Latency function estimation under the mixture cure model when the cure status is available.

This paper addresses the problem of estimating the conditional survival function of the lifetime of the subjects experiencing the event (latency) in the mixture cure model when the cure status information is partially available. The approach of past work relies on the assumption that long-term survivors are unidentifiable because of right censoring. However, in some cases this assumption is invalid since some subjects are known to be cured, e.g., when a medical test ascertains that a disease has entirely disappeared after treatment. We propose a latency estimator that extends the nonparametric estimator studied in López-Cheda et al. (TEST 26(2):353-376, 2017b) to the case when the cure status is partially available. We establish the asymptotic normality distribution of the estimator, and illustrate its performance in a simulation study. Finally, the estimator is applied to a medical dataset to study the length of hospital stay of COVID-19 patients requiring intensive care.

Correction: A product-limit estimator of the conditional survival function when cure status is partially known.

An error was detected in the derivation of the expression of the cumulative hazard function in a recently published paper by Safari, W. C., López-de-Ullibarri, I., and Jácome, M. A. (2021), A product-limit estimator of the conditional survival function when cure status is partially known. Biometrical Journal, 63(5), 984-1005, https://doi.org/10.1002/bimj.202000173. This short article aims to correct this error. There are some changes in the model notation in Section 2, the derivation of the expression of the cumulative hazard function in the Appendix, and the proofs of Lemmas 3 and 4 in the Supporting Information. Moreover, there is a small change in the generation of the values of the censoring variable C ∗ in the simulation study. As a consequence, the simulation results in Section 4 are affected. A corrected version of these sections is given in the Supporting Information.

A product-limit estimator of the conditional survival function when cure status is partially known.

We introduce a nonparametric estimator of the conditional survival function in the mixture cure model for right-censored data when cure status is partially known. The estimator is developed for the setting of a single continuous covariate but it can be extended to multiple covariates. It extends the estimator of Beran, which ignores cure status information. We obtain an almost sure representation, from which the strong consistency and asymptotic normality of the estimator are derived. Asymptotic expressions of the bias and variance demonstrate a reduction in the variance with respect to Beran's estimator. A simulation study shows that, if the bandwidth parameter is suitably chosen, our estimator performs better than others for an ample range of covariate values. A bootstrap bandwidth selector is proposed. Finally, the proposed estimator is applied to a real dataset studying survival of sarcoma patients.

Small-Bowel Crohn Disease Treated With Anti-Tumor Necrosis Factor-α Therapy: MR Enterography Score Changes After 1 Year Predict Long-Term Outcomes.

OBJECTIVE. The purpose of this article is to assess the ability of MR enterography (MRE) to predict the evolution of Crohn disease (CD) under anti-tumor necrosis factor-α (anti-TNF) therapy. In particular, we analyzed the effect of achieving a radiologic response (RR) on long-term patient outcomes. MATERIALS AND METHODS. We included patients with small-bowel CD who successfully started receiving anti-TNF (infliximab or adalimumab) therapy and achieved clinical remission between 2008 and 2015. MRE was performed at baseline and close to 1 year after treatment initiation. The degree of CD activity was evaluated on the basis of a per-patient MRE score used at our hospital. Individual scores were calculated and recorded on the day of analysis. The median duration of follow-up after induction therapy was 5 years (interquartile range, 2.5-9.0 years). Cumulative probabilities of not having a loss of response (LOR) were assessed using the Kaplan-Meier method and compared using the log-rank test. RESULTS. Thirty-four patients fulfilled the prerequisites for inclusion in the study. Complete RR was achieved in nine patients (26.5%), partial RR in 13 (38.2%), and either no RR or worsening in 12 (35.3%). For the three aforementioned response groups, the estimated probability of absence of LOR at 5 years was 0.88, 0.69, and 0.25, respectively, and the log-rank test suggested that the risk rates for LOR were different (p = 0.023). Based on Cox regression, an MRE score reduction of less than 50% at close to 1 year after treatment initiation was an independent risk factor for LOR (hazard ratio, 0.257; 95% CI, 0.070-0.953; p = 0.027). CONCLUSION. The MRE response after 1 year is a predictor of the efficacy of anti-TNF treatment.

A parametric approach to kinship hypothesis testing using identity-by-descent parameters.

There is a large number of applications where family relationships need to be determined from DNA data. In forensic science, competing ideas are in general verbally formulated as the two hypotheses of a test. For the most common paternity case, the null hypothesis states that the alleged father is the true father against the alternative hypothesis that the father is an unrelated man. A likelihood ratio is calculated to summarize the evidence. We propose an alternative framework whereby a model and the hypotheses are formulated in terms of parameters representing identity-by-descent probabilities. There are several advantages to this approach. Firstly, the alternative hypothesis can be completely general. Specifically, the alternative does not need to specify an unrelated man. Secondly, the parametric formulation corresponds to the approach used in most other applications of statistical hypothesis testing and so there is a large theory of classical statistics that can be applied. Theoretical properties of the test statistic under the null hypothesis are studied. An extension to trios of individuals has been carried out. The methods are exemplified using simulations and a real dataset of 27 Spanish Romani individuals.

Logrank-type tests with presmoothing.

The logrank test is the most popular choice for testing the equality of two survival distributions with time-to-event data. It is based on the comparison of the Nelson-Aalen estimates of the corresponding cumulative hazard functions. The improvements of the logrank test in the literature have been accomplished using weighted logrank tests, with the weight chosen appropriately to maximize power. Notwithstanding, power also depends on the efficiency of the estimation of the cumulative hazard function. The presmoothed estimator has been shown to be more efficient than the Nelson-Aalen estimator under some general assumptions. We introduce a new logrank-type test that, instead of the Nelson-Aalen estimator, is based on its presmoothed counterpart. An extensive simulation study has been conducted to compare the performance of this new test with the classical one. This study shows that the new test has the proper size under the null hypothesis, while improving the power over a wide range of alternatives. The new test is illustrated with several real data examples.

Feasibility, efficacy and safety of early lens extraction in patients with pseudoexfoliation glaucoma: a feasibility and pilot study.

PURPOSE: To evaluate the feasibility of a trial to compare the efficacy and safety of initial lens extraction surgery versus medical treatment for people with pseudoexfoliation glaucoma (PXFG) or ocular hypertension (OHT) and pseudoexfoliation syndrome. METHODS: This is a feasibility and pilot randomized controlled trial (RCT) in patients with newly diagnosed PXFG and mild cataract. The study was prospectively registered at ClinicalTrials.gov. An online survey was conducted among members of UK and Eire Glaucoma Society (UKEGS) and Spanish Glaucoma Society (SEG) with the aim of understanding current practices related to interventions for PXFG, the role of phacoemulsification and the willingness to participate in a definite trial. Participants were randomized into either early lens extraction surgery or medical treatment and deferred surgery Primary clinical outcome was intraocular pressure (IOP) at 12 months. RESULTS: The study was conducted between May 2019 and February 2021. Twelve patients were randomized, six in each group. Median IOP decreased significantly in both arms. Among the secondary outcomes of BVCA, reduction in the number of treatments and quality of life, statistically significant differences were found in favor of lens extraction. There were no differences in other secondary outcomes. No adverse effects occurred. Glaucoma experts would be willing to participate in a RCT. CONCLUSIONS: A trial on early lens extraction surgery compared with medication in PXFG is feasible. Early lens extraction appears to be an effective treatment for PXFG, reducing the number of hypotensive drugs after surgery as well as improving patients' quality of life.

Wastewater early warning system for SARS-CoV-2 outbreaks and variants in a Coruña, Spain.

Wastewater-based epidemiology has been widely used as a cost-effective method for tracking the COVID-19 pandemic at the community level. Here we describe COVIDBENS, a wastewater surveillance program running from June 2020 to March 2022 in the wastewater treatment plant of Bens in A Coruña (Spain). The main goal of this work was to provide an effective early warning tool based in wastewater epidemiology to help in decision-making at both the social and public health levels. RT-qPCR procedures and Illumina sequencing were used to weekly monitor the viral load and to detect SARS-CoV-2 mutations in wastewater, respectively. In addition, own statistical models were applied to estimate the real number of infected people and the frequency of each emerging variant circulating in the community, which considerable improved the surveillance strategy. Our analysis detected 6 viral load waves in A Coruña with concentrations between 103 and 106 SARS-CoV-2 RNA copies/L. Our system was able to anticipate community outbreaks during the pandemic with 8-36 days in advance with respect to clinical reports and, to detect the emergence of new SARS-CoV-2 variants in A Coruña such as Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529 and BA.2) in wastewater with 42, 30, and 27 days, respectively, before the health system did. Data generated here helped local authorities and health managers to give a faster and more efficient response to the pandemic situation, and also allowed important industrial companies to adapt their production to each situation. The wastewater-based epidemiology program developed in our metropolitan area of A Coruña (Spain) during the SARS-CoV-2 pandemic served as a powerful early warning system combining statistical models with mutations and viral load monitoring in wastewater over time.

Nonparametric kernel estimation of the probability of cure in a mixture cure model when the cure status is partially observed.

Cure models are a class of time-to-event models where a proportion of individuals will never experience the event of interest. The lifetimes of these so-called cured individuals are always censored. It is usually assumed that one never knows which censored observation is cured and which is uncured, so the cure status is unknown for censored times. In this paper, we develop a method to estimate the probability of cure in the mixture cure model when some censored individuals are known to be cured. A cure probability estimator that incorporates the cure status information is introduced. This estimator is shown to be strongly consistent and asymptotically normally distributed. Two alternative estimators are also presented. The first one considers a competing risks approach with two types of competing events, the event of interest and the cure. The second alternative estimator is based on the fact that the probability of cure can be written as the conditional mean of the cure status. Hence, nonparametric regression methods can be applied to estimate this conditional mean. However, the cure status remains unknown for some censored individuals. Consequently, the application of regression methods in this context requires handling missing data in the response variable (cure status). Simulations are performed to evaluate the finite sample performance of the estimators, and we apply them to the analysis of two datasets related to survival of breast cancer patients and length of hospital stay of COVID-19 patients requiring intensive care.

Surgical and laser interventions for pseudoexfoliation glaucoma systematic review of randomized controlled trials.

To assess the comparative effectiveness and safety of different surgical and laser techniques in people with pseudoexfoliation glaucoma (PXFG). We conducted a systematic review including randomized controlled trials (RCT) that compared any pair of surgical or laser treatment versus other type of intervention in PXFG. RCT were identified by a highly sensitive search of electronic databases and two individuals independently assessed trial eligibility, abstracted data and assessed risk of bias. We performed Bayesian Meta-Analysis when outcomes were comparable. The search strategy identified 6171 records. Six studies (262 subjects) were included. Two trials analyzed the same pair of surgical interventions comparing phacoemulsification as solo procedure or combined with trabecular aspiration and we performed meta-analysis. Other RCTs compared the following interventions: trabecular aspiration associated with phacoemulsification versus phacotrabeculectomy, non-penetrating deep sclerectomy associated or not with phacoemulsification, selective versus argon laser trabeculoplasty and one-site versus two-site phacotrabeculectomy. For IOP data, none of the trials reported a difference between pairs of surgical techniques, nor changes in visual acuity or number of post-operative medications. The overall risk of bias is moderate to high. There are no apparent differences in efficacy and safety, although with large uncertainty, between surgical or laser techniques for PXFG. Based on the low-quality evidence from the six studies included in this review, it is not possible to justify the preferential use of non-penetrating surgery, MIGS or trabecular aspiration (with or without cataract surgery) in PXFG. Further research is needed to determine the optimal management of this condition.

Validation of a questionnaire of knowledge and attitudes about the subcutaneous venous reservoir in nursing.

OBJECTIVE: design and validate a questionnaire to evaluate the knowledge and attitudes of nurses about the subcutaneous venous reservoir. METHOD: pilot test: 30 specialized care nurses. Main study: 236 nurses of primary and specialized care. Content validity was evaluated by Lawshe index, reliability by test-retest, internal consistency by Cronbach alpha, and construct validity by exploratory factorial analysis. RESULTS: Items with a Lawshe index lower than 0.51 were eliminated. In the test-retest, the intraclass correlation coefficient was higher than 0.75 for all items. The Cronbach alpha of the attitude questionnaire reached 0.865. The Cronbach alpha value for knowledge was 0.750. The exploratory factor analysis identified a set of four dimensions for each part that explain 64% (attitude) to 80% (knowledge) of variability. CONCLUSION: the analysis of the reliability and validity of the questionnaire supports its use as an instrument to assess the knowledge and attitudes of nurses towards the subcutaneous venous reservoir.

ROC Curves for the Statistical Analysis of Microarray Data.

A receiver operating characteristic (ROC) curve is a graphical plot that illustrates the diagnostic ability of a binary classifier as a function of its discrimination threshold. This chapter is an overview on the use of ROC curves for microarray data. The notion of ROC curve and its motivation is introduced in Subheading 1. Relevant scientific contributions concerning the use of ROC curves for microarray data are briefly reviewed in Subheading 2. The special case with covariates is considered in Subheading 3. Two relevant aspects are reviewed in this section: the use of LASSO techniques for selecting and combining relevant markers and how to correct for multiple testing when a large number of markers are available. Finally, some conclusions are included.

Challenges and Future Trends for Microarray Analysis.

The current situation in microarray data analysis and prospects for the future are briefly discussed in this chapter, in which the competition between microarray technologies and high-throughput technologies is considered under a data analysis view. The up-to-date limitations of DNA microarrays are important to forecast challenges and future trends in microarray data analysis; these include data analysis techniques associated with an increasing sample sizes, new feature selection methods, deep learning techniques, covariate significance testing as well as false discovery rate methods, among other procedures for a better interpretability of the results.

Validation of a questionnaire of knowledge and attitudes about the subcutaneous venous reservoir in nursing / Validação de um questionário de conhecimentos e atitudes sobre o cateter venoso totalmente implantado em Enfermagem / Validación de un cuestionario de conocimientos y actitudes sobre el reservorio venoso subcutáneo en enfermería

Objective: design and validate a questionnaire to evaluate the knowledge and attitudes of nurses about the subcutaneous venous reservoir. Method: pilot test: 30 specialized care nurses. Main study: 236 nurses of primary and specialized care. Content validity was evaluated by Lawshe index, reliability by test-retest, internal consistency by Cronbach alpha, and construct validity by exploratory factorial analysis. Results: Items with a Lawshe index lower than 0.51 were eliminated. In the test-retest, the intraclass correlation coefficient was higher than 0.75 for all items. The Cronbach alpha of the attitude questionnaire reached 0.865. The Cronbach alpha value for knowledge was 0.750. The exploratory factor analysis identified a set of four dimensions for each part that explain 64% (attitude) to 80% (knowledge) of variability. Conclusion: the analysis of the reliability and validity of the questionnaire supports its use as an instrument to assess the knowledge and attitudes of nurses towards the subcutaneous venous reservoir.

Objetivo: construir e validar um questionário para avaliar os conhecimentos e as atitudes dos profissionais de enfermagem sobre o cateter venoso totalmente implantado. Método: teste piloto: 30 enfermeiros de atendimento especializado. Estudo principal: 236 enfermeiros de atendimento primário e especializado. Avaliou-se a validade de conteúdo por meio do índice de Lawshe, a confiabilidade por meio do teste-reteste, a consistência interna mediante o alfa de Cronbach, e a validade de construto por meio de uma análise fatorial exploratória. Resultados: foram eliminados os itens com um índice de Lawshe inferior a 0,51. No teste-reteste, o coeficiente de correlação intraclasse foi maior que 0,75 para todos os itens. O alfa de Cronbach do questionário de atitude atingiu um valor de 0,865. O valor de alfa de Cronbach para o de conhecimentos foi de 0,750. A análise fatorial exploratória identificou um conjunto de quatro dimensões para cada parte, que explicam a variabilidade de 64% (atitude) a 80% (conhecimentos). Conclusão: a análise da confiabilidade e a validade do questionário endossam seu uso como instrumento para avaliar os conhecimentos e as atitudes dos profissionais de enfermagem em relação ao cateter venoso totalmente implantado.

Objetivo: diseñar y validar un cuestionario para evaluar los conocimientos y las actitudes del personal de enfermería sobre el reservorio venoso subcutáneo. Método: prueba piloto con 30 enfermeros/as de atención especializada. Estudio principal con 236 enfermeros/as de atención primaria y especializada. Se evaluó la validez de contenido mediante el índice de Lawshe, la fiabilidad mediante test-retest, la consistencia interna mediante el alfa de Cronbach y la validez de constructo con un análisis factorial exploratorio. Resultados: se eliminaron los ítems con un índice de Lawshe inferior a 0,51. En el test-retest, el coeficiente de correlación intraclase resultó ser mayor que 0,75 para todos los ítems. El alfa de Cronbach del cuestionario de actitud alcanzó un valor de 0,865. El valor de alfa de Cronbach para el de conocimientos fue de 0,750. El análisis factorial exploratorio identificó un conjunto de cuatro dimensiones para cada parte que explican del 64% (actitud) al 80% (conocimientos) de la variabilidad. Conclusión: el análisis de la fiabilidad y la validez del cuestionario avalan su uso como instrumento para valorar los conocimientos y actitudes del personal de enfermería en torno al reservorio venoso subcutáneo.

Classification tree analysis for the discrimination of pleural exudates and transudates.

BACKGROUND: Classification and regression tree (CART) analysis is a non-parametric technique suitable for the generation of clinical decision rules. We have studied the performance of CART analysis in the separation of pleural exudates and transudates. METHODS: Basic demographic, radiologic and laboratory data were retrospectively evaluated in 1257 pleural effusions (204 transudates and 1053 exudates, according to standard clinical criteria) and submitted for CART analysis. The model's discriminative ability was compared with that of Light's criteria, in both the original formulation and an abbreviated version, i.e., deleting the pleural fluid (PF)/serum lactate dehydrogenase (LDH) ratio from the triad. RESULTS: A first CART model built starting from all available data identified PF/serum protein ratio and PF LDH ratios as the two best discriminatory parameters. This algorithm achieved a sensitivity of 96.8%, slightly lower than that of classical Light's criteria (98.5%) and comparable to that of the abbreviated Light's criteria (97.0%), and significantly better specificity (85.3%) compared to both classical (74.0%) and abbreviated (79.4%) Light's criteria. A second CART model developed after excluding serum measurements selected PF protein and PF LDH as the most discriminatory variables, and correctly classified 97.2% of exudates and 77.0% of transudates. CONCLUSIONS: CART-based algorithms can efficiently discriminate between pleural exudates and transudates.