Introducing novel and comprehensive models for predicting recurrence in breast cancer using the group LASSO approach: are estimates of early and late recurrence different?

Abstract

Background

In here, we constructed personalized models for predicting breast cancer (BC) recurrence according to timing of recurrence (as early and late recurrence).

Methods

An efficient algorithm called group LASSO was used for simultaneous variable selection and risk factor prediction in a logistic regression model.

Results

For recurrence < 5 years, age (OR 0.96, 95% CI = 0.95–0.97), number of pregnancies (OR 0.94, 95% CI = 0.89–0.99), family history of other cancers (OR 0.73, 95% CI = 0.60–0.89), hormone therapy (OR 0.76, 95% CI = 0.61–0.96), dissected lymph nodes (OR 0.98, 95% CI = 0.97–0.99), right-sided BC (OR 0.87, 95% CI = 0.77–0.99), diabetes (OR 0.77, 95% CI = 0.60–0.98), history of breast operations (OR 0.38, 95% CI = 0.17–0.88), smoking (OR 5.72, 95% CI = 2.11–15.55), history of breast disease (OR 3.32, 95% CI = 1.92–5.76), in situ component (OR 1.58, 95% CI = 1.35–1.84), tumor necrosis (OR 1.87, 95% CI = 1.57–2.22), sentinel lymph node biopsy (SLNB) (OR 2.90, 95% CI = 2.05–4.11) and SLNB+axillary node dissection (OR 3.50, 95% CI = 2.26–5.42), grade 3 (OR 1.79, 95% CI = 1.46–2.21), stage 2 (OR 2.71, 95% CI = 2.18–3.35), stages 3 and 4 (OR 5.01, 95% CI = 3.52–7.13), and mastectomy+radiotherapy (OR 2.97, 95% CI = 2.39–3.68) were predictors of recurrence < 5 years. Moreover, relative to mastectomy without radiotherapy (as reference for comparison), quadrantectomy without radiotherapy had a noticeably higher odds ratio compared to quadranectomy with radiotherapy for recurrence < 5 years. (OR 17.58, 95% CI = 6.70–46.10 vs. OR: 2.50, 95% CI = 2–3.12).

Accuracy, sensitivity, and specificity of the model were 82%, 75.6%, and 74.9%, respectively.

For recurrence > 5 years, stage 2 cancer (OR 1.67, 95% CI = 1.31–2.14) and radiotherapy+mastectomy (OR 2.45, 95% CI = 1.81–3.32) were significant predictors; furthermore, relative to mastectomy without radiotherapy (as reference for comparison), quadranectomy without radiotherapy had a noticeably higher odds ratio compared to quadranectomy with radiotherapy for recurrence > 5 years (OR 7.62, 95% CI = 1.52–38.15 vs. OR 1.75, 95% CI = 1.32–2.32). Accuracy, sensitivity, and specificity of the model were 71%, 78.8%, and 55.8%, respectively.

Conclusion

For the first time, we constructed models for estimating recurrence based on timing of recurrence which are among the most applicable models with excellent accuracy (> 80%).

https://ift.tt/2CN6sHi

Diagnostic Accuracy of Bronchodilator Response for Asthma in a Population of South China

Abstract

Introduction

A significant bronchodilator response is commonly defined as a 12% or greater and 200 ml or greater change in FEV₁ from baseline according to the 2005 American Thoracic Society (ATS)/European Respiratory Society (ERS) criterion. A number of studies have shown that the ATS/ERS criterion has limitations in asthma diagnosis, and some experts have argued for correcting the criteria. The aim of this study is to investigate the diagnostic value of acute bronchodilator response for asthma in a Southern Chinese population.

Methods

We prospectively evaluated 805 patients with obstructive lung disease (309 for asthma, 496 for non-asthma). Spirometry was performed according to the ATS/ERS guidelines. Data were analyzed by SPSS 18.0. The receiver-operating characteristic (ROC) curve was drawn to assess the diagnostic accuracy of the ATS/ERS criterion based on FEV₁. Linear regression was used to analyze the factors of FEV₁ change.

Results

The sensitivity and specificity of the acute bronchodilator test when judged by the ATS/ERS criteria (200 ml or higher and 12% improvement) were 68.6% and 78.2%, respectively. For the ATS/ERS criteria, the Youden Index, which comprehensively reflects the authenticity of a diagnostic test, was 46.8%. The absolute change of FEV₁ positively correlated with baseline FEV₁ and weight and negatively with age, while the percentage change of FEV₁ was negatively correlated with baseline FEV₁, age and height and positively with weight. Compared with the different diagnostic values, when ∆FEV₁ was 195 ml and ∆FEV_1i% was 14%, the Youden Index was the largest (48.2%) and the diagnostic capability of the test the biggest.

Conclusions

The ATS/ERS criterion for acute bronchodilator response might not be completely suitable for asthma in the Chinese population.

Trial Registration

Chinese Clinical Trial Registry (Registry ID: ChiCTR-DDT-14004976).

Funding

This work was supported by the National Natural Science Foundation of China (grant nos. 81670027, 81270080).

https://ift.tt/2CPd6gb

LGR5, a novel functional glioma stem cell marker, promotes EMT by activating the Wnt/β-catenin pathway and predicts poor survival of glioma patients

Abstract

Background

Tumor recurrence, the chief reason for poor prognosis of glioma, is largely attributed to glioma stem cells (GSCs) and epithelial-mesenchymal transition (EMT). However, the mechanisms among them remain unknown. Here, we determined whether leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), known as a stem cell marker for colon cancer and gastric cancer, can serve as a novel GSC marker involved in EMT and a therapeutic target in glioma.

Methods

Stemness properties were examined in FACS-isolated LGR5⁺/LGR5⁻ cells. Reported stem cell markers, EMT and the Wnt/β-catenin pathway were examined in stable LGR5 knockdown or overexpressed GSCs by Western Blot. The treatment experiment was performed in an intracranial orthotopic xenograft model by knockdown of LGR5 or by using the Wnt/β-catenin pathway inhibitor Wnt-C59. LGR5 expression was determined in 268 glioma specimens by immunohistochemistry.

Results

LGR5⁺ cells possessed stronger stemness properties compared to LGR5⁻ cells. The expression of SOX2, Nanog, CD133, CD44, CD24 and EpCAM was modulated by LGR5. Both LGR5 knockdown and Wnt-C59 reduced tumor invasion and migration and blocked EMT by inhibiting the Wnt/β-catenin pathway in vitro and suppressed the intracranial orthotopic xenograft growth and prolonged the survival of xenograft mice in vivo. Moreover, LGR5 was positively correlated with Ki67, N-cadherin and WHO grade and negatively correlated with IDH1. Glioma patients with high expression of LGR5 showed significantly poorer prognosis.

Conclusions

LGR5 is a new functional GSC marker and prognostic indicator that can promote EMT by activating the Wnt/β-catenin pathway and would thus be a novel therapeutic target for glioma.

https://ift.tt/2p34LMh

Screening and prevention for latent tuberculosis in immunosuppressed patients at risk for tuberculosis: a systematic review of clinical practice guidelines

Objective

Immunosuppressed individuals are at a high risk of latent tuberculosis infection (LTBI) and clinical practice guidelines for the screening and management of LTBI in at-risk patients have been developed. We assessed the scope, quality and consistency of clinical practice guidelines on screening for LTBI and the prevention of tuberculosis infection (TB) in high-risk patient populations.

Design

We conducted a systematic review of clinical practice guidelines. Methodological quality of these guidelines was assessed using the Appraisal of Guidelines for Research and Education (AGREE) II instrument. Textual synthesis was used to summarise and compare the recommendations.

Data sources

Electronic databases (MEDLINE, EMBASE, PsycINFO) and guideline registries were searched from inception to December 2017.

Results

Thirty-eight guidelines were included. Nineteen focused on patients receiving medical immunosuppression, seven on transplantation, three on patients with HIV and nine were generalised across all at risk populations. Most guidelines (n=32, 84%) used a systematic approach to identify and appraise the evidence. The methodological quality of the guidelines varied with the overall mean AGREE II scores ranging from 35% to 80%. Guidelines performed poorly in terms of editorial independence (average score 35%, range 0%–92%); however, most were robust in defining their scope and purpose (average score 80%, range 56%–100%). Guidelines recommended either or both the tuberculin skin test and the interferon gamma release assay for screening. Treatment of LTBI with isoniazid was consistently recommended.

Conclusion

Clinical practice guidelines on LTBI vary in quality and scope. The recommendations for screening varied across guidelines, while recommendations for treatment were largely consistent. Improving the consistency and quality of guidelines may help to optimise the screening and management of LTBI for improved patient outcomes.

https://ift.tt/2Mu0KtG

What are the requirements for developing a successful national registry of auditory implants? A qualitative study

Objectives

Hearing loss is an area of unmet need, and industry is targeting this field with a growing range of surgically implanted hearing devices. Currently, there is no comprehensive UK registry capturing data on these devices; in its absence, it is difficult to monitor clinical and cost-effectiveness and develop national policy. Recognising that developing such a registry faces considerable challenges, it is important to gather opinions from stakeholders and patients. This paper builds on our systematic review on surgical registry development and aims to identify the specific requirements for developing a successful national registry of auditory implants.

Design

Qualitative study.

Participants

Data were collected in two ways: (1) semistructured interviews with UK professional stakeholders; and (2) focus groups with patients with hearing loss. The interview and focus group schedules were informed by our systematic review on registry development. Data were analysed using directed content analysis. Judges mapped the themes obtained against a conceptual framework developed from our systematic review on registry development. The conceptual framework consisted of five categories for successful registry development: (1) planning, (2) registry governance, (3) registry dataset, (4) anticipating challenges, (5) implementing solutions.

Results

Twenty-seven themes emerged from 40 semistructured interviews with professional stakeholders and 18 themes emerged from three patient focus groups. The most important factor for registry success was high rates of data completion. Benefits of developing a successful registry of auditory implants include: strengthening the evidence base and regulation of auditory implants, driving quality and safety improvements, increased transparency, facilitating patient decision-making and informing policy and guidelines development.

Conclusions

This study identifies the requirements for developing a successful national registry of auditory implants, benefiting from the involvement of numerous professional stakeholder groups and patients with hearing loss. Our approach may be used internationally to inform successful registry development.

https://ift.tt/2p34EQR

Impact of body mass index on survival of medical patients with sepsis: a prospective cohort study in a university hospital in China

Objective

To evaluate the impact of body mass index (BMI) on survival of a Chinese cohort of medical patients with sepsis.

Design

A single-centre prospective cohort study conducted from May 2015 to April 2017.

Setting

A tertiary care university hospital in China.

Participants

A total of 178 patients with sepsis admitted to the medical intensive care unit (ICU) were included.

Main outcome measures

The primary outcome was 90-day mortality while the secondary outcomes were in-hospital mortality, length of ICU stay and length of hospital stay.

Results

The median age (IQR) was 78 (66–84) years old, and 77.0% patients were older than 65 years. The 90-day mortality was 47.2%. The in-hospital mortality was 41.6%, and the length of ICU stay and hospital stay were 12 (5–22) and 15 (9–28) days, respectively. Cox proportional hazard regression analysis identified that Sequential Organ Failure Assessment score (HR=1.229, p<0.001), Acute Physiology and Chronic Health Evaluation II score (HR=1.050, p<0.001) and BMI (HR=0.940, p=0.029) were all independently associated with the 90-day mortality. Patients were divided into four groups based on BMI (underweight 33 (18.5%), normal 98 (55.1%), overweight 36 (20.2%) and obese 11 (6.2%)). The 90-day mortality (66.7%, 48.0%, 36.1% and 18.2%, p=0.015) and in-hospital mortality (60.6%, 41.8%, 30.6% and 18.2%, p=0.027) were statistically different among the four groups. Differences in survival among the four groups were demonstrated by Kaplan-Meier survival analysis (p=0.008), with the underweight patients showing a lower survival rate.

Conclusions

BMI was an independent factor associated with 90-day survival in a Chinese cohort of medical patients with sepsis, with patients having a lower BMI at a higher risk of death.

https://ift.tt/2MnWQ5i

Improving access to healthcare for women in Tanzania by addressing socioeconomic determinants and health insurance: a population-based cross-sectional survey

Objective

This study was performed to explore the factors associated with accumulation of multiple problems in accessing healthcare among women in Tanzania as an example of a low-income country.

Design

Population-based cross-sectional survey.

Setting

Nationwide representative data for women of reproductive age obtained from the 2015–2016 Tanzania Demographic and Health Survey were analysed.

Primary outcome measures

A composite variable, 'problems in accessing healthcare', with five (1-5) categories was created based on the number of problems reported: obtaining permission to go to the doctor, obtaining money to pay for advice or treatment, distance to a health facility and not wanting to go alone. Respondents who reported fewer or more problems placed in lower and higher categories, respectively.

Results

A total of 13 266 women aged 15–49 years, with a median age (IQR) of 27 (20–36) years were interviewed and included in the analysis. About two-thirds (65.53%) of the respondents reported at least one of the four major problems in accessing healthcare. Furthermore, after controlling for other variables included in the final model, women without any type of health insurance, those belonging to the poorest class according to the wealth index, those who had not attended any type of formal education, those who were not employed for cash, each year of increasing age and those who were divorced, separated or widowed were associated with greater problems in accessing healthcare.

Conclusion

This study indicated the additive effects of barriers to healthcare in low-income countries such as Tanzania. Based on these results, improving uptake of health insurance and addressing social determinants of health are the first steps towards reducing women's problems associated with accessing healthcare.

https://ift.tt/2p1WJ6r