tbuckley/cabot-search huggingface dataset:
Randomized phase II trial of erlotinib (E) alone or in combination with carboplatin/paclitaxel (CP) in never or light former smokers with advanced lung adenocarcinoma: CALGB 30406.
Authors: P. A. Janne, X. F. Wang, M. A. Socinski, J. Crawford, M. Capelletti, M. J. Edelman, M. A. Villalona-Calero, R. A. Kratzke, E. E. Vokes, V. A. Miller
Journal: Journal of Clinical Oncology (2010)

7503 Background: EGFR kinase inhibitors are effective in never-smokers with NSCLC especially in those harboring EGFR mutations. In a prior phase III study (TRIBUTE) ECP was associated with improved RR, PFS, and OS compared to CP but only in never-smokers. CALGB 30406 prospectively evaluated E and ECP in never/light former smokers with chemotherapy-naïve advanced lung adenoca and evaluated the impact of EGFR mutations on outcome. Methods: Chemotherapy-naïve, never, or light former (≤ 10 pack years, > 1 yr since cessation) smokers, with advanced lung adenoca were randomized to E alone (150 mg/day) or ECP (E 150 mg/day given continuously; C [AUC = 6] and P (200 mg/m2) both q21 days) for 6 cycles followed by E. Primary endpoint was PFS in both arms. Collection of pretreatment tumor for assessment of EGFR mutations was mandatory. Results: Between 8/05 and 4/09 188 pts were accrued; 182 pts randomized (E=82; ECp=100) and treated. Baseline characteristics (E/ECP) were well balanced: Female: 61%/58%; Caucasian: 76%/84%; never smokers: 76%/77%; ECOG PS0: 61%/46%; adenoca: 87%/80%. Median number of cycles: E:6; ECP:7.Toxicity: Grade 3/4 hematologic toxicity: E: 1/0 (1%); ECP: 28/20 (48%). Grade 3/4 nonhematologic toxicity: E: 17/2 (23%); ECP: 39/11 (50%). EGFR genotyping possible in 172 pts (95%). EGFR mutant/wild type: 67 (39%)/105 (61%). Exon 19:36; L858R:31. Outcomes are shown in the Table. Median follow-up is 25 mos. 53% of pts have died in both arms. Primary endpoint was met in both arms. EGFR mut pts had a significantly better RR (p < 0.0001 both arms), PFS (p < 0.0001 both arms) and OS (p = 0.0027 E; p = 0.0009 ECP) than EGFR WT pts. Conclusions: E and ECP have similar efficacy, but E is less toxic, in predominantly Caucasian never smokers with advanced NSCLC. EGFR mutations identify patients most likely to benefit from E and ECP. E (n = 82) RR PFS months (80% CI) OS months (80% CI) All pts 34% 6.7 (4.7-8.2) 24.0 (18.4-27.6) EGFR mutation (n = 32) 66% 16.4 (12.1-23.8) 27.6 (24.0-42.8) EGFR WT (n = 48) 8% 2.8 (1.6-4.1) 15.4 (11.2-19.9) ECP (n = 100) All pts 47% 6.0 (5.6-7.3) 19.6 (14.7-24.6) EGFR mutation (n = 35) 69% 17.2 (11.1-27.6) 39.0 (39.0-NR) EGFR WT (n = 57) 31% 4.8 (4.2–5.6) 13.7 (10.0-18.0 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, AVEO, Boehringer Ingelheim, Genentech, OSI Pharmaceuticals, Roche, Syndax Pharmaceuticals Gatekeeper Pharmaceuticals Genentech, Lilly, Roche, sanofi-aventis Abraxis BioScience, Celgene, Genentech, Lilly, Pfizer, sanofi-aventis Genzyme
Case 32-1998
Authors: Richard L. Kradin, Eugene J. Mark
Journal: New England Journal of Medicine (1998)

Presentation of CaseAn 83-year-old woman was admitted to the hospital because of asthma complicated by pneumonia that was unresponsive to antibiotic treatment.The patient had had asthma since childhood, complicated by seven bouts of pneumonia by the age of 12 years and several episodes of pneumonia or bronchitis as an adult. There was a long history of hypertension and a 10-year history of atrial fibrillation for which she received no treatment. For two years she had had type 2 diabetes mellitus and unstable angina pectoris. She had never smoked and had no history of tuberculosis, recent chest pain, chronic . . .
Midwives’ concerns about eligibility stopped women accessing healthy food vouchers
Authors: Anne Gulland
Journal: BMJ (2016)

A study to boost uptake of food and vitamin vouchers among pregnant women has found that midwives unwittingly prevented women from applying for the benefits.

Public health specialists at NHS Lothian, Scotland, investigated why women were not applying for the Healthy Start vouchers (roughly 25% of women in the United Kingdom did not receive them) and found that midwives were wrongly worrying about women’s eligibility for the scheme.

The vouchers, which can be spent on milk, fresh and frozen fruit …
Authors’ response: Meningococcal vaccine antigen diversity in global databases
Authors: Carina Brehony, Dorothea M. Hill, Jay Lucidarme, Ray Borrow, Martin C. Maiden
Journal: Eurosurveillance (2016)

Preview this article: Authors’ response: Meningococcal vaccine antigen diversity in global databases, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/21/15/eurosurv-21-30192-9-1.gif
In Vivo and in Vitro Evaluation of Liquid Antacids
Authors: John S. Fordtran, Stephen G. Morawski, Charles T. Richardson
Journal: New England Journal of Medicine (1973)

An in vivo test of the efficacy of liquid antacids given after a meal was shown to yield reproducible results. An average dose-response curve, obtained with the use of various doses of a single antacid, was different in subjects whose peak histamine response exceeded 25 mEq per hour and in those whose response was less than 16.6 mEq per hour. In individual subjects, however, the peak histamine response did not accurately predict the in vivo reduction in gastric acidity by antacid. Although the relative in vivo potency of equal volumes of four different antacids varied widely, this potency could be predicted with reasonable accuracy by means of an in vitro test, which showed the potency per milliliter of antacid to vary 17-fold among different commercial products. These experiments indicate that when antacids are prescribed, dosage should be determined by the milli-equivalents of neutralizing capacity rather than by an arbitrary volume or number of tablets of different antacids, that the variable responses of individual patients to antacids should be taken into account, and that the doses commonly used in the treatment of duodenal ulcer should be increased. (N Engl J Med 288:923–928, 1973)
Evaluation and Surgical Treatment of Acoustic Neuroma
Authors: Robert G. Ojemann, William W. Montgomery, Alfred D. Weiss
Journal: New England Journal of Medicine (1972)

In 46 consecutive patients treated surgically for acoustic neuroma and followed for a minimum of two years, there was no operative mortality; 90 per cent returned to their previous level of activity, and all were able to care for themselves. Total removal of tumor was possible in 70 per cent, and radical subtotal removal in another 10 per cent. Facial-nerve function was preserved in 80 per cent, even in some patients with a large tumor. Any patient with progressive, unexplained hearing loss should have audiometric vestibular evaluation. If tumor is suspected, x-ray studies are indicated, including tomography and neuroradiologic contrast studies, with positive-contrast encephalography if clinical signs are limited to the eighth nerve, and pneumoencephalography when signs indicate a large lesion. When diagnostic studies suggest a small tumor (less than 2.0 cm in diameter), total removal can usually be accomplished by a translabyrinthine operation unless there is fifth-nerve involvement. Large tumors are treated by a two-stage procedure, with first the translabyrinthine and then the suboccipital approach.
Lack of Efficacy of Light Reduction in Preventing Retinopathy of Prematurity
Authors: James D. Reynolds, Robert J. Hardy, Kathleen A. Kennedy, Rand Spencer, W.A.J. van Heuven, Alistair R. Fielder
Journal: New England Journal of Medicine (1998)

Hospital-nursery lighting has been suggested as a factor in causing retinopathy of prematurity. Despite ongoing debate, a causal relation has not been established.We conducted a prospective, randomized, multicenter study of the effects of light reduction on 409 premature infants with birth weights of less than 1251 g and gestational ages of less than 31 weeks. Two hundred five infants were exposed to reduced light, and 204 to typical nursery lighting. The amount of light reaching the infants' eyes was reduced within 24 hours after birth by placing goggles on the infants that reduced visible-light exposure by 97 percent and ultraviolet-light exposure by 100 percent. The babies wore the goggles until 31 weeks' postconceptional age or 4 weeks after birth, whichever was longer. Once the goggles were removed, ophthalmologists masked to the treatment assignments assessed the infants for retinopathy of prematurity at least biweekly for up to 13 weeks.There were 188 infants in the group that wore goggles and 173 in the control group who survived and were available for follow-up. The mean birth weights were 906 g in the goggles group and 914 g in the control group; the mean gestational ages were 27.4 weeks and 27.2 weeks, respectively. The mean ambient-light level adjacent to the infants' faces was 399 lux for the goggles group and 447 lux for the control group. Retinopathy of prematurity was diagnosed in 102 infants (54 percent) in the goggles group and 100 (58 percent) in the control group (relative risk, 0.9; 95 percent confidence interval, 0.8 to 1.1; P=0.50).A reduction in ambient-light exposure does not alter the incidence of retinopathy of prematurity.
More than 400 pharmacists will be recruited to GP surgeries by next year
Authors: I. Torjesen
Journal: BMJ (2015)

By next year more than 400 clinical pharmacists will provide support to almost 700 general practitioner surgeries and more than seven million patients.

In July NHS England invited applications from GP surgeries for funding to employ a clinical pharmacist in their surgery as part of a pilot scheme. However, because of the overwhelming response from GP surgeries, NHS England has announced that is more than doubling the project’s funding for the initiative from £15m (€21.2m; $22.8m) to £31m.

Seventy three applications for …
Reconstruction of the Hand after Median-Nerve Palsy
Authors: J. Edward Flynn
Journal: New England Journal of Medicine (1957)

MOTOR regeneration of the median nerve after transection and repair of the median nerve at the wrist occurs in only about 5 per cent of cases. The thumb is incapable of abduction and opposition with motor loss of the median nerve. Proper pinch and grasp are lost. Substitution of opposition by apposition occurs in some and provides fair pinch and grasp. In most cases tendon transplantation must be performed to provide proper pinch and grasp.Anatomic ConsiderationsTendon transfer is performed to restore abduction and opposition, when normal passive motions of the thumb have been restored. The main function of . . .
Differential effects of right unilateral and bilateral ECT on heart rate
Authors: R D Lane, S B Zeitlin, R Abrams, C M Swartz
Journal: American Journal of Psychiatry (1989)

In a series of 11 melancholic patients who received both right unilateral and bilateral ECT during a single course of treatment, mean and minimum postictal heart rates were greater after bilateral ECT. Greater catecholamine release during bilateral ECT is the most likely explanation for these effects. These differences complement other evidence that bilateral ECT has a more pronounced physiological impact than unilateral ECT.
Anticoagulant Treatment of Postoperative Venous Thrombosis and Pulmonary Embolism
Authors: James A. Evans, John F. Dee
Journal: New England Journal of Medicine (1948)

ANTICOAGULANT treatment is winning for itself a firm place in the armamentarium against postoperative venous thrombosis and pulmonary embolism. This has been accomplished by the sheer weight of accumulating statistics from various clinics, both in this country and in Sweden.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Since April, 1941, when dicumarol first became available, the drug has provided the predominant method of therapy at the Lahey Clinic. In the majority of cases a combination of heparin and dicumarol has been used. During the first four years heparin was given by continuous intravenous drip to cover the latent period of dicumarol. For the past two years deep . . .
Efficacy of Ondansetron (Gr 38032F) and the Role of Serotonin in Cisplatin-Induced Nausea and Vomiting
Authors: Luigi X. Cubeddu, Irene S. Hoffmann, Nery T. Fuenmayor, Andrew L. Finn
Journal: New England Journal of Medicine (1990)

We compared the efficacy and safety of ondansetron (GR 38032F), a selective antagonist of serotonin S3 receptors, with that of placebo in controlling the nausea and vomiting induced by cisplatin treatment in 28 patients with cancer. The patients received either three intravenous doses of ondansetron (0.15 mg per kilogram of body weight) or normal saline (placebo) at four-hour intervals, beginning 30 minutes before the administration of cisplatin.
Potent and selective in vitro and in vivo inhibition of tumor proliferation by KXO1, a novel non-ATP competitive Src inhibitor
Authors: David Hangauer, Irwin Gelman, Lyn Dyster, Michael Smolinski, Taher Hegab, Lingqiu Gao
Journal: Cancer Research (2007)

3245  Elevated protein and activation levels of Src, a non-receptor tyrosine kinase, are thought to play important roles in primary tumor growth and metastatic progression. Several multikinase Src inhibitors have entered clinical trials (AZD0530, SKI-606) and one has recently reached the market (dasatinib). These multikinase inhibitors target the ubiquitous ATP substrate binding site, as do the vast majority of kinase inhibitors currently under investigation. Kinex Pharmaceuticals has developed a novel platform technology, MimeticaTM, that facilitates the development of peptide substrate site targeted inhibitors of kinases or phosphatases. The peptide substrate site is envisioned to be a more unique binding cavity, leading to more selective inhibitors, due to differing peptide substrate selectivity’s among the kinases. Utilizing this technology, Kinex developed KXO1, a novel small molecule, non-ATP competitive Src kinase inhibitor. Targeting the Src peptide substrate binding site provided much higher selectivity than is obtained with the ATP competitive Src inhibitors, as demonstrated by phosphotyrosine protein level analyses of cell lysates. KXO1 inhibits Src kinase activity in whole cells with low nM potency, Lyn and BCR-Abl at sub-micromolar potencies, yet is >1,000-fold less active against other tyrosine kinases such as EGFR, PDGFR, JAK1, JAK2, ZAP70 and Lck. KXO1 also has low nM potency as an in vitro inhibitor of tumor cell proliferation for a broad range of human cancer types. KXO1 substantially reduces the growth of human HT29 colon tumors in SCID mouse xenografts (T/C=30%) when dosed orally at 5 mg/kg/dose bid, and with no observed toxicity. KXO1 is currently completing late preclinical development and, in 2007, will be the first non-ATP competitive Src inhibitor to enter Phase I clinical trials.
Incidence of Malignant Thyroid Tumors in Humans After Exposure to Diagnostic Doses of Iodine-131. I. Retrospective Cohort Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L E Holm, G Lundell, G Walinder
Journal: JNCI Journal of the National Cancer Institute (1980)

Between 1952 and 1965, 10,133 patients received an average of 60 mu Cl of 131I for diagnostic examinations of the thyroid gland. The examinations were mainly done on adults, and only 5% of the patients were younger than 20 years at the time of examination. Of the patients, 9 appeared in the Swedish Cancer Registry between 1958 and 1977 with a diagnosis of malignant tumor of the thyroid gland more than 5 years after the administration of 131I. Inasmuch as the expected number of malignant thyroid tumors computed from Swedish cancer incidence figures was 8.3, there was no elevation of the incidence of malignant thyroid tumors in these patients receiving diagnostic doses of 131I. The patients were examined because of a suspected thyroid dysfunction and therefore represented a selected group. The investigation is being continued to analyze further parameters that could have a bearing on these results.
Racial Disparities in Access to Renal Transplantation — Clinically Appropriate or Due to Underuse or Overuse?
Authors: Arnold M. Epstein, John Z. Ayanian, Joseph H. Keogh, Susan J. Noonan, Nancy Armistead, Paul D. Cleary, Joel S. Weissman, Jo Ann David-Kasdan, Diane Carlson, Jerry Fuller, Douglas Marsh, Rena M. Conti
Journal: New England Journal of Medicine (2000)

Despite abundant evidence of racial disparities in the use of surgical procedures, it is uncertain whether these disparities reflect racial differences in clinical appropriateness or overuse or underuse of inappropriate care.We performed a literature review and used an expert panel to develop criteria for determining the appropriateness of renal transplantation for patients with end-stage renal disease. Using data from five states and the District of Columbia on patients who had started to undergo dialysis in 1996 or 1997, we selected a random sample of 1518 patients (age range, 18 to 54 years), stratified according to race and sex. We classified the appropriateness of patients as data on candidates for transplantation and analyzed rates of referral to a transplantation center for evaluation, placement on a waiting list, and receipt of a transplant according to race.Black patients were less likely than white patients to be rated as appropriate candidates for transplantation according to appropriateness criteria based on expert opinion (71 blacks [9.0 percent] vs. 152 whites [20.9 percent]) and were more likely to have had incomplete evaluations (368 [46.5 percent] vs. 282 [38.8 percent], P<0.001 for the overall chi-square). Among patients considered to be appropriate candidates for transplantation, blacks were less likely than whites to be referred for evaluation, according to the chart review (90.1 percent vs. 98.0 percent, P=0.008), to be placed on a waiting list (71.0 percent vs. 86.7 percent, P=0.007), or to undergo transplantation (16.9 percent vs. 52.0 percent, P<0.001). Among patients classified as inappropriate candidates, whites were more likely than blacks to be referred for evaluation (57.8 percent vs. 38.4 percent), to be placed on a waiting list (30.9 percent vs. 17.4 percent), and to undergo transplantation (10.3 percent vs. 2.2 percent, P<0.001 for all three comparisons).Racial disparities in rates of renal transplantation stem from differences in clinical characteristics that affect appropriateness as well as from underuse of transplantation among blacks and overuse among whites. Reducing racial disparities will require efforts to distinguish their specific causes and the development of interventions tailored to address them.
Central nervous system disease and acute myeloid leukemia or chronic myeloid leukemia: Cytogenetic profile.
Authors: F. Shihadeh, V. K. Reed, A. Mazloom, J. Phan, H. Kantarjian, S. Faderl, B. S. Dabaja
Journal: Journal of Clinical Oncology (2010)

6577 Background: Central nervous system (CNS) disease in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) is an infrequent occurrence. This study aimed to asses the cytogenetic profile in patients with CNS disease. Methods: The medical records of 1,331 patients treated for AML and CML from a single institution between 2000 and 2008 were retrieved. Institutional Review Board approval was obtained. We found 51 patients with myeloid leukemia and CNS involvement at presentation or at relapse, and these patients are the subject of this study. Demographics, cytogentic abnormalities, treatment, and status at last follow up data were collected. Results: The median age was 48 years (range 2-83), and 26 (51%) were female. CNS involvement was confirmed in all patients by lumbar puncture in 34 patients (67%), and/or magnetic resonance imaging in 42 patients (82%). Cytogentics studies were collected in all patients. Eleven patients (22%) had chronic myeloid leukemia and 40 patients (78%) had acute myeloid leukemia. Six patients (12%) had CNS disease at the time of initial leukemia diagnosis. The median follow up was 3.4 months (range 0.5-107 months). The cytogenetic profile of the 40 patients with acute myeloid leukemia was compared to the published Cancer and Leukemia Group B (CALGB) patients (Blood 2002; 100:4324), and the results are shown in the Table. Patients were treated with systemic chemotherapy, intrathecal chemotherapy, radiation, and/or stem cell transplant. Conclusions: Myeloid leukemia patients with CNS involvement often have poor cytogenetic features at the time of diagnosis. Complex cytogenetic abnormalites are common in patients with CNS disease. Cytogenetic profile This study (n=40), % CALGB study (n=1213), % Normal 25% 48% Inversion 16 15% 8% Trisomy 8 25% 10% Monosomy 5 or 7 12.5% 6% Complex (three or more abnormalities) 35% 11% No significant financial relationships to disclose.
Case 15-2000
Authors: Peter Siao, Lawrence R. Zukerberg
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 69-year-old man was admitted to the hospital because of worsening myasthenia gravis and an anterior mediastinal mass.The anterior mediastinal mass had been detected on a computed tomographic (CT) scan four years earlier (Figure 1) and had not subsequently increased in size. The patient also had asbestosis, which he had acquired while working as a plumber, and mild, nonprogressive exertional dyspnea. The patient was otherwise well until five months before admission, when his speech became slurred while he was talking on a telephone. At about the same time, saliva began to pool in his mouth and . . .
Clinical and Laboratory Findings in the Oculocerebrorenal Syndrome of Lowe, with Special Reference to Growth and Renal Function
Authors: Lawrence R. Charnas, Isa Bernardini, Daniel Rader, Jeffrey M. Hoeg, William A. Gahl
Journal: New England Journal of Medicine (1991)

The oculocerebrorenal syndrome of Lowe is an X-linked disorder whose clinical manifestations include congenital cataracts, mental retardation, and renal tubular dysfunction. We investigated growth, renal function, and serum chemistry values in patients with the oculocerebrorenal syndrome to determine the natural history of the disorder and its heterogeneity with respect to these characteristics.Twenty-three patients with the oculocerebrorenal syndrome, ranging in age from 4 months to 31 years, were examined. Height was compared with bone age. Renal function was assessed by measurements of proteinuria, urinary volume, and fractional excretions of potassium, phosphate, carnitine, and amino acids. Creatinine clearance was determined as a measure of glomerular function.In the oculocerebrorenal syndrome, linear growth decreases after one year of age; bone age lies between chronologic age and height age. Renal dysfunction occurs in the first year of life, characterized by proteinuria (mean [+/- SD], 1.38 +/- 0.77 g of urinary protein per square meter of body-surface area per day; normal, less than or equal to 0.10), generalized aminoaciduria (mean, 686 +/- 505 mumol of urinary amino acid per kilogram of body weight per day; normal, 94 +/- 45), carnitine wasting (mean fractional excretion, 0.10 +/- 0.05; normal, 0.03 +/- 0.01), and phosphaturia progressing into the third decade. Urinary wasting of individual amino acids is milder than in cystinosis, and branched-chain amino acids are relatively spared. Reciprocal serum creatinine levels fall linearly with age, predicting renal failure in the fourth decade. Concentrations of the muscle enzymes creatine kinase, aspartate aminotransferase, and lactate dehydrogenase, as well as of total serum protein, serum alpha 2-globulin, and high-density lipoprotein cholesterol, are elevated.Renal glomerular deterioration is slowly progressive in the oculocerebrorenal syndrome. Renal tubular dysfunction begins early and persists; most patients require alkalinization therapy, and many benefit from supplemental potassium, phosphate, calcium, or carnitine. Serum enzyme elevations suggest muscle involvement in the oculocerebrorenal syndrome.