tbuckley/cabot-search huggingface dataset:
“Low priority” prescription items include silk garments, minocycline, and gluten-free foods
Authors: Gareth Iacobucci
Journal: BMJ (2018)

NHS England has launched a fresh crackdown on GPs’ prescribing of “low priority” items in a bid to save £70m (€79m; $89m) a year to reinvest in other areas.

A consultation launched on 28 November asks for views on restricting the availability of items such as silk garments and bath oils for treating eczema, as well as dronedarone for atrial fibrillation and minocycline for acne.

It also proposes switching prescriptions of some items, such as blood glucose testing strips and the needles used for pre-filled and reusable insulin pens, that are clinically effective but …
Sex‐ and age‐adjusted prevalence estimates of skin types and unpleasant skin sensations and their consequences on quality of life: results of a study of a large representative sample of the French population
Authors: L. Misery, K. Ezzedine, F. Corgibet, N. Dupin, J.F. Sei, C. Philippe, P. Joly, C. Taieb, M.A. Richard
Journal: British Journal of Dermatology (2018)
Neuropathology of Circadian Alterations in Parkinson Disease—Reply
Authors: Eduardo De Pablo-Fernández, Thomas T. Warner, Janice L. Holton
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
Abstract 20073: Waist Circumference is Superior to BMI in Predicting Cardiovascular Risk Factors in a Rural Indigenous Mayan Population in Guatemala
Authors: David Chen, Mark Deboer, Alvaro Rivera-Andrade, Carlos Mendoza-Montano, David Burt, Jessica Gonzalez, Max Luna
Journal: Circulation (2014)

Introduction: Like other developing countries, Guatemala appears to be in epidemiologic transition from infectious diseases to non-communicable diseases such as cardiovascular disease (CVD), unders...
2018 ACC Expert Consensus Decision Pathway on Novel Therapies for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease
Authors: Sandeep R. Das, Brendan M. Everett, Kim K. Birtcher, Jenifer M. Brown, William T. Cefalu, James L. Januzzi, Rita Rastogi Kalyani, Mikhail Kosiborod, Melissa L. Magwire, Pamela B. Morris, Laurence S. Sperling
Journal: Journal of the American College of Cardiology (2018)
STING Promotes Homeostasis via Regulation of Cell Proliferation and Chromosomal Stability
Authors: Diana Rose E. Ranoa, Ryan C. Widau, Stephen Mallon, Akash D. Parekh, Claudia M. Nicolae, Xiaona Huang, Michael J. Bolt, Ainhoa Arina, Renate Parry, Stephen J. Kron, George-Lucian Moldovan, Nikolai N. Khodarev, Ralph R. Weichselbaum
Journal: Cancer Research (2018)

Abstract Given the integral role of stimulator of interferon genes (STING, TMEM173) in the innate immune response, its loss or impairment in cancer is thought to primarily affect antitumor immunity. Here we demonstrate a role for STING in the maintenance of cellular homeostasis through regulation of the cell cycle. Depletion of STING in human and murine cancer cells and tumors resulted in increased proliferation compared with wild-type controls. Microarray analysis revealed genes involved in cell-cycle regulation are differentially expressed in STINGko compared with WT MEFs. STING-mediated regulation of the cell cycle converged on NFκB- and p53-driven activation of p21. The absence of STING led to premature activation of cyclin-dependent kinase 1 (CDK1), early onset to S-phase and mitosis, and increased chromosome instability, which was enhanced by ionizing radiation. These results suggest a pivotal role for STING in maintaining cellular homeostasis and response to genotoxic stress. Significance: These findings provide clear mechanistic understanding of the role of STING in cell-cycle regulation, which may be exploited in cancer therapy because most normal cells express STING, while many tumor cells do not. See related commentary by Gius and Zhu, p. 1295
Sun protection behavior after diagnosis of high-risk primary melanoma and risk of a subsequent primary
Authors: Lena A. von Schuckmann, Louise F. Wilson, Maria Celia B. Hughes, Vanessa L. Beesley, Monika Janda, Jolieke C. van der Pols, B. Mark Smithers, Kiarash Khosrotehrani, Adele C. Green
Journal: Journal of the American Academy of Dermatology (2018)
Whole Genome Sequencing Reveals Recurrent Structural Driver Events in Peripheral T-Cell Lymphomas Not Otherwise Specified
Authors: Francesco Maura, Niccolò Bolli, Daniel Leongamornlert, Cristiana Carniti, Anna Dodero, Federico Abascal, Adele Testi, Bernardo Rodriguez-Martin, Alessio Pellegrinelli, Giulia Biancon, Martina Magni, Annalisa Chiappella, Inigo Martincorena, Jose M. C. Tubio, Giancarlo Pruneri, Peter J. Campbell, Paolo Corradini
Journal: Blood (2018)
Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study
Authors: S. Adams, P. Schmid, H.S. Rugo, E.P. Winer, D. Loirat, A. Awada, D.W. Cescon, H. Iwata, M. Campone, R. Nanda, R. Hui, G. Curigliano, D. Toppmeyer, J. O’Shaughnessy, S. Loi, S. Paluch-Shimon, A.R. Tan, D. Card, J. Zhao, V. Karantza, J. Cortés
Journal: Annals of Oncology (2018)

Treatment options for previously treated metastatic triple-negative breast cancer (mTNBC) are limited. In cohort A of the phase II KEYNOTE-086 study, we evaluated pembrolizumab as second or later line of treatment for patients with mTNBC.
Global childhood pneumonia: the good news, the bad news, and the way ahead
Authors: Stephen R C Howie, David R Murdoch
Journal: The Lancet Global Health (2018)

Globally, pneumonia accounts for a substantial burden of disease among young children, and consequently must be a major focus of efforts to improve child health. In their systematic analysis published in The Lancet Global Health, David A McAllister and colleagues1 report encouraging estimates: between 2000 and 2015, the global incidence of pneumonia in young children (aged <5 years) reduced by 30% and the number of pneumonia deaths in young children almost halved in that time. However, pneumonia remains a leading cause of preventable illness and death in this age group, and overcoming this will require considerable effort.
Abstract 19221: Low Mortality and Rate of Cardiac Events in Patients After Acute Coronary Syndrome Systematically Managed by Office-based Cardiologists in Germany: 1-year Outcomes of the ProAcor Study
Authors: Franz Goss, Winfried Haerer, Johannes Brachmann, Christian W Hamm, Nicolaus Reifart, Benny Levenson
Journal: Circulation (2015)

Background/Introduction: The ProAcor Study assessed the effectiveness of a structured patient management program over 12 months in patients who were discharged from hospital after an acute coronary syndrome (ACS) into ambulatory cardiology care (36 hospitals, 56 office-based cardiologists). Methods: The program comprised patient documentation with a specific instrument (BNK cardiac pass with visit scheduling) done jointly by the hospital physician and the office-based cardiologists, the definition of treatment targets and the structured information of patients in order to optimise adherence to therapy. Results: 992 patients with ACS were included (STEMI 44.3%, NSTEMI 39.5%, unstable angina pectoris UA 15.2%). In these groups, acute intervention PTCA was performed in 98.0%, 91.9% and 81.6% of patients, stent implantation in 98.6%, 95.6% and 92.7%, and coronary artery bypass graft in 0.7%, 2.5% and 3.3%, respectively. Mean hospital stay due to ACS was 6 days (median). At 12 months, 18 patients (1.8%) had died (among these, 9 due to cardiac event), while for 51 the status was unknown (5.1%). Based on a conservative approach that considered patients with unknown status as dead, 1-year mortality was 6.9%. Further data on non-fatal cardiac events, medication and quality of life (QoL) were collected from 796 patients (79.4%). Recurrent cardiac events were noted in 119 patients (14.9%), with an about equal distribution across STEMI and NSTEMI patients. On the EQ-5D visual analogue scale (0= worst, 100 best state of health) at 3 months as well as 12 months the median value was 80 points with little differences between subgroups. The EQ-5D index score was 0.91 ± 0.18 points at inclusion (STEMI 0.92, NSTEMI 0.90, UA 0.89) and was unchanged at 12 months. Conclusion: Compared to data based on usual care (e.g. German MONICA registry 13.3%), the 1-year mortality after ACS of only 6.9% in the structured ProAcor patients management program is remarkably low.
Abstract 19993: Burden of Coronary Atherosclerosis and Cardiovascular Events in Men and Women with Stable Ischemic Heart Disease
Authors: Subroto Acharjee, William Boden, Pamela Hartigan, Koon Teo, David Maron, Steven Sedlis, William Kostuk, John Spertus, Marcin Dada, Bernard Chaitman, G.B John Mancini, William Weintraub
Journal: Circulation (2014)

Background: Recent post hoc analyses from COURAGE have identified coronary anatomic burden, but not ischemic burden, as an important predictor of outcomes in patients with stable ischemic heart dis...
Barriers to widespread implementation of patient-reported outcome platforms for cancer patients.
Authors: Jungyeon Park, Júlia Carolina Almeida Chaves
Journal: Journal of Clinical Oncology (2018)

107 Background: Patient-reported outcome (PRO) platforms for cancer patients have shown to be effective in improving overall survival, quality of life, and adherence to medication in studies. However, due to controlled environments and limited regional scope, they do not shed light on the barriers for widespread PRO implementation. This study aims to identify such barriers by studying user demographics and usage patterns of an existing free Brazilian PRO mobile app. Methods: From Dec. 2016 to Jul. 2018, 1,246 cancer patients voluntarily registered on the mobile app downloadable on Google Play Store. Patients could report symptoms, physical activity, hours of sleep, weight, fever, overall well-being, and reasons for gratitude on the app. Other features included alarms for medications and a record of patients' hospitals and medical staff. Data collected by the app were analyzed for primary outcomes of user demographics and app usage patterns. Results: Out of the 1,246 registered patients, 44.1% were between the ages of 20 and 49 while only 11.3% were over the age of 65. Half of the patients never logged symptoms, and only 3.2% recorded symptoms more than 10 times. Physical activity, hours of sleep, and weight were each reported by less than 2% of patients. Surprisingly, 37.7% of patients recorded reasons for gratitude a mean of 3.2 times (SD = 10.3), more than the mean 2.9 times (SD = 8.6) that patients reported symptoms. Reporting overall well-being was the most used feature with 50.3% of patients having used it at least once with a mean of 3.9 times (SD = 17.2). Conclusions: Compared to closed short-term small-scale studies, patients engaged significantly less with the unrestricted open-access PRO platform, in particular geriatric patients. This is a significant barrier to widespread implementation as PRO's efficacy relies on consistent patient reports, and as cancer is more common among the elderly. These issues may be due to lack of guidance and supervision from medical/non-medical staff, absence of education on PRO's purpose, or access to technology caused by regional cultural differences. Further research on the cause of and solution for low patient engagement is needed for successful implementation in less-guided environments.
Functional Analysis and Fine Mapping of the 9p22.2 Ovarian Cancer Susceptibility Locus
Authors: Melissa A. Buckley, Nicholas T. Woods, Jonathan P. Tyrer, Gustavo Mendoza-Fandiño, Kate Lawrenson, Dennis J. Hazelett, Hamed S. Najafabadi, Anxhela Gjyshi, Renato S. Carvalho, Paulo C. Lyra, Simon G. Coetzee, Howard C. Shen, Ally W. Yang, Madalene A. Earp, Sean J. Yoder, Harvey Risch, Georgia Chenevix-Trench, Susan J. Ramus, Catherine M. Phelan, Gerhard A. Coetzee, Houtan Noushmehr, Timothy R. Hughes, Thomas A. Sellers, Ellen L. Goode, Paul D. Pharoah, Simon A. Gayther, Alvaro N.A. Monteiro
Journal: Cancer Research (2018)

Abstract Genome-wide association studies have identified 40 ovarian cancer risk loci. However, the mechanisms underlying these associations remain elusive. In this study, we conducted a two-pronged approach to identify candidate causal SNPs and assess underlying biological mechanisms at chromosome 9p22.2, the first and most statistically significant associated locus for ovarian cancer susceptibility. Three transcriptional regulatory elements with allele-specific effects and a scaffold/matrix attachment region were characterized and, through physical DNA interactions, BNC2 was established as the most likely target gene. We determined the consensus binding sequence for BNC2 in vitro, verified its enrichment in BNC2 ChIP-seq regions, and validated a set of its downstream target genes. Fine-mapping by dense regional genotyping in over 15,000 ovarian cancer cases and 30,000 controls identified SNPs in the scaffold/matrix attachment region as among the most likely causal variants. This study reveals a comprehensive regulatory landscape at 9p22.2 and proposes a likely mechanism of susceptibility to ovarian cancer. Significance: Mapping the 9p22.2 ovarian cancer risk locus identifies BNC2 as an ovarian cancer risk gene. See related commentary by Choi and Brown, p. 439
#12 Proposed randomised controlled feasibility trial of a novel polyvinylideneflouride (PVDF) mesh (Dynamesh®-HIATUS) cruroplasty versus suture-only repair of large hiatus hernia: the DYNAMIC Study (oral presentation)
Authors: S. Toh, B. Knight, C. Fogg, E. Baddesley, A. Higginson, R. Beable, S. Babu, E. Hawes, M. Moon, J. Shoebridge, P. Meredith, M. Amos-Lyons, P. May-Miller
Journal: International Journal of Surgery (2018)
Interstitial Lung Disease Onset and Its Risk Factors in Japanese Patients With ALK-Positive NSCLC After Treatment With Crizotinib
Authors: Akihiko Gemma, Masahiko Kusumoto, Yasuyuki Kurihara, Noriyuki Masuda, Shigeo Banno, Yutaka Endo, Hiroyuki Houzawa, Naomi Ueno, Emiko Ohki, Akinobu Yoshimura
Journal: Journal of Thoracic Oncology (2018)
A Gene Expression Classifier from Whole Blood Distinguishes Benign from Malignant Lung Nodules Detected by Low-Dose CT
Authors: Andrew V. Kossenkov, Rehman Qureshi, Noor B. Dawany, Jayamanna Wickramasinghe, Qin Liu, R. Sonali Majumdar, Celia Chang, Sandy Widura, Trisha Kumar, Wen-Hwai Horng, Eric Konnisto, Gerard Criner, Jun-Chieh J. Tsay, Harvey Pass, Sai Yendamuri, Anil Vachani, Thomas Bauer, Brian Nam, William N. Rom, Michael K. Showe, Louise C. Showe
Journal: Cancer Research (2018)

Low-dose CT (LDCT) is widely accepted as the preferred method for detecting pulmonary nodules. However, the determination of whether a nodule is benign or malignant involves either repeated scans or invasive procedures that sample the lung tissue. Noninvasive methods to assess these nodules are needed to reduce unnecessary invasive tests. In this study, we have developed a pulmonary nodule classifier (PNC) using RNA from whole blood collected in RNA-stabilizing PAXgene tubes that addresses this need. Samples were prospectively collected from high-risk and incidental subjects with a positive lung CT scan. A total of 821 samples from 5 clinical sites were analyzed. Malignant samples were predominantly stage 1 by pathologic diagnosis and 97% of the benign samples were confirmed by 4 years of follow-up. A panel of diagnostic biomarkers was selected from a subset of the samples assayed on Illumina microarrays that achieved a ROC-AUC of 0.847 on independent validation. The microarray data were then used to design a biomarker panel of 559 gene probes to be validated on the clinically tested NanoString nCounter platform. RNA from 583 patients was used to assess and refine the NanoString PNC (nPNC), which was then validated on 158 independent samples (ROC-AUC = 0.825). The nPNC outperformed three clinical algorithms in discriminating malignant from benign pulmonary nodules ranging from 6-20 mm using just 41 diagnostic biomarkers. Overall, this platform provides an accurate, noninvasive method for the diagnosis of pulmonary nodules in patients with non-small cell lung cancer. SIGNIFICANCE: These findings describe a minimally invasive and clinically practical pulmonary nodule classifier that has good diagnostic ability at distinguishing benign from malignant pulmonary nodules.
Evaluation of Oxalate Osteopathy Secondary to Hyperoxaluria With 18F-FDG PET/CT and 99mTc-HMDP Bone Scan
Authors: François Somme, Cyrille Blondet, Julien Matuszak, Céline Heimburger
Journal: Clinical Nuclear Medicine (2018)

We report a case of a 69-year-old woman with primary hyperoxaluria type I, who developed a severe hypercalcemia despite controlled secondary hyperparathyroidism. Bone scintigraphy showed diffuse increased uptake in axial and peripheral skeleton. F-FDG PET/CT showed countless striking hypermetabolic foci, interesting 2 types of lesions (joint calcifications and periosteal resorptions). Bone biopsy demonstrated inflammatory changes around many calcium oxalate crystals; hypercalcemia was then related to oxalate osteopathy. Immunotherapy with denosumab was thus initiated. Eighteen months later, a second PET/CT showed decreased F-FDG uptake, reflecting treatment efficacy on inflammatory reaction secondary to calcium oxalosis skeletal deposits.
A young woman with fever and loss of consciousness
Authors: Selina J Chavda, Lucy Pickard, Alison Thomas, James Uprichard
Journal: BMJ (2018)

A 22 year old woman was admitted to hospital with confusion, pyrexia, and two episodes of loss of consciousness while at work that day. She described having felt tired in the preceding week. She had no medical history of note and did not smoke or drink alcohol. She did not take any regular medications and did not use recreational drugs. The patient was born in the UK. Her parents were from Nigeria. She had no recent foreign travel or contact with anyone who was unwell.

Her heart rate was 115 beats/min, blood pressure 100/80 mm Hg, temperature 38.5°C, respiratory rate 20 breaths/min, and oxygen saturations 100% on room air. Blood results are shown in table 1 and blood film in fig 1.

View this table:

Table 1 
Blood test results





Fig. 1 
Blood film ×40 magnification



1.  What is the most likely diagnosis?

2.  What other initial tests are important?

3.  How is this condition treated?

### 1. What is the most likely diagnosis?

The following factors make thrombotic thrombocytopenic purpura (TTP) the most likely diagnosis:



Fig. 2 
Blood film ×40 magnification showing schistocytes and thrombocytopenia



TTP requires immediate haematologist assessment. TTP is a thrombotic microangiopathy. Haemolytic uraemic syndrome, another thrombotic microangiopathy, is a differential.

Thrombotic microangiopathy (TMA) is indicated by thrombocytopenia in the full blood count and microangiopathic haemolytic anaemia on the blood film.1 ADAMTS13 enzyme activity …
The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Authors: Konstantin Kazankov, Simon Mark Dahl Jørgensen, Karen Louise Thomsen, Holger Jon Møller, Hendrik Vilstrup, Jacob George, Detlef Schuppan, Henning Grønbæk
Journal: Nature Reviews Gastroenterology & Hepatology (2018)
IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps
Authors: Feng Lan, Hua Zhong, Nan Zhang, Sebastian L. Johnston, Weiping Wen, Nikos Papadopoulos, Luo Zhang, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 19478: Endothelial and Cardiomyocyte -derived C-type Natriuretic Peptide Coordinate Heart Structure and Function
Authors: Amie J Moyes, Sandy M Chu, Reshma S Baliga, Adrian J Hobbs
Journal: Circulation (2015)

Background: Endothelium-derived C-type natriuretic peptide (CNP) plays a key vascular homeostatic role governing vascular tone, blood pressure, leukocyte flux, platelet reactivity and the integrity of the vessel wall. However, relatively little is known about physiological role(s) for endogenous CNP in regulating cardiac structure and function. Herein, we have utilised novel mouse strains with endothelium or cardiomyocyte -specific deletion of CNP to determine if the peptide modulates heart function under basal conditions and during cardiac stress. Methods: Blood pressure and ECG were assessed by radiotelemetry. A Langendorff heart model was used to study coronary vascular reactivity and ischemia-reperfusion (I/R) injury ex vivo. Echocardiography was performed to determine cardiac function at baseline and following pressure overload (trans-aortic constriction; 6 weeks) -induced left ventricular hypertrophy/heart failure. Results: Hearts from endothelium-specific CNP knockout (ecCNP KO) mice exhibited smaller reductions in coronary perfusion pressure (CPP) compared to wildtype (WT) littermates in response to the vasodilators bradykinin (ΔCPP: WT=31.7±2.7%, KO=21.1±2.9%, n=8, p&lt;0.05) and acetylcholine (ΔCPP: WT=36.4±4.4%, KO=18.5±3.8%, n=6, p&lt;0.05). Shear-stress induced coronary dilatation (i.e. reactive hyperaemia) was also blunted in ecCNP KO hearts (AUC: WT=2804±280 [a.u.], KO=1493±280 [a.u.], n=8, p&lt;0.05). Under basal conditions the heart rate (BPM: WT=605±5, KO 579±4, n=5, p&lt;0.001) and contractility (QA interval; WT=13.7±0.1ms, KO=14.8±0.1ms, n=5, p&lt;0.001) were significantly reduced in cardiomyocyte-specific CNP (cmCNP) KO mice compared to WT. Myocardial infarct size was larger in cmCNP KO following I/R injury ex vivo (Infarct size: WT=14.1±6.3%, KO=21.8±1.8 %, n=6, p&lt;0.05). Furthermore, cmCNP KO mice exhibited greater cardiac dysfunction following pressure-overload (e.g. fractional shortening: WT=34.4±0.9%, KO=30.5±1.4%, n=8, p&lt;0.05). Conclusion: These data suggest that CNP of endothelial and cardiomyocyte origin preserves cardiac function and morphology via the regulation of coronary vascular tone, heart rate, and myocardial contractility/hypertrophy.
GMC appeal refused in case of surgeon who escaped sanction for sexual misconduct
Authors: Clare Dyer
Journal: BMJ (2018)

The General Medical Council has lost an appeal against a medical practitioners tribunal’s decision to impose no sanction on a doctor found guilty of sexual misconduct and abuse of trust.1

Three judges at the Court of Session in Edinburgh ruled that the tribunal was entitled to treat Milind Mehta’s case as exceptional because of the steps he took to help others learn from his misconduct.

Mehta, 48, an orthopaedic surgeon at Dr Gray’s Hospital …