The underestimated preventive effects of flexible sigmoidoscopy screening: re-analysis and meta-analysis of randomized trials.

Flexible sigmoidoscopy (FS), which is less invasive, resource intensive and costly than colonoscopy, is among the recommended screening options for colorectal cancer (CRC). Four large randomized trials consistently reported statistically significant, albeit modest effects of screening by FS on CRC incidence. However, their effect estimates included cancers that were already prevalent at recruitment and could not have been prevented by screening. We performed a re-analysis and meta-analysis of two of the trials (including the largest one) to estimate reduction of truly incident cases by a single FS offered between 55 and 64 years of age among the "at risk study population" without prevalent CRC at recruitment. In meta-analyses of data reported after more than 15 years of follow-up, relative risk (95% CI) in intention-to-screen and per-protocol analyses were 0.71 (0.66-0.76) and 0.59 (0.55-0.65) for any CRC, and 0.52 (0.47-0.57) and 0.34 (0.30-0.39) for distal CRC, respectively. These results indicate much stronger effects than those suggested by the original reports and imply that a single screening FS can prevent approximately two out of three distal incident CRC cases within 15 + years of follow-up.

Breast cancer screening programmes and self-reported mammography use in European countries.

Mammography screening has been shown to be able to reduce breast cancer mortality, leading most European countries to implement mammography-based screening programmes. In our study, we analysed key characteristics of breast cancer screening programmes and mammography use in European countries. Information on screening programmes were obtained from the 2017 European Union (EU) screening report, websites from governments and cancer registries, and through literature search in PubMed (studies published up to 20 June 2022). Data on self-reported mammography use in the past 2 years were obtained from Eurostat and had been derived from the European health interview survey (cross-sectional survey), conducted in the 27 EU countries, Iceland, Norway, Serbia, Turkey and the UK in 2013 to 2015 and 2018 to 2020. Data were analysed for each country according to their human development index (HDI). By 2022, all included countries besides Bulgaria and Greece had introduced an organised mammography-based screening programme; Romania and Turkey had only pilot programmes. Screening programmes differ substantially across countries, particularly in timing of implementation (e.g., in Sweden, the Netherlands before 1990; Belgium, France between 2000 and 2004; Denmark, Germany between 2005 and 2009; Austria, Slovakia after 2010). Self-reported mammography use also differed considerably across countries, and went along with HDI-from <36% in all countries with HDI <0.85 to >70% in most countries with HDI >0.90. The data call for efforts to improve mammography screening use across Europe, particularly in countries with lower development levels where breast cancer mortality rates are also among the highest in the region.

Overall and age-specific risk advancement periods of colorectal cancer for men vs women: Implications for gender-sensitive screening offers?

Colorectal cancer (CRC) incidence and mortality are higher among men than among women. We aimed to estimate overall and age-specific risk advancement periods (RAPs) for men compared to women, which quantify how many years earlier comparable levels of risk are reached by men. RAPs were derived by Cox regression models among 331 224 participants aged 40 to 69 at baseline of the UK Biobank with no previous diagnosis of CRC and no previous CRC screening examination who were followed with respect to CRC incidence for up to 13 years. Men were at substantially higher risk of CRC than women in age groups 50 to 59 and 60 to 69, with RAPs (95% confidence intervals) as high as 8.7 (4.5-13.0) and 6.2 (4.5-7.9), respectively. These RAPs were higher than those for family history of CRC in these age groups. By contrast, no significant sex difference but a major impact of family history was seen in age group 40 to 49 (P-value for interaction between sex and age = .00079). The observed patterns suggest that consideration of gender-specific starting ages of screening might be warranted in countries in which screening offers start at ages above 50 years.

Making colonoscopy-based screening more efficient: A "gateopener" approach.

Screening colonoscopy for early detection and prevention of colorectal cancer (CRC) is mostly used inefficiently. Here, we assessed the potential of an innovative approach to colonoscopy-based screening, by use of a single, low threshold fecal immunochemical test (FIT) as a "gateopener" for screening colonoscopy. Using COSIMO, a validated simulation model, we modeled scenarios including either direct invitation to screening colonoscopy or an alternative approach involving mailing a single ("gateopener") FIT along with an invitation to colonoscopy contingent on a FIT value above a low threshold yielding a 50% positivity rate (ie, every other pretest will be positive). Under plausible assumptions on screening offer adherence, we found that such "gateopener screening" (use of screening colonoscopy contingent on a positive, low threshold gateopener FIT) approximately doubled cancer detection rates vs conventional screening. In those spared from screening colonoscopy due to a negative gateopener FIT pretest, numbers needed to screen were 10-times higher vs those for individuals with a positive FIT, peaking in >2000 and >3800 (hypothetically) needed colonoscopies to detect one case of cancer in men and women, respectively. Gateopener screening resulted in 42%-51% and 59%-65% more prevented CRC cases and deaths, respectively. In summary, by directing colonoscopy capacities to those most likely to benefit, offering screening colonoscopy contingent on a "gateopener" low-threshold FIT would substantially enhance efficiency of colonoscopy screening.

Polygenic Risk Score for Defining Personalized Surveillance Intervals After Adenoma Detection and Removal at Colonoscopy.

BACKGROUND & AIMS: Polygenic risk scores (PRSs) could help to define personalized colorectal cancer (CRC) screening strategies. The aim of this study was to evaluate whether a PRS, along with adenoma characteristics, could help to define more personalized and risk-adapted surveillance intervals. METHODS: In a population-based, case-control study from Germany, detailed information on previous colonoscopies and a PRS based on 140 CRC-related, single-nucleotide polymorphisms was obtained from 4696 CRC cases and 3709 controls. Participants were classified as having low, medium, or high genetic risk according to tertiles of PRSs among controls. We calculated the absolute risk of CRC based on the PRS and colonoscopy history and findings. RESULTS: We observed major variations of CRC risk according to the PRS, including among individuals with detection and removal of adenomas at colonoscopy. For instance, the estimated 10-year absolute risk of CRC for 50-year-old men and women with no polyps, for whom repeat screening colonoscopy is recommended after 10 years only, was 0.2%. Equivalent absolute risks were estimated for people with low-risk adenomas and low PRS. However, the same levels of absolute risk were reached within 3 to 5 years by those with low-risk adenomas and high PRS and with high-risk adenomas irrespective of the PRS. CONCLUSIONS: Consideration of genetic predisposition to CRC risk, as determined by a PRS, could help to define personalized, risk-adapted surveillance intervals after detection and removal of adenomas at screening colonoscopy. However, whether the risk variation is strong enough to direct clinical risk stratification needs to be explored further.

When gold standards are not so golden: prevalence bias in randomized trials on endoscopic colorectal cancer screening.

Randomized trials on the effectiveness of screening endoscopy in reducing colorectal cancer (CRC) risk have reported statistically significant, but rather modest reduction of CRC risk by the screening offer. However, risk estimates in these trials included substantial proportions of prevalent CRC cases which were early detected, but could not possibly have been prevented by screening. Thereby, a key principle of randomized prevention trials is violated that only "at risk" persons who do not yet have the disease one aims to prevent should be included in measures of preventive effects. Using recently published data from the Nordic-European Initiative on Colorectal Cancer (NordICC) trial as an example, we illustrate that approaches aimed to account for "prevalence bias" lead to effect estimates that are substantially larger than those reported in the trial and more in line with results from observational studies and real life settings. More rigorous methodological work is needed to develop effective and user-friendly tools to prevent or adjust for prevalence bias in future screening studies.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

A Multi-Pump Magnetohydrodynamics Lab-On-A-Chip Device for Automated Flow Control and Analyte Delivery.

This article shows the development of a computer-controlled lab-on-a-chip device with three magnetohydrodynamic (MHD) pumps and a pneumatic valve. The chip was made of a stack of layers of polymethylmethacrylate (PMMA), cut using a laser engraver and thermally bonded. The MHD pumps were built using permanent magnets (neodymium) and platinum electrodes, all of them controlled by an Arduino board and a set of relays. The implemented pumps were able to drive solutions in the open channels with a flow rate that increased proportionally with the channel width and applied voltage. To address the characteristic low pressures generated by this kind of pump, all channels were interconnected. Because the electrodes were immersed in the electrolyte, causing electrolysis and pH variations, the composition and ionic strength of the electrolyte solution were controlled. Additionally, side structures for releasing bubbles were integrated. With this multi-pump and valve solution, the device was used to demonstrate the possibility of performing an injection sequence in a system that resembles a traditional flow injection analysis system. Ultimately, the results demonstrate the possibility of performing injection sequences using an array of MHD pumps that can perform fluid handling in the 0-5 µL s-1 range.

Complete Additively Manufactured (3D-Printed) Electrochemical Sensing Platform.

Herein, we report a complete additively manufactured (AM) electrochemical sensing platform. In this approach, a fully AM/3D-printed electrochemical system, using a conventional low-cost 3D printer (fused deposition modeling) fabricating both the conductive electrodes and the nonconductive/chemically inert electrochemical cell is reported. The electrodes (working, counter, and pseudo-reference) are AM using a conductive fused-filament comprised of a mixture of carbon black nanoparticles and polylactic acid (CB/PLA). AM components partially coated with silver ink presented a similar behavior to a conventional Ag/AgCl reference electrode. The performance of the AM working electrode was evaluated after a simple and fast polishing procedure on sandpaper and electrochemical activation in a NaOH solution (0.5 mol L-1). Following the electrochemical activation step, a considerable improvement in the electrochemical behavior (current intensity and voltammetric profile) was obtained for model analytes, such as dopamine, hexaammineruthenium(III) chloride, ferricyanide/ferrocyanide, uric acid, and ascorbic acid. Excellent repeatability (RSD = 0.4%, N = 10) and limit of detection (0.1 µmol L-1) were obtained with the all complete AM electrochemical system for dopamine analysis. The electrochemical performance of the developed system (after simple electrochemical activation of the working electrode) was similar or better than those obtained using commercial glassy carbon and screen-printed carbon electrodes. The results shown here represents a significant advance in AM (3D printing) technology for analytical chemistry.

Antenatal care visits during pregnancy and their effect on maternal and fetal outcomes in pre-eclamptic patients.

AIM: The frequency of antenatal care visits during pregnancy was examined to determine their effect on maternal and fetal outcomes in patients with pre-eclampsia. METHODS: This study included 150 pregnant women with pre-eclampsia who attended the Outpatient Clinic of the Obstetrics and Gynecology Department, Ismailia General Hospital. The women were interviewed and their antenatal care visits recorded. Blood pressure control, cardiotocography, ultrasonographic and Doppler evaluations and the administration of methyldopa were recorded. We calculated the distribution of women who attended an adequate versus an inadequate number of antenatal care visits, examined the characteristics of the groups using significance tests, computed the risk of poor maternal and fetal outcomes and created regression analysis models. We also calculated the incidence rate of poor maternal and fetal outcomes, odds ratios and 95% confidence intervals. RESULTS: Women who attended an inadequate number of antenatal care visits had a significantly higher risk of post-partum hemorrhage, eclampsia, and intensive care unit admission compared with women who attended an adequate number of visits. Women who attended an inadequate number of visits had a 12-fold risk of a poor maternal outcome, a 53-fold risk of a poor fetal outcome and a significantly higher risk of neonatal mortality in comparison to women who attended an adequate number of antenatal visits. CONCLUSIONS: The frequency of antenatal care visits during pregnancy has a significant effect on maternal and fetal outcomes in patients with pre-eclampsia.

Customized versus Population-Based Birth Weight References for Predicting Fetal and Neonatal Undernutrition.

OBJECTIVES: The aim of our study was to construct a model of customized birth weight curves based on a Spanish population and to compare the ability of this customized model to our population-based chart to predict a neonatal ponderal index (PI) <10th percentile. METHODS: We developed a model that can predict the 10th percentile for a fetus according to gestational age and gender as well as maternal weight, height, and age. We compared the ability of this customized model to that of our own population-based model to predict a neonatal PI <10th percentile. Data from a large database were used (32,854 live newborns, from 1993 through 2012). Only singleton pregnancies with a gestational age at delivery of 32-42 weeks were included. RESULTS: In the entire pregnant population, the customized method was superior to the population-based method for detecting newborns with a PI <10th percentile (sensitivity: 55 vs. 40.96%; specificity: 99.6 vs. 91.23%; positive predictive value: 11.49 vs. 9.55%, and negative predictive value: 98.84 vs. 98.55%, respectively). In pregnant women with a BMI >90th percentile, the sensitivity was 75%, compared to 50% in the population-based method. In pregnant women with a height >90th percentile, the sensitivity was almost as high as in the population-based method (61.53 vs. 33.33%). CONCLUSION: The customized birth weight curve is superior to the population-based method for the detection of newborns with a PI <10th percentile. This is especially the case in women in the higher scales of height and weight as well as in preterm babies.

In Vivo Pattern Classification of Ingestive Behavior in Ruminants Using FBG Sensors and Machine Learning.

Pattern classification of ingestive behavior in grazing animals has extreme importance in studies related to animal nutrition, growth and health. In this paper, a system to classify chewing patterns of ruminants in in vivo experiments is developed. The proposal is based on data collected by optical fiber Bragg grating sensors (FBG) that are processed by machine learning techniques. The FBG sensors measure the biomechanical strain during jaw movements, and a decision tree is responsible for the classification of the associated chewing pattern. In this study, patterns associated with food intake of dietary supplement, hay and ryegrass were considered. Additionally, two other important events for ingestive behavior were monitored: rumination and idleness. Experimental results show that the proposed approach for pattern classification is capable of differentiating the five patterns involved in the chewing process with an overall accuracy of 94%.

Reduction in colorectal cancer incidence by screening endoscopy.

Colorectal cancer (CRC) incidence rates decreased by up to 50% in older age groups in the USA in the era of the widespread uptake of screening colonoscopy, despite adverse trends in CRC risk factors and increasing CRC incidence at younger ages. However, reported first results from a randomized trial, the NordICC study, suggested rather modest effects of screening colonoscopy. As outlined in this Perspective, the apparent discrepancy between real-world and trial evidence could be explained by strong attenuation of effect estimates from screening endoscopy trials by several factors, including limited screening adherence, widespread uptake of colonoscopy outside the screening offers and the inclusion of prevalent, non-preventable CRC cases in reported numbers of incident cases. Alternative interpretations of screening endoscopy trial results accounting for prevalence bias are in line with trends in CRC incidence reduction in countries offering CRC screening, and should encourage more widespread implementation and uptake of effective CRC screening.

Utilization of colorectal cancer screening tests across European countries: a cross-sectional analysis of the European health interview survey 2018-2020.

Background: Colorectal cancer (CRC) screening has been shown to reduce CRC incidence and mortality, and most European countries have started to implement CRC screening programs in the past 20 years. Consequently, this study aimed to estimate the utilization of fecal tests and colonoscopy, as well as investigate factors associated with their utilization based on specific screening program characteristics in European countries. Methods: We analyzed data from the European Health Interview Survey 2018-2020 to determine the utilization of fecal tests [guaiac-based fecal occult blood test (gFOBT) or fecal immunochemical test (FIT)] within the preceding 2 years or colonoscopy within the preceding 10 years among people aged 50-74 years, based on the type of screening offered in each country. Using multivariable logistic regression and sub-group meta-analysis, factors associated with screening use were determined. Findings: The analyses included data from 129,750 respondents across 29 European countries, with participant counts ranging from 1511 individuals in Iceland to 11,755 individuals in Germany. Unit response rates ranged from 22% to 88%. The use of either test was highest among countries with fully rolled-out programs with fecal tests [from 37.7% (867/2379) in Croatia to 74.9% (2321/3085) in Denmark] and in countries offering colonoscopy as an alternative screening method [from 26.2% (854/3329) in Greece to 75.4% (1192/1760) in Luxembourg]. We observed the lowest utilization of either test in countries with no program or small-scale programs [6.3% (195/3179) in Bulgaria to 34.2% (722/2144) in Latvia]. Across all types of screening offers, younger age, being without a partner, low education, rural residence, and living in large households were associated with lower utilization, as were poor lifestyle scores and prolonged periods without physician consultation. Interpretation: Our findings point to large disparities and much room for improvement in CRC screening offers and utilization across Europe. Funding: There was no funding source for this study.

[Prevention of Neonatal Group B Sreptococcal Infection. Spanish Recommendations. Update 2012. SEIMC/SEGO/SEN/SEQ/SEMFYC Consensus Document]. / Prevención de la infección perinatal por estreptococo del grupo B. Recomendaciones españolas. Actualización 2012. Documento de consenso SEIMC/SEGO/SEN/SEQ/SEMFYC.

Group B streptococci (GBS) remain the most common cause of early onset neonatal sepsis. In 2003 the Spanish Societies of Obstetrics and Gynaecology, Neonatology, Infectious Diseases and Clinical Microbiology, Chemotherapy, and Family and Community Medicine published updated recommendations for the prevention of early onset neonatal GBS infection. It was recommended to study all pregnant women at 35-37 weeks gestation to determine whether they were colonised by GBS, and to administer intrapartum antibiotic prophylaxis (IAP) to all colonised women. There has been a significant reduction in neonatal GBS infection in Spain following the widespread application of IAP. Today most cases of early onset GBS neonatal infection are due to false negative results in detecting GBS, to the lack of communication between laboratories and obstetric units, and to failures in implementing the prevention protocol. In 2010, new recommendations were published by the CDC, and this fact, together with the new knowledge and experience available, has led to the publishing of these new recommendations. The main changes in these revised recommendations include: microbiological methods to identify pregnant GBS carriers and for testing GBS antibiotic sensitivity, and the antibiotics used for IAP are updated; The significance of the presence of GBS in urine, including criteria for the diagnosis of UTI and asymptomatic bacteriuria in pregnancy are clarified; IAP in preterm labour and premature rupture of membranes, and the management of the newborn in relation to GBS carrier status of the mother are also revised. These recommendations are only addressed to the prevention of GBS early neonatal infection, are not effective against late neonatal infection.