Survival after breast cancer according to participation in organised or opportunistic screening and deprivation

BackgroundMany studies have investigated the survival of women by comparing those who participated in organised screening with those who did not. However, among those who do not participate in organised screening, some women undergo opportunistic screening, but these women remain difficult to identify, particularly in France. Therefore, the aim of this study was to identify opportunistic screening, and then to study survival after breast cancer separately according to participation in organised, opportunistic or no screening, and taking into account sociodemographic inequalities.MethodsThe study population was identified from 3 French cancer registries, whose data was crossed with the screening coordination centers and the National Health Data System to identify the different type of screening. The European Deprivation Index was used to define the level of deprivation. We estimated net survival using the Pohar-Perme method.ResultsThe 5-year net survival probabilities were higher for women who attended organised screening (97.0 %) than for women with opportunistic screening (94.1 %) or non-attenders (78.1 %). According to the level of deprivation, a significant difference was observed between the groups of women screened by organised and opportunistic screening, compared to the non-attenders.ConclusionThe identification of opportunistic screening is an important element in identifying women who do not screening. It enables to us to see that women who do not attend any screening have a much higher loss-of-opportunity in terms of survival than those who participate in organised or opportunistic screening, and even more so in the most deprived areas.     

Rapid Cervical Cytology Screening

2030 Papanicolaou-stained cervical smears were submitted for rapid screening prior to routine screening; 30 seconds were allowed for each slide, and those thought to be abnormal were identified. The results were compared with those of conventional screening. All severe and moderately dyskaryotic cases were detected by the rapid technique, as were the majority of mild dyskaryosis and borderline cases. When a laboratory has a backlog it may be worth rapid-screening all slides in addition to routine screening, so that patients most at risk can receive prompt treatment.     

An assessment of partial rescreening as an internal quality control method for cervical smears

Partial screening was performed on 10 800 cervical smears, comprising 8640 filed negative and unsatisfactory smears and 2160 newly received smears prior to conventional screening. Each slide was screened for 30 s and those considered abnormal were reviewed by standard screening. Partial screening led to the detection of 27 additional infections and 44 additional cytological abnormalities. These detection rates are better than those obtained with the traditional method of rescreening only a proportion of smears. Amongst the smears partially screened before conventional screening, partial screening detected 37-66% of infections and 22-71% of cytological abnormalities. We recommend the use of partial rescreening of all negatively reported smears as a method of internal quality control in cervical cytology laboratories.     

Antenatal screening for carriers of cystic fibrosis: randomised trial of stepwise v couple screening.

OBJECTIVE--To perform a rigorous comparative evaluation of stepwise and couple approaches to antenatal carrier screening for cystic fibrosis. DESIGN--Pragmatic randomised trial. SETTING--Hospital antenatal clinic serving a regional population. SUBJECTS--2002 women (couples) attending for booking antenatal visit at less than 17 weeks'' gestation with no family history of cystic fibrosis. INTERVENTIONS--Offering counselling and carrier testing for cystic fibrosis, either to women in the first instance (stepwise) or to couples (couple screening). MAIN OUTCOME MEASURES--Uptake rates; anxiety; knowledge of cystic fibrosis and carrier status (both partners); attitudes to health, pregnancy, the baby, and screening (both partners); and uptake of carrier testing by relatives. RESULTS--Uptake of screening was the same for both approaches (90%). After delivery most women remembered test results and their meaning, but 53/253 (21%) of those with negative results of couple testing had forgotten that repeat testing would be advisable if they had a pregnancy with a new partner. With stepwise screening women identified as carriers had high levels of anxiety when results were received (mean anxiety score 52.3). This dissipated with a reassuring partner''s result (carriers'' mean anxiety score 36.1) to levels similar to those receiving negative results from couple screening. Of those receiving negative results, women who had stepwise screening were significantly less anxious than those who had couple screening (mean score with result 32.1 v 35.4, 95% confidence interval for difference -4.7 to -2.1). CONCLUSIONS--Couple screening allows carriers to avoid transient high levels of anxiety, but is associated with more anxiety and false reassurance among most screenees who will test negative. Stepwise screening gives carriers and their relatives genetic information and is, in our opinion, the better method.     

性周期筛选合笼与非筛选合笼制备大鼠妊娠模型的比较

目的比较制备大鼠妊娠模型时在合笼前进行阴道涂片性周期筛选与不筛选两种方法对大鼠受孕率、受孕速度（合笼次数）的影响。方法 26只SD雌性大鼠随机分为阴道涂片性周期筛选合笼组（涂片组）、不筛选合笼组（自由组）,筛选组雌鼠在合笼前进行阴道涂片性周期筛选,筛选处于动情期或动情前期的雌鼠进行合笼;自由组不进行性周期筛选,直接合笼;实验中大鼠分组、合笼均采用单因素完全随机方法。结果两种合笼方法对大鼠受孕率和受孕速度差异不显著（P〉0.05）。结论鉴于两种合笼方法在制备大鼠妊娠模型的受孕率及受孕速度方面无差异,同时为了减少人为干预对雌鼠的刺激和影响,建议在制备大鼠妊娠模型时考虑采用自由合笼法。     

A note of feature screening via a rank-based coefficient of correlation

Feature screening is a useful and popular tool to detect informative predictors for ultrahigh-dimensional data before developing statistical analysis or constructing statistical models. While a large body of feature screening procedures has been developed, most methods are restricted to examine either continuous or discrete responses. Moreover, even though many model-free feature screening methods have been proposed, additional assumptions are imposed in those methods to ensure their theoretical results. To address those difficulties and provide simple implementation, in this paper we extend the rank-based coefficient of correlation to develop a feature screening procedure. We show that this new screening criterion is able to deal with continuous and binary responses. Theoretically, the sure screening property is established to justify the proposed method. Simulation studies demonstrate that the predictors with nonlinear and oscillatory trajectories are successfully retained regardless of the distribution of the response. Finally, the proposed method is implemented to analyze two microarray datasets.     

Cost-Effectiveness of Colorectal Cancer Screening Protocols in Urban Chinese Populations

Colorectal cancer (CRC) takes a second and fourth position in the incidence and mortality lists respectively among all malignant tumors in urban populations in China. This study was designed to evaluate the cost-effectiveness of two different CRC screening protocols: faecal occult blood test (FOBT) alone, and FOBT plus a high-risk factor questionnaire (HRFQ) as the respective initial screens, followed by colonoscopy. We developed a Markov model to simulate the progression of a cohort of 100,000 average risk asymptomatic individuals moving through a defined series of states between the ages of 40 to 74 years. The parameters used for the modeling came from the CESP (Comparison and Evaluation of Screening Programs for Colorectal Cancer in Urban Communities in China) study and published literature. Eight CRC screening scenarios were tested in the Markov model. The cost-effectiveness of CRC screening under each scenario was measured by an incremental cost-effectiveness ratio (ICER) compared with a scenario without CRC screening. The study revealed that a combined use of FOBT and HRFQ is preferable in CRC screening programs as an initial screening instrument. Annual FOBT+HRFQ screening is recommended for those who have a negative initial result and those who have a positive result but have failed to continue to colonoscopic examination. Repeated colonoscopy (for those with a positive result in initial screening but a negative colonoscopy result) should be performed at a ten-year interval instead of one-year. Such a protocol would cost 7732 Yuan per life year saved, which is the most cost-effective option. In conclusion, the current Chinese Trial Version for CRC Screening Strategy should be revised in line with the most cost-effective protocol identified in this study.     

Meeting report: high-throughput technologies for in vivo imaging agents

Combinatorial chemistry and high-throughput screening have become standard tools for discovering new drug candidates with suitable pharmacological properties. Now, those same technologies are starting to be applied to the problem of discovering novel in vivo imaging agents. Important differences in the biological and pharmacological properties needed for imaging agents, compared to those for a therapeutic agent, require new screening methods that emphasize those characteristics, such as optimized residence time and tissue specificity, that make for a good imaging agent candidate.     

Cost Effectiveness of Cryptococcal Antigen Screening as a Strategy to Prevent HIV-Associated Cryptococcal Meningitis in South Africa

Objectives

Cryptococcal meningitis (CM)-related mortality may be prevented by screening patients for sub-clinical cryptococcal antigenaemia (CRAG) at antiretroviral-therapy (ART) initiation and pre-emptively treating those testing positive. Prior to programmatic implementation in South Africa we performed a cost-effectiveness analysis of alternative preventive strategies for CM.

Design

Cost-effectiveness analysis.

Methods

Using South African data we modelled the cost-effectiveness of four strategies for patients with CD4 cell-counts <100 cells/µl starting ART 1) no screening or prophylaxis (standard of care), 2) universal primary fluconazole prophylaxis, 3) CRAG screening with fluconazole treatment if antigen-positive, 4) CRAG screening with lumbar puncture if antigen-positive and either amphotericin-B for those with CNS disease or fluconazole for those without. Analysis was limited to the first year of ART.

Results

The least costly strategy was CRAG screening followed by high-dose fluconazole treatment of all CRAG-positive individuals. This strategy dominated the standard of care at CRAG prevalence ≥0.6%. Although CRAG screening followed by lumbar puncture in all antigen-positive individuals was the most effective strategy clinically, the incremental benefit of LPs and amphotericin therapy for those with CNS disease was small and additional costs were large (US$158 versus US$51per person year; incremental cost effectiveness ratio(ICER) US$889,267 per life year gained). Both CRAG screening strategies are less costly and more clinically effective than current practice. Primary prophylaxis is more effective than current practice, but relatively cost-ineffective (ICER US$20,495).

Conclusions

CRAG screening would be a cost-effective strategy to prevent CM-related mortality among patients initiating ART in South Africa. These findings provide further justification for programmatic implementation of CRAG screening.     

Impact of genetic counseling and testing on colorectal cancer screening behavior

One goal of cancer genetic counseling is to improve early detection and prevention of cancers by identifying individuals at risk and providing screening recommendations. This study determined the impact of genetic counseling and testing on patient's post-genetic risk assessment colorectal cancer screening behaviors. Follow-up data from patients seen August, 1996, through May, 1998, at the Johns Hopkins Cancer Risk Assessment Clinic were analyzed. Eligible patients included those without cancer who were due for a colon examination by the time of follow-up, based on recommendations given during genetic risk assessment (GRA). We analyzed the role of gender, age, time since GRA, prior screening, genetic testing decision, mutation status, and post-GRA screening. Of 65 patients evaluated, 50 (76.9%) had undergone at least one endoscopic colon exam prior to visiting the Cancer Risk Assessment Clinic. At the time of GRA, 37 of 65 (56.9%) were overdue for a colon exam and at the time of follow-up, 15/65 (23.1%) were past due (p < 0.001). Patients with mutation-positive genetic tests were more likely to adhere to screening guidelines than those with negative gene tests (100% vs. 40.5%, p = 0.05). Genetic counseling and testing increases overall patient adherence with recommended colon screening, especially for those with positive genetic test results. However, patients with negative results may receive false reassurance about cancer risks and fail to follow recommended screening. Emphasis should be placed on the importance of screening even when genetic test results are negative.     

Screening for cystic fibrosis: feasibility of molecular genetic analysis of dried blood specimens

Direct genotypic analysis for the common Caucasian cystic fibrosis mutation (delta F508) was performed using dried blood specimens in a filter paper matrix (neonatal screening blotter). DNA was obtained from dried and liquid blood samples, amplified, and analyzed by polyacrylamide gel electrophoresis. Additionally, intact 4-mm-diameter punched discs from blotters containing dried blood specimen were used in the amplification reactions and analyzed by electrophoresis. The results agreed completely between these three sample types, demonstrating the feasibility of molecular genetic confirmation of the delta F508 mutation from the neonatal screening blotter among those with positive CF screening results. Such a program could reduce follow-up testing by at least 50% in a CF newborn screening program and would identify immediately those families who would benefit from carrier detection for the delta F508 allele.     

Different strategies for screening and prevention of type 2 diabetes in adults: cost effectiveness analysis

Objective To compare four potential screening strategies, and subsequent interventions, for the prevention and treatment of type 2 diabetes: (a) screening for type 2 diabetes to enable early detection and treatment, (b) screening for type 2 diabetes and impaired glucose tolerance, intervening with lifestyle interventions in those with a diagnosis of impaired glucose tolerance to delay or prevent diabetes, (c) as for (b) but with pharmacological interventions, and (d) no screening.Design Cost effectiveness analysis based on development and evaluation of probabilistic, comprehensive economic decision analytic model, from screening to death.Setting A hypothetical population, aged 45 at time of screening, with above average risk of diabetes.Data sources Published clinical trials and epidemiological studies retrieved from electronic bibliographic databases; supplementary data obtained from the Department of Health statistics for England and Wales, the screening those at risk (STAR) study, and the Leicester division of the ADDITION study.Methods A hybrid decision tree/Markov model was developed to simulate the long term effects of each screening strategy, in terms of both clinical and cost effectiveness outcomes. The base case model assumed a 50 year time horizon with discounting of both costs and benefits at 3.5%. Sensitivity analyses were carried out to investigate assumptions of the model and to identify which model inputs had most impact on the results.Results Estimated costs for each quality adjusted life year (QALY) gained (discounted at 3.5% a year for both costs and benefits) were £14 150 (€17 560; $27 860) for screening for type 2 diabetes, £6242 for screening for diabetes and impaired glucose tolerance followed by lifestyle interventions, and £7023 for screening for diabetes and impaired glucose tolerance followed by pharmacological interventions, all compared with no screening. At a willingness-to-pay threshold of £20 000 the probability of the intervention being cost effective was 49%, 93%, and 85% for each of the active screening strategies respectively.Conclusions Screening for type 2 diabetes and impaired glucose tolerance, with appropriate intervention for those with impaired glucose tolerance, in an above average risk population aged 45, seems to be cost effective. The cost effectiveness of a policy of screening for diabetes alone, which offered no intervention to those with impaired glucose tolerance, is still uncertain.     

Screen technical noise in single cell RNA sequencing data

We proposed a data cleaning pipeline for single cell (SC) RNA-seq data, where we first screen genes (gene-wise screening) followed by screening cell libraries (library-wise screening). Gene-wise screening is based on the expectation that for a gene with a low technical noise, a gene's count in a library will tend to increase with the increase of library size, which was tested using negative binomial regression of gene count (as dependent variable) against library size (as independent variable). Library-wise screening is based on the expectation that across-library correlations for housekeeping (HK) genes is expected to be higher than the correlations for non-housekeeping (NHK) genes in those libraries with low technical noise. We removed those libraries, whose mean pairwise correlation for HK genes is NOT significantly higher than that for NHK genes. We successfully applied the pipeline to two large SC RNA-seq datasets. The pipeline was also developed into an R package.     

Screening Rate for Primary Aldosteronism Among Patients With Apparent Treatment-Resistant Hypertension: Retrospective Analysis of Current Practice

ObjectivePrimary aldosteronism (PA) is the most common secondary cause of hypertension. Patients with PA experience significant cardiovascular and other complications compared with patients with primary hypertension with the same degree of blood pressure control as those with PA. Guidelines have recommended screening all patients with resistant hypertension for PA. The objective of this study was to assess the screening rate for PA among patients with apparent treatment-resistant hypertension and determine the rate of positive screening test result among the group screened.MethodsThis was a retrospective chart review of electronic medical record data of all patients with hypertension aged ≥18 years within a single health system in Minnesota from September 2018 to September 2020.ResultsOf 140 734 patients who were aged ≥18 years and had a diagnosis of hypertension, 18 908 (13.4%) met the criteria for apparent treatment-resistant hypertension after those with congestive heart failure were excluded. Only 795 (4.2%) patients with apparent treatment-resistant hypertension underwent screening for PA in our cohort. Of the 795 patients who underwent screening for PA, 134 (16.9%) had a positive screening test result.ConclusionThe screening rate for PA among patients with resistant hypertension was low. Clinical and public health strategies directed at improving the screening rate for PA are vital.     

Screening and genetic counselling for relatives of patients with colorectal cancer in a family cancer clinic.

OBJECTIVE--To introduce and monitor a screening programme for first degree relatives of patients with colorectal cancer based on their calculated lifetime risk. DESIGN--Lifetime risks were calculated for first degree relatives of patients with colorectal cancer and used to offer screening based on estimated risk. SETTING--A family cancer clinic was set up as part of the North East Thames Regional Genetic Service for relatives of patients who had developed colorectal cancer before the age of 45 and members of families in which multiple cancer had occurred. PATIENTS--Self referrals as well as patients referred by general and hospital practitioners. INTERVENTION--Relatives with a lifetime risk of 1 in 10 or greater (high risk group) were offered screening five yearly by colonoscopy, and those whose risk was between 1 in 10 and 1 in 17 were offered yearly screening for faecal occult blood. Women with family histories compatible with Lynch type II cancer family syndrome were offered screening for breast and pelvic tumours. RESULTS--In four years 715 patients were seen. Acceptance of screening was 90% (644 patients). Of 151 patients screened for faecal occult blood, two were found to have polyps. This screening test was unsatisfactory for the high risk group, having a negative predictive value of 78% in 59 patients tested. Regular screening by colonoscopy was offered to 382 high risk patients; 62 patients with polyps and five with colonic cancer were found. One hundred and ten pedigrees were identified with the Lynch type II cancer family syndrome, and four of 35 women screened were found to have breast cancer. Of 14 relatives aged over 65 with a 1 in 2 risk of site specific colonic cancer or Lynch type II cancer family syndrome, seven were found to have polyps, one of whom had carcinoma in situ. CONCLUSIONS--Family history can be used to identify those at risk of colonic cancer and to target appropriate screening. Colonoscopy detected a high number of premalignant colonic polyps, but faecal occult blood testing was unsatisfactory for those at high risk of colorectal cancer.     

Detecting hypertension: screening versus case finding in Norway.

OBJECTIVE--Evaluation of detection of hypertension in adults in the county of Nord-Trøndelag, Norway. DESIGN--Cross sectional survey with clinical follow up examinations. SETTING--Health survey by screening teams from the national health screening service, and examinations by all 106 general practitioners in the county. SUBJECTS--During 1984-6, 74,977 persons (88.1% of those aged 20 years and over) participated in the health survey. MAIN OUTCOME MEASURES--Hypertension (when assessed by standardised recording and by questionnaires on drug treatment for hypertension) according to the blood pressure thresholds used in the Norwegian treatment programme. Subjects positive on screening were grouped after clinical examination into treatment groups. RESULTS--In all, 2399 subjects were positive for hypertension. Before screening 6210 (8.3%) patients reported taking antihypertensive drugs and another 3849 (5.1%) had their blood pressure monitored regularly. All who screened positive were referred to their general practitioner and evaluated according to a standard programme. As a result, drug treatment was started in 406 (0.5%) participants screened and blood pressure monitoring in another 1007 (1.3%). Of all patients taking antihypertensive drugs after the screening, 6399 (94.0%) had been diagnosed before screening, and of those whose blood pressure was monitored after the screening, 79.3% had been diagnosed before screening. CONCLUSIONS--At the blood pressure screening thresholds used, and when hypertension is defined by an overall clinical diagnosis, the results indicate that general practitioners can find and diagnose hypertensive patients with the case finding strategy.     

Helicobacter pylori and Gastric Cancer: What Are the Benefits of Screening Only for the CagA Phenotype of H. pylori?

Background. Strains of Helicobacter pylori that express the CagA protein are associated with a threefold increased gastric cancer risk as compared to H. pylori strains that do not express CagA. Screening and treatment only for CagA antibodies should target those individuals at highest gastric cancer risk while reducing the number of patients requiring antibiotics. We compared the costs and benefits of screening asymptomatic 50-year-old individuals for CagA, screening for all H. pylori strains, and no screening, both in the United States and abroad.
Materials and Methods. We employed Markov cost-effectiveness analysis using data from randomized, case-control, and cohort studies.
Results. In the United States, CagA screening would result in 1.5 million fewer antibiotic treatments but would prevent 1,400 fewer gastric cancers than would screening for all H. pylori. The incremental cost-effectiveness of CagA screening is $23,900 per life-year gained; for H. pylori screening, it is $25,100. Screening in countries with epidemiological characteristics similar to those of Colombia, Finland, and Japan costs less than $5,000 per life-year gained, and the difference between CagA and H. pylori screening is smaller than that in the United States.
Conclusions. Screening only for CagA-positive H. pylori is not substantially better than is screening for all H. pylori , either in the United States nor abroad. Screening is substantially more cost-effective outside the United States. Whether population screening is justified, however, is uncertain pending conclusive data regarding the reduction in gastric cancer risk from antibiotics.     

Pretreatment weight change is associated with obesity treatment outcomes

Clinical experience suggests some individuals begin obesity treatment weighing more than they did at pretreatment assessment. Weight fluctuations between baseline screening and the first treatment session were examined among individuals enrolling in a group behavioral obesity treatment outcome study. Participants (N = 480, 94% female; 28% African American; M BMI = 35.7) were classified into those who started treatment having gained weight (≥ +1.15% above screening weight), lost weight (≤ -1.15% below screening weight) or remained weight stable. The majority of participants were weight-stable (61%) during the waiting period, but 23% lost weight (-2.36 ± 1.26 kg) and 16% gained weight (+2.11 ± 1.04 kg) between baseline screening and initiating treatment. Those who lost during the pretreatment period went on to have the greatest losses at 6-months (-8.9 ± 4.9 kg), with significantly greater weight losses than either the weight-stable (-6.1 ± 5.8 kg) or the weight-gain (-5.7 ± 5.8 kg) groups. Further, those who lost weight during the waiting period went on to attend a significantly higher proportion of treatment sessions and submitted more self-monitoring diaries than those who gained weight and those who stayed weight stable while waiting. Thus, pretreatment weight change was associated with treatment outcomes and may be relevant for research screening. Further, pretreatment weight change may be a clinical marker for likely success in behavioral weight control and as such warrants additional investigation to inform potential methods for enhancing outcomes for individuals in obesity treatment.     

The impact of driving time on participation in colorectal cancer screening with sigmoidoscopy and faecal immunochemical blood test

BackgroundHigh participation rates are important for a colorectal cancer (CRC) screening programme to be effective. Having a long travelling distance to screening centres may impede participation.MethodsWe analysed the association between driving time from home address to screening centre and participation among individuals invited to screening with faecal immunochemical test (FIT) (n = 68,624) or sigmoidoscopy (n = 46,076) in a randomized trial in Norway in 2012–17. Two screening centres were involved. We fitted multiple logistic regression models, adjusted for demographic, socioeconomic and health characteristics, and reported odds ratios (OR) with 95% confidence intervals (CI).ResultsParticipation rates were 58.9 % (n = 40,445) for FIT and 51.9 % (n = 23,911) for sigmoidoscopy. In sigmoidoscopy, participation was 56.9 % and 47.9 % in those living < 20 and > 60 min by car from the screening centres, respectively. For each 10 min driving time increase, OR for participating in sigmoidoscopy screening was 0.93 (95 % CI 0.91–0.95). There was a significant difference between the two screening centres (p-value for heterogeneity <0.001). Participation in FIT screening were 61.2 % and 57.1 % in those with < 20 and > 60 min driving time, respectively, and the OR was 0.98 (95 % CI 0.96–0.99) for each 10 min increase (heterogeneity between screening methods, P-value <0.001). Among those with a positive FIT, compliance to colonoscopy was higher in those living < 20 compared to > 60 min from the centres (95.1 % vs. 92.9 %, respectively, OR 0.86; 95 % CI 0.77–0.93 for each 10 min increase).ConclusionsDriving time to screening centre was a significant predictor of participation, mainly in sigmoidoscopy. There were local differences in the impact of driving time on participation. Driving time also affected compliance to colonoscopy after a positive FIT. When planning a CRC screening programme, one should consider offering people living far from screening sites special assistance to facilitate their participation.     

RNAi screening for fat regulatory genes with SRS microscopy

Identification of genes regulating fat accumulation is important for basic and medical research; genetic screening for those genes in Caenorhabditis elegans, a widely used model organism, requires in vivo quantification of lipids. We demonstrated RNA interference screening based on quantitative imaging of lipids with label-free stimulated Raman scattering (SRS) microscopy, which overcomes major limitations of coherent anti-Stokes Raman scattering microscopy. Our screening yielded eight new genetic regulators of fat storage.