The value of manual backward contact tracing to control COVID-19 in practice, the Netherlands, February to March 2021: a pilot study.

BackgroundContact tracing has been a key component of COVID-19 outbreak control. Backward contact tracing (BCT) aims to trace the source that infected the index case and, thereafter, the cases infected by the source. Modelling studies have suggested BCT will substantially reduce SARS-CoV-2 transmission in addition to forward contact tracing.AimTo assess the feasibility and impact of adding BCT in practice.MethodsWe identified COVID-19 cases who were already registered in the electronic database between 19 February and 10 March 2021 for routine contact tracing at the Public Health Service (PHS) of Rotterdam-Rijnmond, the Netherlands (pop. 1.3 million). We investigated if, through a structured questionnaire by dedicated contact tracers, we could trace additional sources and cases infected by these sources. Potential sources identified by the index were approached to trace the source's contacts. We evaluated the number of source contacts that could be additionally quarantined.ResultsOf 7,448 COVID-19 cases interviewed in the study period, 47% (n = 3,497) indicated a source that was already registered as a case in the PHS electronic database. A potential, not yet registered source was traced in 13% (n = 979). Backward contact tracing was possible in 62 of 979 cases, from whom an additional 133 potential sources were traced, and four were eligible for tracing of source contacts. Two additional contacts traced had to stay in quarantine for 1 day. No new COVID-19 cases were confirmed.ConclusionsThe addition of manual BCT to control the COVID-19 pandemic did not provide added value in our study setting.

SARS-CoV-2 in lions, gorillas and zookeepers in the Rotterdam Zoo, the Netherlands, a One Health investigation, November 2021.

In November 2021, seven western lowland gorillas and four Asiatic lions were diagnosed with COVID-19 at Rotterdam Zoo. An outbreak investigation was undertaken to determine the source and extent of the outbreak and to identify possible transmission routes. Interviews were conducted with staff to identify human and animal contacts and cases, compliance with personal protective equipment (PPE) and potential transmission routes. Human and animal contacts and other animal species suspected to be susceptible to SARS-CoV-2 were tested for SARS-CoV-2 RNA. Positive samples were subjected to sequencing. All the gorillas and lions that could be tested (3/7 and 2/4, respectively) were RT-PCR positive between 12 November and 10 December 2021. No other animal species were SARS-CoV-2 RNA positive. Forty direct and indirect human contacts were identified. Two direct contacts tested RT-PCR positive 10 days after the first COVID-19 symptoms in animals. The zookeepers' viral genome sequences clustered with those of gorillas and lions. Personal protective equipment compliance was suboptimal at instances. Findings confirm transmission of SARS-CoV-2 among animals and between humans and animals but source and directionality could not be established. Zookeepers were the most likely source and should have periodic PPE training. Sick animals should promptly be tested and isolated/quarantined.

Impact of surgical versus endoscopic management of complex nonmalignant polyps in a colorectal cancer screening program.

BACKGROUND: When complex nonmalignant polyps are detected in colorectal cancer (CRC) screening programs, patients may be referred directly to surgery or may first undergo additional endoscopy for attempted endoscopic removal by an expert. We compared the impact of both strategies on screening effectiveness and costs. METHODS: We used MISCAN-Colon to simulate the Dutch screening program, and projected CRC deaths prevented, quality-adjusted life-years (QALYs) gained, and costs for two scenarios: 1) surgery for all complex nonmalignant polyps; 2) attempted removal by an expert endoscopist first. We made the following assumptions: 3.9 % of screen-detected large nonmalignant polyps were complex; associated surgery mortality was 0.7 %; the rate of successful removal by an expert was 87 %, with 0.11 % mortality. RESULTS: The screening program was estimated to prevent 11.2 CRC cases (-16.7 %) and 10.1 CRC deaths (-27.1 %), resulting in 32.9 QALYs gained (+ 17.2 %) per 1000 simulated individuals over their lifetimes compared with no screening. The program would also result in 2.1 surgeries for complex nonmalignant polyps with 0.015 associated deaths per 1000 individuals. If, instead, these patients were referred to an expert endoscopist first, only 0.2 patients required surgery, reducing associated deaths by 0.013 at the expense of 0.003 extra colonoscopy deaths. Compared with direct referral to surgery, referral to an expert endoscopist gained 0.2 QALYs and saved €12 500 per 1000 individuals in the target population. CONCLUSION: Referring patients with complex polyps to an expert endoscopist first reduced some surgery-related deaths while substantially improving cost-effectiveness of the screening program.

Development and Validation of Three Regional Microsimulation Models for Predicting Colorectal Cancer Screening Benefits in Europe.

Background. Validated microsimulation models have been shown to be useful tools in providing support for colorectal cancer (CRC) screening decisions. Aiming to assist European countries in reducing CRC mortality, we developed and validated three regional models for evaluating CRC screening in Europe. Methods. Microsimulation Screening Analysis-Colon (MISCAN-Colon) model versions for Italy, Slovenia, and Finland were quantified using data from different national institutions. These models were validated against the best available evidence for the effectiveness of screening from their region (when available): the Screening for COlon REctum (SCORE) trial and the Florentine fecal immunochemical test (FIT) screening study for Italy; the Norwegian Colorectal Cancer Prevention (NORCCAP) trial and the guaiac fecal occult blood test (gFOBT) Finnish population-based study for Finland. When published evidence was not available (Slovenia), the model was validated using cancer registry data. Results. Our three models reproduced age-specific CRC incidence rates and stage distributions in the prescreening period. Moreover, the Italian and Finnish models replicated CRC mortality reductions (reasonably) well against the best available evidence. CRC mortality reductions were predicted slightly larger than those observed (except for the Florentine FIT study), but consistently within the corresponding 95% confidence intervals. Conclusions. Our findings corroborate the MISCAN-Colon reliability in supporting decision making on CRC screening. Furthermore, our study provides the model structure for an additional tool (EU-TOPIA CRC evaluation tool: http://miscan.eu-topia.org) that aims to help policymakers and researchers monitoring or improving CRC screening in Europe.

The impact of information about different absolute benefits and harms on intention to participate in colorectal cancer screening: A think-aloud study and online randomised experiment.

BACKGROUND: There is considerable heterogeneity in individuals' risk of disease and thus the absolute benefits and harms of population-wide screening programmes. Using colorectal cancer (CRC) screening as an exemplar, we explored how people make decisions about screening when presented with information about absolute benefits and harms, and how those preferences vary with baseline risk, between screening tests and between individuals. METHOD: We conducted two linked studies with members of the public: a think-aloud study exploring decision making in-depth and an online randomised experiment quantifying preferences. In both, participants completed a web-based survey including information about three screening tests (colonoscopy, sigmoidoscopy, and faecal immunochemical testing) and then up to nine scenarios comparing screening to no screening for three levels of baseline risk (1%, 3% and 5% over 15 years) and the three screening tests. Participants reported, after each scenario, whether they would opt for screening (yes/no). RESULTS: Of the 20 participants in the think-aloud study 13 did not consider absolute benefits or harms when making decisions concerning CRC screening. In the online experiment (n = 978), 60% expressed intention to attend at 1% risk of CRC, 70% at 3% and 77% at 5%, with no differences between screening tests. At an individual level, 535 (54.7%) would attend at all three risk levels and 178 (18.2%) at none. The 27% whose intention varied by baseline risk were more likely to be younger, without a family history of CRC, and without a prior history of screening. CONCLUSIONS: Most people in our population were not influenced by the range of absolute benefits and harms associated with CRC screening presented. For an appreciable minority, however, magnitude of benefit was important.

Colonoscopy-Related Mortality in a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program.

BACKGROUND & AIMS: Many countries have introduced colorectal cancer (CRC) screening programs with fecal immunochemical tests (FITs), and follow-up colonoscopies for individuals with a positive FIT result. In order to make an informed decision to participate, individuals must be informed about the benefits and harms of FIT-based screening and subsequent colonoscopy. Colonoscopy-related fatal complications in FIT-based screening are understudied. We aimed to estimate the colonoscopy-related mortality in a national FIT-based CRC screening program. METHODS: Colonoscopy-related mortality within 30 days after colonoscopy was assessed by analysis of data from national endoscopy complication databases in the Netherlands, determining the excess 30-day rate of death in FIT-positive individuals undergoing colonoscopy vs FIT-negative individuals (based on data from the national screening database), and determining the rate of likely colonoscopy-related deaths based on registered causes of death by the Statistics Netherlands. RESULTS: Between October 2013 and December 2017, 172,797 participants underwent colonoscopy after a positive result from a FIT in the Dutch national CRC screening program; 13,848 participants received a diagnosis of CRC. The reported fatal complication rate was 0.23 per 10,000 FIT-positive participants (or 1 per 43,199; 95% CI, 0.090 - 0.60) undergoing colonoscopy, whereas this was 0.91 per 10,000 FIT-positive participants (or 1 per 10,961; 95% CI, 0.44 - 1.38) according to the excess death rate. Likely colonoscopy-related causes of death were reported in 0.86 per 10,000 FIT-positive participants (or 1 per 11,236; 95% CI, 0.48 - 1.63) who underwent colonoscopy, of which 50% considered cardiovascular events. CONCLUSIONS: Colonoscopy-related mortality within the Dutch FIT-based CRC screening program was estimated to range from 0.23 to 0.91 per 10,000 FIT-positive participants undergoing colonoscopy. These findings indicate underreporting of fatal complications in registries and a noteworthy incidence of fatal cardiovascular adverse events that requires further investigation. Nevertheless, the harm of FIT-based CRC screening is vastly outweighed by the benefits.

Incidence of Interval Colorectal Cancer After Negative Results From First-Round Fecal Immunochemical Screening Tests, by Cutoff Value and Participant Sex and Age.

BACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age. METHODS: We collected data from participants in a population-based CRC screening program in the Netherlands who had a negative result from a first-round of FIT screening. We calculated the cumulative incidence of interval cancer after a negative result from a FIT and the sensitivity of the FIT for detection of CRC at a low (15 µg Hb/g feces) and high (47 µg Hb/g feces) cutoff value. RESULTS: Among the 485,112 participants with a negative result from a FIT, 544 interval cancers were detected; 126 were in the 111,800 participants with negative results from a FIT with the low cutoff value and 418 were in the 373,312 FIT participants with negative results from a FIT with the high cutoff value. The mean age of participants tested with the low cutoff value was 72.0 years and the mean age of participants tested the high cutoff value was 66.7 years. The age-adjusted 2-year cumulative incidence of interval cancer after a negative result from a FIT were 9.5 per 10,000 persons at the low cutoff value vs 13.8 per 10,000 persons at the high cutoff value (P < .005). The age-adjusted sensitivity of the FIT for CRC were 90.5% for the low cutoff value vs 82.9% for the high cutoff (P < .0001). The FIT identified men with CRC with 87.4% sensitivity and women with CRC with 82.6% sensitivity (P < .001). CONCLUSIONS: In an analysis of data from a FIT population-based screening program in the Netherlands, we found that incidence of interval CRC after a negative result from a FIT to be low. Although the sensitivity of detection of CRC decreased with a higher FIT cutoff value, it remained above 80%.

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening.

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 µg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 µg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.

Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a microsimulation modelling study.

OBJECTIVE: To estimate benefits and harms of different colorectal cancer screening strategies, stratified by (baseline) 15-year colorectal cancer risk. DESIGN: Microsimulation modelling study using MIcrosimulation SCreening ANalysis-Colon (MISCAN-Colon). SETTING: A parallel guideline committee (BMJ Rapid Recommendations) defined the time frame and screening interventions, including selection of outcome measures. POPULATION: Norwegian men and women aged 50-79 years with varying 15-year colorectal cancer risk (1-7%). COMPARISONS: Four screening strategies were compared with no screening: biennial or annual faecal immunochemical test (FIT) or single sigmoidoscopy or colonoscopy at 100% adherence. MAIN OUTCOME MEASURES: Colorectal cancer mortality and incidence, burdens, and harms over 15 years of follow-up. The certainty of the evidence was assessed using the GRADE approach. RESULTS: Over 15 years of follow-up, screening individuals aged 50-79 at 3% risk of colorectal cancer with annual FIT or single colonoscopy reduced colorectal cancer mortality by 6 per 1000 individuals. Single sigmoidoscopy and biennial FIT reduced it by 5 per 1000 individuals. Colonoscopy, sigmoidoscopy, and annual FIT reduced colorectal cancer incidence by 10, 8, and 4 per 1000 individuals, respectively. The estimated incidence reduction for biennial FIT was 1 per 1000 individuals. Serious harms were estimated to be between 3 per 1000 (biennial FIT) and 5 per 1000 individuals (colonoscopy); harms increased with older age. The absolute benefits of screening increased with increasing colorectal cancer risk, while harms were less affected by baseline risk. Results were sensitive to the setting defined by the guideline panel. Because of uncertainty associated with modelling assumptions, we applied a GRADE rating of low certainty evidence to all estimates. CONCLUSIONS: Over a 15 year period, all screening strategies may reduce colorectal cancer mortality to a similar extent. Colonoscopy and sigmoidoscopy may also reduce colorectal cancer incidence, while FIT shows a smaller incidence reduction. Harms are rare and of similar magnitude for all screening strategies.

Quality Monitoring of a FIT-Based Colorectal Cancer Screening Program.

BACKGROUND: Quality assessment is crucial for consistent program performance of colorectal cancer (CRC) screening programs using fecal immunochemical test for hemoglobin (FIT). However, literature on the consistency of FIT performance in laboratory medicine was lacking. This study examined the consistency of FIT in testing positive or detecting advanced neoplasia (AN) for different specimen collection devices, lot reagents, and laboratories. METHODS: All participants with a FIT sample with a cutoff concentration of 47 µg Hb/g feces in the Dutch CRC screening program in 2014 and 2015 were included in the analyses. Multivariable logistic regression analyses were performed to estimate the odds ratios of collection devices, reagents, and laboratories on testing positive or detecting AN and positive predictive value (PPV). RESULTS: In total, 87519 (6.4%) of the 1371169 participants tested positive. Positivity rates and detection rates of AN differed between collection devices and reagents (all P < 0.01). In contrast, PPVs were not found to vary between collection devices, reagents, or laboratories (all P > 0.05). Positivity rates showed a small difference for laboratories (P = 0.004) but not for detection rates of AN. Size of the population affected by the deviating positivity rates was small (0.1% of the total tested population). CONCLUSIONS: Variations were observed in positivity and detection rates between collection devices and reagents, but there was no detected variation in PPV. Although the overall population effect of these variations on the screened population is expected to be modest, there is room for improvement.

Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a microsimulation modelling study

OBJECTIVE: To estimate benefits and harms of different colorectal cancer screening strategies, stratified by (baseline) 15-year colorectal cancer risk. DESIGN: Microsimulation modelling study using MIcrosimulation SCreening ANalysis-Colon (MISCAN-Colon).SETTING: A parallel guideline committee (BMJ Rapid Recommendations) defined the time frame and screening interventions, including selection of outcome measures.POPULATION: Norwegian men and women aged 50-79 years with varying 15-year colorectal cancer risk (1-7%).COMPARISONS: Four screening strategies were compared with no screening: biennial or annual faecal immunochemical test (FIT) or single sigmoidoscopy or colonoscopy at 100% adherence. MAIN OUTCOME MEASURES: Colorectal cancer mortality and incidence, burdens, and harms over 15 years of follow-up. The certainty of the evidence was assessed using the GRADE approach. RESULTS: Over 15 years of follow-up, screening individuals aged 50-79 at 3% risk of colorectal cancer with annual FIT or single colonoscopy reduced colorectal cancer mortality by 6 per 1000 individuals. Single sigmoidoscopy and biennial FIT reduced it by 5 per 1000 individuals. Colonoscopy, sigmoidoscopy, and annual FIT reduced colorectal cancer incidence by 10, 8, and 4 per 1000 individuals, respectively. The estimated incidence reduction for biennial FIT was 1 per 1000 individuals. Serious harms were estimated to be between 3 per 1000 (biennial FIT) and 5 per 1000 individuals (colonoscopy); harms increased with older age. The absolute benefits of screening increased with increasing colorectal cancer risk, while harms were less affected by baseline risk. Results were sensitive to the setting defined by the guideline panel. Because of uncertainty associated with modelling assumptions, we applied a GRADE rating of low certainty evidence to all estimates. CONCLUSIONS: Over a 15 year period, all screening strategies may reduce colorectal cancer mortality to a similar extent. Colonoscopy and sigmoidoscopy may also reduce colorectal cancer incidence, while FIT shows a smaller incidence reduction. Harms are rare and of similar magnitude for all screening strategies

Modeling in Colorectal Cancer Screening: Assessing External and Predictive Validity of MISCAN-Colon Microsimulation Model Using NORCCAP Trial Results.

BACKGROUND: Microsimulation models are increasingly being used to inform colorectal cancer (CRC) screening recommendations. MISCAN-Colon is an example of such a model, used to inform the Dutch CRC screening program and US Preventive Services Task Force guidelines. Assessing the validity of these models is essential to provide transparency regarding their performance. In this study, we tested the external and predictive validity of MISCAN-Colon. METHODS: We validated MISCAN-Colon using the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, a randomized controlled trial that examined the effectiveness of once-only flexible sigmoidoscopy (FS) screening. We simulated the study population and design of the NORCCAP trial in MISCAN-Colon and compared 10- to 12-year model-predicted hazard ratios (HRs) for overall and distal CRC incidence and mortality to those observed. In addition, we compared the numbers of screen-detected neoplasia. Finally, we predicted the trial's future results to allow for the assessment of predictive validity. RESULTS: MISCAN-Colon predicted an HR for overall CRC incidence (0.85), distal CRC incidence (0.82), overall CRC mortality (0.68), and distal CRC mortality (0.62). These were within the limits of the 95% confidence intervals of the NORCCAP trial results. Similar results were observed for the number of screen-detected cancers. The model significantly underestimated the number of screen-detected adenomas. Model-predicted HRs for CRC incidence and mortality up to 15- to 17-year follow-up were 0.84 and 0.72, respectively. CONCLUSION: Although the underestimation of screen-detected adenomas requires further investigation, MISCAN-Colon is able to make a valid replication of the CRC incidence and mortality reduction of an FS screening trial, which suggests that it can be considered a useful tool to support decision making on CRC screening.