tbuckley/cabot-search huggingface dataset:
Changes in Retail Prices of Prescription Dermatologic Drugs From 2009 to 2015
Authors: Miranda E. Rosenberg, Steven P. Rosenberg
Journal: JAMA Dermatology (2015)

<h3>Importance</h3> Physicians from many specialties as well as primary care prescribe dermatologic medications; as insurance formularies become increasingly restrictive and more patients are covered with high-deductible insurance plans, many patients are forced to pay high retail prices to obtain their medications. <h3>Objectives</h3> To determine the changes in the prices of commonly prescribed dermatologic medications since 2009 and to identify trends in price increases for different classes of drugs. <h3>Design, Setting, and Participants</h3> Four national chain pharmacies received surveys requesting price data on commonly prescribed dermatologic drugs in 2009, 2011, 2014, and 2015. The initial survey requested information on 72 brand-name drugs. Subsequent surveys increased to eventually include 120 additional brand-name drugs and their generic alternatives when available. Owing to the frequency of prescription, diseases treated, or unusual price increases, 19 brand-name drugs surveyed in all 4 years were selected for final price trend analysis, which was conducted from August 1 to 15, 2015. <h3>Main Outcomes and Measures</h3> Retail prices of topical and systemic drugs for the treatment of various dermatologic conditions. <h3>Results</h3> Prices of surveyed brand-name drugs increased rapidly between 2009 and 2015. Of the 19 brand-name drugs analyzed, the retail prices of 7 drugs more than quadrupled during the study period. Among these 19 drugs, the mean price increase was 401% during the 6-year survey period, with the majority of the price increases occurring after 2011. Prices of topical antineoplastic drugs had the greatest mean absolute and percentage increase ($10 926.58 [1240%]). Prices of drugs in the antiinfective class had the smallest mean absolute increase ($333.99); prices of psoriasis medications had the smallest mean percentage increase (180%). Prices of acne and rosacea medications increased a mean of 195%, and prices of topical corticosteroids increased a mean of 290% during the study period. Selected generic drugs surveyed in 2011 and 2014 also increased a mean of 279% during the 3-year period. <h3>Conclusions and Relevance</h3> The price of prescription dermatologic drugs rose considerably from 2009 to 2015, with the vast majority of price increases occurring after 2011. Percent increases for multiple, frequently prescribed medications greatly outpaced inflation, national health expenditure growth, and increases in reimbursements for physician services.
PIK3CAH1047R Accelerates and Enhances KRASG12D-Driven Lung Tumorigenesis
Authors: Shon Green, Christy L. Trejo, Martin McMahon
Journal: Cancer Research (2015)

KRAS-activating mutations drive human non-small cell lung cancer and initiate lung tumorigenesis in genetically engineered mouse (GEM) models. However, in a GEM model of KRAS(G12D)-induced lung cancer, tumors arise stochastically following a latency period, suggesting that additional events are required to promote early-stage tumorigenic expansion of KRAS(G12D)-mutated cells. PI3Kα (PIK3CA) is a direct effector of KRAS, but additional activation of PI3'-lipid signaling may be required to potentiate KRAS-driven lung tumorigenesis. Using GEM models, we tested whether PI3'-lipid signaling was limiting for the promotion of KRAS(G12D)-driven lung tumors by inducing the expression of KRAS(G12D) in the absence and presence of the activating PIK3CA(H1047R) mutation. PIK3CA(H1047R) expression alone failed to promote tumor formation, but dramatically enhanced tumorigenesis initiated by KRAS(G12D). We further observed that oncogenic cooperation between KRAS(G12D) and PIK3CA(H1047R) was accompanied by PI3Kα-mediated regulation of c-MYC, GSK3β, p27(KIP1), survivin, and components of the RB pathway, resulting in accelerated cell division of human or mouse lung cancer-derived cell lines. These data suggest that, although KRAS(G12D) may activate PI3Kα by direct biochemical mechanisms, PI3'-lipid signaling remains rate-limiting for the cell-cycle progression and expansion of early-stage KRAS(G12D)-initiated lung cells. Therefore, we provide a potential mechanistic rationale for the selection of KRAS and PIK3CA coactivating mutations in a number of human malignancies, with implications for the clinical deployment of PI3' kinase-targeted therapies.
Should be offered to appropriately selected patients
Authors: P. Humphrey, P. Enevoldson, G. Young, P. Harris
Journal: BMJ (1995)

EDITOR,—Roger N Baird and Mark Lambert debate whether carotid endarterectomy should be purchased.1 There is no doubt that carotid endarterectomy works.2 Starting another trial in symptomatic patients with tight stenoses would be unethical as the two large trials in Europe and North America have proved beyond doubt that this operation is highly successful.3 It is medically indefensible not to offer this operation to appropriate patients; if these patients are denied surgery then before long they will seek compensation in the courts and …
EDUCATION AND INTERPRETATION
Authors: George K. Pratt
Journal: American Journal of Psychiatry (1924)

1. Mental hygiene believes it possesses a commodity, the sale and use of which will help in lightening some of the social, health, and economic burdens of every community. 2. The educational portion of a mental hygiene program must be looked on in terms of a commercial problem. 3. Before this commodity can secure public acceptance, a vigorous campaign of education and interpretation must be undertaken. The idea of mental health must be thoroughly sold before its principles can be practically applied through clinical measures. 4. In the process of "selling" mental hygiene to the lay public a disregard for the necessity of getting down to the level of understanding of the average citizen will retard progress. It has been found that even when addressing such professional groups as general physicians, nurses, and college graduates, one must not take for granted any degree of previous knowledge of the subject. This may sound dogmatic but a not inextensive experience in such work confirms this view. 5. Not only is education a prerequisite for "selling" mental health, but a proper interpretation of the principles involved must go hand in hand with enlightenment. 6. The best equipped mental clinic available cannot function to capacity until a clientele is established and until the public knows what it is for, what kinds of cases it treats, and why they should not stigmatize or be suspicious of its purpose. This preparatory work can only be accomplished through an intensive educational campaign, preferably by a neutral, private, and unbiased agency. 7. Methods of education include use of: (a) Lectures. (b) Instruction courses. (c) Literature. (d) Exhibits. (e) Legislation.
Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration
Authors: Francisco A. Folgar, Eric L. Yuan, Monica B. Sevilla, Stephanie J. Chiu, Sina Farsiu, Emily Y. Chew, Cynthia A. Toth
Journal: Ophthalmology (2015)
Influence of treatment schedule on toxicity and efficacy of cyclophosphamide, epirubicin, and fluorouracil in metastatic breast cancer: a randomized trial comparing weekly and every-4-week administration.
Authors: C Blomqvist, I Elomaa, P Rissanen, P Hietanen, K Nevasaari, L Helle
Journal: Journal of Clinical Oncology (1993)

PURPOSE To compare the effect on toxicity and efficacy of the fluorouracil 500 mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 500 mg/m2 (FEC) regimen divided into 4 weekly doses with conventional every-4-week administration in metastatic breast cancer. PATIENTS AND METHODS The inclusion criteria demanded measurable or assessable metastases from breast cancer and a World Health Organization (WHO) performance index of 2 or less. One hundred seventy-three patients with metastatic breast cancer who had not been treated with anthracyclines were randomized to receive FEC once every 4 weeks or once a week. The scheduled monthly doses of the cytotoxic agents were identical in both groups. Three patients were excluded from analysis. RESULTS Hematologic toxicity, alopecia, nausea, and vomiting were significantly more severe in the group that received treatment every 4 weeks. The response rate was higher in the group that received FEC every 4 weeks than in the group treated weekly (47% v 30%, P = .02). Time to progression was significantly (P = .005) longer with every-4-week FEC treatment (median, 9.2 months v 5.4 months for weekly treatment). Patients in the group treated every 4 weeks lived significantly (P = .01) longer than patients treated weekly (median survival times, 21.2 months v 11.8 months, respectively). The actually delivered monthly dose levels and treatment duration were similar in the two groups. CONCLUSION Both efficacy and toxicity of FEC were greater when treatment was administered every 4 weeks rather than once a week, despite identical dose intensity.
A totally implanted venous access system used in pediatric patients with cancer.
Authors: R J Shulman, S Rahman, D Mahoney, W J Pokorny, R Bloss
Journal: Journal of Clinical Oncology (1987)

A safe and effective method of venous access is important in the care and treatment of patients with malignancies. A recently available totally implantable venous access system offers advantages over traditional central vein catheters (Broviac and Hickman, Houston). We report our experience with the implanted venous access system used in 31 pediatric patients with malignancies. The mean age of the patients was 7 years (range, 6 months to 17 years), and the mean indwelling time of the catheters was 232 days (range, 14 to 607 days; total patient days, 7,198). The catheters were used to administer chemotherapy, drugs, blood products, and parenteral nutrition, as well as to draw blood. Clotting occurred in the catheters on four occasions, requiring removal of two catheters. Fever occurred in eight patients; one developed a local infection at the site of implantation and four developed bacteremia. Our use of the implanted venous access system in children resulted in a lower rate of infection compared with that when the traditional Broviac and Hickman catheters were used, and simplified patient management.
Comprehensive analyses using next-generation sequencing and immunohistochemistry enable precise treatment in advanced gastric cancer
Authors: Y. Kuboki, S. Yamashita, T. Niwa, T. Ushijima, A. Nagatsuma, T. Kuwata, T. Yoshino, T. Doi, A. Ochiai, A. Ohtsu
Journal: Annals of Oncology (2015)
PO57SAFETY AND EFFICACY OF PREOPERATIVE CORTICAL MAPPING USING A NAVIGATED TRANSCRANIAL MAGNETIC STIMULATION (NTMS) TECHNOLOGY IN PATIENTS HARBORING BRAIN TUMOURS IN ELOQUENT AREAS
Authors: J. Ekanayake, G. Samandouras
Journal: Neuro-Oncology (2015)

INTRODUCTION: Maximum safe resection of tumours located in eloquent areas is hampered by risk of motor, language and visual deficits. nTMS is a rapidly emerging, non-invasive brain stimulation technique generating pre-operative cortical function maps critical for surgical guidance around eloquent cortex. We report our early experience on efficacy, safety and physiological intraoperative correlation. METHOD: Six patients underwent cortical mapping (1 language, 5 motor) using Nexstim Navigated Brain Stimulation (NBS). Single TMS pulses delivered at intensities evoking responses in abductor pollicis brevis. Patients were co-registered to volumetric T1 or T2-weighted MRI. Surgical corridors and anatomically determined functional regions were identified by applying TMS in a topographically systematic manner. Presence/absence of responses were noted in target muscles (arm/leg). For language mapping, without TMS, baseline responses to line drawings were recorded via built-in video. Five-pulse trains of TMS were applied to language areas. Speech arrest and response errors were compared to baseline. During awake surgery, functional ‘on/off' maps were utilised with intraoperative imaging, fMRI, diffusion tensor imaging, and direct cortical stimulation (DCS). RESULTS: The were no technique-related adverse effects. Patients tolerated the technique well. Comparison of TMS and bipolar DCS maps confirmed a high degree of overlap (<2 mm). CONCLUSION: NBS-TMS is safe and can be used to accurately identify pre-operatively eloquent cortical function, and is comparable to DCS; it may be useful for functional mapping in patients not suitable for awake surgery. More data is required to validate this technique in a larger cohort of patients.
Stromal Expression of miR-143/145 Promotes Neoangiogenesis in Lung Cancer Development
Authors: Nadya Dimitrova, Vasilena Gocheva, Arjun Bhutkar, Rebecca Resnick, Robyn M. Jong, Kathryn M. Miller, Jordan Bendor, Tyler Jacks
Journal: Cancer Discovery (2016)

The two unrelated miRNAs miR-143 and miR-145, coexpressed from the miR-143/145 cluster, have been proposed to act as tumor suppressors in human cancer, and therapeutic benefits of delivering miR-143 and miR-145 to tumors have been reported. In contrast, we found that tumor-specific deletion of miR-143/145 in an autochthonous mouse model of lung adenocarcinoma did not affect tumor development. This was consistent with the lack of endogenous miR-143/145 expression in normal and transformed lung epithelium. Surprisingly, miR-143/145 in the tumor microenvironment dramatically promoted tumor growth by stimulating the proliferation of endothelial cells. Loss of miR-143/145 in vivo led to derepression of the miR-145 target CAMK1D, an inhibitory kinase, which when overexpressed prevents mitotic entry of endothelial cells. As a consequence, tumors in miR-143/145-deficient animals exhibited diminished neoangiogenesis, increased apoptosis, and their expansion was limited by the tumor's ability to co-opt the alveolar vasculature. These findings demonstrate that stromal miR-143/145 promotes tumorigenesis and caution against the use of these miRNAs as agents in cancer therapeutics.This study shows that miR-143/145 expressed from the tumor microenvironment stimulates neoangiogenesis and supports tumor expansion in the lung, demonstrating a surprising role for the putative tumor suppressor miRNA cluster in promoting tumorigenesis. We propose inhibition of miR-143/145 as a therapeutic avenue to modulate tumor neoangiogenesis.
Attitudes, Knowledge, and Risk Perceptions of Women With Breast and/or Ovarian Cancer Considering Testing for <i>BRCA1</i> and <i>BRCA2</i>
Authors: Leslie G. Bluman, Barbara K. Rimer, Donald A. Berry, Nancy Borstelmann, J. Dirk Iglehart, Katherine Regan, Joellen Schildkraut, Eric P. Winer
Journal: Journal of Clinical Oncology (1999)

PURPOSE: This study examined baseline knowledge, beliefs, and risk perceptions among a group of 200 women with breast and/or ovarian cancer who participated in a trial designed to improve decision making about genetic testing for BRCA1 and BRCA2. PATIENTS AND METHODS: Women were identified by self-referral, physician referral, and tumor registry extraction and invited to participate in a randomized trial in which testing for BRCA1 and BRCA2 was offered free of charge. Subjects completed baseline questionnaires and interviews that assessed knowledge, attitudes, and perceptions of risk of having an alteration in BRCA1 or BRCA2. RESULTS: Sixty percent of women overestimated their chances of having a BRCA1 or BRCA2 mutation compared with estimates from a BRCA1/BRCA2 risk model. Women who have at least three relatives with breast or ovarian cancer were one third (95% confidence interval, 0.2 to 0.6) as likely to overestimate their risk of having a BRCA1 or BRCA2 mutation compared with women who have two or fewer affected relatives. Knowledge was limited about BRCA1 and BRCA2 mutations and cancer risk associated with gene mutations. Eighty-four percent of the women indicated a probable or definite interest in testing. CONCLUSION: A high proportion of the high-risk women in this study had knowledge deficits about BRCA1 and BRCA2 and overestimated their risk of having a mutation. Although some degree of caution should be used in generalizing the results of this study to practice settings, the data provide insight into the challenges clinicians will face in communicating with patients about cancer genetics.
Biomarker Development for Chronic Obstructive Pulmonary Disease. From Discovery to Clinical Implementation
Authors: Don D. Sin, Zsuzsanna Hollander, Mari L. DeMarco, Bruce M. McManus, Raymond T. Ng
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<Biomarkers as a Possible ...The “Roadmap” for Biomark...Type of SamplesType of PlatformsStatistical Approaches to...Clinical Assay Developmen...ConclusionsReferencesCITING ARTICLES
Tuberculosis screening using ability to provide sputum in an endemic emergency department
Authors: Eduardo Ticona, Moises A. Huaman, Luz Maria Huaroto, Marcos Burgos, Meghan Brett, Rod Escombe, David A.J. Moore
Journal: European Respiratory Journal (2015)

Tuberculosis causes an enormous burden of morbidity and mortality worldwide [1]. Increasing rates of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis pose a serious threat to ongoing efforts in controlling the epidemic, particularly in low- and middle-income countries [2]. Screening all comers able to provide a sputum sample increased TB detection in an emergency department in Peru <http://ow.ly/T7pHA>
In hospitalized patients, the Hospital-patient One-year Mortality Risk score predicted 1-year mortality
Authors: Stephan D. Fihn
Journal: Annals of Internal Medicine (2015)

Source Citation van Walraven C, McAlister FA, Bakal JA, Hawken S, Donzé J. External validation of the Hospital-patient One-year Mortality Risk (HOMR) model for predicting death within 1 year after hospital admission. CMAJ. 2015;187:725-33. 26054605
Oral Antibiotic Therapy for Serious Infections
Authors: Arnold L. Smith
Journal: Annual Review of Medicine (1988)

After a pathogen has been identified and the antibiotic susceptibility determined, parenteral antibiotic administration can be replaced by the oral route for certain patients with meningitis, brain abscess, endocarditis, and skeletal infections. Antibiotics should be administered with the stomach empty and accompanied by 3 ml/kg of water. Direct instillation into the lumen of the small intestine may be advantageous with selected patients. Documenting adequate antibiotic absorption and ensuring compliance are essential to efficacious therapy.
The Role of Prolactin in Bone Metastasis and Breast Cancer Cell–Mediated Osteoclast Differentiation
Authors: Ashley Sutherland, Amanda Forsyth, Yingying Cong, Laurel Grant, Tzu-Hua Juan, Jae K Lee, Alexander Klimowicz, Stephanie K Petrillo, Jinghui Hu, Angela Chan, Florence Boutillon, Vincent Goffin, Cay Egan, Patricia A Tang, Li Cai, Don Morris, Anthony Magliocco, Carrie S Shemanko
Journal: JNCI Journal of the National Cancer Institute (2015)

Metastasis to the bone is a deleterious aspect of breast cancer and is a preferred site that results in bone loss. Hormones such as prolactin (PRL) have not yet been studied for their role in modulating the secondary tumor bone microenvironment.We used quantitative immunohistochemistry with 134 samples of human primary breast cancer and 17 matched primary breast cancers and bone metastases. A Cox proportional hazards regression model was fitted to evaluate the associations between high prolactin receptor (PRLR) expression and time to bone metastasis, adjusting for estrogen receptor status, lymph node status, and chemotherapy status. We assessed osteoclast differentiation, osteoclast size, and measured pit formation in dentine slices. Statistical tests were two-sided.High PRLR expression in the primary breast tumor was associated with a shorter time to metastasis that includes bone (PRLRAQUA Max-per 100 unit hazard ratio = 1.04, 95% confidence interval = 1.00 to 1.07, P = .03). We observed the PRLR in rare samples of bone metastases and matched primary breast cancer. PRL treatment of breast cancer cells induced osteoclast differentiation and bone lysis via secreted factors and was abrogated by a PRLR antagonist (delta1-9-G129R-hPRL). We demonstrated that sonic hedgehog is a PRL-regulated cytokine in breast cancer cells and part of the mechanism that induces osteoclast differentiation.Our evidence indicates that PRL-PRLR can escalate the impact of breast cancer on bone metastasis and that the presence of the PRLR in the tumor microenvironment of breast cancer bone metastasis has the potential to modulate the microenvironment to induce lytic osteoclast formation.
Transfer Factor: Past, Present and Future
Authors: H H Fudenberg, H H Fudenberg
Journal: The Annual Review of Pharmacology and Toxicology (1989)

Adoptive transfer of cell-mediated immunity to specific antigens in humans was first demonstrated by Lawrence (1) in 1949, thus opening a new avenue of research that has led both to increased understanding of basic immune mechanisms and to the development of immunomodulation therapy. Law­ rence originally showed that transfer of whole viable lymphocytes from a normal tuberculin skin test-positive donor to a normal skin test-negative recipient resulted in a conversion of the recipient to skin-test positivity, but this observation created little interest in the immunologic community for several reasons. In 1955, the lymphocyte was mentioned for the first time as a possible immunologic organ. Traditionally, the lymphocyte had been studied in hematologic rather than in immunologic terms . In the third edition of his classic textbook on the anatomy of the lymphoid system, Professor A. Joffy of the University of Bristol proposed three questions to lymphocytes: Where do you come from, where do you go and what do you do, if anything? In 1962(2) , 1. Miller showed that the immune system in chickens could be divided into two components , namely the B lymphocyte derived from the bursal system (B cell) producing antibodies that protect against infection from microorganisms (pneumococcus , meningococcus, streptococcus, gonococ­ cus, etc) and thymic-dependent (T cell) systems that protect against fungi, parasites , viruses, mycobacteria, and cancer metastases . Previously, Law­ rence (3) demonstrated that delayed cutaneous hypersensitivity (DH) respon­ siveness could also be transferred by soluble extracts of leukocytes