tbuckley/cabot-search huggingface dataset:
Efficacy of an intervention to improve communication about randomised clinical trials (RCTS) in cancer
Authors: V. A. Jenkins, L. J. Fallowfield, C. I. Langridge, V. Farewell, I. Solis-Trapala
Journal: Journal of Clinical Oncology (2004)

6040 Background: Fewer than 5% of eligible patients worldwide are offered entry into RCTs. Recruitment problems impede introduction of potentially efficacious treatments. To aid communication about RCTs we designed and evaluated a comprehensive training program. The program comprises 4 modules with videotaped scenarios, interactive exercises and a handbook. Video 1 deals with generic issues about RCTs. 3 further videos each contain 2 scenarios dealing with adjuvant trials, those with palliation as the goal and trials where patients have a preference for one treatment arm. Patient characteristics eg the deferential, highly suspicious or overly informed are illustrated throughout. Methods: 101 participants were evaluated. Subjective and objective assessments were made pre (T1) and post (T2) workshop. Participants self-rated their confidence about different aspects of trial discussion. All were videotaped discussing a trial with a simulated patient at T1 and T2: an experienced rater, blinded to time point, viewed these tapes to check for the presence/absence of key information required by Good Clinical Practice(GCP) Guidelines. Simulated patients also assessed the interviews at each time point. Results: Skills of 33 clinicians and 68 research nurses were evaluated. Significant improvements were found on subjective and objective measures of their communication post-workshop. Self-confidence increased significantly across all areas (P<0.0001). Patient simulator ratings revealed a global improvement in discussions about trials (P<0.0001) odds ratio showed significant changes for 13/15 key items Objective analysis of video assessments demonstrated a positive shift with odds ratios showing significant changes for 10/15 GCP items. ConclusionsAn intensive 1. 5-day program significantly improved the confidence and competence of communication about RCTs. More interventions are needed to promote better understanding about trials and to encourage clinicians to approach more eligible patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cancer Research UK
An oral dosage formulation of azacitidine: A pilot pharmacokinetic study
Authors: M. R. Ward, M. L. Stoltz, J. B. Etter, L. M. Patton, G. Garcia Manero, S. Sharma
Journal: Journal of Clinical Oncology (2007)

7084 Background: Azacitidine, a cytidine analog, induces DNA demethylation that leads to tumor suppressor gene expression. Cellular effects of azacitidine treatment include differentiation, cell cycle arrest and/or apoptosis. There is a complex, non-linear relationship between plasma exposure and pharmacodynamic effect of azacitidine that can be fully explored with an oral formulation of azacitidine, enabling alternate dosing strategies ranging from intermittent high dose to continuous, low-dose approaches to DNA demethylation. Methods and Results: A pharmacokinetic study in dogs given oral azacitidine demonstrated rapid absorption with absolute bioavailability of 67% (compared to 71% following SC dosing). When comparing a single parenteral dose of 75 mg/m 2 (∼2 mg/kg) given SC to humans vs. a single oral dose of 16 mg/m 2 (0.8 mg/kg) given to dogs, plasma concentrations of azacitidine were similar despite the 4- to 5-fold difference in dose as calculated by body surface area (BSA). A 14-day toxicology study in dogs evaluated the oral doses of 0.2, 0.4, and 0.8 mg/kg/day. The high dose is the previously identified MTD of 0.55 mg/kg/day based on an oral bioavailability of 67% (approximately equal to 16 mg/m 2 /day). Hematologic toxicity, a known and expected effect of azacitidine administered in a repeat-dose regimen was observed at the two highest doses. The oral MTD was determined to be 0.2 mg/kg/day for 14 consecutive days followed by a 21-day recovery period. This provides a cumulative MTD of 2.8 mg/kg for the14 day dosing regimen, which is similar to that seen with IV dosing (2.75 mg/kg over 5 days). Based on the preclinical studies, a multicenter, single-treatment study of oral azacitidine is underway in subjects with MDS, AML, or solid tumors. The trial assesses the safety, tolerability and pharmacokinetics of escalating single doses of orally administered azacitidine. Clinical data from this study will be presented. [Table: see text]
Treatment of Calcific Aortic Stenosis With the Percutaneous Heart Valve
Authors: Alain Cribier, Helene Eltchaninoff, Christophe Tron, Fabrice Bauer, Carla Agatiello, Deborah Nercolini, Sydney Tapiero, Pierre-Yves Litzler, Jean-Paul Bessou, Vasilis Babaliaros
Journal: Journal of the American College of Cardiology (2006)
Oral Etoposide for Refractory and Relapsed Neuroblastoma
Authors: Brian H. Kushner, Kim Kramer, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To describe the efficacy of oral etoposide against resistant stage 4 neuroblastoma. PATIENTS AND METHODS: Patients with refractory or recurrent stage 4 neuroblastoma were treated with etoposide 50 mg/m 2 taken orally each day, in two or three divided doses, for 21 consecutive days. Treatment could be repeated after a 1-week period. Extent-of-disease studies included imaging with 131-iodine-metaiodobenzylguanidine and extensive bone marrow (BM) sampling. RESULTS: Oral etoposide was used in 20 children between the ages of 2 and 11 years (median, 6 years). Prior treatment included high doses of alkylating agents and a median of 4.5 cycles of etoposide-containing chemotherapy, with cumulative etoposide doses of 1,800 mg/m 2 to 3,935 mg/m 2 (median, 2,300 mg/m 2 ). Oral etoposide produced antineuroblastoma effects in four of four children with disease refractory to intensive induction treatment; sampling variability could account for resolution (n = 3) or reduction (n = 1) of BM involvement, but improvement in other markers also occurred. Antineuroblastoma effects were also evident in five of five children with asymptomatic relapses after a long chemotherapy-free interval: BM disease resolved and all other disease markers significantly improved in two patients, and disease markers improved or stabilized in three patients on treatment for more than 6 months. In these nine patients, extramedullary toxicity was absent, neutropenia did not occur, transfusional support was not needed, and preliminary data suggested little immunosuppression (phytohemagglutinin responses). Oral etoposide was ineffective in all (11 of 11) patients with rapidly growing tumor masses. CONCLUSION: Given the absence of toxicity to major organs, the minimal myelosuppression or immunosuppression, and the antineoplastic activity in patients with low tumor burdens after high-dose chemotherapy, limited use of low-dose oral etoposide should be considered for inclusion in postinduction consolidative treatment programs aimed at eradicating minimal residual disease.
Increased risk of school age asthma following multiple trigger wheeze, independent of atopy
Authors: Emma Goksör, Petra Loid, Bernt Alm, Rolf Pettersson, Per Möllborg, Laslo Erdes, Nils Åberg, Göran Wennergren
Journal: European Respiratory Journal (2014)

Background: Multiple trigger wheeze (MTW) i.e. wheezing also apart from colds has been associated with an increased risk of later asthma compared to episodic viral wheeze (EVW) i.e . wheezing with colds only. However, the predictive value of these phenotypes has been questioned. The aim of this study was to analyse the risk of school age asthma in preschool children with MTW vs EVW.

Methods: Data were obtained from a prospective, longitudinal study of a cohort of children born in western Sweden. The parents answered questionnaires at 6 months and 1, 4.5 and 8 years of age. The response rate at 8 years was 80% of the questionnaires distributed (4,051/5,044), i.e. 71% of the families entering the study (4,051/5,654).

Results: The prevalence of doctor-diagnosed asthma at 8 years was 67% in children with MTW and 33 % in children with EVW. The risk of asthma was increased both in children with MTW (OR 48.9, CI 95% 29.3-81.6) and EVW (OR 16.2, 10.3-25.6) compared to no wheeze at age 4.5 and in MTW vs EVW (OR 3.4, 1.8-6.5), independent of atopic heredity and other allergic manifestations at preschool age. The increased risk of asthma in MTW vs EVW, was evident also when analysing only subjects without allergy at preschool age (OR 3.6, 1.8-7.1). In children with MTW, atopic asthma was more common and both the risk of atopic asthma (OR 6.2, 3.1-12.7) and non-atopic asthma (OR 2.3, 1.03-4.9) was higher vs EVW.

Conclusion: The risk of doctor-diagnosed asthma at 8 years was increased among preschool children with MTW vs EVW, independent of heredity and preschool allergy, and also in children without preschool allergy. In addition, atopic asthma at 8 years was more common among children with MTW.
Repeated Dosing Of Anti-KIR (IPH2101) As Maintenance Therapy In Ederly Patients With Acute Myeloid Leukemia
Authors: Norbert Vey, Jean-Henri Bourhis, Christian Recher, Anne Etienne, Aude Charbonnier, Pascale Andre, Jérôme Rey, Franceline Calmels, Robert Zerbib, Renaud Buffet, Thomas Prebet
Journal: Blood (2013)
Comparison of negative pressure wound therapy and secondary intention healing after excision of acral lentiginous melanoma on the foot
Authors: B.H. Oh, S.H. Lee, K. A. Nam, H.B. Lee, K.Y. Chung
Journal: British Journal of Dermatology (2013)

Background Melanoma in dark‐skinned individuals often develops in an acral lentiginous fashion on the foot and wide excision usually results in a substantial defect. Various repair methods, including free flap, full‐thickness skin graft and secondary intention healing (SIH), are used to repair these defects. Recently, use of negative pressure wound treatment (NPWT) has been shown to accelerate wound healing in different types of wound. Objectives To compare the functional and cosmetic results of NPWT and SIH in patients who underwent wide excision of melanomas on the foot. Methods The wound defects of 22 patients after wide excision of melanoma on the foot were treated using SIH (n =13) or NPWT (n =9). Results There was no significant difference in time to complete wound healing between the two groups. However, evaluation using the Vancouver Burn Scar Assessment Scale at the time of complete healing showed that the mean score of the NPWT group was significantly lower than that of the SIH group. The NPWT group also had significantly better results than the SIH group in terms of total score, vascularity and height of the scars. As for complications, no wound infection was encountered in the NPWT group, whereas eight of the 13 patients in SIH group had wound infections during the course of treatment despite frequent and meticulous aseptic dressing changes. Conclusions These results show that, despite the drawback of rather prolonged healing time, NPWT is an excellent therapeutic option for wounds after wide excision of melanoma on the foot, with acceptable functional and cosmetic outcomes.
HIV infection en route to endogenization: two cases
Authors: P. Colson, I. Ravaux, C. Tamalet, O. Glazunova, E. Baptiste, E. Chabriere, A. Wiedemann, C. Lacabaratz, M. Chefrour, C. Picard, A. Stein, Y. Levy, D. Raoult
Journal: Clinical Microbiology and Infection (2014)

The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3-100% per gene) and 24% overall (0-50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication.
Study confirms previous findings
Authors: A. Ponzetto, M. T. La Rovere, P. Sanseverino, F. Bazzoli
Journal: BMJ (1996)

EDITOR,—P Patel and colleagues' study substantiates our observation of an association between infection with Helicobacter pylori and coronary heart disease.1 The first report from the group2 prompted our retrospective serological study among patients presenting to the emergency care unit of our hospital.3 Currently we are recruiting all patients admitted to the coronary unit of our hospital with …
Abstract 15979: Change in Body Mass Index is a Major Determinant of Lifestyle Induced Changes in Lipoprotein Particle Size and Number in the Diabetes Prevention Program (DPP)
Authors: Ronald Goldberg, Marinella Temprosa, Elizabeth Barrett-Connor, Richard Arakaki, Kieren Mather, James Otvos, Karol Watson, Steve Haffner
Journal: Circulation (2011)

Insulin resistant states are characterized by increased large VLDL, small LDL and small HDL particles (p) which may contribute to atherosclerosis risk. We have previously shown that lifestyle (ILS)...
Thyroid function test changes with adjuvant tamoxifen therapy in postmenopausal women with breast cancer.
Authors: C C Mamby, R R Love, K E Lee
Journal: Journal of Clinical Oncology (1995)

PURPOSE While tamoxifen has been shown to alter concentration of many hormones and their binding globulins, there have been conflicting results regarding its effects on thyroid function tests. We sought to clarify these effects by studying subjects in a controlled clinical trial. PATIENTS AND METHODS We evaluated a subset of postmenopausal women who had participated in a longitudinal, double-blind, randomized, placebo-controlled toxicity study of tamoxifen 10 mg orally, twice daily. There were 14 subjects in both the tamoxifen and placebo groups. Measurement of thyroid-binding globulin (TBG), thyroxine uptake (T-Uptake), thyroxine (T4), and thyroid-stimulating hormone (TSH), and an indirect estimate of the free T4 index (FTI), were made for each subject before and after 3 months of treatment. RESULTS For T-Uptake, T4, and TBG, there were significant increases in the mean change from baseline to 3 months in the tamoxifen group compared with the placebo group (P = .02, .0001, and .003, respectively), while there were no significant changes in the measured TSH and in the calculated FTI. CONCLUSION We conclude that tamoxifen therapy in postmenopausal women results in increased TBG, with secondary increases in measured T-Uptake and T4 following. However, TSH and FTI levels are unchanged, and treated women remain eumetabolic.
Research Recruitment of Adult Survivors of Neonatal Infections: Is There a Role for Parental Consent?
Authors: Ann J. Melvin, Kathleen M. Mohan, Anna Wald, Kathryn Porter, Benjamin S. Wilfond
Journal: The American Journal of Bioethics (2015)

"Research Recruitment of Adult Survivors of Neonatal Infections: Is There a Role for Parental Consent?." The American Journal of Bioethics, 15(10), pp. 58–59
A comparison of sampling error and standard error
Authors: Philip Sedgwick
Journal: BMJ (2015)

The impact of a diet and physical activity programme on body weight in overweight or obese people initiated through a national colorectal cancer screening programme was investigated. A multicentre randomised controlled trial was performed. The intervention consisted of a personalised, behaviourally focused weight loss programme, delivered over 12 months. The control treatment consisted of a weight loss booklet only. Participants were overweight or obese adults (aged 50-74 years) who had undergone colonoscopy after a positive faecal occult blood test result and had a diagnosis of adenoma confirmed by histopathological examination. In total, 329 participants were recruited and randomised to the intervention (n=163) or control (n=166).1 The primary outcome was weight change over 12 months. At follow-up, data were available on the primary outcome for 148 (91%) participants in the intervention group and 157 (95%) in the control group. At 12 months, mean weight loss was 3.50 kg (95% confidence interval 2.70 to 4.30; standard error 0.40) in the intervention group compared with 0.78 kg (0.19 to 1.38; 0.30) in the control group. The intervention group lost significantly more weight (mean difference 2.69 kg, 1.70 to 3.67; P<0.001). It was concluded that significant weight loss can be achieved by a diet and physical activity intervention initiated within a national colorectal cancer screening programme in older adults, offering considerable potential for reducing the risk of disease. Which of the following statements, if any, are true?
Collaborative Science and the American Thoracic Society
Authors: Theodore F. Reiss, Joel Moss, Molly Osborne, J. Randall Curtis, Nicholas S. Hill
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

was the archetype for a translational scientist.He was the key contributor to the discovery and development of vaccines against measles and mumps.For his achievements, he was awarded the National Medal of Science and was recognized by scientists worldwide.Acceptance within both industry and academic environments was a key to his success (1).Beyond medicine, similarly successful collaborative efforts across academia, government, and industry benefit us daily, including, for example, dramatic advances in communication and electronic technology.Recent advances in the treatment of lymphangioleiomyomatosis, based on research conducted by American Thoracic Society (ATS) members and supported by the ATS, provide another example of the value of such collaborative efforts among academic, industry, and government scientists.These stories highlight the benefit of collaboration and open dialogue to the advances in biomedical research.A significant body of scholarship emphasizes the benefit of diverse teams to problem solving (2).However, there are also situations in which relationships between institutions, for example, industry and either academia or professional societies, have resulted in serious concerns about conflicts of interest and have threatened to undermine public trust in biomedical research.To optimize medical advances in a time of shrinking resources, these differing perspectives must be reconciled.Although the ATS has instituted transparent processes to address conflicts of interest, the recent focus on such conflicts has had the unintended consequence of creating barriers to initiatives fostering collaborative efforts across academia, government, and industry.To take full advantage of the potential of these collaborative efforts, a midcourse correction will be necessary.By addressing this challenge, we hope to further the mission of the ATS "to improve health worldwide by advancing research, clinical care and public health in respiratory disease, critical illness and sleep disorders," while ensuring that perceived conflicts of interest are appropriately identified and managed, promoting ethical conduct as well as public confidence and trust.
Medical negligence and substandard drugs caused deaths in Indian sterilisation programme, report finds
Authors: Sanjeet Bagcchi
Journal: BMJ (2015)

Medical negligence and the distribution of substandard and toxic drugs led to the deaths of 13 women taking part in a government run mass sterilisation programme in India in November 2014, a report has found . 

Thirteen women died and a further 14 became seriously ill at the mass sterilisation camp in Bilaspur, Chhattisgarh, where a 59 year old doctor, R K Gupta, performed laparoscopic sterilisation on 83 women under a government …
Meta-analysis of the literature: Neoadjuvant chemotherapy versus surgery alone in non-small cell lung cancer
Authors: L. Dan, B. Zhu, Z. Chen
Journal: Journal of Clinical Oncology (2008)

7580 Background: Patients with resectable non- small-cell lung cancer (NSCLC) have a low survival rate following standard surgical treatment. The effectiveness of neoadjuvant chemotherapy on the prognosis of the patients was still controversial. We performed a meta-analysis to evaluate the efficiency of neoadjuvant chemotherapy on the prognosis of the patients in non-small cell lung cancer. Methods: Randomized studies published in English and Chinese until 2007 were included in our study. Ten eligible randomized controlled trails including 2,546 patients were combined and used in the present meta-analysis (1,291 in the study group, 1,255 in the control group). Relative risk was calculated from the reports of the studies available and then combined together to get estimate of efficacy. Results: Neoadjuvant chemotherapy improved survival with a relative risk of 0.91(95% confidence interval, 0.86–0.96; p=0.0007). Conclusions: Our meta-analysis shows a benefit of neoadjuvant chemotherapy to the patients with resectable NSCLC. However, higher quality of trials is still needed, especially with neoadjuvant chemotherapy based on platinum/3rd generation medicine. No significant financial relationships to disclose.
Cardiopulmonary Exercise Testing: Physiologic Principles and Clinical Applications
Journal: Thorax (1987)

Background: Vitamin D is known for its anti-cancerogenous potential. Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) is a proliferation and inflammation activating agent. The production of PGE<sub>2</sub> is dependent on the activity of cyclooxygenase-2 (COX-2). A link between vitamin D and PGE<sub>2</sub> metabolism was recently shown. Materials and Methods: In MDA-MB-231 and MCF-7 breast cancer cell lines we investigated the influence of calcitriol and the COX-2 inhibitor celecoxib regarding cell growth via MTT test, as well as on the protein and mRNA expression of COX-2 using western blot and qRT-PCR. Results: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX-2 inhibitor celecoxib and even stronger by their combination. Moreover, calcitriol inhibited the COX-2 protein expression in MDA-MB-231, as well as the COX-2 mRNA expression in both cell lines. Conclusion: The combination of calcitriol and celecoxib demonstrated a cooperative growth-inhibiting effect in breast cancer cell lines.
An Audit of Autopsy Rates in an Inner London General Hospital
Authors: E J Lazda, D C Brown
Journal: Journal of the Royal Society of Medicine (1994)

Low autopsy rates are of continuing concern to pathologists. The aim of this study was to investigate the reasons why autopsy did not happen, and to determine whether carrying out the investigation and providing some feedback of the results would have any effect on autopsy rates. The main reasons why autopsy did not happen were that junior doctors considered it unnecessary because the diagnosis and cause of death appeared to be well established, and that patients' relatives declined to give permission for autopsy. No increase in autopsy rates was demonstrated, but possible avenues of approach were suggested and these are being implemented.