tbuckley/cabot-search huggingface dataset:
Overestimation of the Effect Size in Group Sequential Trials
Authors: Jenny J. Zhang, Gideon M. Blumenthal, Kun He, Shenghui Tang, Patricia Cortazar, Rajeshwari Sridhara
Journal: Clinical Cancer Research (2012)

Group sequential designs (GSD), which provide for interim monitoring of efficacy data and allow potential early trial termination while preserving the type I error rate, have become commonplace in oncology clinical trials. Although ethically appealing, GSDs tend to overestimate the true treatment effect size at early interim analyses. Overestimation of the treatment effect may exaggerate the benefit of a drug and provide imprecise information for physicians and their patients about a drug's true effect. The cause and effect of such a phenomenon are generally not well understood by many in clinical trial practice. In this article, we provide a graphical explanation for why the phenomenon of overestimation in GSDs occurs. The potential overestimation of the magnitude of the treatment effect is of particular concern in oncology, in which the more subjective endpoint of progression-free survival has increasingly been adopted as the primary endpoint in pivotal phase III trials.
Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction
Authors: L. Barile, V. Lionetti, E. Cervio, M. Matteucci, M. Gherghiceanu, L. M. Popescu, T. Torre, F. Siclari, T. Moccetti, G. Vassalli
Journal: Cardiovascular Research (2014)

AimsRecent evidence suggests that cardiac progenitor cells (CPCs) may improve cardiac function after injury. The underlying mechanisms are indirect, but their mediators remain unidentified. Exosomes and other secreted membrane vesicles, hereafter collectively referred to as extracellular vesicles (EVs), act as paracrine signalling mediators. Here, we report that EVs secreted by human CPCs are crucial cardioprotective agents.
Carbon monoxide poisoning in an infant.
Authors: H Venning, D Roberton, A D Milner
Journal: BMJ (1982)

Carbon monoxide poisoning presents two risks to infants.The non-specific presenting symptoms make it difficult to diagnose, and the special characteristics of fetal haemoglobin may lead to greater tissue hypoxia than in older children or adults. Case reportA 13-week-old baby girl travelled for six hours in a carry-cot that had been placed behind the rear seat of a one-year-old estate car.At the end of the journey she was hypotonic and had vomited.She was taken in the same car to a local hospital and was transferred by ambulance to our care.Shortly after arrival she began convulsing.There was no clinical evidence of hyperpyrexia, aspiration, or infection.Plasma electrolyte, glucose, and ammonia concentrations and a chest x-ray examination were normal.Her arterial blood pH was 7 33, with a base deficit of 8 mmol (mEq)/l.The cerebrospinal fluid was normal.Her blood carboxyhaemoglobin (COHb)
Tobacco companies say regulations are unconstitutional
Authors: D. Spurgeon
Journal: BMJ (2002)

Canada's three largest tobacco companies have begun a legal fight to defeat the country's tobacco act and regulations, which the World Health Organization says are being used as a model in some 40 other countries worldwide.

The companies, JTI-Macdonald, Imperial Tobacco Canada, and Rothmans, Benson and Hedges, asked the Quebec Superior Court in Montreal to declare unconstitutional the 1997 Tobacco Act and two subsequent regulations, saying that they violated the companies' right to freedom of expression under Canada's Charter of Rights and Freedoms.

The legislation bans tobacco …
Incidence of non-specific abdominal pain in children during school term: population survey based on discharge diagnoses
Authors: N. Williams, D. Jackson, P. C Lambert, J M. Johnstone
Journal: BMJ (1999)

Abdominal pain remains a common problem in childhood and often results in admission to hospital. 1 Of these children, however, only 30-40% will require surgical intervention. 2 3Most are discharged with a diagnosis of non-specific abdominal pain. 4 To elucidate whether non-specific abdominal pain is more common during the school term compared with the school holiday we investigated the admission rates for non-specific abdominal pain and acute appendicitis throughout the school year.
Mercury perchloride in surgery.
Authors: J. C. Gingell, J. Clegg, M. Wallace
Journal: BMJ (1967)

Previously an uninterrupted recovery could confidently have been expected in this type of poisoning once the patient had regained consciousness.This case would suggest that relapse and sudden death may occur in poisoning by tricyclic antidepressant compounds after apparent recovery.The forced diuresis may have kept the patient alive initially and there could be an argument for continuing this treatment in order to wash out the possible second wave of metabolites, which would otherwise contribute to an unexpected relapse.
Macrolide antibiotics and cystic fibrosis
Authors: D G Peckham
Journal: Thorax (2002)

Do the macrolides have a role in the treatment of cystic fibrosis?

There is growing interest in the potential use of macrolide antibiotics as anti-inflammatory agents in cystic fibrosis. This stems from the dramatic success of long term erythromycin in the treatment of diffuse panbronchiolitis (DPB), a condition with a high prevalence in Japan but rare elsewhere.1–3 Clinically, DPB exhibits some similarities to cystic fibrosis including chronic productive cough, exertional dyspnoea, chronic sinusitis, mucoid Pseudomonas aeruginosa colonisation, and bronchiectasis. The introduction of erythromycin as a treatment for DPB has had a dramatic impact on mortality, increasing 10 year survival from 12.4–21.9% to over 90% in those colonised with P aeruginosa .3,4 Similar success has been reported with clarithromycin, roxithromycin, and azithromycin.1,3 While the aetiology of both conditions may be very different, it is the similarities which beg the question “do the macrolides have a role in the treatment of cystic fibrosis?”

The macrolide antibiotics are an intriguing group of drugs with both anti-inflammatory and antibacterial …
The release of endogenous norepinephrine from the coccygeal artery of spontaneously hypertensive and Wistar-Kyoto rats.
Authors: M P Galloway, T C Westfall
Journal: Circulation Research (1982)

The potassium (K+)-induced release of endogenous norepinephrine from the coccygeal artery of spontaneously hypertensive rats has been studied as a function of the development of hypertension. The absolute amount of norepinephrine released by potassium was greater in spontaneously hypertensive rat than the normotensive Wistar-Kyoto rat, regardless of age or blood pressure. However, the %-fractional release was elevated only in the rats with chronic hypertension. Preincubation of tissues with the alpha 2-antagonist, yohimbine, significantly enhanced norepinephrine overflow in all tissues studied. Young hypertensive animals demonstrated an enhancement equal to the Wistar-Kyoto rat controls. In the adult spontaneously hypertensive rat, however, there was a significantly lesser enhancement produced by yohimbine. Levels of norepinephrine in the nerves supplying the artery were greater in the prehypertensive spontaneously hypertensive rat than the age-matched Wistar-Kyoto rat. The norepinephrine content in arteries from adult animals was equivalent. The explanation for the attenuation of the yohimbine effect of chronic hypertensive animals is unclear. Although several explanations are possible, the data are consistent with the hypothesis that spontaneously hypertensive rats with chronic hypertension have subsensitive prejunctional alpha 2-receptors as evidenced by an increased %-fractional release of norepinephrine and a decreased enhancement of overflow in the presence of yohimbine. Clearly, further studies are needed to answer this provocative question and to understand the complex interactions of adrenergic neurotransmission in hypertensive animals.
South Africa: Patterns of Rheumatic Disease
Authors: STANLEY S. GILDER
Journal: Annals of Internal Medicine (1976)

Abroad1 March 1976South Africa: Patterns of Rheumatic DiseaseSTANLEY S. GILDER, M.D.STANLEY S. GILDER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-3-336 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhen i was a student, older textbooks still said that the Irish had a racial predisposition to tuberculosis and the Jews to Buerger's disease. Both statements, like many made about ethnic groups, were wrong. When I attended a rheumatology congress years ago, someone said that rheumatoid arthritis was rare in black Africans, yet I frequently discover early cases among my mostly urbanized and exclusively black clientele. So I was very interested to read a series of much needed epidemiologic studies on rheumatic diseases recently published in theSouth African Medical Journal, and one important article in theBritish Medical Journal.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: STANLEY S. GILDER, M.D.Affiliations: 110 Nuffield St., Rietondale, Pretoria 0002, Republic of South Africa PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1976Volume 84, Issue 3Page: 336-336KeywordsEpidemiologyJewish peopleRheumatoid arthritisRheumatology ePublished: 1 December 2008 Issue Published: 1 March 1976 PDF downloadLoading ...
Early Versus Delayed Enalapril in Patients With Left Ventricular Systolic Dysfunction: Impact on Morbidity and Mortality 15 Years After the SOLVD Trial
Authors: Sylvie A. Ahn, Philip Jong, Salim Yusuf, Shrikant I. Bangdiwala, Hubert G. Pouleur, Michel F. Rousseau
Journal: Journal of the American College of Cardiology (2006)
Comparison of intestinal anaphylactic reactions in sensitized mice challenged with untreated bovine milk and homogenized bovine milk
Authors: O. M. Poulsen, B. R. Nielsen, A. Basse, J. Hau
Journal: Allergy (1990)

Outbred NMRI mice were sensitized for high IgE production either by subcutaneous injections of low doses of untreated bovine milk or homogenized bovine milk in combination with intraperitoneal injections of Freund's Complete Adjuvant or by oral administration of untreated or homogenized bovine milk without adjuvant. When analysed in murine passive cutaneous anaphylaxis test both types of milk resulted in production of reaginic antibodies against bovine milk proteins when given subcutaneously. When given orally, homogenized milk resulted in reagin production in 10 out of 14 mice, whereas untreated milk resulted in reagin production in only one out of 12 mice. The sensitized mice, and control mice, were orally challenged with either untreated milk, homogenized milk or 0.9% NaCl. Examination of the intestines 40 min after oral administration revealed that homogenized milk, contrary to untreated milk or 0.9% NaCl, resulted in a large increase in the mass of the proximal gut segment of mice sensitized orally with homogenized milk compared with control mice orally challenged with saline ( P &lt; 0.001), and only mice both sensitized and challenged orally with homogenized milk showed degranulation of mast cells in the intestinal wall. By contrast, subcutaneously sensitized mice or mice sensitized orally with untreated bovine milk showed no significant intestinal reaction upon oral challenge with either homogenized or untreated bovine milk. These observations may indicate that the route of sensitization is of great importance when intestinal reactions are to be studied, and that homogenization of bovine milk may render the milk more agressive with respect to its ability to induce intestinal reactions. The study indicates that mice may be an attractive experimental animal model for mimicking the intestinal anaphylactic reactions of cow milk‐allergic humans.
Analysis of flow characteristics in poststenotic regions of the human coronary artery during bypass graft surgery.
Authors: F Kajiya, K Tsujioka, Y Ogasawara, Y Wada, S Matsuoka, S Kanazawa, O Hiramatsu, S Tadaoka, M Goto, T Fujiwara
Journal: Circulation (1987)

Poststenotic blood flow velocities were evaluated in nine patients with 75% to 99% stenosis of the left anterior descending coronary artery (LAD) during coronary artery bypass graft surgery. We used the 20 MHz 80-channel pulsed Doppler velocimeter developed in our laboratory. An operator placed a specially designed probe on the native LAD with his fingers. Before induction of extracorporeal circulation, LAD blood velocities were measured at several locations distal to the stenosis. The poststenotic flow velocities were rich in systolic flow component with reduced diastolic component. The velocity configuration in the poststenotic portions was characterized by the presence of reverse flow velocities and/or irregularity of the velocity pattern near the vessel wall, indicating the existence of flow separation and recirculation in the regions. The broadening of the velocity spectrum observed at central axial regions suggested the occurrence of flow disturbances. After grafting, the velocity waveform in the LAD beyond a vein bypass graft changed to a diastolic-predominant pattern with a relatively small systolic component. A transient bypass graft occlusion caused a marked reduction in diastolic flow velocity. The systolic-to-diastolic velocity ratio increased from 0.27 +/- 0.07 to 1.50 +/- 0.50 (p less than .01) by the graft occlusion.
Retraction: Cheng B-Q, et al. Chemoembolization combined with radiofrequency ablation for patients with hepatocellular carcinoma larger than 3 cm: a randomized controlled trial. &lt;emph type="ital"&gt;JAMA&lt;/emph&gt;. 2008;299(14):1669-1677.
Authors: Catherine D. DeAngelis
Journal: JAMA (2009)

Chemoembolization Combined With Radiofrequency Ablation for Patients With Hepatocellular Carcinoma Larger Than 3 cm
Appropriate vs Clinically Useful Diagnostic Tests
Authors: John P. A. Ioannidis
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Christopher Michael Wragg
Authors: L. Wood
Journal: BMJ (2014)

When we stepped from the packed chapel to the flower display after Chris Wragg’s funeral, the crematorium rang to the sound of laughter, as we swopped anecdotes about this iconic Yorkshireman.

He had spent half his career in AE poling himself down a corridor on a trolley, singing “Just One Cornetto”; and taking advantage of an empty waiting room (it was a long time ago), to sit and pretend to be a patient, then storm out, inviting the new arrivals to follow. Utterly unacceptable behaviour, of course, even by those days’ …
Human leukocyte antigen in primary biliary cirrhosis: An old story now reviving
Authors: Pietro Invernizzi
Journal: Hepatology (2011)

Primary biliary cirrhosis (PBC) is an autoimmune biliary disease characterized by injury of small and medium size bile ducts, eventually leading to liver cirrhosis and death. Although the causes remain enigmatic, recent evidence has strengthened the importance of genetic factors in determining the susceptibility to the disease. Besides the strong heritability suggested by familial occurrence and monozygotic twins concordance, for decades there has not been a clear association with specific genes, with the only exception of a low risk conferred by a class II human leukocyte antigen (HLA) variant, the DRB1*08 allele, at least in some populations. The picture has become more complete when strong protective associations between PBC and the HLA DRB1*11 and DRB1*13 alleles were found in Italian and UK series. However, HLA genes have begun again to attract interest thanks to recent genome-wide association studies (GWAS), which clearly demonstrated that the major components of the genetic architecture of PBC are within the HLA region. As expected in a genetically complex disease, GWAS also identified several novel non-HLA variants, but it is worth noting that all of them are in immuno-related genes. In this review, the paradigmatic tale of what, and how, we learned about HLA genes in PBC will be retraced with particular focus on how GWAS are enabling a rewriting the story of PBC pathogenesis. These recent discoveries will not only drive functional studies but will also hold the promise of developing novel disease-specific treatments.
Bicarbonate secretion in vivo by rat distal tubules during alkalosis induced by dietary chloride restriction and alkali loading.
Authors: D Z Levine, M Iacovitti, V Harrison
Journal: Journal of Clinical Investigation (1991)

To examine in vivo the separate effects on distal tubule JtCO2, of dietary chloride restriction, bicarbonate loading, and changes in luminal chloride concentration, we microperfused distal tubules at a physiologic flow rate (8 nl/min) with solutions containing either 45 or 0 mM chloride (after gluconate substitution). Rats were fed a diet containing zero, minimal, or normal amounts of chloride, while drinking either water or a solution of 0.15 M sodium bicarbonate. Neither extracellular fluid volume contraction nor negative chloride balance ensued. Analysis of covariance with repeated measures demonstrated that dietary chloride, drinking sodium bicarbonate, and perfusion with either 45 mM or zero chloride, each have separate and significant modulating effects on distal tubule bicarbonate secretion. During mild alkalemia, there is modest bicarbonate secretion which is significantly different from zero (-9.9 +/- 3.2 pmol.min-1.mm-1, P less than 0.01), and which is suppressed after perfusion with zero chloride. In contrast, during more pronounced metabolic alkalosis after supplemental bicarbonate drinking, the bicarbonate secretory flux is brisk (-26 +/- 3 pmol.min-1.mm-1) and significantly different from zero and persists (-11 +/- 3 pmol.min-1.mm-1) even during perfusion with zero luminal chloride. Accordingly, in this two-day model of alkalosis induced by dietary chloride restriction, there is regulatory secretion of bicarbonate by distal tubules in vivo which is modulated by luminal chloride concentration.
Factors affecting liver fibrosis in human immunodeficiency virus–and hepatitis C virus–coinfected patients: Impact of protease inhibitor therapy
Authors: Yves Benhamou, Vincent Di Martino, Marie Bochet, Geneviève Colombet, Vincent Thibault, Amélie Liou, Christine Katlama, Thierry Poynard
Journal: Hepatology (2001)

Hepatitis C virus (HCV)–related liver fibrosis progression is accelerated in human immunodeficiency virus (HIV)–infected patients. The effect of protease inhibitor (PI) therapy on liver fibrosis is unknown. The aim of this work was to analyze the impact of PI therapy on HCV–related liver fibrosis in HIV/HCV coinfected patients. We evaluated in a long–term follow–up retrospective cohort study the influence of antiretroviral therapy containing PI on liver fibrosis in 182 consecutive HIV/HCV coinfected patients. At liver biopsy, 63 patients had received PI and 119 patients had never been treated with PI. Relationships between liver histologic features, age, alcohol consumption, CD4 cell count, HIV–RNA load, and antiretroviral regimens were analyzed. Liver fibrosis stage was lower in patients receiving PIs by comparison with patients who had never received PIs ( P = .03). The 5–, 15–, and 25–year cirrhosis rates were 2% versus 5%, 5% versus 18%, and 9% versus 27%, respectively, in patients who had received PIs compared with PI–untreated patients ( P = .0006). Multivariate analysis identified 4 independent predictors of progression to cirrhosis: absence of protease inhibitor therapy (relative risk [RR] = 4.74, 95% confidence interval [CI], 1.34–16.67), heavy alcohol consumption (≥ 50 g daily) (RR = 4.71, 95% CI, 1.92–11.57), low CD4 cell count (&lt;200/μL) (RR = 2.74, 95% CI, 1.17–6.41), and age at HCV contamination (≥20 years) (RR = 2.37, 95% CI, 1.04–5.38). In conclusion, protease inhibitor therapy might not accelerate progression to HCV–related cirrhosis. Furthermore, chronic use of antiretroviral therapy containing PI together with reduction of alcohol consumption and maintenance of high CD4 count could have a beneficial impact on liver fibrosis progression in HIV/HCV coinfected patients.
Madrid March 11, 2004
Authors: Alice Gifford
Journal: Annals of Internal Medicine (2006)

Ad Libitum7 March 2006Madrid March 11, 2004Alice GiffordAlice GiffordFrom Augusta, ME 04330.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-5-200603070-00009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail How have you broken into my heartAll you who have gone?Who never said goodbyeNor adios nor adieuNor any other farewellTo those you lovedNor said "Look after the children"Or its equivalent in any languageBut simply went torn and shoelessInto the heavensWhile those who sent you dreamed of Paradise. Author, Article, and Disclosure InformationAffiliations: From Augusta, ME 04330.Current Author Address: Alice M. Gifford, 72 Smith Street, Unit 1, Augusta, ME 04330. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 March 2006Volume 144, Issue 5Page: 343KeywordsChildrenHeart ePublished: 7 March 2006 Issue Published: 7 March 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
US sees no surge in new patient visits despite increase in health insurance
Authors: M. McCarthy
Journal: BMJ (2014)

Although an estimated 20 million people in the United States have obtained health insurance under the Affordable Care Act, US doctors have not yet seen a surge in new patient visits, a new report has claimed.1

The report was the first to be released by the ACAView project, an effort to track the effects of the 2010 health reform law on physicians’ day to day practice. The initiative is a joint project of the Robert Wood Johnson Foundation and athenaResearch—a department of athenahealth, which is a healthcare information technology company that provides electronic health record and practice management services to 52 000 US healthcare providers.

Data entered by providers into athenahealth’s ambulatory care management service gave a “near real time” view of the types of patients visiting doctors, the type of care they receive, and how their care affects the economics of medical practice, the ACAView analysts wrote.

The three year project will continue to track practice changes through to 2016. …