tbuckley/cabot-search huggingface dataset:
Minimum target prices for production of direct‐acting antivirals and associated diagnostics to combat hepatitis C virus
Authors: Nikolien van de Ven, Joe Fortunak, Bryony Simmons, Nathan Ford, Graham S. Cooke, Saye Khoo, Andrew Hill
Journal: Hepatology (2014)

Combinations of direct‐acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment‐naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large‐scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12‐week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK‐8742+MK‐5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Conclusions : Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171‐360 per person without genotyping or US$261‐450 per person with genotyping. These cost estimates assume that existing large‐scale treatment programs can be established. (H epatology 2015;61:1174–1182)
The Hard Part
Authors: Jody Bolz
Journal: JAMA (2005)

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
K-ras wild-type status predicts response to cetuximab plus FOLFIRI or FOLFOX-4 in first-line therapy of metastatic colorectal cancer
Authors: Li-Chen Yen, Erh-Jung Hsueh, Shiu-Ru Lin, Jaw-Yuan Wang
Journal: Clinical Cancer Research (2008)

B7    Background:  The combinations of cetuximab with irinotecan-based or oxaliplatin-based chemotherapy for the first-line treatment of mCRC (metastatic colorectal cancer) have been proven to be promisingly efficient; however, the response rate is variable and markers predictive of response are urgently required.  K-ras  mutation status and epidermal growth factor receptor (EGFR) have been suggested to be candidate markers for predicting survival of these patients.   Materials and Methods:  We retrospectively analyzed 78 mCRC patients receiving cetuximab plus the FOLFIRI or FOLFOX-4 chemotherapy with regard to the correlation between response rate and progression-free survival rate (PFS) as well as  K-ras  mutation status/EGFR mRNA expression using direct sequencing and membrane-array, respectively.   Results:  Of 78 mCRC patients,  K-ras   mutations were identified in 30 (38.5%) cases, and EGFR mRNA overexpression were observed in 65 patients (83.3%). Twenty-nine of 65 (44.6%) patients with EGFR mRNA overexpression responded to cetuximab, while only two patients (2/13, 15.4%) without EGFR mRNA overexpression of responded to cetuximab ( P  = 0.049, diagnostic accuracy of EGFR mRNA = 51.3%). Moreover, only patients with tumors that expressed wild-type  K-ras   responded to cetuximab_an objective response was recorded in 31 of 48 (64.6%) patients with wild-type  K-ras   tumor status but in none of the 30 patients with  K-ras   mutations ( P   K-ras  mutation status = 78.2%).  K-ras  mutation status seems to be a better predictive marker than EGFR mRNA expression for mCRC patients receiving cetuximab therapy. Additionally, patients with wild-type  K-ras   tumor status had a significantly longer median PFS than patients with  K-ras   mutations (48 weeks v.s 26 weeks;  P  = 0.023).   Conclusions:   K-ras   mutation status may be used to identify the subgroup of mCRC patients treated with cetuximab plus FOLFIRI or FOLFOX-4 in first-line therapy who are most likely to respond.
Diseases and Injuries of the Eye, with Their Medical and Surgical Treatment.
Authors: George Lawson, Arnold Lawson
Journal: JAMA (1903)

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
Randomized Trial of Acetylcysteine in Idiopathic Pulmonary Fibrosis
Authors: Fernando J. Martinez, Joao A. de Andrade, Kevin J. Anstrom, Talmadge E. King, Ganesh Raghu
Journal: New England Journal of Medicine (2014)

Acetylcysteine has been suggested as a beneficial treatment for idiopathic pulmonary fibrosis, although data from placebo-controlled studies are lacking.In our initial double-blind, placebo-controlled trial, we randomly assigned patients who had idiopathic pulmonary fibrosis with mild-to-moderate impairment in pulmonary function to receive a three-drug regimen of prednisone, azathioprine, and acetylcysteine; acetylcysteine alone; or placebo. The study was interrupted owing to safety concerns associated with the three-drug regimen. The trial continued as a two-group study (acetylcysteine vs. placebo) without other changes; 133 and 131 patients were enrolled in the acetylcysteine and placebo groups, respectively. The primary outcome was the change in forced vital capacity (FVC) over a 60-week period.At 60 weeks, there was no significant difference in the change in FVC between the acetylcysteine group and the placebo group (-0.18 liters and -0.19 liters, respectively; P=0.77). In addition, there were no significant differences between the acetylcysteine group and the placebo group in the rates of death (4.9% vs. 2.5%, P=0.30 by the log-rank test) or acute exacerbation (2.3% in each group, P>0.99).As compared with placebo, acetylcysteine offered no significant benefit with respect to the preservation of FVC in patients with idiopathic pulmonary fibrosis with mild-to-moderate impairment in lung function. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00650091.).
Abstract 11534: HMG-CoA Reductase Inhibition Enhances Renoprotective Effects of Angiotensin Receptor1 Antagonism in Salt-Sensitive Hypertensive Rats
Authors: Lina HU, Xian Wu Cheng, Zhe Huang, Takeshi Sasaki, Aiko Inoue, Hongxian Wu, Enbo Zhu, Masafumi Kuzuya, Toyoaki Murohara, Kenji Okumura
Journal: Circulation (2014)

Introduction: The mineralocorticoid receptor has been implicated in the pathogenesis of chronic cardiorenal disease. 3-hydroxy-3methylgutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, improved renal dysfunction in patients with proteinuric kidney disease. Objective: We aimed to clarify the potential effect of a statin to enhance the inhibitory effect of an angiotensin type1 receptor blocker (ARB) on renal injury and the cellular mechanism of the effect of ARB on renal remodeling and proteinuria. Methods and Results: Dahl salt-sensitive (DS) rats on a high-salt diet were randomly assigned to four groups (n = 10 for each group) that were treated with either vehicle (0.5% carboxymethyl cellulose), a low or high dosage of olmesartan (1 or 3 mg/kg/d), or pitavastatin (1 mg/kg/d) plus olmesartan (1 mg/kg/d) from 12 to 19 weeks of age. Rats fed a low-salt diet served as age-matched controls. Rats on the high-salt diet developed massive proteinuria and glomerulosclerosis, and these changes were attenuated by olmesartan in a dose-dependent manner. The amounts of mRNAs for AT1R, mineralocorticoid receptor (MR), osteopontin, monocyte chemoattractant protein-1 and collagen type I, and the activities for matrix metalloproteinase-9 and cathepsin S were significantly higher in the failing kidneys of vehicle-treated rats than in the age-matched control rats; olmesartan significantly attenuated these changes. Olmesartan attenuated both the decrease in the ratio of reduced glutathione to oxidized glutathione and the increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity apparent in the kidney cortex of vehicle-treated rats. Furthermore, olmesartan inhibited kidney cortex vascular inflammation and renal fibrosis. The addition of pitavastatin significantly enhanced these beneficial effects by AT1R antagonism via anti-inflammation and anti-proteolysis. Conclusions: The beneficial renal effects of AT1R antagonism are likely attributable, at least in part, to the attenuation of renal oxidative stress and renal vascular inflammation induced by the AT1R-MR signaling interaction. The combination of statin with ARB may be a potential therapeutic strategy for renal injury with proteinuria.
Samuel Broder, MD, Reflects on the 30th Anniversary of the National Cancer Act
Authors: S Broder
Journal: JAMA (2001)

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
Prehospital care for road traffic casualties
Authors: M. J Coates
Journal: BMJ (2002)

Editor—Coats and Davies make the point in their article that the prehospital arena is not an area where untrained and inexperienced doctors can be expected to perform at a high level.1 The point is also made, however, that all doctors may expect to pass or come across motor vehicle accidents during their lifetime and should be able to provide at least good quality first aid until other emergency services arrive at the scene. What equipment is required to enable the inexperienced doctor to provide this first aid?

Most preventable trauma deaths occurring before the emergency services arrive are caused by an obstructed airway. Many doctors carry pieces of equipment and kit just in case something happens—intravenous cannulae or drips, for example—but in reality, surprisingly little equipment is required.



A high visibility jacket is essential.


A supply of latex gloves will enable airways to be cleared and opened and pressure to be applied to bleeding points.


A pocket mask will enable ventilatory support to be given to apnoeic patients (whether due to trauma or medical causes).




Medical practitioners can rely on all other supplies coming in the ambulance response. This equipment will enable a doctor to save most salvageable trauma patients likely to die in the time between an accident occurring and an ambulance arriving, and I would recommend it as being cheap, easily acquired, and with a long life.
NIH Stem Cell Registry Online
Authors: Brian Vastag
Journal: JAMA (2001)

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
The Scientific Paper: How to Prepare It, How to Write It, A Handbook for Students and Research Workers in All Branches of Science
Authors: Sam Farlow Trelease
Journal: JAMA (1952)

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
Abstract 155: Expressions of autophagy-related proteins positively correlate with infiltration of immune cells and disease progression in oral squamous cell carcinoma
Authors: Koichi Sakakura, Hideyuki Takahashi, Kyoichi Kaira, Minoru Toyoda, Tetsunari Oyama, Kazuaki Chikamatsu
Journal: Cancer Research (2014)

Abstract Introduction: Autophagy is an endogenous process that degrades bulk proteins and organelles to maintain energy homeostasis under cellular stress and nutrient starvation. It has been still unclear whether autophagy promotes or suppresses tumor progression in various cancer patients. To date, several studies have shown that autophagy-related molecules such as LC3 and Beclin-1 play important roles in tumor progression; however, few studies regarding immunological significance of these autophagy components in tumor microenvironment exist. The objective of this study is to clarify association between the expression of autophagy-related proteins and immune infiltrates by immunohistochemistry (IHC). Patients and methods: Expression of two representative autophagy-associated molecules, LC3 and Beclin-1, and CD1a (dendritic cell), CD3 (T cell) and CD56 (NK cell) cells were examined by IHC in 74 patients with oral squamous cell carcinoma (OSCC). HLA class I heavy chain, HLA class II, Ki-67 and p53 were also stained and assessed. Two regions, central site and peripheral site in tumor tissues were evaluated, separately. Moreover, the association with various clinicopathological parameters including progression free and overall survival was evaluated. Results: LC3 and Beclin-1 were accumulated in both 27 of 74 cases (36.5%) OCCC examined. LC3 expression in peripheral margin was significantly associated with increasing dendritic cell (DC) and T cell infiltration. Interestingly, peripheral Beclin-1 expression showed statistically significant relation to increasing HLA class II expression on tumor cells. On the other hand, LC3 and Beclin-1 significantly correlates with several unfavorable clinicopathological parameters including short overall survival. In addition, LC3 and Beclin-1 expression in OSCC significantly related to lymphatic invasion by tumor cells. Conclusion: Significant association between LC3 and DC/T cell infiltration suggests that autophagy is likely to actively participate in immunological phenomena within tumor microenvironment. Furthermore, peripheral Beclin-1 may contribute to antigen presentation by tumor cells, while these two autophagy components also relates to unfavorable prognosis. Taken together, autophagy seems to promote immunogenicity of cancer cells, whereas it facilitates tumor progression. Citation Format: Koichi Sakakura, Hideyuki Takahashi, Kyoichi Kaira, Minoru Toyoda, Tetsunari Oyama, Kazuaki Chikamatsu. Expressions of autophagy-related proteins positively correlate with infiltration of immune cells and disease progression in oral squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 155. doi:10.1158/1538-7445.AM2014-155
103. Comparison of the Efficacy on Gene Transfer by AAV Vectors Delivered by Distinct Routes of Administration to the Liver of Hemophilia B Dogs
Authors: Valder Arruda, Ciaran Scallan, Haiyan Jiang, Linda Couto, Roland W. Herzog, Timothy Nichols, Glenn Pierce, Katherine A. High
Journal: Molecular Therapy (2004)

We and others showed long-term expression of therapeutic levels of FIX in small as well as large animal models treated by muscle-directed or liver-directed administration of an AAV-2 vector. Liver-directed gene transfer in hemophilia B dogs resulted in significantly higher levels (10–20 fold) of FIX than IM injection of the same vector dose. Intravenous injection of rAAV-2 results in 4–10 fold less hepatic transduction when compared to portal vein infusion in mice. Others have reported that infusion of vector via portal vein is more efficient than hepatic artery in large animals (Blood,100:1662, 2002). In an ongoing Phase I clinical study the vector has been delivered through a catheter placed in the hepatic artery of subjects with severe hemophilia B. The procedure has been safe and well tolerated at doses tested. Here we sought to determine whether delivery of AAV-2 vector encoding canine F.IX under the control of a liver specific promotor (hAAT/ApoE) to the liver by hepatic artery (HA) or portal vein (PV) would differ in terms of transgene expression. Three dogs with severe hemophilia B AAV-2 vector at doses ranging from 1×1012 to 1×1013 vg/kg through a catheter placed in the hepatic artery. Circulating F.IX increased slowly over a period of weeks following vector injection. After 4 weeks, mean F.IX plasma levels were 317 ng/ml and 359 ng/ml from animals treated with the high dose, and 190 ng/ml for the animal treated with 1 × 1012 vg/kg. No abnormalities of liver enzymes and no inhibitor to F.IX were detected. For portal vein injection we injected three dogs with doses of ~1×1012 vg/kg resulting in F.IX plasma levels of 300–400 ng/ml. These data though not statistically different, suggest that portal vein delivery may be more efficient than hepatic artery. This question merits further study in large animal model.
Evidence based paediatrics: Evidence based well child care
Authors: E. Dinkevich, J. Hupert, V. A Moyer
Journal: BMJ (2001)

This is the first in a series of five articles 

Your primary care paediatric practice has recently decided to review its preventive care practices before deciding which to include in a new computerised record system. You know that these practices vary considerably among group members, even as to how many check ups a child really needs. The value of some specific manoeuvres, such as the Adams forward bend test for scoliosis, for which adolescents are often referred from school, is doubted. You determine to find the best evidence for common preventive health interventions for children.

#### Summary points

Fewer visits than in the standard schedules for children up to age 2 years are sufficient to detect physical abnormalities and psychosocial and developmental outcomes

Group care is as effective as individual care for routine checks

The Adams forward bend test is not accurate enough for screening for idiopathic scoliosis

Proving the value of check ups for healthy children and finding new and more effective ways to provide preventive care to all children remain major challenges

Routine checks on apparently healthy children are an important part of preventive services available for children. In developed countries outside the United States, paediatricians are trained to practise as hospital based specialists providing clinical care, while general practitioners and public health nurses are responsible for preventive care, including care of healthy children.1 In the United States, general paediatricians provide both preventive and clinical care and spend as much as 40% of their time checking healthy children.2

The major objective of these check ups is maintenance of health and prevention of disease. This is traditionally accomplished by repeated evaluations of healthy children under five heads: screening, health promotion, disease prevention, patient management, and follow up.

A routine check up includes history taking, physical examination, observation of parent-child interaction, …