tbuckley/cabot-search huggingface dataset:
Evidence and policy: interpreting the Delphic oracle
Authors: R. Klein
Journal: Journal of the Royal Society of Medicine (2003)

So wrote Edwin Chadwick more than a hundred years ago. Not only was he one of the pioneers of the public health movement, equally, he was the 19th century father of much 20th century social inquiry. To cite him is to underline that there is nothing new—except, possibly, the phrase itself— about evidence-based policy (EBP). As Royal Commissions and government committees of inquiry have demonstrated over the decades, policy makers have always sought evidence. The extent to which subsequent policy decisions were actually based on that evidence, as distinct from the use of such evidence to legitimate them, is another question: Chadwick himself has often been criticized for manipulating evidence to support his preconceived ideas, notoriously so in the case of the 1834 Poor Law Report. So why the sudden rush of enthusiasm for EBP today? One answer must be that it reflects the success of the evidence-based medicine (EBM) movement (and this is a ‘movement’ insofar as it has prophets, missionaries and zealots). If medicine can be based on evidence, so surely can policy. The proposition seems self-evident. The trouble is that a sleight of hand is involved in making the transition. EBM is distinguished by the fact that it privileges particular kinds of evidence—‘scientific’ evidence, with a strong emphasis on randomized controlled trials and systematic reviews. It is not at all self-evident that this model is appropriate for, or indeed relevant to, the making of policy. In the case of policy, evidence tends to be something of a Delphic oracle—difficult to decipher and apt to be misinterpreted. Much has been written about the pitfalls of, and the delusive hopes held out by, EBP. So this paper asks whether it is possible to plot out a sensible course between a platitude and a nonsense. The platitude is that policy should be informed by evidence. Who could possibly disagree? The nonsense is that policy should be based on scientific evidence. This is to misunderstand the nature of both the policy process and the role of evidence in it.2–4 The way forward is to disaggregate the notions of both policy and evidence: different stages of the policy process may call for different types of evidence. Consider, first, the different types of evidence or knowledge that are relevant for the policy process. There does exist scientific evidence—i.e. research-based, usually peer-reviewed, evidence. Next there is what might be called organizational evidence—in the case of health policy, the experience of those actually working in the NHS. As a Cabinet Office paper on policy-making5 has put it:
Constipation in people with learning disability
Authors: J. Coleman, G. Spurling
Journal: BMJ (2010)

#### Case scenario A 48 year old woman with mild intellectual impairment and epilepsy (for which she takes phenytoin) presented with left sided abdominal pain. She had mentioned this before but had denied constipation or diarrhoea. We found an archived radiograph showing moderate faecal loading. When pressed, she admitted not knowing what “constipation” meant and, in fact, had been manually evacuating but was too ashamed to tell anyone. Chronic constipation is surprisingly common in people with learning disability. Communication difficulties, the vagueness of the symptoms, and the presence of other priorities often mean that carers and clinicians miss looking for this problem.1 #### How common is it?
Diastolic dysfunction is a predictor of poor outcomes in patients with cirrhosis, portal hypertension, and a normal creatinine
Authors: Luís Ruíz-del-Árbol, Linette Achécar, Regina Serradilla, Miguel Á. Rodríguez-Gandía, Miguel Rivero, Elena Garrido, José J. Natcher
Journal: Hepatology (2013)

We investigated left ventricular diastolic dysfunction (LVDD) and its relationship with circulatory function and prognosis in cirrhosis with portal hypertension and normal creatinine. Conventional and tissue Doppler (TDI) echocardiography, systemic and hepatic hemodynamics, and the activity of endogenous vasoactive systems (AEVS) were measured prospectively in 80 patients. Plasma renin activity (PRA; &gt;4 ng/mL/hour) was used as a surrogate of effective arterial blood volume. Patients were followed up for 12 months. Thirty-seven patients had LVDD (19 with grade 1 and 18 with grade 2). Left ventricular hypertrophy, left atrial volume, AEVS, and natriuretic peptide levels were significantly greater in patients with LVDD than without LVDD. Patients with grade 2 LVDD, compared to grade 1 LVDD and without LVDD, had significantly lower mean arterial pressure and higher Model for End-Stage Liver Disease (MELD) score, E-wave transmitral/early diastolic mitral annular velocity (E/e′ ratio), cardiopulmonary pressures, PRA, and natriuretic peptide levels. Systolic and cardiac chronotropic function were significantly lower in patients with grade 2 LVDD than without LVDD. LVDD was more frequent in patients with ascites and increased PRA than patients without ascites or with ascites but normal PRA. Fourteen patients with LVDD developed hepatorenal syndrome (HRS) type 1 on follow-up. Survival was different according to degree of LVDD (without LVDD: 95%; grade 1 LVDD: 79%; grade 2 LVDD: 39%; P &lt; 0.001). Independent predictive factors of mortality were MELD score and E/e′ ratio. Conclusion: LVDD occurs simultaneously with other changes in cardiac structure and function and is associated with an impairment of effective arterial blood volume. LVDD is a sensitive marker of advanced cirrhosis, type 1 HRS development, and mortality. (Hepatology 2013;58:1732–1741)
A Hard-Wired Glutamatergic Circuit Pools and Relays UV Signals to Mediate Spectral Preference in Drosophila
Authors: Thangavel Karuppudurai, Tzu-Yang Lin, Chun-Yuan Ting, Randall Pursley, Krishna V. Melnattur, Fengqiu Diao, Benjamin H. White, Lindsey J. Macpherson, Marco Gallio, Thomas Pohida, Chi-Hon Lee
Journal: Neuron (2014)
The BMJ, of all places
Authors: R. Poluri
Journal: BMJ (2009)

It was 25 years ago but seems like yesterday—the day I stepped out of the Air India Boeing, feeling awkward in my brother’s black jacket. It was not as cold as I thought it would be, though a fine drizzle was falling. My cousin and his son drove me out of London towards Gloucester, where they lived. They had sponsored me to appear for the Professional and Linguistic Assessments Board (PLAB) examination, the test that the General Medical Council requires overseas doctors to undergo before they can practise in the UK.

Everything was new: the buildings, the traffic, the red London buses, the orderly silence under the grey January sky that seemed to envelop everything. The people: how healthy they looked! They had beautiful complexions and were obviously all bright, as they all spoke English. I gaped at them in wonder. Some of them smiled back at me.

A week later my heart missed a beat when I saw an advertisement at the back of the BMJ job section: “Gay Medical Association meets monthly for befriending and social and professional support.” The address was the …
Jews, Medicine, and Medieval Society
Authors: David L. Freeman
Journal: JAMA (1996)

<b>Jewish Thought and Scientific Discovery in Early Modern Europe</b>, by David B. Ruderman, 392 pp, $30, ISBN 0-300-06112-9, New Haven, Conn, Yale University Press, 1995. For more than a century, medieval Jewish physicians have been the object of scholarly inquiry.<i>The Jews and Medicine</i>, Harry Friedenwald's still valuable work published 50 years ago, chronicled the careers of hundreds of Jewish physicians who lived during the Middle Ages. By his time, Jewish doctors had been brought into focus as a curious social anomaly. They came from a religious community that was ghetto confined, despised, feared, and persecuted; they were prohibited by law from treating Christians and excluded from medical schools until the 16th century. Nevertheless, Jews were called often to attend popes, kings, and other notables, because they were considered to be especially skilled in the art of cure. The affinity of medieval Jews for medicine was thought to have resulted
Abstract A41: Hypoxia-dependent modification of collagen networks promotes sarcoma metastasis
Authors: T.S. Karin Eisinger-Mathason, Minsi Zhang, Qiu Qiong, Nicolas Skuli, Michael S. Nakazawa, Tatiana Karakasheva, Vera Mucaj, Jessica E.S. Shay, Lars Stangenberg, Ellen Pure, Sam S. Yoon, David G. Kirsch, M. Celeste Simon
Journal: Cancer Research (2015)

Abstract Intratumoral hypoxia and expression of Hypoxia Inducible Factor 1α (HIF1α) correlate with metastasis and poor survival in sarcoma patients. We demonstrate here that hypoxia controls sarcoma metastasis through a novel mechanism wherein HIF1α enhances expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2). We show that loss of HIF1α or PLOD2 expression disrupts collagen modification, cell migration and pulmonary metastasis (but not primary tumor growth) in allograft and autochthonous LSL-KrasG12D/+; Trp53fl/fl murine sarcoma models. Biochemical analyses revealed that overexpression of HIF1α and PLOD2 in sarcoma cells alters collagen structure and organization. The increase in lysyl hydroxylation and concomitant loss of prolyl hydroxylation, promotes adherence of tumor cells, collagen-associated migration and tumor cell dissemination. Furthermore, ectopic PLOD2 expression restores migration and metastatic potential in HIF1α-deficient tumors, and analysis of human sarcomas reveal elevated HIF1α and PLOD2 expression in metastatic primary lesions. Pharmacological inhibition of PLOD enzymatic activity suppresses metastases. Collectively, these data indicate that HIF1α controls sarcoma metastasis through PLOD2-dependent collagen modification and organization in primary tumors. We conclude that PLOD2 is a novel therapeutic target in sarcomas and successful inhibition of this enzyme may reduce tumor cell dissemination. Citation Format: T.S. Karin Eisinger-Mathason, Minsi Zhang, Qiu Qiong, Nicolas Skuli, Michael S. Nakazawa, Tatiana Karakasheva, Vera Mucaj, Jessica E.S. Shay, Lars Stangenberg, Ellen Pure, Sam S. Yoon, David G. Kirsch, M. Celeste Simon. Hypoxia-dependent modification of collagen networks promotes sarcoma metastasis. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A41. doi:10.1158/1538-7445.CHTME14-A41
Parenteral Fluid Therapy of Burns
Authors: J. Frederick Eagle
Journal: JAMA (1960)

A single intravenous solution containing 5% glucose, 0.66% sodium chloride, and 2% protein has been used for the parenteral fluid therapy of 28 patients with second- and third-degree burns involving 15% or more of the body surface area. Only the rate of administration must be changed to accommodate the size of the patient and the extent of the burn. Only one death occurred during the first 48 hours. Because this solution replaces water, salt, and protein continuously at the same rates at which they are being lost from the circulation, it has theoretical advantages over other regimens which replace these factors discontinuously by alternate infusions of plasma, saline, or dextrose and water. Its greatest value lies in the ease of management and the virtual absence of fluid and electrolyte problems.
Learning from failure: congestive heart failure in the postgenomic age
Authors: Ivor J. Benjamin, Michael D. Schneider
Journal: Journal of Clinical Investigation (2005)

The prognosis of heart failure is worse than that of most cancers, but new therapeutic interventions using stem and other cell-based therapies are succeeding in the fight against it, and old drugs, with new twists, are making a comeback. Genetically engineered animal models are driving insights into the molecular mechanisms that cause hearts to fail, accelerating drug discoveries, and inspiring cell-based therapeutic interventions for both acquired and inheritable cardiac diseases.
Multiparameter Computational Modeling of Tumor Invasion
Authors: Elaine L. Bearer, John S. Lowengrub, Hermann B. Frieboes, Yao-Li Chuang, Fang Jin, Steven M. Wise, Mauro Ferrari, David B. Agus, Vittorio Cristini
Journal: Cancer Research (2009)

Abstract Clinical outcome prognostication in oncology is a guiding principle in therapeutic choice. A wealth of qualitative empirical evidence links disease progression with tumor morphology, histopathology, invasion, and associated molecular phenomena. However, the quantitative contribution of each of the known parameters in this progression remains elusive. Mathematical modeling can provide the capability to quantify the connection between variables governing growth, prognosis, and treatment outcome. By quantifying the link between the tumor boundary morphology and the invasive phenotype, this work provides a quantitative tool for the study of tumor progression and diagnostic/prognostic applications. This establishes a framework for monitoring system perturbation towards development of therapeutic strategies and correlation to clinical outcome for prognosis.[Cancer Res 2009;69(10):4493–501] Major Findings We apply a biologically founded, multiscale, mathematical model to identify and quantify tumor biologic and molecular properties relating to clinical and morphological phenotype and to demonstrate that tumor growth and invasion are predictable processes governed by biophysical laws, and regulated by heterogeneity in phenotypic, genotypic, and microenvironmental parameters. This heterogeneity drives migration and proliferation of more aggressive clones up cell substrate gradients within and beyond the central tumor mass, while often also inducing loss of cell adhesion. The model predicts that this process triggers a gross morphologic instability that leads to tumor invasion via individual cells, cell chains, strands, or detached clusters infiltrating into adjacent tissue producing the typical morphologic patterns seen, e.g., in the histopathology of glioblastoma multiforme. The model further predicts that these different morphologies of infiltration correspond to different stages of tumor progression regulated by heterogeneity.
Lack of evidence of circulating retroviral antibodies in patients with classic Hodgkin's disease
Authors: T. L. Chorba, V. S. Kalyanaraman, M. J. Lacher, R. S. Schulof
Journal: American Journal of Hematology (1988)

Abstract Because of the T‐cell abnormalities observed in Hodgkin's disease and the growing number of Hodgkin's disease cases observed in association with the acquired immunodeficiency syndrome (AIDS), concern has been expressed that a retrovirus may be the primary cause of Hodgkin's disease. We examined plasma specimens from 17 patients with Hodgkin's disease that were drawn in 1979. Because serum containing antibodies to either human T‐lymphotropic virus type I (HTLV‐I) or HTLV‐II precipitate the major core protein, p24, of HTLV‐I, lack of reactivity to HTLV‐I p24 in all the specimens demonstrated absence of antibodies to HTLV‐I or ‐II. None of the specimens was reactive to human immunodeficiency virus type 1 (HIV‐1) by ELISA. None of the specimens were reactive on Western blot assays for HTLV‐I or ‐II or HIV‐1. Lack of evidence of cross‐reacting antibodies to prototype strains of those retroviruses in specimens drawn before the AIDS epidemic suggests that classic Hodgkin's disease is not the result of infection with one of the known human lymphocytotropic retroviruses or a closely related agent.
The terrible peril: a historical perspective on the venereal diseases.
Authors: M W Adler
Journal: BMJ (1980)

I have chosen a historical theme for my lecture today to mark the creation of the first chair of genitourinary medicine in the world. The first part is concerned with the events leading to the creation of an organised clinical service for the venereal diseases in the UK and its subsequent growth. In the second part I will examine the history of the Middlesex Hospital in relation to these diseases and the development of the new academic depart ment. During the nineteenth and early twentieth centuries govern ment reports and legislation did not manage to control these diseases, and, if anything, created more controversy than the illnesses themselves. The Contagious Diseases Acts of 1864 and 1866 required the compulsory registration and police super vision of all prostitutes plus regular examinations and even compulsory hospital detention. The Royal Commission on Poor Laws of 1909 also recommended detention orders for patients with these diseases, and the Royal Commission on Divorce of 1912 reported that the passing on of a venereal disease was an act of cruelty second to none as grounds for divorce. Society was happier ignoring the problems of these illnesses and, if forced to face them, developed suitable defence mechanisms. One was to project the blame on to the prostitute, or treat her as a non-person. George Vivian Poore, discussing the rape of prostitutes by Jack the Ripper in his book on medical jurisprudence, maintained that they were not violated because most of them were prostitutes.1 Other mechanisms to contain the realities of the problem were by detaining the patient or classifying the passing on of such disease as cruelty. The medical profession often added to this censorious and moralistic sup pression. Dr Samuel Solly, president of the Royal Medical and Chirurgical Society, giving evidence to a government com mittee, said of syphilis that it was self-inflicted, was avoidable by refraining from sexual activity, and was intended as a punishment for our sins and that we should not interfere in the matter.2 Even though this was said in 1868, attitudes had not greatly changed by the turn of the century, and some doctors still refused to treat venereal diseases. It was reported that one had written to a patient as follows, You have had the disease one year, and I hope it may plague you many more to punish you for your sins and I would not think of treating you.3
Malaria
Authors: Blake E. Waterhouse
Journal: JAMA (1967)

Malaria develops in a significant number of servicemen who return from Vietnam. One hundred consecutive cases seen in a three-month period at Darnall Army Hospital, Fort Hood, Tex, are reported. One fourth to one half of such patients experience symptoms while on leave in a civilian community. Illness in the typical patient has its onset within two months following the return from Vietnam and is characterized by the sudden development of fever, chills, headaches, and myalgia. Splenomegaly, when present, is usually of only moderate degree and may represent the only significant abnormality on physical examination. Diagnosis is made by demonstrating the malaria parasites in peripheral blood smears. The most common species in this study was<i>Plasmodium vivax</i>(83%). Correct treatment depends on species identification and is effective. The incidence of malaria in Vietnam returnees represents a significant medical problem for civilian physicians.
Free radicals and reperfusion arrhythmias. Commentaries on this month's Controversy articles From William Coetzee
Authors: W. A Coetzee
Journal: Cardiovascular Research (1994)

Journal Article Free radicals and reperfusion arrhythmias. Commentaries on this month's Controversy articles From William Coetzee Get access William A Coetzee William A Coetzee Cardiovascular Research, The Rayne Insitute, St Thomas' Hospital, London SEl 7EH. UK. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 3, March 1994, Pages 425–426, https://doi.org/10.1093/cvr/28.3.425 Published: 01 March 1994
High-throughput mutational screen of the tyrosine kinome in chronic myelomonocytic leukemia
Authors: J W Tyner, M M Loriaux, H Erickson, C A Eide, J Deininger, M MacPartlin, S G Willis, T Lange, B J Druker, T Kovacsovics, R Maziarz, N Gattermann, M W Deininger
Journal: Leukemia (2008)
Historical treatment of chronic hepatitis B and chronic hepatitis C.
Authors: P Ferenci
Journal: Gut (1993)

Interferon is currently considered to be the only accepted effective treatment for chronic viral hepatitis. A history of the treatment of chronic hepatitis B and C before the use of interferon is presented here. Hepatitis B virus does not seem to be directly cytopathic and the disease is known to be modulated largely by the host's immune response. Experience with immunosuppressant and immunostimulant drugs and a wide variety of antiviral agents, however, has indicated that none of these are of any benefit in patients with chronic hepatitis B, with the possible exception of adenine arabinoside. In view of the much more recent identification of the hepatitis C virus, studies of therapy for chronic hepatitis C are inevitably less extensive. A pilot study using acyclovir in patients with chronic non-A, non-B hepatitis did not show any benefit, although the treatment period may have been too short for the results to be conclusive. The only agent other than alpha interferon to be tried in chronic hepatitis C is ribavirin, which may have some activity. Many of the agents studied in chronic hepatitis B should also be investigated for the treatment of patients with chronic hepatitis C.
Erythromycin estolate and jaundice.
Authors: W H Inman, N S Rawson
Journal: BMJ (1983)

Using prescription-event monitoring to determine whether erythromycin estolate was a more frequent cause of jaundice than erythromycin stearate or tetracycline 12 208 patients, for whom 5343 doctors had prescribed one of the three drugs, were identified by the Prescription Pricing Authority. Of the questionnaires sent to general practitioners about the possible occurrence of jaundice, 76% were returned. There were 16 reports of jaundice, of which four were attributable to gall stones, three to cancer, six to viral hepatitis, and only three were possibly related to an antibiotic. All three patients, in whom the antibiotic was a possible cause, had been treated with erythromycin stearate. No case was attributable to the estolate which had previously been suspected of being a more frequent cause of jaundice. Although the incidence is unknown, it is very unlikely to be more than one in 100.
Bacteriuria in a Healthy Population and Its Relation to Hypertension and Pyelonephritis
Authors: Sam Switzer
Journal: New England Journal of Medicine (1961)

ALTHOUGH many physicians regard chronic pyelonephritis as a relatively common cause of hypertension1 a dissenting opinion stresses the rarity of an etiologic relation.2 , 3 Longcope4 is credited with having first suggested hypertension as a late manifestation of pyelonephritis, and Weiss and Parker,5 presenting additional cases, subsequently established the current histologic criteria for the diagnosis. In both studies, however, the authors refrain from assaying the prevalence of the association. Goldblatt's6 classic experiments producing hypertension with renal ischemia lent a partial explanation for an association, and the implication that occult, chronic pyelonephritis might commonly cause hypertension became prevalent. Actually, the cases presented, being . . .
An Outbreak of Streptococcal Skin Sepsis in a Closed Community
Authors: C. I. Backhouse, R. Y. Cartwright
Journal: BMJ (1974)

An outbreak of skin sepsis due to beta-haemolytic streptococcus group A M33, T3/13/B3264 occurred in a closed community. Staphylococcus aureus was also present in many of the lesions, but different strains were recognizable by phage typing. Environmental contamination was found. The outbreak was controlled by isolating infected boys and decontaminating the environment. Various aspects of the epidemiology and the pathogenesis of streptococcal infections are discussed.