tbuckley/cabot-search huggingface dataset:
Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression
Authors: K. G. Blumenthal, Y. Li, W. W. Acker, Y. Chang, A. Banerji, S. Ghaznavi, C. A. Camargo, L. Zhou
Journal: Allergy (2018)

Abstract Background The epidemiology of multiple drug intolerance syndrome ( MDIS ) and multiple drug allergy syndrome ( MDAS ) is poorly characterized. We used electronic health record ( EHR ) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression. Methods Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS / MDAS . Results Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS ; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [ aOR ] 1.72 [1.65, 1.80]), depression ( aOR 1.46 [1.41, 1.52]), and both anxiety and depression ( aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS . Depression was associated with increased odds of MDAS ( aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety ( aOR 1.13 [0.99, 1.30]) nor both depression and anxiety ( aOR 1.13 [0.92, 1.38]). Conclusion While 6% of patients had MDIS , only 1% had MDAS . MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS . MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS ; physiologic causes for MDAS warrant further investigation.
Clinical Prediction Performance of Glaucoma Progression Using a 2-Dimensional Continuous-Time Hidden Markov Model with Structural and Functional Measurements
Authors: Youngseok Song, Hiroshi Ishikawa, Mengfei Wu, Yu-Ying Liu, Katie A. Lucy, Fabio Lavinsky, Mengling Liu, Gadi Wollstein, Joel S. Schuman
Journal: Ophthalmology (2018)
Looking at the recent farce regarding the job application process for final year medical students, I am concerned that I, like 30 of our current final years, may graduate from medical school without a confirmed foundation year 1 placement. Could you give me some advice as to what I could be doing over the coming years to maximise my chances of getting a job on graduation?
Authors: Sarah Burnett
Journal: BMJ (2006)

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>
Guidance, what guidance?
Authors: Peter Cross
Journal: BMJ (2005)

Almost everything you need to know about guidelines is covered in this week's issue: where to find them, how to create them, and when to ignore them. You might imagine that the Medical Defence Union's Paul Colbrook advocates sticking to guidelines in all cases. If so you'd be wrong. A doctor's first duty is to look after a patient's best interests, and that might mean deviating from normal good practice. However you'll …
USEFULNESS OF NOVEL ROADMAP GUIDED PERCUTANEOUS CORONARY INTERVENTION FOR BIFURCATION LESIONS (THE WORLD'S FIRST CASES)
Authors: Hideyuki Takimura, Toshiya Muramatsu, Reiko Tsukahara, Masatsugu Nakano, Satoshi Nishio, Yukako Takimura, Takayuki Yabe, Mami Kawano, Tasuku Hada
Journal: Journal of the American College of Cardiology (2018)
Management of hepatitis C viral infection in chronic kidney disease patients on hemodialysis in the era of direct-acting antivirals
Authors: Soon Young Ko, Won Hyeok Choe
Journal: Clinical and Molecular Hepatology (2018)

The advent of novel, direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) infection has revolutionized its treatment by producing a sustained virologic response of more than 95% with few side effects and no comorbidities in the general population. Until recently, ideal DAA regimens have not been available to patients with severe renal impairment and end-stage renal disease because there are limited data on the pharmacokinetics, safety, and efficacy of treatment in this unique population. In a hemodialysis context, identifying patients in need of treatment and preventing HCV transmission may also be a matter of concern. Recently published studies suggest that a combination of paritaprevir/ ritonavir/ombitasvir and dasabuvir, elbasvir/grazoprevir, or glecaprevir/pibrentasvir successfully treats HCV infection in chronic kidney disease stage 4 or 5 patients with or without hemodialysis. Keywords: Chronic Hepatitis C; Hemodialysis; Direct-acting antivirals
Children’s crusade
Authors: Elizabeth Loder
Journal: BMJ (2018)

Curtis Compton/ZUMA/PA

Last week tens of thousands of US students walked out of class in a peaceful protest against gun violence, including these protesters in Atlanta, Georgia. Their words and signs were powerful: “The adults have failed us. If any elected official gets in our way, we will vote them out.” “Fix this before I text my mom from under a desk.”

One of the most memorable things about the horrible aftermath of …
Bridging the data gap in global health: an electronic surgical outcomes database at Mbarara Regional Referral Hospital, Uganda
Authors: Gustaf Drevin, Katherine Albutt, Frank Sanyu, Deus Twesigye, Godfrey R Mugyenyi, Joseph Ngonzi, Stephen S Ttendo, Paul G Firth
Journal: The Lancet Global Health (2018)

BackgroundAnnually, an estimated 17 million lives are lost from conditions requiring surgical care and at least 77·2 million disability-adjusted life-years could be averted through provision of basic surgical services. Despite the staggering burden of surgical disease, there are scarce data available to track current capacity, volume, epidemiology, outcomes, and quality of surgical care delivery in low-income and middle-income countries. We aimed to organise the hospital record system into a high-quality and high-fidelity searchable database that can be used to measure and guide expansion and provision of quality care at Mbarara Regional Referral Hospital (MRRH) in western Uganda.MethodsInitiated in 2013, the Surgical Services QUality Assessment Database (SQUAD) arose from a shared commitment to improving surgical quality and capacity through a collaboration between MRRH and Massachusetts General Hospital. SQUAD systematically enrols and collects data on all surgical patients admitted to MRRH. Data are extracted from patient charts and admission, discharge, and operation logbooks by trained clerks—a process overseen by a data manager/statistician. Data variables are grouped into patient demographics, disease characteristics, cadre of clinicians, interventions, outcomes, and time. Data access and use is supervised by a committee of representatives.FindingsTo date, SQUAD contains more than 49 000 patient records in a searchable electronic database. Quality assurance reports have been produced for internal use at MRRH, and in-hospital initiatives have been made in response to findings. SQUAD was prospectively validated in 2016, and retrospective validation studies are currently underway.InterpretationOngoing challenges include transitioning data capture methods from chart and log book review to a point-of-care electronic medical register and record system, while maintaining data entry. A future objective is the dissemination of clinical outcome reports through peer reviewed publications by authors from the collaborating institutions.FundingGE Foundation, Milton Foundation, Kletjian Foundation, and MGH Department of Anesthesia, Critical Care and Pain Medicine.
Prognostic implication of appendicular skeleton bone marrow abnormalities detected using low-dose multidetector computed tomography in patients with myelodysplastic syndrome
Authors: Yoshiaki Abe, Tomotaka Ugai, Manabu Fujisawa, Yuya Matsue, Kentaro Narita, Masami Takeuchi, Kosei Matsue
Journal: Leukemia (2018)
Abstract P2-05-07: Whole exome sequencing of extreme responders reveals low mutation burden in metastatic breast cancer
Authors: J Sohn, SM Lim, E Kim, S Kim, JS Koo, SI Kim, S Park, HS Park, N-J Kwon, GM Kim, S Kim
Journal: Cancer Research (2018)

Abstract Background: Extreme responders to anticancer therapy are rarely encountered in the treatment of advanced breast cancer patients, but their treatment response have not been investigated on the whole exome level. We performed whole exome analysis to characterize genomic landscape of extreme responders in metastatic breast cancer patients. Methods: Clinical samples were obtained from patients who showed exceptional response to anti-HER2 therapy or hormonal therapy. Non-responders were selected among those who did not respond. Matched breast tumor tissue (somatic DNA) and blood samples (germline DNA) were collected from a total of 18 responders (12 ER+, 6 HER2+) and 8 non-responders (6 ER+, 1 HER2+, 1 TNBC). Whole exome sequencing using Illumina HiSeq2500 was performed on the 26 patients (52 samples). Somatic single nucleotide variants (SNVs), indels and copy number variants (CNVs) were identified for each patient genome. Group specific somatic variants and mutation burden were statistically analyzed. Findings: Cancer exomes were characterized by 1,455 somatic single-nucleotide variants (1,327 missense, 80 nonsense, 36 splice-site, 12 start/stop-lost), 149 insertions/deletions (108 frameshift, 41 inframe), with a median of 1 mutations per Mb (0.2 to 2.7 mutations per Mb) in all patients. Responders harbored a significantly lower non-synonymous mutation burden than non-responders (median, 27 vs. 90.5, P=0.01), and copy number variation burden was also lower (median 23 vs. 31, P=0.14). Multivariate analyses of factors influencing progression-free survival showed that high mutation burden and visceral metastases were significantly related with progression. Interpretation: Extreme responders of metastatic breast cancer are characterized by low nonsynonymous mutational burden. Citation Format: Sohn J, Lim SM, Kim E, Kim S, Koo JS, Kim SI, Park S, Park HS, Kwon N-J, Kim GM, Kim S. Whole exome sequencing of extreme responders reveals low mutation burden in metastatic 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 P2-05-07.
Effect of intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist G100 on a clinical response and CD4 T-cell response locally and systemically.
Authors: Yongwoo David Seo, Jing Zhou, Kevin Morse, Jeremy Patino, Sean Mackay, Edward Y. Kim, Ernest U. Conrad, Ryan Blair O'Malley, Lee D. Cranmer, Hailing Lu, Frank J. Hsu, Yuexin Xu, Elizabeth Trice Loggers, Taylor Hain, Venu Gopal Pillarisetty, Gabrielle Kane, Stanley Riddell, Jan H. ter Meulen, Robin Lewis Jones, Seth Pollack
Journal: Journal of Clinical Oncology (2018)

71 Background: Soft tissue sarcomas (STS) are heterogeneous tumors which are morbid and lethal. G100 is under investigation in multiple clinical trials and contains a potent TLR4 agonist (oil-in-water emulsion of glucopyranosyl lipid A) that has been tested as vaccine adjuvant. We hypothesized IT G100 would induce robust local and potentially systemic anti-tumor immune response, leading to improved outcomes. Methods: 15 metastatic STS patients with superficial lesions were treated with weekly IT G100 for 8-12 wks; 12 patients received radiation (RT) for 2 wks to start, while 3 received IT G100 for 6 wks prior to RT. Biopsies and PBMC were collected pre and post treatment, and flow cytometry was performed on biopsies. TIL and PBMC were analyzed with TCR deep sequencing. PBMC were analyzed by single cell multiplex cytokine profiling. Results: No grade ≥ 3 toxicity was observed, and local tumor control was achieved in all evaluable tumors (14/14). Treated tumors tracked post-trial (mean 156 days) had persistent local control with 1 CR (7%), 1 PR (7%), and 11 SD (79%). In 3 patients with long term follow up, treated lesions remained controlled vs index lesions (-53% vs +31% at mean 235 days, p = 0.002). In all tumors after G100 alone, T cell infiltration increased. In P14, CD3 live cells in tumor rose from &lt; 1% to 62%. PBMC clonality increased in 8/14 tested including P06, who had 4× increase in clonality and CR in the injected lesion; PBMC and TIL TCR overlap increased from 13.4% to 21.5%. P13 had a 2.3× rise in TIL clonality; the top clone (a CD4 T cell) expanded from 0.1% to 38% and expressed more TNFα than the rest (p &lt; 0.0001). Single cell cytokine analysis of PBMC showed 7/13 (54%) increased in polyfunctionality (producing &gt; 2 cytokines) in CD4 T cells; no consistent increase was seen in CD8 T cells. TNFα levels in pre-treatment monocytes correlated with PFS (R 2 = 0.5, p = 0.02). Conclusions: IT G100 is a viable agent for local control of metastatic STS lesions. With or without RT, G100 appears to cause CD4 T cell mediated local and systemic response. Combination of G100 with other immunomodulators could induce clinically significant systemic responses, as seen in follicular NHL treated with G100. Clinical trial information: NCT02180698.
More than 80% of general practices have registered with CQC
Authors: Helen Jaques
Journal: BMJ (2013)

More than 80% of general practices in England have successfully registered with the Care Quality Commission, but two practices have been refused registration.

Since the application window opened in September 2012, 7589 applications have been received, equivalent to 95% of all GP service providers expected to register. Over 80% of providers have …
CT-based texture characterization of lymphadenopathy in urothelial carcinoma: Prediction of treatment response.
Authors: Tapas K Tejura, David Quinn, Bino Varghese, Steven Yong Cen, Darryl Hwang, Frank K Chen, Bhushan Desai, Ting-Wei Fan, Vinay Duddalwar
Journal: Journal of Clinical Oncology (2018)

514 Background: Promising treatments are emerging for urothelial carcinoma, although there is no reliable method for predicting treatment response on an individual basis. Extraction of quantitative tumor-texture features from clinical radiologic images may distinguish between cancers which may be more responsive to treatment. Our purpose is to analyze CT-based textural features of urothelial cancer lymph node metastases prior to treatment and classify them to categories for response. Methods: In this IRB approved retrospective study, 36 patients with a proven diagnosis of urothelial cancer who were scheduled to have chemotherapy (Eribulin) and had pre- and post-treatment imaging were included. A total of 66 abnormally enlarged lymph nodes (&gt; 1.5 cm short-axis) were identified. Using RECIST 1.1 as treatment standard, lymph nodes were categorized into 3 categories: Complete or partial response (CR, PR), Stable disease (SD), and Progressive disease (PD). Texture analysis was performed using six different textural methods ranging from 1 st order statistical methods such as histogram analysis to higher-order methods such as image-frequency analysis. Depending on data normality, ANOVA or Kruskal Wallis test were used to assess signal difference across CR/PR, SD, and PD categories univariately. Classification Tree (CART) was used to explore potential multivariate prediction model. Results: 34 lymph nodes were categorized as CR/PR, 19 categorized as SD, and 13 categorized as PD. Univarate data analysis showed that of the various textural, histogram-based metrics: Correlation, Variance, Standard deviation, Sum/difference of averages, Homogeneity/Dissimilarity have statistically significantly difference across response categories (p&lt;0.05). CART analysis show preliminary evidence of predicting PD with 85% sensitivity but 54% false positive. Conclusions: CT-based textural features can differentiate between urothelial cancers which are more likely to respond to treatment. Validation with larger sample size and inclusion of data from other sites of metastases will aid in the identification of reliable imaging-texture based biomarkers for treatment stratification.
Abstract P2-11-08: Risk factors for fibrosis after whole breast radiation therapy in lateral position : A large scale single center experience
Authors: E Bronsart, S Dureau, HP Xu, E Costa, P Poortmans, A Chilles, F Berger, A Stilhart, A Fourquet, Y Kirova
Journal: Cancer Research (2018)

Abstract Background and Purpose: We previously confirmed the efficacy and safety of our technique of whole breast radiation therapy (WBRT) in isocentric lateral decubitus (ILD) position. The purpose of this work is to evaluate the risk factors for long-term fibrosis in patients treated in ILD position. Material and methods: We studies 832 consecutive female patients with early stage BC treated by conservative surgery followed by 3D-conformal WBRT at Institut Curie between 2005 and 2010. Fibrosis and deformation were evaluated at the end of the treatment and subsequently every 6 months during at least 5 years, using NCI CTC v3.0 scale. Different fractionation schedules were used: 66Gy in 33 fractions, 50Gy in 25 fractions, 40Gy in 15 fractions, 41.6Gy in 13 fractions and 30Gy in 5 weekly fractions. Results: Median age is 61.5 years (range: 29 - 90); median follow up is 6.4 years (range: 1.5 - 12.4). During the follow-up, 308 patients (38.9%) had grade 1 fibrosis, and 36 patients (4.3%) only, had grade 2-3 fibrosis. Among patients with grade 1 to 3 fibrosis, the median time to development of fibrosis was 1.6 years (range: 9 days – 8.3 years). In univariate and multivariate analysis, age, cup size and chemotherapy administration had no significant influence on development of breast fibrosis. The hypo fractionated schedule of 30Gy in 5 fractions significantly increased the fibrosis rate (OR=12.5; [2.7; 57.1] p=0.001). On the other hand, 40 Gy/15 fr and 41.6 Gy/13 fr had no significative influence (OR=2.2 [0.5; 11.1] p=0.32) as well as the 66 Gy/33 fr schedule (OR=3.6 [0.8; 15.4] p=0.09) compared to standard scheme of 50 Gy/25 fr. The cosmetic result was good or excellent for 84.8% of cases at the first evaluation. The 30 Gy in 5 fractions schedule significantly influenced the cosmetic result in the multivariate analysis (OR=11.2 [3.1; 43.9]; p&amp;lt;0.001), with increased rates of breast deformation. The risk of breast deformity was also worse for large breast size (OR=2.7 [1.3; 5.8]; p=0.02). Conclusion: Whole breast radiation therapy in ILD position is well tolerated with good cosmesis and low rates of fibrosis, except for the 30 Gy in 5 weekly fractions schedule. Large breast size has a significantly negative influence on cosmetic results and fibrosis. Citation Format: Bronsart E, Dureau S, Xu HP, Costa E, Poortmans P, Chilles A, Berger F, Stilhart A, Fourquet A, Kirova Y. Risk factors for fibrosis after whole breast radiation therapy in lateral position : A large scale single center experience [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 P2-11-08.
Publisher Correction: Temporally precise single-cell-resolution optogenetics
Authors: Or A. Shemesh, Dimitrii Tanese, Valeria Zampini, Changyang Linghu, Kiryl Piatkevich, Emiliano Ronzitti, Eirini Papagiakoumou, Edward S. Boyden, Valentina Emiliani
Journal: Nature Neuroscience (2018)
Tracking preleukemic cells in vivo to reveal the sequence of molecular events in radiation leukemogenesis
Authors: Tom Verbiest, Rosemary Finnon, Natalie Brown, Lourdes Cruz-Garcia, Paul Finnon, Grainne O’Brien, Eleanor Ross, Simon Bouffler, Cheryl L. Scudamore, Christophe Badie
Journal: Leukemia (2018)

Epidemiological studies have demonstrated an increased leukemia incidence following ionizing radiation exposure, but to date, the target cells and underlying mechanisms of radiation leukemogenesis remain largely unidentified. We engineered a mouse model carrying a different fluorescent marker on each chromosome 2, located inside the minimum deleted region occurring after radiation exposure and recognized as the first leukemogenic event. Using this tailored model, we report that following radiation exposure, more than half of asymptomatic CBA Sfpi1 GFP/mCh mice presented with expanding clones of preleukemic hematopoietic cells harboring a hemizygous interstitial deletion of chromosome 2. Moreover, following isolation of preleukemic hematopoietic stem and progenitor cells irradiated in their native microenvironment, we identified the presence of Sfpi1 point mutations within a subpopulation of these preleukemic cells expanding rapidly (increasing from 6% to 55% in 21 days in peripheral blood in one case), hence identifying for the first time the presence of such cells within a living animal. Importantly, we also report a previously undescribed gender difference in the phenotype of the preleukemic cells and leukemia, suggesting a gender imbalance in the radiation-induced leukemic target cell. In conclusion, we provide novel insights into the sequence of molecular events occurring during the (radiation-induced) leukemic clonal evolution.
GMC is to limit how long doctors’ sanctions are listed online
Authors: Abi Rimmer
Journal: BMJ (2015)

The General Medical Council is proposing to change the way it publishes doctors’ sanctions on its online register.1

It is consulting on plans to introduce limits on the length of time sanctions are published on its online medical register or disclosed to the general public. 

Currently the online medical register lists, for an indefinite period, details of a doctor’s history of fitness to practise from 20 October 2005, which was when the electronic register was introduced. This listing includes …
SUPER HIGH RESOLUTION µOCT FOR ENDOTHELIAL CELL VISUALIZATION IN THE CORONARY ARTERIES EX VIVO
Authors: Kensuke Nishimiya, Biwei Yin, Zhonglie Piao, Gargi Sharma, Hany Osman, Joseph A. Gardecki, Guillermo J. Tearney
Journal: Journal of the American College of Cardiology (2018)
Who should I contact and which hospitals are more competitive for an elective attachment in psychiatry?
Authors: Jim Bolton
Journal: BMJ (2005)

<b>www.bmjcareers.com/advicezone</b> 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.