaccination (OR = 2.91, 95% CI: 1.27–6.65).
In contrast to screening attendance, ethnicity plays an important role in HPV testing. Specific cultural barriers should be identified and addressed to ensure ethnic disparities in testing are limited. While marital status is associated with screening attendance, HPV testing could overcome this bias. Sociodemographic variables seem to play a limited role in HPV vaccine acceptance among mothers making vaccine decisions for their daughters, but as with other studies, age of daughter is important. The scientific reasons for vaccinating at 12–13 years should be emphasized in HPV information.
To assess whether human papillomavirus (HPV) testing is a safe enough approach to warrant extension of the screening intervals of baseline Papanicolaou (Pap)–/HPV– women in low-income settings.
Of the >1000 women prospectively followed up as part of the Latin American Screening (LAMS) Study in São Paulo, Campinas, Porto Alegre) and Buenos Aires, 470 women with both baseline cytology and Hybrid Capture 2 (HC2) results available were included in this analysis. These baseline Pap-negative and HC2– or HC2+ women were controlled at six-month intervals with colposcopy, HC2 and Pap to assess the cumulative risk of incident Pap smear abnormalities and their predictive factors.
Of the 470 women, 324 (68.9%) were high-risk HPV (hrHPV) positive and 146 (31.1%) were negative. Having two or more lifetime sex partners (odds ratio [OR] = 2.63; 95% CI 1.70–3.51) and women using hormonal contraception (OR = 2.21; 95% CI 1.40–3.51) were at increased risk for baseline hrHPV infection. Baseline hrHPV+ women had a significantly increased risk of incident abnormal Pap smears during the follow-up. Survival curves deviate from each other starting at month 24 onwards, when hrHPV+ women start rapidly accumulating incident Pap smear abnormalities, including atypical squamous cells (ASC) or worse (log-rank; P < 0.001), low-grade squamous intraepithelial lesions (LSIL) or worse (P < 0.001) and high-grade squamous intraepithelial lesions (HSIL) (P = 0.03). Among the baseline hrHPV– women, the acquisition of incident hrHPV during the follow-up period significantly increased the risk of incident cytological abnormalities (hazard ratio = 3.5; 95% CI 1.1–11.7).
These data implicate that HPV testing for hrHPV types might be a safe enough approach to warrant extension of the screening interval of hrHPV–/Pap–women even in low-resource settings. Although some women will inevitably contract hrHPV, the process to develop HSIL will be long enough to enable their detection at the next screening round (e.g. after three years).