tbuckley/cabot-search huggingface dataset:
Blinded Independent Central Review of Progression-Free Survival in Phase III Clinical Trials: Important Design Element or Unnecessary Expense?
Authors: Lori E. Dodd, Edward L. Korn, Boris Freidlin, C. Carl Jaffe, Lawrence V. Rubinstein, Janet Dancey, Margaret M. Mooney
Journal: Journal of Clinical Oncology (2008)

Progression-free survival is an important end point in advanced disease settings. Blinded independent central review (BICR) of progression in randomized clinical trials has been advocated to control bias that might result from errors in progression assessments. However, although BICR lessens some potential biases, it does not remove all biases from evaluations of treatment effectiveness. In fact, as typically conducted, BICRs may introduce bias because of informative censoring, which results from having to censor unconfirmed locally determined progressions. In this article, we discuss the rationale for BICR and different ways of implementing independent review. We discuss the limitations of these approaches and review published trials that report implementing BICR. We demonstrate the existence of informative censoring using data from a randomized phase II trial. We conclude that double-blinded trials with consistent application of measurement criteria are the best means of ensuring unbiased trial results. When such designs are not practical, BICR is not recommended as a general strategy for reducing bias. However, BICR may be useful as an auditing tool to assess the reliability of marginally positive results.
Grave Words: Notifying Survivors about Sudden, Unexpected Deaths
Authors: Frederic W. Platt
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes4 April 2000Grave Words: Notifying Survivors about Sudden, Unexpected DeathsFrederic W. Platt, MDFrederic W. Platt, MDUniversity of Colorado School of Medicine, Denver, Colorado. (Platt)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-7-200004040-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Iserson KV. 342 pages. Tucson, AZ: Galen Pr; 1999. $38.95. ISBN 1883620023. Order phone 800-442-5369.Field of medicine: Patient care.Format: Paperback book.Audience: Clinicians who are called on to tell family or friends of the unexpected death of a loved person, as well as nonclinicians whose professions may place them in a similar position (for example, military, police, and airline personnel).Purpose: Few physicians have been trained in the requisite skills for notification of unexpected death, and few have an organized approach to it. This book provides a thorough understanding of the problem, protocols for the clinical task, and ... Author, Article, and Disclosure InformationAffiliations: University of Colorado School of Medicine, Denver, Colorado. (Platt) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 April 2000Volume 132, Issue 7Page: 604KeywordsArmed forcesEmotionsHealth carePatientsResuscitationSoftware tools ePublished: 15 August 2000 Issue Published: 4 April 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Controversy rekindled over pill and risk of breast cancer
Authors: R. Woodman
Journal: BMJ (1999)

Controversy about the contraceptive pill and its effect on the risk of breast cancer was rekindled this week in an editorial by a professor of epidemiology, who said that recent reassurances may be “seriously misplaced” (Journal of Epidemiology and Community Health 1999;53:258-60).

Large studies have shown that the slight increase in the risk of breast cancer among women who currently use the contraceptive pill gradually decreases when they stop taking it until, after 10 years, there seems to be no excess risk.

However, …
Effect of coronary sinus occlusion on coronary flow, resistance, and zero flow pressure during maximum vasodilatation in swine
Authors: G. A PANTELY, J D. BRISTOW, H. D LADLEY, C. G ANSELONE
Journal: Cardiovascular Research (1988)

The effects of coronary sinus occlusion on the relation between coronary artery pressure and flow during maximum vasodilatation were studied in seven swine. The left anterior descending (LAD) coronary artery was instrumented with two catheters, a hydraulic occluder, and a flowprobe. Mean flow was measured at a series of pressures produced by partial LAD occlusion during maximum vasodilatation induced by an intracoronary infusion of adenosine. Observations were made under control conditions and during occlusion of the coronary sinus produced by inflating the balloon on the catheter positioned in the coronary sinus. Systemic haemodynamic variables did not change significantly after the coronary sinus was occluded. The mean right atrial pressure was 4 mmHg. At any given LAD perfusion pressure mean flow during coronary sinus occlusion was always less than during the control state: at LAD pressure 30 mmHg, control flow was 53 ml·min−1vs occluded flow 24 ml·min−1; at LAD pressure 40 mmHg, control flow 79 ml·min−1vs occluded flow 49 ml·min−1; and at LAD pressure 50 mmHg, control flow 105 ml·min−1vs occluded flow 74 ml·min−1; p <0.001 for all comparisons. The mean(SD) LAD pressure at which flow stopped (Pzf) when the coronary sinus was unobstructed was 10(2) mmHg. The Pzf during occlusion of the coronary sinus was significantly higher at 20(4) mmHg (p <0.001). The slopes of the mean pressure-flow relations were not significantly different during the control state (2.62(0.65) ml·min−1 per mmHg) vs the occluded state (2.47(0.63) ml·min−1 per mmHg), indicating no change in vascular resistance. Occlusion of the coronary sinus resulted in a decrease in coronary flow at any given LAD perfusion pressure during maximum vasodilatation. This was due entirely to an increase in the pressure at which flow stopped without a change in coronary vascular resistance or right atrial pressure. The increase in Pzf was probably due to an increase in extravascular pressure affecting mainly the venous system or to an intrinsically higher zero flow pressure in the extracoronary sinus drainage pathways.
Association Between Physician Follow-Up and Outcomes of Care After Chest Pain Assessment in High-Risk Patients
Authors: Andrew Czarnecki, Alice Chong, Douglas S. Lee, Michael J. Schull, Jack V. Tu, Ching Lau, Michael E. Farkouh, Dennis T. Ko
Journal: Circulation (2013)

Background— Assessment of chest pain is one of the most common reasons for emergency department visits in developed countries. Although guidelines recommend primary care physician (PCP) follow-up for patients who are subsequently discharged, little is known about the relationship between physician follow-up and clinical outcomes. Methods and Results— An observational study was conducted on patients with higher baseline risk, defined as having diabetes mellitus or established cardiovascular disease, who were evaluated for chest pain, discharged, and without adverse clinical outcomes for 30 days in Ontario from 2004 to 2010. Multivariable proportional hazard models were constructed to adjust for potential confounding between physician groups (cardiologist, PCP, or none). Among 56767 included patients, 17% were evaluated by cardiologists, 58% were evaluated by PCPs alone, and 25% had no physician follow-up. The mean age was 66±15 years, and 53% were male. The highest rates of diagnostic testing, medical therapy, and coronary revascularization were seen among patients treated by cardiologists. At 1 year, the rate of death or MI was 5.5% (95% confidence interval, 5.0–5.9) in the cardiology group, 7.7% (95% confidence interval, 7.4–7.9) in the PCP group, and 8.6% (95% confidence interval, 8.2–9.1) in the no-physician group. After adjustment, cardiologist follow-up was associated with significantly lower adjusted hazard ratio of death or MI compared with PCP (hazard ratio, 0.85; 95% confidence interval, 0.78–0.92) and no physician (hazard ratio, 0.79; 95% confidence interval, 0.71–0.88) follow-up. Conclusions— Among patients with higher baseline cardiovascular risk who were discharged from the emergency department after evaluation for chest pain in Ontario, follow-up with a cardiologist was associated with a decreased risk of all-cause mortality or hospitalization for MI at 1 year compared with follow-up with a PCP or no physician follow-up.
Flaw in WHO Framework Convention on Tobacco Control
Authors: Clive Bates
Journal: BMJ (2004)

EDITOR—Sehmi writes that the WHO Framework Convention on Tobacco Control has a major flaw.1 However, the main problem with the way the framework convention handles smokeless tobacco is not that it is inadequate but that it is undifferentiated from smoking tobacco. However, in many crucial respects—notably, risk of death …
Use of Board Certification and Recertification of Pediatricians in Health Plan Credentialing Policies
Authors: Gary L. Freed
Journal: JAMA (2006)

Health plans conduct credentialing processes to select and retain qualified physicians who will provide high-quality care to their subscribers. One of the tools available to health plans to help ensure physician competence is assessment of board certification status.To determine the credentialing policies of health plans regarding the use of board certification and recertification for general pediatricians and pediatric subspecialists.Telephone survey conducted February through July 2005 of credentialing personnel from a US national sample of 244 health plans stratified by enrollment size, Medicaid proportion, and for-profit or not-for-profit status.Proportion of health plans that require general or subspecialty board certification at initial contract or at any time during association with the plan and recertification to maintain credentialing or to bill as a specialist or subspecialist; percentage of physicians credentialed in each health plan and credentialing goals for each plan regarding the proportion of physicians to be board certified.Response rate was 193 of 244 (79%). Overall, 174 (90%) of the plans do not require general pediatricians to be board certified at the time of initial credentialing, and only 41% ever require a general pediatrician to become board certified. Similarly, only 80 (40%) ever require subspecialists to become board certified in their subspecialty. Although 80 of 192 (41%) report requiring recertification of general pediatricians, almost half do not have a time frame in which recertification must occur. Seventy-seven percent of plans allow physicians to bill as subspecialists with expired certificates.These findings, although specific to pediatrics, likely apply to other primary care disciplines and raise questions regarding the ability of plans to ensure initial or continued competence of their credentialed physicians. Growing public concern regarding patient safety, as well as demonstrated patient preferences for certified physicians, will likely result in greater emphasis on quality assessments in physician credentialing.
New bid to legalise assisted suicide reaches Scottish parliament
Authors: B. Christie
Journal: BMJ (2013)

Renewed attempts are being made in Scotland to legalise assisted suicide, although doctors’ leaders remain firmly opposed to changing the current law.

An Assisted Suicide (Scotland) Bill has been tabled at the Scottish parliament by the independent MSP Margo MacDonald, who said it was an idea “whose time has come.” MacDonald, who has Parkinson’s disease, failed to convince the parliament in 2010 to pass a previous bill.

She believes that the new bill answers the …
Deprivation of liberty in healthcare
Authors: R. Cairns, M. Hotopf, G. S. Owen
Journal: BMJ (2014)

UK Supreme Court judgment has changed the rules

The right to liberty in UK healthcare has been greatly strengthened this year. In March, the House of Lords Select Committee on the Mental Capacity Act (2005) published a report that severely criticised inconsistent safeguarding provisions for patients without mental capacity who are deprived of their liberty.1 Later that month, the UK Supreme Court gave judgment in a case “Cheshire West,” which involved three adults with severe learning disability and answered the general question “what is a deprivation of liberty?”2

The judgment introduces a new disability neutral test—an “acid test”—which aims to ensure that the right to liberty applies equally to people with and without mental incapacity. The test will greatly increase safeguards owed to people without mental capacity in healthcare. Government, and society in general, has an important new challenge.

This decision steers away from the approach to deprivation of liberty taken by the Percy Commission of 1957, which sought legal informality for people without mental capacity who did not object to the offer of healthcare. Cheshire West harks back to the “legalism” of the Lunacy Act of 1845, enacted when society sought to counter …
P2-12-07: Pooled Analysis of Outcomes of T1a/bN0, HER2−Amplified Breast Cancer.
Authors: E Amir, B Seruga, A Ocaña, L Carlsson, P Bedard
Journal: Cancer Research (2011)

Abstract Background: Breast tumors with HER2 amplification have a worse prognosis than those with normal HER2 expression. This finding is independent of tumor size and other classical prognostic factors used in the adjuvant setting. The prognosis of node negative, sub-centimeter (T1a/bN0) tumors is usually excellent. However, little is known about the prognostic impact of HER2−amplification in this group. This study therefore, aimed to evaluate the relative and absolute prognostic impact of HER2−amplification in T1a/bN0 tumors. Materials and Methods: Published data from studies assessing the outcomes of patients with HER2−amplified, node negative, T1a/bN0 tumors were included in a pooled analysis. Odds ratios (OR), 95% confidence intervals (CI) and absolute risks were computed for recurrence and distant recurrence at 5 years. Pooled hazard ratios (HR) for disease-free survival (DFS), were also assessed. Results: A total of 3 case-control studies were included in the analysis and comprised 485 patients with HER2−amplified breast cancer (57.3% were also hormone receptor positive) and 1096 patients with HER2−normal disease (82.2% were hormone receptor positive). Among the HER2−amplified group, 4.1% received trastuzumab and 18.6% received chemotherapy. In the HER2−normal group, 4.3% received chemotherapy Estimated median follow-up was 5.7 years. HER2−amplification was associated worse DFS (HR = 2.60, 95% CI 1.53−4.41, p&amp;lt;.001) and increased odds for recurrence at 5 years (OR = 3.79, 95% CI 2.35−6.10, p&amp;lt;.001). There was a non-significant trend towards increased odds of distant recurrence at 5 years (OR = 2.51, 95% CI 0.82−7.67, p=.11). Compared with HER2−normal cancers, those with HER2−amplification showed lower absolute probability of recurrence-free survival at 5 years (90.1% vs. 94.6%, p&amp;lt;.001) and distant recurrence-free survival at 5 years (95.1% vs. 97.6%, p&amp;lt;.001). Among HER2−amplified cancers, tumor size 0.6−1.0cm (T1b) was associated with a trend for higher odds of recurrence at 5 years compared with those 0.5cm or smaller (T1a, pooled OR = 1.58, 95% CI 0.96−2.60, p=.07). Conclusions: HER2−amplification is associated with worse outcome in T1a/bN0 tumors. However, recurrence-free and distant recurrence-free survival at 5 years is excellent in this group, particularly in those with T1a tumors. These data question the role of adjuvant chemotherapy and trastuzumab in these patients unless associated with other high risk features. A differentially lower risk for distant recurrence suggests the possible role for more aggressive local therapy such as surgery and/or radiation therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-07.
Andrew Wakefield is accused of paying children for blood samples
Authors: Owen Dyer
Journal: BMJ (2007)

Andrew Wakefield, whose warnings about a possible link between the measles, mumps, and rubella (MMR) vaccine and autism sparked a public health scare, was accused this week by the General Medical Council of paying children £5 (€7.40; $10) each to give blood samples at his son's birthday party. 

The accusation was made in the GMC's case involving three doctors who collaborated on a 1998 Lancet paper on developmental disorders in children. Dr Wakefield, John Walker-Smith, and Simon Murch are accused of ignoring limitations placed on them by the research ethics committee of the Royal Free Hampstead NHS Trust …
Cutaneous photosensitivity in dermatomyositis
Authors: W.-K. CHEONG, G.R. VHUGHES, P.G. NORRIS, J.L. MHAWK
Journal: British Journal of Dermatology (2006)

The incidence and nature of cutaneous photosensitivity were studied in 10 patients suffering from dermatomyositis. Five reported an abnormality, which consisted of photoaggravation of preexisting cutaneous lesions in three, and abnormal transient erythemal responses in two. Monochromatic irradiation testing of all 10 patients demonstrated reduced minimal erythemal doses in two, at 307.5 nm, and at 340 and 360 nm, respectively; only the latter individual had clinical light sensitivity. Exposure to low-dose, solar-simulated radiation of the unaffected skin of the former patient, and five others who agreed to the procedure, three of whom complained of light sensitivity, induced a lesion with the clinical and immunofluorescence characteristics of dermatomyositis in only the first one. Four other patients replied to a mailed questionnaire, and three of these reported aggravation of their rash and provocation of new lesions by sunlight. Photosensitivity may thus be an important cutaneous feature of dermatomyositis.
Carnitine transport in isolated adult rat heart myocytes and the effect of 7,8-diOH chlorpromazine.
Authors: J Bahl, T Navin, A A Manian, R Bressler
Journal: Circulation Research (1981)

We studied the carnitine transport system in isolated adult rat heart myocytes able to tolerate physiological concentrations of calcium. Carnitine uptake occurred against a concentration gradient and was inhibited by 2,4-dinitrophenol (2,4-DNP). The transport system had a Km of 60 microM and a Vmax of 110 pmol/mg protein per hour. The carnitine precursor deoxycarnitine, acetylcarnitine, and both the D and L isomers were effective inhibitors of uptake. The transport of carnitine was not dependent on sodium ions, but was stimulated by decreasing concentrations of calcium ions. Decreased uptake was observed in the presence of beta-adrenergic agonists and antagonists, dibutyrl cyclic AMP, local anesthetics, and ouabain. No significant alteration of uptake was effected by atropine, carbachol or a variety of tricyclic agents. The auto-oxidation product of 7,8-dihydroxychlorpromazine (7,8-diOH CPZ) decreased carnitine efflux from myocytes, which were highly permeable to low molecular weight compounds. We found that this effect was not substrate specific, and is discussed as possibly resulting from a change in the arrangement or state of polymerization of subcellular structural components.
USE OF SUPRARENAL EXTRACT TO FACILITATE CATHETERIZATION IN PATIENTS WITH HYPERTROPHIED PROSTATE.
Authors: A. E. PRINCE
Journal: JAMA (1907)

Although not engaged in general practice, it has fallen to my lot to use adrenalin three times with the most gratifying result in cases of retention of urine associated with prostatic enlargement. In commenting on my experience, I have come to believe that the knowledge of this use of the remedy is not general. This is my excuse for offering the following brief notes, which are intended simply to call attention to the matter: <h3>Case 1.</h3> —The patient was an old man who had been operated on. I was called up in the night by the nurse, who had failed to relieve the distress occasioned by retention of urine. I found the patient in agony, and my efforts were not more successful than those of the nurse. Formerly, I had frequently resorted to suprapubic aspiration, and I had almost made up my mind that this would be the wisest course
Abstract LB-74: The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling
Authors: Ricardo G. Correa, Maryla Krajewska, Carl F. Ware, Motti Gerlic, John C. Reed
Journal: Cancer Research (2014)

Abstract Prostate cancer (PCa) is among the leading causes of cancer-related death in men. Androgen receptor (AR) signaling plays a seminal role in prostate development and homeostasis, and dysregulation of this pathway is intimately linked to prostate cancer pathogenesis and progression. Here, we identify the cytosolic NLR-related protein NWD1 as a novel modulator of AR signaling. We determined that expression of NWD1 becomes elevated during prostate cancer progression, based on analysis of primary tumor specimens. Experiments with cultured cells showed that NWD1 expression is up-regulated by the sex-determining region Y (SRY) proteins. Gene silencing by short hairpin RNA (shRNA), in conjunction with transcriptional profiling, showed that NWD1 is required for expression of PDEF (prostate-derived Ets factor), which is known to bind and co-regulate AR. Of note, NWD1 modulates AR protein levels. Silencing NWD1 in PCa cell lines reduces the levels of androgen-stimulated accumulation of nuclear AR and suppresses activity of androgen-driven reporter genes. NWD1 knockdown potently suppressed growth of androgen-dependent LNCaP prostate cancer cells, thus showing its functional importance in an AR-dependent tumor cell model. Proteomics analysis suggested that NWD1 associates with various molecular chaperones commonly related to AR complexes. Altogether, our data suggest a role for tumor-associated over-expression of NWD1 in the dysregulation of AR signaling in PCa. Citation Format: Ricardo G. Correa, Maryla Krajewska, Carl F. Ware, Motti Gerlic, John C. Reed. The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-74. doi:10.1158/1538-7445.AM2014-LB-74
More Uses for Apheresis-Reply
Authors: John D. Clough
Journal: JAMA (1985)

<h3>In Reply.—</h3> The panel thanks Drs Taelman and Muylle for their comments on apheresis in the treatment of overwhelming loiasis and<i>P falciparum</i>malaria. As may be realized, these are diseases not normally encountered in North America, where, with few exceptions, our main attention was directed. However, as noted by Files et al,<sup>1</sup>with more frequent travel to endemic areas, increasing numbers of cases may be seen here in the future. The rationale for apheresis in these conditions seems well founded, and we would probably have placed them in category II, conditions in which available evidence tends to favor efficacy. It certainly will be necessary to update the panel's findings and recommendations periodically as additional indications for apheresis are suggested and as new data pertaining to existing indications become available.
Demonstration of diastolic and presystolic purkinje potentials as critical potentials in a macroreentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia
Authors: Akihiko Nogami, Shigeto Naito, Hiroshi Tada, Koichi Taniguchi, Yoshihiro Okamoto, Shigeyuki Nishimura, Yasuteru Yamauchi, Kazutaka Aonuma, Masahiko Goya, Yoshito Iesaka, Michiaki Hiroe
Journal: Journal of the American College of Cardiology (2000)
ZAP-70 Expression as a Surrogate for Immunoglobulin-Variable-Region Mutations in Chronic Lymphocytic Leukemia
Authors: Marta Crespo, Francesc Bosch, Neus Villamor, Beatriz Bellosillo, Dolors Colomer, María Rozman, Silvia Marcé, Armando López-Guillermo, Elies Campo, Emili Montserrat
Journal: New England Journal of Medicine (2003)

The mutational status of immunoglobulin heavy-chain variable-region (IgVH ) genes in the leukemic cells of chronic lymphocytic leukemia (CLL) is an important prognostic factor in the disease. We investigated whether the expression of ZAP-70 by CLL cells correlated with the IgVH mutational status, disease progression, and survival.