tbuckley/cabot-search huggingface dataset:
Delays in completion and results reporting of clinical trials under the Paediatric Regulation in the European Union: A cohort study
Authors: Thomas J. Hwang, Paolo A. Tomasi, Florence T. Bourgeois
Journal: PLoS Medicine (2018)

Background Few medicines have been approved for children, leading to rates of off-label prescribing reported to be as high as 90%. In 2007, the European Union adopted the Paediatric Regulation, which mandates that pharmaceutical companies conduct paediatric studies for all new medicines, unless granted a waiver. We aimed to evaluate the availability of paediatric trial results from studies required under the Paediatric Regulation for new medicines authorised in the EU. Methods and findings The European Medicines Agency (EMA) public database of paediatric investigation plans was searched for new medicines centrally authorised in the EU between 1 January 2010 and 31 December 2014 with at least 1 required paediatric study. For our study cohort of paediatric clinical trials required for these medicines, we used internal EMA databases and publicly available trial registries to determine changes to the planned completion date or study design, rates of trial completion, time to trial completion, and results reporting (peer-reviewed publication or posting on trial registry). Cox proportional hazards regression models were constructed to examine factors associated with study completion. A total of 326 paediatric clinical trials were required for 122 novel medicines authorised by the EMA between 2010 and 2014. In all, 76% (247/326) of paediatric studies were not planned to be completed until after the initial marketing authorisation. The planned completion dates for 50% (162/326) were further postponed by a median of 2.2 years. Overall, 38% (124/326) of paediatric studies were completed as of 30 November 2017. The rate of trial completion for paediatric studies planned to be completed after initial marketing authorisation was 23% (56/247), versus 86% (68/79) for trials planned to be completed before authorisation (adjusted hazard ratio 0.11; 95% CI 0.06–0.19). Among completed studies, the results were reported in a public registry or in the peer-reviewed literature for 85% (105/124) at a median of 1.1 years after study completion, and 60% (74/124) were published in a peer-reviewed journal. Limitations of this study include the potential lack of generalisability to medicines not authorised by the EMA and the possibility for more of these trials to be completed or published in the future. Conclusions The completion of many paediatric studies required under the Paediatric Regulation has been delayed. Paediatric studies planned to be completed after marketing authorisation were associated with a lower likelihood of eventual completion, highlighting the need to examine the implementation of current policies in ensuring timely availability of important paediatric information.
MSc in orthopaedic engineering
Authors: Munier Hossain
Journal: BMJ (2005)

This two year part time MSc course is designed for medical graduates with an interest in biomechanics. Cardiff School of Engineering and University of Wales College of Medicine jointly award the degree.

Effective understanding of biomechanics is essential to apply modern orthopaedic practice successfully. The human body is a three dimensional structure and subject to the laws of mechanics. Load application and resultant fracture follow a predictable pattern. Knowledge of this helps to formulate the right treatment option. Orthopaedic surgeons today have to choose from an enormous variety of available prostheses and metal implants. With a thorough grounding in biomechanics they can make an informed and confident choice.

Competition for training posts is currently very high. An MSc degree would …
Melanoma staging: Varying precision and terminal digit clustering in Breslow thickness data is evident in a population-based study
Authors: Marit B. Veierød, Christian M. Page, Stein Aaserud, Assia Bassarova, Kari D. Jacobsen, Per Helsing, Trude E. Robsahm
Journal: Journal of the American Academy of Dermatology (2018)
Distinguishing fibrosis/necrosis from teratoma or viable disease in the retroperitoneum in post-chemotherapy, nonseminomatous testicular germ cell tumor using quantitative CT texture analysis.
Authors: Kevin George King, Sumeet Bhanvadia, Saum Ghodoussipour, Darryl Hwang, Bino Varghese, Steven Yong Cen, Siamak Daneshmand, Vinay Duddalwar
Journal: Journal of Clinical Oncology (2018)

563 Background: In metastatic nonseminomatous testicular germ cell tumor (NSGCT), post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is indicated for residual masses &gt; 1 cm because of these 45% will be fibrosis/necrosis, 45% will be teratoma and 15% will be viable malignancy. There is no imaging test that reliably distinguishes lymph nodes (LNs) with tumor (teratoma or malignancy) from LNs with fibrosis/necrosis. We evaluated whether quantitative CT texture analysis (TA) could make this differentiation. Methods: Pre- and post-chemotherapy CTs (all same phase and slice thickness) were reviewed in 22 NSGCT patients with RP LNs &gt; 1 cm post chemotherapy. After manual segmentation of RP LNs on a 3D workstation, 187 TA metrics were derived, using 2D/3D gray-level co-occurrence matrix (GLCM), 2D/3D gray-level difference matrix (GLDM), and spectral analysis. Metrics were derived 2 ways: from post-chemotherapy CTs alone, and also as a difference between pre- and post-chemotherapy CTs, resulting in 374 metrics. PC-RPLND pathology was correlated with CT data at 88 LN stations in these 22 patients. Results: 15 imaging metrics showed a significant difference (p ≤ 0.05) between LN stations with only fibrosis/necrosis and those with teratoma or viable tumor. Seven were derived from the difference between pre- and post-chemotherapy CTs: 4 using a 2D GLCM (coronal standard deviation, coronal square root of variance, coronal mean, and coronal sum of average), and 3 using a 2D GLDM (axial variance, axial square root of variance, and coronal variance). The other 8 were derived from post-chemotherapy CTs alone: 7 using a 2D GLCM (sagittal square root of variance, sagittal standard deviation, coronal square root of variance, coronal mean, coronal standard deviation, coronal sum of average, and coronal entropy) and 1 using a 2D GLDM (sagittal sum entropy). Conclusions: CT TA shows promise in differentiating necrosis from teratoma or viable tumor in RP LNs in post-chemotherapy NSGCT. A larger study is needed to further test this method, towards a long-term goal of potentially allowing some patients to avoid PC-RPLND.
More to episodic memory than epistemic assertion: The role of social bonds and interpersonal connection
Authors: William Hirst, Gerald Echterhoff
Journal: Behavioral and Brain Sciences (2018)

Remembering is dynamically entangled in conversations. The communicative function of episodic memory can be epistemic, as suggested by Mahr & Csibra (M&C). However, remembering can have genuinely social functions, specifically, the creation or consolidation of interpersonal relationships. Autonoesis, a distinct feature of episodic memory, is more likely to have evolved in the service of social binding than of epistemic assertiveness.
A pilot case control study: Could a gastric cancer risk screening tool help identify high risk patients for endoscopic screening in the United States?
Authors: Haejin In, Marisa Langdon-Embry, Lauren Gordon, Judith Wylie-Rosett, Clyde Schechter, Philip Castle, Margaret Kemeny, Bruce D. Rapkin
Journal: Journal of Clinical Oncology (2018)

64 Background: Gastric cancer incidence varies greatly among US racial/ethnic groups. Few studies have examined ethnicity, birth country, immigration and cultural diet as gastric cancer risk factors in the US. These factors, in combination with known risk factors may narrow a target population for gastric cancer screening. Methods: Two racially diverse hospital systems were used to recruit gastric cancer cases using the cancer registry, and primary care (PC) controls from waiting rooms or phone. Community controls were recruited at community gatherings. Participants were eligible if 40-85 years old, not under endoscopic surveillance and without genetic syndromes. The survey items (n = 227) included conventional risk factors, plus items about ethnicity, birth country, acculturation, and ethnic diet. Results: Of 150 participants, 39 cases, 41 PC-controls, and 44 community controls were eligible for analysis. PC-controls generally completed phone interviews (72% vs 28%), while community controls generally completed paper surveys (92% vs 8%). Gastric cancer cases were more likely to be foreign born (85% vs. 49%, p = &lt; 0.01), from a country with gastric cancer incidence &gt; 5 per 100,000: (62% vs. 30%, p = &lt; 0.01) and report daily consumption of cultural food at ages 15 to 18 (69% vs. 35%, p = &lt; 0.01) compared to controls. Cases were also older, male, Hispanic, and had stronger family history of gastric cancer. Cases and controls had similar frequency of alcohol consumption, smoking, acculturation, and barbequed food consumption. In multivariate analysis, increased age (per year, aOR 1.4, 95%CI 1.07-1.21), daily consumption of cultural foods at ages 15 to 18 (aOR 19.58, 95%CI 1.54-248.99), having less than high school education (aOR 7.24, 95%CI 1.49-35.10), and being foreign born (aOR 11.81, 95%CI 1.69-82.64) were associated with case status. Conclusions: A risk assessment tool that addresses awareness of gastric cancer risk factors, ethnicity, cultural habits and immigration patterns has potential to identify high-risk persons from multicultural areas within the US, who might benefit from endoscopic screening for gastric cancer. (Support: UG1CA189823)
CHA2DS2-VASC AND HAS-BLED SCORES IN PREDICTING THE RISK OF STROKE VERSUS INTRACRANIAL BLEED: THE FIBSTROKE STUDY
Authors: Samuli Jaakkola, Tuomas Kiviniemi, Ilpo Nuotio, Juha Hartikainen, Pirjo Mustonen, Antti Palomäki, Jussi Jaakkola, Antti Ylitalo, Paivi Hartikainen, Juhani Airaksinen
Journal: Journal of the American College of Cardiology (2018)
HEART FAILURE WITH PRESERVED EJECTION FRACTION IS A COMMON CARDIAC EVENT, AND LEFT VENTRICULAR EJECTION FRACTION HAS LIMITED UTILITY AS A SCREENING TOOL, DURING PROTEASOME INHIBITOR THERAPY FOR MULTIPLE MYELOMA
Authors: Cherie N. Dahm, Robert F. Cornell, Bonnie Ky, Trafina Jadhav, Amanda M. Smith, Deepak Gupta, Daniel J. Lenihan
Journal: Journal of the American College of Cardiology (2018)
DIFFUSE INTERSTITIAL MYOCARDIAL FIBROSIS IS ASSOCIATED WITH ABNORMAL LEFT ATRIAL MECHANICS
Authors: Julio A. Chirinos, Amer A. Syed, Rachana Miller, Khuzaima Javaid, Harry Oldland, Bilal Ansari, Anila Hussain, Swapna Varakantam, Jonathan Lee, Scott Akers
Journal: Journal of the American College of Cardiology (2018)
What is the best way for a UK qualified doctor to return to medicine, particularly anaesthetics, after a two year break?
Authors: Michael Dobson
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>
The Evidence for Cognitive Behavioral Therapy—Reply
Authors: Falk Leichsenring, Christiane Steinert
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Newcastle head and neck cadaver dissection course
Authors: Naveed Kara
Journal: BMJ (2011)

This course is aimed at trainees in otolaryngology (ear, nose, and throat (ENT)) and maxillofacial surgery who would like to develop their skills in surgical dissection. It is suitable for junior trainees who are looking for an introduction to head and neck surgical anatomy and dissection and also for senior trainees who wish to revise their anatomy and to fine tune their dissection skills and techniques. Participants on the course when I did it also included theatre nursing staff looking to gain a better understanding of the surgical procedures in which they are regularly involved.

Head and neck anatomy is complex, and although textbooks are informative there is no substitute for hands-on anatomical dissection. Having already spent some time in head and neck surgery as a higher surgical trainee in ENT, I signed up for this course to further consolidate what I had …
Transcriptional regulation of stress kinase JNK2 in pro-arrhythmic CaMKIIδ expression in the aged atrium
Authors: Xianlong Gao, Xiaomin Wu, Jiajie Yan, Jingqun Zhang, Weiwei Zhao, Dominic DeMarco, Yongguo Zhang, Mamdouh Bakhos, Gregory Mignery, Jun Sun, Zhenyu Li, Michael Fill, Xun Ai
Journal: Cardiovascular Research (2018)

c-jun N-terminal kinase (JNK) is a critical stress response kinase that activates in a wide range of physiological and pathological cellular processes. We recently discovered a pivotal role of JNK in the development of atrial arrhythmias in the aged heart, while cardiac CaMKIIδ, another pro-arrhythmic molecule, was also known to enhance atrial arrhythmogenicity. Here, we aimed to reveal a regulatory role of the stress kinase JNK2 isoform on CaMKIIδ expression. Activated JNK2 leads to increased CaMKIIδ protein expression in aged human and mouse atria, evidenced from the reversal of CaMKIIδ up-regulation in JNK2 inhibitor treated wild-type aged mice. This JNK2 action in CaMKIIδ expression was further confirmed in HL-1 myocytes co-infected with AdMKK7D-JNK2, but not when co-infected with AdMKK7D-JNK1. JNK2-specific inhibition (either by a JNK2 inhibitor or overexpression of inactivated dominant-negative JNK2 (JNK2dn) completely attenuated JNK activator anisomycin-induced CaMKIIδ up-regulation in HL-1 myocytes, whereas overexpression of JNK1dn did not. Moreover, up-regulated CaMKIIδ mRNA along with substantially increased phosphorylation of JNK downstream transcription factor c-jun [but not activating transcription factor2 (ATF2)] were exhibited in both aged atria (humans and mice) and transiently JNK activated HL-1 myocytes. Cross-linked chromatin-immunoprecipitation assays (XChIP) revealed that both c-jun and ATF2 were bound to the CaMKIIδ promoter, but significantly increased binding of c-jun only occurred in the presence of anisomycin and JNK inhibition alleviated this anisomycin-elevated c-jun binding. Mutated CaMKII consensus c-jun binding sites impaired its promoter activity. Enhanced transcriptional activity of CaMKIIδ by anisomycin was also completely reversed to the baseline by either JNK2 siRNA or c-jun siRNA knockdown. JNK2 activation up-regulates CaMKIIδ expression in the aged atrium. This JNK2 regulation in CaMKIIδ expression occurs at the transcription level through the JNK downstream transcription factor c-jun. The discovery of this novel molecular mechanism of JNK2-regulated CaMKII expression sheds new light on possible anti-arrhythmia drug development.
MINIMALLY INVASIVE MITRAL VALVE SURGERY: THE NEW GOLD STANDARD?
Authors: Anna Olds, Bassel Bashjawish, Siavash Saadat, Viktor Dombrovskiy, Karen Odroniec, Anthony Lemaire, Aziz Ghaly, George Batsides, Leonard Lee, Rutgers Robert
Journal: Journal of the American College of Cardiology (2018)
GPs must push back against work dumped on them by hospitals, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

GPs should push back on inappropriate work given to them by hospitals, the BMA has said.

The BMA has published guidance for GPs on how to transfer unnecessary work back to secondary care managers.1 The organisation said that the 2017/18 NHS standard contract for secondary care trusts, which came into force …
Continuous infusion fluorouracil (5FU) in heavily pre-treated mCRPC patients.
Authors: Charlotte Manogue, Marcus Marie Moses, Brian E. Lewis, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2018)

257 Background: Pts with mCRPC resistant to novel hormones (abi/enza), and taxane chemotherapy are challenging. Extensive pre-treatment typically poses an issue for clinical trials, and there is no consensus regarding how to manage patients who no longer respond to conventional therapies but maintain a good performance status. Methods: 13 mCRPC pts were treated with 5FU at 200mg/m 2 continuous infusion as a novel treatment option for those with heavily pretreated mCRPC. Data was retrospectively collected at Tulane Cancer Center for patient treatment history, and laboratory parameters. Results: All treated patients had prior exposure to an average of 8.7 lines of treatment. 5FU was used as median 8 th line therapy. All pts had extensive bony disease and 6 had liver involvement. Median PSA at start of treatment was 356 ng/dL. 5 pts progressed within a month of initiation of therapy, and 2 pts did not respond. 8 (61%) patients had treatment for &gt;1 month with 6 having &gt;30% PSA reduction, 4 with a &gt;50% PSA reduction and 2 with a &gt;90% PSA reduction (Table). Median time on therapy was 4.5 months with 2 patients remaining on treatment for &gt;6 months despite multiple pretreatments and far advanced disease. 5FU was well tolerated with improvement in both performance status and symptoms in several patients. Conclusions: Continuous 5FU is active in select highly pretreated pts and targets folate metabolism via inhibition of thymidylate synthase. It is one of the few chemotherapies that can be administered with little myelosuppression, an important issue in far-advanced pts. Prostate specific membrane antigen (PSMA) expression is upregulated in CRPC, especially after abi/enza treatment. PSMA hydrolyzes polyglutamated folates and functions as a folate transporter; its over-expression stimulates both folate transport and prostate cancer cell line growth. We hypothesize that 5FU, functioning as an anti-folate, antagonizes the downstream effects of PSMA over-expression. PSA data for pts on treatment &gt; 1 month. [Table: see text]
Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery
Authors: Anna Slita, Anna Egorova, Eudald Casals, Anton Kiselev, Jessica M. Rosenholm
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine) (hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered siRNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated siRNA/MSN complexes provide more effective delivery of siRNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.
Reduced Left Ventricular Ejection Fraction in Patients With Aortic Stenosis
Authors: Saki Ito, William R. Miranda, Vuyisile T. Nkomo, Heidi M. Connolly, Sorin V. Pislaru, Kevin L. Greason, Patricia A. Pellikka, Bradley R. Lewis, Jae K. Oh
Journal: Journal of the American College of Cardiology (2018)
UK should train more generalist doctors, says review
Authors: Helen Jaques
Journal: BMJ (2013)

The United Kingdom should train more generalist doctors to support the move towards caring for patients outside of hospitals, a review of postgraduate medical education and training has concluded.

Most organisations and individuals who responded to the Shape of Training review agreed that more doctors should be trained to deal with a varied range of conditions and care settings.

Medical royal colleges and other organisations representing doctors have rejected the possibility that generalists should be trained to a basic or “subconsultant” level, with many instead arguing that they would require a longer training period than specialists.

The Shape of Training Review, led by David Greenaway, vice chancellor of Nottingham University, …
A 25-Year Experience of US Food and Drug Administration Accelerated Approval of Malignant Hematology and Oncology Drugs and Biologics
Authors: Julia A. Beaver, Lynn J. Howie, Lorraine Pelosof, Tamy Kim, Jinzhong Liu, Kirsten B. Goldberg, Rajeshwari Sridhara, Gideon M. Blumenthal, Ann T. Farrell, Patricia Keegan, Richard Pazdur, Paul G. Kluetz
Journal: JAMA Oncology (2018)

<h3>Importance</h3> Accelerated approval (AA) is a US Food and Drug Administration (FDA) expedited program intended to speed the approval of drugs and biologics that may demonstrate a meaningful advantage over available therapies for diseases that are serious or life-threatening. <h3>Observations</h3> This review describes all malignant hematology and oncology AAs from inception of the program on December 11, 1992, to May 31, 2017. During this period, the FDA granted AA to 64 malignant hematology and oncology products for 93 new indications. Of these AAs, 53 were for new molecular entities. Overall, the end point of response rate, including hematologic response rates, accounted for most AAs (81 [87%]), followed by time-to-event end points of progression-free survival or time to progression (8 [9%]) and disease-free survival or recurrence-free survival (4 [4%]). Single-arm trial designs provided the data for 67 (72%) of the initial AA indications. Of the 93 AAs, 51 (55%) have fulfilled their postmarketing requirement and verified benefit in a median of 3.4 years after their initial AA. Thirty-seven (40%) indications have not yet completed confirmatory trial(s) or verified benefit, and 5 indications receiving AA (5%) have been withdrawn from the market. <h3>Conclusions and Relevance</h3> The use of the AA program during the past 25 years has increased over time, and only a small portion of indications under the AA program fail to verify clinical benefit. For patients with serious or life-threatening oncologic diseases, AA brings products to the market years before confirmatory trials are typically completed.