tbuckley/cabot-search huggingface dataset:
Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care
Authors: Anita Jain
Journal: BMJ (2014)

#### The paper

Effect of fixed dose combination treatment on adherence and risk factor control among patients at high risk of cardiovascular disease: randomised controlled trial in primary care by A Selak and colleagues (BMJ 2014;348:g3318). 

The past few decades have witnessed a shift in the global health burden from infectious diseases to non-communicable diseases. Ischaemic heart disease is now the primary cause of disability adjusted life years, with high blood pressure a leading risk factor. Recognising the threat posed by non-communicable diseases, the World Health Assembly in 2012 adopted a target of a 25% relative reduction in mortality from non-communicable diseases by 2025. The World Heart Federation has set a target to provide at least 50% of eligible people at risk of cardiovascular disease with necessary drug treatment to prevent heart attack and stroke.1

The rise in cardiovascular disease has been paralleled by increased life expectancy globally, with more people requiring multiple drugs for multiple conditions as they get older. International guidelines recommend antiplatelet treatment, statins, and one or more blood pressure lowering drugs in patients with established cardiovascular disease. However, treatment coverage globally remains poor.2 Poor adherence to medication may be due to many reasons, including the complexity of a regimen, socioeconomic considerations, poor patient-provider interaction, lack of access, or patient related factors such as physical or cognitive impairment.3

Fixed dose combination drugs, or polypills, which combine multiple drugs in a single tablet, offer the promise of improving adherence by simplifying the treatment regimen.4 The IMPACT (Improving Adherence using Combination Therapy) Trial was conducted to find out whether fixed dose combination drugs improve adherence and control of risk factors in primary care settings in New Zealand and to assess satisfaction of patients and …
The junior doctor survival guide
Authors: Isobel Weinberg
Journal: BMJ (2013)

How to cope with on-calls, night shifts, and everything else #### How to survive your first day ##### Karin Purshouse, foundation year 1 doctor, Oxford University Hospitals Trust, karinpurshouse@googlemail.com I pulled the sheets back . . . and there was melaena everywhere. I felt a cold rush of panic. “I . . . I’ll be back in a minute . . .” I got the nearest nurse to take a set of observations while I breathed a heavy sigh of relief—the registrar had just appeared. A massive upper gastrointestinal bleed was the final straw on a terrifying first day as a medical foundation year 1 doctor in a new hospital in a new deanery. How do you request an echocardiogram again? Where do the blood request forms for the phlebotomist go? How have I forgotten my radiology/computer/patient record passwords so quickly? I don’t even know the dose for oral co-amoxiclav . . . With a medical emergency in the middle of all of this, my to do list was getting ever longer. By the time my senior house officer arrived in the afternoon, the patient was stable, but I was mopping my tears. The first day will always be frightening, but here are some “glad I dids” and “wish I’d knowns.”
Abstract P4-11-03: Withdrawn
Authors: EY Kim, YL Park, CH Park, BC Suh
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Kim EY, Park YL, Park CH, Suh BC. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-11-03.
Abstract P2-06-03: The 3′UTR signature defines a highly metastatic subgroup of triple-negative breast cancer
Authors: L Wang, X Hu, P Wang, Z-M Shao
Journal: Cancer Research (2017)

Abstract Purpose. Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with an aggressive clinical course. TNBC relapse or metastasis is associated with an unfavorable prognosis so predictive models are needed to chart potential patient outcomes. Alternative polyadenylation (APA) has recently gained attention as a major player influencing the kinetics of gene regulation under diverse physiological and pathological status, resulting in the dynamic usage of 3′ untranslated region (3′UTR). We postulate that alternative 3′UTR patterns, if incorporated into a single model, could improve postoperative risk stratification and identify a highly metastatic subgroup of TNBC. In this study, we used alternative 3′UTR patterns to improve postoperative risk stratification. Experimental Design. We collected 327 publicly available microarrays and randomly stratified samples in a training (n = 164) and validation set (n = 163). Then, 1,933 3′UTRs were generated based on expression ratios of alternative 3′UTR. After initial feature filtering, we built a 17-3′UTR-based classifier using an elastic net model and validated the prognostic accuracy in both training and validation sets. Results. Time-dependent ROC comparisons and Kaplan–Meier analyses confirmed an outstanding discriminating power of our prognostic model for TNBC patients. In the training cohort, 5-year event-free survival (EFS) was 78.6% (95% CI 71.2–86.0) for the low-risk group, and16.3%(95% CI 2.3–30.4) for the high-risk group (log-rank p &amp;lt; 0.0001; hazard ratio [HR] 8.29, 95% CI 4.78–14.4), In the validation set, 5-year EFS was 75.6% (95% CI 68.0–83.2) for the low-risk group, and 33.2% (95% CI 17.1–49.3) for the high-risk group (log-rank p &amp;lt; 0.0001; HR 3.17, 95% CI 1.66–5.42). The 17-3′UTR-based classifier could be used to independently predict outcomes and this outperformed prognosis using classical clinicopathological risk factors. Conclusions. Our 17-3′UTR-based classifier provides a superior prognostic performance for estimating disease recurrence and metastasis in TNBC patients and it may permit personalized management strategies. Citation Format: Wang L, Hu X, Wang P, Shao Z-M. The 3′UTR signature defines a highly metastatic subgroup of triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-06-03.
An Ecological Framework for Modeling the Geography of Disease Transmission
Authors: Erica E. Johnson, Luis E. Escobar, Carlos Zambrana-Torrelio
Journal: Trends in Ecology & Evolution (2019)

Ecological niche modeling (ENM) is widely employed in ecology to predict species' potential geographic distributions in relation to their environmental constraints and is rapidly becoming the gold-standard method for disease risk mapping. However, given the biological complexity of disease systems, the traditional ENM framework requires reevaluation. We provide an overview of the application of ENM to disease systems and propose a theoretical framework based on the biological properties of both hosts and parasites to produce reliable outputs resembling disease system distributions. Additionally, we discuss the differences between biological considerations when implementing ENM for distributional ecology and epidemiology. This new framework will help the field of disease ecology and applications of biogeography in the epidemiology of infectious diseases.
Meeting a carer in a forensic setting
Authors: Madelaine Eddleston, Adrian Brown, Irene Cormac
Journal: BMJ (2010)

These relatives and friends have specific needs When looking after patients, it is easy to forget the family and friends who provide them with vital support. It is especially easy to forget carers when the patient has a mental disorder that has led to their detention in a high security hospital for many years. As a medical student, Madelaine Eddleston had a placement at the high security Rampton Hospital. There she had the opportunity to meet the carers of detained patients. #### Definition of a carer The mental health charity Rethink ( www.rethink.org/carers) defines a carer as, “Someone who provides or intends to provide practical and emotional support to someone with a mental health problem. This may be a relative, partner, friend or neighbour.” They are unpaid and are often unprepared for their role. The Royal College of Psychiatrists makes these recommendations about carers and forensic psychiatric services1:
Abstract P6-17-32: Impact of the line of treatment on progression-free survival in patients treated with T-DM1 for metastatic breast cancer
Authors: FP Duhoux, V Dufour, A van Maanen, M Berliere, D Taylor, J-L Canon
Journal: Cancer Research (2019)

Abstract Background Trastuzumab emtansine (T-DM1) is a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) receptors, conjugated with a cytotoxic component (a microtubule inhibitor). It is indicated as second-line treatment for HER2-positive metastatic or unresectable locally advanced breast cancer, after progression on trastuzumab and a taxane-based chemotherapy. In HER2-negative metastatic breast cancer, progression-free survival (PFS) declines with each line of therapy, while patients with HER2-positive disease receive the most lines of chemotherapy and the longest duration for every line. We wished to investigate whether the line of treatment in which T-DM1 is administered has an impact on PFS. We also wished to explore whether prior treatment with capecitabine / lapatinib or pertuzumab had an impact on PFS, as none of the patients included in the registration trial had received these treatments before their inclusion in the trial. Methods This is a multicenter retrospective study performed in 3 Belgian institutions. All patients received T-DM1 for HER2 positive metastatic or unresectable locally advanced breast cancer. The primary outcome was PFS with T-DM1, defined as the period between the first administration of T-DM1 and the first radiological or clinical assessment demonstrating progression of the disease. Results We included 51 patients. One patient had to be excluded from the analyses because she no longer had HER positive disease. The median PFS was 9.01 months. The line of treatment in which T-DM1 was administered had no influence on PFS (hazard ratio 0.976, CI95 0.835-1.142). There was no statistically significant difference in PFS between patients who had not received capecitabine / lapatinib before T-DM1 and those who had (9.11 vs 8.91 months, p-value 0.466). Median PFS was 10.07 months when T-DM1 was administered prior to pertuzumab, and 5 months when administered after pertuzumab. Patients who received pertuzumab before T-DM1 thus tended to exhibit a shorter PFS. However, this difference is not statistically significant (p-value 0.096). Conclusions Unlike with conventional chemotherapy, the line of treatment in which T-DM1 is administered does not influence PFS in metastatic breast cancer patients. Citation Format: Duhoux FP, Dufour V, van Maanen A, Berliere M, Taylor D, Canon J-L. Impact of the line of treatment on progression-free survival in patients treated with T-DM1 for metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-32.
Reply to the letter to the editor ‘European cancer mortality predictions for the year 2019 with focus on breast cancer, by Malvezzi M et al’ by Marsden and Hamoda, On behalf of the British Menopause Society Medical Advisory Council
Authors: M. Malvezzi, G. Carioli, P. Bertuccio, P. Boffetta, F. Levi, C. La Vecchia, E. Negri
Journal: Annals of Oncology (2019)
How to set up a society for widening participation in medicine
Authors: Declan Murphy, Laura Glenny
Journal: BMJ (2018)

Medical students can play a key role in improving access to courses for applicants from less privileged backgrounds Some think that a career in medicine is only for the privileged few. In 2014, the Medical Schools Council’s Selecting for Excellence report stated that 80% of all medical students come from just 20% of schools in the United Kingdom, with most of these schools being private or independent institutions.1 After the publication of this report, all 33 medical schools in the UK were required by the Medical Schools Council to improve their widening participation or widening access schemes by providing information about careers in medicine to pupils from lower socioeconomic backgrounds and to schools that have low numbers of students applying to study medicine.2 One way that students can help their medical schools to encourage a more diverse range of applicants is to set up a widening participation in medicine society. This can help prospective students gain an understanding of what it is like to study medicine and provide them with advice on how to get a place at medical school. This article offers guidance on how to set up your own society, the activities you can offer, and how to measure your success. ### Step 1: Set your objectives The Medical Schools Council provides guidance on what outreach programmes should aim to achieve.3 This includes:
Scandal and self experimentation
Authors: Oliver Ellis
Journal: BMJ (2011)

The MMR scandal has been rumbling on for ages now. Andrew Wakefield and colleagues’ Lancet paper, which (incorrectly) suggested a link between the measles, mumps, and rubella vaccine and a “new syndrome” of autism and bowel disease, was published in 1998. Although the paper had obvious flaws, it triggered a scare among parents who worried that their children might be harmed by the jab.

In an editorial (doi: 10.1136/bmj.c7452) , BMJ editor in chief Fiona Godlee and colleagues describe the Wakefield paper as …
Heather’s Story
Authors: Chris Thomas
Journal: BMJ (2013)

I was in my second year when I met Heather Pratten. Like many medical students, I’d become disillusioned. The endless cycle of lectures can become a slog, far removed from what we thought medical school would entail. Occasionally, though, you’re privy to an experience that not only reaffirms your decision to study medicine, but is so affecting as to have a lasting impact on your future practice. For me, talking to Heather was such an experience.

I had been told little before meeting Heather; only that Huntington’s disease had affected her life. Before she arrived I dredged up the information I’d been given about the condition in lectures. Those medical titbits …
Iatrogenic esophageal perforation during fundoplication: treatment with endoscopic negative pressure therapy
Authors: Gunnar Loske, Tobias Schorsch, Wolfgang Schulze, Norbert Rolf, Christian T. Mueller
Journal: Endoscopy (2019)

Iatrogenic esophageal perforation caused by insertion of a gastric tube during a fundoplication operation is a severe and rare intraoperative complication. A 64-year-old woman underwent laparoscopic Nissen fundoplication. Intraoperatively, a large-bore gastric tube was inserted as a placeholder for the esophageal lumen. At 5 days after the procedure, increasing inflammation parameters and thoracic pain led to endoscopic examination.
Financial Incentives to Increase Cardiac Rehabilitation Participation Among Low-Socioeconomic Status Patients
Authors: Diann E. Gaalema, Rebecca J. Elliott, Patrick D. Savage, Jason L. Rengo, Alex Y. Cutler, Irene Pericot-Valverde, Jeffrey S. Priest, Donald S. Shepard, Stephen T. Higgins, Philip A. Ades
Journal: JACC Heart Failure (2019)
Abstract P4-10-10: Assessment of short inter-pregnancy interval in breast cancer diagnosed during pregnancy
Authors: H Diaz-Perez, R Del Toro-Mijares, EA Lopez-Martinez, JF Muñoz-Lozano, A Fonseca, A Platas, BA Martinez-Cannon, R Barragan-Carrillo, J Castro-Carrasco, S Limon-Gomez, C Villarreal-Garza
Journal: Cancer Research (2019)

Abstract Background: The relationship between pregnancy and breast cancer (BC) risk is not fully understood. Most of the literature has described this interaction in terms of the age at first pregnancy and the number of full-term pregnancies. During the prospective accrual of the “Joven &amp; Fuerte” young women with BC program in Mexico, we identified patients with pregnancy-associated BC (PABC) that experienced a short inter-pregnancy interval (SIPI) (&amp;lt;18 months between a live birth and the beginning of a following pregnancy). To our knowledge, there are no descriptions of the interaction between SIPI and PABC. Objective: We aim to assess the occurrence of SIPI in patients with PABC, as well as describe their clinical features at presentation. Results: We included patients accrued in the “Joven &amp; Fuerte” program from August 2014 and June 2018 at three Mexican cancer centers. A total of 375 patients ≤40 years-old with newly-diagnosed BC were assessed. 37 patients were diagnosed with PABC (10%), 21 during pregnancy and 16 after pregnancy. 6/37 (16%) patients with PABC experienced a SIPI, all diagnosed during pregnancy (28% of 21). The main clinicopathological features are described in the table 1. Table 1.Clinicopathological features of patients with PABC and SIPICaseAge at BC diagnosis (years)IPI (months)Pregnancy trimester at diagnosisStageBC subtype131183rdIIBNot available23262ndIIIAHR neg, HER2 pos337143rdIIAHR neg, HER2 pos436152ndIVHR pos, HER2 neg53142ndIIIAHR pos, HER2 neg63142ndIIICNot available Conclusion: According to the phenomena seen in this cohort of young BC patients, we hypothesize that SIPI may increase the incidence and/or modify the clinical outcomes of PABC. The evidence from clinical and laboratory data suggest that the mechanisms that could alter the interaction include, but are not limited to, the prolongation of the exposure to high concentrations of estrogens or their genotoxic metabolites, interaction with the effect of progesterone and other pregnancy-associated hormones on breast tissue, and immunologic factors. To date, to our knowledge there is no evidence about the effect of SIPI in PABC. Thus, research in this area should be encouraged, particularly in vulnerable women in limited-resource settings, where SIPI is, unfortunately, a common occurrence, and might represent a risk factor for BC/PABC. Citation Format: Diaz-Perez H, Del Toro-Mijares R, Lopez-Martinez EA, Muñoz-Lozano JF, Fonseca A, Platas A, Martinez-Cannon BA, Barragan-Carrillo R, Castro-Carrasco J, Limon-Gomez S, Villarreal-Garza C. Assessment of short inter-pregnancy interval in breast cancer diagnosed during pregnancy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-10.
Nitrosative stress in patients with asthma–chronic obstructive pulmonary disease overlap
Authors: Yorihiko Kyogoku, Hisatoshi Sugiura, Tomohiro Ichikawa, Tadahisa Numakura, Akira Koarai, Mitsuhiro Yamada, Naoya Fujino, Yutaka Tojo, Katsuhiro Onodera, Rie Tanaka, Kei Sato, Hirohito Sano, Shun Yamanaka, Koji Itakura, Ayumi Mitsune, Tsutomu Tamada, Takaaki Akaike, Masakazu Ichinose
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract P2-06-04: Enhancing abiraterone acetate efficacy in androgen receptor-positive triple negative breast cancer: Chk1 as a potential target
Authors: T Grellety, C Callens, E Richard, M Pulido, A Goncalves, P Gestraud, G MacGrogan, H Bonnefoi, B Cardinaud
Journal: Cancer Research (2019)

Abstract Purpose: Our aim was to identify predictive factors of abiraterone acetate (AA) efficacy and putative new druggable targets in androgen receptor (AR)-positive triple-negative breast cancer (TNBC) treated in the UCBG 2012-1 trial. Material and methods: We defined AA response as either complete or partial response, or stable disease at 6 months. Using Ampliseq, we sequenced 91 general and breast cancerassociated genes from the tumor DNA samples. We analyzed transcriptomes from the extracted RNA samples on a Nanostring platform and performed immunohistochemistry (IHC) on tumor samples using tissue microarrays. We assessed AA and CHK1 inhibitors (GDC-0575 and AZD7762) efficacies, either alone or in combination, on cell lines grown in vitro and in vivo. Results: Classical IHC apocrine markers, including AR, FOXA1, GGT1 and GCDFP15, allowed identifying AA responders and non-responders. All responders have clear apocrine features. Transcriptome analysis revealed that 31 genes were differentially expressed in the two subgroups, 9 of them being linked to proliferation and DNA damage repair. One of the most significant differences was the overexpression in non-responders of CHEK1, a gene encoding Chk1, a protein kinase that can be blocked by specific inhibitors. In vitro, AA and Chk1 inhibitor combination showed additive or slightly synergistic effect on cell viability, cell cycle, apoptosis and accumulation of DNA damages. In vivo, orthotopic xenograft experiments confirmed the efficacy of this combination therapy. Conclusions: This study suggests that apocrine features can be helpful in the identification of AA-responders. We identified Chk1 as a putative drug target in AR-positive TNBCs. Citation Format: Grellety T, Callens C, Richard E, Pulido M, Goncalves A, Gestraud P, MacGrogan G, Bonnefoi H, Cardinaud B. Enhancing abiraterone acetate efficacy in androgen receptor-positive triple negative breast cancer: Chk1 as a potential target [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-04.
Abstract SY31-01: The role of autophagy in cancer progression and therapy
Authors: Eileen P. White
Journal: Cancer Research (2010)

Abstract Autophagy is induced by metabolic stress and can promote cell survival by maintaining energy homeostasis and by damage mitigation. Autophagy is negatively regulated by activation of mammalian target of rapamycin (mTOR) that links nutrient and growth factor availability to cell growth and catabolism. mTOR inhibitors have shown efficacy in renal cell carcinoma (RCC) but the role of autophagy stimulation and potentially counterproductive promotion of tumor cell stress tolerance was not known. We have found that the mTOR inhibitor CCI-779 (temsirolimus) promoted autophagy-mediated stress tolerance and that inhibition of autophagic degradation with chloroquine enhanced kidney tumor cell death in vitro and in vivo. Thus, autophagy inhibition may be a useful strategy to enhance the anti-tumor activity of mTOR inhibitors in RCC. Although therapeutic inhibitors of the mTOR pathway have been demonstrated to slow progression of advanced RCC in patients, and were approved by the FDA as a standard therapy for RCC, this beneficial effect is only temporary. One possible mechanism of resistance may be due to autophagy as a survival response. Additionally, metabolic stress caused by insufficient angiogenesis and the resulting mTOR inhibition activate tumor cell survival by autophagy, and tumor cells in these hypoxic regions respond most poorly to treatment. We reveal a new therapeutic paradigm of coordinate mTOR and autophagy inhibition to block the survival advantage and enhance tumor cell death to maximize therapeutic benefit. Citation Format: Eileen P. White. The role of autophagy in cancer progression and therapy [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY31-01