tbuckley/cabot-search huggingface dataset:
Extending the CONSORT Statement to Randomized Trials of Nonpharmacologic Treatment: Explanation and Elaboration
Authors: Isabelle Boutron, David Moher, Douglas G. Altman, Kenneth F. Schulz, Philippe Ravaud
Journal: Annals of Internal Medicine (2008)

Adequate reporting of randomized, controlled trials (RCTs) is necessary to allow accurate critical appraisal of the validity and applicability of the results. The CONSORT (Consolidated Standards of Reporting Trials) Statement, a 22-item checklist and flow diagram, is intended to address this problem by improving the reporting of RCTs. However, some specific issues that apply to trials of nonpharmacologic treatments (for example, surgery, technical interventions, devices, rehabilitation, psychotherapy, and behavioral intervention) are not specifically addressed in the CONSORT Statement. Furthermore, considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement. Therefore, the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments. A consensus meeting of 33 experts was organized in Paris, France, in February 2006, to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments. The participants extended 11 items from the CONSORT Statement, added 1 item, and developed a modified flow diagram. To allow adequate understanding and implementation of the CONSORT extension, the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting. This extension, in conjunction with the main CONSORT Statement and other CONSORT extensions, should help to improve the reporting of RCTs performed in this field.
A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases
Authors: U. Veronesi, C. De Cicco, V.E. Galimberti, J.R. Fernandez, N. Rotmensz, G. Viale, G. Spano, A. Luini, M. Intra, P. Veronesi, A. Berrettini, G. Paganelli
Journal: Annals of Oncology (2006)
International Studies of Prenatal Exposure to Polycyclic Aromatic Hydrocarbons and Fetal Growth
Authors: Hyunok Choi, Wieslaw Jedrychowski, John Spengler, David E. Camann, Robin M. Whyatt, Virginia Rauh, Wei-Yann Tsai, Frederica P. Perera
Journal: Environmental Health Perspectives (2006)

ObjectivesPolycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed human mutagens and carcinogens. However, lack of adequate air monitoring data has limited understanding of the effects of airborne PAHs on fetal growth. To address this gap in knowledge, we examined the association between prenatal exposure to airborne PAHs and birth weight, birth length, and birth head circumference, respectively, in Krakow, Poland, and New York City (NYC).MethodsThe parallel prospective cohort studies enrolled nonsmoking, healthy, and nonoccupationally exposed women and their newborns. Personal air monitoring of pregnant women was conducted over 48 hr. To control for maternal environmental tobacco smoke (ETS) exposure, we excluded those with umbilical cord plasma cotinine concentrations > 25 ng/mL. Mean cord plasma cotinine concentrations in both ethnic groups were ≤ 0.5 ng/mL.ResultsPrenatal PAH exposure was 10-fold higher in Krakow than in NYC. Prenatal PAH exposure was associated with significantly reduced birth weight in both Krakow Caucasians (p < 0.01) and in NYC African Americans (p < 0.01), controlling for known and potential confounders, but not in NYC Dominicans. Within the lower exposure range common to the two cities (1.80–36.47 ng/m3), the effect per unit PAH exposure on birth weight was 6-fold greater for NYC African Americans than for Krakow Caucasians (p = 0.01).ConclusionsThese results confirm the adverse reproductive effect of relatively low PAH concentrations in two populations and suggest increased susceptibility of NYC African Americans. Fetal growth impairment has been linked to child developmental and health problems. Thus, substantial health benefits would result from global reduction of PAH emissions.
Causes of Death and Relative Survival of Older Women After a Breast Cancer Diagnosis
Authors: Mara A. Schonberg, Edward R. Marcantonio, Long Ngo, Donglin Li, Rebecca A. Silliman, Ellen P. McCarthy
Journal: Journal of Clinical Oncology (2011)

Purpose To understand the impact of breast cancer on older women's survival, we compared survival of older women diagnosed with breast cancer with matched controls. Methods Using the linked 1992 to 2003 Surveillance, Epidemiology, and End Results (SEER) -Medicare data set, we identified women age 67 years or older who were newly diagnosed with ductal carcinoma in situ (DCIS) or breast cancer. We identified women not diagnosed with breast cancer from the 5% random sample of Medicare beneficiaries residing in SEER areas. We matched patient cases to controls by birth year and registry (99% or 66,039 patient cases matched successfully). We assigned the start of follow-up for controls as the patient cases' date of diagnosis. Mortality data were available through 2006. We compared survival of women with breast cancer by stage with survival of controls using multivariable proportional hazards models adjusting for age at diagnosis, comorbidity, prior mammography use, and sociodemographics. We repeated these analyses stratifying by age. Results Median follow-up time was 7.7 years. Differences between patient cases and controls in sociodemographics and comorbidities were small (&lt; 4%). Women diagnosed with DCIS (adjusted hazard ratio [aHR], 0.7; 95% CI, 0.7 to 0.7) or stage I disease (aHR, 0.8; 95% CI, 0.8 to 0.8) had slightly lower mortality than controls. Women diagnosed with stage II disease or higher had greater mortality than controls (stage II disease: aHR, 1.2; 95% CI, 1.2 to 1.2). The association of a breast cancer diagnosis with mortality declined with age among women with advanced disease. Conclusion Compared with matched controls, a diagnosis of DCIS or stage I breast cancer in older women is associated with better survival, whereas a diagnosis of stage II or higher breast cancer is associated with worse survival.
Extraction, Purification, and Assay of Human Renin Free of Angiotensinase
Authors: ERWIN HAAS, HARRY GOLDBLATT, EDWIN C. GIPSON, LAVERA LEWIS
Journal: Circulation Research (1966)

Three procedures are described for the extraction and purification of renin from 0.05 to 500 g of human kidneys. A uniform yield of renin, free of angiotensinase, resulted from all three procedures. All tests for renin were carried out in dogs. When more than 10 g of renal tissue was used, renin was determined by the direct method; with smaller amounts, the indirect method, involving the production and the assay of angiotensin, was employed. Renin substrate free of angiotensinase, suitable for the indirect assay of human renin, was prepared from pooled human serum by a simple procedure. The angiotensinase-free renin and substrate permitted prolonged incubation for the production of the angiotensin required for the indirect assay. The mean ratio of angiotensin produced (unit per milliter of serum) to the amount of renin added (unit per milliliter of serum) was 1,482 for an 18-hour period of incubation. The large amount of angiotensin produced permitted the indirect assay of minute amounts of human renin (as little as 0.0005 unit, from 5 mg of renal tissue) in the dog. Unless the angiotensinase present in extracts of renal tissue or serum is first removed, the accurate, indirect assay of the renin is not possible.
Tolterodine and Tamsulosin for Treatment of Men With Lower Urinary Tract Symptoms and Overactive Bladder
Authors: Steven A. Kaplan, Claus G. Roehrborn, Eric S. Rovner, Martin Carlsson, Tamara Bavendam, Zhonghong Guan
Journal: JAMA (2006)

Men with overactive bladder and other lower urinary tract symptoms may not respond to monotherapy with antimuscarinic agents or alpha-receptor antagonists.To evaluate the efficacy and safety of tolterodine extended release (ER), tamsulosin, or both in men who met research criteria for both overactive bladder and benign prostatic hyperplasia.Randomized, double-blind, placebo-controlled trial conducted at 95 urology clinics in the United States involving men 40 years or older who had a total International Prostate Symptom Score of 12 or higher and, an International Prostate Symptom Score quality-of-life (QOL) item score of 3 or higher, a self-rated bladder condition of at least moderate bother, and a bladder diary documenting micturition frequency (>or=8 micturitions per 24 hours) and urgency (>or=3 episodes per 24 hours), with or without urgency urinary incontinence. Patients were recruited between November 2004 and February 2006, and the study was completed May 2006.Patients were randomly assigned to receive placebo (n = 222), 4 mg of tolterodine ER (n = 217), 0.4 mg of tamsulosin (n = 215), or both tolterodine ER plus tamsulosin (n = 225) for 12 weeks.Patient perception of treatment benefit, bladder diary variables, International Prostate Symptom Scores, and safety and tolerability were assessed.A total of 172 men (80%) receiving tolterodine ER plus tamsulosin reported treatment benefit by week 12 compared with 132 patients (62%) receiving placebo (P<.001), 146 (71%) receiving tamsulosin (P=.06 vs placebo), or 135 (65%) receiving tolterodine ER (P=.48 vs placebo). Patients receiving tolterodine ER plus tamsulosin compared with placebo experienced significant reductions in urgency urinary incontinence (-0.88 vs -0.31, P=.005), urgency episodes without incontinence (-3.33 vs -2.54, P=.03), micturitions per 24 hours (-2.54 vs -1.41, P<.001), and micturitions per night (-0.59 vs -0.39, P.02). Patients receiving tolterodine ER plus tamsulosin demonstrated significant improvements on the total International Prostate Symptom Score (-8.02 vs placebo, -6.19, P=.003) and QOL item (-1.61 vs -1.17, P=.003). All interventions were well tolerated. The incidence of acute urinary retention requiring catheterization was low (tolterodine ER plus tamsulosin, 0.4%; tolterodine ER, 0.5%; tamsulosin, 0%; and placebo, 0%).These results suggest that treatment with tolterodine ER plus tamsulosin for 12 weeks provides benefit for men with moderate to severe lower urinary tract symptoms including overactive bladder. Clinical Trials Registration clinicaltrials.gov Identifier: NCT00147654.
The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research
Authors: Martin A. Cheever, James P. Allison, Andrea S. Ferris, Olivera J. Finn, Benjamin M. Hastings, Toby T. Hecht, Ira Mellman, Sheila A. Prindiville, Jaye L. Viner, Louis M. Weiner, Lynn M. Matrisian
Journal: Clinical Cancer Research (2009)

The purpose of the National Cancer Institute pilot project to prioritize cancer antigens was to develop a well-vetted, priority-ranked list of cancer vaccine target antigens based on predefined and preweighted objective criteria. An additional aim was for the National Cancer Institute to test a new approach for prioritizing translational research opportunities based on an analytic hierarchy process for dealing with complex decisions. Antigen prioritization involved developing a list of "ideal" cancer antigen criteria/characteristics, assigning relative weights to those criteria using pairwise comparisons, selecting 75 representative antigens for comparison and ranking, assembling information on the predefined criteria for the selected antigens, and ranking the antigens based on the predefined, preweighted criteria. Using the pairwise approach, the result of criteria weighting, in descending order, was as follows: (a) therapeutic function, (b) immunogenicity, (c) role of the antigen in oncogenicity, (d) specificity, (e) expression level and percent of antigen-positive cells, (f) stem cell expression, (g) number of patients with antigen-positive cancers, (h) number of antigenic epitopes, and (i) cellular location of antigen expression. None of the 75 antigens had all of the characteristics of the ideal cancer antigen. However, 46 were immunogenic in clinical trials and 20 of them had suggestive clinical efficacy in the "therapeutic function" category. These findings reflect the current status of the cancer vaccine field, highlight the possibility that additional organized efforts and funding would accelerate the development of therapeutically effective cancer vaccines, and accentuate the need for prioritization.
Hip labral tears, economics in sports medicine and guidelines for NSAID use
Authors: K M Khan
Journal: British Journal of Sports Medicine (2009)

I was going to entitle this WarmUp “ Paris, ‘Outliers’ and Kudos to Scandinavia” but that would have meant that people Googling the Paris Hilton video would have ended up here. Didn’t want them. Why mention Paris (the place)? What struck me on a recent vacation in Paris was not its stunning architecture, amazing art collections or expensive cappuccinos — it was the level of smoking! Beautiful young Parisians clearly in love — with cigarettes. Smokers pack the best tables on streetside cafes; literally cheek by anoxic jowl with each other. The City of Lights is now the City that Lights. But relevance to BJSM you ask?

The persistence of Parisian smoking in the absence of effective legislation illustrates what has been described as the “socioecological model” of behaviour change.1 In short, you cannot change societal behaviour one clinical consultation at a time. In lay language you can think of the expression “it takes a village to raise a child” — big changes need multi-level efforts. In popular literature, …
Clinical Efficacy of Polymer-Based Paclitaxel-Eluting Stents in the Treatment of Complex, Long Coronary Artery Lesions From a Multicenter, Randomized Trial
Authors: Keith D. Dawkins, Eberhard Grube, Giulio Guagliumi, Adrian P. Banning, Krzysztof Zmudka, Antonio Colombo, Leif Thuesen, Karl Hauptman, Jean Marco, William Wijns, Jeffrey J. Popma, Joerg Koglin, Mary E. Russell
Journal: Circulation (2005)

Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking.TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively (P=0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively (P=0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients (P<0.0001).The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice.
Hedging against Antiviral Resistance during the Next Influenza Pandemic Using Small Stockpiles of an Alternative Chemotherapy
Authors: Joseph T. Wu, Gabriel M. Leung, Marc Lipsitch, Ben S. Cooper, Steven Riley
Journal: PLoS Medicine (2009)

Mathematically simulating an influenza pandemic, Joseph Wu and colleagues predict that using a secondary antiviral drug early in local epidemics would reduce global emergence of resistance to the primary stockpiled drug.
Sustained durability and tolerability of etanercept in ankylosing spondylitis for 96 weeks
Authors: J C Davis
Journal: Annals of the Rheumatic Diseases (2005)

To evaluate the continued safety and durability of clinical response in patients with ankylosing spondylitis receiving etanercept.277 patients who had participated in a previous randomised, double blind, placebo controlled 24 week trial were eligible to continue in this open label extension study. All patients who enrolled in the open label extension (n = 257) received subcutaneous etanercept 25 mg twice weekly for up to 72 weeks, for a combined 96 weeks of cumulative trial and open label experience. For the patients who had received etanercept for 24 weeks in the double blind trial, this represented almost 2 years of continuous etanercept treatment.Patients continuing etanercept treatment had a sustained response for almost 2 years, with 74% achieving an ASsessments in Ankylosing Spondylitis 20% (ASAS 20) response after 96 weeks of etanercept treatment. Patients who had received placebo in the preceding double blind trial had similar responses, with 70% of patients attaining an ASAS 20 response after 24 weeks of etanercept treatment and 78% achieving an ASAS 20 response after 72 weeks. Improved spinal mobility was seen in both groups. Etanercept was well tolerated in patients treated for up to 96 weeks.The subcutaneous administration of twice weekly doses of etanercept provided sustained durability of response in the improvement of signs and symptoms of ankylosing spondylitis for nearly 2 years.
PIK3IP1, a Negative Regulator of PI3K, Suppresses the Development of Hepatocellular Carcinoma
Authors: Xin He, Zhenqi Zhu, Carla Johnson, John Stoops, Amanda E. Eaker, William Bowen, Marie C. DeFrances
Journal: Cancer Research (2008)

Phosphatidylinositol-3-kinase (PI3K) is a well-known regulator of cell division, motility, and survival in most cell types. Recently, we characterized a novel protein that we call PI3K Interacting Protein 1 (PIK3IP1), which binds to the p110 catalytic subunit of PI3K and reduces its activity in vitro. Little is known about the role of PIK3IP1 in normal and neoplastic growth in vivo. Proper liver function and development depend on intact PI3K signal transduction; when dysregulated, the PI3K pathway is linked to the development of liver cancer. To begin to dissect the contribution of PIK3IP1 to hepatic PI3K signaling in vivo and to liver tumorigenesis in particular, we formulated the following hypothesis: because PIK3IP1 down-regulates PI3K signaling and uncontrolled PI3K signaling is associated with liver cancer, then PIK3IP1-mediated down-regulation of the PI3K pathway should inhibit hepatocellular carcinoma (HCC) development. To test this idea, we generated transgenic mice overexpressing PIK3IP1 in hepatocytes in a mouse strain prone to develop HCC. Isolated PIK3IP1 transgenic mouse hepatocytes showed blunted PI3K signaling, DNA synthetic activity, motility, and survival compared with controls. In vivo, spontaneous liver tumorigenesis was significantly dampened in the transgenic animals. This was accompanied by decreased hepatic PI3K activity and reduced hepatocyte proliferation in the transgenics compared with controls. We also observed that human HCC expressed less PIK3IP1 protein than adjacent matched liver tissue. Our data show that PIK3IP1 is an important regulator of PI3K in vivo, and its dysregulation can contribute to liver carcinogenesis.
Inhibition of Podocyte FAK Protects against Proteinuria and Foot Process Effacement
Authors: Hong Ma, Akashi Togawa, Keita Soda, Junhui Zhang, Sik Lee, Ming Ma, Zhiheng Yu, Thomas Ardito, Jan Czyzyk, Lonnette Diggs, Dominique Joly, Shinji Hatakeyama, Eiji Kawahara, Lawrence Holzman, Jun Lin Guan, Shuta Ishibe
Journal: Journal of the American Society of Nephrology (2010)

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that plays a critical role in cell motility. Movement and retraction of podocyte foot processes, which accompany podocyte injury, suggest focal adhesion disassembly. To understand better the mechanisms by which podocyte foot process effacement leads to proteinuria and kidney failure, we studied the function of FAK in podocytes. In murine models, glomerular injury led to activation of podocyte FAK, followed by proteinuria and foot process effacement. Both podocyte-specific deletion of FAK and pharmacologic inactivation of FAK abrogated the proteinuria and foot process effacement induced by glomerular injury. <i>In vitro</i>, podocytes isolated from conditional FAK knockout mice demonstrated reduced spreading and migration; pharmacologic inactivation of FAK had similar effects on wild-type podocytes. In conclusion, FAK activation regulates podocyte foot process effacement, suggesting that pharmacologic inhibition of this signaling cascade may have therapeutic potential in the setting of glomerular injury.
CALCIUM AND INORGANIC PHOSPHORUS IN THE BLOOD OF RABBITS
Authors: Wade H. Brown
Journal: The Journal of Experimental Medicine (1929)

A series of experiments was carried out for the purpose of determining whether a light environment comprising radiations of comparatively long wave-length and only a small amount of energy was capable of affecting the chemical equilibrium of the blood as indicated by the calcium and inorganic phosphorus content of the blood of normal rabbits. A study was made of effects produced by prolonged exposure to fixed environmental conditions (neon light and darkness) as compared with a varying environment of diffuse, filtered sunlight and by a change from one environment to another. It was found that the chemical equilibrium of the blood was definitely affected by the conditions employed and that the effects produced could be correlated with differences in organic constitution on the one hand, and on the other, with certain differences in the functional activity of the same animals, involving nutrition and growth and the proliferative activity of hair follicles.