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Objective: To compare the NHS Health Check Programme with the Polypill Prevention Programme in the primary prevention of heart attacks and strokes. Design: Use of published data and methodology to produce flow charts of the two programmes to determine screening performance and heart attacks and strokes prevented. Setting: The UK population. Intervention: The NHS Health Check Programme using a QRISK score on people aged 40–74 to select those eligible for a statin is compared with the Polypill Prevention Programme in people aged 50 or more to select people for a combination of a statin and three low-dose blood pressure lowering agents. In both programmes, people had no history of heart attack or stroke. Main outcome measures: In 1000 people, the number of heart attacks and strokes prevented in the two programmes. Results: In the hypothetical perfect situation with 100% uptake and adherence to the screening protocol, in every 1000 persons, the NHS Health Check would prevent 287 cases of a heart attack or stroke in individuals who would gain on average about 4 years of life without a heart attack or stroke amounting to 1148 years in total, the precise gain depending on the extent of treatment for those with raised blood pressure, and 136 would be prescribed statins with no benefit. The corresponding figures for the Polypill Prevention Programme are 316 individuals who would, on average, gain 8 years of life without a heart attack or stroke, amounting to 2528 years in total, and 260 prescribed the polypill with no benefit. Based on published estimates of uptake and adherence in the NHS Health Check Programme, in practice only 24 cases per 1000 are currently benefitting instead of 287, amounting to 96 years gained without a heart attack or stroke. Conclusions: The Polypill Prevention Programme is by design simpler with the potential of preventing many more heart attacks and strokes than the NHS Health Check Programme. [ABSTRACT FROM AUTHOR]

Objectives: Human papillomavirus (HPV) primary testing for cervical screening is being implemented around the world. We explored HPV awareness, and knowledge about primary screening in Great Britain (England, Scotland and Wales), where it has been in place for several years, ahead of extended screening intervals being implemented in England. Setting/Methods: Women aged 18–70 (n = 1995) were recruited by YouGov from their online panel in August 2022. The weighted sample (n = 1930) was population-representative by age, region, education and social grade. We measured HPV awareness, knowledge (excluding those unaware of HPV) using eight true/false items, and understanding of the role of HPV testing in cervical screening. Results: Overall, 77.6% (1499/1930) of women were aware of HPV. When asked to identify the statement describing how cervical screening works, only 12.2% (236/1930) correctly selected the statement reflecting HPV primary screening (13.5% (194/1436) in screening-eligible women). Excluding those unaware of HPV, most participants had heard about the virus in the context of cervical screening (981/1596; 61.5%) or HPV vaccination (1079/1596; 67.6%). Mean knowledge score was 3.7 out of 8 (SD = 2.2) in this group. Most knew that an HPV-positive result does not mean a woman will definitely develop cervical cancer (1091/1499; 72.8%) but far fewer were aware of the long timeline for HPV to develop into cervical cancer (280/1499; 18.7%). Conclusions: Only three-quarters of women in Britain are aware of HPV, and knowledge of primary screening is very low, even among screening-age women. This points to continued need for awareness-raising campaigns to ensure informed choice about screening and mitigate public concern when screening intervals are extended. [ABSTRACT FROM AUTHOR]

Objectives: As one of the most common hereditary diseases, thalassemia affects a large number of people in China. The aim of this study was to investigate the feasibility of a method based on next-generation sequencing (NGS) for screening of thalassemia carriers among high school students in the Shaoguan area. Materials and Methods: The NGS-based method was performed using 25,910 high school students recruited from 38 schools. The screening yield was systematically analyzed. Before screening, a lecture on how the disease is inherited, the symptoms of thalassemia, and how to prevent it was given to 28,780 students. Results: Implying successful delivery of information on the disease, 90.03% (25,910 of 28,780) of the students agreed to join this program for thalassemia screening. A thalassemia carrier rate of 15.99% (4144 of 25,910) was found. Also, 69 rare genotypes (28 of α-thalassemia and 41 of β-thalassemia) and 9 novel variants were identified. Conclusions: This NGS-based method provided a feasible platform for high school population thalassemia screening. Combined with a clinical follow-up strategy, it could help eventually to prevent the births of affected children. [ABSTRACT FROM AUTHOR]

Objectives: Hemoglobinopathies are the commonest inherited blood disorders and form a serious burden worldwide, affecting communities, patient quality of life and healthcare resources. The Kingdom of Bahrain has issued a law obligating couples to undergo premarital screening to detect those at risk of having children affected with these disorders. The aim of this study was to analyze the marital decisions of couples at risk for hemoglobinopathies and follow up the outcomes. Methods: A retrospective study was conducted on couples at risk for hemoglobinopathies identified during the premarital screening program at local health centers in the Kingdom of Bahrain and referred to the genetics department in the Salmaniya Medical Complex for genetic counselling in 2018–2020. Results: A total of 189 couples were found to be at risk for hemoglobinopathies, of whom 159 completed the survey. Of these, 107 (67%) decided to proceed with their marriage and 26 couples achieved pregnancy. Out of 24 at-risk pregnancies with known outcome, 83.3% were spontaneous whereas only 16.7% underwent in-vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD). Eight out of 20 infants born to couples after spontaneous conception were affected. A positive attitude toward IVF with PGD was held by 60% of at-risk couples. Conclusions: Despite undergoing premarital screening and genetic counselling, a large percentage of at-risk couples proceeded with their marriage. Most of them justified their decision due to the availability of advanced methods that aid in the prevention of having an affected child. However, the cost of such intervention was a major barrier for the majority of couples. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to develop a risk-scoring model in the Scottish Bowel Screening Programme incorporating faecal haemoglobin concentration with other risk factors for colorectal cancer. Methods: Data were collected for all individuals invited to participate in the Scottish Bowel Screening Programme between November 2017 and March 2018 including faecal haemoglobin concentration, age, sex, National Health Service Board, socioeconomic status, and screening history. Linkage with The Scottish Cancer Registry identified all screening participants diagnosed with colorectal cancer. Logistic regression was performed to identify which factors demonstrated significant association with colorectal cancer and could be used in the development of a risk-scoring model. Results: Of 232,076 screening participants, 427 had colorectal cancer: 286 diagnosed following a screening colonoscopy and 141 arising after a negative screening test result giving an interval cancer proportion of 33.0%. Only faecal haemoglobin concentration and age showed a statistically significant association with colorectal cancer. Interval cancer proportion increased with age and was higher in women (38.1%) than men (27.5%). If positivity in women were mirrored in men at each age quintile interval cancer proportion would still have remained higher in women (33.2%). Moreover, an additional 1201 colonoscopies would be required to detect 11 colorectal cancers. Conclusions: Development of a risk scoring model using early data from the Scottish Bowel Screening Programme was not feasible due to most variables showing insignificant association with colorectal cancer. Tailoring the faecal haemoglobin concentration threshold according to age could help to diminish some of the disparity in interval cancer proportion between women and men. Strategies to achieve sex equality using faecal haemoglobin concentration thresholds depend considerably on which variable is selected for equivalency and this requires further exploration. [ABSTRACT FROM AUTHOR]

Objective: A rolling circle amplification (RCA) based commercial methodology using cell-free (cf)DNA to screen for common trisomies became available in 2018. Relevant publications documented high detection but with a higher than expected 1% false positive rate. Preliminary evidence suggested assay variability was an issue. A multi-center collaboration was created to explore this further and examine whether subsequent manufacturer changes were effective. Methods: Three academic (four devices) and two commercial (two devices) laboratories provided run date, chromosome 21, 18, and 13 run-specific standard deviations, number of samples run, and reagent lot identifications. Temporal trends and between-site/device consistency were explored. Proportions of run standard deviations exceeding pre-specified caps of 0.4%, 0.4% and 0.6% were computed. Results: Overall, 661 RCA runs between April 2019 and July 30, 2022 tested 39,756 samples. In the first 24, subsequent 9, and final 7 months, proportions of capped chromosome 21 runs dropped from 39% to 22% to 6.0%; for chromosome 18, rates were 76%, 36%, and 4.0%. Few chromosome 13 runs were capped using the original 0.60%, but capping at 0.50%, rates were 28%, 16%, and 7.6%. Final rates occurred after reformulated reagents and imaging software modifications were fully implemented across all devices. Revised detection and false positive rates are estimated at 98.4% and 0.3%, respectively. After repeat testing, failure rates may be as low as 0.3%. Conclusion: Current RCA-based screening performance estimates are equivalent to those reported for other methods, but with a lower test failure rate after repeat testing. [ABSTRACT FROM AUTHOR]

Objectives: To systematically review the accuracy of artificial intelligence (AI)-based systems for grading of fundus images in diabetic retinopathy (DR) screening. Methods: We searched MEDLINE, EMBASE, the Cochrane Library and the ClinicalTrials.gov from 1st January 2000 to 27th August 2021. Accuracy studies published in English were included if they met the pre-specified inclusion criteria. Selection of studies for inclusion, data extraction and quality assessment were conducted by one author with a second reviewer independently screening and checking 20% of titles. Results were analysed narratively. Results: Forty-three studies evaluating 15 deep learning (DL) and 4 machine learning (ML) systems were included. Nine systems were evaluated in a single study each. Most studies were judged to be at high or unclear risk of bias in at least one QUADAS-2 domain. Sensitivity for referable DR and higher grades was ≥85% while specificity varied and was <80% for all ML systems and in 6/31 studies evaluating DL systems. Studies reported high accuracy for detection of ungradable images, but the latter were analysed and reported inconsistently. Seven studies reported that AI was more sensitive but less specific than human graders. Conclusions: AI-based systems are more sensitive than human graders and could be safe to use in clinical practice but have variable specificity. However, for many systems evidence is limited, at high risk of bias and may not generalise across settings. Therefore, pre-implementation assessment in the target clinical pathway is essential to obtain reliable and applicable accuracy estimates. [ABSTRACT FROM AUTHOR]

Objective: To describe the development and implementation of a population-based screening programme for sickle cell disease (SCD) implemented in 12 SCD-endemic and tribal-dominated primary/community health centres (PHCs/CHCs) across six districts of India. Setting: India reports a huge burden of SCD, especially among indigenous (tribal) communities. However, there is no state-led SCD programme in many places, and systematic screening is absent. This situation necessitates developing a model of population screening. Methods: This programme was meant to screen all people and was carried out in three tiers. The first tier was a symptomatic survey carried out by community health workers. Regular health workers then screened those referred by sickle cell solubility test at sub-health centres as the second tier. The third tier was confirmation by haemoglobin electrophoresis at PHCs/CHCs. Communities were mobilised and prepared to accept the screening. Capacity building of health facilities was ensured through training and supply of equipment and material. Results: Initial observation based on six months' data revealed that out of the 110,754 tribal population of 12 PHCs/CHCs, 8418 (7.6%) were identified in the symptomatic survey. Subsequently, 9416 people, including the above 8418, underwent the solubility test, and 2607 (27.7%) were found to be positive. Of these, 1978 (78.9%) underwent electrophoresis. About 64.2% were found to be positive for sickle haemoglobin (233 (18.4%) SCD and 1036 (81.6%) SCD trait). Conclusions: The study demonstrates the feasibility of establishing a population-based screening programme in the primary health care system. It is easy to implement in tribal habitations as part of the proposed national SCD/haemoglobinopathies programme. [ABSTRACT FROM AUTHOR]

Objective: To report the diagnostic challenges of newborn screening for abnormal haemoglobins. Setting: Cord blood samples from 13 hospitals in southwest Jamaica taken in 2008–2019. Methods: Blood spots, collected from the umbilical cord, were analysed by high pressure liquid chromatography (HPLC) to reveal phenotypes for HbSS and HbCC, but genotype confirmation may require parental studies or gene sequencing. Such cases that were successfully traced were analysed in this follow-up study. Results: HPLC screening of 121,306 samples detected HbAS in 11,846 (9.8%), HbAC in 4508 (3.7%) and other electrophoretic abnormalities in 1090 babies. Among 101 previously unconfirmed cases, 34/90 (38%) with HPLC evidence of a HbSS phenotype had other genotypes, and 7/11 (64%) with a HbCC phenotype had other genotypes. Syndromes from the interaction of β thalassaemia occurred in 112 babies (85 with HbS, 27 with HbC) and of genes for hereditary persistence of fetal haemoglobin (HPFH) in 18 (12 with HbS, 6 with HbC). Variants other than HbS and HbC occurred in 270 babies, 16 in combination with either HbS or HbC, and 254 as traits. Most variants are benign even when inherited with HbS, although HbO Arab, HbD Punjab, or Hb Lepore Washington, which occurred in 6 cases, may cause sickle cell disease. Conclusions: Genes for β thalassaemia and HPFH are common in western Jamaica and when associated with HbS may present diagnostic challenges in newborns, as HbF and HbA2 have not reached diagnostic levels. Family and DNA studies may be necessary for genotype confirmation. [ABSTRACT FROM AUTHOR]

Objective: Roll-out of population-based colorectal cancer (CRC) screening with faecal immunochemical test (FIT) is limited by availability of further investigations, particularly colonoscopy and examination of excised lesions. Our objective was to assess whether variation in number of faecal samples and threshold adjustment can optimise resource utilisation and CRC detection rate. Methods: Three different screening strategies were compared for the same FIT threshold using a quantitative FIT system: one FIT, positive when > 20 µg Hb/g faeces; two FIT, positive when either was > 20 µg Hb/g faeces; and two FIT, positive when the mean was > 20 µg Hb/g faeces. We calculated changes in the size of population the provider could invite to screening for an equal number of screening positive results, and CRC and adenoma detected. Results: In our setting, Region of Murcia, south of Spain (not fully rolled out screening programme), changing the usual strategy of two FIT, positive when either to positive when the mean was > 20 µg Hb/g faeces, would increase population invited by 37.81% with the same number of positive results (which would generate a CRC detection rate of 19.2%). In a fully rolled out programme, changing the strategy from one to two FIT (positive when the mean is > 20 µg Hb/g faeces), would increase CRC detection rate by 4.64% with an increase of only 13.34% in positive FIT. Conclusions: In a population-based CRC screening programme, smart use of number of FITs and positivity threshold can increase population invited and CRC detection without increasing the number of colonoscopies and pathological examinations needed. [ABSTRACT FROM AUTHOR]

Obesity levels and mortality from breast cancer are higher in more deprived areas of the UK, despite lower breast cancer incidence. Supplemental imaging for women with dense breasts has been proposed as a potential improvement to screening, but it is not clear how stratification by percentage mammographic density (%MD) would be reflected across socioeconomic groups. This study aims to clarify the associations between breast composition (dense and fatty tissue) and socioeconomic status in a multi-ethnic screening population.Demographic characteristics were collected for 62,913 participants in a UK breast screening programme (age, ethnicity, Index of Multiple Deprivation (IMD)). Automated mammographic measurements were derived: dense volume (DV), non-dense volume (NDV) and percent density (%MD). Correlations between deprivation and mammographic composition were examined before and after adjustment for age, ethnicity and NDV, using non-dense breast volume as a proxy for body mass index (BMI).There was negligible correlation between deprivation and DV (r = 0.017; P < 0.001 in all cases), but NDV increased with increasing deprivation (Pearson r = 0.101). Correlations were weaker in the Asian and Chinese ethnic groups. %MD decreased with deprivation (r = −0.094) and adjustment for ethnicity did not alter the association between %MD and IMD (relative change, most to least deprived quintile IMD: 1.18; 95% confidence interval: 1.16, 1.21).Deprivation-related differences in %MD in the screening population are largely explained by differences in breast fat volume (NDV) which reflects BMI. Women in more deprived areas, where obesity and breast cancer mortality rates are higher, have increased breast adiposity and may miss out on risk-adapted screening if stratification is based solely on %MD or BIRADS classification. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) algorithms have been retrospectively evaluated as replacement for one radiologist in screening mammography double-reading; however, methods for resolving discordance between radiologists and AI in the absence of ‘real-world’ arbitration may underestimate cancer detection rate (CDR) and recall. In 108,970 consecutive screens from a population screening program (BreastScreen WA, Western Australia), 20,120 were radiologist/AI discordant without real-world arbitration. Recall probabilities were randomly assigned for these screens in 1000 simulations. Recall thresholds for screen-detected and interval cancers (sensitivity) and no cancer (false-positive proportion, FPP) were varied to calculate mean CDR and recall rate for the entire cohort. Assuming 100% sensitivity, the maximum CDR was 7.30 per 1000 screens. To achieve >95% probability that the mean CDR exceeded the screening program CDR (6.97 per 1000), interval cancer sensitivities ≥63% (at 100% screen-detected sensitivity) and ≥91% (at 80% screen-detected sensitivity) were required. Mean recall rate was relatively constant across sensitivity assumptions, but varied by FPP. FPP > 6.5% resulted in recall rates that exceeded the program estimate (3.38%). CDR improvements depend on a majority of interval cancers being detected in radiologist/AI discordant screens. Such improvements are likely to increase recall, requiring careful monitoring where AI is deployed for screen-reading. [ABSTRACT FROM AUTHOR]

To quantify the resource use of revising breast cancer screening guidelines to include average-risk women aged 40–49 years across Canada from 2024 to 2043 using a validated microsimulation model.OncoSim-Breast microsimulation platform was used to simulate the entire Canadian population in 2015–2051.We compared resource use between current screening guidelines (biennial screening ages 50–74) and alternate screening scenarios, which included annual and biennial screening for ages 40–49 and ages 45–49, followed by biennial screening ages 50–74. We estimated absolute and relative differences in number of screens, abnormal screening recalls without cancer, total and negative biopsies, screen-detected cancers, stage of diagnosis, and breast cancer deaths averted.Compared with current guidelines in Canada, the most intensive screening scenario (annual screening ages 40–49) would result in 13.3% increases in the number of screens and abnormal screening recalls without cancer whereas the least intensive scenario (biennial screening ages 45–49) would result in a 3.4% increase in number of screens and 3.8% increase in number of abnormal screening recalls without cancer. More intensive screening would be associated with fewer stage II, III, and IV diagnoses, and more breast cancer deaths averted.Revising breast cancer screening in Canada to include average-risk women aged 40–49 would detect cancers earlier leading to fewer breast cancer deaths. To realize this potential clinical benefit, a considerable increase in screening resources would be required in terms of number of screens and screen follow-ups. Further economic analyses are required to fully understand cost and budget implications. [ABSTRACT FROM AUTHOR]

Cervical cancer incidence in Estonia ranks among the highest in Europe, but screening attendance has remained low. This randomized study aimed to evaluate the impact of opt-in and opt-out human papillomavirus (HPV) self-sampling options on participation in organized screening.A random sample of 25,591 women were drawn from the cervical cancer screening target population who were due to receive a reminder in autumn 2021 and thereafter randomly allocated to two equally sized intervention arms (opt-out and opt-in) receiving a choice between HPV self-sampling or clinician sampling. In the opt-out arm, a self-sampler was sent to home address by regular mail; the opt-in arm received an e-mail containing a link to order a self-sampler online. The remaining 30,102 women in the control group received a standard reminder for conventional screening. Participation by intervention arm, age and region of residence was calculated; a questionnaire was used to assess self-sampling user experience.A significant difference in participation was seen between opt-out (41.7%) (19.8% chose self-sampling and 21.9% clinician sampling), opt-in (34.1%) (7.9% self-sampling, 26.2% clinician sampling) and control group (29.0%, clinician sampling only). All age groups and regions in the intervention arms showed higher participation compared to the control group, but the size of the effect varied. Among self-sampling users, 99% agreed that the device was easy to use and only 3.5% preferred future testing at the clinic.Providing women with a choice between self-sampling and clinician sampling significantly increased participation in cervical cancer screening. Opt-in and opt-out options had a different effect across age groups, suggesting the need to adapt strategies. [ABSTRACT FROM AUTHOR]

This editorial discusses the use of flow-charting to improve the clarity of describing screening protocols in medical research. The author argues that the current practice of selecting a specific target group or eligible population for screening can lead to an overestimation of the effectiveness of the screening. Instead, the author suggests using a step-wise approach that considers the entire population and divides them into affected and unaffected groups. The article provides a hypothetical example to illustrate the difference in results between the target approach and the step-wise approach. The author concludes that the step-wise approach merits consideration in screening protocols. [Extracted from the article]

To assess performance endpoints of a combination of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) compared with FFDM only in breast cancer screening.This was a prospective population-based screening study, including eligible (50–69 years) women attending the Capital Region Mammography Screening Program in Denmark. All attending women were offered FFDM. A subgroup was consecutively allocated to a screening room with DBT. All FFDM and DBT underwent independent double reading, and all women were followed up for 2 years after screening date or until next screening date, whichever came first.6353 DBT + FFDM and 395 835 FFDM were included in the analysis and were undertaken in 196 267 women in the period from 1 November 2012 to 12 December 2018. Addition of DBT increased sensitivity: 89.9% (95% confidence interval (CI): 81.0–95.5) for DBT + FFDM and 70.1% (95% CI: 68.6–71.6) for FFDM only, p < 0.001. Specificity remained similar: 98.2% (95% CI: 97.9–98.5) for DBT + FFDM and 98.3% (95% CI: 98.2–98.3) for FFDM only, p = 0.9. Screen-detected cancer rate increased statistically significantly: 11.18/1000 for DBT + FFDM and 6.49/1000 for FFDM only, p < 0.001. False-positive rate was unchanged: 1.75% for DBT + FFDM and 1.73% for FFDM only, p = 0.9. Positive predictive value for recall was 39.0% (95% CI: 31.9–46.5) for DBT + FFDM and 27.3% (95% CI: 26.4–28.2), for FFDM only, p < 0.0005. The interval cancer rate decreased: 1.26/1000 for DBT + FFDM and 2.76/1000 for FFDM only, p = 0.02.DBT + FFDM yielded a statistically significant increase in cancer detection and program sensitivity. [ABSTRACT FROM AUTHOR]

Objectives: Previously, based on 6 months of follow-up, we showed that HPV self-sampling improved participation in cervical screening compared to a reminder letter for Pap testing for never- and under-screened women. Here, we report follow-up and related screening outcomes for women who participated in the initial self-sampling over two screening rounds. Setting: The randomised controlled trial was conducted in Australia. Methods: Never- and under-screened women were randomly allocated to the HPV self-sampling or the reminder for Pap test arm and followed at 6 and 36 months since the kits were first mailed. Results: The first round of HPV self-sampling kits were mailed from May–July 2014 to 12 572 women. After 36 months, 19% of never-screened and 9% of under-screened women returned a kit for HPV testing; 2.7% were HPV 16/18 and 5.8% non-16/18 HPV positive. Compliance with first round follow-up was 84% (95% CI: 77.1–89.5%). Non-compliant and cytology triage negative women were mailed another kit at 12 months. Compliance at 12-month follow-up was 59.3% (49.4 to 68.6%). Of 37 women with a 12-month repeat HPV, 70% were positive. Of women who tested negative for HPV in the first round (n = 1573), 25% attended regular screening in the next round and none had CIN2 + detected. The overall prevalence of CIN2 + was 8.5 per 1000 screened (4.8 to 13.9 per 1000). Conclusion: While self-sampling can successfully engage women, compliance with repeat testing may require monitoring. The clinician-supported self-collection pathway now in use in Australia will likely improve women's engagement with follow-up. [ABSTRACT FROM AUTHOR]

Objectives: Few studies in China have focused on the economic evaluation of newborn screening (NBS) for inherited metabolic disorders (IMDs) by tandem mass spectrometry (MS/MS). This study assesses the total costs, benefits, benefit–cost ratio (BCR), cost–utility ratio (CUR) and incremental cost–utility ratio (ICUR) of NBS using MS/MS compared to the non-screened group. Methods: The NBS outcomes of newborns who underwent MS/MS screening for IMDs in 2009–2018 were retrospectively reviewed. Records were extracted from a screening management system at the NBS Center of Zhejiang province. A cost–benefit analysis of screening was conducted, assessing screening costs for each subject, and direct and indirect treatment costs for IMDs detected by screening. The putative benefit of clinical outcomes related to early diagnosis was assumed to be improvement in quality of life and prolonged life expectancy in the screened group, as compared to the non-screened group. Results: Of the 3,040,815 newborns screened, 735 (2.86%) cases were diagnosed through gene sequence analysis. The most frequently occurring types of IMD were amino acid disorders (n = 276), then fatty acid oxidation disorders (n = 248), followed by organic acidaemias (n = 211). The difference in quality-adjusted life-years (QALYs) ranged from 0.78 to 15.4 in the screened group. The CUR was CNY¥ 116,183.89/QALY in the screened group and CNY¥ 3,078,823.65/QALY in the non-screened group. The ICUR was CNY¥ –768,428.76/QALY, and the BCR was 6.09. Conclusions: NBS using MS/MS can be considered cost-effective in China. The nationwide promotion of NBS using MS/MS deserves priority consideration and sufficient publicity. [ABSTRACT FROM AUTHOR]

Objectives: To determine the agreement between artificial intelligence software (AI) and radiographers in assessing breast positioning criteria for mammograms from standard digital mammography and digital breast tomosynthesis. Methods: Assessment of breast positioning was performed by AI and by four radiographers in pairs of two on 156 examinations of women screened in Bergen, April to September 2019, as part of BreastScreen Norway. Ten criteria were used; three for craniocaudal and seven for mediolateral-oblique view. The criteria evaluated the appearance of the nipple, breast rotation, pectoral muscle, inframammary fold and pectoral nipple line. Intraclass correlation and Cohen's kappa coefficient (κ) were used to investigate the correlation and agreement between the radiographer's assessments and AI. Results: The intraclass correlation for the pectoral nipple line between the radiographers and AI was >0.92. A substantial to almost perfect agreement (κ > 0.69) was observed between the radiographers and AI on the nipple in profile criterion. We observed a slight to moderate agreement for the other criteria (κ = 0.06–0.52) and generally a higher agreement between the two pairs of radiographers (mean κ = 0.70) than between the radiographers and AI (mean κ = 0.41). Conclusions: AI has great potential in evaluating breast position criteria in mammography by reducing subjectivity. However, varying agreement between radiographers and AI was observed. Standardized and evidence-based criteria for definitions, understandings and assessment methods are needed to reach optimal image quality in mammography. [ABSTRACT FROM AUTHOR]

The article presents the Great Britain National Screening Committee's position on child–parent screening for familial hypercholesterolaemia and the age results in a healthier diet at age 20 years and lower low-density lipoprotein cholesterol levels than children randomized to no dietary advice.

Objective: To classify interval colorectal cancers as false negatives or newly occurring cases in a biennial Fecal immunochemical test (FIT) screening program and by various interscreening intervals. Setting: Data from the Taiwanese biennial colorectal cancer screening program involving FIT from 2004 to 2014 were used to estimate the incidence rate of asymptomatic colorectal cancer and the rate of its subsequent progression to clinical mode. Methods: The sensitivity of detecting asymptomatic colorectal cancers excluding newly developed colorectal cancers was compared to the conventional estimate of sensitivity, the complementary FIT interval cancer rate as a percentage of the expected incidence rate ((1-I/E)%). The relative contribution of newly developed or false-negative cases to FIT interval colorectal cancers was estimated by age and interscreening intervals. Results: The Taiwanese biennial fecal immunochemical test screening program had a conventional sensitivity estimate of 70.2%. After newly developed colorectal cancers were separated from FIT interval cancers, the ability to detect asymptomatic colorectal cancers increased to 75.5%. FIT interval colorectal cancers from the biennial program mainly resulted from newly developed colorectal cancers (68.8%). The corresponding figures decreased to 61.1% for the annual program but increased to 74.7% for the triennial program. The preponderance of newly developed colorectal cancers among FIT interval cancers was more prominent in screenees aged 50–59 than in those aged 60–69. Conclusions: Newly developed colorectal cancers showed a predominance among the FIT interval colorectal cancers in particular in the younger population screened. It is desirable to identify high-risk individuals to offer them a short interscreening interval or advanced detection methods to reduce their odds of developing interval cancer. [ABSTRACT FROM AUTHOR]

Objective: Despite Australia's National Cervical Screening Program, Indigenous women have a disproportionately high burden of cervical cancer. We describe temporal and area-level patterns in prevalence of histologically conformed high-grade cervical abnormalities (hHGA) among cytologically screened women by Indigenous status. Methods: This was a population-based study of 2,132,925 women, aged 20–69, who underwent cervical screening between 2008 and 2017, in Queensland, Australia. Of these, 47,136 were identified as Indigenous from linked hospital records. Overall patterns in hHGA prevalence by Indigenous status were quantified using prevalence rate ratios (PrRR) from negative binomial models. Bayesian spatial models were used to obtain smoothed prevalence estimates of hHGA across 528 small areas compared to the state average. Results are presented as maps and graphs showing the associated uncertainty of the estimates. Results: Overall, screened Indigenous women had significantly higher hHGA prevalence than non-Indigenous women. However, the magnitude of the difference reduced over time (p < 0.001). Adjusted for age and area-level variables, Indigenous women had 36% higher hHGA prevalence (PrRR 1.36, 95% confidence interval [1.21–1.52]) than non-Indigenous women between 2013 and 2017. The overall effect of age decreased over time (p = 0.021). Although there was evidence of moderate spatial variation in 10-year prevalence estimates for both groups of women, the high levels of uncertainty for many estimates, particularly for Indigenous women, limited our ability to draw definitive conclusions about the spatial patterns. Conclusions: While the temporal reduction in Indigenous: non-Indigenous differential in hHGA prevalence is encouraging, further research into the key drivers of the continuing higher risk among Indigenous women is warranted. [ABSTRACT FROM AUTHOR]

Background: The incidence of inborn errors of metabolism varies widely across countries. Very few studies have analyzed the incidence of these disorders in Mainland China. We aimed to estimate the overall and disease-specific incidences of inborn errors of metabolism in Chinese newborns and investigate the geographical distribution of these disorders. Methods: A national cross-sectional survey was conducted to investigate newborn inborn errors of metabolism screening by tandem mass spectroscopy in Mainland China between 2016 and 2017. A total of 246 newborn screening centers were surveyed using a standardized questionnaire. We examined the cumulative and disease-specific incidences of inborn errors of metabolism in Mainland China as a whole and in different geographical locations. Results: Over 7 million newborns were screened and 2747 were diagnosed with inborn errors of metabolism, yielding an overall incidence of 38.69 per 100,000 births (95% confidence interval: 37.27–40.17). The most common disorders were amino acid disorders (17.14 per 100,000 births, 95% confidence interval: 16.21–18.13), followed by organic acid disorders (12.39 per 100,000 births, 95% confidence interval: 11.60–13.24) and fatty acid oxidation disorders (9.16 per 100,000 births, 95% confidence interval: 8.48–9.89). The overall and disease-specific incidence rates differed significantly across geographical locations (P < 0.001). Conclusions: The overall incidence of inborn errors of metabolism in Chinese newborns is relatively high. It is urgent to establish the recommended uniform screening panel for inborn errors of metabolism to guide the national and regional tandem mass spectroscopy newborn screening programs. [ABSTRACT FROM AUTHOR]

Objective: To identify factors associated with delayed adherence to follow-up in lung cancer screening. Methods: Utilizing a data warehouse and lung cancer screening registry, variables were collected from a referred sample of 3110 unique participants with follow-up CT during the study period (1 January 2016 to 17 October 2018). Adherence was defined as undergoing chest CT within 90 days and 30 days of the recommended time for follow-up and was determined using proportions and multiple variable logistic regression models across the American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS®) categories. Results: Of 1954 lung cancer screening participants (51.9% (1014/1954) males, 48.1% (940/1954) female; mean age 65.7 (range 45–87), smoking history median 40 pack-years, 60.2% and 44.5% did not follow-up within 30 and 90 days, respectively. Participants receiving Lung-RADS® category 1 or 2 presented later than those with Lung-RADS® category 3 at 90 days (coefficient −27.24, 95% CI −51.31, −3.16, p = 0.027). Participants with Lung-RADS® category 1 presented later than those with Lung-RADS® category 2 at both 90- and 30-days past due (OR 0.76 95% CI [0.59–0.97], p = 0.029 and OR 0.63 95% CI [0.48–0.83], p = 0.001, respectively). Conclusions: Adherence to follow-up was higher among participants receiving more suspicious Lung-RADS® results at index screening CT and among those who had undergone more non-lung cancer screening imaging examinations prior to index lung cancer screening CT. These observations may inform strategies aimed at prospectively identifying participants at risk for delayed or nonadherence to prevent potential morbidity and mortality from incident lung cancers. [ABSTRACT FROM AUTHOR]

Objective: To explore the factors associated with attendance and attendance pattern in BreastScreen Norway. Methods: We evaluated the number of invitations (n = 1,253,995) and attendances, 2015-2019, stratified by age, invitation method, screening unit and time of appointment. Attendance pattern was analysed for women invited 10 times (n = 47,979), 1996-2019. The association of education level, body mass index, physical activity and smoking status with attendance was analysed for a sub-sample of women (n = 37,930). Descriptive statistics were used to analyse attendance, and negative binomial regression was used to analyse the association between the total number of attendances and education level and lifestyle factors. Results: The attendance rate was 76.0%, 2015-2019. The rate was 78.0% for women aged >64 and 73.9% for those <55. We found a rate of 82.0% for women who received a digital invitation, while it was 73.7% for those invited by post. The rate was 78.1% for invitations in the late afternoon, 3-6 p.m., while later appointments reached a rate of 73.7%. Half of the women invited 10 times attended all times. The predicted total number of attendances was 9 out of 10 for the factors investigated. Conclusion: The highest attendance rates were shown for women aged >64, those who received digital invitations and those having appointments in late afternoon. The differences in predicted number of attendances between the investigated factors were minor. Overall, BreastScreen Norway has a high attendance rate. However, efforts aimed at increasing the attendance in specific groups should be considered. [ABSTRACT FROM AUTHOR]

Objective: To assess faecal immunochemical test sensitivity for cancer in a very large population-based cohort followed up for six rounds with biennial faecal immunochemical test repetition. Methods: This study is based on interval colorectal cancers diagnosed in a cohort of subjects aged 50-69 undergoing repeated faecal immunochemical test screening (six rounds) from 2002 to 2015. Test sensitivity was calculated using both the Proportional Interval Cancer Rate and the Interval Cancer Proportion method. Results: Among 441,647 faecal immunochemical tests (123,347 individuals), 150 interval colorectal cancers were detected after a negative faecal immunochemical test. Interval colorectal cancer incidence rate was 1.87 per 10,000 person-years (95%CI: 1.60-2.20), and it was higher during the second interval year (rate ratio: 1.78; 95%CI: 1.28-2.47), for proximal locations (rate ratio: 3.00; 95%CI: 1.92-4.68), and among 60-71 year old subjects (rate ratio: 2.37; 95%CI: 1.61-3.50). The Proportional Interval Cancer Rate was 13.1%, with an overall faecal immunochemical test sensitivity of 86.9% (95%CI: 84.7-89.0). Sensitivity was lowest at the first round (81.5%; 95%CI: 75.6-86.2), and increased to 91.9% (95%CI: 83.9-96.5) for subsequent rounds. Applying the Interval Cancer Proportion method, sensitivity was 83.9% (95%CI: 81.3-86.2), and it was highest at the first round (89.0%; 95%CI: 85.7-91.6), ranging between 73% and 83.1% at subsequent rounds. Conclusions: A faecal immunochemical test sensitivity for cancer higher than 80% resulted in a low incidence of interval colorectal cancers, representing an accurate estimate of one of the major limits of screening programmes. Due to intrinsic biases, the Proportional Interval Cancer Rate and the Interval Cancer Proportion methods generated different trends in faecal immunochemical test sensitivity by screening round. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the improved precision of nuchal translucency (NT) measurement used in antenatal screening for Down's syndrome observed over time as evidenced by a decrease in the multiple of the median (MoM) standard deviation requires a modification to the NT MoM truncation limits to maintain accurate risk estimation. Methods: Probability plots were derived from the measurements of NT MoM values used in a 2018 audit of 22,362 unaffected pregnancies. The plots were used to determine whether the NT MoM upper truncation limit should be lowered. Validation plots were used to assess the screening accuracy of Down's syndrome risk estimates calculated from observed NT MoM values in the 22,362 unaffected pregnancies and 69 Down's syndrome pregnancies for original and revised NT MoM truncation limits. Results: Probability plots indicated that with improved precision of NT measurements, there was deviation from a Gaussian distribution at less high MoM values than with less precise measurements. Validation plots showed that using the current NT MoM upper truncation limit of 2.5 MoM with improved precision NT measurements overestimates the Down's syndrome risk (median risk in highest risk category expressed as an odds was 53.3:1 and observed prevalence was 1:1.1). The large discrepancy was corrected by changing the NTupper truncation limit to 2.0 MoM (median risk in highest risk category expressed as an odds was 1:1.78 and observed prevalence 1:2.7). Conclusion: The NT MoM upper truncation limit should be reduced from 2.5 to 2.0 MoM. [ABSTRACT FROM AUTHOR]

Objectives: Introduction of new technologies into cervical screening programmes has allowed more efficient programmes with less resources. We present an overview of screening technologies introduced into the Cervical Screening Wales programme and their evolution over time. Methods: Data from the programme's statistical report were used to evaluate its performance over a 17-year period between 2001/02 and 2017/18. Results: The introduction of liquid-based cytology has had a substantial impact on reducing inadequate sample rates and on increasing the positive predictive value of cytology. Inadequate rates have increased following the implementation of human papilloma virus testing as a triage test for cytology. Further knock-on effects on standard reporting ranges are expected following the introduction of human papilloma virus testing as the primary screening test. New performance standards have been introduced to better reflect the performance of the programme at a time when disease prevalence is expected to fall as women vaccinated against human papilloma virus reach screening age. Conclusions: Improvements to this cervical cancer screening programme as illustrated through performance indicator ranges suggest a major role played by technology. [ABSTRACT FROM AUTHOR]

Objectives: Georgia has a high prevalence of hepatitis C virus (HCV) infection. In 2015 a national HCV elimination program was launched providing free access to screening and treatment. To achieve elimination, innovative approaches to increase screening coverage and linkage to care are needed. This study estimates feasibility, acceptability, and outcomes of the door-to-door pilot HCV testing program in three cities. Methods: Households were approached by system random sampling and all members were invited for study participation. Researchers used a detailed guide for conducting door-to-door testing and served as case navigators to link anti-HCV-positive individuals to care. Results: Testing acceptance rate was high. In total 4804 individuals were tested and 48 (1.0%) were HCV positive. Among the entire sample of newly and previously tested individuals, overall HCV antibody prevalence was 3.6%. Through case navigation, of 48 newly identified and 26 previously identified anti-HCV-positive individuals, 42 (87.5%) and 17 (65.4%), respectively, were successfully linked to care. Conclusions: Door-to-door HCV testing has potential to increase testing uptake. Such community-based approaches not only improve testing, but can also serve to increase linkage to care, which is important in achieving the goal of HCV elimination. The study provides a model for high prevalence countries aiming to eliminate hepatitis C. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the relationship between patterns of gynaecological check-up and body mass index while accounting for various determinants of health care use. Methods: Sequence analysis and clustering were used to highlight patterns of gynaecological check-up, which included the regularity of breast and cervical cancer screening and visits to the gynaecologist over four years, among 6182 women aged 54–65 included in the CONSTANCES cohort between 2013 and 2015 in France. Multinomial logistic regressions were used to study the association between these patterns and women's body mass index. Results: We identified four patterns of gynaecological check-up, from (A) no or inappropriate check-up (20%) to (D) almost one visit to the gynaecologist every year, overscreening for cervical cancer and frequent use of opportunistic breast cancer screening (12%). From patterns A to D, the proportion of obese women decreased and that of women with normal body mass index increased. Obese and overweight women underwent more breast than cervical cancer screening and were less often overscreened than normal weight women. These differences were only partly explained by the lower socioeconomic situation of overweight and obese women. Beyond the financial barrier, the screening modality and the type of exam may play a role. Among women who were screened for cervical cancer, obese and overweight women were less often screened by a gynaecologist. Conclusion: Further efforts should be made to enhance the take-up of screening among obese women who are deterred by the healthcare system. [ABSTRACT FROM AUTHOR]

Objective: In the first STROKESTOP atrial fibrillation screening study, participation was influenced by socio-demographic and geographic factors. To improve uptake in the second study, two screening sites were added, closer to low-income neighbourhoods which had very low participation in the first study. This paper aims to analyse the geographic and socio-demographic disparities in uptake in the second trial and compare the results with the first trial. Methods: Inhabitants of the Stockholm region born in 1940 and 1941 were randomised 1:1 to be invited to screening or serve as controls. Medical history, blood samples and single-lead-ECG were collected. Invitee's residential parish was used for geo-mapping analysis of the geographical disparities in participation, using hierarchical Bayes methods. Individual data for participants and non-participants were obtained for the socioeconomic variables: educational level, disposable income, immigrant and marital status. Results: Higher participation was observed in those with higher education, high income, among non-immigrants and married individuals. Participation between the first and second studies improved significantly, where additional screening sites were introduced. These improvements were generally significant, in each population group according to socio-demographic characteristics. Conclusion: Decentralisation of screening sites in an atrial fibrillation screening program yielded a significantly positive impact on screening uptake. Adding local screening sites in areas with low uptake had beneficial impact on participation across a wide spectrum of socio-demographic groups. Decentralised screening substantially increased the screening uptake in deprived areas. [ABSTRACT FROM AUTHOR]

The objective was to determine if a screening tool for obstructive sleep apnea could be used to predict adverse perinatal outcomes. This was a prospective observational study of patients receiving prenatal care and universally screened for obstructive sleep apnea with the STOP Questionnaire (four questions related to S noring, T iredness during daytime, O bserved apnea, and high blood P ressure). Confounding variables were included in a backwards logistic regression model to predict adverse perinatal outcomes. The study population of 442 women had positive STOP screens (64; 14.5%) associated with preterm delivery and neonatal intensive care unit admissions. For preterm delivery, history of preterm delivery was the strongest predictor with odds ratios of 4.2 (95% confidence interval 2.0–8.8; p < 0.001), followed by STOP, odds ratios 2.8 (95% confidence interval 1.4–5.8; p = 0.004) and nulliparity, odds ratios 2.3 (95% confidence interval 1.2–4.4; p = 0.013). A positive STOP was the only significant predictor for neonatal intensive care unit admissions, odds ratios 2.5 (95% confidence interval 1.1–5.7; p = 0.036). STOP screening test performance indicated low sensitivity but high specificity: preterm delivery (28.3%, 87.4%), neonatal intensive care unit admissions (27.3%, 86.6%), low birth weight (25.0%, 86.9%), and preeclampsia (16.7%, 85.6%). As a stand-alone tool, the STOP Questionnaire has limited performance, but could be explored in combination with other factors that might increase sensitivity to predict preterm delivery and neonatal intensive care unit admission. [ABSTRACT FROM AUTHOR]

Objectives: If prostate cancer screening practices relate to occupation, this would have important implications when studying the aetiological role of workplace exposures on prostate cancer. We identified variations in screening by occupation among men in Montreal, Canada (2005–2012). Methods: Prostate specific antigen testing and digital rectal examination (ever-screened and frequency of screening, previous five years) were examined among population controls from the Prostate Cancer & Environment Study. Face-to-face interviews elicited lifestyle and occupational histories. Multivariable logistic regression was used to estimate the odds of ever-screening for the longest-held occupation, adjusting for potential confounders. Negative binomial models were used to examine relationships with screening frequency. Results: Among 1989 controls, 81% reported ever having had a prostate specific antigen test, and 77% a digital rectal examination. Approximately 40% of men reported having a prostate specific antigen test once a year, on average. Compared with those in management or administrative jobs, men in primary industry (odds ratio 0.26, 95% confidence interval 0.10–0.65), construction (0.44, 0.25–0.79), machining (0.45, 0.21–0.97), and teaching (0.37, 0.20–0.70) were less likely to have undergone prostate specific antigen screening. Results were similar when considering the most recent job. Conclusions: Our findings highlight substantial variations in prostate cancer screening by occupation. Men in occupations where carcinogen exposures are more common are less likely to participate in prostate screening activities. This could be an important source of bias, and occupational studies of prostate cancer should account for screening practices. [ABSTRACT FROM AUTHOR]

Objective: Several studies have shown that there is an upward shift in the classification of cervical cytology when high-risk human papillomavirus (hrHPV) status is known to be positive. The Netherlands implemented primary hrHPV screening with reflex cytology as the primary screening test in 2017. Prior to implementation of the new programme, we investigated whether knowledge of hrHPV status influences cytology rating. Methods: Using a set of 200 cytology slides that had been previously tested, two pairs of cytotechnicians rated 100 slides per pair twice: first without knowledge of hrHPV status and then, after a wash-out period of two months, with knowledge of hrHPV status. Results: We found that hrHPV positive slides were more likely to be rated up over the referral threshold (i.e. from negative for intraepithelial lesion or malignancy to atypical squamous cells of undetermined significance+) than hrHPV negative slides at the second review when hrHPV status was known (relative risk = 3.2; 95% confidence interval: 1.3–7.9). Conclusions: If the same upward shift in ratings were to be observed in the national programme, it may have implications for referrals of women with low-grade lesions. [ABSTRACT FROM AUTHOR]

Objective: Little research exists on what predicts individual return to screening after a false-positive faecal immunochemical test in a population bowel screening programme. We aimed to quantify the impact of false-positive faecal immunochemical test in the first round of screening on re-attendance in BowelScreen, the National Bowel Screening Programme in Ireland. Methods: A retrospective cohort study was conducted. False-positivity was defined as a positive faecal immunochemical test with subsequent colonoscopy showing no evidence of malignancy or surveillance requirement. In those with a false-positive faecal immunochemical test, logistic regression was used to predict repeat participation in the second round. Results: Of 196,149 individuals who attended the first screening round, 108,075 were eligible and re-invited in the second round, and 93,971 accepted the invitation (86.9%). Second round uptake was higher in faecal immunochemical test-negative individuals compared with those having false-positive results (87.5% vs. 73.1%; p < 0.001). Older age (odds ratio (OR) 0.75; 95% confidence interval (CI) 0.60–0.94), computed tomography colonography (unsuitability/failed colonoscopy) (OR 0.40; 95% CI 0.21–0.73), and longer duration from screening invitation to faecal immunochemical test result (OR 0.991; 95% CI 0.9872–0.995) were predictors of non-re-attendance in the next screening round. Conclusion: There is a significant reduction in re-attendance rates for individuals with false-positive faecal immunochemical test results. The letter sent following a negative colonoscopy is being reviewed to ensure that it provides adequate encouragement to re-attend. There are roles for screening promotion and for Gastroenterologists and Advanced Nurse Practitioners to emphasize the importance of regular faecal immunochemical tests after a negative colonoscopy. [ABSTRACT FROM AUTHOR]

Objective: In the United States, colorectal cancer incidence has increased in adults under age 55. Although debate remains about whether this rise is a result of increased detection because of more colonoscopy utilization, population-based trends in colonoscopy among this age group are unknown. We examined changes in colonoscopy rates, as well as colorectal cancer incidence, among adults aged 40–54, using nationally representative data. Methods: Recent (past year) colonoscopy rates were computed among 53,175 respondents aged 40–54 in National Health Interview Survey data from 2000 through 2015 by five-year age group. Colorectal cancer incidence rates and incidence rate ratios were estimated from 18 population-based Surveillance Epidemiology and End Result registries during the same period. Results: Among respondents aged 40–44, past-year colonoscopy rates were stable during 2000–2015, and ranged from 2.3% to 3.5% (p -value for trend = 0.771). In contrast, colonoscopy rates increased from 2.5% in 2000 to 5.2% in 2015 among ages 45–49, and from 5.0% to 14.1% in ages 50–54 (test for trend p -values < 0.001). During 2000–2015, colorectal cancer incidence rates increased by 28% in people aged 40–44 (incidence rate ratio = 1.28, 95% CI 1.20, 2.37), 15% in those aged 45–49 (incidence rate ratio = 1.15, 95%CI 1.10, 1.21), and 17% in those aged 50–54 (incidence rate ratio = 1.17, 95%CI 1.13, 1.21), respectively. Conclusion: Increases in colonoscopy rates were confined to ages 45–54, whereas colorectal cancer incidence rates rose in those aged 40–44, 45–49, and 50–54. Colonoscopy trends do not fully align with colorectal cancer incidence patterns. [ABSTRACT FROM AUTHOR]

An editorial is presented on medical screening. Topics include process of selection with the purpose of identifying the individuals who are at a sufficiently high risk of a specific disorder to warrant further investigation or sometimes direct preventive action; and seeking medical attention on account of symptoms of the disease for which screening is being conducted.

An editorial is presented on primary prevention of disease usually making poor screening tests. Topics include quantitative association between causal risk factors and disease being usually too small for the risk factor to be a useful screening test; and incremental value of polygenic risk scores (PRS) over traditional risk factor scores in the prediction of coronary heart disease.

Objective: Biliary atresia, a rare newborn liver disease, is the most common cause of liver-related death in children and the main indication for paediatric liver transplantation. Early detection and surgical intervention with a Kasai portoenterostomy offers the best chance for long-term patient survival. We conducted a cost-effectiveness analysis to compare no universal screening with screening using either a home-based infant stool colour card with passive card distribution strategy, or conjugated bilirubin testing. Methods: A Markov model was developed, with structure, costs, and probabilities informed by the literature and clinical expert opinion, to simulate a newborn cohort over a 10-year time horizon. Health benefits were expressed as life-years gained. This analysis was conducted from the perspective of the Canadian publicly funded health care system (all costs in Canadian dollars). Both deterministic and probabilistic analyses were conducted. Results: Screening using a home-based colour card with passive card distribution was a cost-effective option. For a population of 392,902 annual births in Canada, this strategy cost approximately $192,000 more than no universal screening but led to eight life-years gained (incremental cost-effectiveness ratio (ICER) = $24,065 per life-year gained). Screening using conjugated bilirubin testing versus the colour card cost $2,369,199 more and led to five more life-years gained (ICER= $473,840 per life year gained), and so was not cost-effective. Conclusions: A home-based screening program using infant stool colour cards with a passive distribution strategy could be highly cost-effective when administered at a low unit cost and with a reasonable screening performance. [ABSTRACT FROM AUTHOR]

Objective: Cervical cancer mortality has halved in Australia since the national cervical screening program began in 1991, but elevated mortality rates persist for Aboriginal and Torres Strait Islander women (referred to as Aboriginal women in this report). We investigated differences by Aboriginal status in abnormality rates predicted by cervical cytology and confirmed by histological diagnoses among screened women. Methods: Using record linkage between cervical screening registry and public hospital records in South Australia, we obtained Aboriginal status of women aged 20–69 for 1993–2016 (this was not recorded by the registry). Differences in cytological abnormalities were investigated by Aboriginal status, using relative risk ratios from mixed effect multinomial logistic regression modelling. Odds ratios were calculated for histological high grade results for Aboriginal compared with non-Aboriginal women. Results: Of 1,676,141 linkable cytology tests, 5.8% were abnormal. Abnormal results were more common for women who were younger, never married, and living in a major city or socioeconomically disadvantaged area. After adjusting for these factors and numbers of screening episodes, the relative risk of a low grade cytological abnormality compared with a normal test was 14% (95% confidence interval 5–24%) higher, and the relative risk of a high grade cytological abnormality was 61% (95% confidence interval 44–79%) higher, for Aboriginal women. The adjusted odds ratio of a histological high grade was 76% (95% confidence interval 46–113%) higher. Conclusions: Ensuring that screen-detected abnormalities are followed up in a timely way by culturally acceptable services is important for reducing differences in cervical cancer rates between Aboriginal and non-Aboriginal women. [ABSTRACT FROM AUTHOR]

Objectives: A large proportion of women have a preference for a same-gender endoscopy practitioner. We tested how information about practitioner gender affected intention to have bowel scope screening in a sample of women disinclined to have the test. Methods: In an online experimental survey, women aged 35–54 living in England who did not intend to participate in bowel scope screening (N = 1060) were randomised to one of four experimental conditions: (1) control (practitioner's gender is unknown), (2) opposite-gender (male practitioner by default), (3) same gender (female practitioner by default), and (4) active choice (the patient could choose the gender of the practitioner). Intention was measured following the interventions. Results: Of 1010 (95.3%) women who completed the survey, most were White-British (83.6%), and working (63.3%). Compared with control, both active choice and same-gender conditions increased intention among disinclined women (9.3% vs. 16.0% and 17.9%; OR: 1.85; 95% CI: 1.07–3.20 and OR: 2.07; 95% CI: 1.23–3.50). There were no differences in intention between the opposite-gender and control conditions (9.8% vs. 9.3%; OR: 1.06; 95% CI: 0.60–1.90) or the active choice and same-gender conditions (16.0% vs. 17.9%: OR: 0.89; 95% CI: 0.55–1.46, using same gender as baseline). Conclusions: Offering disinclined women a same-gender practitioner, either by choice or default, increased subsequent intention, while an opposite gender default did not negatively affect intention. Reducing uncertainty about gender of practitioner could positively affect uptake in women, and should be tested in a randomised controlled trial. [ABSTRACT FROM AUTHOR]

Objective: Beta thalassaemias are a group of hereditary red cell disorders resulting in a reduced or absent production of the main adult haemoglobin, adult haemoglobin. In England, the NHS Sickle Cell & Thalassaemia Screening Programme recommends reporting newborn beta thalassaemia disease as an incidental finding when detected whilst screening for sickle cell disease. The current action value to initiate further investigations is 1.5% adult haemoglobin, using high-performance liquid chromatography or capillary electrophoresis. We examined the reliability of this action value. Methods: A 44-month country-wide prospective study using data from 13 newborn screening laboratories in England. Results: There were 81 cases reported with an adult haemoglobin of 1.5% or less at first-line screen, of which nine were lost to follow-up. The six false-positive results were all of 32 weeks' gestation or less. Of the 66 true-positives, 36 had confirmatory molecular results (11 of these cases also have results from tandem mass spectrometry), 19 had clinical confirmation and 11 had the results of both parents available which were consistent with the screening result. There was one false-negative, a confirmed beta thalassaemia major case with an adult haemoglobin of 1.7%, above the action value at first-line screen but known to be at risk from parental results and therefore referred into clinical care by the laboratory. Conclusions: This study demonstrates a positive predictive value of 91.7%, with a specificity of 99.9% and a sensitivity of 98.5%. These results confirm the reliability of the current action value. [ABSTRACT FROM AUTHOR]

Objective: To integrate child–parent screening and cascade testing into a single pathway-child-parent cascade screening (CPCS), for the identification of familial hypercholesterolaemia in the population and to estimate the number of new familial hypercholesterolaemia cases identified per child screened and the associated costs. Methods: We applied the results from the published MRC Child–Parent Screening Study to 10,000 children, together with cascade testing first degree relatives of parents with a familial hypercholesterolaemia mutation identified by child–parent screening. We estimated the number of familial hypercholesterolaemia cases identified per child screened, the median cost per familial hypercholesterolaemia case identified and the median cost per child screened to identify one case using a range of cholesterol and familial hypercholesterolaemia mutation testing costs. We present a case study to illustrate the application of CPCS in practice. Results: CPCS identifies one new familial hypercholesterolaemia case per 70 children screened at a median estimated cost of £960 per new familial hypercholesterolaemia case or £4 per child screened. CPCS identifies an average of four new familial hypercholesterolaemia cases per family. In the case study, six new familial hypercholesterolaemia cases were identified, and preventive treatment started in five, with the index child expected to start when older. Conclusion: CPCS for familial hypercholesterolaemia are complementary strategies. The sustainability of cascade testing relies on identifying new unrelated index cases. This is achieved with population-wide child–parent screening. Integrated CPCS is currently better than either method of familial hypercholesterolaemia detection alone. It has the potential to identify all, or nearly all, individuals with familial hypercholesterolaemia in the population at low cost. [ABSTRACT FROM AUTHOR]

Objective To determine whether signed family physician reminder letters to women overdue for screening mammography prompts rescreening. Methods A randomized double-blind trial conducted in 2013 among women aged 51–73 and overdue for screening by 6–24 months. The study was carried out by the publicly funded British Columbia Cancer Agency Screening Mammography Program, which routinely sends standard reminder postcards to women who are due for mammography. Participating family physicians signed letters for the overdue women in their practices. The overdue women were mailed either the signed reminder letter and the standard reminder postcard, or the standard reminder postcard alone. The primary endpoint was the proportion of overdue women that attended a screening mammogram appointment within six months of mailing the study letters. The analysis was by intention to treat. Results In total, 822 family physicians participated and 5638 women were randomized. Mammography attendance by six months after mailing the reminders was 34.4% (947/2749) for women in the signed family physician letter arm, compared with 24.0% (660/2749) for women in the control arm (p < 0.0001). Adjusting for age, number of previous screening mammograms, and months overdue, women in the signed letter arm were significantly more likely to return for screening than women in the control arm (RR 1.41; 95% confidence interval: 1.30–1.54). Conclusion A signed family physician reminder letter improved mammography attendance for women who were overdue for screening mammography. [ABSTRACT FROM AUTHOR]

Objectives The English Bowel Cancer Screening Programme offers biennial guaiac faecal occult blood test (gFOBT) screening to 60–74-year-olds. Participants with positive results are referred for follow-up, but many do not have significant findings. If they remain age eligible, these individuals are reinvited for gFOBT screening. We evaluated the performance of repeat screening in this group. Methods We analysed data on programme participants reinvited to gFOBT screening after either previous negative gFOBT (n = 327,542), or positive gFOBT followed by a diagnostic investigation negative for colorectal cancer (CRC) or adenomas requiring surveillance (n = 42,280). Outcomes calculated were uptake, test positivity, yield of CRC, and positive predictive value (PPV) of gFOBT for CRC. Results For participants with a previous negative gFOBT, uptake in the subsequent screening round was 87.5%, positivity was 1.3%, yield of CRC was 0.112% of those adequately screened, and the PPV of gFOBT for CRC was 9.1%. After a positive gFOBT and a negative diagnostic investigation, uptake in the repeat screening round was 82.6%, positivity was 11.3%, CRC yield was 0.172% of participants adequately screened, and the PPV of gFOBT for CRC was 1.7%. Conclusion With high positivity and low PPV for CRC, the suitability of routine repeat gFOBT screening in two years among individuals with a previous positive test and a negative diagnostic examination needs to be carefully considered. [ABSTRACT FROM AUTHOR]

Objectives Routine analysis showed that between 1 June and 30 November 2014, only 47.6% of expected follow-up visits at the diagnostic level were registered in the Polish Universal Neonatal Hearing Screening Programme central database. We attempted to detect and analyse the reasons for this low percentage. Methods A telephone survey questionnaire was developed for parents whose children had not registered for consultation at the diagnostic level, or had not received a final diagnosis according to the programme database. Questions aimed to verify the database records and compare these with information received from and given to parents. From the 7888 children not registered at the diagnostic level, 3239 records were randomly selected, i.e. 52.4% of those who had been expected to attend. Results Questions were answered by 1950 parents (60.2% of the selected group). Of these, 52.1% (n = 734) had attended for diagnostic tests, but this was not recorded in the database. The most common reasons for not attending were the long waiting time for the visit (36.09%), lack of referral to a visit (25.9%) and conscious parent decision (16.35%). Conclusion The telephone survey disclosed omissions in database registration, and that in fact 83.6% of children had attended at the diagnostic level. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the French cystic fibrosis newborn screening algorithm, based on data tracked by a centralized monitoring process, from 2002 to 2014. The programme aimed to attain European Standards in terms of positive predictive value, sensitivity, the ratio of screen positive patients diagnosed with cystic fibrosis to infants who screen positive but with inconclusive diagnosis (CFSPID), and time to diagnosis. Methods Retrospective analysis of programme performance, compliance with the algorithm, and changes in screening strategy. Results Modifications in the flow chart protocol improved the positive predictive value to 0.31 while maintaining the sensitivity at 0.95. Among infants diagnosed with cystic fibrosis, or identified as CFSPID, sweat test results were obtained for 94%, and two mutations were identified after exhaustive screening for the gene, when applicable, in 99.6%. The rate of pending diagnosis was very low (0.5%). The ratio of infants with cystic fibrosis:CFSPID was 6.3:1. Age at initial visit at the CF centre was ≤ 35 days, respectively, in 53%/26%. Conclusion Performances were in agreement with European standards, but timeliness of initial visit needed improvement. Our data complement an accumulating body of evidence demonstrating that attention must be paid to such ethical considerations as limiting carrier detection and inconclusive diagnosis. Newborn screening programmes should have a rigorous centralized monitoring process to warrant adjustments for improving performance to attain consensus guidelines. [ABSTRACT FROM AUTHOR]

Objectives To compare abdominal aortic aneurysm screening outcomes of men with non-visualized aorta at original scan with subsequent scans and to determine predictors of non-visualized aorta. Methods In the Northern Ireland Abdominal Aortic Aneurysm screening programme, outcomes (discharge, annual surveillance, three-monthly surveillance, or vascular referral) and patient and programme characteristics (age, deprivation quintile, family history, technician experience, and screening location) for men with non-visualized aorta were investigated at original scan, and first and second rescans. Results Non-visualized aorta proportions were 2.9, 11.4, and 4.7% at original, first, and second rescan, respectively. There were no differences in screening outcomes between scanning stages (98.4, 97.6, and 97.4% <3 cm). There were 42 men (0.13%) with aortas ≥5.5 cm at original scan, but none at first and second rescan. A significantly greater proportion with non-visualized aorta were from more deprived (5.0%) than less deprived areas (1.7%). Deprivation quintile and staff role were significant independent non-visualized aorta predictors at original scan, and staff role at first rescan. Men from less deprived areas were three times as likely to have aortas visualized than those from more deprived areas (OR = 3.0, CI = 2.4–3.8) at original scan. A man scanned by screening technician compared with lead sonographer was 51% less likely to have aorta visualized at original scan and 94% less likely at first rescan. Conclusions The risk of abdominal aortic aneurysm in men with non-visualized aorta on first or subsequent rescans is no more than for those with visualized aorta on original scanning. Men from deprived areas are much more likely to have non-visualized aorta at original scan. [ABSTRACT FROM AUTHOR]

Objectives To determine the necessary screening interval for retinopathy in diabetic patients with no retinopathy based on time to laser therapy and to assess long-term visual outcome following screening. Methods In a population-based community screening programme in North Wales, 2917 patients were followed until death or for approximately 12 years. At screening, 2493 had no retinopathy; 424 had mostly minor degrees of non-proliferative retinopathy. Data on timing of first laser therapy and visual outcome following screening were obtained from local hospitals and ophthalmology units. Results Survival analysis showed that very few of the no retinopathy at screening group required laser therapy in the early years compared with the non-proliferative retinopathy group (p < 0.001). After two years, <0.1% of the no retinopathy at screening group required laser therapy, and at three years 0.2% (cumulative), lower rates of treatment than have been suggested by analyses of sight-threatening retinopathy determined photographically. At follow-up (mean 7.8 ± 4.6 years), mild to moderate visual impairment in one or both eyes due to diabetic retinopathy was more common in those with retinopathy at screening (26% vs. 5%, p < 0.001), but blindness due to diabetes occurred in only 1 in 1000. Conclusions Optimum screening intervals should be determined from time to active treatment. Based on requirement for laser therapy, the screening interval for diabetic patients with no retinopathy can be extended to two to three years. Patients who attend for retinal screening and treatment who have no or non-proliferative retinopathy now have a very low risk of eventual blindness from diabetes. [ABSTRACT FROM AUTHOR]