Predictors of re-attendance at biennial screening mammography following a false positive referral: A study among women in the south of the Netherlands.

AIM: A false positive (FP) referral after screening mammography may influence a woman's likelihood to re-attend the screening program. The impact of having a FP result in the first or subsequent screening round on re-attendance after a FP result was investigated. In addition, we aimed to study differences in re-attendance rates between women who underwent non-invasive and invasive additional examinations as part of the diagnostic work-up following a FP referral. METHODS: A consecutive series of 13,597 women with a FP referral following biennial screening mammography in the south of the Netherlands between 2009 and 2019 was included. RESULTS: The screening re-attendance rate was 81.2% after a FP referral, and 91.3% when also including women who had clinical mammographic follow-up. Women who received a FP referral in the first screening round were less likely to re-attend the screening programme in the following three years, compared to those with a FP test in any subsequent round (odds ratio (OR): 0.59, 95%-confidence interval (CI): 0.51-0.69). Women with a FP referral who underwent invasive examinations after referral were less likely to re-attend the screening programme than those who only received additional imaging (OR, 0.48; 95% CI 0.36-0.64). CONCLUSION: Women with a FP referral are less likely to re-attend the screening programme if this referral occurs at their first screening round or when they undergo invasive diagnostic workup. Hospitals and screening organizations should prioritize informing women about the importance of re-attending the programme following a FP referral.

Breast Cancer Incidence After a False-Positive Mammography Result.

Importance: False-positive mammography results are common. However, long-term outcomes after a false-positive result remain unclear. Objectives: To examine long-term outcomes after a false-positive mammography result and to investigate whether the association of a false-positive mammography result with cancer differs by baseline characteristics, tumor characteristics, and time since the false-positive result. Design, Setting, and Participants: This population-based, matched cohort study was conducted in Sweden from January 1, 1991, to March 31, 2020. It included 45 213 women who received a first false-positive mammography result between 1991 and 2017 and 452 130 controls matched on age, calendar year of mammography, and screening history (no previous false-positive result). The study also included 1113 women with a false-positive result and 11 130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. Statistical analysis was performed from April 2022 to February 2023. Exposure: A false-positive mammography result. Main Outcomes and Measures: Breast cancer incidence and mortality. Results: The study cohort included 497 343 women (median age, 52 years [IQR, 42-59 years]). The 20-year cumulative incidence of breast cancer was 11.3% (95% CI, 10.7%-11.9%) among women with a false-positive result vs 7.3% (95% CI, 7.2%-7.5%) among those without, with an adjusted hazard ratio (HR) of 1.61 (95% CI, 1.54-1.68). The corresponding HRs were higher among women aged 60 to 75 years at the examination (HR, 2.02; 95% CI, 1.80-2.26) and those with lower mammographic breast density (HR, 4.65; 95% CI, 2.61-8.29). In addition, breast cancer risk was higher for women who underwent a biopsy at the recall (HR, 1.77; 95% CI, 1.63-1.92) than for those without a biopsy (HR, 1.51; 95% CI, 1.43-1.60). Cancers after a false-positive result were more likely to be detected on the ipsilateral side of the false-positive result (HR, 1.92; 95% CI, 1.81-2.04) and were more common during the first 4 years of follow-up (HR, 2.57; 95% CI, 2.33-2.85 during the first 2 years; HR, 1.93; 95% CI, 1.76-2.12 at >2 to 4 years). No statistical difference was found for different tumor characteristics (except for larger tumor size). Furthermore, associated with the increased risk of breast cancer, women with a false-positive result had an 84% higher rate of breast cancer death than those without (HR, 1.84; 95% CI, 1.57-2.15). Conclusions and Relevance: This study suggests that the risk of developing breast cancer after a false-positive mammography result differs by individual characteristics and follow-up. These findings can be used to develop individualized risk-based breast cancer screening after a false-positive result.

Online false discovery rate control for LORD++ and SAFFRON under positive, local dependence.

Online testing procedures assume that hypotheses are observed in sequence, and allow the significance thresholds for upcoming tests to depend on the test statistics observed so far. Some of the most popular online methods include alpha investing, LORD++, and SAFFRON. These three methods have been shown to provide online control of the "modified" false discovery rate (mFDR) under a condition known as CS. However, to our knowledge, LORD++ and SAFFRON have only been shown to control the traditional false discovery rate (FDR) under an independence condition on the test statistics. Our work bolsters these results by showing that SAFFRON and LORD++ additionally ensure online control of the FDR under a "local" form of nonnegative dependence. Further, FDR control is maintained under certain types of adaptive stopping rules, such as stopping after a certain number of rejections have been observed. Because alpha investing can be recovered as a special case of the SAFFRON framework, our results immediately apply to alpha investing as well. In the process of deriving these results, we also formally characterize how the conditional super-uniformity assumption implicitly limits the allowed p-value dependencies. This implicit limitation is important not only to our proposed FDR result, but also to many existing mFDR results.

False-positive HIV screening tests during the COVID-19 pandemic, a passing trend?

False-positive fourth-generation HIV screening tests are rare and are usually associated with various infections and autoimmune diseases. SARS-CoV-2 infection and vaccination were recently linked with false-positive HIV screening test results. However, little is known about false-positives in people who performed HIV screening tests after outbreaks of different SARS-CoV-2 strains and vaccination campaigns. Here, we examined the false-positive rates in samples collected by the Israeli AIDS Task Force in 2018--2022, with respect to such factors.

False-positive Aspergillus galactomannan immunoassay in the glucose component of total parenteral nutrition products.

IMPORTANCE: This manuscript describes an occurrence of false-positive GM tests in patients receiving TPN products from a manufacturer who had recently changed the supplier of the glucose component. We describe the clinical presentation of nine false-positive cases and the results of serologic and microbiological investigations of the TPN products suspected of contamination with GM. Attempts to detect GM in parenteral nutrition products were made since the detection of GM in sodium gluconate-containing solutions in 2007, but none of them identified the source of elevated GM indexes in TPN products. However, the present study demonstrated that the glucose component of the TPN products contained a high level of GM antigen, which caused false-positive GM assay results. The source of GM was glucoamylase, which was derived from A. niger in the manufacturing process. Physicians and clinical microbiology laboratories should be aware of this issue to improve interpretation and patient care.

[False positives in infectious serology : a rare issue that should not be ignored]. / Faux positifs en sérologie infectieuse : un problème rare à ne pas ignorer.

Although rare, false-positive results from infectious serology tests can mislead the practitioner and have harmful consequences for the patient. The causes are not always clear, but there are certain principles that are important to be aware of, and that help to interpret these diagnostic puzzles correctly. Similarities between different families of pathogens, the technical characteristics of the tests used, the use of therapeutic human immunoglobulins, the detection of vaccine-induced antibodies or even the detection of vaccine antigens themselves can cause non-specific reactions. This article uses examples from routine laboratory practice to illustrate the problem and draw the attention of the treating physician to this issue.

Bien que rares, les résultats faussement positifs des tests de sérologies infectieuses peuvent induire en erreur le praticien et entraîner des conséquences délétères pour le patient. Leurs causes ne sont pas toujours claires, mais certains principes sont importants à connaître et permettent d'interpréter correctement ces casse-têtes diagnostiques. Des similarités entre différentes familles de pathogènes, les caractéristiques techniques des tests utilisés, l'utilisation d'immunoglobulines humaines thérapeutiques, la détection d'anticorps induits par des vaccins ou même la détection des antigènes vaccinaux eux-mêmes peuvent causer des réactions non spécifiques. Cet article illustre ce problème par des exemples tirés de la routine du laboratoire afin d'attirer l'attention du médecin traitant sur ce problème.

Reconstrucción mamaria diferida con colgajo de dorsal ancho: aportación de la ecografía Doppler-Dúplex / Delayed breast reconstruction with latissimus dorsi fiap: contribution of Doppler-Duplex ultrasound

Introducción y objetivo: Para obtener buenos resultados en reconstrucción mamaria autóloga con colgajo de dorsal ancho se requiere verificar la presencia de una vascularización tóracodorsal adecuada. En el presente trabajo evaluamos la aportación de la ecografía Doppler-Dúplex para la localización de la arteria torácodorsal, previa a la reconstrucción mamaria diferida con colgajo de dorsal ancho. Material y método: Revisión de 51 pacientes con antecedentes de cirugía axilar por cáncer de mama candidatas a reconstrucción diferida con colgajo homolateral del músculo dorsal ancho. La exploración ecográfica la realizó un solo radiólogo utilizando la modalidad ecográfica Doppler-Dúplex. Resultados: Entre las 51 pacientes, se localizó la arteria tóracodorsal mediante ecografía en 39 casos (76.47%). En 12 casos no se pudo localizar o bien su identificación resultó dudosa. Entre estos 12 casos, en 8 se realizó angio-tomografía computarizada o bien angio-resonancia magnética que identificaron la arteria en 5 casos. En los otros 3, las pacientes rechazaron las exploraciones y no se sometieron a reconstrucción mediante la técnica estudiada o bien no se reconstruyeron. Se dispone de datos confirmados en 47 casos, entre los cuales no se ha visualizado vascularización tóracodorsal en 3 casos, lo que supone un 6.38%. Los parámetros diagnósticos resultantes fueron: sensibilidad 88.63%; especificidad 100%; valor predictivo positivo 100%;y valor predictivo negativo 37.50%, con una exactitud del 89.36%. Conclusiones: En base a nuestra experiencia podemos concluir que, siempre que se disponga de la experiencia y los medios técnicos adecuados, la ecografía Doppler-Dúplex debería ser el primer procedimiento a utilizar para la evaluación de la vascularización tóracodorsal. y en el caso de no reunir tales requisitos o bien si la ecografía fuera dudosa/negativa, realizar otros métodos como la angio-tomografía computarizada o la angio-resonancia magnética(AU).

Background and objective: To obtain good results with autologous latissimus dorsi flap in breast reconstruction it's necessary to verify the presence of adequate thoracodorsal vascularity. In this paper we evaluate the contribution of Doppler-Duplex ultrasound for the localization of the thoracodorsal vessels prior to delayed breast reconstruction with a dorsal fap. Methods: Review of 51 patients with a history of axillary surgery for breast cancer, candidates for delayed breast reconstruction with an ipsilateral flap of the latissimus dorsi muscle. The ultrasound examination was performed by a single radiologist using the Doppler-Duplex ultrasound modality. Results: Among the 51 patients, the thoracodorsal artery was located by ultrasound in 39 cases (76.47%). In 12 cases it could not be located or its identification was doubtful. Among these 12 cases, 8 underwent computed tomography angiography or magnetic resonance angiography, which identified the artery in 5 cases. In the remaining 3 cases the patients refused such examinations and did not undergo reconstruction. Confirmed data are available in 47 cases, among which thoracodorsal vasculature was not visualized in 3 cases, which represents 6.38%,The resulting diagnostic parameters were: sensitivity 88.63%; specificity 100%; positive predictive value 100%; and negative predictive value 37.50%, with an accuracy of 89.36%. Conclusions: From our experience we can conclude that,when the appropriate experience and equipment are available, Doppler-Duplex ultrasound should be the first procedure to be used for the evaluation of the thoracodorsal vasculature. And in the case of not meeting these requirements or the ultrasound was doubtful/negative, perform other methods such as computed tomography angiography or magnetic resonance angiography. Level of evidence 5c Diagnostic.(AU)

Long-term psychosocial consequences of false-positive screening mammography: a cohort study with follow-up of 12-14 years in Denmark.

OBJECTIVE: To compare the long-term psychosocial consequences of mammography screening among women with breast cancer, normal results and false-positive results. DESIGN: A matched cohort study with follow-up of 12-14 years. SETTING: Denmark from 2004 to 2019. PARTICIPANTS: 1170 women who participated in the Danish mammography screening programme in 2004-2005. INTERVENTION: Mammography screening for women aged 50-69 years. OUTCOME MEASURES: We assessed the psychosocial consequences with the Consequences Of Screening-Breast Cancer, a condition-specific questionnaire that is psychometrically validated and encompasses 14 psychosocial dimensions. RESULTS: Across all 14 psychosocial outcomes, women with false-positive results averagely reported higher psychosocial consequences compared with women with normal findings. Mean differences were statistically insignificant except for the existential values scale: 0.61 (95% CI (0.15 to 1.06), p=0.009). Additionally, women with false-positive results and women diagnosed with breast cancer were affected in a dose-response manner, where women diagnosed with breast cancer were more affected than women with false-positive results. CONCLUSION: Our study suggests that a false-positive mammogram is associated with increased psychosocial consequences 12-14 years after the screening. This study adds to the harms of mammography screening. The findings should be used to inform decision-making among the invited women and political and governmental decisions about mammography screening programmes.

Low-Value Prostate-Specific Antigen Screening in Older Males.

Importance: The US Preventive Services Task Force guidelines advise against prostate-specific antigen (PSA) screening for prostate cancer in males older than 69 years due to the risk of false-positive results and overdiagnosis of indolent disease. However, this low-value PSA screening in males aged 70 years or older remains common. Objective: To characterize the factors associated with low-value PSA screening in males 70 years or older. Design, Setting, and Participants: This survey study used data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a nationwide annual survey conducted by the Centers for Disease Control and Prevention that collects information via telephone from more than 400 000 US adults on behavioral risk factors, chronic illnesses, and use of preventive services. The final cohort comprised male respondents to the 2020 BRFSS survey who were categorized into the following age groups: 70 to 74 years, 75 to 79 years, or 80 years or older. Males with a former or current prostate cancer diagnosis were excluded. Main Outcomes and Measures: The outcomes were recent PSA screening rates and factors associated with low-value PSA screening. Recent screening was defined as PSA testing within the past 2 years. Weighted multivariable logistic regressions and 2-sided significance tests were used to characterize factors associated with recent screening. Results: The cohort included 32 306 males. Most of these males (87.6%) were White individuals, whereas 1.1% were American Indian, 1.2% were Asian, 4.3% were Black, and 3.4% were Hispanic individuals. Within this cohort, 42.8% of respondents were aged 70 to 74 years, 28.4% were aged 75 to 79 years, and 28.9% were 80 years or older. The recent PSA screening rates were 55.3% for males in the 70-to-74-year age group, 52.1% in the 75-to-79-year age group, and 39.4% in the 80-year-or-older group. Among all racial groups, non-Hispanic White males had the highest screening rate (50.7%), and non-Hispanic American Indian males had the lowest screening rate (32.0%). Screening increased with higher educational level and annual income. Married respondents were screened more than unmarried males. In a multivariable regression model, discussing PSA testing advantages with a clinician (odds ratio [OR], 9.09; 95% CI, 7.60-11.40; P < .001) was associated with increased recent screening, whereas discussing PSA testing disadvantages had no association with screening (OR, 0.95; 95% CI, 0.77-1.17; P = .60). Other factors associated with a higher screening rate included having a primary care physician, a post-high school educational level, and income of more than $25 000 per year. Conclusions and Relevance: Results of this survey study suggest that older male respondents to the 2020 BRFSS survey were overscreened for prostate cancer despite the age cutoff for PSA screening recommended in national guidelines. Discussing the benefits of PSA testing with a clinician was associated with increased screening, underscoring the potential of clinician-level interventions to reduce overscreening in older males.

Cumulative risks of false positive recall and screen-detected breast cancer after multiple screening examinations.

Women tend to make a decision about participation in breast cancer screening and adhere to this for future invitations. Therefore, our study aimed to provide high-quality information on cumulative risks of false-positive (FP) recall and screen-detected breast cancer over multiple screening examinations. Individual Dutch screening registry data (2005-2018) were gathered on subsequent screening examinations of 92 902 women age 49 to 51 years in 2005. Survival analyses were used to calculate cumulative risks of a FP and a true-positive (TP) result after seven examinations. Data from 66 472 women age 58 to 59 years were used to extrapolate to 11 examinations. Participation, detection and additional FP rates were calculated for women who previously received FP results compared to women with true negative (TN) results. After 7 examinations, the cumulative risk of a TP result was 3.7% and the cumulative risk of a FP result was 9.1%. After 11 examinations, this increased to 7.1% and 13.5%, respectively. Following a FP result, participation was lower (71%-81%) than following a TN result (>90%). In women with a FP result, more TP results (factor 1.59 [95% CI: 1.44-1.72]), more interval cancers (factor 1.66 [95% CI: 1.41-1.91]) and more FP results (factor 1.96 [95% CI: 1.87-2.05]) were found than in women with TN results. In conclusion, due to a low recall rate in the Netherlands, the cumulative risk of a FP recall is relatively low, while the cumulative risk of a TP result is comparable. Breast cancer diagnoses and FP results were more common in women with FP results than in women with TN results, while participation was lower.