tbuckley/cabot-search huggingface dataset:
Gemcitabine and carboplatin in the treatment of metastatic cholangiocarcinoma and gallbladder cancer
Authors: R. Suresh, J. Picus, S. Sorscher, C. Fournier, B. R. Tan
Journal: Journal of Clinical Oncology (2007)

15102 Background: There is currently no standard therapy for patients with unresectable or metastatic biliary tract cancers. Gemcitabine has been shown to be active against these tumors with a 20–30% response in various phase II studies. Gemcitabine is also synergistic with platinum compounds. Aim: We conducted a Phase II study of gemcitabine plus carboplatin in patients with unresectable or metastatic choloangiocarcinoma or gallbladder cancer to assess the regimen’s safety and efficacy. Methods: Since 3/2002, 49 (48 evaluable) patients were treated with gemcitabine at 1000 mg/m 2 IV over 30 minutes days 1 and 8 with carboplatin at AUC 5 IV on day 1 of a 21 day cycle. There were 34 women and 15 men enrolled. Ages ranged from 34 to 87 with a median age of 65 years. Results: Best radiologic responses - 5CR, 9 PR, 24 stable disease and 10 progression. CR+PR 14/48 (29.2%) and stable disease 24/48 (50%). Toxicity: Hematological toxicities: Grade 3 neutropenia 33%, febrile neutropenia 0.02%, anemia 12.5% and thrombocytopenia 14.6%. Grade 4 hematological toxicites were rare - neutropenia 0.04%, and thrombocytopenia 0.06%. Non-hematologic toxicities were generally mild (fatigue, edema, nausea, vomiting, elevated liver enzymes, electrolyte abnormalities). Except for one patient who had depression there were no grade 4 non-hematological toxicity. Grade 3 non- hematological toxicites were also rare occurring only in 1 to 3 patients. Conclusions: Gemcitabine and carboplatin is active against biliary cancer and is highly tolerable. This study is being supported by Eli Lilly &amp; Co. No significant financial relationships to disclose.
NICE calls for safer use of controlled drugs
Authors: Jacqui Wise
Journal: BMJ (2016)

GPs should advise patients on the safe storage of controlled drugs such as morphine, methadone, and diazepam, new guidance from the National Institute for Health and Care Excellence (NICE) states.1

The guidance brings together legislation and existing advice to help minimise the potential harms associated with controlled drugs. A seven year review of safety incidents reported to the National Reporting and Learning System in England and Wales found that the risk of death was far greater with controlled drugs than with …
Enterohemorrhagic<i>Escherichia coli</i>
Authors: R. Bradley Sack
Journal: New England Journal of Medicine (1987)

The syndrome of hemorrhagic colitis was defined as a clinically distinct entity only about 15 years ago. Although it may have features similar to bacterial dysenteries due to shigella or campylobacter, pseudomembranous enterocolitis due to Clostridium difficile, ischemic colitis, and acute inflammatory bowel disease, hemorrhagic colitis is distinguished by a natural progression from watery to bloody diarrhea over the course of a few days and a relative lack of the usual signs of inflammation, such as fever and large numbers of pus cells in the stool.1 The cause of the syndrome was unknown until 1982, when the occurrence of . . .
Light-to-Moderate Alcohol Consumption and the Risk of Stroke among U.S. Male Physicians
Authors: Klaus Berger, Umed A. Ajani, Carlos S. Kase, J. Michael Gaziano, Julie E. Buring, Robert J. Glynn, Charles H. Hennekens
Journal: New England Journal of Medicine (1999)

Several studies have shown U- or J-shaped relations between alcohol consumption and the risk of stroke. We evaluated the effect of light-to-moderate alcohol intake on the risk of stroke, with separate analyses of ischemic stroke and hemorrhagic stroke.Our analyses were based on a prospective cohort study of 22,071 male physicians, 40 to 84 years old, who were participating in the Physicians' Health Study. At base line, the participants reported that they had no history of stroke, transient ischemic attack, or myocardial infarction and were free of cancer. Alcohol intake, reported by 21,870 participants at base line, ranged from none or almost none to two or more drinks per day.During an average of 12.2 years of follow-up, 679 strokes were reported. As compared with participants who had less than one drink per week, those who drank more had a reduced overall risk of stroke (relative risk, 0.79; 95 percent confidence interval, 0.66 to 0.94) and a reduced risk of ischemic stroke (relative risk, 0.77; 95 percent confidence interval, 0.63 to 0.94). There was no statistically significant association between alcohol consumption and hemorrhagic stroke. The overall relative risks of stroke for the men who had one drink per week, two to four drinks per week, five or six drinks per week, or one or more drinks per day were 0.78 (95 percent confidence interval, 0.59 to 1.04), 0.75 (95 percent confidence interval, 0.58 to 0.96), 0.83 (95 percent confidence interval, 0.62 to 1.11), and 0.80 (95 percent confidence interval, 0.64 to 0.99), respectively, in an analysis in which we controlled for major risk factors for stroke.Light-to-moderate alcohol consumption reduced the overall risk of stroke and the risk of ischemic stroke in men. The benefit is apparent with as little as one drink per week. Greater consumption, up to one drink per day, does not increase the observed benefit.
Fatal Acute Pancytopenia Following Tridione Treatment
Authors: Thomas J. Carnicelli, C. G. Tedeschi
Journal: New England Journal of Medicine (1948)

TRIDIONE, since first proposed in 1945 as an anticonvulsant agent, has been generally accepted for the control of petit-mal and major psychomotor attacks. The favor it met with was justified by a number of reports, all claiming the efficiency of the drug in the control of convulsive disorders and the apparent absence of toxic manifestations. No side effects were seen by Everett and Richards1 in a large series of animals, including mice, guinea pigs, cats and rabbits, in which the anticonvulsant properties of the new drug were compared with those of Dilantin and phenobarbital; no toxic manifestations were found by . . .
Soundings: Learning in boxes
Authors: Trisha Greenhalgh
Journal: BMJ (2001)

Along with some colleagues from the more creative fringes of our discipline, I will shortly be running a conference on narrative in health care. My vision is that doctors, nurses, anthropologists, psychotherapists, literary critics, historians, linguists, and service users will spend two days sharing experiences of illness and healing through the simple, time honoured, and universal technique of storytelling.

I expect that the stories they tell and hear in formal, timetabled presentations may prove less valuable than the ones they will share in the more permissive environment of the lunch queue or the bar. The organisers' declared aim of promoting discussion on research rigour and some small print qualitative techniques will no doubt appeal to an academically inclined minority. But from the applications I have seen so far, most people are coming because they have a story to tell—and a hunger for the stories of others.

For the benefit of my fellow general practitioners, I am seeking the Postgraduate Educational Allowance (PGEA) kitemark from the Royal College of General Practitioners—and I am mightily frustrated. The first question on my application form for PGEA is how I have assessed the needs of the intended learners. The second is whether this learning experience should be categorised as “disease management,” “service management,” or “health promotion.” And the last one—which I'm particularly stuck on—is what explicit and measurable learning objectives I have in mind for the punters.

I've picked up a thing or two about learning objectives in recent years. Indeed, somewhat ironically, I will be presenting a paper at the conference on how to set appropriate objectives for university courses in narrative techniques. But this conference isn't a degree module—it is a rare opportunity for busy professionals to take time out, talk, listen, and emerge refreshed.

A few months ago I found myself exchanging stories of clinical practice with a small group of fellow GPs whose individual experience ranged from six months to some 40 years. As we parted, one of the more experienced GPs commented to me: “Stories are wonderful, aren't they? You never know what you're going to learn from them but you always learn something.”

I hope he'll forgive me for spilling the beans, but my wise informant was the college president.
Efficacy and Safety Of Pegaspargase With Gemcitabine and Oxaliplatin In Patients With Treatment-naïve, Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Single-Centre Experience
Authors: Yan Gao, Hui-qiang Huang, Cai QiChun, XiaoXiao Wang, QinfQing Cai, Zhongjun Xia, Bing Bai, Wei Zhao, Wenqi Jiang, ZhongZhen Guan
Journal: Blood (2013)
Economic analysis of decitabine versus best supportive care in the treatment of intermediate- and high-risk myelodysplastic syndromes (MDS).
Authors: E. Kim, F. Pan, S. Peng, R. Fleurence
Journal: Journal of Clinical Oncology (2010)

6600 Background: Myelodysplastic syndromes (MDS) are heterogeneous bone marrow stem cell disorders characterized by peripheral cytopenias and risk of progression to acute myeloid leukemia (AML). Decitabine is one of the few approved treatments for MDS. The aim of this analysis is to compare the economic consequences of decitabine with best supportive care (BSC) versus BSC alone among US adult with International Prognostic Scoring System IPSS score intermediate or high MDS. Two decitabine dosing schedules – 3-day inpatient and 5-day outpatient – are evaluated separately against BSC. Methods: A decision analytic model was developed with three distinct health states: MDS, AML and death. Transitions between the health states are determined by survival without AML and overall survival, which were estimated using data from one decitabine phase III clinical trial. Health outcome measures are survival without AML, survival with AML, and quality-adjusted life years. Cost inputs include drug and administration, BSC with transfusion, BSC without transfusion, and costs after patients progressed to AML. All costs are obtained from published literature and inflated to 2009 US dollars. Results: Compared to BSC alone, decitabine+BSC is estimated to yield 0.474 years of AML-free survival, and 0.586 fewer years with AML. Since AML is associated with a lower quality of life, decitabine is associated with 0.098 more QALYs than BSC. The total lifetime costs associated with decitabine are $109,623 for 5-day outpatient dosing, and $131,221 for 3-day inpatient dosing. Total BSC costs are $102,152. Conclusions: In the treatment of MDS, decitabine+BSC postpones progression to AML compared to BSC alone, leading to better quality adjusted life and cost offsets due to a shorter duration of time with AML. Supportive care alone is quite costly as a result of dependence on transfusions and growth factors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai, United BioSource Corporation United BioSource Corporation United BioSource Corporation
Myasthenia Gravis and the Thyroid Gland
Authors: Daniel B. Drachman
Journal: New England Journal of Medicine (1962)

THE occurrence of thyrotoxicosis in patients with myasthenia gravis is not rare, over 90 such cases having been reported since the turn of the century.1 , 2 Various estimates place the incidence of hyperthyroidism in myasthenic patients at 3 to 6 per cent.3 , 4 However, myasthenia gravis occurs in only a fraction of 1 per cent of the thyrotoxic population.5 The two diseases often do not begin simultaneously; either one may precede the other by many months or years. In the Mayo Clinic series hyperthyroidism was noted first in 54 per cent of cases; myasthenia gravis occurred earlier in 37 per cent. Only . . .
Association between bipolar affective disorder and multiple sclerosis
Authors: R B Schiffer, N M Wineman, L R Weitkamp
Journal: American Journal of Psychiatry (1986)

Emotional disturbances are highly prevalent with an early onset in patients with multiple sclerosis (MS) The presence of psychiatric symptoms in MS was underlined and systematically described as early as in 1877 by Charcot.Many of these symptoms are described and are not necessarily related to the psychological impact of such a chronic and disabling disease. Objectives:To discuss the possible etiological hypothesis and treatment options for patients with MS and bipolar disorder. Methods:We propose two cases and a review of the literature. Results:Discussion : The first case describes a man with a long history of MS who developed a bipolar disorder.In this case, the most likely hypothesis advanced to explain this comorbidity would be a casual association.However, Joffe et al. have shown that manic depressive psychosis appears to be significantly more common in MS patients than in the general population [1].Etiopathogenic bases explaining this association are not yet understood. One hypothesis is that mood disorders could be an inaugural manifestation in MS [2].or may be the presenting symptom of MS before the development of neurological signs [3].
Effects of Urea and Cyanate on Sickling in Vitro
Authors: George B. Segel, Stephen A. Feig, William C. Mentzer, Ronald P. McCaffrey, Roe Wells, H. Franklin Bunn, Stephen B. Shohet, David G. Nathan
Journal: New England Journal of Medicine (1972)

Erythrocytes from patients with SS disease were incubated under reduced oxygen tension to determine the comparative effects of urea and cyanate upon the sickling phenomenon. At a urea concentration of 0.2 M (BUN, 560 mg per 100 ml), no inhibition of sickling could be demonstrated. A more sensitive index of the rate of sickling used for further studies involved measurement of the rate of potassium loss from sickle cells undergoing sickling in a hypoxic environment. Whereas 20 mM CNO- markedly inhibited sickling and potassium loss under 3 per cent oxygen, potassium loss was only slightly decreased by 0.2 M urea and was not significantly reduced by 0.1 M urea (BUN, 280 mg per 100 ml). In other studies, oxygen affinity of hemoglobin S was increased by 0.4 M urea (BUN, 1120 mg per 100 ml) but not by 0.1 M urea. Hypoxia-induced hyperviscosity of sickle blood was only slightly decreased by 0.1 M urea. Thus, urea appears to have an inhibitory effect on sickling in vitro but only at concentrations exceeding those that can be practically achieved in vivo.
Abnormal Porphyrin Metabolism and Polymorphic Photodermatitis
Authors: W. L. Curwen, M. A. Pathak
Journal: New England Journal of Medicine (1964)

THE diagnosis of cutaneous porphyria is suggested by the clinical findings of photosensitivity, hyperpigmentation, hirsutism and increased fragility of the skin. This diagnosis is confirmed by the demonstration that the urinary and fecal excretion of porphyrins is abnormally large; in urine there is usually excess uroporphyrin whereas in feces there is excess coproporphyrin and protoporphyrin.1 For many years it has been noted that a large variety of cutaneous lesions (macules, papules, plaques, wheals, vesicles, bullae, eczematous dermatitis and so forth) develop in certain persons after exposure to sunlight. The nomenclature of such abnormal cutaneous responses has depended . . .
P-266 Aflibercept as a second line chemotherapy in metastatic colorectal cancer. One centre experience
Authors: B. González-Astorga, E. González-Flores, M.T. Delgado Ureña, J. García-García, V. Conde, C. Sánchez-Toro, A. Villaescusa
Journal: Annals of Oncology (2015)
Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) to prolong progression-free survival in first-line colorectal cancer (CRC) in subjects who are not suitable candidates for first-line CPT-11
Authors: F. F. Kabbinavar, J. Schulz, M. McCleod, T. Patel, J. Hamm, J. Hecht, B. Perrou, S. Griffing, B. Nelson, W. Novotny
Journal: Journal of Clinical Oncology (2004)

3516 Background: Bevacizumab [Avastin (BV)] is a recombinant, humanized monoclonal antibody directed against vascular endothelial growth factor. As presented at ASCO 2003, the addition of BV to IFL chemotherapy prolonged median survival from 15.61 months to 20.34 months (p = 0.00004). This was a companion trial that studied the addition of BV to FU/LV chemotherapy in subjects who were not optimal candidates for first-line irinotecan because of age or performance status. Methods: Approximately 200 patients were to be randomized to receive the Roswell Park regimen of FU/LV placebo or FU/LV/BV (5 mg/kg every two weeks). The primary efficacy endpoint was survival; secondary efficacy endpoints included progression free survival (PFS), objective response rate (ORR) and duration of response. Results: 209 patients were randomized between September 7, 2000 and May 6, 2002. For the two groups, FU/LV/Placebo and FU/LV/BV, baseline characteristics were similar. Efficacy and selected safety results are as follows: Conclusions: The addition of BV to FU/LV chemotherapy, in subjects who are not optimal candidates for first-line CPT-11 resulted in a clinically meaningful and statistically significant prolongation of progression-free survival and trends towards improved response rate,duration of response, and survival as compared with FU/LV chemotherapy alone. The addition of BV to FU/LV was well tolerated; Grade 3 hypertension, easily managed with oral medications was increased with BV, The uncommon but life-threatening event of gastrointestinal perforation occurred in 2 patients in the FU/LV/BV arm Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc. Genentech, Inc. Genentech, Inc.
Metastatic soft tissue sarcomas (MSTS): Second line chemotherapy (CT) using two different schedules of high dose ifosfamide (HDI)
Authors: A. Comandone, C. Oliva, O. Dal Canton, P. Bergnolo, P. Pochettino, F. Garetto, S. Chiado Cutin, A. Boglione, G. Gino, E. Brach Del Prever
Journal: Journal of Clinical Oncology (2004)

9035 Background. Results of CT in MSTS remain disappointing. Only 3 agents are active (Adriamycin, Ifosfamide, Deticene) with RR of 16–25% as single agent and 20–40% in poliCT. The 2nd line is more frustrating. The same drugs at different doses or schedules therapy offer 10–15% objective responses, TTP of 3–4 months and MS of 10–12 months. HDI (12–16 g/m2) on continuous intravenous infusion has demonstrated significant antitumor activity. Two different schedules have been published: 4 days c.i. (Le Cesne, JCO 1995) and 14 days c.i. (Frustaci & Comandone Proc ASCO 1998) with the same total dose of 14 g/m2. Methods. We treated from 1996 to 2003 90 pts with pretreated MSTS using both schedules. We report the results of the two protocols as perspective phase II trials independently analyzed. 90 pts with measurable MSTS previously treated with Antracyclines entered the study. Both sexes, age from 18 to 70 years, histological demonstration, PS 0–2 ECOG, good renal and hematological function, informed consent were requested. Protocol A): 54 pts treated with HDIFO in 4 days c.i. (3,5 g/m2/d + Mesna equidose). Protocol B): 36 pts received IFO 1 g/m2/d c.i. for 14 days + Mesna equidose). The two schedules were repeated every 21–28 days following the complete recovery from toxicities. Leiomiosarcomas, MFH, Synovialsarcomas and Liposarcomas were the most represented histological types. Lung and local failure were the two most common sites of relapse. Results. In protocol A Neutropenia G3/G4 (100%), Thrombocytopenia G3/G4 (30%), Anemia (28%), Alopecia G3 (100%), N&V G3 (28,4%) and Ipokaliemia (17%) were the most common toxicities. In protocol B Neutropenia G3/G4 (7%), N&V G3 (5%) were the most serious adverse effects. In protocol A 6 RR (12%, 1 CR) and 11 SD (22,4%) were recorded; TTP 6,7 mo, MS 12 mo. In protocol B 4 RR (12%, 1CR) and 9 SD (27%) were seen, TTP 4,2 mo, MS 10,4 mo. Conclusions. The activity of HDI in pretreated MSTS suggests a dose response relationship. Both protocols guarantee a percentage of RR not exceeding 12%. Maintained SD in about 25% of the pts must be considered a positive result in 2nd line CT for MSTS. HDI in 4 days c.i. seems to be more toxic. No significant financial relationships to disclose.
Phase I/II study of gemcitabine (GEM) and concomitant radiotherapy (RT) in locally advanced carcinoma of the cervix (LACC)
Authors: K. Boualga, N. Aksil, M. Ayad, N. Hasnaoui, D. Moussaoui
Journal: Journal of Clinical Oncology (2005)

5142 Background: Carcinoma of the cervix is a significant problem in Algeria with an incidence rate of 10 new cases/100,000 women. Concomitant cisplatin/RT is the standard treatment for LACC, but new active agents are needed. GEM has shown a potent radiosensitizing activity; therefore, we conducted a study to determine the maximum tolerable dose (MTD), efficacy, and toxicity of concurrent GEM and RT in LACC Methods: Patients with histologically confirmed, previously untreated LACC (FIGO IIIA-IVA), PS 0–2, and adequate organ function received RT 45 Gy for 4 to 5 weeks with 1 week rest, followed by 20 Gy boost for 2 weeks for a total dose of 65 Gy with concomitant GEM infusion (days 1, 8, 15, 40, and 47) starting at 300 mg/m2dose level 1) for 3 patients, 500 mg/m2 (dose level 2) for 13 patients and 600 mg/m2 (dose level 3) for 3 patients. Results: From April to December 2000, 19 patients with mean age of 48 years (range, 32–70) and stage IIIA (n=7), IIIB (n=5), or IVA (n=7) disease were enrolled. At dose level 1 (n=3), no grade 3/4 toxicities occurred; at dose levels 2 (n=13) and 3 (n=3), grade 2 diarrhea (n=5), grade 1 cystitis (n=3), and grade 1 anemia (n=4) was seen. The toxicity was acceptable and the MTD was not yet determinate All were evaluable for efficacy; 14 patients (74%) had complete response (3 had hysterectomy and lymphadenectomy [2 had histologically confirmed tumor-free margins]). 3 patients (16%) had partial response, and 2 (11%) progressed with either liver metastasis (n=1) or vaginal and cervical invasion (n=1; this patient died 5 months later). At 42 months follow up, 9 patients (47%) were alive, and 10 patients (53%) were dead. Conclusions: GEM and RT seem to be a highly active combination with a low toxicity profile. Patients were treated on an outpatient basis and surgery was possible in 16% of them. However, longer follow-up is needed to confirm disease-free and overall survival. In future studies, we aim to increase the dose of GEM 800 mg/m2with RT 65 Gy. No significant financial relationships to disclose.
Valsalva's Maneuver and Weber's Experiment
Authors: Vincent J. Derbes, Andrew Kerr
Journal: New England Journal of Medicine (1955)

FORCEFUL expiration against the closed glottis is commonly known as the "Valsalva experiment." The detailed report of Weber contrasts with the absence of documentation linking Valsalva with the experiment. We therefore consider the eponym not entirely suitable.Valsalva1 described a maneuver useful in expelling pus from the middle ear. It consisted of expiring against the closed nose and mouth. No observations of the circulatory effects were mentioned. Valsalva's original statement and our translation are as follows:... si, inquam, iste clauso ore et naribus aerem intro comprimere conetur; inde sanies in meatum auditorium ita copiose solet eodem actu protrudi, ut . . .