Search

Purpose We conducted a systematic review to analyse the performance of the sentinel lymph-node biopsy (SLNB) after the neoadjuvant chemotherapy, compared to axillary lymph-node dissection, in terms of false-negative rate (FNR) and sentinel lymph-node identification rate (SLNIR), sensitivity, negative predictive value (NPV), need for axillary lymph-node dissection (ALND), morbidity, preferences, and costs. Methods MEDLINE, Embase, Scopus, and The Cochrane Library were searched. We assessed the quality of the included systematic reviews using AMSTAR2 tool, and estimated the degree of overlapping of the individual studies on the included reviews. Results Six systematic reviews with variable quality were selected. We observed a very high overlapping degree across the included reviews. The FNR and the SLNIR were quite consistent (FNR 13-14%; SLNIR- 90% or higher). In women with initially clinically node-negative breast cancer, the FNR was better (6%), with similar SLNIR (96%). The included reviews did not consider the other prespecified outcomes. Conclusions It would be reasonable to suggest performing an SLNB in patients treated with NACT, adjusting the procedure to the previous marking of the affected lymph node, using double tracer, and biopsy of at least three sentinel lymph nodes. More well-designed research is needed.

Biliary tract neoplasms; Biological therapy; Immunotherapy Neoplàsies de les vies biliars; Teràpia biològica; Immunoteràpia Neoplasias de las vias biliares; Terapia biológica; Inmunoterapia Background: The trade-off between systemic oncological treatments (SOTs) and UPSC in patients with primary advanced hepatobiliary cancers (HBCs) is not clear in terms of patient-centred outcomes beyond survival. This overview aims to assess the effectiveness of SOTs (chemotherapy, immunotherapy and targeted/biological therapies) versus UPSC in advanced HBCs. Methods: We searched for systematic reviews (SRs) in PubMed, EMBASE, the Cochrane Library, Epistemonikos and PROSPERO. Two authors assessed eligibility independently and performed data extraction. We estimated the quality of SRs and the overlap of primary studies, performed de novo meta-analyses and assessed the certainty of evidence for each outcome. Results: We included 18 SRs, most of which were of low quality and highly overlapped. For advanced hepatocellular carcinoma, SOTs showed better overall survival (HR = 0.62, 95% CI 0.55–0.77, high certainty for first-line therapy; HR = 0.85, 95% CI 0.79–0.92, moderate certainty for second-line therapy) with higher toxicity (RR = 1.18, 95% CI 0.87–1.60, very low certainty for first-line therapy; RR = 1.58, 95% CI 1.28–1.96, low certainty for second-line therapy). Survival was also better for SOTs in advanced gallbladder cancer. No outcomes beyond survival and toxicity could be meta-analysed. Conclusion: SOTs in advanced HBCs tend to improve survival at the expense of greater toxicity. Future research should inform other patient-important outcomes to guide clinical decision making. This study is funded through a grant from Instituto de Salud Carlos III (PI18/00034), co-financed by funds from the European Regional Development Fund.

To understand the evolution of coping among women diagnosed with breast cancer over time, and the effect of age and family income on coping. Using a phenomenological qualitative study, data was collected through semi-structured interviews with sixteen women in a hospital in Barcelona (Spain) between January 2018 and June 2019. An analysis of thematic content and discursive profile was carried out, assisted by the Nvivo v.12 program. Coping strategies change according to the meaning of breast cancer in each phase and the age and family income. In the acute phase, multiple coping strategies are identified, and this variety was more frequent among the young women in the study. In the extended phase, planning, distancing, and seeking social support become important. The latter used during treatment by older women in the study, regardless of family income. In the follow-up phase, distancing stands out, but also the search for social support among young women with fewer resources. Coping with breast cancer evolves according to the meaning that the disease receives in each phase. In addition, the analysis by discursive profile shows how the social support context is also related to the coping strategies in each phase.

To identify, describe, and organise currently available evidence regarding systemic oncological treatments (SOTs) (chemotherapy, targeted/biological therapies, and immunotherapy) compared to best supportive care (BSC) for patients with advanced pancreatic cancer (PC).We conducted a scoping review and evidence mapping, adhering to PRISMA-ScR checklist. We searched MEDLINE, EMBASE, Cochrane Library, Epistemonikos, PROSPERO, and clinicaltrials.gov for eligible studies. We included systematic reviews (SRs), randomised controlled trials (RCTs), quasi-experimental, and observational studies evaluating SOTs compared to BSC or no treatment in patients with advanced PC. Two independent reviewers performed the screening process and data extraction. We developed evidence maps as an interactive visualization display, including the assessed interventions and outcomes.Of the 50,601 records obtained from our search, we included 43 studies: 2 SRs, 16 RCTs, 4 quasi-experimental studies, 20 observational studies, and 1 protocol for a quasi-experimental study. Forty-two studies reported survival-related outcomes and most favoured SOTs, while five reported toxicity and most favoured BSC. Other patient-centred outcomes, such as quality of life, were scarcely reported.This study highlights the current evidence gaps in studies assessing treatments for patients with advanced PC, mainly the lack of reports of non-survival-related outcomes, pointing out research areas that need further attention to make better recommendations for these patients.

Neoadjuvant chemotherapy based on anthracyclines and ifosfamide for high-risk soft tissue sarcomas (STS) of the extremities and trunk is a controversial treatment option. There are substantial interindividual differences in clinical outcomes in patients treated with neoadjuvant chemotherapy. The aim of this study was to evaluate, as biomarkers, polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, or drug targets and their association with toxicity and survival in STS patients treated with neoadjuvant chemotherapy. We analysed variants in genes involved in anthracycline metabolism (ABCB1, ABCC2, NQO1, CBR3, and SLC22A16) and in ifosfamide catabolism (ALDH1A1) in 79 treated patients. Two genes showed significant association after adjusted multivariate analysis: ABCC2 and ALDH1A1. In patients treated with anthracyclines, ABCC2 rs3740066 was associated with risk of febrile neutropenia (p = 0.031), and with decreased overall survival (OS) (p = 0.024). ABCC2 rs2273697 was associated with recurrence-free survival (RFS) (p = 0.024). In patients treated with ifosfamide, ALDH1A1 rs3764435 was associated with RFS (p = 0.046). Our pharmacogenetic study shows for the first time that variants in genes regulating the metabolism of neoadjuvant chemotherapy may be helpful to predict toxicity and survival benefit in high-risk STS treated with neoadjuvant chemotherapy. Further validation studies are needed to establish their clinical utility.

To understand the evolution of coping among women diagnosed with breast cancer over time, and the effect of age and family income on coping.Using a phenomenological qualitative study, data was collected through semi-structured interviews with sixteen women in a hospital in Barcelona (Spain) between January 2018 and June 2019. An analysis of thematic content and discursive profile was carried out, assisted by the Nvivo v.12 program.Coping strategies change according to the meaning of breast cancer in each phase and the age and family income. In the acute phase, multiple coping strategies are identified, and this variety was more frequent among the young women in the study. In the extended phase, planning, distancing, and seeking social support become important. The latter used during treatment by older women in the study, regardless of family income. In the follow-up phase, distancing stands out, but also the search for social support among young women with fewer resources.Coping with breast cancer evolves according to the meaning that the disease receives in each phase. In addition, the analysis by discursive profile shows how the social support context is also related to the coping strategies in each phase.

Background Esophageal and gastric cancers are a significant public health problem worldwide, with most patients presenting with advanced-stage disease and, consequently, poor prognosis. Systemic oncological treatments (SOT) have been widely used over more conservative approaches, such as supportive care. Nevertheless, its effectiveness in this scenario is not sufficiently clear. This paper provides an overview of systematic reviews that assessed the effectiveness of SOT compared with the best supportive care (BSC) or placebo in patients with advanced esophageal or gastric cancers in an end-of-life context. Methods We searched MEDLINE, EMBASE, The Cochrane Library, Epistemonikos, and PROSPERO for eligible systematic reviews (SRs) published from 2008 onwards. The primary outcomes were overall survival (OS), progression-free survival (PFS), functional status, and toxicity. Two authors assessed eligibility and extracted data independently. We evaluated the methodological quality of included SRs using the AMSTAR-2 tool and the overlap of primary studies (corrected covered area, CCA). Also, we performed a de novo meta-analysis with data reported for each primary study when it was possible. We assessed the certainty of evidence using the GRADE approach. Results We identified 16 SRs (19 included trials) for inclusion within this overview. Most reviews had a critically low methodological quality, and there was a very high overlap of primary studies. It is uncertain whether SOT improves OS and PFS over more conservative approaches due to the very low certainty of evidence. Conclusions The evidence is very uncertain about the effectiveness of SOT for advanced esophageal or gastric cancers. High-quality SRs and further randomized clinical trials that include a thorough assessment of patient-centered outcomes are needed. Trial registration Open Science Framework, 10.17605/OSF.IO/7CHX6.

Background Patients with advanced pancreatic cancer (PC) have a high risk of dying in the short or medium-term. This overview aimed to assess the evidence regarding systemic oncological treatments (SOT) versus supportive care for advanced PC. Methods We searched for systematic reviews (SRs) in MEDLINE, Embase, The Cochrane Library, Epistemonikos, and PROSPERO. Two authors assessed eligibility independently. Data extraction and methodological quality assessment were conducted by one author and cross-checked by another one. We evaluated the overlap of primary studies, performed a de novo meta-analysis, and assessed the certainty of evidence. Primary outcomes were overall survival (OS), quality of life (QoL), functional status (FS), and toxicity. Results We identified three SRs that assessed SOT versus supportive care in patients with advanced PC. All SRs had critically low methodological quality. At 12 months, OS improved with chemotherapy, radiotherapy followed by chemotherapy, and immunotherapy, but the certainty of the evidence supporting these findings is very low. The evidence on chemotherapy is very uncertain about its effects on QoL; it suggests a slight increase in toxicity and little to no difference in FS. The evidence on immunotherapy is very uncertain about its effects in toxicity. Conclusions The identified evidence is very uncertain about the benefits of oncological treatments on OS and QoL in patients with advanced PC with a high risk of dying in the short or medium-term, so its use should be proposed only to selected patients. Further studies that include a thorough assessment of patient-centred outcomes are needed.

Objective Alzheimer’s disease is a major health problem in our society. To date, pharmacological treatments have obtained poor results and there is a growing interest in finding non-pharmacological interventions for this disease. Transcranial magnetic stimulation (TMS) is a non-invasive technique that is able to induce changes in brain activity and long-term modifications in impaired neural networks, becoming a promising clinical intervention. Our goal is to study the benefit of individualized TMS targeting based on the patient’s functional connectivity (personalized targeting), and short duration TMS protocol, instead of current non-individualized and longer session approaches. A double blind randomized controlled trial will be conducted to assess the effects of TMS treatment immediately, 1 month, 3 months and 6 months after the end of the intervention. Fifty-four patients with a diagnosis of Alzheimer’s disease will be randomly allocated into experimental (active TMS), sham control, or conventional intervention control group. We will quantify changes in cognitive, functional, and emotional deficits in Alzheimer patients, as well as the functional connectivity changes induced by the TMS treatment. Results We expect to demonstrate that personalized TMS intervention has a measurable positive impact in cognition, emotion, daily living activities and brain connectivity, thus representing a potential treatment for Alzheimer’s disease. Trial registration The trial has been prospectively registered at ClinicalTrials.gov, identifier NCT03121066. Date of registration: 04/19/2017

Assessing the long-term risk of breast cancer after diagnosis of benign breast disease by mammography is of utmost importance to design personalised screening strategies. We analysed individual-level data from 778,306 women aged 50–69 years with at least one mammographic screening participation in any of ten breast cancer screening centers in Spain from 1996 to 2015, and followed-up until 2017. We used Poisson regression to compare the rates of incident breast cancer among women with and without benign breast disease. During a median follow-up of 7.6 years, 11,708 (1.5%) women had an incident of breast cancer and 17,827 (2.3%) had a benign breast disease. The risk of breast cancer was 1.77 times higher among women with benign breast disease than among those without (95% CI: 1.61 to 1.95). The relative risk increased to 1.99 among women followed for less than four years, and remained elevated for two decades, with relative risk 1.96 (95% CI: 1.32 to 2.92) for those followed from 12 to 20 years. Benign breast disease is a long-term risk factor for breast cancer. Women with benign breast disease could benefit from closer surveillance and personalized screening strategies.

Population ageing within Europe has major social and economic consequences. One of the most devastating conditions that predominantly affects older people is dementia. The SMART4MD (Support Monitoring and Reminder Technology for Mild Dementia) project aims to develop and test a health application specifically designed for people with mild dementia. The aim of this feasibility study was to evaluate the design of the SMART4MD protocol, including recruitment, screening, baseline examination and data management, and to test the SMART4MD application for functionality and usability before utilization in a full-scale study. The feasibility study tested the protocol and the app in Spain and Sweden. A total of nineteen persons with cognitive impairment, and their informal caregivers, individually performed a task-based usability test of the SMART4MD app model in a clinical environment, followed by four-week testing of the app in the home environment. By employing a user-centered design approach, the SMART4MD application proved to be an adequate and feasible interface for an eHealth intervention. In the final usability test, a score of 81% satisfied users was obtained. The possibility to test the application in all the procedures included in the study generated important information on how to present the technology to the users and how to improve these procedures. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. open access

Cancer-related fatigue (CRF) is one of the most prolonged discomforts suffered by people who have had cancer. Seventy-eight to ninety-six percent of cancer patients experience fatigue, especially while undergoing treatment. CRF is related to insomnia, anxiety, depression, and also varies depending on age. However, little is known about the factors contributing to CRF and better understanding of determinants of CRF makes it easier to identify early patients at risk and in designing intervention planning. The aim of this study was to assess the influence of precipitating factors (diagnosis of breast cancer and other clinical aspects) and perpetuating factors (social network, quality of life, mental disorders) on the presence of chronic fatigue in women from our cultural context, by social class each other determinants. Methods It was carried out a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were data from the Brief Fatigue Inventory questionnaire and hospital medical records. The dependent variable was fatigue and the independent variables were age, social class, time since diagnoses, cohabitation, comorbidity, relapse, body mass index, mental health (anxiety and depression), social network, social support, and quality of life. Results Seventy-two percent of the women in the DAMA cohort reported moderate to severe fatigue. Risk of suffering from severe fatigue was greatest among individuals with low social class, those aged under 50 years, those with chronic disorders who had relapsed, and those with symptoms of anxiety and depression. In our study, CRF did not appear to be related to the stage of the cancer at diagnosis, or to the time since diagnosis. Conclusions CRF is an element that the professionals responsible for the control and monitoring of women should take into account as another element to be taken into consideration.

Background Information and communication technologies are promising tools to increase the quality of life of people with dementia or mild cognitive impairment and that of their caregivers. However, there are barriers to their use associated with sociodemographic factors and negative attitudes, as well as inadequate knowledge about technologies. Objective The aim of this study was to analyze technophilia (attitudes toward new technologies) and the use of smartphones and tablets along with associated factors in people with dementia/mild cognitive impairment and their caregivers. Methods Data from the first visit of the Support Monitoring and Reminder for Mild Dementia (SMART4MD) randomized multicenter clinical trial were used for this analysis. Data were obtained from two European countries, Spain and Sweden, and from three centers: Consorci Sanitari de Terrassa (Catalonia, Spain), Servicio Andaluz de Salud (Andalusia, Spain), and the Blekinge Institute of Technology (Sweden). Participants with a score between 20 and 28 in the Mini Mental State Examination, with memory problems (for more than 6 months), and who were over the age of 55 years were included in the study, along with their caregivers. The bivariate Chi square and Mann-Whitney tests, and multivariate linear and logistic regression models were used for statistical analysis. Results A total of 1086 dyads were included (N=2172). Overall, 299 (27.53%) of people with dementia/mild cognitive impairment had a diagnosis of dementia. In addition, 588 (54.14%) of people with dementia/mild cognitive impairment reported using a smartphone almost every day, and 106 (9.76%) used specific apps or software to support their memory. Among the caregivers, 839 (77.26%) used smartphones and tablets almost every day, and 181 (16.67%) used specific apps or software to support their memory. The people with dementia/mild cognitive impairment showed a lower level of technophilia in comparison to that of their caregivers after adjusting for confounders (B=0.074, P=.02) with differences in technology enthusiasm (B=0.360, P Conclusions Technophilia was associated with a better quality of life and sociodemographic variables in people with dementia/mild cognitive impairment and caregivers, suggesting potential barriers for technological interventions. People with dementia/mild cognitive impairment frequently use smartphones and tablets, but the use of specific apps or software to support memory is limited. Interventions using these technologies are needed to overcome barriers in this population related to sociodemographic characteristics and the lack of enthusiasm for new technologies. Trial Registration ClinicalTrials.gov NCT03325699; https://clinicaltrials.gov/ct2/show/NCT03325699

Background:The benefit of cognitive stimulation (CS) treatments in dementia is unequal. This study has sought to identify cognitive and functional measurements before and after the treatment which are indicative of a better response to a one-year CS program.Methods:A retrospective observational study was conducted between 2004 and 2012 in a sample of 60 users diagnosed with mild Alzheimer's disease (AD) who followed a one-year CS program and underwent a cognitive and functional assessment before and after the intervention. As a primary measure of treatment response, we used the annual change of the Mini-Mental State Examination (MMSE) scores, which distinguished good responders (R) from non-responders (NR).Results:51.7% of patients classified as R at baseline had a higher cognitive performance in attention, immediate verbal memory, language, and working memory compared to NR. No initial statistically significant differences were found between R and NR in any sociodemographic variables, medical conditions, anxiety and/or depressive symptoms, treatment with cholinesterase inhibitors (ChEIs), level of insight, global cognitive function (MMSE), or functional capacity. After 12 months of treatment, R had significantly better results than NR on MMSE, temporal orientation, category evocation, and Philadelphia Geriatric Center-Instrumental Activities of Daily Living (PGC-IADL).Conclusion:The response to a CS treatment of some subjects over others is linked to cognitive and functional capacity. This research contributes to characterize the neuropsychological profile that differentiates subjects who respond better than others before and after the treatment. This should contribute to customize and optimize neuropsychological interventions in patients with AD.

Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age-adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false-positive results was 1.84 (95% CI: 1.73, 1.95; P < .001). The risk was higher in women who had calcifications, whether they were (HR, 2.73; 95% CI: 2.28, 3.28; P < .001) or were not (HR, 2.24; 95% CI: 2.02, 2.48; P < .001) associated with masses. Women in whom mammographic features showed changes in subsequent false-positive results were those who had the highest risk (HR, 9.13; 95% CI: 8.28, 10.07; P < .001). Conclusion Women with false-positive results had an increased risk of breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. (©) RSNA, 2016 Online supplemental material is available for this article.

Background: Many countries are witnessing a trend of growth in the number and proportion of older adults within the total population. In Europe, population aging has had and will continue to have major social and economic consequences. This is a fundamentally positive development where the added life span is of great benefit for both the individual and the society. Yet, the risk for the individual to contract noncommunicable diseases and disability increases with age. This may adversely affect the individual’s ability to live his or her life in the way that is desired. Cognitive conditions constitute a group of chronic diseases that predominantly affects older people. Recent technology advancements can help support the day-to-day living activities at home for people with cognitive impairments. Objective: A digital platform (Support Monitoring and Reminder for Mild Dementia; SMART4MD) is created to improve or maintain the quality of life for people with mild cognitive impairment (PwMCI) and their carers. The platform will provide reminders, information, and memory support in everyday life, with the purpose of giving structure and lowering stress. In the trial, we will include participants with a diagnosed neurocognitive disorder as well as persons with an undiagnosed subjective memory problem and cognitive impairment, that is, 20 to 28 points on the Mini-Mental State Examination. Methods: A pragmatic, multicenter RCT is being conducted in Spain, Sweden, and Belgium. The targets for recruitment are 1200 dyads—split into an intervention group and a control group that are in usual care. Intervention group participants will be provided with a data-enabled computer tablet with the SMART4MD app. Its core functionalities, intended to be used daily at home, are based on reminders, cognitive supporting activities, and sharing health information. Results: Inclusion of participants started in December 2017, and recruitment is expected to end in February 2019. Furthermore, there will be 3 follow-up visits at 6, 12, and 18 months after the baseline visit. Conclusions: This RCT is expected to offer benefits at several levels including in-depth knowledge of the possibilities of introducing a holistic multilayered information and communication technology solution for this group. SMART4MD has been developed in a process involving the structured participation of PwMCI, their informal carers, and clinicians. The adoption of SMART4MD faces the challenge of this age group’s relative unfamiliarity with digital devices and services. However, this challenge can also be an opportunity for developing a digital device tailored to a group at risk of digital exclusion. This research responds to the wider call for the development of digital devices which are accessible and affordable to older people and this full scale RCT can hopefully serve as a model for further studies in this field. Trial Registration: ClinicalTrials.gov NCT03325699; https://clinicaltrials.gov/ct2/show/NCT03325699 International Registered Report Identifier (IRRID): DERR1-10.2196/13711

Background The main objective of this research was to evaluate the acceptance of technology based on a wearable lifelogging camera in a sample of older adults diagnosed with mild cognitive impairment (MCI). Methods A mixed-method design was used, consisting of a self-report questionnaire, numerous images taken by users, and a series of focus group discussions. The patients were involved in an individualized training programme. Results Nine MCI patients and their caregiver relatives were included. They showed good acceptance of the camera and downloaded an appropriate number of images on a daily basis. Perceived severity and ease of use were the main factors associated with the intention to use the device. Conclusions Older adults with MCI can become competent users of lifelogging wearable cameras with a good level of acceptance. Privacy concerns are outweighed by the potential benefits for memory. Limitations, strengths and implications for future research are discussed. Electronic supplementary material The online version of this article (10.1186/s12877-019-1132-0) contains supplementary material, which is available to authorized users.

Background The effect of changes in mammographic density over time on the risk of breast cancer remains inconclusive. Methods We used information from four centres of the Breast Cancer Screening Program in Spain in the period 1996–2015. We analysed individual level data from 117,388 women first screened age 50–54, with at least two screening examinations. Breast density was determined using the BI-RADS classification (A to D in increasing order) at earliest and latest screening examination. Adjusted Poisson regression models were used to estimate the relative risk (RR) and 95% confidence intervals (95%CI) of the association between changes in mammographic density and breast cancer risk over time. Results During an average 5.8 years of follow-up, 1592 (1.36%) women had a breast cancer diagnosis. An increase in density category increased breast cancer risk, and a decrease in density decreased the risk, compared with women who remained in the same BI-RADS category. Women whose density category increased from B to C or B to D had a RR of 1.55 (95%CI = 1.24–1.94) and 2.32 (95%CI = 1.48–3.63), respectively. The RR for women whose density increased from C to D was 1.51 (95%CI = 1.03–2.22). Changes in BI-RADS density were similarly associated with the risk for invasive cancer than for ductal carcinoma in situ. Conclusions Although a modest proportion of women changed BI-RADS density category, mammographic density changes modulated the risk of breast cancer and identified women at a differential risk. Using two longitudinal measures of BI-RADS density could help target women for risk-based screening strategies.

Xavier Bonfill,1–3 Ingrid Arevalo-Rodriguez,4,5 Laura Martínez García,3 Maria Jesús Quintana,1,2 Diana Buitrago-Garcia,4 Diego Lobos Urbina,6 José Antonio Cordero7 On behalf of the IADT Spanish Study Group 1Department of Clinical Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau, Institut de Recerca Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2CIBER of Epidemiology and Public Health, Barcelona, Spain; 3Iberoamerican Cochrane Centre, Barcelona, Spain; 4Centro de Investigación en Salud Pública y Epidemiología Clínica, Facultad de Ciencias de la Salud Eugenio Espejo, Universidad Tecnológica Equinoccial, Quito, Ecuador; 5Hospital Ramon y Cajal (IRYCIS), Clinical Biostatistics Unit, CIBER of Epidemiology and Public Health, Madrid, Spain; 6Pontificia Universidad Católica de Chile, Santiago, Chile; 7School of Health Sciences Blanquerna– Ramon Llull University, Barcelona, Spain Purpose: The purpose of this study was to provide evidence-based recommendations of intermittent androgen deprivation therapy (IADT) compared with continuous androgen deprivation therapy (CADT) for men with prostate cancer (PCA). Methods: We conducted a comprehensive search in MEDLINE, EMBASE, The Cochrane Library, CINAHL, and ECONLIT, from the database inception to December 2017. We adhered to the Grading of Recommendations, Assessment, Development and Evaluation framework to assess the quality of the evidence and to formulate recommendations. Results: We included one systematic review with 15 trials as well as three additional studies that assessed IADT versus CADT, all of them focused on PCA patients in advanced stages. The findings did not show differences for critical and important outcomes, including adverse events. Trials reported the benefits of IADT in terms of selected domains of health-related quality of life, although with high heterogeneity. Evidence quality was considered moderate or low for most of the assessed outcomes. We identified a patient preference study reporting a high preference for IADT, due to issues related to quality of life, general well-being, and side effects, among others. We did not identify economic studies comparing these regimes. We formulate four recommendations: one no-recommendation, one conditional recommendation, and two good practice points. Conclusion: For men in early stages of PCA, it is not possible to make any recommendation about the preferable use of IADT or CADT due to the lack of available evidence. For men in advanced stages of the disease, an IADT should be considered as soon as clinically reasonable (weak recommendation and low certainty of the evidence). Clinicians should discuss the risks and benefits of IADT and CADT with their patients, taking into account their values and preferences. Keywords: hormone deprivation therapy, prostate cancer, prostate neoplasm, evidence-based medicine, GRADE approach

Background: Our aim was to assess the cumulative risk of false-positive screening results, screen-detected cancer, and interval breast cancer in mammography screening among women with and without a previous benign breast disease and a family history of breast cancer. Methods: The cohort included 42 928 women first screened at the age of 50-51 years at three areas of the Spanish Screening Programme (Girona, and two areas in Barcelona) between 1996 and 2011, and followed up until December 2012. We used discrete-time survival models to estimate the cumulative risk of each screening outcome over 10 biennial screening exams. Results: The cumulative risk of false-positive results, screen-detected breast cancer, and interval cancer was 36.6, 5.3, and 1.4 for women with a previous benign breast disease, 24.1, 6.8, and 1.6% for women with a family history of breast cancer, 37.9, 9.0, and 3.2%; for women with both a previous benign breast disease and a family history, and 23.1, 3.2, and 0.9% for women without either of these antecedents, respectively. Conclusions: Women with a benign breast disease or a family history of breast cancer had an increased cumulative risk of favourable and unfavourable screening outcomes than women without these characteristics. A family history of breast cancer did not increase the cumulative risk of false-positive results. Identifying different risk profiles among screening participants provides useful information to stratify women according to their individualised risk when personalised screening strategies are discussed.

Background: Breast cancer continues to be the most commonly diagnosed cancer in women. Breast cancer survivors face numerous problems, especially after completing the first year of intense treatment. We present the protocol for an ongoing study to analyze the impact of a series of factors on breast cancer survival related to lifestyle, emotional well-being, and use of complementary and alternative medicine (CAM). Objective: We aim to analyze the influence of social determinants, lifestyle changes, emotional well-being, and use of CAM in the progression of breast cancer in women diagnosed with breast cancer between 2003 and 2013 in Barcelona, Spain. Methods: We will perform a mixed cohort study (prospective and retrospective) of women diagnosed with breast cancer, created using a convenience sample in which we study the evolution of the disease (relapse, death, or remaining disease-free). Once identified, we sent the women information about the study and an informed consent form that they are required to sign in order to participate; a total of 2235 women were recruited. We obtained the following information from all participants: sociodemographic profile via a phone interview, and a self-administered survey of information about the study’s objectives (lifestyles, emotional well-being, health care services, and the use of CAM). Lastly, we examined clinical records to obtain data on the tumor at the time of diagnosis, the treatment received, the occurrence of relapses (if any), and the tumor typology. We present data on the women’s social profile based on descriptive data obtained from the telephone interview (welcome survey). Results: Based on the welcome survey, which was completed by 2712 women, 14.42% (391/2712) of respondents were 65 years of age. A total of 43.69% (1185/2712) belonged to the highest social classes (I and II), 31.27% (848/2712) to the middle class (III), and 23.49% (637/2712) to the working classes (IV and V). Approximately 22.71% (616/2712) lived alone, 38.31% (1039/2712) lived with one person, and 38.97% (1057/2712) lived with two or more people. Conclusions: We obtained information from a large cohort of women, but this study has limitations related to the convenience sampling strategy, one of which is reduced representativeness. Conversely, being a self-administered survey, the study introduces biases, especially from respondents that answered on paper. However, the information that the study provides will serve as the basis for designing future interventions aimed at improving the knowledge gaps indicated for women with breast cancer.

The purpose of this study was (a) to evaluate the association between cigarette smoking and the prevalence of distal colorectal polyps and adenocarcinoma and (b) to analyse genetic alterations representing different molecular pathways of the colorectal carcinogenesis. A total of 623 asymptomatic male (mean age: 53 years; 50-65) car factory workers were included. Information on smoking habits and other lifestyle factors were collected followed by a 60 cm colonoscopy. APC and KRAS mutations and microsatellite status were determined in colorectal lesions (colorectal carcinoma (CRC), hyperplastic (HP) and adenomatous polyps (AP)). Data were analysed using unconditional multiple logistic regression models. Smokers had a higher prevalence of AP (OR 2.1; 95% CI 1.2-3.6; p < 0.05) and HP (OR 5.4; 95% CI 2.6-11.1; p < 0.05). No differences in CRC were observed. There was a dose-response relationship with the number of cigarettes smoked. The risk of developing AP or HP decreased after smoking cessation, even among heavy smokers (a parts per thousand yen20 packs/year). KRAS mutations were more prevalent among smokers AP (OR 5.6; 95% CI 1.6-20.4; p=0.007). There was a trend of positive association with APC mutations (OR 3.5; 95% CI 0.9-4.4; p=0.096). APC and KRAS mutations were found in 36% and 61% of the HP of smokers, but were absent in non-smokers (p=0.89 and 0.78, respectively). There were no differences in MSI between smokers and non-smokers. Cigarette smoking is associated with a higher risk of developing both HP and AP and a higher prevalence of mutations in APC and KRAS.

Resumen Fundamento y objetivo Determinar la prevalencia y el tipo de tratamiento hormonal sustitutivo (THS) en participantes de un programa de cribado de cancer de mama de Barcelona. Pacientes y metodo La prevalencia de consumo de THS se obtuvo a traves de una encuesta. Se recogio informacion sobre tipo de THS, antecedentes ginecologicos, situacion laboral y nivel de estudios. La prevalencia se calculo con sus intervalos de confianza (IC) del 95%. Resultados Entre mayo de 2001 y junio de 2005 participaron en el programa de cribado de cancer de mama 21.835 mujeres con una edad media de 57,6 anos (el 86,7% posmenopausicas). La prevalencia confirmada de consumo de THS fue del 5,2% (IC del 95%: 5,3–6,0), y se administro con mayor frecuencia a mujeres entre 55 y 59 anos. Los tipos mas frecuentes fueron la tibolona (39,5%) y la combinacion de estrogenos y progestagenos (30,4%). El nivel educativo alto se relaciono con mayor consumo de THS. No hubo diferencias estadisticamente significativas en el resultado del cribado segun consumo o tipo de THS. Conclusiones La prevalencia de uso del THS fue del 5,2%. Los tipos de THS mas frecuentes fueron la tibolona y la combinacion de estrogenos y progestagenos.

To analyze phenotypic classification and other risk factors for interval breast cancer, focusing on true interval and false negative cancers. A nested case-control study was performed among 115 cancers detected between two screening mammograms (interval cancers) and 115 screen-detected cancers diagnosed between 1995 and 2008 in a population-based breast cancer screening program in Barcelona (Spain). Bivariate and multivariate analyses were performed to compare patient and tumor molecular characteristics among all interval cancers, true intervals and false negatives, and screen-detected cancers. A total of 42.5% of interval cancers were true interval tumors and 16.2% were false negatives. High breast density and triple negative phenotype were more frequent in true interval cancers than in screen-detected cancers (57.6 and 34.1%, respectively for breast density, p = 0.023; 28.1 and 7.5%, respectively for triple negative phenotype, p = 0.028), while no statistically significant differences were observed between false negatives and screen-detected cancers. The main adjusted factors associated with true interval cancers compared with screen-detected cancers were high breast density and triple negative phenotype (OR = 3.1, 95% CI, 1.03-9.24 and OR = 8.9, 95% CI, 2.03-38.62, respectively). A more aggressive molecular phenotype and high breast density were identified in breast tumors that truly arise in the interval between screenings.

Objective To describe the development of a novel on-line database aimed to serve as a source of information concerning healthcare interventions appraised for their clinical value and appropriateness by several initiatives worldwide, and to present a retrospective analysis of the appraisals already included in the database. Methods and Findings Database development and a retrospective analysis. The database DianaHealth.com is already on-line and it is regularly updated, independent, open access and available in English and Spanish. Initiatives are identified in medical news, in article references, and by contacting experts in the field. We include appraisals in the form of clinical recommendations, expert analyses, conclusions from systematic reviews, and original research that label any health care intervention as low-value or inappropriate. We obtain the information necessary to classify the appraisals according to type of intervention, specialties involved, publication year, authoring initiative, and key words. The database is accessible through a search engine which retrieves a list of appraisals and a link to the website where they were published. DianaHealth.com also provides a brief description of the initiatives and a section where users can report new appraisals or suggest new initiatives. From January 2014 to July 2015, the on-line database included 2940 appraisals from 22 initiatives: eleven campaigns gathering clinical recommendations from scientific societies, five sets of conclusions from literature review, three sets of recommendations from guidelines, two collections of articles on low clinical value in medical journals, and an initiative of our own. Conclusions We have developed an open access on-line database of appraisals about healthcare interventions considered of low clinical value or inappropriate. DianaHealth.com could help physicians and other stakeholders make better decisions concerning patient care and healthcare systems sustainability. Future efforts should be focused on assessing the impact of these appraisals in the clinical practice.

Benign breast disease increases the risk of breast cancer. This association has scarcely been evaluated in the context of breast cancer screening programs although it is a prevalent finding in mammography screening. We assessed the association of distinct categories of benign breast disease and subsequent risk of breast cancer, as well as the influence of a family history of breast cancer. A retrospective cohort study was conducted in 545,171 women aged 50-69 years biennially screened for breast cancer in Spain. The median of follow-up was 6.1 years. The age-adjusted rate ratio (RR) of breast cancer for women with benign breast disease, histologically classified into nonproliferative and proliferative disease with and without atypia, compared with women without benign breast disease was estimated by Poisson regression analysis. A stratified analysis by family history of breast cancer was performed in a subsample. All tests were two-sided. The age-adjusted RR of breast cancer after diagnosis of benign breast disease was 2.51 (95 % CI: 2.14-2.93) compared with women without benign breast disease. The risk was higher in women with proliferative disease with atypia (RR = 4.56, 95 % CI: 2.06-10.07) followed by those with proliferative disease without atypia (RR = 3.58; 95 % CI = 2.61-4.91). Women with nonproliferative disease and without a family history of breast cancer remained also at increased risk of cancer (OR = 2.23, 95 % CI: 1.86-2.68). An increased risk of breast cancer was observed among screening participants with proliferative or nonproliferative benign breast disease, regardless of a family history of breast cancer. This information may be useful to explore risk-based screening strategies.

The purpose of the study was to determine the prevalence and type of hormone replacement therapy (HRT) in participants in a breast cancer screening program (BCSP) in Barcelona.Prevalence of use of HRT was obtained through a survey. Information about type of HRT, gynecological history and socioeconomic and educational level was collected. Prevalence was calculated with its corresponding 95% confidence interval.From May 2001 to June 2005 there were 21835 participants in the BCSP with a mean age of 57,6 years. Most of the participants were postmenopausal (86,7%). Confirmed prevalence of use of HRT was 5,2%(CI95% 5,3-6,0) with a greater use among women aged 55 to 59 years. The most frequent types of HRT were tibolone (39,5%) followed by combined estrogens plus progestin (30,4%). Higher education was associated with a higher use of HRT. Neither the use or the type of HRT influenced the results of the screening program.Prevalence of use of HRT was 5,2% in this study. The most frequently used agents were tibolone and combined estrogens plus progestin.

Objective To compare sensitivity an effectiveness of ThinPrep vs. Pap Test and determine whether the Hybrid Capture System II (HCII) for detection of human papillomavirus (HPV) could increase the sensitivity and effectiveness of cervical screening in a low risk population. Study design We present a comparative observer, blind, "split sample" study of ThinPrep and Papanicolaou staining in a population of 2026 consecutive women. Results Conventional Papanicolaou stain detected lesions in 62 cases (3.06%), including 1 atypical glandular cell of undetermined significance (AGUS), 34 atypical squamous cells of undetermined significance (ASCUS) (1.73% of atypias), 20 (0.99%) low grade squamous intraepithelial lesions (LSIL), and 7 (0.35%) high grade squamous intraepithelial lesions (HSIL). ThinPrep detected lesions in 63 cases (3.11%), including 26 (1.28%) ASCUS, 27 (1.33%) LSIL and 10 (0.49%) HSIL. Despite this overall similarity, only 35 had a coincident cytopathologic result by both methods. The kappa concordance index between ThinPrep and Pap was 0.546. Sensitivity and specificity were 74.6 and 45.0 in ThinPrep and 69.5 and 25.0 in Papanicolaou-stained smears. High risk HPV (HR-HP 17) was positive in 13 of ZOASCUS and in 21 of 22 SIL. Conclusion Technologies now widely available such as Thin Prep and viral detection aim to improve accuracy of screening.

To assess the impact of different factors on response rate (RR), time to tumor progression (TTP), and overall survival time (OS) in patients with locally advanced or metastatic soft tissue sarcoma (ASTS), included in three protocols with high-dose ifosfamide (HDIF).One hundred fifty six ASTS patients included in three consecutive phase II trials with HDIF (10 g/m(2)), alone or in combination with doxorubicin (DX), were analyzed. Cofactors were institution, trial, gender, age, performance status, histologic type, grade of malignancy, prior radiotherapy, presence of locoregional disease, metastatic site, salvage surgery, number of organs involved, and disease-free interval.By multivariate analysis performance status0 and lack of salvage surgery correlated with a poorer survival. A good-risk and a poor-risk group were identified, with median survival time (OS) of 29, 5, and 10 months, respectively (P = 0.00001). The 1-, 2-, and 3-year OS for 83 good-risk patients (either with PS = 0 or receiving salvage surgery) was 83, 44, and 29%, respectively, those figures being 37, 7, and 3% for 73 poor-risk patients.The design of randomized trials in ASTS including HDIF should consider those prognostic factors as stratification variables.

1120 Background: Sentinel lymph node biopsy (SLNB) is a widely used staging method for patients with early breast cancer. Neoadjuvant Therapy (NT) modifies the anatomical conditions in the breast and axilla, and thus reliability of SLNB after NT remains controversial. The aim of this study is to prospectively evaluate the feasibility and accuracy of this procedure in this particular group of patients. Methods: Between December 2007-2011, 69 patients (mean age 56 years) with locally advanced breast cancer (LABC) were prospectively studied. Patients were T1-4, N0-1, M0. Prior to surgery, 61 patients received chemotherapy (CT) (adryamicin/cyclophosphamide followed by docetaxel) and 8 patients endocrine therapy (ET). Thirty nine patients were initially node-negative (cN0) and 30 patients had clinical/ultrasound node-positive confirmed by cytology (cN1) at presentation. All patients were clinical and ultrasound node-negative after NT. The study contained two groups of patients: group A (validation) included the first 29, associated with an axillary lymph node dissection (ALND) after NT, in order to validate the study, and group B included the last 40, only associated with an ALND when SLNB was positive or not found. Results: Whole SLNB identification rate was 89.9%, and no significant differences were found between patients initially cN0 (92%; 36/39) and initially cN1 (87%; 26/30). Four of 7 patients in whom SLNB was not found had residual nodal metastasis after NT (3 of them were initially cN1). Sentinel lymph nodes were successfully identified in 87% (7/8) of patients after ET and in 90% (55/61) of patients after CT. There was one false negative (FN) case after CT in group A (9% of overall false negative rate, initially cN0) and there were no FN cases after ET. Positive SLNB were higher in initially cN1 group (53%; 16/30) than in initially cN0 group (18%; 7/39). Conclusions: SLNB after NT (CT or ET) is safe and feasible in patients with LABC, not only in initially cN0 but also in initially cN1. It accurately predicts the status of the axilla and avoids unnecessary ALND.

Background: Anxiety and depression are the most prevalent mental health pathologies among women with breast cancer. Social, clinical and contextual variables may influence emotional stress among women with breast cancer. The aim of this work is to study anxiety and depression in a cohort of women diagnosed with breast cancer between 2003 and 2013 in Barcelona. We evaluate social and clinical determinants. Methods: We performed a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were the Hospital Anxiety and Depression questionnaire and hospital medical records. Dependent variables were anxiety and depression; independent variables were social class, age, employment status, tumour stage at diagnosis, time since diagnosis, social network and social support. We performed a descriptive analysis, a bivariate analysis, and a multivariate logistic regression analysis. Results: A total of 1086 (48.6%) women had some degree of anxiety-related problem. As for depression. In the case of depression, 225 (15%) women had some degree of depression-related problem. Low emotional support and social isolation were clear risk factors for having more anxiety and depression. Low social class was also a risk factor, and age also played a role. Discussion: Our results show that women long period of cancer survival have high prevalences of anxiety than depression, and this prevalence of anxiety is higher than the general population. In addition, we found inequalities between social classes and the isolation and social support are worse too in low social class.