tbuckley/cabot-search huggingface dataset:
Ifosfamide, Carboplatin, and Etoposide With Midcycle Vincristine Versus Standard Chemotherapy in Patients With Small-Cell Lung Cancer and Good Performance Status: Clinical and Quality-of-Life Results of the British Medical Research Council Multicenter Randomized LU21 Trial
Authors: Nicholas Thatcher, Wendi Qian, Peter I. Clark, Penelope Hopwood, Robert J. Sambrook, Robert Owens, Richard J. Stephens, David J. Girling
Journal: Journal of Clinical Oncology (2005)

Ifosfamide, carboplatin, etoposide, and vincristine, alone and in combination, are highly active against small-cell lung cancer (SCLC). This trial was designed to investigate whether survival could be improved by a regimen of all four drugs (ICE-V) compared with standard chemotherapy in patients with SCLC and good performance status, and to assess the patients' quality of life (QL).Patients were randomly assigned to receive six cycles of either ICE-V at 4-week intervals without dose reduction or standard chemotherapy administered according to local practice. The recommended standard control regimens were cyclophosphamide, doxorubicin, and etoposide; and cisplatin and etoposide.A total of 402 patients were randomly assigned, and 350 (87%) patients have died. Overall survival was longer in the ICE-V group (hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P = .0049), median survival was 15.6 months in the ICE-V group and 11.6 months in the control group, and 2-year survival rates were 20% and 11%, respectively. There was no evidence that the relative survival benefit for ICE-V was less in extensive-stage than in limited-stage patients. An increased rate of septicemia was reported in the ICE-V group (15% v 7% in the control group), but this did not result in an increase in reported treatment-related deaths (four patients [2%] in both groups). The findings on QL were broadly similar in both groups, with some benefit in favor of ICE-V.Compared with standard chemotherapy, the ICE-V regimen improves overall survival without QL penalties, despite an increased but manageable level of toxicity.
Replacing the mercury sphygmomanometer
Authors: E. O'Brien
Journal: BMJ (2000)

When Scipione Riva-Rocci published his papers on a new sphygmomanometric technique in 18961 he could not have anticipated that his method was to become the mainstay of clinical measurement for over a century. Because of this long and fruitful record of service any threat to the familiar mercury sphygmomanometer is met with resistance—which may be interpreted as arising more from sentimentality than from scientific principle. But is this fair? May there not be more to the Riva-Rocci/Korotkoff technique than meets the eye?

Clinical sphygmomanometry will change as we move into the next millennium. Firstly, we will no longer be allowed to use mercury, and with its passing will disappear the main argument against introducing the kilopascal as the unit of measurement—namely, that we measure what we see. Mercury will no longer be permitted because it is toxic to the environment, and the replacement of the millimetre of mercury with the kilopascal, used throughout science as the unit of pressure, may be seen as an opportunity to tidy up an irksome anomaly in scientific nomenclature.2 3

The mercury …
Recommended Patient-Reported Core Set of Symptoms to Measure in Head and Neck Cancer Treatment Trials
Authors: Bhishamjit S. Chera, Avraham Eisbruch, Barbara A. Murphy, John A. Ridge, Patrick Gavin, Bryce B. Reeve, Deborah Watkins Bruner, Benjamin Movsas
Journal: JNCI Journal of the National Cancer Institute (2014)

We identified a standard core set of patient-reported symptoms and health-related quality-of-life (HRQOL) domains to be assessed in head and neck (H&N) cancer clinical trials. The core symptom and HRQOL domain scores were used to guide recommendations by a working group of experts as part of a National Cancer Institute Symptom Management and HRQOL Clinical Trials Planning Meeting. A PubMed search was conducted using the search terms of "health-related quality of life" and "head & neck cancer," limited to publications from January 1, 2000, to December 31, 2010. Fifty-four articles were used to guide the choice of recommendations. Twenty-nine symptoms and nine domains were identified, from which 12 H&N-specific core symptoms and HRQOL domains were recommended: swallowing, oral pain, skin changes, dry mouth, dental health, opening mouth/trismus, taste, excess/thick mucous/saliva, shoulder disability/motion, voice/hoarseness, social domain, and functional domain. This core set of 12 H&N-specific, patient-reported symptoms and HRQOL domains should be assessed in future H&N cancer clinical trials.
Efficacy and Safety of Ivacaftor in Patients Aged 6 to 11 Years with Cystic Fibrosis with a <i>G551D</i> Mutation
Authors: Jane C. Davies, Claire E. Wainwright, Gerard J. Canny, Mark A. Chilvers, Michelle S. Howenstine, Anne Munck, Jochen G. Mainz, Sally Rodriguez, Haihong Li, Karl Yen, Claudia L. Ordoñez, Richard Ahrens
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Ivacaftor (VX-770), a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has been shown to improve lung function, pulmonary exacerbation rate, respiratory symptoms, and weight gain compared with placebo in patients with cystic fibrosis aged 12 years or older with a G551D-CFTR mutation.This randomized, double-blind, placebo-controlled trial evaluated ivacaftor in patients with cystic fibrosis aged 6-11 years with a G551D-CFTR mutation on at least one allele.Patients were randomly assigned to receive ivacaftor administered orally at 150 mg (n = 26) or placebo (n = 26) every 12 hours for 48 weeks in addition to existing prescribed cystic fibrosis therapies.Despite near-normal mean baseline values in FEV1, patients receiving ivacaftor had a significant increase in percent predicted FEV1 from baseline through Week 24 versus placebo group (treatment effect, 12.5 percentage points; P < 0.001). Effects on pulmonary function were evident by 2 weeks, and a significant treatment effect was maintained through Week 48. Patients treated with ivacaftor gained, on average, 2.8 kg more than those receiving placebo at Week 48 (P < 0.001). The change from baseline through Week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor was -53.5 mmol/L (P < 0.001) versus placebo. The incidence of adverse events was similar in the two groups.In patients who are younger and healthier than those in previously studied populations, ivacaftor demonstrated a significant improvement in pulmonary function, weight, and CFTR activity compared with placebo. Clinical trial registered with www.clinicaltrials.gov (NCT00909727).
Unusual Thoracic Problems in Patients With Malignancies
Authors: Rattiya Cheewakriangkrai, Alan Litwin, Maria E. Nava, Nithya Ramnath
Journal: Journal of Clinical Oncology (2005)

A 45-year-old white male was diagnosed with pulmonary alveolar proteinosis (PAP) when he was 31 years old. He was treated with periodic bronchoalveolar lavage to remove large volumes of proteinaceous material from his lungs (last lavage in December 2002). In September 2003, he presented with a 6-week history of right-sided pleuritic chest pain, progressive shortness of breath, and weight loss of 14 kgs over the previous 2 months. Chest radiographs revealed bilateral alveolar infiltration with a right pleural effusion. Initial computed tomography of the chest showed bilateral air-space disease, and a right pleural effusion. There was no pleural thickening or lymphadenopathy. At thoracentesis, 1,500 mL of hemorrhagic pleural fluid was removed. The fluid reaccumulated in 48 hours, requiring a video-assisted thoracoscopy, drainage, and pleurodesis with talc. At thoracoscopy, a 3-cm mass was seen in the superior segment of the right lower lobe, and pleural implants were biopsied. He was referred to our facility with a diagnosis of malignant mesothelioma. The patient was a nonsmoker with no family history of cancer or exposure to asbestos. On examination, he was using oxygen at 2 l/min. His breath sounds were diminished on the right side. A repeat computed tomography scan (Figs 1A and 1B) showed pleural implants, areas of PAP, as well as a mass in the right lung with hilar adenopathy. Pathologic exam (Figs 1C and 1D) revealed clusters of malignant mesothelial cells that were strongly positive for calretinin stain, consistent with a diagnosis of malignant mesothelioma. Treatment for mesothelioma was instituted with chemotherapy consisting of cisplatin and pemetrexed on an expanded-access program. The patient has had a marked decrease in the mass and adenopathy, and no longer required oxygen after two cycles of chemotherapy. PAP is a rare condition with an estimated annual incidence and prevalence of 0.36 and 3.70 cases per million population, respectively. This disorder is a disease of alveolar macrophage dysfunction caused by excessive intraalveolar surfactant accumulation. The signaling pathways in these macrophages are turned on by granulocyte-macrophage colony-stimulating–factor. PAP has been described in association with congenital disorders, immunodeficiency states, hematologic malignancies, myelodysplastic syndrome, infection with Pneumocystis carinii, and inorganic dust exposure. There are no previously reported cases of PAP associated with mesothelioma. However, changes resembling those of alveolar proteinosis have been reported in the lung adjacent to
Gender and ethnic differences in chronic myelogenous leukemia prognosis and treatment response: a single-institution retrospective study
Authors: Justin P Lee, Elliott Birnstein, David Masiello, Dongyun Yang, Allen S Yang
Journal: Journal of Hematology & Oncology (2009)

In the last decade the importance of ethnicity, socio-economic and gender differences in relation to disease incidence, diagnosis, and prognosis has been realized. Differences in these areas have become a major health policy focus in the United States. Our study was undertaken to examine the demographic and clinical features of chronic myelogenous leukemia (CML) patients presenting initially at the LAC+USC Medical Center, which serves an ethnically diverse population.
An Alu-Based Phylogeny of Gibbons (Hylobatidae)
Authors: Thomas J. Meyer, Adam T. McLain, J. Michael Oldenburg, Christopher Faulk, Matthew G. Bourgeois, Erin M. Conlin, Alan R. Mootnick, Pieter J. de Jong, Christian Roos, Lucia Carbone, Mark A. Batzer
Journal: Molecular Biology and Evolution (2012)

Gibbons (Hylobatidae) are small, arboreal apes indigenous to Southeast Asia that diverged from other apes ∼15-18 Ma. Extant lineages radiated rapidly 6-10 Ma and are organized into four genera (Hylobates, Hoolock, Symphalangus, and Nomascus) consisting of 12-19 species. The use of short interspersed elements (SINEs) as phylogenetic markers has seen recent popularity due to several desirable characteristics: the ancestral state of a locus is known to be the absence of an element, rare potentially homoplasious events are relatively easy to resolve, and samples can be quickly and inexpensively genotyped. During radiation of primates, one particular family of SINEs, the Alu family, has proliferated in primate genomes. Nomascus leucogenys (northern white-cheeked gibbon) sequences were analyzed for repetitive content with RepeatMasker using a custom library. The sequences containing Alu elements identified as members of a gibbon-specific subfamily were then compared with orthologous positions in other primate genomes. A primate phylogenetic panel consisting of 18 primate species, including 13 gibbon species representing all four extant genera, was assayed for all loci, and a total of 125 gibbon-specific Alu insertions were identified. The resulting amplification patterns were used to generate a phylogenetic tree. We demonstrate significant support for Symphalangus as the most basal lineage within the family. Our findings also place Nomascus as a derived lineage, sister to Hoolock, with the Nomascus-Hoolock clade sister to Hylobates. Further, our analysis groups N. leucogenys and Nomascus siki as sister taxa to the exclusion of the other Nomascus species assayed. This study represents the first use of SINEs to determine the genus level phylogenetic relationships within the family Hylobatidae. These relationships have been resolved with robust support at most internal nodes, demonstrating the utility of SINE-based phylogenetic analysis. We postulate that hybridization and rapid radiation may have contributed to the complex and contradictory findings of the previous studies. Our findings will aid in the conservation of these threatened primates and inform future studies of the biogeographical history and distribution of modern gibbon species.
Response to Comment on Duran et al. Introduction of IADPSG Criteria for the Screening and Diagnosis of Gestational Diabetes Mellitus Results in Improved Pregnancy Outcomes at a Lower Cost in a Large Cohort of Pregnant Women: The St. Carlos Gestational Diabetes Study. Diabetes Care 2014;37:2442–2450
Authors: Alejandra Durán, Isabelle Runkle, Miguel A. Rubio, Nuria García de la Torre, Alfonso L. Calle-Pascual
Journal: Diabetes Care (2015)

We sincerely appreciate the comments from Addison and Belalcazar (1) on our study (2) and their concern with the risk of hypoglycemia after initiation and intensification of insulin therapy. To address this issue, we would like to point out that:

1.  The treatment of gestational diabetes mellitus (GDM) and glycemic control targets remained unchanged during both study periods (2). Insulin therapy was initiated or the dose increased when blood glucose levels were >95 mg/dL (5.3 mmol/L) for fasting and preprandial values or >140 mg/dL (7.8 mmol/L) for 1-h postprandial levels, as currently accepted (3). Thus, the hypoglycemic risk as based on target …
Pain and Emotional Well-Being Outcomes in Southwest Oncology Group–Directed Intergroup Trial S0205: A Phase III Study Comparing Gemcitabine Plus Cetuximab Versus Gemcitabine As First-Line Therapy in Patients With Advanced Pancreas Cancer
Authors: Carol M. Moinpour, Nancy L. Vaught, Bryan Goldman, Mary W. Redman, Philip A. Philip, Barbara Millwood, Scott M. Lippman, Thomas E. Seay, Patrick J. Flynn, Eileen M. O'Reilly, Kendrith M. Rowland, Ralph P. Wong, Jacqueline Benedetti, Charles D. Blanke
Journal: Journal of Clinical Oncology (2010)

Purpose S0205 was a randomized clinical trial that compared the therapeutic impact of gemcitabine versus gemcitabine plus cetuximab. Study results for patient-reported health-related quality of life (HRQL) outcomes are reported. Patients and Methods Patients completed the Brief Pain Inventory and a measure of emotional well-being (each measured on a 0 to 10 scale) at baseline and at weeks 5, 9, 13, and 17 postrandom assignment. Worst pain status was classified as palliated (worst pain scores &lt; 5 maintained for 2 consecutive cycles) or not palliated (remaining patients) and tested with a χ 2 test. Change in emotional well-being and worst pain (exploratory analysis) were assessed over 17 weeks using generalized estimating equations with inverse probability of censoring weights. Results Seven hundred twenty of 766 enrolled patients contributed baseline HRQL data. The two treatment arms did not differ statistically in the percentage of patients with successful worst pain palliation. Longitudinal analyses showed significantly improved emotional well-being for patients on both arms by weeks 13 and 17 (P &lt; .01 and P &lt; .001). An exploratory longitudinal analysis of worst pain showed significant decreases at all time points for both arms (P &lt; .01 and P &lt; .001). Significant treatment arm differences for either worst pain or emotional well-being were not observed at any of the assessment times. Conclusion We observed palliated pain and improved well-being for patients on this trial. However, these improvements were similar in both treatment arms, suggesting that the addition of cetuximab did not contribute to improvement in these HRQL outcomes.
Cost-Effectiveness Analysis Based on the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS)
Authors: Shalini L. Kulasingam, Jane J. Kim, William F. Lawrence, Jeanne S. Mandelblatt, Evan R. Myers, Mark Schiffman, Diane Solomon, Sue J. Goldie
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: The ALTS (atypical squamous cells of undetermined significance [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study) suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing followed by referral to colposcopy of only those women with oncogenic HPV (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS trial to determine whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three cytology examinations. Methods: Data from the ALTS trial were used in conjunction with medical care costs in a short-term decision model. The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. Results: The least costly and least sensitive strategy was conservative management with one repeat cytology examination using a threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to colposcopy. Compared with this strategy, triage to colposcopy based on a positive HPV DNA test result had an ICER of $3517 per case of CIN3+ detected. Immediate colposcopy and conservative management with up to three repeat cytology visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing. Immediate colposcopy became cost-effective at $20 370 compared with HPV DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive. Conclusions: HPV DNA testing is an economically viable strategy for triage of ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs to be accounted for in future clinical guidelines and policy analyses.
Circulatory Support for Long-Term Treatment of Heart Failure
Authors: Stephen Westaby, Adrian P. Banning, Satoshi Saito, David W. Pigott, Xu Y. Jin, Pedro A. Catarino, Desiree Robson, Narain Moorjani, Attila Kardos, Philip A. Poole-Wilson, Robert Jarvik, O.H. Frazier
Journal: Circulation (2002)

Background — A lifetime mechanical solution for advanced heart failure must be reliable, with a low risk of life-threatening complications. After extensive laboratory testing, we began clinical trials with an axial flow pump for long-term treatment of New York Heart Association class IV, transplant-ineligible patients. Methods and Results — The Jarvik 2000 is a continuous flow device that is implanted in the apex of the left ventricle with offloading to the descending thoracic aorta. Skull-based percutaneous power delivery was derived from cochlear implant technology. We used this system in 4 patients with end-stage dilated cardiomyopathy. Exercise capacity, quality of life, device parameters, and native heart function were monitored serially. One patient died from right heart failure at 3 months. The other patients were discharged from hospital between 3 and 8 weeks postoperatively and are currently New York Heart Association I or II. Follow-up lasted between 9 and 20 months. There has been no device failure or hemolysis. Native heart function and quality of life were markedly improved. Conclusions — The Jarvik 2000 is a true assist (rather than replacement) device that functions synergistically with the native left ventricle and provides excellent quality of life. Adverse events are infrequent. This blood pump may provide a mechanical solution for end-stage heart failure in the community.
Natural History of Asymptomatic Left Ventricular Systolic Dysfunction in the Community
Authors: Thomas J. Wang, Jane C. Evans, Emelia J. Benjamin, Daniel Levy, Elizabeth C. LeRoy, Ramachandran S. Vasan
Journal: Circulation (2003)

Background— Information is limited regarding the rates of progression to congestive heart failure (CHF) and death in individuals with asymptomatic left ventricular systolic dysfunction (ALVD). We sought to characterize the natural history of ALVD, by studying unselected individuals with this condition in the community. Methods and Results— We studied 4257 participants (1860 men) from the Framingham Study who underwent routine echocardiography. The prevalence of ALVD (visually estimated ejection fraction [EF]≤50% without a history of CHF) was 6.0% in men and 0.8% in women. During up to 12 years of follow-up, rates of CHF among subjects with normal left ventricular systolic function (EF &gt;50%, n=4128) and ALVD (n=129) were 0.7 and 5.8 per 100 person-years, respectively. After adjustment for cardiovascular disease risk factors, ALVD was associated with a hazards ratio (HR) for CHF of 4.7 (95% CI 2.7 to 8.1), compared with individuals without ALVD. An elevated risk of CHF after ALVD was observed even in individuals without prior myocardial infarction or valvular disease, with an adjusted HR of 6.5 (CI 3.1 to 13.5). Mild ALVD (EF 40% to 50%, n=78) and moderate-to-severe ALVD (EF &lt;40%, n=51) were associated with adjusted HRs for CHF of 3.3 (CI 1.7 to 6.6) and 7.8 (CI 3.9 to 15.6), respectively. ALVD was also associated with an increased mortality risk (adjusted HR 1.6, CI 1.1 to 2.4). The median survival of ALVD subjects was 7.1 years. Conclusion— Individuals with ALVD in the community are at high risk of CHF and death, even when only mild impairment of EF is present. Additional studies are needed to define optimal therapy for mild ALVD.
Molecular Classification Identifies a Subset of Human Papillomavirus–Associated Oropharyngeal Cancers With Favorable Prognosis
Authors: Paul M. Weinberger, Ziwei Yu, Bruce G. Haffty, Diane Kowalski, Malini Harigopal, Janet Brandsma, Clarence Sasaki, John Joe, Robert L. Camp, David L. Rimm, Amanda Psyrri
Journal: Journal of Clinical Oncology (2006)

Purpose We sought to determine the prevalence of biologically relevant human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC). Retinoblastoma (Rb) downregulation by HPV E7 results in p16 upregulation. We hypothesized that p16 overexpression in OSCC defines HPV-induced tumors with favorable prognosis. Methods Using real-time polymerase chain reaction for HPV16, we determined HPV16 viral load in a cohort of 79 OSCCs annotated with long-term patient follow-up. A tissue microarray including these cases was also analyzed for p53, p16, and Rb utilizing in situ quantitative protein expression analysis. Seventy-seven tumors were classified into a three-class model on the basis of p16 expression and HPV-DNA presence: class I, HPV–, p16 low; class II, HPV+, p16 low; and class III, HPV+, p16 high. Results Sixty-one percent of OSCCs were HPV16+; HPV status alone was of no prognostic value for local recurrence and was barely significant for survival times. Overall survival was improved in class III (79%) compared with the other two classes (20% and 18%; P = .0095). Disease-free survival for the same class was 75% versus 15% and 13% (P = .0025). The 5-year local recurrence was 14% in class III versus 45% and 74% (P = .03). Only patients in class III had significantly lower p53 and Rb expression (P = .017 and .001, respectively). Multivariable survival analysis confirmed the prognostic value of the three-class model. Conclusion Using this system for classification, we define the molecular profile of HPV+ OSCC with favorable prognosis, namely HPV+/p16 high (class III). This study defines a novel classification scheme that may have value for patient stratification for clinical trials testing HPV-targeted therapies.