tbuckley/cabot-search huggingface dataset:
ST CHANGES IN ELECTROCARDIOGRAPHIC LEADS V4-V6 IN PATIENTS WITH INFERIOR MYOCARDIAL INFARCTION PREDICT EXTENT AND DISTRIBUTION OF ISCHEMIC INJURY AS EVALUATED BY CARDIAC MAGNETIC RESONANCE: ANALYSIS FROM THE MITOCARE STUDY
Authors: Xiaoming Jia, Einar Heiberg, Maria Ripa, Henrik Engblom, Hakan Arheden, Peter Clemmensen, David Erlinge, Sigrun Halvorsen, Alf Inge Larsen, Jan Erik Nordrehaug, Svend Eggert Jensen, Dan Atar, Yochai Birnbaum
Journal: Journal of the American College of Cardiology (2018)
Most second wave CCGs have authorisation conditions imposed
Authors: Helen Jaques
Journal: BMJ (2013)

More than two thirds of clinical commissioning groups (CCGs) in the second wave of groups authorised by the NHS Commissioning Board have had conditions imposed on their new status. 

Of the 67 CCGs in the second wave, 45 have been authorised with conditions, meaning that they will receive some formal support to help them fully meet all the criteria. Nineteen of the groups met all 119 authorisation criteria and have been authorised with no conditions. …
Transient elastography is useful in diagnosing biliary atresia and predicting prognosis after hepatoportoenterostomy
Authors: Jia‐Feng Wu, Chee‐Seng Lee, Wen‐Hsi Lin, Yung‐Ming Jeng, Huey‐Ling Chen, Yen‐Hsuan Ni, Hong‐Yuan Hsu, Mei‐Hwei Chang
Journal: Hepatology (2018)

We investigated the utility of transient elastography (TE) for diagnosing biliary atresia (BA) in cholestatic infants and predicting the outcome of BA. Forty-eight cholestatic infants (9-87 days of age) with direct bilirubin level >1 mg/dL were enrolled. Liver stiffness measurement (LSM) by TE was performed during the cholestasis workup, and 15 subjects were diagnosed as BA. We assessed liver histology using liver biopsies from 36 subjects and graded fibrosis status using the METAVIR score. BA infants had significantly higher LSM values and METAVIR scores than non-BA cholestatic infants. A receiver operating characteristic (ROC) curve analysis showed that an LSM >7.7 kPa was predictive of BA among cholestatic infants (sensitivity = 80%; specificity = 97%; area under the curve [AUC] = 85.3%; P = 0.0001). Cholestatic infants with an LSM >7.7 kPa were more likely to be diagnosed with BA (odds ratio [OR] = 128; P < 0.001). Very early measurement of LSM after hepatoportoenterostomy (HPE) is associated with occurrence of thrombocytopenia, splenomegaly, and esophageal varices 6 months post-HPE. Five of the BA subjects were awaiting or had received liver transplantation (LT), and they had a significantly higher LSM measured 1 week post-HPE than that in the other BA subjects (26.0 vs. 10.8 kPa; P = 0.006). A Cox proportional analysis demonstrated that the need for LT was significantly higher in BA subjects with LSM >16 kPa measured 1 week post-HPE than other BA subjects (hazard ratio [HR] = 10.16; P = 0.04).LSM assessment during the workup of cholestatic infants may facilitate the diagnosis of BA. LSM post-HPE may predict complications and the need for early LT in infants with BA. (Hepatology 2018).
Exome-wide analyses identify low-frequency variant in CYP26B1 and additional coding variants associated with esophageal squamous cell carcinoma
Authors: Jiang Chang, Rong Zhong, Jianbo Tian, Jiaoyuan Li, Kan Zhai, Juntao Ke, Jiao Lou, Wei Chen, Beibei Zhu, Na Shen, Yi Zhang, Ying Zhu, Yajie Gong, Yang Yang, Danyi Zou, Xiating Peng, Zhi Zhang, Xuemei Zhang, Kun Huang, Tangchun Wu, Chen Wu, Xiaoping Miao, Dongxin Lin
Journal: Nature Genetics (2018)
Premature Cardiac Disease and Death in Women Whose Infant Was Preterm and Small for Gestational Age
Authors: Orli Silverberg, Alison L. Park, Eyal Cohen, Deshayne B. Fell, Joel G. Ray
Journal: JAMA Cardiology (2018)

Women with an infant with preterm birth (PTB) or who was severely small for gestational age (SGA) are at higher future risk of premature cardiovascular disease and related death.To determine the risk of cardiac disease or death among women with an infant with both PTB and SGA.This population-based cohort study used electronic health records from the province of Ontario, Canada, where health care is universally available, between April 1, 2002, and March 31, 2016. All singleton live births between 23 to 42 weeks' gestation among 710 501 nulliparous women aged 16 to 50 years without prepregnancy cardiac disease were analyzed.Risk of a composite outcome of heart failure, atrial or ventricular dysrhythmia, or all-cause mortality, starting 30 days after the index birth. Hazard ratios were adjusted for maternal age, income quintile, and preeclampsia/eclampsia (each at the index birth), as well as diabetes, chronic hypertension, obesity, dyslipidemia, drug dependence or smoking, and kidney disease (each within 24 months before the index birth date and time-varying from the birth date onward).Of 710 501 singleton live births, 15 082 mothers (2.1%) were older than age 40 years. Relative to having an infant without PTB or severe SGA (4.1 per 10 000 person-years), the incidence rate of the composite outcome of heart failure, dysrhythmia, or death was 11.3 per 10 000 person-years among mothers with an infant with PTB-SGA (crude hazard ratio, 2.79; 95% CI, 1.85-4.21) (adjusted hazard ratio, 1.66; 95% CI, 1.09-2.52).Women who had an infant with PTB-SGA may be at higher future risk of premature cardiac disease or death.
CHARACTERISTICS OF PERSISTENT TRICUSPID REGURGITATION AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Jun Yoshida, Atsushi Hayashi, Satoshi Yamaguchi, Takafumi Nagaura, Tetsuo Kamiyama, Raj Makkar, Robert Siegel, Florian Rader, Takahiro Shiota
Journal: Journal of the American College of Cardiology (2018)
PD-L1 and CD8 expression and association with outcomes in patients (pts) with <i>BRAF</i> V600E/K–mutant metastatic melanoma (MM) who received dabrafenib + trametinib (D+T) in the randomized phase 3 COMBI-v study.
Authors: Dirk Schadendorf, Georgina V. Long, Jean Jacques Grob, Paul D. Nathan, Antoni Ribas, Michael A. Davies, Keith Flaherty, Matthew Squires, Savina Jaeger, William Powell, Puay Tan, Caroline Robert
Journal: Journal of Clinical Oncology (2018)

183 Background: The phase 3 COMBI-v study (NCT01597908) showed that D+T significantly improved outcomes vs vemurafenib in pts with BRAF V600E/K–mutant MM. Checkpoint inhibitors also provide clinical benefit in some pts with MM. To date, characterization of markers associated with response to anti–PD-1 therapy has identified positive associations with PD-L1 expression and immune cell infiltration. Here we describe expression of PD-L1 and the T-cell marker CD8 in tumor samples from pts randomized to receive D+T in COMBI-v and associations with clinical outcomes. Methods: Biopsies from 74 of 352 D+T pts (21%) in COMBI-v were assessed for expression of PD-L1 (PD-L1 IHC 22C3 pharmDx assay; Dako) and CD8 (anti-CD8 antibody, clone C8/144B; Dako). PD-L1 positivity was determined as a percentage of stained tumor cells and MEL score (staining on both tumor and mononuclear inflammatory cells; 0 or 1 [negative]: &lt; 1% staining; 2-5 [positive]: ≥ 1% staining; Daud et al. J Clin Oncol. 2016). Results: Of 74 pts analyzed, 54 (73%) had PD-L1–positive tumors, and the largest MEL score subgroup was 2 (45%). A significant association ( P &lt; .0001) was observed between PD-L1 and CD8 expression. Overall response rate, tumor shrinkage, progression-free survival, overall survival (OS), and duration of response with D+T were not associated with PD-L1 (MEL score of ≥ 2) or CD8 positivity. However, a significant association ( P = .04) with improved OS was observed in tumors with high PD-L1 expression (≥ 20% of cells PD-L1 positive), and a trend ( P = .06) was seen in pts with a MEL score of ≥ 3. Among PD-L1–negative pts, improved OS was seen in those with high CD8 positivity ( P = .03), particularly in the stromal compartment. Conclusions: These data, representing PD-L1 and CD8 expression profiles for a BRAF-mutant MM population in the context of outcomes following D+T, showed that clinical benefit was maintained regardless of immune phenotype. The results also suggest that an immune component has an impact on outcomes following targeted therapy. Clinical trial information: NCT01597908.
Can anybody tell me how to prepare for the general practice vocational training scheme (GPVTS) interview? I have already appeared at interview for the same scheme—but I wasn't selected.
Authors: Fiona Jewkes
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Targeted next-generation sequencing (NGS) of germline DNA to identify genetic predisposition to gastric cancer (GC) in patients with <i>CDH1</i>-mutation negative early-onset (EO) or familial GC (FGC).
Authors: Geoffrey Yuyat Ku, Semanti Mukherjee, Chizoba Okoro, Medha Sharma, Vignesh Ravichandran, Kenneth Offit, Vijai Joseph, Yelena Yuriy Janjigian, Zsofia Kinga Stadler, David Paul Kelsen
Journal: Journal of Clinical Oncology (2018)

20 Background: While GC arises as part of several hereditary cancer syndromes, a genetic etiology is not identified for most FGC kindreds and EOGC patients. We hypothesize that NGS of germline DNA may reveal previously unsuspected genomic alterations that predispose to EOGC/FGC. Methods: We identified 42 Pts from a prospective GC registry with CDH1-mutation negative EOGC (≤50 years old) and/or with FGC. Germline DNA was analyzed by MSK-IMPACT, a 468-gene targeted NGS panel that includes &gt; 70 genes associated with known cancer predisposition syndromes. GATK HaplotypeCaller (HTC) was used to call SNVs and Indels simultaneously from the sequence read data and joint calling of all samples was used to generate VCF files. We annotated the VCF with public annotators and public allele frequencies from large sequencing studies. Manual variant curation was performed and were classified by ACMG criteria (Genet Med 2015;17:405), with only likely pathogenic and pathogenic variants included. Results: 41 Pts (98%) had early onset and 11 Pts (26%) had FGC (9 had ≥1 1 st or 2 nd degree relatives with GC). Median age was 40 (range, 18 to 55) and 23 (55%) were men. Ethnicities were 21 (50%) White, 13 (31%) Black, 6 (14%) Asian and 2 (5%) unknown. 40 (95%) had poorly differentiated and/or diffuse histology. Pathogenic mutations were diagnosed in 4 Pts (10%). 1 Pt had a BRCA2 mutation; his father had prostate CA and a paternal aunt had breast CA but he did not meet current NCCN criteria for BRCA testing. Three additional pathogenic mutations were FGFR1, SOX17 and KMT2D; none has previously been described in GC susceptibility but are associated with GC carcinogenesis. All 3 Pts had EOGC. None had FGC but all 3 had ³1 1 st -degree relative with CA ( FGFR1: breast, uterine, appendix; SOX17: breast; KMT2D: osteosarcoma). Further functional work of these variants and segregation analysis is on-going. Conclusions: MSK-IMPACT identified germline mutations in 10% of Pts; most are previously not known GC predisposition genes. NGS can be an important clinical tool for screening multiplex families and also a research tool for discovering genes that predispose to GC.
Eicosapentaenoic Acid Reduces Fecal Levels of Calprotectin and Prevents Relapse in Patients With Ulcerative Colitis
Authors: Eleonora Scaioli, Alessandro Sartini, Matteo Bellanova, Massimo Campieri, Davide Festi, Franco Bazzoli, Andrea Belluzzi
Journal: Clinical Gastroenterology and Hepatology (2018)
A spectroscopic serum based blood test for brain tumours: Optimisation for high-throughput sampling and the health economic impacts
Authors: Holly Butler, Matthew Baker, Mark Hegarty, Duncan Finlayson
Journal: Neuro-Oncology (2018)

It has recently been demonstrated that a spectroscopic test using blood-serum is able to effectively identify brain tumours in patients with sensitivities and specificities as high as 91.5% and 83% respectively. The approach employs Attenuated Total Reflectance - Fourier Transform Infrared (ATR-FTIR) spectroscopy to derive a disease specific spectroscopic signature, that using pattern recognition and machine learning algorithms is able to identify brain tumour cases. The ability to identify brain cancer cases based on serum samples alone raises the possibility of systematic screening prior to investigation with more expensive (MRI/CT imaging) and invasive (biopsy) tests. However, current methodology is currently limited to single patient analysis due to limitations in standard instrumentation. Here, we investigate the performance of a novel ATR-FTIR spectroscopic approach that allows automated, disposable, and multi-patient sampling. Our results indicate that this optimised approach is able to stratify brain tumour patients at performances equivalent to previous approaches, with sensitivities and specificities as high as 94.56% and 87.65% respectively. In advance of any prospective clinical study results being available, a cost-effectiveness analysis (CEA) was conducted to calculate the effects on health outcomes and health service costs of introducing this technology as a triage tool in primary and secondary care. Results indicate that using a serum spectroscopy test for brain tumours in both scenarios may be considered highly cost-effective in an HTA agency decision making process. Incremental cost-effectiveness ratios were well below standard threshold values of £20,000 to £30,000 per quality adjusted life year (QALY) gained used in the UK, and similar thresholds used internationally. In primary care, the test has the potential to be both more effective and cost saving for the health service.
Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease
Authors: Shyue-Luen Chang, Yau-Li Huang, Mei-Ching Lee, Sindy Hu, Yen-Chang Hsiao, Su-Wei Chang, Chee Jen Chang, Pei-Chun Chen
Journal: JAMA (2018)

<h3>Importance</h3> Varicose veins are common but rarely associated with serious health risks. Deep venous thrombosis (DVT), pulmonary embolism (PE), and peripheral artery disease (PAD) are also vascular diseases but associated with serious systemic effects. Little is known about the association between varicose veins and the incidence of other vascular diseases including DVT, PE, and PAD. <h3>Objective</h3> To investigate whether varicose veins are associated with an increased risk of DVT, PE, or PAD. <h3>Design, Setting, and Participants</h3> A retrospective cohort study using claims data from Taiwan’s National Health Insurance program. Patients aged 20 years and older with varicose veins were enrolled from January 1, 2001-December 31, 2013, and a control group of patients without varicose veins were matched by propensity score. Patients previously diagnosed with DVT, PE, or PAD were excluded. Follow-up ended December 31, 2014. <h3>Exposures</h3> Presence of varicose veins. <h3>Main Outcomes and Measures</h3> Incidence rates of DVT, PE, and PAD were assessed in people with and without varicose veins. Cox proportional hazards models were used to estimate relative hazards, with the control group as reference. <h3>Results</h3> There were 212 984 patients in the varicose veins group (mean [SD] age, 54.5 [16.0] years; 69.3% women) and 212 984 in the control group (mean [SD] age, 54.3 [15.6] years; 70.3% women). The median follow-up duration was 7.5 years for DVT, 7.8 years for PE, and 7.3 years for PAD for patients with varicose veins, and for the control group, follow-up duration was 7.6 years for DVT, 7.7 years for PE, and 7.4 years for PAD. The varicose veins group had higher incidence rates than the control group for DVT (6.55 vs 1.23 per 1000 person-years [10 360 vs 1980 cases]; absolute risk difference [ARD], 5.32 [95% CI, 5.18-5.46]), for PE (0.48 for the varicose veins group vs 0.28 for the control group per 1000 person-years [793 vs 451 cases]; ARD, 0.20 [95% CI, 0.16-0.24]), and for PAD (10.73 for the varicose veins group vs 6.22 for the control group per 1000 person-years [16 615 vs 9709 cases]; ARD, 4.51 [95% CI, 4.31-4.71]). The hazard ratios for the varicose veins group compared with the control group were 5.30 (95% CI, 5.05-5.56) for DVT, 1.73 (95% CI, 1.54-1.94) for PE, and 1.72 (95% CI, 1.68-1.77) for PAD. <h3>Conclusions and Relevance</h3> Among adults diagnosed with varicose veins, there was a significantly increased risk of incident DVT; the findings for PE and PAD are less clear due to the potential for confounding. Whether the association between varicose veins and DVT is causal or represents a common set of risk factors requires further research.
Abstract P3-10-09: The association age-related parity and HER2 over-expression in breast cancer
Authors: SY Bae, J Kim, JY You, SP Jung, JW Bae
Journal: Cancer Research (2018)

Abstract Backgrounds Reproductive factors, such as age at menarche, parity, age at first birth, and breast feeding, are known to be associated with risk of breast cancer. Recent studies show the association between the reproductive factors and the molecular subtypes of breast cancer, especially in luminal-like subtypes. Nulliparity is known a risk factor of breast cancer, multiparity is considered a protective factor. However, pregnancy associated breast cancers show the high expression of HER2, Therefore, we hypothesized the number of birth (multiparity) is correlated with the over-expression of HER2. Methods We reviewed the database of 2,594 breast cancer patients were over 20 years of age, diagnosed between January 2000 and April 2017 at Korea University of Anam Hospital, Seoul, Korea. According the number of birth, nulliparous (the number of birth = 0; 271 patients), primiparous (the number of birth = 1; 420 patients) and multiparous (the number of birth≥2; 1,903 patients) groups were classified. Results The median age (range) of nulliparous, primiparous and multiparous groups was 43 (22-77), 48 (27-87) and 51 (26-86) years (P&amp;lt;0.001). In univariate analysis, the number of birth was associated with the expression of ER and HER2, nulliparous patients showed higher ER positivity (P=0.013) and multiparous patients showed higher HER2 overexpression (P=0.048). There was no association with PR and Ki-67 level. In logistic regression with age, the parity was negative correlation with ER positivity (OR 0.83, 95% CI 0.72-0.95, P=0.010) and positive correlation with HER2 overexpression (OR1.18, 95% CI 1.02-1.36, P=0.021) P=0.009) and multiparity was higher HER2 overexpression (OR 1.41, 95% CI 1.02-1.94, P=0.033). By subgroup analysis with menopausal status, there was statistically significance in only premenopausal women, not in postmenopausal women. In premenopausal women, the parity was negatively associated with ER positivity (OR 0.78, 95%CI 0.64-0.94, P=0.010) and multiparity was associated with HER2 overexpression (OR 1.72, 95%CI 1.12-2.63, P=0.013), there was no difference in HER2 overexpression between nulliparous and primiparous patients. Conclusion Parity was associated with ER and HER2 expression, multiparous patients were associated with ER negativity and HER2 overexpression, especially in premenopausal women. This suggests that pregnancy could affect risk of breast cancer, especially in HER2 positive breast cancer subtype (ER- HER2+ tumors), before menopause. We need further investigation and evaluation. Citation Format: Bae SY, Kim J, You JY, Jung SP, Bae JW. The association age-related parity and HER2 over-expression in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-09.
Human C-to-U Coding RNA Editing Is Largely Nonadaptive
Authors: Zhen Liu, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2018)

Abstract C-to-U RNA editing enzymatically converts the base C to U in RNA molecules and could lead to nonsynonymous changes when occurring in coding regions. Hundreds to thousands of coding sites were recently found to be C-to-U edited or editable in humans, but the biological significance of this phenomenon is elusive. Here, we test the prevailing hypothesis that nonsynonymous editing is beneficial because it provides a means for tissue- or time-specific regulation of protein function that may be hard to accomplish by mutations due to pleiotropy. The adaptive hypothesis predicts that the fraction of sites edited and the median proportion of RNA molecules edited (i.e., editing level) are both higher for nonsynonymous than synonymous editing. However, our empirical observations are opposite to these predictions. Furthermore, the frequency of nonsynonymous editing, relative to that of synonymous editing, declines as genes become functionally more important or evolutionarily more constrained, and the nonsynonymous editing level at a site is negatively correlated with the evolutionary conservation of the site. Together, these findings refute the adaptive hypothesis; they instead indicate that the reported C-to-U coding RNA editing is mostly slightly deleterious or neutral, probably resulting from off-target activities of editing enzymes. Along with similar conclusions on the more prevalent A-to-I editing and m6A modification of coding RNAs, our study suggests that, at least in humans, most events of each type of posttranscriptional coding RNA modification likely manifest cellular errors rather than adaptations, demanding a paradigm shift in the research of posttranscriptional modification.
Independent relationships between cardinal features of obstructive sleep apnea and glycometabolism: a cross-sectional study
Authors: Juanjuan Zou, Yunyan Xia, Huajun Xu, Yiqun Fu, Yingjun Qian, Xinyi Li, Xiaolong Zhao, Jianyin Zou, Lili Meng, Suru Liu, Huaming Zhu, Hongliang Yi, Jian Guan, Bin Chen, Shankai Yin
Journal: Metabolism (2018)
INCREASED BODY MASS INDEX (BMI) PROMOTES HYPERTENSION AND WORSENS BLOOD PRESSURE CONTROL AMONG US VETERANS
Authors: Ross D. Fletcher, Ronald Jones, Hans Moore, Richard Amdur, Ali Ahmed, Raya Kheirbek, David Maron, Charles Faselis, Vasilios Papademetriou
Journal: Journal of the American College of Cardiology (2018)
Effects of functional electrical stimulation of lower limb muscles on circulating endothelial progenitor cells, CD34+ cells and vascular endothelial growth factor-A in heart failure with reduced ejection fraction
Authors: Nikolas Magkoutis, Vassiliki Mantzaraki, Dimitrios Farmakis, Aris Spathis, Periklis Foukas, Vasiliki Bistola, Georgios Bakosis, Stefanos Konstantoudakis, Efstratios Trogkanis, Georgios Papingiotis, Erifili Hatziagelaki, Ignatios Ikonomidis, Apostolos Karavidas, Gerasimos Filippatos, John Parissis
Journal: European Journal of Heart Failure (2018)
Ibuprofen + acetaminophen did not differ from opioids + acetaminophen for reducing acute extremity pain at 2 h
Authors: Catherine Varner, Christopher R. Carpenter
Journal: Annals of Internal Medicine (2018)

Source Citation Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a single dose of oral opioid and nonopioid analgesics on acute extremity pain in the emergency department: a randomized clinical trial. JAMA. 2017;318:1661-7. 29114833