tbuckley/cabot-search huggingface dataset:
Impact of Informative Censoring on the Kaplan-Meier Estimate of Progression-Free Survival in Phase II Clinical Trials
Authors: Federico Campigotto, Edie Weller
Journal: Journal of Clinical Oncology (2014)

Informative censoring in a progression-free survival (PFS) analysis arises when patients are censored for initiation of an effective anticancer treatment before the protocol-defined progression, and these patients are at a different risk for treatment failure than those who continue on therapy. This may cause bias in the estimated PFS when using the Kaplan-Meier method for analysis. Although there are several articles that discuss this issue from a theoretical perspective or in randomized phase III studies, there are little data to demonstrate the magnitude of the bias on the estimated quantities from a phase II trial. This article describes the issues by using two oncology phase II trials as examples, evaluates the impact of the bias using simulations, and provides recommendations. The two trials were selected because they demonstrate two different reasons for censoring. Simulations show that the magnitude of the bias depends primarily on the proportion of patients who are informatively censored and secondarily on the hazard ratio between the group of patients who remain on study and the group of patients who are informatively censored. Recommendations include using an alternative end point, which includes inadequate response and initial signs of clinical progression as treatment failure, and a competing risk analysis for studies in which competing events preclude or modify the probability of observing the primary event of interest. If informative censoring cannot be avoided, then all patients should be observed until progression, and sensitivity analyses should be used as appropriate.
A NEW SELF-STERILIZING, NONSPILLABLE, DEMOUNTABLE CLINICAL THERMOMETER AND CASE
Authors: Charles S. Tomlinson
Journal: JAMA (1928)

The case of this thermometer is constructed of nickel plated metal to which is attached a glass barrel to be filled with a suitable antiseptic solution, such as alcohol. The alcohol immerses the thermometer when it is not in use; by this means the physician may be assured of a completely sterile instrument at all times.  The case is fitted with a unique valve preventing the liquid from spilling after the thermometer has been removed from the case. It does not require any cork or cap, and may be placed in any position without danger of losing any of the contained liquid.  The instrument is fully demountable; that is, unscrewing the cap permits it to be completely taken apart, so that any part may be renewed without sacrifice of the entire instrument. This feature makes for economy and a highly practicable instrument, giving rise to the name Life Long.
Coronary Heart Disease and Future Expectation of Life
Authors: ALEXANDER R. P. WALKER
Journal: Circulation (1968)

Mortality from coronary heart disease (CHD) has risen enormously over the last generation. Some regard the concomitant increase in life expectancy as the sole explanation; others maintain the increases at least in part to be real. Irrespective of the true causes, the question arises: If increases in CHD mortality continue in certain of the populations most affected, may not expectation of life ultimately decrease? An answer is sought by examining relevant information (1) on a large community of rural Indians having a low prevalence of CHD, and (2) on the offspring of Indian immigrants to South Africa, whose CHD mortality now exceeds that of the local whites. It is concluded that while promotive factors linked with urbanization and prosperity are chiefly responsible, the bearing of an ethnic propensity cannot be excluded. Continuation of the present CHD mortality trend in South African Indians almost undoubtedly will decrease their life expectancy, which, even at present, appears to compare unfavorably from youth onward with that of the rural Indian group described.
Abuse of the Elderly
Authors: Joanne Lynn
Journal: JAMA (1981)

To the Editor.—  The editoral Violence Begins at Home by Samuel Vaisrub, MD (1981;245:1852), reports two increasingly recognized forms of domestic violence—child and spouse abuse—whose victims now receive some small protection by laws and social services. It ignores, however, an even more hidden and shameful group of abused people—the elderly living at home. This group has failed to receive even the minimal protections provided by child abuse laws. Usually the victim is burdensome and confused and is absolutely dependent on his abuser for food, shelter, and human contact. The signs of abuse are easily overlooked, and the physician and social worker have strong incentive to overlook them, since raising the issue does not allow any options for improvement in the patients' situation. We have seen patients drugged, beaten, starved, and taunted by overburdened families and have had to expend extraordinary efforts to improve the situation. With a declining economy, a
We must argue against choice
Authors: Jim Boddington
Journal: BMJ (2005)

EDITOR—Godlee raises concerns about the choice bandwagon,1 but I disagree that it is hard to argue against choice in health care. Choice is great when buying a car or a bottle of wine, but the advantages transfer to health care only if patients are consumers in a marketplace. Such a model is in nobody's interest. Patients do not need choice but properly funded …
Treatment of Enuresis
Authors: David T. Mahony
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Dr. John Prutting recently expressed his concern that widely circulated promotional material may lead to inappropriate and indiscriminate use of imipramine hydrochloride in treatment of bed-wetting children (225:315, 1973). I share his concern, but for somewhat different reasons. Experience in our clinic indicates that, contrary to the popular belief, a lower urinary tract organic factor, often an obstructive lesion correctible by minor surgery, is the cause of simple bedwetting in the majority of enuretic children (<i>J Urol</i>106:951, 1971). Detrusor hypertrophy and hypercontractility and sphincter weakness are basic to the detrusor-sphincter imbalance that is the common cause of juvenile urinary incontinence. Accordingly, lower urinary tract voiding studies are necessary to evaluate adequately the cause of childhood enuresis. Several well-controlled studies have shown anticholinergic drugs to be largely ineffective in eliminating childhood enuresis.<sup>1</sup>Several equally valid studies show imipramine to be highly effective in treating daytime urinary
Transfusions and Hepatitis: Update in '78
Authors: George F. Grady
Journal: New England Journal of Medicine (1978)

The good news is that the average patient requiring a transfusion today has a lower probability of contracting hepatitis from it than in previous years. The bad news is that technologic gains in the ability to identify infective donors have increased impatience with the loopholes that remain. The result is pressure to add partially effective and often nonspecific screening methods that not only are costly but, if carried to extremes, could reduce substantially the usable fraction of the marginally adequate national blood supply. Testing for hepatitis B surface antigen (HBsAg) in donor blood has been a success for more than . . .
Corrigendum to “Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis” [J Hepatol 45 (2006) 786–796]
Authors: Markus Neef, Monika Ledermann, Hans Saegesser, Vreni Schneider, Juerg Reichen
Journal: Journal of Hepatology (2007)
Dipyridamole in Treatment Of Angina Pectoris
Authors: Marvin C. Becker
Journal: JAMA (1968)

<h3>To the Editor:—</h3> I must disagree with placing the paper, "Dipyridamole in the Treatment of Angina Pectoris," in a section ofThe Journaldevoted to NEGATIVE RESULTS (<b>201</b>:865,1967). Unfortunately, Drs. Sbar and Schlant in their double-blind evaluation have not compared both treatment periods to placebo. They have, however, even by comparing the latter trimester of therapy with the first trimester, shown a clinical trend suggesting a superiority of dipyridamole over placebo in the 28 cases that could be evaluated with data. To be sure, one cannot argue for statistical significance in 28 cases where the placebo response is so high. The results are obviously not statistically significant, but I feel there is an apparent trend, a trend which might have been more apparent if compared with pretreatment values. I must also argue against inclusion of the additional 19 patients whose data were considered "inaccurate or unreliable" in the overall
THE CLINICAL SIGNIFICANCE OF VARIATIONS OF WRIST AND ANKLE.
Authors: THOMAS DWIGHT
Journal: JAMA (1906)

The paper which I have the honor to present to the Association contains little that is new to professional anatomists, but the underlying facts have not yet been brought, through the text books, to the cognizance of practical surgeons. The purpose is to call attention to matters of clinical importance, ignoring so far as may be, all abstract science. It were superfluous to show that variations are very numerous. I wish to insist on the practical point that they are to be expected at certain definite places. These variations are of four classes. The first is due to an increase in the number of bones, owing to the persistence of elements which normally fuse or disappear; the second, to a diminution of bones, owing to the union of elements usually distinct; the third, to unusual relations between bones; and the fourth to the exceptional development of processes usually small or
The DEBR rat, alopecia areata and autoantibodies to the hair follicle
Authors: K. J. McELWEE, P. PICKETT, R. F. OLIVER
Journal: British Journal of Dermatology (1996)

Many attempts have been made to implicate hair follicle-specific autoantibodies in the pathogenesis of alopecia areata (AA), a suspected autoimmune disease. Using the DEBR rat model for AA, we developed a refined indirect immunofluorescent technique to examine the sera from individual rats for the presence of autoantibodies to the hair follicle and to other tissues. Sera were tested on cryostat sections from normal PVG/Ola rats and DEBR rats. We found that DEBR sera contained IgG autoantibodies specific for hair follicle epidermal differentia. While individual sera revealed detailed differences, the target tissues identified were hair cortex and cuticle and the inner root sheath, especially the Henle's layer. Some sera also contained autoantibodies specific for skeletal muscle and nuclear components. Of 10 young prelesional rats with apparently normal coats of hair, three had hair follicle autoantibodies and seven had skeletal muscle autoantibodies. Nine of 10 active lesional rats with progressing hair loss had follicle autoantibodies and four had skeletal muscle autoantibodies. All 10 established lesional rats had follicle autoantibodies and one had muscle autoantibodies. Control sera from eight PVG/Ola rats showed no specific positive staining for hair follicle components or other tissues. Autoantibodies to intracellular hair follicle differentiation products were readily detected in DEBR rat sera. As these antibodies appeared to be generated after the appearance of the mononuclear follicular infiltrate, such autoantibodies may be a secondary effect. We conclude that, while the presence of autoantibodies in the DEBR rat model is associated with autoimmune activity, their role in the pathogenic progression of AA has yet to be ascertained.
Severe placental malaria and maternal shortness, thinness, and small skeletal size in rural Congo: cohort study
Authors: Hermione J Lovel, Rachel M Newby, Valerie F Hillier
Journal: BMJ (2005)

lactic surgery, but that two companies also gave credit for enrolment on a mammographic surveillance programme.Another company reported that this will be part of a review of policy, and in future it may also credit mammographic surveillance.The variation in the industry's responses show that women with a family history who are offered a high rating by one company may receive a lower rating if they approach a second company.No respondent said that they would request further family history to see if second degree relatives were affected.Disclosure of more cases of cancer in second degree relatives could considerably increase the assessed risk.The artificial nature of the survey might have implied, however, that no further family history existed to be disclosed, so we cannot comment on whether second degree relative information would be requested in reality.How access to adverse test results for BRCA1 or BRCA2 would influence the response to a similar survey in the future remains to be seen.We thank the life insurance companies for participating in the study, and Adam Butterworth, Cambridge Genetics Knowledge Park, and Alan Tyler, independent insurance and health consultant, for advice and review of the manuscript.
The Mechanism of Flecainide Action in CPVT Does Not Involve a Direct Effect on RyR2
Authors: Mark L. Bannister, N. Lowri Thomas, Markus B. Sikkel, Saptarshi Mukherjee, Chloe Maxwell, Kenneth T. MacLeod, Christopher H. George, Alan J. Williams
Journal: Circulation Research (2015)

Rationale: Flecainide, a class 1c antiarrhythmic, has emerged as an effective therapy in preventing arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) refractory to β-adrenergic receptor blockade. It has been proposed that the clinical efficacy of flecainide in CPVT is because of the combined actions of direct blockade of ryanodine receptors (RyR2) and Na + channel inhibition. However, there is presently no direct evidence to support the notion that flecainide blocks RyR2 Ca 2+ flux in the physiologically relevant (luminal-to-cytoplasmic) direction. The mechanism of flecainide action remains controversial. Objective: To examine, in detail, the effect of flecainide on the human RyR2 channel and to establish whether the direct blockade of physiologically relevant RyR2 ion flow by the drug contributes to its therapeutic efficacy in the clinical management of CPVT. Methods and Results: Using single-channel analysis, we show that, even at supraphysiological concentrations, flecainide did not inhibit the physiologically relevant, luminal-to-cytosolic flux of cations through the channel. Moreover, flecainide did not alter RyR2 channel gating and had negligible effect on the mechanisms responsible for the sarcoplasmic reticulum charge-compensating counter current. Using permeabilized cardiac myocytes to eliminate any contribution of plasmalemmal Na + channels to the observed actions of the drug at the cellular level, flecainide did not inhibit RyR2-dependent sarcoplasmic reticulum Ca 2+ release. Conclusions: The principal action of flecainide in CPVT is not via a direct interaction with RyR2. Our data support a model of flecainide action in which Na + -dependent modulation of intracellular Ca 2+ handling attenuates RyR2 dysfunction in CPVT.
Comparison of Various Vascular Beds in Man
Authors: WALTER REDISCH, LOTHAR WERTHEIMER, CLAUDE DELISLE, J. MURRAY STEELE, HARVARD REITER
Journal: Circulation (1954)

Blood flow to the extremities and kidneys was measured simultaneously in normal subjects, hypertensive patients and patients with obliterative arterial disease of the lower extremities. The latter group showed diminished basal flow in the lower extremities, increased basal flow in the upper extremities, and a delayed and diminished response to reflex heating, compared with the normal and hypertensive subjects. In all three groups, the increase in extremity blood flow was regularly accompanied by a concomitant decrease in renal blood flow. No significant change in arterial pressure was observed.
1073-142 Transthoracic doppler echocardiography as a noninvasive tool to assess coronary artery stenoses: A comparison with quantitative coronary angiography
Authors: Risto Vesalainen, Markku Saraste, Antti Ylitalo, Marianne Vaittinen, Jyri Toikka, Juha Koskenvuo, Jaakko Hartiala, Juhani Airaksinen
Journal: Journal of the American College of Cardiology (2004)
A Problem With Prematurity
Authors: Gordon E. Maxwell
Journal: JAMA (1968)

<h3>To the Editor:—</h3> As a liberal Protestant obstetrician, I have tried—really tried—to support liberalized abortion laws. I have argued against embodying one's personal belief in legal codes; I have tried to think of the anxiety and distress of the women with unwanted pregnancies; I have fretted about population explosions and the hazards of illicit abortion, but you have undone my efforts again. When I read the cool detached laboratory report on the 980-gm (2 lb 3 oz) fetus extracted for therapeutic abortion reasons (<b>202</b>:302, 1967) attached to an oxygenator, maintained several hours, and then observed to electrocardiographic death, I was really gripped with horror and unbelief. Didn't they know that they could have ruptured the membranes and resuscitated the baby and that he probably could have survived? I'm afraid this will harden my attitude against liberalized therapeutic abortion. If 2- to 3- to 4- lb babies are going to
Goals of Displaying Health Care Prices to Physicians—Reply
Authors: Kevin R. Riggs, Matthew DeCamp
Journal: JAMA (2015)

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
Longer Intervals Between Hematopoietic Stem Cell Transplantation and Subsequent 90Y-Ibritumomab Radioimmunotherapy May Correlate With Better Tolerance
Authors: Franz Buchegger, John O. Prior, Gilles Allenbach, Sébastien Baechler, Marek Kosinski, Claudine Helg, Yves Chalandon, Osman Ratib, Angelika Bischof Delaloye, Nicolas Ketterer
Journal: Clinical Nuclear Medicine (2012)

Purpose This study aimed to evaluate the efficacy and toxicity of radioimmunotherapy (RIT) in recurrent lymphoma after hematopoietic stem cell transplantation (HSCT). Methods We reviewed 9 patients, 7 with follicular lymphoma (DLBCL), 1 with mantle cell lymphoma (MCL), and 1 with diffuse large B-cell lymphoma treated with 90Y-ibritumomab tiuxetan 6 to 140 months after HSCT. Patients underwent 111In-ibritumomab scintigraphy and were treated 1 week later with standard 14.8 MBq/kg (n = 4) or 11.1 MBq/kg (n = 4) 90Y-ibritumomab. One patient who had allo-HSCT had reduced activity (70%) treatment. Results Among the 7 FL patients, we observed complete response (CR) in 2 patients and partial response (PR) in 5 patients. One patient with CR relapsed after 15 months; the other persisted 43.5 months after RIT. Of 5 patients with PR, 3 relapsed between 13 and 17 months; 1 persisted until unrelated death at 11.5 months. The fifth patient with PR received adoptive immunotherapy and improved to metabolic (FDG-PET) CR that persists 45.5 and 41 months after 90Y-ibritumomab and immunotherapy, respectively. Patients with MCL and DLBCL progressed or experienced stabilization (5 months), respectively. Six patients had grade 1 to 3 bone marrow (BM) toxicity and recovered within 3 months. Three patients having 90Y-ibritumomab 6, 14, and 24 months after HSCT experienced grade 4 BM toxicity. One of them (RIT 24 months after HSCT) recovered after 3 months, another delayed after 9 months, and the third patient only partially recovered, eventually developed myelodysplasia, and was allografted. Conclusions Radioimmunotherapy after HSCT is an effective rescue therapy in FL. However, BM toxicity may be important; 3 of 8 patients treated with standard 90Y-ibritumomab activity experienced grade 4 BM toxicity, with incomplete recovery 3 months after RIT in 2 patients, both treated early (6 and 14 months) after HSCT.
Estrogen-Imipramine Interaction
Authors: Ramesh C. Khurana
Journal: JAMA (1972)

<h3>To the Editor.—</h3> The report "Estrogen may well affect response to antidepressant" in the<i>Medical News</i>section ofThe Journal(219:143, 1972), which cites Dr. Arthur J. Prange's work, should be read by every practicing physician because it clearly describes the interaction of 150 mg of imipramine and 50μg estrogen. We discovered this phenomenon to be operative in one patient whose symptoms since 1968 have clearly been attributable to the said interaction. The patient was a 32-year-old white woman who had been taking 2.5 mg of conjugated estrogen and 100 mg of imipramine since early 1968. A retrospective review of her three monthly office visits revealed that she almost always complained of lethargy, and showed signs of depersonalization and occasional tremor. All endocrine indices were considered within normal limits. In 1970 she herself increased her estrogen dose to 5 and then 7.5 mg daily to get more pep, but in
Endocrine-Disrupting Chemicals
Authors: M. J. Friedrich
Journal: JAMA (2013)

1Zeneca, Macclesfield, Cheshire, United Kingdom; 2Akzo Nobel Chemicals, Amersfoort, The Netherlands; 3Unilever, Bedford, UK; 4Ciba-Geigy, Basel, Switzerland; 5Rh6ne-Poulenc Agro, Sophia Antipolis, France; 6Bayer Ag, Wuppertal, Germany; 7Procter & Gamble, Strombeek-Bever, Belgium; 8Union Carbide Corporation, Danbury, CT 06817-0001 USA; 9European Centre for Ecotoxicology and Toxicology of Chemicals, Brussels, Belgium; 10Zeneca, Brixham, Devon, UK
Activation of the<i>c-myc</i>Oncogene in a Precursor-B-Cell Blast Crisis of Follicular Lymphoma, Presenting as Composite Lymphoma
Authors: Daphne de Jong, Betsie M.H. Voetdijk, Geoffrey C. Beverstock, Gert Jan B. van Ommen, Roel Willemze, Philip M. Kluin
Journal: New England Journal of Medicine (1988)

B-CELL lymphomas are considered to represent "frozen" stages in the maturation of normal B cells. However, progression to a more malignant histologic form is frequently observed in low-grade lymphomas.1 Cytogenetic studies have shown that sub-clones can develop during the course of the disease, identifiable by a cascade of multiple recurrent chromosomal abnormalities.2 , 3 In follicular lymphoma, for example, these abnormalities may be superimposed on translocation t(14;18)(q32;q21), which is found as a marker in about 85 percent of cases and involves the putative oncogene bcl-2.4 Although several of these aberrations could be correlated with histologic progression, development of leukemia, or a poor . . .