tbuckley/cabot-search huggingface dataset:
Interim report of on-study demographics and toxicity from E1505, a phase III randomized trial of adjuvant (adj) chemotherapy (chemo) with or without bevacizumab (B) for completely resected early-stage non-small cell lung cancer (NSCLC).
Authors: H. A. Wakelee, S. E. Dahlberg, S. M. Keller, D. R. Gandara, S. L. Graziano, N. B. Leighl, A. A. Adjei, J. H. Schiller
Journal: Journal of Clinical Oncology (2011)

7013 Background: Adj chemo has been shown to improve absolute survival after resection of early stage NSCLC by 5-15%. Encouraging results with B on E4599 in advanced stage NSCLC led to trial development of B with adj chemo. Methods: E1505 aims to enroll 1500 pts with resected stage IB (>/= 4 cm) – IIIA (by AJCC 6) NSCLC. All pts receive 4 x 3 wk cycles of doublet chemo with cisplatin (C) plus vinorelbine (V), docetaxel (D), gemcitabine (G) or pemetrexed (P). P option was added in 2009. Pts are randomized 1:1 to chemo alone or chemo + B (B continued up to 1 yr). Inclusion criteria for this interim toxicity analysis included randomization at least one year prior to the data pull (Jan 5, 2011). Fisher's exact test was used to test for differences in categorical data; Wilcoxon rank sum test was used to test for differences in continuous variables. Toxicities were graded using CTCAE v 3.0. Results: Included here are 557 pts (enrolled Aug 2007-Jan 5, 2010) (282 Chemo/275 Chemo+B) median age 61 (range 36-86 yo), 340 (61%) ECOG PS 0, 291 (52%) women, 490 (88%) white, 302 (54%) adenocarcinoma, 172 (31%) squamous histology. Stages enrolled were: 129 (23%) IB, 244 (43%) II, 158 (29%) IIIA-N2, 22 (4%) IIIA-T3N1 and only a minority had had a pneumonectomy 73 (13%). All demographic features were well balanced. Adj chemo was CV- 155 (28%), CD 186 (34%), CG 145 (26%), CP 69 (12%), balanced by arm. There is a significant increase in risk of grades 3/4 hypertension (0.7 vs. 19.7%, p<0.001), proteinuria (0.7 vs. 3.4%, p=0.03), abdomen pain (0.4 vs. 4.6%, p=0.001), and overall grade 3/4 toxicity (68.5% vs. 83.4%, p<0.001) associated with B. Grade 5 toxicity rates were not significantly different at 2.5% vs 3.8% -/+ B, p=0.46. Only 1 case each of fatal hemoptysis and non-fatal bronchopleural fistula have been seen in pts receiving B. Conclusions: This report provides interim demographic safety data for E1505, revealing no unexpected toxicities. Enrollment challenges include lack of adequate lymph node sampling in otherwise eligible pts. The study remains open to accrual with projected enrollment completion in 2013.
Impaired smooth pursuit eye movement: vulnerability marker for schizotypal personality disorder in a normal volunteer population
Authors: Larry J Siever, Robert D. Coursey, Ina S. Alterman, Monte S. Buchsbaum, Dennis L. Murphy
Journal: American Journal of Psychiatry (1984)

Impaired smooth pursuit eye movement has been proposed as a possible biologic marker for schizophrenia. Preliminary studies have suggested that this impairment may be associated with social introversion and related psychopathology in a nonpsychiatric population. To evaluate the relationship between dysfunctional smooth pursuit eye movement and schizophrenia-related psychopathology, the authors screened a new, volunteer sample of 284 male college students for eye tracking accuracy. Volunteers identified as low-accuracy trackers were significantly more likely to be diagnosed (blindly) as having a schizotypal personality disorder by DSM-III criteria than those identified as high-accuracy trackers. The authors suggest that disordered smooth pursuit eye movement may reflect a vulnerability marker for schizotypal personality disorder.
Abstract 12328: Differentiation Between Tachyccardia Induced Cardiomyopathy and Dilated Cardiomyopathy
Authors: Takehito Tokuyama, Yukiko Nakano, Noboru Oda, Kazuyoshi Suenari, Yuko Makita, Kenta Kajihara, Akinori Sairaku, Chikaaki Motoda, Mai Fujiwara, Iwasaki Toshitaka, Yoshikazu Watanabe, Yasuki Kihara
Journal: Circulation (2011)

Backgroud: The clinical manifestations of tachycardia-induced cardiomyopathy (TIC) and dilated cardiomyopathy (DCM) with tachyarrhythmia are similar. It is difficult to differentiate between them prior to treatment. Objective: To clarify the differentiation of general clinical data between TIC and DCM. Methods: We evaluated clinical data derived from 12-lead electrocardiography(ECG) during tachyarrhythmia, echocardiography, and 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy of 21 patients with TIC (TIC group, 60.3 ± 18.5 years, 11 males) and 24 patients with DCM (DCM group 51.7 ± 18.6 years, 21 males). Results: The ejection fraction (EF) prior to treatment was similar in both groups. However, the EF of the TIC group improved from 37.3 ± 11.4% to 53.5 ± 7.7% after treatment, while that of the DCM group did not improve. The left ventricular diastolic and systolic dimensions (LVDd&LVDs) were smaller in the TIC group than that in the DCM group (LVDd 51.7 ± 6.7 mm vs 63.3 ± 9.0 mm, LVDs 40.8 ± 7.4 mm vs...
Long-term outcome results of the phase III PROMISE-GIM6 study evaluating the role of LHRH analog (LHRHa) during chemotherapy (CT) as a strategy to reduce ovarian failure in early breast cancer (BC) patients.
Authors: Matteo Lambertini, Luca Boni, Andrea Michelotti, Teresa Gamucci, Nina Olmeo, Stefania Gori, Monica Giordano, Ornella Garrone, Alessia Levaggi, Francesca Poggio, Sara Giraudi, Claudia Bighin, Paolo Pronzato, Lucia Del Mastro
Journal: Journal of Clinical Oncology (2014)

105 Background: The PROMISE-GIM6 phase III randomized study showed that the use of triptorelin-induced temporary ovarian suppression during CT in premenopausal patients with early-stage BC reduced the occurrence of CT-induced early menopause (Del Mastro L, JAMA 2011). The 2013 ASCO and ESMO guidelines on fertility preservation in cancer patients consider this strategy still experimental due to the absence of data on long-term ovarian function and pregnancy rates, and some concerns exist on the safety of this procedure particularly for hormone-receptor positive BC patients. The present analysis reports long-term outcome results of the study. Methods: From October 2003 to January 2008, 281 premenopausal women with stage I through III BC who were candidates for adjuvant or neoadjuvant CT were randomized to receive CT alone or combined with triptorelin. The primary objective was to compare the incidence of CT-induced early menopause in patients treated with CT alone or combined with triptorelin. The present analysis considers data on recurrences, pregnancies and long-term ovarian function. Results: A total of 133 pts were enrolled in the CT alone arm and 148 in the CT + LHRHa arm; 82% and 79% of pts had hormone receptor positive-disease, respectively. The median follow-up at the time of the analysis was 7.3 years (interquartile range: 6.3-8.2 years). No differences in the 5-year disease-free survival (DFS) between treatment arms were observed (83.7% in CT alone arm vs 80.5% in CT plus LHRHa: HR=1.17; 95% CI 0.72-1.92, p=0.519). After the end of adjuvant treatments, 4 pregnancies (3.0%; incidence rate per 100 person-year=0.4) occurred in the CT-alone group and 8 pregnancies (5.4%; incidence rate per 100 person-year=0.8) occurred in the CT plus triptorelin group (CT + LHRHa arm vs CT alone: OR=1.84; 95% CI 0.54-6.27, p=0.39). Conclusions: The administration of LHRHa with CT was associated with the occurrence of more pregnancies; no differences in DFS were observed. The analysis on long-term ovarian function is still ongoing and will be presented at the meeting. Clinical trial information: NCT00311636.
A Difficult Case: Severe gastroparesis diabeticorum in a young patient with insulin dependent diabetes
Authors: C. J Dowling, S. Kumar, A. J M Boulton
Journal: BMJ (1995)

being evaluated for another current illness.This is most likely to occur in patients from areas where B burgdorferi is endemic.Misdiagnosis is by far the most common reason for an apparent lack of response to antibiotic treatment.24The American College of Rheumatologists and the Council of the Infectious Diseases Society of America have recommended that patients with non-specific symptoms such as chronic fatigue or myalgia without a history of classic features of Lyme disease but with positive serology do not receive parenteral antibiotic treatment: cost effective- ness analysis has shown that treating such patients results in many more cases of antibiotic toxicity and other complications than cures of atypically sympto- matic Lyme disease.
Myocardial Bridging
Authors: Michel T. Corban, Olivia Y. Hung, Parham Eshtehardi, Emad Rasoul-Arzrumly, Michael McDaniel, Girum Mekonnen, Lucas H. Timmins, Jerre Lutz, Robert A. Guyton, Habib Samady
Journal: Journal of the American College of Cardiology (2014)
Abstract 16003: Association of 25 (OH) D With Lower All-Cause and Cardiovascular Mortality Is Consistent Across Race and Gender in Healthy Adults: Findings from the National Health and Nutrition Examination Survey (NHANES), 2001-2004
Authors: Muhammad Amer, Oluwaseyi Bolorunduro, Muhammad B Bakht, Rehan Qayyum
Journal: Circulation (2011)

Background: Association of serum 25-hydroxyvitamin D [25(OH) D] with lower all-cause and cardiovascular (CV) mortality is well known. We have previously shown that this association holds up to 21 n...
Effects of Fondaparinux on Mortality and Reinfarction in Patients With Acute ST-Segment Elevation Myocardial Infarction: The OASIS-6 Randomized Trial
Authors: Salim Yusuf, Shamir R Mehta, Susan Chrolavicius, Rizwan Afzal, Janice Pogue, Christopher B Granger, Andrzej Budaj, Ron J G Peters, Jean-Pierre Bassand, Lars Wallentin, Campbell Joyner, Keith A A Fox
Journal: JAMA (2006)

ContextDespite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy.ObjectiveTo evaluate the effect of fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI.Design, Setting, and ParticipantsRandomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12 092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment.Main Outcome MeasuresComposite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months).ResultsDeath or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with fondaparinux at 9 days.ConclusionIn patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes.Trial RegistrationClinicalTrials.gov Identifier NCT00064428Published online March 14, 2006 (doi:10.1001/jama.295.13.joc60038).
Book: Transplant: From Myth to Reality
Authors: Peter A Andrews
Journal: BMJ (2004)

I read this book with some interest—firstly to learn more about the history of a field in which I have been practising for the past 15 years but also because I was fascinated by a seemingly simple question: why has the author chosen to write this book?​book?




Figure 1



Yale University Press, £19.95, pp 320 ISBN 0 300 09963 0

Rating: ★★




What did I learn? That it is very difficult to summarise a complex, evolving field in a short book, especially when attempting to satisfy a number of target audiences. Transplantation is sexy. It is also multifaceted, and areas such as the ethics of transplantation and the commercialisation of immunosuppression deserve greater coverage than a book such as this can give their due. Perhaps it would have been better to select a single target audience, a single theme, or a single organ.

Where literature succeeds—and medical history is no exception—is in bringing experience to life. Even in these days of evidence based medicine the case report has its place in the medical literature, because it is enjoyable and people remember it. This book, though well researched and written, cries out for a personal narrative. What did the author do? What does he believe? Who are the heroes and villains? The Puzzle People, Thomas Starzl's highly personal account of liver and other solid organ transplantation, published in 1992, succeeded by creating a sense of involvement, by making the reader care. In Tilney's rather dry text, however, history runs the risk of becoming simply a list of dates.

There is much to write about and to celebrate. In the United Kingdom 2400 people receive solid organ transplants each year (although it is shameful that a further 7000 are on an ever lengthening waiting list). Transplantation improves quality of life and is highly cost effective. After the first year kidney transplantation costs £4000 ($7500;€5900) to £6000, compared with £25 000 to £30 000 a year for dialysis.

Less commonly recognised is that transplantation also improves life expectancy, especially kidney transplantation. The expected survival of a dialysis dependent diabetic patient who receives a kidney transplant increases by 82%, even after adjustment for the higher comorbidity of patients who are not listed for a transplant. Similar stories of economic, personal, and (dare I say it) institutional benefit may be evinced in the cases of heart, lung, liver, multiple organ, and other transplantation.

To return to my original question, why write a book? Certainly not for money: hour for hour a dustman earns more than a medical author. For prestige? To set the record straight? For education? For personal satisfaction? For fun?

I confess that I have no idea why books are written, any more than doctoral theses (average readership less than 10, including the parents) or book reviews. Is it simply that we enjoy writing? For most authors that will need to be reward enough.
Suicides after pregnancy
Authors: C. L. Morgan, M. Evans, J. R Peters, C. Currie, S. Mitchison, M. Gissler, E. Hemminki, J. Lonnqvist
Journal: BMJ (1997)

Malignant cerebral glioma Modern radiotherapy can give good quality survival for six monthsEditor-We wish to correct misinformation reported by Elizabeth Davies and colleagues in their study of survival after radiotherapy for malignant cerebral glioma. 1 Contrary to their suggestion in the acknowledgements, the study had not been supported by the Medical Research Council Brain Tumour Working Party.As the poor study design indicates, the study had never been officially submitted to the Medical Research Council and had therefore not been subjected to its rigorous protocol review process.For example, Davies and colleagues report that their criteria for assessment of treatment toxicity were derived in a "pragmatic fashion after discussion" by a "process of elimination," without evidence from imaging to exclude tumour progression.This would be totally unacceptable, let alone publishable.The impression that the 105 patients represent an unselected consecutive series is difficult to believe as the seven centres should, over two years, have seen 400-800 eligible patients. 2 The reported adverse prognostic factors in patients with high grade glioma have been known for over 18 years. 3Although the authors appropriately conclude that severely disabled patients have a poor prognosis and may not be suitable for active treatment, the fact that they were considered for intensive treatment at all is surprising.Centres specialised in the treatment of patients with brain tumours would not have accepted patients with such a poor prognosis for high dose radiotherapy.Most of the patients also seemed to receive initial whole brain radiotherapy followed by a radiation boost to the tumour.Whole brain radiotherapy is nothing but toxic and has not been practised in specialist centres for many years.Given the use of outdated and often inappropriate high dose, wide field radiotherapy and the flawed assessment of morbidity from treatment, the conclusion that radiation is of little value and simply results in adverse effects seems ill advised.High grade gliomas are among the most devastating of malignancies, with few useful treatment options.Modern radiotherapy, although not curative, offers a survival benefit of about six months, 3 and for most patients without functional impairment the quality of survival is good.Without com-parative data on the quality of life, how can we decide whether prolongation of survival by six months with clinical deterioration in a small proportion of patients is worse than the alternative of progressive functional decline, which happens in all patients without treatment?Yes, we do need more effective treatments without morbidity, but to throw out a proved treatment on the basis of misinformation is a travesty to evidence based medicine, to which the BMJ claims allegiance.
Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial
Authors: PC Onyebujoh, JB Levin, FB Fourie, Garhiram, LC Tembe, NP Phili, Tcp Mthiyane, T Moniwa, G Bayer, IM Ramajoe, Tab Mncwabe, Lgm Mallisar, Tnm Saul, Thfg Jackson, S Suparsad, Pem Fine, Djs Pendlebury, E Fine, I Houghton, J Clyde, HP Vos, N Padayatchi, A Pala, A Ramjee, M Ramjee, J Ramdeen, IH Masters, G Osbourne, K Naidu, S Bamba, B Mazur, R Czarnocki, K Landers, G Ndlovu, N Maphumulo, AW Sturm, J Moodley, C Pillay, L Roux, R Moodley, A Sarawan, T Jali, F Manickam, A Smith, Gopaul, T Durosanmi, R Moonsammy, P Wyld, J McCallum, C Fulton, K Bisset, S Henderson, D Stewart, O Nticinka, D Watson, N Tuckwell, D Kennard, JL Stanford, GA Rook, JM Grange, AA Zumla, E Bateman, P Hopwell, J Darbyshire, L Geiter, A Nunn, K Weyer, Durban Immunotherapy Trial Grp
Journal: The Lancet (1999)
Abstract 717: Utility of Biochemical and Echocardiographic Measures of Subclinical Organ Damage in Risk Prediction for First Ischemic Stroke: The Strong Heart Study
Authors: Maria G Karas, David O Wiebers, Jack P Whisnant, James M Galloway, Thomas K Welty, Elisa T Lee, Lyle G Best, Barbara V Howard, Mary J Roman, Richard B Devereux, Jorge R Kizer
Journal: Circulation (2009)

Background: American Indians suffer disproportionately high rates of stroke, surpassing whites and even African Americans. Improved prediction could enhance prevention efforts in this population. A...
Abstract 4365: A Recombinant A-Type Natriuretic Peptide Improves Cardiac Function Probably through Suppression of Intracellular ROS in Heart Failure
Authors: Takehisa Susa, Shigeki Kobayashi, Takeshi Suetomi, Xiaojuan Xu, Makoto Ono, Hitoshi Uchinoumi, Takeo Tanaka, Takayuki Okamura, Syuji Kawamura, Takeshi Yamamoto, Masafumi Yano, Masunori Matsuzaki
Journal: Circulation (2008)

Background: We previously reported that reactive oxygen species (ROS) causes Ca2+ leak through the ryanodine receptor (RyR), leading to contractile dysfunction, and eventually heart failure (HF). Here, we clarified an antioxidant action of carperitide, an exogenous A-type natriuretic peptide (ANP) in patients with heart failure and in isolated canine failing cardiomyocytes as well. Methods and Results: In control subjects (N: n=10) and patients with HF (n=20), blood sampling was simultaneously performed from coronary sinus (CS) and artery (A) to measure 8-hydroxy-2-deoxyguanosine (8-OHdG: ng/ml), a marker of oxidative DNA damage. The serum 8-OHdG level was higher in (CS) than in (A) only in HF (HF: 0.57 ±0.33 in CS; 0.31 ± 0.16 in A; N: 0.17±0.07 in CS; 0.16 ± 0.06 in A), indicating that ROS is produced in failing cardiac tissue. The difference in the serum 8-OHdG between (CS) and (A) was increased as NYHA class elevates (r=0.65, p&lt;0.01). The urine 8-OHdG/creatinine level (ng/mg) also correlated with the NYHA class (r= 0.62, p&lt;0.001), LVEF (r=0.43, p &lt;0.001) and PCWP (r=0.54, p&lt;0.001). As protocol 1, we examined whether ANP (0.25 micrograms/kg/min, i.v.) decreases urine 8-OHdG/creatinine during the treatment of HF (n=8, for 3 days), as compared with that of nitroglycerin (NTG; n=8, for 3 days). Either treatment with ANP or NTG similarly improved hemodynamic parameters, such as cardiac index, PCWP, systemic vascular resistance, and pulmonary arterial resistance. In ANP-treated group, however, urine 8-OHdG/creatinine significantly decreased as compared with in NTG-treated group (ANP: 9.8±3.5; NTG:14.5±4.2, p&lt;0.05). As Protocol 2, we produced canine tachycardia-induced HF model by 4-week’s rapid RV pacing (250 bpm) (EF 27±5%, n=6). Then, using the failing cardiomyocytes, we investigated the direct effect of ANP on intracellular ROS (by 2,7,-dichlorofluorescin diacetate fluorescence). In the failing cardiomyocytes, intracellular ROS markedly increased, as compared with normal cardiomyocyte. Interestingly, ANP (1×10 – 8 mol/L) significantly suppressed ROS production seen in failing cardiomyocyte. Conclusion: Exogenous ANP has a potent antioxidant action that may contribute to an improvement of hemodynamics in patients with HF.