tbuckley/cabot-search huggingface dataset:
New combination of the old drugs for elderly patients with small-cell lung cancer: a phase II study of the PAVE regimen.
Authors: V Westeel, N Murray, K Gelmon, A Shah, F Sheehan, M McKenzie, F Wong, J Morris, C Grafton, V Tsang, K Goddard, K Murphy, C Parsons, R Amy, R Page
Journal: Journal of Clinical Oncology (1998)

PURPOSE A regimen of cisplatin, doxorubicin, vincristine, and etoposide (PAVE) was designed for patients with small-cell lung cancer (SCLC) who were older than 65 years, with the following objectives compared with standard chemotherapy regimens: maintain efficacy, diminish toxicity, enhance compliance, and improve chemotherapy administration convenience at an acceptable cost. PATIENTS AND METHODS The PAVE regimen consisted of cisplatin 30 mg/m2 intravenously (i.v.) day 1; doxorubicin 40 mg/m2 i.v. day 1; vincristine 1.0 mg/m2 i.v. day 1; and etoposide 100 mg/m2 i.v. day 1 and orally days 3 and 5. Cycles were repeated every 3 weeks for four cycles. Patients with limited-stage disease and selected patients with extensive-stage disease received thoracic irradiation delivered concurrently with etoposide-cisplatin (EP) at the time of the second chemotherapy cycle. RESULTS Sixty-six eligible patients were treated, which included 25 patients with limited-stage disease and 41 patients with extensive-stage disease. Median survival was 70 weeks and 5-year survival was 25% for limited-stage disease. Median survival was 46 weeks for extensive-stage disease. Only one treatment-related death occurred and severe toxicity was infrequent. The median delivered dose-intensity was according to protocol and the mean delivered total dose was 80% of intended. CONCLUSION The treatment outcome achieved with PAVE in a phase II study of elderly patients compared favorably with published results of standard regimens in patient populations with better prognostic factors. Because the PAVE regimen can be delivered with good compliance, has acceptable toxicity, and is associated with logistic advantages compared with standard regimens, this protocol is suitable for further investigative trials in elderly patients with SCLC.
Screening people with a family history of cancer
Authors: R. Bell, M. Petticrew, P. W Rose, M. A Suchard
Journal: BMJ (1997)

More widespread public debate on rationing is essentialEditor-We find it significant that none of the clinicians who contributed to the conference "Rationing in the NHS: Time to Get Real" signed the open letter to Frank Dobson. 1 In the letter, rationing is defined as occurring when not all health services can be provided to everybody who might benefit from them, a definition so broad that it can be said always to have existed.Yet most British clinicians would not recognise the examples given as rationing.A young woman with high cholesterol as a single risk factor for coronary heart disease may be "denied" drug treatment and given dietary advice instead simply because the risks of side effects outweigh the marginal benefit; this is rational, not rationing.Again, "denying" magnetic resonance imaging for uncomplicated migraine in a young person has nothing to do with cost: the risks of iatrogenic anxiety and distress are far greater than any possible benefit from such intervention.The authors do the cause of so called smart rationing a disservice by these examples.This debate is too important to be "dumbed down" in this way.Whenever rationing is discussed there is a tension between those whose professional discipline (health economics, medical ethics, or policy analysis) allows them to work with broad underlying principles and those who are constantly brought face to face with the limitations of these principles through daily contact with patients.The former are much more likely to believe that it is possible and appropriate to base all rationing decisions on a series of well argued principles.Life for the latter is far messier: it is often impossible to apply broad principle to individual cases, let alone find a "currency of comparison" 2 that will enable the claims of, for example, a dying older person on an understaffed geriatric ward to be ranked against those of a patient with multiple sclerosis who might benefit from interferon beta.Struggling to make these sorts of comparisons is painful; the examples given in the open letter tax no one and thereby offer false hope of easy solutions.It is because the choices are difficult that more widespread public debate is essential.Only through such a debate can we all, as citizens, realise what is happening to the NHS, consider if that is the NHS that we want, and decide how much of our taxes an NHS worthy of the name deserves.
Transmission patterns of human enterovirus 71 to, from and among European countries, 2003 to 2013
Authors: Chervin Hassel, Audrey Mirand, Alexander Lukashev, Elena TerletskaiaLadwig, Agnes Farkas, Isabelle Schuffenecker, Sabine Diedrich, Hartwig P Huemer, Christine Archimbaud, Hélène Peigue-Lafeuille, Cécile Henquell, Jean-Luc Bailly
Journal: Eurosurveillance (2015)

Enterovirus 71 (EV-71) is involved in epidemics of hand, foot, and mouth disease (HFMD) and has been reported to occur with severe neurological complications in eastern and south-east Asia. In other geographical areas, the transmission of this virus is poorly understood. We used large sequence datasets (of the gene encoding the viral protein 1, VP1) and a Bayesian phylogenetic approach to compare the molecular epidemiology and geographical spread patterns of EV-71 subgenogroups B4, B5, C1, C2, and C4 in Europe relative to other parts of the world. For the study, European countries considered were European Union (EU) Member States and Iceland, Norway and Switzerland. Viruses of the B4, B5, and C4 subgenogroups circulate mainly in eastern and south-east Asia. In Europe sporadic introductions of these subgenogroups are observed, however C1 and C2 viruses predominate. The phylogenies showed evidence of multiple events of spread involving C1 and C2 viruses within Europe since the mid-1990s. Two waves of sporadic C2 infections also occurred in 2010 and 2013. The 2007 Dutch outbreak caused by C2 and the occurrence of B5 and C4 infections in the EU between 2004 and 2013 arose while the circulation of C1 viruses was low. A transmission chain involving a C4 virus was traced from Japan to the EU and then further to Canada between 2001 and 2006. Recent events whereby spread of viruses have occurred from, to, and within Europe appear to be involved in the long term survival of EV-71, highlighting the need for enhanced surveillance of this virus.
The Role of Myeloid Growth Factors in Acute Leukemia
Authors: Martha Wadleigh, Richard M. Stone
Journal: Journal of the National Comprehensive Cancer Network (2009)

Myeloid growth factors granulocyte-colony stimulating and granulocyte macrophage colony-stimulating factors have been extensively studied in acute leukemias. Whether administered before, during, or after chemotherapy for acute myeloid leukemia and acute lymphoblastic leukemia, these agents reduce the duration of neutropenia and seem to be safe and well tolerated. Despite consistently showing a shorter duration of neutropenia, multiple, prospective, randomized trials have documented only modest benefits in terms of reduction in the incidence and severity of infections, without substantial gains or impact in complete remission, overall survival, and disease-free survival rates. Growth factors have also been used to recruit quiescent leukemia cells into the S-phase of the cell cycle to increase their susceptibility to chemotherapy with the goal to reduce relapse and resistance. Randomized trials evaluating this priming strategy have consistently shown improvement in disease- or event-free survival in the intermediate-risk group of patients with acute myeloid leukemia, but no overall survival benefit. This article focuses on the clinical experience with these agents as adjuncts to the treatment of acute leukemias.
Prevalence and impact of symptoms related to restless legs in patients with obstructive sleep apnea syndrome
Authors: Helder Novais e Bastos, Filipa Soares Pires, Maria Sucena, Anabela Marinho, Marta Drummond, João Almeida, João Winck
Journal: European Respiratory Journal (2013)

Patients with Obstructive Sleep Apnea Syndrome (OSA) frequently report the feeling of restless legs (RL), but the relevance of this association remains uncertain. The aim of this study was to evaluate the prevalence and the impact of symptoms related to RL in OSA patients.  This prospective study included newly diagnosed OSA patients that met criteria to CPAP treatment. They filled in the Sleep Disorders Questionnaire (SDQ) and 2 groups were defined, according to the absence (G1) or presence (G2) of symptoms related to RL.  We evaluated 147 patients (72.8% G1, 27.2% G2), 71.4% of male gender, age (mean±SD) 55.3±11.7 years-old, body mass index (BMI) 32.8±5.6 Kg/m2, Epworth Sleepiness Scale (ESS) 11.4±5.9 and Apnea-Hypopnea Index (AHI) 42.2±20.5 events/h. Only a minority of male gender patients were allocated in G2 (78.1% G1 vs 21.9% G2; X2=5.2, p=0.022). Patients in G2 were older (53.7±11.7 G1 vs 59.4±10.9 G2; t=-2.7, p=0.008), had more prevalence of heart disease (2.8% G1 vs 22.5% G2; X2=15.1, p  We report a significant frequency of symptoms related to RL in patients with OSA. Restless legs symptoms may be a clinical predictor of increased affective or psychiatric disturbances and cardiovascular risk.
The Burden of Asthma in the United States
Authors: Anne L. Fuhlbrigge, Robert J. Adams, Theresa W. Guilbert, Evie Grant, Paula Lozano, Susan L. Janson, Fernando Martinez, Kevin B. Weiss, Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Asthma imposes a growing burden on society in terms of morbidity, quality of life, and healthcare costs. Although federally sponsored national surveys provide estimates of asthma prevalence, these surveys are not designed to characterize the burden of asthma by self-reported disease activity. We sought to characterize asthma burden in the United States. This study was based on a cross-sectional random-digit-dial household telephone survey designed to identify adult patients and parents of children with current asthma. Global asthma burden was comprised of three components: short-term symptom burden (4-week recall), long-term symptom burden (past year), and functional impact (activity limitation). Using this construct, only 10.7% of individuals were classified as having a global asthma burden consistent with mild intermittent disease, and 77.3% had moderate to severe persistent disease. These results suggest that a majority of the United States population with asthma experiences persistent rather than intermittent asthma burden. In addition, the discordance in type and distribution of asthma symptoms reported by individual subjects suggests that the exact estimate of the burden of asthma is related to how the National Asthma Education and Prevention Program classification is operationalized. Inquiry into recent day or nighttime symptoms alone underestimates the burden of asthma and may lead to inadequate treatment of asthma based on national guideline recommendations.
Adjuvant Chemotherapy for Adult Soft Tissue Sarcomas of the Extremities and Girdles: Results of the Italian Randomized Cooperative Trial
Authors: Sergio Frustaci, Franco Gherlinzoni, Antonino De Paoli, Marco Bonetti, Alberto Azzarelli, Alessandro Comandone, Patrizia Olmi, Angela Buonadonna, Giovanni Pignatti, Enza Barbieri, Gaetano Apice, Hassan Zmerly, Diego Serraino, Piero Picci
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Adjuvant chemotherapy for soft tissue sarcoma is controversial because previous trials reported conflicting results. The present study was designed with restricted selection criteria and high dose-intensities of the two most active chemotherapeutic agents. PATIENTS AND METHODS: Patients between 18 and 65 years of age with grade 3 to 4 spindle-cell sarcomas (primary diameter ≥ 5 cm or any size recurrent tumor) in extremities or girdles were eligible. Stratification was by primary versus recurrent tumors and by tumor diameter greater than or equal to 10 cm versus less than 10 cm. One hundred four patients were randomized, 51 to the control group and 53 to the treatment group (five cycles of 4′-epidoxorubicin 60 mg/m 2 days 1 and 2 and ifosfamide 1.8 g/m 2 days 1 through 5, with hydration, mesna, and granulocyte colony-stimulating factor). RESULTS: After a median follow-up of 59 months, 60 patients had relapsed and 48 died (28 and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The median disease-free survival (DFS) was 48 months in the treatment group and 16 months in the control group (P = .04); and the median overall survival (OS) was 75 months for treated and 46 months for untreated patients (P = .03). For OS, the absolute benefit deriving from chemotherapy was 13% at 2 years and increased to 19% at 4 years (P = .04). CONCLUSION: Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an intensified treatment in similar cases. Although cure is still difficult to achieve, a significant delay in death is worthwhile, also considering the short duration of treatment and the absence of toxic deaths.
Endogenous hydrogen sulfide (H2S) in serum and sputum as novel biomarker of asthma
Authors: Junpei Saito, Qingling Zhang, Christopher Hui, Andrew Menzies-Gow, Pankaj Bhavsar, Kian Fan Chung
Journal: European Respiratory Journal (2012)

Background;  Hydrogen sulfide (H 2 S) is considered to be the third gasotransmitter along with nitric oxide and carbon oxide. However little is known about the role. We examined whether H 2 S in serum or sputum can be used as a biomarker of asthma.  Methods;  Forty asthmatic subjects and 15 healthy volunteers were recruited in this study. Subjects were asked to answer asthma control questionnaire and take bloods, induced sputum, lung function tests, and exhaled nitric oxide (Fe NO ) measurements. H 2 S concentrations in sputum and serum samples of patients with severe and non-severe asthma and of healthy subjects were measured using a sulfide-sensitive electrode and compared H 2 S levels with other clinical parameters.  Results;  H 2 S levels in sputum from severe and non-severe asthmatic patients were significantly higher than those from healthy subjects but there was no difference between the severe and non-severe group. Serum H 2 S levels were 10 times higher than in sputum and these were also higher in severe and non-severe asthmatic subjects compared to healthy subjects. There was a positive correlation between sputum and serum H 2 S levels (r=0.42, p 2 S levels were inversely correlated with FEV 1  %predicted (r= -0.41, p=0.005), and with reversibility to salbutamol (r= -0.53, p 2 S and sputum neutrophils and macrophages (r= 0.464 and r= -0.456, p=0.001, respectively), and a negative correlation between sputum H 2 S and Fe NO  levels (r=-0.510, p=0.003).  Conclusions;  Sputum H 2 S levels may represent a novel biomarker of asthma, particularly useful as a marker of neutrophilic inflammation, chronic airflow obstruction and bronchodilator responsiveness.
Detecting Overall Survival Benefit Derived From Survival Postprogression Rather Than Progression-Free Survival
Authors: Satoshi Morita, Kentaro Sakamaki, Guosheng Yin
Journal: JNCI Journal of the National Cancer Institute (2015)

Broglio and Berry (2009) examined the impact of survival postprogression (SPP) on overall survival (OS) when progression-free survival (PFS) was used to assess treatment effect in metastatic cancer. Their simulation studies found no statistical difference in OS because of dilution effect from SPP, although there was a statistical difference in PFS between treatment arms. Recently, two phase III clinical trials showed efficacy of experimental treatments in OS, but not PFS. These results seem counterintuitive, because it may be reasonable to consider that the effect of treatment in prolonging PFS can influence OS prolongation. We conducted simulations to examine the role of SPP in OS under the assumption that only SPP, and not PFS, differed between treatment arms. We also explored the impact of patient heterogeneity on the OS analysis. Our study offers a reasonable explanation for the two phase III trials and recommends further discussion of PFS as an adequate endpoint and what role SPP might play in OS to evaluate current treatment regimens.
Multiple Cancer—an Epidemiologic Exercise in Finland
Authors: L Teppo, E Pukkala, E Saxén
Journal: JNCI Journal of the National Cancer Institute (1985)

The material of the Finnish Cancer Registry from 1953-79 (279,745 cancer patients, 774,518 person-yr at risk) was analyzed for the occurrence of multiple cancer. There were 5,871 new primary cancers in the series (excluding the first 12 mo from diagnosis of the first cancer). A positive association between cancers with similar etiology could be demonstrated, e.g., between cancers of the lip, larynx, and lung (smoking) and between cancers of the breast and endometrium (hormones, reproductive history). Clustering of different risk factors resulted, e.g., in an excess risk of colon cancer among female breast cancer patients (risk factors in both cancers are prevalent particularly in higher-social classes). Differences in the distribution of the risk factors resulted in risk deficits, e.g., low relative risk of lung cancer among male colon cancer patients (the prevalence of smoking was highest in the lower-social classes and the prevalence of risk factors in colon cancer was highest in the higher-social classes). The risk of leukemia was increased among patients with cancers of the breast, endometrium, and thyroid (possibly due to irradiation). There was a high relative risk of salivary gland cancer among patients with skin cancer other than melanoma or basal cell carcinoma in both sexes. The relative risk of a new primary cancer decreased with increasing age at diagnosis of the first cancer. The length of follow-up was positively associated with the relative risk of many cancers, although this finding was not as consistent as that with age.
Sleep breathing disorders, nocturnal atrial fibrillation and nCPAP treatment
Authors: Ventsislava Pencheva, Daniela Petrova, Ognian Georgiev, Emil Manov
Journal: European Respiratory Journal (2014)

Background:  Sleep breathing disorders (SBD) are one of the major health problems in recent years. Although the different symptoms and signs one of the most important organ that is affected is heart. Atrial fibrillation (AF) occurs more frequently in patients with SBD than in the rest of the population.   Aim:  The aim of the study is to determine the prevalence of nocturnal AF in asymptomatic patients with SBD and the effect of nCPAP treatment on it.   Materials and methods : 24-hours electrocardiography (ECG) records were performed in 59 patients with polysomnography diagnosed SBD and no history of arrhythmias or thyroid disorders. They all were with normal ECG during the day. The mean age was 53.88±10.339 and 53 (89.8%) of them were men.   Results:  In 8 (13.6%) of the patients were registered paroxysmal nocturnal attacks of AF. They were occurred predominantly in subjects with body mass index (BMI) >35. SBD were corrected with nCPAP treatment. 24-hours ECG records were done after a month in these patients. From the control data we did not find episodes of AF or other arrhythmias.   Conclusions:  The relationship between SBD and AF is well established. The correction of respiratory disturbances during sleep and related with them nocturnal hypoxemia leads to normalization of heart rhythm.
Adenine Phosphoribosyltransferase Activities of Mouse Ascites Tumors and Derived Tumorigenic and Nontumorigenic Tissue Cultures&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D. G. R. Blair, S. J. Peesker, M. Dommasch, M. D. Heuchert, J. F. Morgan
Journal: JNCI Journal of the National Cancer Institute (1972)

Adenine phosphoribosyltransferase was tested as a possible “marker” enzyme for tumorigenicity of cultured mouse ascites tumor cells. Enzyme-specific activities were determined for cell-free extracts of 4 types of mouse ascites tumors (Ehrlich and Ehrlich-Lettré carcinomas, 6C3HED lymphoma, and TA3 adenocarcinoma) and for their derived tumorigenic and nontumorigenic tissue cultures. Adenine phosphoribosyltransferase activity was not correlated with the tumorigenicity of the cells. Whereas the activities were similar and relatively high among the 4 types of ascites tumor cells obtained directly from the mice, those among both tumorigenic and nontumorigenic cultured cells were 33–75% lower. Tumorigenic and nontumorigenic cultured cells could not be distinguished by enzyme activity. The lower enzyme activities of cultured cells occurred by the fifth passage after culture initiation; they were not attributable to differences in pH optima or optimal concentrations of magnesium ion, adenine, or 5-phosphoribosyl-α-1 -pyrophosphate. The possibilities that the decreased enzyme activities of the cultured cells were due to the presence of inhibitors or to decreased enzyme stability were also examined. Extracts from cultured cells did not inhibit the activities of extracts of ascites tumor cells. Freshly prepared cell extracts were generally used for most enzyme assays, but sometimes samples stored at − 20°C were used. The stability of enzyme activity was similar, but not uniform, for extracts of ascites tumor or tissue culture cells stored at − 20°C. However, there was little or no loss of activity within 33 days of storage. The lowered enzyme activity of cultured cells appears to be an adaptation to growth in vitro.
A phase I and pharmacokinetic clinical trial of the orally administered retinoic acid receptor-α Agonist, AGN 195183
Authors: C. W. Taylor, P. Walker, D. Tang-Liu, T. Joshi, C. Gebremarian, S. Jordan, Z. Yu, D. Von Hoff, L. Garland
Journal: Journal of Clinical Oncology (2004)

2022 Background: AGN 195183 is a novel retinoid that trans-activates retinoic acid receptor-α (RAR-α). In preclinical models, AGN 195183 caused less skin toxicity compared to RAR interactive agents lacking RAR-α specificity and demonstrated anti-tumor activity in breast cancer and leukemia models. We initiated a clinical trial of AGN 195183 in advanced solid tumor patients (pts) in order to establish toxicity and pharmacokinetic profiles and to establish the maximum tolerated dose (MTD). Methods: Fifteen pts with advanced solid tumors meeting standard phase I entry criteria were enrolled on study; mean age was 60 years (range 45–79). Pts took AGN 195183 (5 and 50 mg soft gelatin capsules) by mouth with or without food on a continuous daily dosing schedule. Pharmacokinetic (PK) blood samples were collected on the days 1 and 14 prior to dosing and at 0.5, 1, 1.5, 2, 3, 5, 8, and 24 hours post-dose and prior to and 1 hour post-dose on days 7, 21, and 28. Results: Five pts were treated at the starting dose level of 60 mg/m2/d; 2 pts had a dose limiting toxicity (DLT) including grade 3 elevation of alk phos (pt also had progressing liver metastases) and gr 3 mucositis. Drug was de-escalated to 30 mg/m2/d; 2 of 4 pts treated had gr 3 elevation of alkaline phosphatase. Further de-escalation to 15 mg/m2/d has been well tolerated by 6 pts for 17 treatment cycles, with no grade 3 or higher toxicity noted. Preliminary PK studies for 60 mg/m2/d dose level show the drug is absorbed rapidly and reached peak concentration at about one hour post-dose. The average terminal elimination half-life was 4.17 hours. Cmax ranged from 684 to 7660 ng/mL and AUC from 4140 to 31246 95183 ng-hr/mL in 3 pts. Conclusion: AGN 195183 is a novel retinoid that trans-activates retinoic acid receptor-α (RAR-α); it has been well tolerated on an oral daily dosing schedule of 15 mg/m2/d, which is the MTD and recommended Phase II dose. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Allergan Allergan Allergan