Rapid point-of-care test for diagnosis of peritonitis in peritoneal dialysis patients.

BACKGROUND: Periplex® is a rapid point-of-care test based on the detection of interleukin-6 (IL-6) or matrix metalloproteinase-8 (MMP-8) to diagnose peritonitis in peritoneal dialysis (PD) patients. METHODS: This single-centre study was conducted in Singapore General Hospital from 2019 to 2022. The study recruited PD patients suspected of having peritonitis. Periplex was performed at the presentation and recovery of peritonitis. Primary outcomes were sensitivity and specificity of Periplex at presentation. The positive and negative predictive values of tests were also performed. RESULTS: A total of 120 patients were included in the study. The mean age was 60.9 ± 14.9 years, 53% were male, 79% were Chinese and 47.5% had diabetes mellitus. Periplex was positive in all patients with peritonitis (n = 114); sensitivity of 100%; 95% confidence interval (CI): 100-100%. Periplex was falsely positive in three patients with non-infective eosinophilic peritonitis, resulting in a low specificity of 50%; 95% CI: 41.1-59.0%. Periplex had a positive predictive value of 97.4% and a negative predictive value of 100%. During recovery from peritonitis, Periplex had high specificity (93.6%) and negative predictive value (98.7%) to indicate the resolution of infection. MMP-8 was more sensitive than IL-6 in detecting peritonitis. Periplex was positive in all patients with peritonitis regardless of the types of PD solutions used. CONCLUSIONS: Periplex had high sensitivity, and positive and negative predictive values in the diagnosis of peritonitis can be considered as a screening tool for peritonitis. Given its high specificity and negative predictive value, it may also be used to document the resolution of peritonitis.

Hospital readmissions for fluid overload among individuals with diabetes and diabetic kidney disease: risk factors and multivariable prediction models.

AIMS: Hospital readmissions due to recurrent fluid overload in diabetes and diabetic kidney disease can be avoided with evidence-based interventions. We aimed to identify at-risk patients who can benefit by developing risk prediction models for readmissions for fluid overload in people living with diabetes. METHODS: Single-center retrospective cohort study of 1531 adults with diabetes and hospitalized for fluid overload, including congestive heart failure, pulmonary edema and generalized edema, between 2015 and 2017. The multivariable regression models for 30-day and 90-day readmission for fluid overload were compared with the LACE score for discrimination, calibration, sensitivity, specificity and net reclassification index (NRI). RESULTS: Readmissions for fluid overload within 30 days and 90 days occurred in 8.6% and 17.2% of patients with diabetes, and 8.2% and 18.3% of patients with diabetic kidney disease, respectively. After adjusting for demographics, comorbidities, clinical parameters, and medications, a history of alcoholism (HR 3.85, 95% CI 1.41-10.55) and prior hospitalization for fluid overload (HR 2.50, 95% CI 1.26- 4.96) were independently associated with 30-day readmission in patients with diabetic kidney disease, as well as in individuals with diabetes. Additionally, current smoking, absence of hypertension and high-dose intravenous furosemide were also associated with 30-day readmission in individuals with diabetes. Prior hospitalization for fluid overload (HR 2.43, 95% CI 1.50-3.94), cardiovascular disease (HR 1.44, 95% CI 1.03-2.02), eGFR ≤45 ml/min/1.73 m2 (HR 1.39, 95% CI 1.003-1.93) were independently associated with 90-day readmissions in individuals with diabetic kidney disease. Additionally, thiazide at discharge reduced 90-day readmission in diabetic kidney disease while high-dose intravenous furosemide predicted 90-day readmission in diabetes. The clinical and clinico-psychological models for 90-day readmission in individuals with diabetes and diabetic kidney disease had better discrimination and calibration than the LACE score. The NRI for the clinico-psychosocial models to predict 30- and 90-day readmissions in diabetes were 22.4% and 28.9%, respectively. The NRI for the clinico-psychosocial models to predict 30- and 90-day readmissions in diabetic kidney disease were 5.6% and 38.9%, respectively. CONCLUSION: The risk models can potentially be used to identify patients at-risk of readmission for fluid overload for evidence-based interventions such as patient education or transitional care programs to reduce preventable hospitalizations. .

Early repeat hospitalization for fluid overload in individuals with cardiovascular disease and risks: a retrospective cohort study.

AIMS: Fluid overload is a common manifestation of cardiovascular and kidney disease and a leading cause of hospitalizations. To identify patients at risk of recurrent severe fluid overload, we evaluated the incidence and risk factors associated with early repeat hospitalization for fluid overload among individuals with cardiovascular disease and risks. METHODS: Single-center retrospective cohort study of 3423 consecutive adults with an index hospitalization for fluid overload between January 2015 and December 2017 and had cardiovascular risks (older age, diabetes mellitus, hypertension, dyslipidemia, kidney disease, known cardiovascular disease), but excluded if lost to follow-up or eGFR < 15 ml/min/1.73 m2. The outcome was early repeat hospitalization for fluid overload within 30 days of discharge. RESULTS: The mean age was 73.9 ± 11.6 years and eGFR was 54.1 ± 24.6 ml/min/1.73 m2 at index hospitalization. Early repeat hospitalization for fluid overload occurred in 291 patients (8.5%). After adjusting for demographics, comorbidities, clinical parameters during index hospitalization and medications at discharge, cardiovascular disease (adjusted odds ratio, OR 1.66, 95% CI 1.27-2.17), prior hospitalization for fluid overload within 3 months (OR 2.52, 95% CI 1.17-5.44), prior hospitalization for any cause in within 6 months (OR 1.33, 95% CI 1.02-1.73) and intravenous furosemide use (OR 1.58, 95% CI 1.10-2.28) were associated with early repeat hospitalization for fluid overload. Higher systolic BP on admission (OR 0.992, 95% 0.986-0.998) and diuretic at discharge (OR 0.50, 95% CI 0.26-0.98) reduced early hospitalization for fluid overload. CONCLUSION: Patients at-risk of early repeat hospitalization for fluid overload may be identified using these risk factors for targeted interventions.

A first principles derivation of energy-conserving momentum jumps in surface hopping simulations.

The fewest switches surface hopping (FSSH) method proposed by Tully in 1990 [Tully, J. Chem. Phys. 93, 1061 (1990)]-along with its many later variations-forms the basis for most practical simulations of molecular dynamics with electronic transitions in realistic systems. Despite its popularity, a rigorous formal derivation of the algorithm has yet to be achieved. In this paper, we derive the energy-conserving momentum jumps employed by FSSH from the perspective of quantum trajectory surface hopping (QTSH) [Martens, J. Phys. Chem. A 123, 1110 (2019)]. In the limit of localized nonadiabatic transitions, simple mathematical and physical arguments allow the FSSH algorithm to be derived from first principles. For general processes, the quantum forces characterizing the QTSH method provide accurate results for nonadiabatic dynamics with rigorous energy conservation, at the ensemble level, within the consistency of the underlying stochastic surface hopping without resorting to the artificial momentum rescaling of FSSH.

Upscaling cervical cancer screening and treatment for women living with HIV at a rural referral hospital in Tanzania: protocol of a before-and-after study exploring HPV testing and novel diagnostics.

BACKGROUND: Cervical cancer (CC) is nearly always caused by persistent human papillomavirus (HPV) infection. It is the most common cancer among women living with HIV (WLWH) and is the leading cause of cancer-related death in women in East Africa, with 10,241 new cases reported in Tanzania in 2020. In 2019, the World Health Organization (WHO) presented a global strategy for the elimination of CC as a public health problem, proposing targets to meet by 2030 for HPV vaccine coverage (90% of all 15-year-old girls), CC screening (70% of all women once at 35 and again at 45 years of age) and treatment delivery, to be scaled at national and subnational levels with a context-sensitive approach. This study aims to evaluate the upscaling of screening and treatment services at a rural referral hospital in Tanzania in order to address the second and third WHO targets. METHODS: This is an implementation study with a before-and-after design performed at St. Francis Referral Hospital (SFRH) in Ifakara (south-central Tanzania). CC screening and treatment services are integrated within the local HIV Care and Treatment Center (CTC). The standard of care, consisting of visualization of the cervix with acetic acid (VIA) and cryotherapy has been up-scaled with self-sampled HPV testing and also involved the introduction of mobile colposcopy, thermal ablation and loop electrosurgical excision procedure (LEEP). Participants are WLWH aged 18 to 65 years. Outcome measures included the percentage of women screened, HPV prevalence and genotype, and adherence to screening, treatment and follow-up plan. Additionally, we will explore the performance of novel diagnostic tests (QG-MPH®, Prevo-Check® and PT Monitor®), which share the features of being manageable and inexpensive, and thus a potential tool for effective triage in HPV high-prevalence cohorts. DISCUSSION: The study will provide relevant information about HPV prevalence and persistence, as well as reproductive and lifestyle indicators in a CC high-risk cohort of WLWH and about upscaling screening and treatment services at the level of a rural referral hospital in Tanzania. Furthermore, it will provide exploratory data on novel assays. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05256862, date of registration 25/02/2022. Retrospectively registered.

Maternal and child biomonitoring strategies and levels of exposure in western Canada during the past seventeen years: The Alberta Biomonitoring Program: 2005-2021.

The Alberta Biomonitoring Program (ABP) was created in 2005 with the initial goal of establishing baseline levels of exposure to environmental chemicals in specific populations in the province of Alberta, Canada, and was later expanded to include multiple phases. The first two phases focused on evaluating exposure in pregnant women (Phase One, 2005) and children (Phase Two, 2004-2006) by analyzing residual serum specimens. Phase Three (2013-2016) employed active recruitment techniques to evaluate environmental exposures using a revised list of chemicals in paired serum pools from pregnant women and umbilical cord blood. These three phases of the program monitored a total of 226 chemicals in 285 pooled serum samples representing 31,529 individuals. Phase Four (2017-2020) of the ABP has taken a more targeted approach, focusing on the impact of the federal legalization of cannabis on the exposure of pregnant women in Alberta to cannabis, as well as tobacco and alcohol using residual prenatal screening serum specimens. Chemicals monitored in the first three phases include herbicides, neutral pesticides, metals, metalloids, and micronutrients, methylmercury, organochlorine pesticides, organophosphate pesticides, parabens, phthalate metabolites, perfluoroalkyl substances (PFAS), phenols, phytoestrogens, polybrominated compounds, polychlorinated biphenyls (PCBs), dioxins and furans, polycyclic aromatic hydrocarbons (PAHs), and tobacco biomarkers. Phase Four monitored six biomarkers of tobacco, alcohol, and cannabis. All serum samples were pooled. Mean concentrations and 95% confidence intervals (CIs) were calculated for the chemicals detected in ≥25% of the sample pools. cross the first three phases, the data from the ABP has provided baseline exposure levels for the chemicals in pregnant women, children, and newborns across the province. Comparison within and among the phases has highlighted differences in exposure levels with age, geography, seasonality, sample type, and time. The strategies employed throughout the program phases have been demonstrated to provide effective models for population biomonitoring.

Diagnostic accuracy of an interdisciplinary tertiary center evaluation in children referred for suspected congenital anomalies of the kidney and urinary tract on fetal ultrasound - a retrospective outcome analysis.

BACKGROUND: Fetal ultrasound organ screening has become a standard of care in most high-income countries. This has resulted in increased detection of congenital abnormalities, which may lead to major uncertainty and anxiety in expectant parents, even though many of them are of minor relevance. In order to optimize prenatal counselling, we introduced an interdisciplinary approach for all pregnant women referred to our center by private obstetricians for a co-assessment of suspected relevant fetal abnormalities of the kidney or urinary tract, involving both experienced prenatal ultrasound specialists and a pediatric nephrologist or urologist. METHODS: In a retrospective analysis, we evaluated reports of intrauterine evaluation and postnatal follow-up in order to assess accuracy of explicit intrauterine diagnoses and outcome of hydronephroses according to their severity in this setting. RESULTS: A total of 175 fetuses were examined between 2012 and 2019 and followed postnatally at our Pediatric Nephrology or Urology Department. There was a high concordance (85.9%) between explicit intrauterine and final diagnoses. Resolution rate of hydronephrosis was higher in patients with intrauterine low-grade than high-grade hydronephrosis (61.8% versus 11.9%). An etiological diagnosis was found in 62.5%, 52.0%, and 11.1% of patients with intrauterine bilateral high-grade, unilateral high-grade, and unilateral high-grade with contralateral low-grade hydronephrosis, respectively, but in none of the patients with intrauterine low-grade hydronephrosis. CONCLUSIONS: The results of our study demonstrate that, through interdisciplinary teamwork, intrauterine assessment of the fetal kidneys and urinary tract is highly accurate and allows a good discrimination between relevant and transient/physiological hydronephroses. A higher resolution version of the Graphical abstract is available as Supplementary information.

Group B streptococcal colonization in elderly women.

BACKGROUND: In non-pregnant adults, the incidence of invasive Group B Streptococcus (GBS) disease is continuously increasing. Elderly and immunocompromised persons are at increased risk of infection. GBS commonly colonizes the vaginal tract, though data on colonization in the elderly are scarce. It is unknown whether the prevalence of GBS colonization is increasing in parallel to the observed rise of invasive infection. We conducted a three-year (2017-2019) prospective observational cross-sectional study in two teaching hospitals in Switzerland to determine the rate of GBS vaginal colonization in women over 60 years and i) to compare the proportions of known risk factors associated with invasive GBS diseases in colonized versus non-colonized women and ii) to evaluate the presence of GBS clusters with specific phenotypic and genotypic patterns in this population. METHODS: GBS screening was performed by using vaginal swabs collected during routine examination from women willing to participate in the study and to complete a questionnaire for risk factors. Isolates were characterized for antibiotic resistance profile, serotype and sequence type (ST). RESULTS: The GBS positivity rate in the elderly was 17% (44/255 positive samples), and similar to the one previously reported in pregnant women (around 20%). We could not find any association between participants' characteristics, previously published risk factors and GBS colonization. All strains were susceptible to penicillin, 22% (8/36) were not susceptible to erythromycin, 14% (5/36) were not susceptible to clindamycin and 8% (3/36) showed inducible clindamycin resistance. Both M and L phenotypes were each detected in one isolate. The most prevalent serotypes were III (33%, 12/36) and V (31%, 11/36). ST1 and ST19 accounted for 11% of isolates each (4/36); ST175 for 8% (3/36); and ST23, ST249 and ST297 for 6% each (2/36). Significantly higher rates of resistance to macrolides and clindamycin were associated with the ST1 genetic background of ST1. CONCLUSIONS: Our findings indicate a similar colonization rate for pregnant and elderly women. TRIAL REGISTRATION: Current Controlled Trial ISRCTN15468519 ; 06/01/2017.

A microelectric cell sensing technique for in vitro assessment of ocular irritation.

The animal-based Draize test remains the gold standard for assessment of ocular irritation. However, subjective scoring methods, species differences, and animal welfare concerns have spurred development of alternative test methods. In this study, a novel in vitro method for assessing ocular irritancy was developed using a microelectric cell sensing technology, real-time cell analysis (RTCA). The cytotoxicity of sixteen compounds was assessed in two cell lines: ARPE-19 (human retina) and SIRC (rabbit cornea). In vitro inhibitory (IC50 and AUC50) values were determined at 6, 12, 24, 48, 72, and 96 h exposure, with a subset of values confirmed with MTT testing. The values displayed comparable predictivity of in vivo ocular irritation on the basis of a linear regression between the calculated values and each compounds' corresponding Draize-determined modified maximum average score (MMAS), but the ARPE-19 derived values were more strongly correlated than those from SIRC cells. Hence, IC50 values derived from ARPE-19 cells were used to predict the UN GHS/EU CLP classification of each test compound. The method was determined to have sensitivity of 90%, specificity of 50%, and overall concordance of 75%. Thus, RTCA testing may be best incorporated into a top-down tiered testing strategy for identification of ocular irritants in vitro.

Proposition of a severity scale for lichen sclerosus: The "Clinical Lichen Sclerosus Score".

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease of the anogenitalarea leading to itch, burning, sexual dysfunction and impaired quality of life. An unmet need in the context of LS is a practical, easily assessable grading scale to classify disease severity and to allow intra- and interindividual comparisons. The objectives of this study were i) to assess the prevalence and severity of 23 items proposed by a recent Delphi consensus group in patients with adult VLS. ii) to develop a clinical severity scale and, iii) to test the interrater reliability of this novel severity scale. A retrospective assessment of the prevalence and severity of 23 items in 143 patients was performed by using patient records and photo documentation to develop a novel clinical severity scale (i.e. the "Clinical Lichen Sclerosus Score" = CLISSCO) for VLS. Thereafter, the CLISSCO was validated by 16 raters. We found that the items proposed by the consensus group vary markedly in frequency and severity. Following selection of the most relevant items, the CLISSCO was developed consisting of 3 "Symptoms", 3 "Signs" and 6 "Architectural changes" rated on a 0-4 point Likert-scale. The intraclass correlation coefficient was excellent for each item, the applicability of the CLISSCO considered user-friendly by the raters. We conclude that the CLISSCO proved to be a user-friendly, reliable tool to assess disease severity in VLS. However, further studies are needed to validate its applicability and value in daily practice and clinical research.

A Novel Edge Effect Detection Method for Real-Time Cellular Analyzer Using Functional Principal Component Analysis.

Real-time cellular analyzer (RTCA) has been generally applied to test the cytotoxicity of chemicals. However, several factors impact the experimental quality. A non-negligible factor is the abnormal time-dependent cellular response curves (TCRCs) of the wells located at the edge of the E-plate which is defined as edge effect. In this paper, a novel statistical analysis is proposed to detect the edge effect. First, TCRCs are considered as observations of a random variable in a functional space. Then, functional principal component analysis (FPCA) is adopted to extract the principal component (PC) functions of the TCRCs, and the first and second PCs of these curves are selected to distinguish abnormal TCRCs. The average TCRC of the inner wells with the same culture environment is set as the standard. If the distance between the scoring point of the standard curve and one designated scoring point exceeds the defined threshold, the corresponding TCRC of the designated point should be removed automatically. The experimental results demonstrate the effectiveness of the proposed algorithm. This method can be used as a standard method to resolve general time-dependent series issues.

Vaginal-perineal cultures for detecting group B streptococci and extended spectrum ß-lactamase producing bacteria in pregnancy.

OBJECTIVE: To compare the detection rates of vaginal-perineal cultures for group B streptococci (GBS) with the standard vaginal and rectal cultures and evaluate the diagnostic yield of vaginal-perineal vs. rectal swabs for extended spectrum ß-lactamase producing Enterobacterales (ESBL-E) during the third trimester of pregnancy. STUDY DESIGN: Vagino-perineal and rectal swabs were collected cross-sectionally from pregnant women between 35-37 weeks gestation and tested for the presence of GBS and ESBL-E. Accuracy of the vagino-perineal swab was compared to the combined vagino-perineal/rectal swab. Risk factors for ESBL carriage were examined. Degrees of pain, discomfort and stress related to the rectal swab were analyzed on visual analogue scales. RESULTS: 48 out of 250 participants (19.2%) were GBS positive. The vagino-perineal swab was positive in 44 of 48 women (91.7%) yielding a negative predictive value of 98.1%. Agreement (kappa) between the two methods was 0.95. Six out of 190 women with additional ESBL-E screening (3.2%) tested positive by rectal swab. Of these, only two had also a positive vagino-perineal swab. The rectal swab caused overall little subjective discomfort, pain or stress, as indicated by low scores indicated on the visual scales. CONCLUSIONS: The GBS detection rate of the vagino-perineal swab was lower compared to the reference standard. However, agreement between the two screening methods was high and there were no cases of GBS neonatal sepsis in the recruited population, supporting this less invasive screening strategy. In contrast, the vaginal-perineal swab was inferior to the rectal swab for detecting ESBL-E, indicating that this less invasive method for detecting antibiotic resistant bacteria that may be potentially transferred to the neonate during labor and delivery would be inappropriate for ESBL-E screening in pregnant women. The low ESBL-E carriage rate among pregnant women likely reflects the prevalence in the general population.

Impact of nationwide health insurance coverage for non-invasive prenatal testing.

OBJECTIVE: To describe the changes in women's choices for prenatal testing after the introduction of nationwide health insurance coverage for non-invasive prenatal testing (NIPT) in Switzerland. METHODS: The present retrospective study reviewed data from all women with singleton pregnancies who presented at the prenatal unit of Basel University Hospital, Switzerland, for first-trimester screening between July 15, 2014, and December 31, 2015. Women were divided into three categories according to their risk for aneuploidy, and the uptake of NIPT in the period before and after the introduction of the nationwide coverage for NIPT was compared. RESULTS: Overall, 887 women were included in the study: 573 screens were carried out before (group 1) and 314 after (group 2) the introduction of insurance coverage for NIPT. In group 1, 53 (9.2%) had NIPT as compared with 72 (22.9%) in group 2. Among women with intermediate risk for aneuploidies and basic insurance coverage, NIPT increased by 56% (12/88 [14%] vs 32/46 [70%]; P<0.001). CONCLUSION: There was a notable increase in the uptake of NIPT; uptake was most significant among women with basic health insurance and intermediate risk for aneuploidy.

Modeling and simulation for toxicity assessment.

The effect of various toxicants on growth/death and morphology of human cells is investigated using the xCELLigence Real-Time Cell Analysis High Troughput in vitro assay. The cell index is measured as a proxy for the number of cells, and for each test substance in each cell line, time-dependent concentration response curves (TCRCs) are generated. In this paper we propose a mathematical model to study the effect of toxicants with various initial concentrations on the cell index. This model is based on the logistic equation and linear kinetics. We consider a three dimensional system of differential equations with variables corresponding to the cell index, the intracellular concentration of toxicant, and the extracellular concentration of toxicant. To efficiently estimate the model's parameters, we design an Expectation Maximization algorithm. The model is validated by showing that it accurately represents the information provided by the TCRCs recorded after the experiments. Using stability analysis and numerical simulations, we determine the lowest concentration of toxin that can kill the cells. This information can be used to better design experimental studies for cytotoxicity profiling assessment.

Why prevention of repeat abortion is so challenging: psychosocial characteristics of women at risk.

OBJECTIVES: Abortion rates have declined in recent decades; however, the rate of repeat abortion remains high. In order to identify keys to making efficient interventions against repeat abortion, our objectives were: to assess the percentage of repeat abortions in women opting for termination of pregnancy over a period of 1 year; to identify the risk factors for repeat abortion; and to assess the characteristics of women who opted for a further pregnancy termination despite having received standard post-abortion care. METHODS: A retrospective cross-sectional survey was carried out among 362 women who underwent pregnancy termination during a 1-year period. Women with and without repeat abortion were compared with regard to age, nationality, marital status, parity and use of contraception. In a subsample of 160 women who were available for follow-up over 4 years, those who underwent a further pregnancy termination during the observation period were also analysed qualitatively. RESULTS: The rate of repeat abortion was 30.1% in the survey population. Age and immigrant status were identified as risk factors. The use of long-acting reversible contraception (LARC) was significantly higher after repeat abortion than after a first termination of pregnancy. Among women with repeat abortion in the follow-up group, those with psychological problems tended to discontinue contraception and those with partnership conflicts were prone to using unreliable contraceptive methods. CONCLUSION: Aside from promoting LARC methods, strategies to reduce repeat abortion should consider the psychosocial risk factors and characteristics of women at risk identified in this study. An interdisciplinary approach including social care and counselling would be the most appropriate means to enable this.

Breast cancer screening attendance in two Swiss regions dominated by opportunistic or organized screening.

BACKGROUND: In Switzerland, the French-speaking region has an organized breast cancer (BC) screening program; in the German-speaking region, only opportunistic screening until recently had been offered. We evaluated factors associated with attendance to breast cancer screening in these two regions. METHODS: We analyzed the data of 50-69 year-old women (n = 2769) from the Swiss Health Survey 2012. Factors of interest included education level, place of residence, nationality, marital status, smoking history, alcohol consumption, physical activity, diet, self-perceived health, history of chronic diseases and mental distress, visits to medical doctors and cervical and colorectal cancer screening. Outcome measures were dichotomized into ≤2 years since most recent mammography versus >2 years or never. RESULTS: In the German- and French-speaking regions, mammography attendance within the last two years was 34.9 % and 77.8 %, respectively. In the French region, moderate alcohol consumption (adjusted OR 2.01, 95 % CI 1.28-3.15) increased screening attendance. Compared to those with no visit to a physician during the recent year, women in both regions with such visits attended statistically significantly more often BC screening (1-5 times vs. no visit: German (adjusted OR 3.96, 95 % CI 2.58-6.09); French: OR 7.25, 95 % CI 4.04-13.01). Non-attendance to cervical screening had a negative effect in both the German (adjusted OR 0.44, 95 % CI 0.25-0.79) and the French region (adjusted OR 0.57, 95 % CI 0.35-0.91). The same was true for colorectal cancer screening (German (adjusted OR 0.66, 95 % CI 0.52-0.84); French: OR 0.52, 95 % CI 0.33-0.83). No other factor was associated with BC screening and none of the tests of interaction comparing the two regions revealed statistically significant results. CONCLUSION: The effect of socio-demographic characteristics, lifestyle, health factors and screening behavior other than mammography on non-attendance to BC screening did not differ between the two regions with mainly opportunistic and organized screening, respectively, and did not explain the large differences in attendance between regions. Other potential explanations such as public promotion of attendance for BC screening, physicians' recommendations regarding mammography participation or women's beliefs should be further investigated.

Unintended pregnancy during the first year after breast cancer diagnosis.

OBJECTIVES: Young women experience high levels of anxiety and distress during cancer diagnosis and therapy, and it can be devastating to become pregnant in this vulnerable state. Pregnancy during cancer treatment is strongly discouraged, as radiotherapy and chemotherapy administered during the first trimester of pregnancy result in increased congenital malformations. METHODS: In this study, we analysed an unselected, consecutive cohort of young breast cancer (BC) patients with regard to unintended pregnancy during the first year after BC diagnosis. We analysed all patients who were ≤40 years of age at initial BC diagnosis (n = 100, mean age at diagnosis: 35.9 years), according to data from the Basel Breast Cancer Database. The frequency of unintended pregnancy was assessed, and particular attention was given to patients' obstetric and reproductive history. RESULTS: Forty-two percent of the cohort (mean age 36.5 years) were identified as not at risk of unintended pregnancy during the first year after BC diagnosis. However, 58% of the cohort (mean age 35.6 years) were using an ineffective contraceptive method and thus were at risk of unintended pregnancy. The rate of unintended pregnancy was 3.5% in this group (two patients). Oncologists should be aware that the use of reliable contraception should be discussed before starting, and also during, adjuvant therapy. CONCLUSIONS: Oncologists should consider actively referring young BC patients to a gynaecologist to ensure proper contraceptive counselling.

Machine learning algorithms for mode-of-action classification in toxicity assessment.

BACKGROUND: Real Time Cell Analysis (RTCA) technology is used to monitor cellular changes continuously over the entire exposure period. Combining with different testing concentrations, the profiles have potential in probing the mode of action (MOA) of the testing substances. RESULTS: In this paper, we present machine learning approaches for MOA assessment. Computational tools based on artificial neural network (ANN) and support vector machine (SVM) are developed to analyze the time-concentration response curves (TCRCs) of human cell lines responding to tested chemicals. The techniques are capable of learning data from given TCRCs with known MOA information and then making MOA classification for the unknown toxicity. A novel data processing step based on wavelet transform is introduced to extract important features from the original TCRC data. From the dose response curves, time interval leading to higher classification success rate can be selected as input to enhance the performance of the machine learning algorithm. This is particularly helpful when handling cases with limited and imbalanced data. The validation of the proposed method is demonstrated by the supervised learning algorithm applied to the exposure data of HepG2 cell line to 63 chemicals with 11 concentrations in each test case. Classification success rate in the range of 85 to 95 % are obtained using SVM for MOA classification with two clusters to cases up to four clusters. CONCLUSIONS: Wavelet transform is capable of capturing important features of TCRCs for MOA classification. The proposed SVM scheme incorporated with wavelet transform has a great potential for large scale MOA classification and high-through output chemical screening.

Contraception counseling for young breast cancer patients: A practical needs assessment and a survey among medical oncologists.

BACKGROUND/METHODS: We analyzed an unselected, consecutive cohort of young breast cancer (BC) patients (≤40 years, n = 100) with regard to the contraceptive methods used at the time of diagnosis. Based on this data, we assessed the individual need for contraceptive counseling before cancer therapy. Secondly, in a study-specific self-report questionnaire, we surveyed 101 medical oncologists with the aim of evaluating attitudes towards contraception and how young patients are being counseled in the practical clinical setting. RESULTS: In 62% of our cohort of young BC patients, we identified situations in which contraceptive counseling was necessary at the time of BC diagnosis. The patients did not use contraception or used an ineffective method (TIER III/IV, 42%), or were using hormonal methods (12%) or IUDs (8%). Almost all respondents of the survey (99%) stated that contraception is an important aspect in the surveillance of young BC patients and the vast majority (90%) discussed this item before starting therapy. Only 20% of the respondents reported that they a) inform the patients that reliable contraception is necessary before starting therapy, b) ask whether contraceptive methods are used during ongoing therapy, and c) regularly refer their patients to specialist counseling by a gynecologist. CONCLUSIONS: A large proportion of young women require contraceptive counseling after newly diagnosed BC. Oncologists should be aware that the use of reliable contraceptive methods should not only be discussed before starting therapy, but also during ongoing therapy. Oncologists should consider actively referring their young patients to gynecologists to ensure proper contraceptive counseling.

Use of Palliative Endocrine Therapy in Patients with Hormone Receptor-Positive Distant Metastatic Breast Cancer: How Often, How Effective, How Long?

BACKGROUND: This study provides real-world clinical evidence regarding palliative endocrine therapy (ET) in breast cancer (BC). The main questions to be answered were: how often and how long did patients receive ET? A particular aspect was the analysis of compliance and persistence with ET. METHODS: An analysis of a nonselected/consecutive cohort of women with distant metastatic hormone receptor-positive BC (n = 205) was conducted. RESULTS: In all, 165 patients (80.5%) received ET during the palliative disease course. The noncompliance rate was 1.5%. Sixty-seven patients (40.6%) had ET as the only antineoplastic therapy. The median number of therapy lines was 2, and the median duration was 18 months. The median metastatic disease survival (MDS) was 34 months. In patients who had an MDS of ≥9 months (n = 145; 87.9%), during 70.6% of the MDS time only ET had been administered. Patients who were naïve to ET more often had a good response to and a longer duration of palliative ET than those who were not. The nonpersistence rate was 4.3%. CONCLUSIONS: Excluding the few patients who had a rapidly progressive course, the disease was controlled for about 70% of the entire palliative disease course with ET alone. Only very few patients were nonpersistent with ET and consciously stopped a still effective, ongoing ET.