tbuckley/cabot-search huggingface dataset:
Effect of reporting bias on meta-analyses of drug trials: reanalysis of meta-analyses
Authors: B. Hart, A. Lundh, L. Bero
Journal: BMJ (2012)

<b>Objective</b> To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials. <b>Design</b> Reanalysis of meta-analyses. <b>Data sources</b> Drug trials with unpublished outcome data for new molecular entities that were approved by the FDA between 2001 and 2002 were identified. For each drug, eligible systematic reviews containing at least one meta-analysis were identified by searches of Medline, Embase, and the Cochrane Library in November 2010. <b>Selection criteria</b> Eligible systematic reviews were done after FDA approval of the drug, were published in English, and had outcomes and comparators that were the same as those of the trials with unpublished FDA trial outcomes, and the characteristics of participants in the systematic reviews were consistent with the FDA approved indication for the drug. Clinical guidelines, conference proceedings, duplicate systematic reviews, and systematic reviews in which included trials were not referenced or that combined trials across multiple drug classes were excluded. Systematic reviews using non-standard meta-analytic techniques (such as Bayesian or network meta-analyses) and those that used inappropriate or invalid methods for calculation of summary statistics (such as unweighted pooled analyses) were also excluded. <b>Data extraction</b> Two authors independently extracted data from both the published systematic reviews and the FDA's medical and statistical reviews of the trials submitted to FDA. <b>Main outcome measure</b> Summary statistics (risk ratios, odds ratios, or weighted mean differences) for relevant outcomes with and without unpublished FDA trial data. <b>Results</b> 42 meta-analyses (41 efficacy outcomes, one harm outcome) for nine drugs across six drug classes were reanalysed. Overall, addition of unpublished FDA trial data caused 46% (19/41) of the summary estimates from the meta-analyses to show lower efficacy of the drug, 7% (3/41) to show identical efficacy, and 46% (19/41) to show greater efficacy. The summary estimate of the single harm outcome showed more harm from the drug after inclusion of unpublished FDA trial data. <b>Conclusion</b> The effect of including unpublished FDA trial outcome data varies by drug and outcome. Unpublished FDA trial outcome data should be available and included in meta-analysis. Making these data easily accessible is particularly important because the effects of including unpublished data vary.
Human milk and the preterm baby.
Authors: A F Williams
Journal: BMJ (1993)

practices.Indeed, the best solution to the underlying problems might be to introduce a purchaser-provider model like that introduced into the NHS.The Advisory Council on Science and Technology suggested this to Mr Waldegrave, but he turned it down.With this proposal the MRC (and the other research councils) would become purchasers of research and have no responsibility for managing providers.The units would become providers of research and would compete for contracts from the research councils, the charities, government departments, and other bodies.The remote, heavy handed management style of the councils would become irrelevant, and the units would develop their own management styles and flourish or die.This system would allow what the management guru Tom Peters calls "fast failure,"6 which would be overt, swift, and predictable in contrast to the slow, covert, and questionable procedures currently used to close units.Resources could quickly be released for more rewarding research.Mr Waldegrave seems to recognise the need to shift research management from being top down to bottom up, and he hopes that this will be achieved through his proposed "foresight procedures"2: in these procedures researchers and others are systematically questioned about research prospects and the information derived is combined with information from marketing people to develop a strategy that is scien- tifically advanced and fits with what the market needs.But Mr Waldegrave seems to have neglected the effector arm of this process.If the management styles of the research councils are not radically reformed-perhaps to the point of a purchaser- provider split being introduced-then nothing will change.
Bile, bacteria and bowel cancer.
Authors: M J Hill
Journal: Gut (1983)

Leading articleBile, bacteria and bowel cancerThe large bowel is one of the commonest sites of carcinogenesis in western populations; it is the commonest site in the United States, West Germany, Australia, and New Zealand and is the second commonest in England and Wales, Sweden, Denmark and many other west European countries.It is, however, rare in Africa, Asia and South America and studies of migrants, religious subgroups and the like, indicated that the disease has an environmental aetiology.Most epidemiologists agree that diet is important in the causation of the disease although there is little agreement concerning which specific dietary item is most strongly implicated.This lack of agreement probably indicates that the relation between diet and colorectal carcinogenesis is not simple and is probably mediated by some factor, the concentration of which is in turn determined by diet.In 1969 Aries et all postulated that colorectal cancer is caused by metabolites produced in the colon from some benign substrate by the bacterial flora.As the diet would control both the concentration of substrate and the composition and metabolic activity of the flora, it would determine the amount of metabolite; this would explain both the fact that the risk of colorectal cancer is related to diet and that the relationship is far from simple.In following up this hypothesis most investigators have pursued the
Blood Gases: Arterial or Venous?
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1986)

The determination of "blood gases" in the current clinical vernacular means the measurement of pH, partial pressure of carbon dioxide (PCO2), and partial pressure of oxygen (PO2) in fresh samples of whole blood drawn without exposure to air and usually protected from glycolysis and coagulation by prompt cooling and the addition of heparin. With the use of the Henderson–Hasselbalch equation, the concentration of bicarbonate in the plasma can also be calculated from the pH and PCO2, and this value is usually included with the report of the blood gases.These data have found increasing . . .
THE ROLE OF THE FATHER IN FAMILIES WITH A SCHIZOPHRENIC PATIENT
Authors: MURRAY BOWEN, ROBERT H. DYSINGER, BETTY BASAMANIA
Journal: American Journal of Psychiatry (1959)

A small number of fathers, mothers, and their schizophrenic children have been studied as a group and treated in family psychotherapy for periods up to 2½ years. The view of the family as a single organism provides a broader, more distant perspective than is possible with close up views of individual family members. An effort is made to avoid the use of terms and descriptions that are associated with the more familiar individual perspective. The father is described as he is seen to function in terms of the broader family perspective. Several prominent patterns have emerged when the family has been viewed from this position. The family members, particularly the father and mother, function in reciprocal relation to each other. They are separated from each other by an emotional barrier which, in some ways, has characteristics of an "emotional divorce." Either father or mother can have a close emotional relationship with the patient when the other parent permits. The patient's function is similar to that of an unsuccessful mediator of the emotional differences between the parents. The most frequent family pattern is an intense two-some between mother and patient which excludes the father and from which he permits himself to be excluded. The family pattern changes under varying individual and family circumstances in the course of daily living.
Review: Long-term use of inhaled corticosteroids increases fracture risk in COPD
Authors: Joram S. Seggev
Journal: Annals of Internal Medicine (2012)

Source Citation Loke YK, Cavallazzi R, Singh S. Risk of fractures with inhaled corticosteroids in COPD: systematic review and meta-analysis of randomised controlled trials and observational studies. Thorax. 2011;66:699-708. 21602540
Innate immune response to double-stranded RNA in biliary epithelial cells is associated with the pathogenesis of biliary atresia
Authors: Kenichi Harada, Yasunori Sato, Keita Itatsu, Kumiko Isse, Hiroko Ikeda, Mitsue Yasoshima, Yoh Zen, Akira Matsui, Yasuni Nakanuma
Journal: Hepatology (2007)

Abstract Infections of Reoviridae consisting of a double-stranded RNA (dsRNA) genome are a possible cause of biliary atresia (BA). The aim of the present study is to clarify the pathophysiological function of dsRNA viruses in the pathogenesis of BA. The expression of dsRNA pattern-recognizing receptors, Toll-like receptor 3 (TLR3), retinoic acid inducible gene I (RIG-I), melanoma differentiation-associated gene-5 (MDA-5), and dsRNA-activated protein kinase R (PKR) was constitutively detected in cultured human biliary epithelial cells (BECs). Stimulation with polyinosinic-polycytidylic acid [poly(I:C), a synthetic analog of viral dsRNA] induced the activation of transcription factors [nuclear factor (NF)-κB and interferon regulatory factor 3 (IRF3)] and the production of interferon-β1 (IFN-β1) and MxA as potent antiviral responses. Moreover, poly(I:C) up-regulated the expression of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), and both poly(I:C) and TRAIL reduced the viability of cultured human BECs by enhancing apoptosis. Experiments in vivo using tissue sections of extrahepatic bile ducts from patients with BA and controls (choledochal cysts and nonbiliary diseases) showed that the activation of NF-κB, interferon regulatory factor-3 (IRF-3), and PKR, and the enhancement of TRAIL and single-stranded DNA (ssDNA)–positive apoptosis were significant in BA, although extrahepatic bile ducts diffusely and constantly expressed TLR3 in all diseases. Conclusion : dsRNA viruses could directly induce the expression of TRAIL and apoptosis in human biliary epithelial cells as a result of the biliary innate immune response, supporting the notion that Reoviridae infections are directly associated with the pathogenesis of cholangiopathies in cases of BA. (HEPATOLOGY 2007.)
Oral tacrolimus in refractory inflammatory bowel disease - long term treatment outcomes and follow-up in a UK cohort
Authors: J. Landy, S. T. Peake, N. Karim, N. Ikin, S. Ng, A. Akbar, A. L. Hart
Journal: Gut (2011)

<h3>Introduction</h3> Previous reports suggest tacrolimus is effective for induction of remission in refractory inflammatory bowel disease (IBD).1 There are limited data regarding the long term outcomes of tacrolimus for inflammatory bowel disease. The authors reviewed the long term experience of patients treated with tacrolimus at a tertiary centre. <h3>Methods</h3> In this retrospective, single centre study the authors reviewed the clinical records of 18 adult patients between 2006 and 2010 with refractory IBD (UC 9; CD 8; Pouchitis 1) treated with oral tacrolimus. Clinical activity was evaluated using modified Truelove and Witts Score (mTW), CDAI and PDAI respectively. Response and remission were considered mTW reduction ≥50%/&lt;4 points, CDAI reduction ≥70/CDAI&lt;150 or reduction of PDAI ≥3/PDAI≥7. Tacrolimus was administered orally in all patients (0.1 mg/kg body weight/day) aiming for serum trough levels of 5–10 ng/ml. <h3>Results</h3> Mean duration of treatment with tacrolimus was 14.6 months (range 1–50) and mean duration of follow-up was 37.7 months (range 23–67). Mean disease duration for both UC and CD patients was 6 years (range 2–25 years). 7 UC patients had pancolonic and 2 left sided disease. Disease distribution for CD patients was colonic (3); ileocolonic (3); ileal and upper GI disease (1), perianal (1). 2 CD patients had a history of previous surgery. 3/9 UC and 4/8 CD were taking concurrent azathioprine and 4 patients (2 UC, 2 CD) had previously lost response to infliximab therapy. One patient achieved remission at 3 months, stopped tacrolimus due to renal impairment, but maintained remission up to 54 months on no medication. 5 patients (2 UC, 3 CD) had a sustained response to treatment, but did not achieve remission. 3 other patients (2 UC, 1 CD) stopped treatment due to adverse effects (leucopoenia – 11 months, headache – 6 months, paresthesia – 5 months). The remaining 9 patients lost response to tacrolimus. Three patients (2 UC and 1 CD) showed endoscopic improvement. 6 patients (33%&gt;4 UC, 2 CD) required surgery in the treatment or follow-up period. <h3>Conclusion</h3> In our experience, one third of patients treated with long term tacrolimus required surgery. Although a proportion responded to tacrolimus therapy, the majority of patients ultimately required alternative therapies.
Waging Nuclear Peace: The Technology and Politics of Nuclear Weapons
Authors: Jane M. Orient
Journal: JAMA (1985)

<b>Nuclear Winter: The Human and Environmental Consequences of Nuclear War</b>, by Mark A. Harwell, 179 pp, 27 illus, $16.95, New York, Springer-Verlag, 1984. Policy should be based on a dispassionate and complete assessment rather than on emotional oversimplifications, even if the subject is nuclear war. Robert Ehrlich, chairman of the physics department at George Mason University, Fairfax, Va, suggests that overstatement of the consequences of a nuclear attack could be just as perilous as understatement. His comprehensive description of weapons effects emphasizes the variables and the uncertainties. While not denying their significance for public health, he puts the long-term effects into some perspective. For example, the loss of life expectancy from exposure to 100 rem of radiation is about 0.2 years, compared with 6.0 years from smoking cigarettes. The most catastrophic delayed event might be the nuclear winter; however, after a critical examination of the assumptions, Ehrlich concludes that a
Segmental Necrosis of Small Bronchi after Prolonged Intakes of <i>Sauropus androgynus</i> in Taiwan
Authors: YIH-LEONG CHANG, YU-TUNG YAO, NAI-SAN WANG, YUNG-CHIE LEE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Since 1994 an endemic of chronic obstructive pulmonary disease (COPD) has developed in Taiwan after a prevalent use of a body-weight-reducing vegetable, Sauropus androgynus (SA). All conventional treatments for COPD, including steroids and bronchodilators, had been ineffective. Studies of limited lung biopsy specimens from these patients revealed bronchiolitis obliterans. A few patients died, but many developed protracted chronic respiratory failure. Because of the chronic debilitation and ineffective conventional treatments, single lung transplants were performed as the last resort in four patients. The excised lungs revealed focal fibromuscular sclerosis and obliteration of bronchial arteries in the wall of large bronchi 4 to 5 mm in diameter with segmental necrosis of bronchi 2 to 4 mm in diameter. Bronchi immediately proximal to the necrotic zone showed fibrosis and atrophy of cartilage, bronchial glands, and smooth muscle cells; bronchioles immediately distal showed obstruction or dilatation. Most bronchi larger than 5 mm, pulmonary vessels, small bronchioles, and alveoli were little altered. The pathologic changes were most consistent with segmental ischemic necrosis of bronchi at the water-shed zone of bronchial and pulmonary circulation. The specific etiologic agent and detail of pathogenesis of this SA-related COPD needs further investigation.
Rickettsialpox
Authors: George Pike, Sidney Cohen, Edward S. Murray
Journal: New England Journal of Medicine (1950)

THE natural occurrence of rickettsialpox, a specific infectious disease caused by Rickettsia akari, has been observed only in New York City, where many cases have been reported since 1946.1 2 3 4 5 A reservoir of the infectious agent exists in the common house mouse (Mus musculus) and transmission to man is believed to be effected by the mouse mite (Allodermanyssus sanguineus.)6 7 8 The illness is marked by a primary cutaneous lesion, fever, systemic symptoms and a generalized exanthem.The purpose of this paper is to report a case history clinically and serologically characteristic of rickettsialpox in a patient who . . .
Serum thrombopoietin levels are linked to liver function in untreated patients with hepatitis C virus-related chronic hepatitis
Authors: Edoardo Giannini, Paolo Borro, Federica Botta, Alessandra Fumagalli, Federica Malfatti, Elena Podestà, Paola Romagnoli, Emanuela Testa, Bruno Chiarbonello, Simone Polegato, Mario Mamone, Roberto Testa
Journal: Journal of Hepatology (2002)
A genome-wide association study identifies two risk loci for congenital heart malformations in Han Chinese populations
Authors: Zhibin Hu, Yongyong Shi, Xuming Mo, Jing Xu, Bijun Zhao, Yuan Lin, Shiwei Yang, Zhengfeng Xu, Juncheng Dai, Shandong Pan, Min Da, Xiaowei Wang, Bo Qian, Yang Wen, Juan Wen, Jinliang Xing, Xuejiang Guo, Yankai Xia, Hongxia Ma, Guangfu Jin, Shiqiang Yu, Jiayin Liu, Zuomin Zhou, Xinru Wang, Yijiang Chen, Jiahao Sha, Hongbing Shen
Journal: Nature Genetics (2013)
Penalties mean hospitals might need to make 7% of savings each year, warns regulator
Authors: H. Mooney
Journal: BMJ (2011)

<h3>Abstract</h3> <h3>Background</h3> Computed tomography (CT) is the preferred imaging method for diagnosing 2019 novel coronavirus (COVID19) pneumonia. Our research aimed to construct a system based on deep learning for detecting COVID-19 pneumonia on high resolution CT, relieve working pressure of radiologists and contribute to the control of the epidemic. <h3>Methods</h3> For model development and validation, 46,096 anonymous images from 106 admitted patients, including 51 patients of laboratory confirmed COVID-19 pneumonia and 55 control patients of other diseases in Renmin Hospital of Wuhan University (Wuhan, Hubei province, China) were retrospectively collected and processed. Twenty-seven consecutive patients undergoing CT scans in Feb, 5, 2020 in Renmin Hospital of Wuhan University were prospectively collected to evaluate and compare the efficiency of radiologists against 2019-CoV pneumonia with that of the model. <h3>Findings</h3> The model achieved a per-patient sensitivity of 100%, specificity of 93.55%, accuracy of 95.24%, PPV of 84.62%, and NPV of 100%; a per-image sensitivity of 94.34%, specificity of 99.16%, accuracy of 98.85%, PPV of 88.37%, and NPV of 99.61% in retrospective dataset. For 27 prospective patients, the model achieved a comparable performance to that of expert radiologist. With the assistance of the model, the reading time of radiologists was greatly decreased by 65%. <h3>Conclusion</h3> The deep learning model showed a comparable performance with expert radiologist, and greatly improve the efficiency of radiologists in clinical practice. It holds great potential to relieve the pressure of frontline radiologists, improve early diagnosis, isolation and treatment, and thus contribute to the control of the epidemic.
Hypercalcemia and Elevated 1,25-Dihydroxyvitamin D Levels in a Patient with End-Stage Renal Disease and Active Tuberculosis
Authors: Peter J. Gkonos, Roger London, Ernesto D. Hendler
Journal: New England Journal of Medicine (1984)

HYPERCALCEMIA has been reported to occur in association with several granulomatous disorders, including sarcoidosis, tuberculosis, fungal infections, and chronic beryllium disease.1 2 3 4 Recent reports suggest that extrarenal production of 1,25-dihydroxyvitamin D (1,25-(OH)2D) is involved in the pathogenesis of the hypercalcemia of sarcoidosis. These reports include an anephric patient5 and a patient with end-stage renal disease6 (both of whom were on hemodialysis) who had sarcoidosis, hypercalcemia, and elevated 1,25-(OH)2D levels. Although no such reports are available in the case of tuberculosis, some studies have suggested that hypercalcemia is more likely to occur in patients with tuberculosis who are . . .
Subcutaneous nodules on the buttocks as a manifestation of dialysis-related amyloidosis: a clinicopathological entity?
Authors: S. Shimizu, C. Yasui, K. Yasukawa, H. Nakamura, H. Shimizu, K. Tsuchiya
Journal: British Journal of Dermatology (2003)

Summary While β2-microglobulin amyloidosis occurring in patients undergoing long-term dialysis is frequently associated with joint involvement, skin lesions have rarely been encountered. We report a 57-year-old man with extensive subcutaneous amyloid deposition forming large nodules on the buttocks; the patient had been on maintenance dialysis for 28 years. Although this condition is rare, a review of the literature indicates that the majority of such lesions occur around the buttock region.
Ethics and Public Health Emergencies: Restrictions on Liberty
Authors: Matthew K. Wynia
Journal: The American Journal of Bioethics (2007)

Responses to public health emergencies can entail difficult decisions about restricting individual liberties to prevent the spread of disease. The quintessential example is quarantine. While isolating sick patients tends not to provoke much concern, quarantine of healthy people who only might be infected often is controversial. In fact, as the experience with severe acute respiratory syndrome (SARS) shows, the vast majority of those placed under quarantine typically don't become ill. Efforts to enforce involuntary quarantine through military or police powers also can backfire, stoking both panic and disease spread. Yet quarantine is part of a limited arsenal of options when effective treatment or prophylaxis is not available, and some evidence suggests it can be effective, especially when it is voluntary, home-based and accompanied by extensive outreach, communication and education efforts. Even assuming that quarantine is medically effective, however, it still must be ethically justified because it creates harms for many of those affected. Moreover, ethical principles of reciprocity, transparency, non-discrimination and accountability should guide any implementation of quarantine.
CXCL12 (SDF1α)-CXCR4/CXCR7 Pathway Inhibition: An Emerging Sensitizer for Anticancer Therapies?
Authors: Dan G. Duda, Sergey V. Kozin, Nathaniel D. Kirkpatrick, Lei Xu, Dai Fukumura, Rakesh K. Jain
Journal: Clinical Cancer Research (2011)

Abstract Addition of multiple molecularly targeted agents to the existing armamentarium of chemotherapeutics and radiotherapies represents a significant advance in the management of several advanced cancers. In certain tumor types with no efficacious therapy options, these agents have become the first line of therapy, for example, sorafenib in advanced hepatocellular carcinoma or bevacizumab in recurrent glioblastoma. Unfortunately, in many cases, the survival benefits are modest, lasting only weeks to a few months. Moreover, they may not show benefit in patients with localized disease (i.e., in the adjuvant setting). Recent studies have provided increasing evidence that activation of the chemokine CXCL12 (SDF1α) pathway is a potential mechanism of tumor resistance to both conventional therapies and biological agents via multiple complementary actions: (i) by directly promoting cancer cell survival, invasion, and the cancer stem and/or tumor-initiating cell phenotype; (ii) by recruiting “distal stroma” (i.e., myeloid bone marrow–derived cells) to indirectly facilitate tumor recurrence and metastasis; and (iii) by promoting angiogenesis directly or in a paracrine manner. Here, we discuss recent preclinical and clinical data that support the potential use of anti-CXCL12 agents (e.g., AMD3100, NOX-A12, or CCX2066) as sensitizers to currently available therapies by targeting the CXCL12/CXCR4 and CXCL12/CXCR7 pathways. Clin Cancer Res; 17(8); 2074–80. ©2011 AACR.