tbuckley/cabot-search huggingface dataset:
Making information about clinical trials publicly available
Authors: R. L Smyth
Journal: BMJ (2009)

Open access to information on the EudraCT database will improve transparency

Recognition of the commercial and non-commercial benefits of greater transparency within clinical research has increased in the past decade. Public dissemination of the conduct and outcome of all clinical trials, including those performed as part of marketing authorisation applications, will ensure that professionals and patients have more information about how the safety and effectiveness of drugs has been evaluated. This will also prevent unnecessary duplication of research and, by encouraging greater scrutiny of clinical trials, will ensure that their ethical and scientific quality is improved. Wider dissemination of knowledge will also drive innovation and the conduct of further, more relevant, research.

This effort was considerably enhanced in 2004, when the International Committee of Medical Journal Editors (ICMJE) announced that an essential criterion for publication of a trial in one of their journals was that the details of the trial should be publicly available in a clinical trials register.1 2 These requirements have been an important factor in driving public registration of clinical trials and the development of registers …
Role of blood flow in regulating insulin-stimulated glucose uptake in humans. Studies using bradykinin, [15O]water, and [18F]fluoro-deoxy-glucose and positron emission tomography.
Authors: P Nuutila, M Raitakari, H Laine, O Kirvelä, T Takala, T Utriainen, S Mäkimattila, O P Pitkänen, U Ruotsalainen, H Iida, J Knuuti, H Yki-Järvinen
Journal: Journal of Clinical Investigation (1996)

Defects in insulin stimulation of blood flow have been used suggested to contribute to insulin resistance. To directly test whether glucose uptake can be altered by changing blood flow, we infused bradykinin (27 microgram over 100 min), an endothelium-dependent vasodilator, into the femoral artery of 12 normal subjects (age 25+/-1 yr, body mass index 22+/-1 kg/m2) after an overnight fast (n = 5) and during normoglycemic hyperinsulinemic (n = 7) conditions (serum insulin 465+/-11 pmol/liter, 0-100 min). Blood flow was measured simultaneously in both femoral regions using [15O]-labeled water ([15O]H2O) and positron emission tomography (PET), before and during (50 min) the bradykinin infusion. Glucose uptake was measured immediately after the blood flow measurement simultaneously in both femoral regions using [18F]-fluoro-deoxy-glucose ([18F]FDG) and PET. During hyperinsulinemia, muscle blood flow was 58% higher in the bradykinin-infused (38+/-9 ml/kg muscle x min) than in the control leg (24+/-5, P<0.01). Femoral muscle glucose uptake was identical in both legs (60.6+/-9.5 vs. 58.7+/-9.0 micromol/kg x min, bradykinin-infused vs control leg, NS). Glucose extraction by skeletal muscle was 44% higher in the control (2.6+/-0.2 mmol/liter) than the bradykinin-infused leg (1.8+/-0.2 mmol/liter, P<0.01). When bradykinin was infused in the basal state, flow was 98% higher in the bradykinin-infused (58+/-12 ml/kg muscle x min) than the control leg (28+/-6 ml/kg muscle x min, P<0.01) but rates of muscle glucose uptake were identical in both legs (10.1+/-0.9 vs. 10.6+/-0.8 micromol/kg x min). We conclude that bradykinin increases skeletal muscle blood flow but not muscle glucose uptake in vivo. These data provide direct evidence against the hypothesis that blood flow is an independent regulator of insulin-stimulated glucose uptake in humans.
Perinatal Risk and Cerebral Palsy
Authors: Robert J. Sokol
Journal: JAMA (1984)

A relationship between perinatal risk, ie, obstetric complications, and cerebral palsy has been documented for more than 120 years.<sup>1</sup>Interest in this association increased in the mid-20th century and was one of the factors that produced the Collaborative Project, for which data were collected at 12 teaching hospitals from 1959 to 1966, ie, about 20 years ago. The resulting data base continues to yield interesting and useful findings, such as those from the study in this issue ofThe Journalby Nelson and Ellenberg.<sup>2</sup>Of the numerous observations reported by these authors, two seem to be key findings. Among infants of normal birth weight (&gt;2,500 g), there was a relatively low risk for cerebral palsy, regardless of obstetric complications, as long as the five-minute Apgar score was normal (≥7). Similarly, the risk for cerebral palsy was not particularly high with a very low five-minute Apgar score (≤3),
Abstract 1867: The natural product sulforaphane protects epidermal tissue from individuals at increased risk for melanoma from the effects of UV radiation
Authors: Pamela B. Cassidy, John Quackenbush, Jennifer Campbell, Philip J. Moos, Sancy A. Leachman
Journal: Cancer Research (2011)

Abstract Our study focuses on the design and testing of melanoma-prevention strategies for use in high-risk populations. Individuals who have germline loss-of-function (LOF) mutations at the highly polymorphic MC1R locus are at 4-fold increased risk for melanoma. Much of this increase likely arises from the loss of MC1R-mediated upregulation of antioxidant, DNA repair, pigment synthesis and anti-apoptotic pathways that protect epidermal melanocytes from the mutagenic effects of UV radiation. We have found that the natural product sulforaphane (SF) protects normal human melanocytes in culture from UV-induced apoptosis and oxidative stress in the absence of MC1R stimulation by its ligand α-MSH. This led us to propose that SF might be useful for protecting the skin of human subjects with LOF MC1R mutations from the harmful effects of UV light. We have sequenced MC1R in volunteers both with and without the red hair phenotype that is typical for humans with LOF mutations. Sequencing was necessary in all volunteers because many individuals with heterozygous LOF mutations do not have the signature pigmentary phenotype, but are still at increased (2-fold) risk for melanoma. Shave biopsies were harvested from those with either wild-type MC1R or two LOF alleles. The epidermal tissues were treated ex vivo with UV and/or SF then analyzed histologically and by qPCR. We found that SF ameliorated many of the effects of UV radiation in tissues from donors with LOF MC1R. This study demonstrates the promise of SF as an agent for protection of human skin in individuals with high-risk MC1R genotypes from the harmful effects of UV radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1867. doi:10.1158/1538-7445.AM2011-1867
Dermatophyte identification in skin and hair samples using a simple and reliable nested polymerase chain reaction assay
Authors: J. Verrier, L. Krähenbühl, O. Bontems, M. Fratti, K. Salamin, M. Monod
Journal: British Journal of Dermatology (2012)

Dermatophyte identification in tinea capitis is essential for choosing the appropriate treatment and in tinea infections to identify the possible source. The failure of fungi to grow in cultures frequently occurs, especially in cases of previous antifungal therapy.To develop a rapid polymerase chain reaction (PCR) sequencing assay for dermatophyte identification in tinea capitis and tinea corporis.Fungal DNA was extracted from hair and skin samples that were confirmed to be positive by direct mycological examination. Dermatophytes were identified by the sequence of a 28S ribosomal DNA subunit amplicon generated by nested PCR.Nested PCR was found to be necessary to obtain amplicons in substantial amounts for dermatophyte identification by sequencing. The results agreed with those of classical mycological identification in 14 of 23, 6 of 10, and 20 of 23 cases of tinea capitis, tinea corporis and tinea pedis, respectively, from which a dermatophyte was obtained in culture. In seven of the 56 cases, another dermatophyte was identified, revealing previous misidentification. A dermatophyte was identified in 12 of 18, three of five, and four of nine cases of tinea capitis, tinea corporis and tinea pedis, respectively, in cases in which no dermatophyte grew in culture.Although the gold standard dermatophyte identification from clinical samples remains fungal cultures, the assay developed in the present study is especially suitable for tinea capitis. Improved sensitivity for the identification of dermatophyte species was obtained as it is possible to identify the dermatophyte when the fungus fails to grow in cultures.
Reginald Frederick Bolam
Authors: S. Bolam
Journal: BMJ (2008)

<h3>BACKGROUND:</h3> Although quality control standards are recommended to ensure accurate test results, the coefficient of variation for the FVC and FEV<sub>1</sub> biologic quality control (BioQC) is not specified. The primary aim of this study was to evaluate variations in spirometry BioQCs in a large and diverse cohort of individuals to determine an acceptable standard for the coefficient of variation. <h3>METHODS:</h3> The FVC and FEV<sub>1</sub> biologic control data were secondary analyses from an inhaled medication trial that was conducted over 3 y ending in 2018 that included 114 laboratories. Results were sent to a central repository for expert review. The FVC and FEV<sub>1</sub> coefficients of variation were based upon a minimum of 10 spirometry values annually separated by at least 5 d. A second method of computing the coefficient of variation used 10 values within 28 d. Descriptive statistics were computed. Wilcoxon signed-rank tests were conducted to compare whether the median coefficient of variation values between the 2 methods differed, tested at α = 0.05 using SPSS. <h3>RESULTS:</h3> Of 249 biologic control participants, 170 met the first year’s inclusion criteria. The coefficient of variation for the 5-d separated method was &lt; 5% for 94.1% of FVC and 93.5% of FEV<sub>1</sub> values in the first year. By year 3, 90% of FVC and FEV<sub>1</sub> coefficient of variation values were &lt; 4%. The medians for the 5-d separated and the 28-d measure showed no difference for either FVC coefficient of variation or FEV<sub>1</sub> coefficient of variation, <i>Z</i> = −1.764, <i>P</i> = .78, and <i>Z</i> = −0.980, <i>P</i> = .33, respectively. <h3>CONCLUSIONS:</h3> Interlab biologic control variation values of &lt; 4% for FVC and FEV<sub>1</sub> are achievable; however, individual labs should strive to attain lower values. Acceptable coefficients of variation can be achieved within 28 d.
Efficacy of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults
Authors: Himal Lal, Anthony L. Cunningham, Olivier Godeaux, Roman Chlibek, Javier Diez-Domingo, Shinn-Jang Hwang, Myron J. Levin, Janet E. McElhaney, Airi Poder, Joan Puig-Barberà, Timo Vesikari, Daisuke Watanabe, Lily Weckx, Toufik Zahaf, Thomas C. Heineman
Journal: New England Journal of Medicine (2015)

In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response.We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults.A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups.The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).
THE BATH IN MODERN MEDICINE.
Authors: CHAS. H. SHEPARD
Journal: JAMA (1895)

The advance of modern medicine in the prevention of disease is gratifying to all whose studies have been in that direction. Preventive medicine touches the keynote of medical science, and its possibilities reach to the perfection of mental and physical manhood. It is in this line of medical research that the greatest good to the greatest number is to come. As mankind are enlightened they will seek necessarily, more, and more, those who can teach them to observe mental and physical laws, that thereby they may secure a sound mind in a sound body; and, inasmuch as the onward march of sanitary science will bring about a condition in which the mere healer of diseases will be in less and less demand, a broader field will be found for the constantly increasing supply of graduated physicians in such work as instructors, lecturers, health inspectors, etc. It is a hopeful sign
Cell-specific activation and detoxification of benzene metabolites in mouse and human bone marrow: identification of target cells and a potential role for modulation of apoptosis in benzene toxicity.
Authors: D Ross, D Siegel, D G Schattenberg, X M Sun, J L Moran
Journal: Environmental Health Perspectives (1996)

The role of cell-specific metabolism in benzene toxicity was examined in both murine and human bone marrow. Hemopoietic progenitor cells and stromal cells are important control points for regulation of hemopoiesis. We show that the selective toxicity of hydroquinone at the level of the macrophage in murine bone marrow stroma may be explained by a high peroxidase/nicotanimide adenine dinucleotide phosphate, reduced [NAD(P)H]:quinone oxidoreductase (NQO1) ratio. Peroxidases metabolize hydroquinone to the reactive 1,4-benzoquinone, whereas NQO1 reduces the quinones formed, resulting in detoxification. Peroxidase and NQO1 activity in human stromal cultures vary as a function of time in culture, with peroxidase activity decreasing and NQO1 activity increasing with time. Peroxidase activity and, more specifically, myeloperoxidase, which had previously been considered to be expressed at the promyelocyte level, was detected in murine lineage-negative and human CD34+ progenitor cells. This provides a metabolic mechanism whereby phenolic metabolites of benzene can be bioactivated in progenitor cells, which are considered initial target cells for the development of leukemias. Consequences of a high peroxidase/NQO1 ratio in HL-60 cells were shown to include hydroquinone-induced apoptosis. Hydroquinone can also inhibit proteases known to play a role in induction of apoptosis, suggesting that it may be able to inhibit apoptosis induced by other stimuli. Modulation of apoptosis may lead to aberrant hemopoiesis and neoplastic progression. This enzyme-directed approach has identified target cells of the phenolic metabolites of benzene in bone marrow and provided a metabolic basis for benzene-induced toxicity at the level of the progenitor cell in both murine and human bone marrow.
Neutropenia Probably Resulting From Nafcillin
Authors: Michael Sandberg
Journal: JAMA (1975)

SEVERE neutropenia has been noted as a complication of the administration of penicillin and many of its derivatives but not of nafcillin. This may be a result of the less extensive use of nafcillin.1Lack of apparent hematologic complications with nafcillin has led some clinicians to conclude that it is a safer drug; however, it is probably best to consider nafcillin to be a member of the same family of drugs and likely, therefore, to have complications similar to those of other penicillins. To our knowledge, this is the first report of a case of neutropenia in a patient treated with nafcillin. Our findings tend to support the point of view that nafcillin may induce complications similar to those induced by other members of the penicillin family.  Report of a Case  A 24-year-old man with a history of intravenous drug use was admitted to the District of Columbia General
BM-03 * REVISED GRADED PROGNOSTIC ASSESSMENT FOR MELANOMA PATIENTS WITH BRAIN METASTASIS (MBM)
Authors: V. A. Venur, S. Chao, P. Elson, M. Ahluwalia
Journal: Neuro-Oncology (2014)

BACKGROUND: Melanoma is third most common cause of brain metastasis (MBM). We evaluated prognostic factors that predict overall survival (OS) in MBM treated at a single tertiary care institution in contemporary cohort. METHODS: With IRB approval, the Cleveland Clinic's database was used to identify MBM patients treated between 2000 and 2013. OS from the diagnosis of MBM was the primary end point. Cox proportional hazards models with stepwise variable selection were used for data analysis. RESULTS: 256 patients with median age of 55 (20-85) years were included for analysis. Karnofsky performance scale (KPS) was 100 in 17, 90 in 88, 80 in 64, ≤ 70 in 58 patients. Seventy four patients (30%) were treated with stereotactic radiosurgery (SRS), 60 (24%) with whole brain radiation therapy (WBRT), 37 (15%) with WBRT and SRS, 35 (14%) underwent surgery and WBRT, 21 (8%) surgery and SRS. Median OS was 5.7 months (95% C.I. 4.9-6.6 months). Genomic data was available for 73 patients; 34 had BRAF mutation and 39 were BRAF negative. Disease specific graded prognostic assessment (GPA) for MBM is based on KPS and age at diagnosis. Overall it was prognostic for OS (p <.0001) however separation between groups was variable. KPS, age at diagnosis of brain metastasis, gender, number of extra- cranial metastasis sites and number of BM were found to be independently prognostic for survival in our cohort. A revised GPA can be derived by assigning "points" (weights) to the levels within each of these five factors that are proportional to the regression coefficient estimates in the final model; and then adding the total number of points present. The new GPA has four groups' unfavorable, intermediate 1, intermediate 2 and favorable with OS of 1.5, 4.4, 6.6 and 11.5 months respectively. CONCLUSIONS: A revised graded prognostic assessment is proposed for MBM.
Welcome to Year 83
Authors: Emily Friedman
Journal: JAMA (1995)

In this competitive society, Roger Evans, PhD, has written, the plight of the uninsured poor "reflects the unwillingness of our sociopolitical system to reward failure."<sup>1</sup>What, then, should be the response of health care folk to the failure of the sociopolitical system to protect the uninsured? One response—which is eagerly anticipated by some—is to fold the tents and go home. After all, more than 80% of the population (including most people who work in health care) have coverage,<sup>2</sup>although some of it (notably Medicaid) is threadbare on its good days, and little of it is reliable in the face of catastrophic disease or injury. Furthermore, is the battle not lost? Congress was unwilling even to pass reforms that would guarantee coverage (albeit at high cost) to those Americans whose health status makes it impossible for them to obtain private insurance, to protect 13 million uninsured children, or to
Sports trainers have accurate but incomplete recall of injury details
Authors: R A Braham, C F Finch, P McCrory
Journal: British Journal of Sports Medicine (2003)

Silence on clinical fundamentalsYour point about lifesaving hand washing to prevent diarrhoeal illness 1 is well made.I have found that the inattention you have noted to such clinical fundamentals in textbooks on sports medicine is mirrored by the absence of any notation, affirmative or otherwise, in many textbooks on pain, correlating the symptom (pain) with the physical sign (tenderness), a rudimentary clinical confirmation of the validity of pain, according to my clinical training in Ireland, that could distinguish malingering from a genuine complaint of pain, for example.Perhaps I have received a false impression but, if so, the utility of eliciting tenderness, a longstanding custom during physical examination, seems a mystery.In November 2002, I attended a conference in Florida on prescribing addictive drugs.None of the purportedly expert presenters mentioned the issue spontaneously.When I collared one of them after his lecture and enquired specifically about the point, he claimed that chronic, non-malignant pain and tenderness are usually ''dissociated''that is, a patient can suffer chronic, nonmalignant pain in the absence of tenderness of the painful part, on physical examination.This assertion seemed contrary to my own, admittedly anecdotal, experience over some 24 years.Furthermore, it would seem to (a) render chronic, non-malignant pain, and maybe all pain, unknowable and undetectable (except perhaps to the alleged sufferer, although nobody else can tell), (b) place the assessment of pain in the realm of ''pathological science'', 5 and (c) invalidate the very idea of regulation of narcotic drugs to ensure that the practitioner prescribe one only when it ''corresponds to the ailment''. 5 The silence on the subject in the medical literature seemed anomalous.A Boolean Pubmed search on the keywords ''pain'' and ''tenderness'' revealed no relevant articles.I examined all 114 textbooks on pain in the medical library of the University of Southern California (USC) and found two 2 3 that addressed the issue.
Secondary Consequences of β Cell Inexcitability: Identification and Prevention in a Murine Model of KATP-Induced Neonatal Diabetes Mellitus
Authors: Maria Sara Remedi, Harley T. Kurata, Alexis Scott, F. Thomas Wunderlich, Eva Rother, Andre Kleinridders, Ailing Tong, Jens C. Brüning, Joseph C. Koster, Colin G. Nichols
Journal: Cell Metabolism (2009)