tbuckley/cabot-search huggingface dataset:
Tau in Chronic Traumatic Encephalopathy—Reply
Authors: Breton M. Asken, Michael S. Jaffee, Russell M. Bauer
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
What low back pain is and why we need to pay attention
Authors: Jan Hartvigsen, Mark J Hancock, Alice Kongsted, Quinette Louw, Manuela L Ferreira, Stéphane Genevay, Damian Hoy, Jaro Karppinen, Glenn Pransky, Joachim Sieper, Rob J Smeets, Martin Underwood, Rachelle Buchbinder, Jan Hartvigsen, Dan Cherkin, Nadine E Foster, Chris G Maher, Martin Underwood, Maurits van Tulder, Johannes R Anema, Roger Chou, Stephen P Cohen, Lucíola Menezes Costa, Peter Croft, Manuela Ferreira, Paulo H Ferreira, Julie M Fritz, Stéphane Genevay, Douglas P Gross, Mark J Hancock, Damian Hoy, Jaro Karppinen, Bart W Koes, Alice Kongsted, Quinette Louw, Birgitta Öberg, Wilco C Peul, Glenn Pransky, Mark Schoene, Joachim Sieper, Rob J Smeets, Judith A Turner, Anthony Woolf
Journal: The Lancet (2018)
Four year GP training is on cards for 2013
Authors: Helen Jaques
Journal: BMJ (2012)

Training of GPs could be extended from three to four years from as early as 2013 if plans set out by the Committee of General Practice Education Directors (COGPED) and the Royal College of General Practitioners go ahead.

If the Department of Health, the Medical Programme Board, and the secretary of state for health approve the proposals in meetings this spring, the four year programme could be implemented for junior doctors who start their GP training in 2013. 

Although the current three year GP programme allows trainees to attain core competences, many …
BMA must promote doctors’ professionalism, members say
Authors: Abi Rimmer
Journal: BMJ (2014)

The BMA must raise the public’s awareness of doctors’ professionalism, value, and integrity, members of the association have said. Delegates at the BMA’s annual representative meeting in Harrogate voted overwhelmingly in favour of a motion stating that “professionalism is at the heart of quality healthcare delivery.”

Presenting the motion, Peter Holden, a negotiator for the BMA’s General Practitioners …
INCIDENCE AND PREDICTORS OF RENAL DYSFUNCTION FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT: IMPACT OF ACUTE KIDNEY INJURY DEFINITIONS
Authors: Ruben Rodriguez, Mohammed Hasoon, Steven R. Bailey, Anand Prasad, Marvin Eng, Joel Michalek, Qianqian Liu, Brian Hernandez
Journal: Journal of the American College of Cardiology (2018)
The Importance of Adequately Powered Clinical Studies: Response to Khan et al.
Authors: Stephen R. Marder, Thomas Laughren, Steven J. Romano
Journal: American Journal of Psychiatry (2018)

Are Innovative Drugs Failing in Phase III?" (1), brings up a critical topic: the frequent failure of phase III trials for CNS programs.The authors effectively summarized investigations into this issue.However, we believe that a possible explanation for phase III trial failure was minimized, as noted in the commentary: "that the phase II results were misleading" (1, p. 829).It is perhaps an underappreciated truism that statistically underpowered studies with small sample sizes (often earlyphase studies) are highly likely to both under-and overestimate treatment effect sizes (2, 3).By considering large effects from small studies to be true effects rather than overestimation errors, some researchers have concluded that smaller trials are more advantageous.Take, for example, the citation of Undurraga and Baldessarini, who suggest limiting phase III antidepressant trials to 30-75 patients (4, p. 860).Testing this suggestion using data from Food and Drug Administration (FDA) antidepressant phase III trials, we found that treatment arms with Ns of #75 had both the highest (0.75) and lowest (20.29) effect sizes of the entire group of 115 arms and that they achieved statistical significance only 50% of the time.In contrast, the largest treatment arms (with Ns of $350) had a 100% rate of statistical significance and little variation in effect size (from 0.24 to 0.33).These smaller trials empirically demonstrate the chance findings of underpowering-they are no more reliable than tossing a coin.These findings are unsurprising, given that a two-arm trial with Ns of #75 would be powered only at 50% for an effect size of 0.5 (2).Underreporting negative studies in published research may mask the downside of the underpowering coin, which can be seen in the FDA data; that is, those "unlucky" underpowered trials resulting in failure and underestimations of drug effect.The increase in size of phase III trials should not be viewed as a design flaw because this rejects the statistical principles of the scientific method.If phase II results are a reflection of the true magnitude of treatment effects, by rule they should be replicated in a larger sample.If they are not, then the phase II results were likely misleading.Seeking to replicate such lucky results from underpowered studies by underpowering future studies only perpetuates scientifically unsound methods and high failure rates.
Evaluation of serial measurements of C-reactive protein: Albumin ratio in patients with clear cell renal cell carcinoma.
Authors: Dattatraya H Patil, Ella N Anastasiades, Mersiha Torlak, Aaron Lay, Mehrdad Alemozaffar, John Pattaras, Omer Kucuk, Bradley Curtis Carthon, Mehmet Asim Bilen, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2018)

695 Background: Sequential measurements of prognostic markers is an important protocol for accurate prediction of clinical outcomes in clear cell RCC. We propose that change in value of C-Reactive Protein to albumin ratio before and after surgery would be a good prognostic indicator for assessment of overall survival and risk stratification in clear cell RCC. Methods: Patients that underwent nephrectomy for clear cell RCC between 2007 and 2016 were followed up with CRP-Albumin measurements for 3 post-op visits (1, 3, 6 months). All measurements between post-op day 1 to 21 were excluded from analysis owing to possible confounding effect due to surgical stress. We assessed if change in CRP-Albumin ratio from pre-operative level is associated with any patient and tumor characteristics by fitting linear regression generalized estimating equations models to account for correlation in repeated measures. Average change in level for each post-op visit was used to stratify for an eventual end of follow-up outcome. Results: 302 clear cell RCC patients were treated with nephrectomy with mean age at surgery was 59.9±11 years, and mean BMI of 30.1± 6.6. 103 patients had at least 2 time-points available after surgery. Table 1 depicts mean CRP-Albumin ratio with 95% CI for each visit stratified with vital status. A linear GEE model fitted for baseline factors affecting change in ratio , identified t-stage, Fuhrman nuclear grade, gender, and BMI as significantly associated (p &lt; 0.05). Conclusions: Serial measurement of CRP/Albumin ratio is useful factor for personalized risk-stratification for prognosticating overall survival as well as recurrence in patients with clear cell RCC. Significant effect of T-stage, tumor grade, and BMI depicts close relationship of CA-ratio and established risk predictors. [Table: see text]
Diploma in the History of Medicine (DHMSA)
Authors: Ann Ferguson
Journal: BMJ (2005)

This is a postgraduate diploma which is undertaken mainly by doctors, medical students, and other healthcare professionals but also by people with an interest in the history of medicine—for example, Blue Badge guides.

I did it the year after I retired, so I had plenty of time to attend the course run by the Society of Apothecaries and do the associated reading, as well as attending all the other lectures available on various aspects of medical history.

I did it for interest …
Advanced Endoscopic Navigation: Surgical Big Data, Methodology, and Applications
Authors: Xiongbiao Luo, Kensaku Mori, Terry M. Peters
Journal: Annual Review of Biomedical Engineering (2018)

Interventional endoscopy (e.g., bronchoscopy, colonoscopy, laparoscopy, cystoscopy) is a widely performed procedure that involves either diagnosis of suspicious lesions or guidance for minimally invasive surgery in a variety of organs within the body cavity. Endoscopy may also be used to guide the introduction of certain items (e.g., stents) into the body. Endoscopic navigation systems seek to integrate big data with multimodal information (e.g., computed tomography, magnetic resonance images, endoscopic video sequences, ultrasound images, external trackers) relative to the patient's anatomy, control the movement of medical endoscopes and surgical tools, and guide the surgeon's actions during endoscopic interventions. Nevertheless, it remains challenging to realize the next generation of context-aware navigated endoscopy. This review presents a broad survey of various aspects of endoscopic navigation, particularly with respect to the development of endoscopic navigation techniques. First, we investigate big data with multimodal information involved in endoscopic navigation. Next, we focus on numerous methodologies used for endoscopic navigation. We then review different endoscopic procedures in clinical applications. Finally, we discuss novel techniques and promising directions for the development of endoscopic navigation.
Phase I dose-escalation study of <sup>225</sup>Ac-J591 for progressive metastatic castration resistant prostate cancer (mCRPC).
Authors: Scott T. Tagawa, Shankar Vallabhajosula, Yuliya Jhanwar, Karla V. Ballman, Amy Hackett, Lauren Emmerich, John Babich, A. Oliver Sartor, Lauren Christine Harshman, Himisha Beltran, Ana M. Molina, David M. Nanus, Neil Harrison Bander
Journal: Journal of Clinical Oncology (2018)

TPS399 Background: PC is a radiosensitive disease. PSMA is overexpressed in advanced PC with upregulation by androgen receptor (AR) pathway dysregulation; limited expression exists in other organs. A series of sequential studies of beta-emitting radiolabeled anti-PSMA monoclonal antibody (mAb) J591 have demonstrated accurate targeting, efficacy with dose-response effect, and safety with predictable, reversible dose-limiting myelosuppression. Alpha emitters are significantly more potent with a shorter range than beta emitters. Though there is no direct tumor-targeting, the bone-targeting alpha emitter Ra223 is approved. Anecdotal reports of PSMA small molecule targeted alpha emitters have hinted at efficacy but are limited by xerostomia and in mouse models may lead to long-term renal damage. Intact mAb J591 has comparatively no to minimal distribution in salivary glands and kidneys. Preclinical studies demonstrated purity, immunoreactivity, and stability with efficacy in a xenograft model [AACR 2017]. Methods: Men with progressive mCRPC following at least 1 potent AR-targeted agent (e.g. abi/enza) and docetaxel (or unfit/refuse chemo) without limit of # prior therapies (excluding beta-emitting bone-targeted radioisotopes) provided adequate organ function will undergo imaging with 68 Ga-PSMA-11 PET/CT followed by a single dose of 225 Ac-J591. Single-subject cohorts will be enrolled until grade &gt; 1 attributable toxicity, then transition to 3+3 design. Cohort 1 = 13.3 KBq/kg with planned escalation up to 93.3 KBq/kg of 225 Ac with fixed 20 mg J591. Dose-limiting toxicity (DLT) is defined as attributable grade 4 heme toxicity or grade 3/4 non-heme toxicity. Planned cohort expansion will occur at recommended phase 2 dose (RP2D) in a 2-stage design. The primary endpoint is determination of DLT and RP2D. Secondary endpoints include toxicity, PSA decline rate, RECIST response, PFS, rPFS, OS, and patient reported outcomes (FACT-P and BPI-SF). Correlatives include baseline/follow up PSMA imaging, CTC count (CellSearch) changes, tissue and circulating genomic assessment, and immune studies. Enrollment began in October, 2017. Clinical trial information: NCT03276572.
Proposed CCG configurations and budgets are announced
Authors: Helen Jaques
Journal: BMJ (2012)

The NHS Commissioning Board has confirmed the proposed names, configurations, member practices, patient populations, and running costs of the 212 clinical commissioning groups (CCGs) that will be established in England in April 2013, subject to authorisation by the board.

Each proposed CCG has determined its own configuration within the framework set by the board, which ensured that member practices have signed up, that geographical coverage is appropriate, and that each proposed CCG is a viable organisation in terms of sharing roles and …
Perfluorocarbon Enhanced Glasgow Oxygen Level Dependent (GOLD) Magnetic Resonance Metabolic Imaging Identifies the Penumbra Following Acute Ischemic Stroke
Authors: Graeme A Deuchar, David Brennan, William M Holmes, Martin Shaw, I Mhairi Macrae, Celestine Santosh
Journal: Theranostics (2018)

The ability to identify metabolically active and potentially salvageable ischaemic penumbra is crucial for improving treatment decisions in acute stroke patients. Our solution involves two complementary novel MRI techniques (Glasgow Oxygen Level Dependant (GOLD) Metabolic Imaging), which when combined with a perfluorocarbon (PFC) based oxygen carrier and hyperoxia can identify penumbra due to dynamic changes related to continued metabolism within this tissue compartment. Our aims were (i) to investigate whether PFC offers similar enhancement of the second technique (Lactate Change) as previously demonstrated for the T2*OC technique (ii) to demonstrate both GOLD metabolic imaging techniques working concurrently to identify penumbra, following administration of Oxycyte® (O-PFC) with hyperoxia. Methods: An established rat stroke model was utilised. Part-1: Following either saline or PFC, magnetic resonance spectroscopy was applied to investigate the effect of hyperoxia on lactate change in presumed penumbra. Part-2; rats received O-PFC prior to T2*OC (technique 1) and MR spectroscopic imaging, which was used to identify regions of tissue lactate change (technique 2) in response to hyperoxia. In order to validate the techniques, imaging was followed by [14C]2-deoxyglucose autoradiography to correlate tissue metabolic status to areas identified as penumbra. Results: Part-1: PFC+hyperoxia resulted in an enhanced reduction of lactate in the penumbra when compared to saline+hyperoxia. Part-2: Regions of brain tissue identified as potential penumbra by both GOLD metabolic imaging techniques utilising O-PFC, demonstrated maintained glucose metabolism as compared to adjacent core tissue. Conclusion: For the first time in vivo, enhancement of both GOLD metabolic imaging techniques has been demonstrated following intravenous O-PFC+hyperoxia to identify ischaemic penumbra. We have also presented preliminary evidence of the potential therapeutic benefit offered by O-PFC. These unique theranostic applications would enable treatment based on metabolic status of the brain tissue, independent of time from stroke onset, leading to increased uptake and safer use of currently available treatment options.
RESTING ECHOCARDIOGRAPHIC DIASTOLIC MEASURES FAIL TO PREDICT OCCULT DIASTOLIC DYSFUNCTION AFTER RIGHT HEART CATHETERIZATION WITH FLUID CHALLENGE
Authors: Vineet Agrawal, Ivan Robbins, Tufik Assad, John M. Newman, Meredith Pugh, Anna Hemnes, Evan Brittain
Journal: Journal of the American College of Cardiology (2018)
Clinical significance of surgical treatment for imatinib-resistant gastrointestinal stromal tumors.
Authors: Tadayoshi Hashimoto, Tsuyoshi Takahashi, Yukinori Kurokawa, Ryo Kato, Noriko Wada, Koji Tanaka, Yasuhiro Miyazaki, Tomoki Makino, Makoto Yamasaki, Kiyokazu Nakajima, Masaki Mori, Yuichiro Doki
Journal: Journal of Clinical Oncology (2018)

189 Background: The standard first-line treatment for unresectable metastasis or recurrence gastrointestinal stromal tumors (GIST) is imatinib mesylate(IM), a selective tyrosine kinase inhibitor. Although IM has markedly improved the prognosis of patients with advanced GIST, half of the patients experience tumor progression within two years because of resistance to IM. And IM-resistant GIST is basically treated by other kind of TKI, in addition, surgical treatment can be considered as one of treatment options. The aim of this study was to clarify the significance of surgical treatment for IM-resistant GIST in the era of second-line TKI treatment. Methods: We retrospectively analyzed consecutive 35 GIST patients who have developed IM-resistance between 2004 and 2015. We assessed clinicopathological characteristics, postoperative outcomes, imatinib-failure free survival(IFFS), and overall survival(OS) in patients who underwent surgical resection for the IM-resistant lesions. Results: The study enrolled 24 male patients and 11 female patients. The median [range] age was 61 [39-83] years. The primary sites were stomach / small intestine / duodenum: 16 / 14 / 5 cases and resection for primary sites was performed in 32 cases. The median [range] period of IM administration until resistance was 26 [2-119] months, and the resistant lesion sites were liver / peritoneum / primary lesion / local recurrence / bone: 17 / 18 / 2 / 1 / 1 cases (with duplication). Resection for resistant lesions was performed in 18 cases (51%), of which 13 cases (72%) underwent R0 / 1 resection. The postoperative complications ( &gt; Clavien-Dindo classification Grade II) were observed in 3 patients: Biliary leakage, abdominal abscess, and diaphragmatic hernia. IM was resumed promptly after surgery in all 18 patients who underwent resection for IM-resistant lesions, and the median [range] period of IM administration was 22.2 [0.9-56] months. In 5 cases, multiple surgical treatments were performed and second-line TKI was administered in all except for two patients who have still been treated as IM. The median OS was 49 months. Conclusions: It was suggested that surgical treatment for IM-resistant GIST may be safe and effective for appropriate cases.
Gastric Metastasis of Prostate Cancer as an Unusual Presentation Using 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Hugo Enrique Solis Lara, Natalia Villarreal del Bosque, Miguel Antonio Sada Treviño, Masao Yamamoto Ramos, Rocío del Carmen Argueta Ruiz
Journal: Clinical Nuclear Medicine (2018)

A 79-year-old man with prostate cancer underwent Ga prostate-specific membrane antigen (Ga-PSMA) dual-time-point PET/CT scan to evaluate tumor activity due to early satiety, unquantified weight loss, and elevation of prostate-specific antigen (PSA), demonstrating thickening of the gastric wall with intense tracer uptake. The immunohistochemistry of gastric biopsy showed CDX2 and CK20: negative; CK7, focal positive; PSA, positive, which confirmed metastatic disease. Metastatic disease was also found in bones, right lung, and retroperitoneal and pelvic lymphadenopathies.
Plan to shorten medical training would leave doctors unable to treat complex patients without supervision, say royal colleges
Authors: Abi Rimmer
Journal: BMJ (2015)

Medical royal colleges have raised concern about the introduction of credentialing and shortening medical training, in an assessment of the Shape of Training review.1

Earlier this year the Academy of Medical Royal Colleges carried out a “mapping exercise” to find out how the royal colleges could develop recommendations made by the UK-wide Shape of Training review, which was carried out by David Greenaway, vice chancellor of Nottingham University. It received submissions from 10 royal colleges and five faculties.

One of the Shape of Training review’s recommendations was for the length of medical training to be shortened and for more doctors to become generalists.2 In a report on its mapping exercise, the Academy of Medical Royal Colleges said that almost all responses from the colleges and faculties did not support shortening …
DOES MINIMALLY-INVASIVE BYPASS SURGERY AFFORD A LONG-TERM SURVIVAL ADVANTAGE COMPARED WITH DRUG-ELUTING STENT FOR ISOLATED COMPLEX DISEASE OF THE LEFT ANTERIOR DESCENDING CORONARY ARTERY?
Authors: Nirav C. Patel, Varinder P. Singh, Karthik Seetharam, Jonathan M. Hemli, S. Jacob Scheinerman, Luigi Pirelli, Derek R. Brinster, Cindy L. Grines, Chad A. Kliger, Efstathia A. Mihelis, Michael C. Kim
Journal: Journal of the American College of Cardiology (2018)
Molecular Basis for Dysregulated Activation of <scp>NKX</scp>2‐5 in the Vascular Remodeling of Systemic Sclerosis
Authors: Athina Dritsoula, Ioannis Papaioannou, Sandra G. Guerra, Carmen Fonseca, Javier Martin, Ariane L. Herrick, David J. Abraham, Christopher P. Denton, Markella Ponticos
Journal: Arthritis & Rheumatology (2018)

NKX2-5 is a homeobox transcription factor that is required for the formation of the heart and vessels during development, with significant postnatal down-regulation and reactivation in disease states, characterized by vascular remodeling. The purpose of this study was to investigate mechanisms that activate NKX2-5 expression in diseased vessels, such as systemic sclerosis (scleroderma; SSc)-associated pulmonary hypertension (PH), and to identify genetic variability that potentially underlies susceptibility to specific vascular complications.We explored NKX2-5 expression in biopsy samples from patients with SSc-associated PH and in pulmonary artery smooth muscle cells (PASMCs) from patients with scleroderma. Disease-associated putative functional single-nucleotide polymorphisms (SNPs) at the NKX2-5 locus were cloned and studied in reporter gene assays. SNP function was further examined through protein-DNA binding assays, chromatin immunoprecipitation assays, and RNA silencing analyses.Increased NKX2-5 expression in biopsy samples from patients with SSc-associated PH was localized to remodeled vessels and PASMCs. Meta-analysis of 2 independent scleroderma cohorts revealed an association of rs3131917 with scleroderma (P = 0.029). We demonstrated that disease-associated SNPs are located in a novel functional enhancer, which increases NKX2-5 transcriptional activity through the binding of GATA-6, c-Jun, and myocyte-specific enhancer factor 2C. We also characterized an activator/coactivator transcription-enhancer factor domain 1 (TEAD1)/Yes-associated protein 1 (YAP1) complex, which was bound at rs3095870, another functional SNP, with TEAD1 binding the risk allele and activating the transcription of NKX2-5.NKX2-5 is genetically associated with scleroderma, pulmonary hypertension, and fibrosis. Functional evidence revealed a regulatory mechanism that results in NKX2-5 transcriptional activation in PASMCs through the interaction of an upstream promoter and a novel downstream enhancer. This mechanism can act as a model for NKX2-5 activation in cardiovascular disease characterized by vascular remodeling.