tbuckley/cabot-search huggingface dataset:
AB0445 Exposure–Efficacy Analysis of Mavrilimumab in Rheumatoid Arthritis: Modeling and Simulation of Phase II Clinical Data
Authors: D.C. Jin, C.-Y. Wu, L.K. Roskos, A. Godwood, D. Close, B. Wang
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Mavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor (GM–CSFR) α, is in Phase IIb investigation for the treatment of rheumatoid arthritis (RA). <h3>Objectives</h3> We characterized the exposure–efficacy relationship of mavrilimumab with data from two Phase II randomized controlled trials of patients with moderate to severe RA, via population modeling and clinical simulations. <h3>Methods</h3> In a Phase IIa study, adult patients with active RA received 7 subcutaneous administrations of mavrilimumab (10, 30, 50 or 100 mg every other week [eow]). Mavrilimumab pharmacokinetics and efficacy (DAS28–CRP, ACR20/50) were modeled using a population approach. Clinical simulations were performed to facilitate the design of a Phase IIb trial, in which RA patients received placebo or mavrilimumab (30, 100, or 150 mg eow) for 24 weeks. We developed a joint probability model to describe the risk of voluntary dropouts at each scheduled visit of the Phase IIb study. The exposure–response relationship for mavrilimumab was characterized by clinical simulations via the PK-efficacy dropout model. <h3>Results</h3> Mavrilimumab and placebo treatment effects observed in the Phase IIa study were adequately described by mechanistic PK-efficacy model. Although mavrilimumab 150 mg eow was not evaluated in the Phase IIa study, improved efficacy was observed at this dosage in Phase IIb, as predicted by <i>a priori</i> clinical simulations. The hazard rate of patient dropout prior to next scheduled visits was significantly greater for non-responders, and substantially greater for lower dosage groups at Week 12, when patient rollover to an open-label extension study was permitted. Clinical simulations indicated that the maximum efficacy was reached at the 150-mg eow dosage. <h3>Conclusions</h3> Efficacy outcomes of the Phase IIb study confirmed the rational selection of mavrilimumab 150 mg eow as the best dosage, through modeling of Phase IIa data. Joint modeling of placebo effect, treatment response, and informative dropout greatly facilitates interpretation of Phase IIb results, and will assist in the design of late-stage clinical trials for mavrilimumab. <h3>Disclosure of Interest</h3> D. Jin Shareholder of: AstraZeneca, Employee of: MedImmune, C.-Y. Wu Shareholder of: AstraZeneca, Employee of: MedImmune, L. Roskos Shareholder of: AstraZeneca, Employee of: MedImmune, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, D. Close Shareholder of: AstraZeneca, Employee of: MedImmune, B. Wang Shareholder of: AstraZeneca, Employee of: MedImmune
Esophageal Pressures
Authors: S. MOHSIN SHAH
Journal: Annals of Internal Medicine (1976)

Comments1 March 1976Esophageal PressuresS. MOHSIN SHAH, M.D.S. MOHSIN SHAH, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-84-3-343 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I found Dr. Castell's review of the lower esophageal sphincter (Ann Intern Med83:390-401, 1975) very informative. However, the normal and abnormal pressures listed in Table 1 of his paper can be a source of confusion to the clinician. He should be aware of the variables that affect recording fidelity of pressures (1). In addition, the method used to determine the lower esophageal sphincter pressure will influence the values obtained. In normal subjects the lower esophageal sphincter pressure measured by a rapid pull-through method (24.3 ± 9.5 mm Hg) was significantly greater than the pressure measured by...References1. STEPDODDSHOGAN JWW: Intraluminal esophageal manometry: an analysis of variables affecting recording fidelity of peristaltic pressures. Gastroenterology 67:221-230, 1974 CrossrefMedlineGoogle Scholar2. DODDSHOGANSTEP WWJ: A rapid pull-through technique for measuring lower esophageal sphincter pressure. Gastroenterology 68:437-443, 1975 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Division of Gastroenterology University of Arkansas Medical Center Little Rock, Arkansas 72201 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByA STUDY ON THE HISTORICAL DETAILS OF YOZO YAMAO'S APPOINTMENT AS PRESIDENT OF THE ARCHITECTURAL BUREAU 1 March 1976Volume 84, Issue 3Page: 343-343 Issue Published: 1 March 1976 PDF DownloadLoading ...
Thrombolysis 3 to 4.5 Hours after Acute Ischemic Stroke
Authors: Michel T Torbey, Edward Jauch, David S Liebeskind
Journal: New England Journal of Medicine (2008)

To the Editor: Since the 1995 publication of a study1 reporting the efficacy of intravenous thrombolysis with alteplase for limiting the devastating effects of acute ischemic stroke, we have learned repeatedly that successful thrombolysis is time-dependent. Despite initial skepticism regarding the benefit of such therapy, subsequent trials have replicated similar efficacy, effectiveness, and safety and have continued to emphasize that “time is brain.” In the European Cooperative Acute Stroke Study (ECASS) III trial (Sept. 25 issue),2 Hacke et al. discuss the benefit of intravenous thrombolysis with alteplase administered up to 4.5 hours after the onset of stroke symptoms. Although the findings of previous trials of extended-treatment windows were inconclusive,3 the success of ECASS III beyond 3 hours may reflect earlier treatment (an average of 30 minutes sooner) than the previous extended-window study, reaffirming the need for speed. In addition, interval improvements in stroke care with the development of stroke systems and comprehensive attention to multiple care aspects beyond thrombolysis may also underlie the success shown in ECASS III. Yet, complacency about time must not prevail. Much work remains, including understanding pathophysiology that limits time, exploring physiology that may extend time, and developing approaches for late-presenting patients with stroke. It is clearly time to erase any vestige of nihilism from acute stroke treatment.
PWE-422 The impact of an alcohol awareness day in a large district general hospital
Authors: P Chopra, N Sahi, J Cooper
Journal: Gut (2015)

<h3>Introduction</h3> The Princess Royal University Hospital (PRUH) is held an alcohol awareness day in January to encourage local people to reflect upon their drinking habits and make positive lifestyle changes. The awareness day came in response to the number of patients requiring the hospital’s services due to the effects of excessive alcohol consumption. In November and December 2014, the number of people who attended the PRUH–s Emergency Department (ED) due to excessive alcohol consumption totalled 92, and of that number 36 patients had to be admitted for further treatment. Ninety-one per cent of those who attended the ED due to alcohol-related problems were of working age. An audit of 100 inpatients found that 16 were drinking at potentially hazardous levels. <h3>Method</h3> Information was made available on the recommended weekly maximum levels of alcohol consumption and sources of help. A stand was erected at the hospital front entrance and literature disseminated to staff and patients given plus a direct opportunity to ask questions. Reflection of weekly alcohol consumption was aided by the use of diary cards. <h3>Results</h3> Over the course of the day, 145 people visited the stand and our team disseminated information on recommended weekly alcohol limits. Staff were particularly interested in understanding the units they were consuming and patients were surprised to learn that they should have three alcohol-free days per week. Visitors to the stand were encouraged to keep a diary of their drinking habits and take part in our competitions to create non-alcoholic recipes for smoothies and mocktails. A few quotes from staff included “it is a real eye opener to keep a diary card”, “alcohol histories are often take too long to pin down an answer”. Patients semed particularly keen to ask about binge drinking and many were unaware about the need for alcohol free days. <h3>Conclusion</h3> The number of people we are seeing across our services as a result of alcohol misuse – from the Emergency department to outpatients and endoscopy illustrates the damaging effect it can have. Lack of awareness of the maximum weekly consumption plays a big part. The New Year is an ideal time for people to reflect on their health and consider making lifestyle changes. It is up to individuals to recognise the problem and want to make a positive change in their lives. The alcohol awareness day was local success and both patients and staff gained insight into the impact of alcohol on our current NHS resources. <h3>Disclosure of interest</h3> None Declared.
Analysis of Plasma Proteins by Turbidimetry: An Unsuccessful Aid in Cancer Diagnosis&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: J. H. Hill, M.D., Samuel W. Greenhouse
Journal: JNCI Journal of the National Cancer Institute (1957)

Analysis of Plasma Proteins by Turbidimetry: An Unsuccessful Aid in Cancer Diagnosis Get access J. H. Hill, M.D., J. H. Hill, M.D. Mathematical Statistician, Department of Pathology and Oncology, University of Kansas Medical School, Kansas City, Kansas, and Biometrics Branch, National Institute of Mental Health,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Samuel W. Greenhouse Samuel W. Greenhouse Mathematical Statistician, Department of Pathology and Oncology, University of Kansas Medical School, Kansas City, Kansas, and Biometrics Branch, National Institute of Mental Health,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 2, February 1957, Pages 291–299, https://doi.org/10.1093/jnci/18.2.291 Published: 01 February 1957 Article history Received: 29 August 1956 Published: 01 February 1957
Effect of Acetazolamide on Sweat Electrolytes in Mucoviscidosis
Authors: R RICHTERICH, B FRIOLET
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Soundings: Great Toe of This Assembly
Authors: Liam Farrell
Journal: BMJ (2006)

Referring to yourself in the third person usually signifies an unpleasantly inflated ego—for example, “The Lady's not for turning.” But I can do better, with echoes of the politically incorrect “Liver in ward 3.”

It was a cold winter's night, and the wind was moaning through the eaves like a patient having an ingrown toenail removed who has been given too little local anaesthetic (come on, haven't we all done it?), the kind of night when doctors huddle a little closer to the fire, like a blob of phlegm on the uvula.

Then the phone call. “What about The Toe?” said a voice, and that was all it said.

I was silent for a long moment, lost in the ambiguity. “What about The Toe?” I repeated it softly to myself, a question leading only to more questions. Whose toe? Why are we here? What was wrong with The Toe to begin with?

Yet there was information to be gleaned: an implacable self confidence, certainty that his voice would be instantly recognised, and that his Toe was unforgettable, contempt for Galileo and Copernicus and all those who had endured persecution in search of scientific truth. The earth doesn't revolve around the sun, everything revolves around me. Me, me, I am the centre of the universe, the Great Panjandrum.

I wished, once again, that Sigmund Freud was still around to help; note the subject's terse and precise language, he would say. “How anal of you to notice,” I would reply. “Oh, everything's anal to you,” he would scoff. “Why, does it remind you of your mummy?” I would retort. “You speak the truth, my young Oedipus,” he would say. “We must investigate.”

When I arrived at the farm, everything was quiet, apart from the slavering guard dog. “Too quiet,” I thought, remembering my westerns.

A hawthorn grew in the centre of the yard, which made turning awkward. It hadn't been chopped down, as the hawthorn had a reputation as a faery tree, so I resisted the temptation to drive over it.

The Toe was reclining on a velvet cushion. I gave it a respectful little massage and some antibiotics (what else?) and advised it to rest.

The owner regarded me with satisfaction. “Look on The Toe, Ozymandias, King of Kings,” he said, “and despair.”
New Viral Exanthems
Authors: A. Martin Lerner, Jerome O. Klein, James D. Cherry, Maxwell Finland
Journal: New England Journal of Medicine (1963)

Clinical laboratory findings. Peripheral white-cell counts were usually below 10,000, but counts between 10,000 and 15,000 were not uncommon, and occasionally they were over 20,000.76,105 Erythrocyte sedimentation rates were frequently elevated.69,80,82,88,102,105 Solomon and his co-workers105 reported elevations in 37 of 43 cases, with 5 having values greater than 50 mm. per minute.Urinary abnormalities were noted in several reports.69,82,105 In Boston105 only 11 patients with slight pyuria and 3 with microscopic hematuria were reported, whereas in Milwaukee69 there was microscopic hematuria in 50 per cent and proteinuria in 10 per cent of patients. Wesslen and his co-workers82 also noted . . .
IMPS-32GLIOBLASTOMA MULTIFORME AFTER SEVERE WEST NILE VIRUS NEUROINVASIVE DISEASE
Authors: Scott Spritzer, Marie Grill, Arturo Leis, Alyx Porter
Journal: Neuro-Oncology (2015)

OBJECTIVE: Acute West Nile Virus infection has been shown to cause a broad spectrum of neurological disorders. Beyond cognitive symptoms, little is described regarding long-term sequelae in patient that have suffered from acute West Nile neuroinvasive disease. CASE: We present a case of a patient that suffered from severe West Nile neuroinvasive disease with full recovery, however was subsequently diagnosed with glioblastoma multiforme and passed away two years later. DISCUSSION: We also note a potential mechanism in which the west nile infection may cause changes on a cellular molecular signaling level that may explain a correlation between the two disease processes. West Nile infection has been shown to result in increased expression of S100B, a glial protein biomarker with broad functions. S100B is known to increase expression of RAGE (receptor for advanced glycosylation end products), a protein documented to be in abundance in GBM tumors. CONCLUSION: To our knowledge, this is the first reported case of a patient with known history of West Nile neuroinvasive disease being subsequently diagnosed with GBM. WNV has potential for altering cellular signaling at a molecular level and increasing expression of molecules known to be in abundance in high grade glioma. Given this association, further investigations are warranted looking into the potential risk for developing CNS neoplasm, as well as further studying the potential relation between the two diseases.
Pathogenesis of diabetic microangiopathy.
Authors: G Caimi, R Lo Presti
Journal: BMJ (1977)

Pathogenesis of diabetic microangiopathyNeither retinopathy nor nephropathy is found at the onset of diabetes.'Thickening of the capillary basement membrane, an early change, is first detectable by electronmicroscopy of the glomeruli after 1 --21 years of juvenile-onset diabetes.2Similar changes have been described in skeletal muscle3 and in myocardial4 and retinal capillaries in diabetic animals and man. 5 6
Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias
Authors: J M Silverman, J C Breitner, R C Mohs, K L Davis
Journal: American Journal of Psychiatry (1986)

The investigation of genetic and other causes of Alzheimer's disease requires reliable and valid methods of gathering historical data on elderly relatives. To assess the reliability of the family history method in the study of late-onset dementing illness, the authors studied families with Alzheimer's disease probands and control families. The results indicated that family history data obtained from multiple informants with standardized instruments are consistent across informants. The rate of Alzheimer's disease in the families studied was similar to rates found in previous studies.
Effect Of Recombinant Human Soluble Thrombomodulin On Clinical Outcomes Of patients With Coagulopathy After Hematopoietic Stem Cell Transplantation
Authors: SungGi Chi, Takayuki Ikezoe, Asako Takeuchi, Kazuki Anabuki, Tsukie Kim, Mizu Sakai, Ayuko Taniguchi, Kazuto Togitani, Akihito Yokoyama
Journal: Blood (2013)
Childhood antecedents of homelessness in psychiatric patients
Authors: E S Susser, S P Lin, S A Conover, E L Struening
Journal: American Journal of Psychiatry (1991)

This study examined the relationship between childhood experience and homelessness in psychiatric patients.Three large and diverse samples of homeless patients (N = 512) were compared with a sample of patients who had never been homeless (N = 271), with respect to childhood experience of foster care, group home placement, and running away. One of the homeless samples and the never homeless sample were drawn from patients admitted to a state mental hospital. In this state hospital population, risk ratios for lifetime prevalence of homelessness could be derived.In the three homeless samples, over 15% had a history of foster care, over 10% had a history of group home placement, and over 20% had a history of running away. These figures compared with 2%, 1%, and 5%, respectively, in the never homeless sample. In the state hospital, the lifetime prevalence of homelessness in patients with any one of these childhood experiences was about threefold that of other patients. A history of homelessness was reported by the great majority of state hospital patients who had had one of these childhood experiences.These childhood experiences were strongly associated with adult homelessness in these psychiatric patients. It might be possible to prevent homelessness in some cases by interventions aimed at patients with such childhood histories.
Toward a rational pharmacotherapy of depression
Authors: S L Stern, A J Rush, J Mendels
Journal: American Journal of Psychiatry (1980)

The authors review several approaches that show promise for predicting which antidepressant medication will be best for a particular patient and for achieving maximum benefit from each drug. These include delineation of clinical and historical characteristics associated with response to various drugs, use of psychological tests, assessment of biochemical and electroencephalographic parameters, evaluation of mood response to amphetamine, determination of acetylator status, and measurement of plasma tricyclic levels and degree of inhibition of platelet monoamine oxidase. The authors believe that the use of these approaches may improve our ability to help depressed patients.
AB1066 The Pattern of Power Doppler Signal at the Joint Level in Patients with Rheumatoid Arthritis: Its Association with Disease Activity:
Authors: M.J. Audisio, G.E. Py, A.M. Bertoli
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Power Doppler (PD) ultrasound examination is nowadays being routinely used for the assessment of disease activity in patients with rheumatoid arthritis (RA). Several scores have been proposed and validated; however, less information is available regarding the pattern of PD signal at the joint level and its possible association with disease activity. <h3>Objectives</h3> To address if a specific synovial flow pattern at the joint level (peripheral vs juxta-cortical) is associated with disease activity in patients with RA. <h3>Methods</h3> We examined 820 metacarpophalangeal (MCP9s) joints of patients with diagnosis of RA (1987 ACR criteria). The pattern of synovial flow was assessed with PD ultrasound and classified as peripheral (when observed in any point of the joint surface but never near or in contact to the bone cortex) and juxta-cortical (when near or in contact to the bone cortex). For the purpose of these analyses, we included only the MCP9s with positive PD signal, irrespective of its intensity. Disease activity was assessed using the DAS28-ESR. The association of the PD signal pattern and the DAS28 and its components [(tender joint count, swollen joint count, patient global assessment of disease activity (PtGADA) and erythrocyte sedimentation rate (ESR)] was analyzed using the Mann-Whitney U test. A <i>p</i> value ≤0.05 was considered statistically significant. <h3>Results</h3> Patients were predominantly females (80.5%), with a mean age of 50.5 (SD 13.1) years and a median (IQR) disease duration of 80.0 (82.0) months. Median DAS-ESR was 3.1 (0.9). Among the 820 MCP9s, 46 had peripheral PD signal pattern and 41 juxta-cortical PD signal pattern. The table below depicts the median (IQR) DAS28-ESR and its components according to the PD signal pattern. <h3>Conclusions</h3> In this study we identified two distinct patterns of PD signal at the joint level in patients with RA, peripheral and yuxta-cortical. We also found that the peripheral pattern has a tendency towards an association with disease activity when measured with the DAS28-ESR and a clear association with the number of swollen joints and the ESR. More studies are needed, however, to confirm these findings. <h3>References</h3> Mandl P, Naredo E et al. A Systematic Literature Review Analysis of Ultrasound Joint Count and Scoring Systems to Assess Synovitis in Rheumatoid Arthritis According to the OMERACT Filter. J Rheumatol 2011; 38:2055–62. <h3>Disclosure of Interest</h3> None declared