tbuckley/cabot-search huggingface dataset:
Developing and evaluating a training intervention to address fear of cancer recurrence.
Authors: Julie Berrett-Abebe, Peter Maramaldi, Tamara Cadet
Journal: Journal of Clinical Oncology (2018)

13 Background: Growing numbers of cancer survivors are increasingly receiving care from primary care providers (PCPs), who often lack cancer-specific expertise. In addition to long-term effects from cancer, survivors tend to be older with multiple chronic conditions, often leaving psychosocial concerns such as fear of cancer recurrence (FCR) unaddressed. This study reports the development and testing of a continuing education intervention to train PCPs to identify and address FCR. Methods: The training was developed through key-informant interviews with 42 health care professionals, researchers, and cancer survivors. The 30-minute training was then delivered and pilot-tested with a total of 46 participants, including physicians, PAs, NPs, nurses, and social workers in six discrete primary care practices. A one group pre-test, post-test design was used to evaluate the effectiveness of the training. Participants completed self-report surveys consisting of 5 domains developed from Social Cognitive Theory and Kirkpatrick’s Evaluation of Training Programs. Data were analyzed using descriptive statistics, paired-sample t-tests, and ANOVAs. Results: ± 10.9. Participants reported high levels of confidence that the training would change their practice, although they also identified barriers to action. Results of t-tests indicated that the training significantly increased participants’ knowledge and self-efficacy. With the except of 1 knowledge domain, no significant differences were found in multivariate analyses. Conclusions: This study demonstrated that a brief, on-site interprofessional training is feasible in a range of primary care practices, well-received by participants, and achieved goals of improved knowledge, self-efficacy and confidence to implement anticipated practice behavior changes. Such training efforts are important, as quality healthcare for increasing numbers of cancer survivors can be improved through continuing education efforts for their PCPs.
Assessing the efficacy of peripherally acting mu-opioid receptor antagonists (PAMORAs) in the treatment of opioid-induced constipation
Authors: Victor Chedid, Michael Camilleri
Journal: Gut (2018)

We read with interest the recent systematic review and network meta-analysis on the efficacy of pharmacological treatment of opioid-induced constipation (OIC).1 The authors reviewed 27 randomised controlled trials (RCTs) involving 9149 patients and concluded that naloxone was the best drug in patients with OIC, followed by naldemedine. We believe that several factors impacted the appraisal of relative efficacy and deserve discussion especially in network meta-analyses with no head-to-head drug trials.

1.  Distribution and potential for opioid withdrawal: Naloxone is a lipophilic, non-selective and competitive opioid receptor antagonist. The oral formulation of naloxone has a bioavailability of ~2%; however, it is widely distributed, has a narrow therapeutic index and the oral doses required to treat OIC can increase the risk of opioid withdrawal symptoms. On the other hand, peripherally acting mu-opioid receptor antagonists such as naldemedine and …
B Cell–Activating Factor Neutralization Aggravates Atherosclerosis
Authors: Dimitrios Tsiantoulas, Andrew P. Sage, Laura Göderle, Maria Ozsvar-Kozma, Deirdre Murphy, Florentina Porsch, Gerard Pasterkamp, Jörg Menche, Pascal Schneider, Ziad Mallat, Christoph J. Binder
Journal: Circulation (2018)

Atherosclerotic cardiovascular disease (heart attacks and strokes) is the major cause of death globally and is caused by the buildup of a plaque in the arterial wall. Genomic data showed that the B cell-activating factor (BAFF) receptor pathway, which is specifically essential for the survival of conventional B lymphocytes (B-2 cells), is a key driver of coronary heart disease. Deletion or antibody-mediated blockade of BAFF receptor ablates B-2 cells and decreases experimental atherosclerosis. Anti-BAFF immunotherapy is approved for treatment of autoimmune systemic lupus erythematosus, and can therefore be expected to limit their associated cardiovascular risk. However, direct effects of anti-BAFF immunotherapy on atherosclerosis remain unknown.To investigate the effect of BAFF neutralization in atherosclerosis, the authors treated Apoe-/- and Ldlr-/- mice with a well-characterized blocking anti-BAFF antibody. Moreover, to investigate the mechanism by which BAFF impacts atherosclerosis, the authors studied atherosclerosis-prone mice that lack the alternative receptor for BAFF: transmembrane activator and calcium modulator and cyclophilin ligand interactor.The authors demonstrate here that anti-BAFF antibody treatment increased atherosclerosis in mice, despite efficient depletion of mature B-2 cells, suggesting a unique mechanism of action. Indeed, myeloid cell-specific deletion of transmembrane activator and calcium modulator and cyclophilin ligand interactor also results in increased atherosclerosis, while B cell-specific transmembrane activator and calcium modulator and cyclophilin ligand interactor deletion had no effect. Mechanistically, BAFF-transmembrane activator and calcium modulator and cyclophilin ligand interactor signaling represses macrophage IRF7-dependent (but not NF-κB-dependent) Toll-like receptor 9 responses including proatherogenic CXCL10 production.These data identify a novel B cell-independent anti-inflammatory role for BAFF in atherosclerosis and may have important clinical implications.
Impact of metaplastic histology (MpBC) in triple-negative breast cancer (TNBC) patients (pts) receiving neoadjuvant systemic therapy (NAST).
Authors: Clinton Yam, Kenneth R. Hess, Jennifer Keating Litton, Wei Tse Yang, Lumarie Santiago, Rosalind P Candelaria, Elizabeth A. Mittendorf, Rashmi Krishna Murthy, Senthil Damodaran, Thorunn Helgason, Lei Huo, Alastair Mark Thompson, Michelle Barton, Monica L Huang, Elsa M Arribas, Deanna L Lane, Gaiane M Rauch, Beatriz E Adrada, Michael Z Gilcrease, Stacy L. Moulder
Journal: Journal of Clinical Oncology (2018)

593 Background: MpBCs are aggressive cancers, often TNBC, and considered chemo-resistant, such that some providers avoid NAST. Using data from an IRB approved prospective trial, we compared characteristics and outcomes between MpBC and non-metaplastic (non-MpBC) TNBC pts receiving NAST. Methods: Per protocol, pts began a planned 4 cycles of Adriamycin-based chemo (AC). Volumetric change by ultrasound (vUS) was performed after 2 (optional) and 4 cycles of AC and evaluated as a predictor of response in MpBC pts. Pts with chemo-insensitive disease during/after AC were enrolled in targeted therapy trials (TT) as the 2nd phase of NAST. Sensitive disease received taxane-based therapy (T). Residual Cancer Burden (RCB) was assessed after surgery. Differences between MpBC and non-MpBC were analyzed by Fisher’s exact, Wilcoxon rank sum and Student’s t tests as appropriate. Results: 170 pts (21 MpBC, 149 non-MpBC) were evaluable for RCB including 2 pt deaths during AC (counted as RCB II-III). Despite lower rates of nodal positivity, [p = 0.002] and lower grade [p = 0.009], MpBC pts had higher rates of progression (PD) on AC (24 vs 8%; p = 0.041) and RCB II-III status after NAST [67 vs 42%; p = 0.036] (Table). Of the MpBCs with RCB 0-I (n = 7, 33%), 6 received AC-T and 1 had TT. 14 MpBC pts underwent vUS after 2 cycles of AC. Among these 14 pts, 21% had PD on vUS after 2 cycles of AC. Notably, pts with ≥60% volumetric reduction in the primary tumor (n = 4) had significantly higher RCB 0-I rates than those with < 60% (n = 10) [100 vs 10%, p = 0.005]. Conclusions: This is the largest prospective series of NAST outcomes in MpBC. A clinically acceptable RCB 0-I rate of 33% and the opportunity to participate in neoadjuvant and adjuvant trials supports the use of NAST in MpBC. MpBC pts should be monitored closely for PD while receiving NAST. MpBC (n = 21) Non-MpBC (n = 149) p-value Median age (range) 56 (34-74) 54 (27-78) 0.64 Mean tumor size - cm (SD) 4.2 (3.4) 3.4 (1.9) 0.08 n (%) Node Neg 18 (86) 74 (50) 0.002 Pos 3 (14) 75 (50) Grade 1 1 (5) 0 0.009 2 5 (24) 14 (9) 3 15 (71) 135 (91) Progression on AC No 16 (76) 137 (92) 0.041 Yes 5 (24) 12 (8) Targeted Trial No 13 (62) 115 (77) 0.17 Yes 8 (38) 34 (23) Outcome RCB 0-I 7 (33) 87 (58) 0.036 RCB II-III 14 (67) 62 (42)
Effects of antihistamine use on survival in breast cancer.
Authors: Hakan Lars Olsson, Per Broberg, Richard Einefors, Ildiko Fritz
Journal: Journal of Clinical Oncology (2018)

e12527 Background: Tumors maintain an inflammatory microenvironment, leading to a potential for anti-inflammatory medication in cancer therapy. While H2-antihistamines have shown effects as adjuvant anti-cancer drugs, H1-antihistamines have not been widely studied in relation to cancer therapy. Methods: We investigated the effects of six antihistamines on breast cancer-specific and overall mortality in a nation-wide register-based study of all 61,627 Swedish women with newly diagnosed breast cancer between July 1st 2005 and December 31st 2013. 14,711 women used at least one of the antihistamines. The effects of both peri- and post-diagnostic antihistamine use, as well as the use among different subgroups of patients with regard to age, stage and estrogen receptor status, were analyzed. Results: We found a consistently beneficial effect of desloratadine and loratadine use on breast cancer survival (with HRs ranging from 0.47-0.84 for desloratadine users relative to non-use), regardless of age, stage and estrogen receptor status, and a consistently negative effect on breast cancer survival of clemastine use. Conclusions: We suggest trials of high-dose and long-duration desloratadine and loratadine as adjuvant treatment of breast cancer. Further studies on the effects of ebastine and possibly fexofenadine are merited, while neither cetirizine nor clemastine are viable candidates. We also suggest further studies of antihistamines, particularly desloratadine, as treatment options for other malignancies Breast cancer mortality All-cause mortality Antihistamine type HR** 2.5 % 97.5 % P Antihistamine type HR** 2.5 % 97.5 % P Cetirizine 0.97 0.83 1.13 0.671 Cetirizine 0.94 0.83 1.08 0.389 Clemastine 1.24 1.05 1.47 0.013 Clemastine 1.32 1.15 1.51 < 0.001 Desloratadine 0.79 0.63 0.99 0.044 Desloratadine 0.68 0.56 0.82 < 0.001 Ebastine 0.57 0.32 1.03 0.064 Ebastine 0.95 0.66 1.37 0.783 Fexofenadine 1.14 0.61 2.13 0.671 Fexofenadine 1.00 0.58 1.73 0.988 Loratadine 0.78 0.63 0.97 0.022 Loratadine 0.80 0.67 0.95 0.010 *Antihistamine use is defined as use within six months preceding and six months following diagnosis. Of the 61,627 women with breast cancer included in this study, 10,517 died in the study period. 6,668 deaths of breast cancer.
Pregabalin: what the patent litigation means for doctors and drug companies
Authors: Darren Smyth, Richard Croker, Ben Goldacre
Journal: BMJ (2018)

Darren Smyth , Richard Croker, and Ben Goldacre explain the arguments over the patent case and explore the wider implications for the NHS and drug development Generic prescribing is near universal in the UK, taught in all medical schools, and recommended (with few exceptions) in the BNF .1 It has substantial clinical and cost benefits: generic drugs are usually cheaper than branded products and the generic names make it easier for clinicians and patients to know which class each drug belongs to, providing a harmonised nomenclature that can help reduce the risk of drug errors. However, in an unprecedented step, in 2015, NHS England wrote to all clinical commissioning groups (CCGs) instructing them to ensure that doctors prescribe pregabalin as branded Lyrica when it was being used to treat pain. The letter, which caused clinicians much concern, was the most visible output from a complex and extensive web of interlocking legal battles about patent protection (box 1). Collectively, these cases have enormous financial consequences for the NHS and raise important issues around medical autonomy, incentives for innovation, the role of regulators, and the entire legal framework around new uses for old drugs. Box 1 ### How the pregabalin litigation unfoldedRETURN TO TEXT
Serial Measurement of Natriuretic Peptides and Cardiovascular Outcomes in Patients With Type 2 Diabetes in the EXAMINE Trial
Authors: Petr Jarolim, William B. White, Christopher P. Cannon, Qi Gao, David A. Morrow
Journal: Diabetes Care (2018)

OBJECTIVE Patients with type 2 diabetes are at increased risk of developing heart failure (HF). Enhanced recognition of patients at risk for HF would help guide therapeutic decisions. RESEARCH DESIGN AND METHODS We investigated the prognostic implications of changes in N-terminal B-type natriuretic peptide (NT-proBNP) concentration in patients with type 2 diabetes and ischemic heart disease who were enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial, a phase 3b trial of alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor. Patients with type 2 diabetes and a recent acute coronary syndrome event were eligible. NT-proBNP was measured at baseline and 6 months. Cardiovascular (CV) death or hospitalization for HF was the end point of principal interest for this analysis. RESULTS We observed a strong graded relationship between increasing baseline and 6-month NT-proBNP concentration and the incidence of major CV events (P &amp;lt; 0.001). After adjusting for potential confounders, NT-proBNP at baseline was independently associated with the development of major CV events, in particular hospitalization for HF. Patients who had persistently high NT-proBNP (P &amp;lt; 0.001) or developed high NT-proBNP at 6 months (P &amp;lt; 0.001) were at a significantly higher risk for CV death/HF than those in whom NT-proBNP remained low at both time points or who had a high NT-proBNP value at baseline that subsequently declined to the low category. Absolute changes in NT-proBNP by 6 months were also strongly associated with subsequent outcomes. Treatment with a DPP-4 inhibitor did not meaningfully alter NT-proBNP concentrations (P = 0.20). CONCLUSIONS Serial monitoring of NT-proBNP in patients with type 2 diabetes and ischemic heart disease may be useful for identifying patients at highest risk for HF.
Health Insurance Coverage by Occupation Among Adults Aged 18–64 Years — 17 States, 2013–2014
Authors: Winifred L. Boal, Jia Li, Aaron Sussell
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Lack of health insurance has been associated with poorer health status and with difficulties accessing preventive health services and obtaining medical care, especially for chronic diseases (1-3). Among workers, the prevalence of chronic conditions, risk behaviors, and having health insurance has been shown to vary by occupation (4,5). CDC used data from the 2013 and 2014 Behavioral Risk Factor Surveillance System (BRFSS) to estimate the prevalence of having no health care coverage (e.g., health insurance, prepaid plans such as health maintenance organizations, government plans such as Medicare, or Indian Health Service) by occupation. Among all workers aged 18-64 years, the prevalence of being uninsured declined significantly (21%) from 16.0% in 2013 to 12.7% in 2014. In both years there were large differences in the prevalence of being uninsured among occupational groups, ranging from 3.6% among the architecture and engineering occupations to 37.9% among the farming, fishing, and forestry occupations in 2013 and 2.7% among community and social services; and education, training, and library occupations to 37.0% among building and grounds cleaning and maintenance occupations in 2014 (p<0.001). In 2014, more than 25% of workers in four occupational groups reported having no health insurance (construction and extraction [29.1%]; farming, fishing, and forestry [34.6%]; food preparation and serving related [35.5%]; and building and grounds cleaning and maintenance [37.0%]). Identifying factors affecting differences in coverage by occupation might help to address health disparities among occupational groups.
Long-term risk of cardiovascular disease among colorectal cancer survivors in a population-based cohort study.
Authors: David Baraghoshi, Makenzie L. Hawkins, Sarah Abdelaziz, Jihye Park, Yuan Wan, Alison M Fraser, Ken R Smith, Vikrant Deshmukh, Michael Newman, Kerry G. Rowe, John Snyder, Shane Lloyd, Niloy Jewel Samadder, Mia Hashibe
Journal: Journal of Clinical Oncology (2018)

113 Background: In the United States, colorectal cancer is the fourth most common cancer and one of the leading causes of cancer death. Few studies have examined the relationship between colorectal cancer survivorship and long-term cardiovascular disease (CVD) risk. Methods: Individuals diagnosed with colorectal cancer were identified using the Utah Population Database. For a comparison group, up to 5 cancer-free individuals were matched by birth year, birth state, follow-up time and sex to each cancer case. For individuals with &gt; 10 years of follow-up, we estimated CVD risk &gt; 10 years after cancer diagnosis. Cox regression models were used to estimate hazard ratios (HR) and 95% Confidence Intervals. Results: Among 1,749 colorectal cancer survivors who had survived for at least 10 years, 1,001 (57.2%) were diagnosed with CVD &gt; 10 years after cancer diagnosis. Compared to the general population, colorectal cancer survivors had an increased risk of CVD &gt; 10 years after cancer diagnosis: HR = 2.84 (95% CI = 2.59, 3.11) for hypertension; HR = 2.66 (95% CI 2.37, 2.98) for diseases of the heart; HR = 3.91 (95% CI = 3.33, 4.58) for diseases of the arteries, arterioles and capillaries; HR = 2.58 (95% CI = 2.46, 2.99) for diseases of the veins and lymphatics; HR = 2.98 (95% CI = 2.36, 3.76) for cerebrovascular disease. Colorectal cancer survivors with ≥1 comorbidity had an increased risk of CVD &gt; 10 years after cancer diagnosis compared to survivors with no comorbidities (HR = 1.7, 95% CI = 1.49, 1.95). Colorectal cancer survivors who were ≥65 years had an increased risk of CVD &gt; 10 years after cancer diagnosis. Colorectal cancer survivors who were obese at the time of diagnosis had an increased risk of CVD &gt; 10 years after cancer diagnosis when compared to survivors with normal BMIs (HR = 1.25; 95% CI = 1.06, 1.49). Conclusions: Compared to the general population, colorectal cancer survivors had an increased risk of CVD during the &gt; 10 year follow-up period. Within colorectal cancer survivors, there was an increased risk of CVD for those that were older, had ≥1 comorbidity and were obese. The increased risk of CVD among survivors may be attributable to the lifestyle risk factors shared by colorectal cancer and CVD.
Jacques FORESTIER, a visionary of the clinical epidemiology in rheumatology
Authors: Maxime Dougados
Journal: Annals of the Rheumatic Diseases (2018)

Starting my personal research work on spondyloarthritis in the 1980s, I was surprised that my mentor Bernard AMOR proposed me to read the book written in the 1950s by Jacques FORESTIER.1 In fact, I have been really impressed by the content of this book in terms of extreme detailed clinical data (eg, the description of the four different patterns of hip involvement: (a) arthritis a minima, (b) sclerotic pattern, (c) crenellated shape and (d) ankylosing pattern; the latter being probably in relation with periarticular enthesitis) and in terms of the quality of the provided statistics (prevalence and incidence of the different clinical presentations of spondyloarthritis).

Thanks to a specific book dedicated to the personal and professional life of Jacques FORESTIER written by Professor Jacques ARLET,2 I am now even more impressed by this ‘colleague’ (who was one of the first doctors opening an outpatient clinic dedicated to rheumatic patients in Cochin hospital) for several reasons:

This French doctor did not hesitate to cross the ocean in order to present his data in different departments in the …
Ythdf2-mediated m6A mRNA clearance modulates neural development in mice
Authors: Miaomiao Li, Xu Zhao, Wei Wang, Hailing Shi, Qingfei Pan, Zhike Lu, Sonia Peña Perez, Rajikala Suganthan, Chuan He, Magnar Bjørås, Arne Klungland
Journal: Genome biology (2018)

N 6 -methyladenosine (m6A) modification in mRNAs was recently shown to be dynamically regulated, indicating a pivotal role in multiple developmental processes. Most recently, it was shown that the Mettl3-Mettl14 writer complex of this mark is required for the temporal control of cortical neurogenesis. The m6A reader protein Ythdf2 promotes mRNA degradation by recognizing m6A and recruiting the mRNA decay machinery.We show that the conditional depletion of the m6A reader protein Ythdf2 in mice causes lethality at late embryonic developmental stages, with embryos characterized by compromised neural development. We demonstrate that neural stem/progenitor cell (NSPC) self-renewal and spatiotemporal generation of neurons and other cell types are severely impacted by the loss of Ythdf2 in embryonic neocortex. Combining in vivo and in vitro assays, we show that the proliferation and differentiation capabilities of NSPCs decrease significantly in Ythdf2 -/- embryos. The Ythdf2 -/- neurons are unable to produce normally functioning neurites, leading to failure in recovery upon reactive oxygen species stimulation. Consistently, expression of genes enriched in neural development pathways is significantly disturbed. Detailed analysis of the m6A-methylomes of Ythdf2 -/- NSPCs identifies that the JAK-STAT cascade inhibitory genes contribute to neuroprotection and neurite outgrowths show increased expression and m6A enrichment. In agreement with the function of Ythdf2, delayed degradation of neuron differentiation-related m6A-containing mRNAs is seen in Ythdf2 -/- NSPCs.We show that the m6A reader protein Ythdf2 modulates neural development by promoting m6A-dependent degradation of neural development-related mRNA targets.
Integrative therapies for symptom management in cancer survivors: Assessment of an on-site integrative medicine (IM) program.
Authors: Asma Ali Dilawari, Leatt Gilboa, Renee Kakareka, Emily Ratner
Journal: Journal of Clinical Oncology (2018)

142 Background: Up to 89% of oncology patients utilize integrative therapies with reported improvements in quality of life. However, less than half of patients report IM use to providers, potentially impeding optimal care. In September 2016, MedStar Montgomery Medical Center (MMMC), part of the MedStar Georgetown Cancer Network, opened the Center for Integrative Medicine (CIM) with support from MedStar’s Institute for Innovation (MI2). This clinical program offers IM consultation, acupuncture, mindfulness, psychology services, nutrition, and reiki. The purpose of this analysis is to examine oncology patient utilization of the CIM. Methods: Medical records of 174 patients seen September 2016 - October 2017 were reviewed, and 39 patients with a cancer diagnosis identified. Data regarding chief complaints, treatments, number of visits, and outcomes were analyzed. Results: 39 (22%) of 174 patients had a cancer diagnosis. After initial consultation, 29 of these patients received IM treatment; 14 returned for ≥5 treatments. Most common chief complaints were pain, stress/anxiety, fatigue, insomnia, and arthralgias (Table 1). The majority of CIM’s oncology patients was female and referred from in-network clinicians. The CIM referred 7 patients to other medical providers for unexpected medical issues and 2 required same-day appointments arranged by the CIM. Conclusions: These data illustrate oncology patients’ utilization and benefit of IM services within a hospital network. Communication between IM and referring providers may address unexpected clinical situations, potentially avoiding care delays and facilitating transparency with the use of IM services. Unpleasant symptom treatment may improve therapy adherence and quality of life. This review illustrates feasibility for an on-site CIM and the benefit to cancer survivors when IM services are offered collaboratively.[Table: see text]