Surveillance Testing Research Articles

Progress in Paratuberculosis Control Programmes for Dairy Herds.

While paratuberculosis control has been studied for over a century, knowledge gaps still exist regarding the uptake and efficacy of control programmes. This narrative review aims to summarise studies on control programmes presented at the IDF ParaTB Fora in 2021 and 2022 and the International Colloquium on Paratuberculosis in 2022. Studies were grouped by topic as follows: successful control, field studies, education and extension, voluntary and compulsory control programmes, and surveillance. Various Map control programmes resulted in a decreasing animal and herd level Map prevalence. Long-term stakeholder commitment, stable funding, involvement of herd veterinarians and incentives for farmers to participate were shown to be pivotal for long-term success. Control measures focused on vertical and calf-to-calf transmission may improve Map control in infected herds. Easy-to-capture visualisation of surveillance test results to inform participants on the progress of Map control in their herds was developed. The probability of freedom from disease and estimated within-herd prevalence were identified as good candidates for categorisation of herds to support low-risk trade of cattle. Results of the surveillance schemes may inform genetic selection for resistance to Map infection. In conclusion, successful paratuberculosis control is feasible at both the herd and country level provided that crucial prerequisites are met.

Impact of gene expression profiling on diagnosis and survival after metastasis in patients with uveal melanoma.

Surveillance frequency for metastasis is guided by gene expression profiling (GEP). This study evaluated the effect of GEP on time to diagnosis of metastasis, subsequent treatment and survival. A retrospective study was conducted of 110 uveal melanoma patients with GEP (DecisionDx-UM, Castle Biosciences, Friendswood, Texas, USA) and 110 American Joint Committee on Cancer-matched controls. Surveillance testing and treatment for metastasis were compared between the two groups and by GEP class. Rates of metastasis, overall survival and melanoma-related mortality were calculated using Kaplan-Meier estimates. Baseline characteristics and follow-up time were balanced in the two groups. Patients' GEP classification was 1A in 41%, 1B in 25.5% and 2 in 33.6%. Metastasis was diagnosed in 26.4% ( n = 29) in the GEP group and 23.6% ( n = 26) in the no GEP group ( P = 0.75). Median time to metastasis was 30.5 and 22.3 months in the GEP and no GEP groups, respectively ( P = 0.44). Median months to metastasis were 34.7, 75.8 and 26.1 in class 1A, 1B and 2 patients, respectively ( P = 0.28). Disease-specific 5-year survival rates were 89.4% [95% confidence interval (CI): 81.0-94.2%] and 84.1% (95% CI: 74.9-90.1%) in the GEP and no GEP groups respectively ( P = 0.49). Median time to death from metastasis was 10.1 months in the GEP group and 8.5 months in the no GEP group ( P = 0.40). There were no significant differences in time to metastasis diagnosis and survival outcomes in patients with and without GEP. To realize the full benefit of GEP, more sensitive techniques for detection of metastasis and adjuvant therapies are required.

Update on Cancer Predisposition Syndromes and Surveillance Guidelines for Childhood Brain Tumors.

Tumors of the central nervous system (CNS) comprise the second most common group of neoplasms in childhood. The incidence of germline predisposition among children with brain tumors continues to grow as our knowledge on disease etiology increases. Some children with brain tumors may present with nonmalignant phenotypic features of specific syndromes (e.g., nevoid basal cell carcinoma syndrome, neurofibromatosis type 1 and type 2, DICER1 syndrome, and constitutional mismatch-repair deficiency), while others may present with a strong family history of cancer (e.g., Li-Fraumeni syndrome) or with a rare tumor commonly found in the context of germline predisposition (e.g., rhabdoid tumor predisposition syndrome). Approximately 50% of patients with a brain tumor may be the first in a family identified to have a predisposition. The past decade has witnessed a rapid expansion in our molecular understanding of CNS tumors. A significant proportion of CNS tumors are now well characterized and known to harbor specific genetic changes that can be found in the germline. Additional novel predisposition syndromes are also being described. Identification of these germline syndromes in individual patients has not only enabled cascade testing of family members and early tumor surveillance but also increasingly affected cancer management in those patients. Therefore, the AACR Cancer Predisposition Working Group chose to highlight these advances in CNS tumor predisposition and summarize and/or generate surveillance recommendations for established and more recently emerging pediatric brain tumor predisposition syndromes.

Systematic testing in cholera surveillance enhances vaccine impact and cost-effectiveness.

Systematic testing in cholera surveillance enhances vaccine impact and cost-effectiveness.

Blood-based liquid biopsy: A promising noninvasive test in diagnosis, surveillance, and prognosis of patients with upper tract urothelial carcinoma

ObjectivesTo assess the efficacy of blood-based liquid biopsy in the diagnosis, surveillance, and prognosis of upper tract urothelial carcinoma (UTUC). Methods and MaterialsIn this prospective study, peripheral blood samples were collected from patients with primary UTUC before surgery with curative intent and follow-up visits at University of Southern California between May 2021 and September 2022. The samples were analyzed using the third-generation comprehensive high-definition single-cell assay (HDSCA3.0) to detect rare events, including circulating tumor cells (CTCs) and oncosomes, based on the immunofluorescence signals of DAPI (D), cytokeratin (CK), CD45/CD31 (CD), and vimentin (V). The findings of pre-surgery liquid biopsies were compared with those of blood samples from normal donors (NDs) and matched follow-up liquid biopsies. The association between liquid biopsy findings and clinical data, including recurrence-free survival (RFS), was also assessed. ResultsTwenty-eight patients with UTUC were included, of whom 21 had follow-up samples. Significant differences in specific rare analytes were detected in the preoperative samples compared to the NDs. In the post- vs. presurgery matched analysis, a significant decrease was detected in total-, CK-, and CK|V oncosomes, as well as in D-, D|V-, and D|V|CD cells. With a median follow-up of 11 months, 8 patients had disease recurrence. Survival analysis demonstrated that patients with >1.95 preoperative CK|V oncosomes (p = 0.020) and those with >4.18 D|CK|V cells (p = 0.050) had worse RFS compared to other patients. ConclusionsThis study demonstrated promising initial evidence for the biomarker role of CTCs and oncosomes in the diagnosis and surveillance of patients with UTUC.

Clozapine clinical toolkit optimizes inpatient clozapine monitoring.

Clozapine is the most effective antipsychotic in the management of treatment-resistant schizophrenia; however, its use is challenging due to the risk of severe adverse effects. Despite the risks associated with clozapine, there is no mandatory monitoring in Canada beyond hematologic testing for agranulocytosis surveillance. This study focuses on the development, implementation, and evaluation of a clozapine clinical toolkit (CTK) targeted at optimizing inpatient clozapine use. A comprehensive literature review was conducted to identify clozapine best practices, experts were consulted, and a comprehensive clozapine CTK was developed and implemented at a large Canadian tertiary hospital in December 2018. To evaluate the CTK, a retrospective chart review was conducted to assess for change in guideline-concordant monitoring pre- and post- CTK implementation. Patients were included if they were > 18 years of age and received clozapine during inpatient admission. Results were analyzed using descriptive and inferential statistics. Among the charts reviewed, 185 and 113 admissions met the pre- and post-CTK inclusion criteria, respectively. Staff used the CTK in the care of 96% of clozapine patients post implementation, and its use resulted in improvements in guideline-concordant monitoring for agranulocytosis and myocarditis. Implementation of the clozapine CTK increased the concordance of clozapine monitoring with best practice recommendations. Future research is necessary to assess the impact of the CTK on clinical outcomes and patient satisfaction.

COVID-19 Infection and Medicines in Pregnancy in Canada

IntroductionAlthough over 100 million pregnant women worldwide are at risk of infection with SARS-CoV-2, little data exists on the impact of COVID-19 and related treatments on maternal/neonatal health.Objectives1) To quantify the prevalence of medication use in pregnancy to treat COVID-19; 2) To quantify and compare the risk of adverse pregnancy/neonatal outcomes in those with and without COVID-19.MethodsIn the Canadian Mother-Child population-based cohort (CAMCCO), two key sub-cohorts were identified using prospective data collection of medical services, prescription drugs, hospitalization archives data, and COVID-19 surveillance testing program (02/28/2020-2021). The first cohort included all pregnant women with at least one completed trimester of pregnancy during the study period regardless of pregnancy status (delivery, induced/planned or spontaneous abortion); this cohort was further stratified on COVID-19 status. The second cohort included all non-pregnant women (aged 15-45) with a positive COVID-19 test. COVID-19 infection in pregnant or non-pregnant women was assessed using COVID-19 test results or ICD-10CM codeU07.1 from hospital data. COVID-19 severity was categorized based on hospital admission. Women were considered exposed to COVID-19 medications if they filled at least one prescription for a medicine included in the WHO list in the 30 days pre- or 30 days post-COVID-19 positive test/diagnosis. Considering potential confounders, association between COVID-19 during pregnancy, treated vs not, and perinatal outcomes were quantified using log-binomial regression models.Results150,345 pregnant women (3,464 (2.3%) had COVID-19), and 112,073 non-pregnant women with COVID-19 diagnoses were included. Pregnant women with COVID-19 were more likely to have severe infections compared to non-pregnant women with COVID-19 (11.4% vs 1.6%, p< 0.001). The most frequent medications used in pregnancy to treat COVID-19 were antibacterials (13.96%), psychoanaleptics (7.35%), and medicines for obstructive airway disease (3.20%). In pregnancy COVID-19 was associated with spontaneous abortions (adjRR 1.76, 95%CI 1.3, 2.25), gestational diabetes (adjRR 1.52, 95%CI 1.18, 1.97), prematurity (adjRR 1.30, 95%CI 1.01, 1.67), NICU admissions (adjRR 1.32, 95%CI 1.10, 1.59); COVID-19 severity was increasing these risks but COVID-19 treatment with study medications reduced all risks.ConclusionsSeverity of COVID-19 was greater in pregnancy. Antibacterials, psychoanaleptics, and medicines for obstructive airway disease were the most used overall. Severe COVID-19 in pregnancy was associated with higher risks of adverse maternal, and neonatal outcomes.Disclosure of InterestNone Declared

Pooling of samples to optimise SARS-CoV-2 detection in nasopharyngeal swabs and gargle lavage self-samples for covid-19 diagnostics and surveillance

Background Testing of pooled samples is an effective strategy for increasing testing capacity while saving resources and time. This study aimed to validate pooled testing and gather real-life data on its use for Covid-19 surveillance with a gargle lavage (GL) self-sampling strategy. Methods Two-stage pooled testing with pools of 6 and 12 samples was used for preventive testing of an asymptomatic population and Covid-19 surveillance in Czech schools. Both GL and nasopharyngeal swabs were used for sampling. Results In total, 61,111 samples were tested. The use of pooled testing for large-scale Covid-19 surveillance reduced consumable costs by almost 75% and increased testing capacity up to 3.8-fold compared to standard methods. RT-PCR experiments revealed a minimal loss of sensitivity (0–2.2%) when using pooled samples, enabling the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes with Ct values >35. The minor loss of sensitivity was counterbalanced by a significantly increased throughput and the ability to substantially increase testing frequencies. Conclusions Pooled testing is considerably more cost-effective and less time-consuming than standard testing for large-scale Covid-19 surveillance even when the prevalence of SARS-CoV-2 is fluctuating. Gargle lavage self-sampling is a non-invasive technique suitable for sample collection without a healthcare worker’s assistance.

Порівняння майстер кривої з нормативним методом оцінки в'язкості руйнування металу корпусу реактора ВВЕР-1000

The paper considers the generalized temperature dependence of the stress intensity factor KJC in the WWER-1000 reactor pressure vessel metal, which was derived based on the surveillance test data for fracture toughness. The consistency of the shape of the Master curve and 95 % upper and lower confidence bounds with the experimental dependence of crack resistance parameters on temperature was studied. From the point of view of the level of conservatism and acceptability, a comparison of the normative curves of fracture toughness according to NPRR (Nuclear Power Rules and Regulations) G-7-002-86 and SOU NNEGC (Standard of organization of Ukraine, National Nuclear Energy Generating Company) 177:2019 with a 5 % confidence bound of the Master curve was carried out. The possibility of using RT0 temperature as a temperature index instead of TK for the normative fracture toughness curve of SOU NNEGC 177:2019 was considered.

Candida auris outbreak at a tertiary care hospital during the COVID-19 pandemic

Candida auris (C auris) is a fungal pathogen that has the potential for environmental persistence leading to outbreaks in health care settings. There has been a worldwide surge in C auris outbreaks during the COVID-19 pandemic. In this report, we describe an outbreak of C auris, its control, patient outcomes, and lessons learned. The outbreak occurred in a 600-bed adult academic tertiary care hospital. Contact tracing was initiated immediately after identification of the index case and surveillance testing for C auris was obtained from patients who were exposed to the index case. Infection prevention measures were closely followed. A total of 560 cultures were performed on 453 unique patients between August 2021 and December 2021. Of those, 31 cultures (5.5%) were positive for C auris; 27 (87.1%) were colonized with C auris, while 4 patients developed a clinical infection (12.9%). The secondary attack rate was 6.8% (31/453). The 30-day all-cause mortality rate for all patients who tested positive for C auris was 9.7%. C auris can cause protracted outbreaks that result in colonization and invasive infections. Multidisciplinary work to improve adherence to infection prevention measures as well as targeted admission screening are essential to limit outbreaks.

Abstract 6373: Effectiveness of tumor surveillance across pediatric cancer predisposition syndromes

Abstract Background: Pediatric oncology patients are increasingly recognized as having an underlying cancer predisposing syndrome (CPS). For individuals diagnosed with a CPS, surveillance is often recommended to detect new tumors at their earliest and most curable stages. Screening is heavily based on radiologic imaging, however data on the effectiveness and outcomes of surveillance are limited. Methods: Patients with a clinical and/or molecular CPS diagnosis, including 274 children and young adults with 35 CPS at a single specialty pediatric oncology center, were monitored using standardized surveillance protocols over an average of 3 years (range 1 month - 12 years). Patients with hereditary retinoblastoma were excluded as surveillance was completed by a separate team. The cohort included 139 patients (50.7%) with a prior tumor history while 135 (49.3%) had no prior cancer. This study reviewed tumors diagnosed, method of detection, clinical course, and patient outcomes. Individual reports from 1,533 surveillance tests including diagnostic imaging, colonoscopy, and upper endoscopy, were assessed and classified for accuracy. Sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were calculated for selected surveillance methods, and themes of common strengths or weaknesses of specific imaging modalities were identified. Results: During the study period from January 1, 2009 - September 31, 2021, 35 asymptomatic tumors were detected in 27 patients through surveillance (9.9% of the cohort), while five symptomatic tumors were detected in five patients (1.8%) outside of surveillance. Ten tumors (28.6%) discovered through surveillance were identified on first surveillance imaging. Among these 35 new tumors, 19 (54.3%) were diagnosed in children with a previously treated cancer, six (17.1%) were diagnosed in patients still being treated for cancer, and 10 (28.6%) were diagnosed in those with no prior cancer history. Malignant solid and brain tumors identified through surveillance were more often localized (20 of 24; 83.3%) than similar tumors detected before CPS diagnosis (71 of 125; 56.8%, p ≤0.0001). Of the 24 tumors identified through surveillance and surgically resected, 17 (70.8%) had completely negative margins. When analyzed across all CPS, the sensitivity (96.4%), specificity (99.6%), PPV (95.7%), and NPV (99.6%) of surveillance testing was high, with few false positive (n=6/1,533, 0.4%) or false negative (n=5/1,533, 0.3%) reports. No invasive interventions were performed due to false positive results. Conclusion: Patients with CPS are at increased risk of primary and secondary tumor development with 10% of our cohort developing a tumor in a short time span. Surveillance effectively enabled early detection of new brain and solid tumors across a wide spectrum of CPS which allowed for complete surgical resection and successful treatment in most cases. Citation Format: Melissa R. Perrino, Alise Blake, Cara E. Morin, Leslie Taylor, Rose B. McGee, Sara Lewis, Stacy Hines-Dowell, Arti Pandey, Paige Turner, Manish Kubal, Yin Su, Li Tang, Laura Howell, Lynn W. Harrison, Zachary Abramson, Ann Schechter, Noah D. Sabin, Kim E. Nichols. Effectiveness of tumor surveillance across pediatric cancer predisposition syndromes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6373.

A measles IgM rapid diagnostic test to address challenges with national measles surveillance and response in Malaysia.

A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

Noninvasive Tests for Bladder Cancer Detection and Surveillance: A Systematic Review of Commercially Available Assays.

An important reason for the high health care costs associated with bladder cancer is the need for frequent cystoscopy for detection and surveillance of this disease. Cytologic analysis of voided urine specimens can assist, but is too inaccurate to replace cystoscopy. In an effort to create reliable, objective, noninvasive mechanisms for detecting bladder cancer, a number of urine-based molecular tests have been developed with the ultimate goal of reducing the frequency of cystoscopy. To summarize the performance of urine-based biomarker tests, currently commercially available in the US, as part of the initial workup for hematuria and for bladder cancer surveillance. In accordance with PRISMA guidelines we performed a systematic review of the literature on the performance of NMP22, BTA, UroVysion, ImmunoCyt/uCyt, CxBladder, and Bladder EpiCheck. Median sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each test based on the included studies. Twenty-eight studies met inclusion criteria for the performance of five urine-based biomarker tests in the setting hematuria workup. Median sensitivity ranged from 65.7% -100% and specificity ranged from 62.5% -93.8%. Median NPV ranged from 94.2% -98.3% and PPV ranged from 29% -58.7%. Fourteen studies met inclusion criteria for the performance of six tests in the setting of bladder cancer surveillance. Median sensitivity ranged from 22.6% -92.0% and specificity from 20.5% -97.9%. Median NPV ranged from 52.9% -96.5% and PPV ranged from 48.1% -75.7%. Our analysis finds that while these tests may provide some clinical utility, none of the assays have thus far demonstrated objective evidence to supplant the gold diagnostic standard.

Longitudinal adherence to surveillance for late effects of cancer treatment: a population-based study of adult survivors of childhood cancer.

Adult survivors of childhood cancer are at elevated risk of morbidity and mortality compared to the general population, but their adherence to lifelong periodic surveillance is suboptimal. We aimed to examine adherence to surveillance guidelines for high-yield tests and identify risk factors for nonadherence in adult survivors of childhood cancer. In this retrospective, population-based cohort study, we used health care administrative data from Ontario, Canada, to identify adult survivors of childhood cancer diagnosed between 1986 and 2014 who were at elevated risk of therapy-related colorectal cancer, breast cancer, or cardiomyopathy. Using a Poisson regression framework, we assessed longitudinal adherence and predictors of adherence to the Children's Oncology Group surveillance guideline. Among 3241 survivors, 327 (10%), 234 (7%), and 3205 (99%) were at elevated risk for colorectal cancer, breast cancer, and cardiomyopathy, respectively. Within these cohorts, only 13%, 6%, and 53% were adherent to recommended surveillance as of February 2020. During a median follow-up of 7.8 years, the proportion of time spent adherent was 14% among survivors at elevated risk for colorectal cancer, 10% for breast cancer, and 43% for cardiomyopathy. Significant predictors of adherence varied across the risk groups, but higher comorbidity was associated with adherence to recommended surveillance. Survivors of childhood cancer in Ontario are rarely up to date for recommended surveillance tests. Tailored interventions beyond specialized clinics are needed to improve surveillance adherence.

IMPROVER (Involving Men with Prostate Cancer in Engaged Research): Assessing Patient Experience With Testing, Diagnosis, And Surveillance

BackgroundOur understanding of patient experiences with prostate cancer testing for diagnosis and surveillance is limited. The aim of this study was to collaborate with patients and clinicians to understand their lived experience and unmet needs around the early detection, diagnosis and monitoring (active surveillance) of prostate cancer. MethodsTwo focus groups were held with patients (n = 20) and healthcare professionals (n = 16), to identify the main challenges in prostate cancer detection, diagnosis, and monitoring. This information formed the basis of an online questionnaire for broader dissemination. ResultsA total of 1138 analyzable responses were obtained from people tested for prostate cancer (69% tested positive) in Europe and the US. Only 29 healthcare professionals completed the survey. Almost one-third of people reported knowing very little/nothing about prostate cancer prior to testing. Prior disease awareness was significantly higher in those who tested negative (P < .0001). Most respondents (n = 857; 75%) felt informed about the steps involved in testing. Receiving written information was a key factor; 91% of those who felt uninformed were not given any written information. Overall, most people felt “satisfied” with the typical prostate cancer tests: PSA, DRE, mpMRI, and biopsy. However, dissatisfaction for prostate biopsy (12%) was almost double that of other tests (P < .0001). Most patients understood why each test was done, and felt that their results and next steps were clearly explained to them; though PSA scored lowest in all of these fields. Apart from PSA, test satisfaction was lower when used repeatedly for surveillance, compared to once-off detection/diagnosis. ConclusionsGreater public awareness and education around prostate cancer, as well as clear and accessible written information for patients at the beginning of their cancer journey is needed. Further research is needed into alternative, less invasive tests, particularly when used repeatedly in the surveillance population.

Protocol for the ONLOOP trial: pragmatic randomized trial evaluating a province-wide system of personalized reminders for evidence-based surveillance tests in adult survivors of childhood cancer in Ontario

BackgroundChildhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time.MethodsThis is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP’s impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants’ consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later.The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed.DiscussionThe results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population.Trial registrationClinicalTrials.gov NCT05832138.

Automated molecular detection of West Nile Virus in mosquito pools using the Panther Fusion system

West Nile Virus (WNV) is an arthropod-borne virus that is spread through mosquito vectors. WNV emerged in the US in 1999 and has since become endemic in the US, causing the most domestically acquired arboviral disease in the country. Mosquito surveillance for WNV is useful to monitor arboviral disease burden over time and across different locations. RT-qPCR is the preferred method for WNV surveillance, but these methods are labor-intensive. The Panther Fusion System has an Open Access feature that allows for laboratory-developed tests (LDTs) to run on a fully automated system for nucleic acid extraction, RT-qPCR, and result generation. This study demonstrates the successful optimization of a WNV multiplex LDT (assay targets: ENV and NS1 genes) for high-throughput environmental surveillance testing of mosquito pool homogenates on the Panther Fusion System. Analytical sensitivity of the assay was 186 and 744 copies/PCR reaction for the ENV and NS1 targets, respectively. To assess the performance of this assay, a total of 80 mosquito pools were tested, including 60 previously tested pools and 20 spiked negative mosquito pools. Among the 60 previously tested specimens, the Panther Fusion WNV LDT demonstrated 100% positive and negative agreement with the CDC West Nile RT-qPCR assay. The Panther Fusion WNV LDT also detected all 20 spiked specimens. The Panther Fusion WNV LDT assay was successfully developed and optimized for high throughput testing with similar performance to the previously used CDC West Nile RT-qPCR assay.

The effects of flux on the radiation-induced embrittlement of reactor pressure vessel steels: review of current understanding and application to high fluences

It is necessary to quantify the effects of flux on reactor pressure vessel steel embrittlement under neutron irradiation, if surveillance or high-flux test reactor data is used to predict vessel embrittlement occurring at lower fluxes. This is particularly important when considering embrittlement occurring during extended (60–80 years) operation for which there is no direct experience. Dedicated investigations are time-consuming and expensive even when only small flux-fluence ranges are investigated, so collating data from multiple campaigns is necessary to provide sufficient information to cover the wide range of fluxes required for vessel assessment in the long term. This paper collates and reviews such data. The review finds that flux dependences probably differ in sign and strength in different regimes (low flux and fluence, intermediate flux at low and high fluence, high flux at low and high fluence) with the regime limits affected by composition and temperature. The current understanding of diffusion processes and microstructural development are invaluable in interpreting the trends and limits. Many contradictory data sets were found, however, and not all contradictions could be dismissed as resulting from poor quality data. Suggestions are made for investigations to clarify the uncertainties. One wide-ranging model of flux effects, based on an extensive data set, is used to compare high-fluence data from different sources, to assess whether embrittlement rates accelerate after a high, threshold fluence. The model helps to identify experiments which investigated comparable flux-fluence-temperature regimes. The comparable data are split evenly between data sets supporting acceleration after a particular fluence and data sets contradicting it. The model identifies regimes in which further campaigns would clarify the causes of these contrasting observations.

Screening and surveillance for hereditary colorectal cancer.

Hereditary colorectal cancer is a type of cancer that is caused by a genetic mutation. Individuals with a family history of colorectal cancer, or who have a known hereditary syndrome, are at an increased risk of developing the disease. Screening and surveillance are important tools for managing the risk of hereditary colorectal cancer. Screening involves a combination of tests that can detect precancerous or cancerous changes in the colon and rectum. Surveillance involves regular follow-up examinations to monitor disease progression and to identify new developments. The frequency and type of screening and surveillance tests may vary depending on an individual's risk factors, genetic profile, and medical history. However, early detection and treatment of hereditary colorectal cancer can significantly improve patient outcomes and reduce mortality rates. By implementing comprehensive screening and surveillance strategies, healthcare providers can help individuals at risk of hereditary colorectal cancer to receive timely interventions and make informed decisions about their health. Specific examples of screening and surveillance tests for hereditary colorectal cancer include colonoscopy, genetic testing, and imaging tests. In this review article, we will discuss detailed screening and surveillance of hereditary colorectal cancer.

FibroScan as a surveillance marker post-cavopulmonary anastomosis for single-ventricle physiology.

Single-ventricle physiology encompasses a group of congenital cardiac malformations with only one functional ventricle. The Fontan procedure is the final palliation of this pathway and has its complications. One of these is Fontan-associated liver disease (FALD). It is known that all patients with Fontan will have FALD, due to the physiology of the Fontan circuit, and only the severity will vary. The pathophysiology of hepatic damage in FALD is unique and not easily detectable by routine non-invasive investigations. Therefore, this study is aimed to identify if FibroScan can be used as a surveillance marker to detect and assess the progression of FALD. Patients who attended the Cardiothoracic and Vascular Surgery Outpatient Department (OPD) for follow-up post-cavopulmonary anastomosis (bidirectional Glenn and Fontan) were enrolled in this study. They underwent routine examinations and tests, and in addition a FibroScan was performed. FibroScan showed that the liver stiffness measurement (LSM) was increased in all patients who had undergone Fontan and a couple of patients who had undergone bidirectional (BD) Glenn. The LSM was 12.29 (± 3.59) kPa in patients post-Fontan and 6.64 (± 4.24) kPa in patients post-BD Glenn. This raised LSM was not associated with a parallel rise in liver enzymes or other laboratory markers associated with liver function. This emphasizes the suitability of FibroScan as an early and non-invasive surveillance tool for monitoring the progression of hepatic venous congestion and FALD. We have found that LSM via FibroScan can effectively be a surveillance or screening test for FALD. Serial FibroScans can be used to monitor the progress of liver disease. Raised LSM may also have a role in predicting the morbidity for completion of Fontan post-BD Glenn operation. Large-scale studies are needed to validate our findings.