bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of electrocardiogram signals using internet of things based on combinatory classification
Authors: Masouleh Marzieh Faridi , Kazemi Mohammad Ali Afshar , Alborzi Mahmood , Eshlaghy Abbas Toloie
Published: February 2017

Combination of computer sciences and electronics has resulted in one of the most remarkable technologies of the recent years called internet of things, considered as a challenge in electronic health systems for taking care of patients. Internet of things presents a promising paradigm for management of digital identification in the form of service customization. The effect of internet of things on healthcare is still in its preliminary stages and requires a substantial development. Various equipment and services are developed and utilized for health systems by providing different things to establish communication and information provision to users at any conditions or places. In this paper, attempts have been made to detect electrocardiogram (ECG) signal through a wireless simple sensing network of body using internet of things operating based on classification and feature extraction.
The application of microtextural and heavy mineral analysis to discriminate between storm and tsunami deposits
Authors: Costa Pedro J. M. , Gelfenbaum G. , Dawson S. , La Selle S. , Milne F. , Cascalho J. , Lira C. Ponte , Andrade C. , Freitas M. C. , Jaffe B.
Published: February 2017

Recent work has applied microtextural and heavy mineral analyses to sandy storm and tsunami deposits from Portugal, Scotland, Indonesia and the USA. We looked at the interpretation of microtextural imagery (scanning electron microscopy) of quartz grains and heavy mineral compositions. We consider inundation events of different chronologies and sources (the AD 1755 Lisbon and 2004 Indian Ocean tsunamis, the Great Storm of 11 January 2005 in Scotland, and Hurricane Sandy in 2012) that affected contrasting coastal and hinterland settings with different regional oceanographic conditions. Storm and tsunami deposits were examined along with potential source sediments (alluvial, beach, dune and nearshore sediments) to determine provenance.

Results suggest that tsunami deposits typically exhibit a significant spatial variation in grain sizes, microtextures and heavy minerals. Storm deposits show less variability, especially in vertical profiles. Tsunami and storm quartz grains had more percussion marks and fresh surfaces compared to potential source material. Moreover, in the studied cases, tsunami samples had fewer fresh surfaces than storm deposits.

Heavy mineral assemblages are typically site-specific. The concentration of heavy minerals decreases upwards in tsunamigenic units, whereas storm sediments show cyclic concentrations of heavy minerals, reflected in the laminations observed macroscopically in the deposits.
Effect of a Quality Improvement Program to Improve Guideline Adherence and Attainment of Clinical Standards in Dialysis Care: Report of Outcomes in Year 1
Authors: Youssouf Sajeda , Nache Azri , Wijesekara Chandrakumaran , Middleton Rachel J. , Lewis David , Shurrab Aladdin E. , O'Riordan Edmond , Lappin Lesley P. , O'Donoghue Donal , Kalra Philip A. , Hegarty Janet
Published: February 2017

Background: Best practice in dialysis is synthesised in clear international guidelines. However, a large gap remains between the international guidelines and the actual delivery of care. In this paper, we report outcomes for the first year of a multifaceted dialysis improvement programme in our network. Methods: One year collaborative involving 3 haemodialysis units and a peritoneal dialysis (PD) programme involving 299 dialysis patients. Each unit addressed a different indicator (unit A - catheter-related bloodstream infection [CRBSI], unit B - pre-dialysis blood pressure [BP], unit C - dialysis dose, unit D - anaemia) with a shared aim to match the top 10% in the UK. Tailored multifaceted approaches include a modified collaborative methodology with an aim, framework, driver diagram, learning sessions, facilitated meetings, plan-do-study-act cycles and continuous measurement. Analysis of outcomes, costings, erythropoietin stimulating agent and iron use, and safety culture attributes. Results: Unit A reduced CRBSI from 2.65 to 0.5 per 1,000 catheter days (p = 0.02). Unit B improved attainment of target BP from 37.5 to 67.2% (p = 0.003). Unit C improved attainment of target urea reduction ratio from 75.8 to 91.4% (p = 0.04). PD unit D improved attainment of target haemoglobin from 45.5 to 62.7% (p = 0.01), with no significant change in the indicators in a non-intervention unit. Safety culture attributes improved. Costs associated with admission for fluid overload and infection, erythropoietin, iron and thrombokinase use decreased 36% (£415,620-£264,143). Conclusions: Units that took part in this collaborative improved guideline adherence compared both to their own pre-intervention performance and a non-intervention unit. Such multifaceted interventions are a useful methodology to improve dialysis care.
Low Serum Levels of Vitamin D are Associated with Progression of Subclinical Atherosclerotic Vascular Disease in Peritoneal Dialysis Patients: A Prospective, Multicenter Study
Authors: Pérez Fontán Miguel , Borràs Sans Mercè , Bajo Rubio Maria Auxiliadora , Rodriguez-Carmona Ana , Betriu Angels , Valdivielso José Maria , Fernández Elvira ,   for the NEFRONA Study investigators
Published: February 2017

Background: The prevalence of subclinical atherosclerosis and the main predictors of progression of this condition in patients undergoing peritoneal dialysis (PD) have been insufficiently investigated. Objectives and Method: Following a prospective, multicenter, observational design, we studied 237 patients who were treated with PD for ≥3 months, without any clinical background of cardiovascular (CV) disease. Our objectives were the following: (1) to investigate the prevalence of subclinical atherosclerosis, as compared to a control group of age- and sex-matched healthy individuals, and (2) to disclose PD technique-related predictors of progression of disease during a 24-month follow-up period. We used vascular ultrasound for characterization of subclinical atherosclerotic disease. Main Results: A total of 123 patients (51.9%) vs. 79 controls (33.5%) presented ≥1 carotid plaque, and 114 patients (48.3%) vs. 72 controls (30.5%) ≥1 femoral plaque, at baseline evaluation (p < 0.0005). Progression of disease, either in clinical or ultrasound (new plaques) terms, affected 62.6% of patients. Multivariate analysis identified age, carotid intima-media thickness, presence of ≥1 carotid plaque, and serum levels of 25OH vitamin D and C-reactive protein (CRP) at baseline as independent correlates of progression of atherosclerotic disease. On the contrary, PD technique-related variables did not show any association with this outcome. Conclusions: Atherosclerotic vascular disease is frequent among asymptomatic patients undergoing PD. Older age, pre-existent disease (assessed by vascular ultrasound), and serum levels of 25OH vitamin D and CRP are independent markers of the progression of this condition. These findings may contribute to improve identification of subpopulations with a high risk of CV events, deserving intensified measures of prevention.
Targeting Immunity in End-Stage Renal Disease
Authors: Baragetti Ivano , El Essawy Basset , Fiorina Paolo
Published: February 2017

Background: Despite the stable incidence of end-stage renal disease (ESRD), it continues to be associated with an unacceptably high cardiovascular risk. Summary: ESRD is characterized by enhanced oxidative stress and severe inflammation, which boost cardiovascular risk, thus increasing cardiovascular-associated mortality rate. While substantial effort has been made in the technological innovation of dialytic techniques, few significant advances have been made to reduce inflammation in patients with ESRD. Indeed, this contrasts with the extensive scientific breakthroughs made in the basic field of science in targeting inflammation. There is thus a pressing need for clinical trials to test the effect of reducing inflammation in patients with ESRD. Here, we will revisit the negative effect of ESRD on inflammation and explore the impact of enhanced inflammation on cardiovascular outcomes and survival in patients with ESRD. Finally, we will discuss the need for clinical trials that target inflammation in ESRD, as well as weigh potential disadvantages and offer novel innovative approaches. Key Message: We will try to understand why the issue of inflammation has not been successfully addressed thus far in patients with ESRD, while at the same time weighing the potential disadvantages and offering novel innovative approaches for targeting inflammation in patients with ESRD.
Effect of Race and Ethnicity on Antihypertensive Medication Utilization Among Women in the United States: Study of Women's Health Across the Nation (SWAN)
Authors: Jackson Elizabeth A. , Ruppert Kristine , Derby Carol A. , Lian Yinjuan , Neal‐Perry Genevieve , Habel Laurel A. , Tepper Ping G. , Harlow Siobán D. , Solomon Daniel H.
Published: February 2017

Background

Antihypertensive medication use may vary by race and ethnicity. Longitudinal antihypertensive medication use patterns are not well described in women.

Methods and Results

Participants from the Study of Women's Health Across the Nation (SWAN), a prospective cohort of women (n=3302, aged 42–52), who reported a diagnosis of hypertension or antihypertensive medication use at any annual visit were included. Antihypertensive medications were grouped by class and examined by race/ethnicity adjusting for potential confounders in logistic regression models. A total of 1707 (51.7%) women, mean age 50.6 years, reported hypertension or used antihypertensive medications at baseline or during follow‐up (mean 9.1 years). Compared with whites, blacks were almost 3 times as likely to receive a calcium channel blocker (odds ratio, 2.92; 95%
CI
, 2.24–3.82) and twice as likely to receive a thiazide diuretic (odds ratio, 2.38; 95%
CI
, 1.93–2.94). Blacks also had a higher probability of reporting use of ≥2 antihypertensive medications (odds ratio, 1.95; 95%
CI
, 1.55–2.45) compared with whites. Use of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and thiazide diuretics increased over time for all racial/ethnic groups. Contrary to our hypothesis, rates of β‐blocker usage did not decrease over time.

Conclusions

Among this large cohort of multiethnic midlife women, use of antihypertensive medications increased over time, with angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers becoming the most commonly used antihypertensive medication, even for blacks. Thiazide diuretic utilization increased over time for all race/ethnic groups as did use of calcium channel blockers among blacks; both patterns are in line with guideline recommendations for the management of hypertension.
The Preter-National: The Southeast Asian Contemporary and What Haunts It
Authors: Teh David
Published: February 2017

Southeast Asian modern art has thus far been historicized largely within national historical frameworks. The region's contemporary art has been pulled, sometimes unwillingly, into those national frameworks, even as it enters a global market and takes part in a more transnational dialogue. What is the geography proper to contemporary art? And what insights might a regional perspective afford about art that speaks to a world beyond the nation, but resists outright assimilation under the rubric of ‘the global’? This essay proposes a calibration of three art historical frames – national, regional and international. I argue that far from meaning transcendence of national frames, even where artists intend it, contemporaneity compounds and complicates them. I examine two specific manifestations of contemporaneity, one that emerged at the height of the Cold War in the work of a Sino-Thai modernist, Chang Sae-tang; the other in the broaching of Cold War trauma in art and film of the ‘post-historical’ twenty-first century. Neither ‘contemporary’ can be understood without its respective national framing, but that framing alone proves inadequate for describing the complex histories, subjectivities, and formal choices with which Southeast Asian artists have grappled. If studies of modern art demanded recourse to specific national histories, the study of contemporary art will require no less specific histories of the international.
To Defend the Revolution Is to Defend Culture—but, Which Version?
Authors: Weiss Rachel
Published: February 2017

In tracing the development of Cuban cultural policy between the years of 1959 and 1976, Rebecca Gordon-Nesbitt conceptualizes that history, and its ideas about the role of culture in society, as a potential “antidote” to contemporary, neoliberal policy paradigms. However, in its intense focus on the positions articulated by the revolutionary leadership, her account of that history shortchanges the ideas of those who held critical or opposing views. This review locates Gordon-Nesbitt's approach in the context of debates about early revolutionary cultural policy, and in relation to the current tendency in cultural policy, which thoroughly instrumentalizes creativity and culture.
“The Readiness is All”
Authors: Azize Joseph
Published: February 2017

The most important of Gurdjieff’s still little-known contemplative techniques was the daily exercise his pupils called the “Preparation.” No notes or recordings of a Preparation given by Gurdjieff himself are known to exist. The chief aim of this article is to publish a transcript of the Preparation as given by George M. Adie (1901–1989), according to indications he had received from Gurdjieff. Other personal pupils of Gurdjieff have attested to the accuracy with which Adie passed on the tradition of the Preparation. Further references to the Preparation are examined, clarifying its various aspects. The study closes by tracing the roots of the Preparation in Gurdjieff’s thought, and its almost complete disappearance from the Gurdjieff tradition; a victim, as it were, of close secrecy and a shift in practices in many Gurdjieff groups.
“Turning Ourselves”
Authors: Robertson David G.
Published: February 2017

In 1974, Robert Fripp—leader of the progressive rock group King Crimson—had a spiritual experience in which “the top of [his] head blew off.” He became a student of J. G. Bennett, himself a former student of G. I. Gurdjieff, at Sherborne House in Gloucestershire, and remains a member of the Bennett Foundation to this day. When Fripp returned to the music industry, it was with an approach that favored disciplined and geometric compositions over the jagged improvisation of the earlier period. This article explores the influence of Gurdjieff and Bennett’s teaching upon Fripp and his work, and his apparent attempts to realize the former’s idea of “objective art” through his music. I pay particular attention to the development of Guitar Craft, in which Fripp applies Gurdjieff’s techniques through the teaching of the guitar. I argue that Fripp’s teaching is a little examined scion of the Gurdjieff lineage, and a case study of discrete cultural production.
Self-referral of Situations to the International Criminal Court: Complementarity in Practice – Complementarity in Crisis
Authors: Hassanein Ahmed Samir
Published: February 2017

Self-referral practice has been the main source of cases before the International Criminal Court (icc) to date. This practice provokes significant questions as to its roots, legality and implications on the jurisdiction of the Court in general and the principle of complementarity in particular. Thus, the article, after considering the legal, factual and political considerations attached to self-referral, argues that self-referral, as utilized and encouraged by the icc since its inception, signals a departure of the purposive rationale of the principle of complementarity as the drafting history and the current wording of the Statute reveals, and this could have a detrimental effect on the credibility and impartiality of the Court.
The taxonomic status of Long-tailed shrews (Mammalia: genus Sorex) from Nuclear Central America
Authors: MATSON JOHN O. , ORDÓÑEZ-GARZA NICTÉ
Published: February 2017

We examined 256 specimens of long-tailed shrews (Sorex) from 53 localities throughout the highlands of Nuclear Central America. We evaluate the efficacy of using three qualitative characteristics to identify populations of Sorex from Nuclear Central America: 1) the presence or the absence of a postmandibular foramen and canal; 2) relative size of U3 compared to U4; and, 3) the presence or absence of a pigmented ridge on the lingual side of each unicuspid tooth. In our data, the first character is invariable for the specimens we examined. Two species groups can be recognized based on the presence (S. salvini species group) or the absence of a postmandibular foramen and canal (S. veraepacis species group). The other two characteristics were useful, but not diagnostic. Based upon Principal Component Analysis we recognize nine species of Sorex in Nuclear Central America. Five species belong to the S. salvini species group: S. cristobalensis, S. salvini, S. sclateri, S. stizodon, and a new species from Honduras. Four species belong to the S. veraepacis species group: S. chiapensis, S. ibarrai, S. veraepacis, and a new species from western Guatemala. We also present evidence that the type locality (Cobán, Alta Verapaz, Guatemala) for S. veraepacis is not correct.
Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature
Authors: Ende-Verhaar Yvonne M. , Cannegieter Suzanne C. , Vonk Noordegraaf Anton , Delcroix Marion , Pruszczyk Piotr , Mairuhu Albert T.A. , Huisman Menno V. , Klok Frederikus A.
Published: February 2017

The incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is relevant for management decisions but is currently unknown.

We performed a meta-analysis of studies including consecutive PE patients followed for CTEPH. Study cohorts were predefined as “all comers”, “survivors” or “survivors without major comorbidities”. CTEPH incidences were calculated using random effects models.

We selected 16 studies totalling 4047 PE patients who were mostly followed up for >2-years. In 1186 all comers (two studies), the pooled CTEPH incidence was 0.56% (95% CI 0.1–1.0). In 999 survivors (four studies) CTEPH incidence was 3.2% (95% CI 2.0–4.4). In 1775 survivors without major comorbidities (nine studies), CTEPH incidence was 2.8% (95% CI 1.5–4.1). Both recurrent venous thromboembolism and unprovoked PE were significantly associated with a higher risk of CTEPH, with odds ratios of 3.2 (95% CI 1.7–5.9) and 4.1 (95% CI 2.1–8.2) respectively. The pooled CTEPH incidence in 12 studies that did not use right heart catheterisation as the diagnostic standard was 6.3% (95% CI 4.1–8.4).

The 0.56% incidence in the all-comer group probably provides the best reflection of the incidence of CTEPH after PE on the population level. The ∼3% incidences in the survivor categories may be more relevant for daily clinical practice. Studies that assessed CTEPH diagnosis by tests other than right heart catheterisation provide overestimated CTEPH incidences.
CEOP-IMVP-Dexa in the treatment of aggressive lymphomas: an Austrian multicenter trial.
Authors: Fridrik M A , Hausmaninger H , Linkesch W , Stöger M , Sill H , Neubauer M , Seewann H L , Klocker J , Haidinger R , Schiller L , Pont J , Raudaschl G , Falk M , Radaszkiewicz T
Published: February 2017

PURPOSE

This trial evaluated the efficacy, toxicity, and practicability of a new intensive chemotherapy regimen in a multicenter setting of university and community hospitals.

PATIENTS AND METHODS

We tested a hybrid protocol of two non-cross-resistant regimens, cyclophosphamide, epirubicin, vincristine, and prednisolone (CEOP) and ifosfamide, etoposide (VP-16), methotrexate, and dexamethasone (IMVP-Dexa) given every fourth week, three to six times according to response, in patients with untreated intermediate- and high-grade non-Hodgkin's lymphoma. Ten Austrian centers entered 81 patients onto this multicenter trial. Eleven patients were excluded. The median age was 55 years. Twenty-six of 70 patients had stage III or IV disease. The distribution among international risk categories low, intermediate-low, intermediate-high, and high was 20%, 34%, 23%, and 23%, respectively.

RESULTS

Of 70 eligible patients, 56 (80%) had a complete remission and seven (10%) a partial remission. After a median observation time of 36 months, the estimated time to relapse and overall survival rates are 67% and 72%, respectively. Age and Karnofsky index were the only independent risk factors for survival. Toxicity was primarily hematologic, with a median granulocyte nadir of 0.56 x 10(9)/L. Sixty-seven percent of patients had infections; 25.7% were severe World Health Organization (WHO) grade III or IV. There were three treatment-related deaths.

CONCLUSION

CEOP-IMVP-Dexa chemotherapy is safe and feasible on a groupwide basis even when used in community hospitals. Neutropenic infections are the major complications. A 72% 3-year survival rate in patients with intermediate- and high-grade non-Hodgkin's lymphoma warrants further studies. These data are the basis for a randomized trial to compare cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with CEOP/IMVP-Dexa.
Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.
Authors: Winter J N , Lazarus H M , Rademaker A , Villa M , Mangan C , Tallman M , Jahnke L , Gordon L , Newman S , Byrd K , Cooper B W , Horvath N , Crum E , Stadtmauer E A , Conklin E , Bauman A , Martin J , Goolsby C , Gerson S L , Bender J , O'Gorman M
Published: February 2017

PURPOSE

To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs).

MATERIALS AND METHODS

Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest.

RESULTS

The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001).

CONCLUSION

Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.
Role of interstitial radiotherapy in the management of clinically organ-confined prostate cancer: the jury is still out.
Authors: D'Amico A V , Coleman C N
Published: February 2017

PURPOSE AND DESIGN

To discuss the evolution of the use of brachytherapy in the treatment of clinically organ-confined prostate cancer and to review modern techniques, results of therapy, and optimal patient selection criteria.

RESULTS

Using modern localization and immobilization techniques, interstitial prostate radiotherapy for patients with a prostate-specific antigen (PSA) level less than 10 ng/mL yields an at least 87% rate of freedom from biochemical relapse at 3 years, which is numerically equivalent to results achieved with external-beam radiotherapy or radical prostatectomy. With a minimum median follow-up time of 24 months, 81% to 85% (2-year actuarial and 3-year crude) potency rates have been reported concomitant with 2-year actuarial rates of 12% for grade > or = 2 rectal complications and 10% for grade > or = 3 urethral complications.

CONCLUSION

The combination of clinical stage, PSA level, and biopsy Gleason sum allows for selection of patients with the highest probability of having all of the prostate cancer encompassed by the high-dose implant volume, while simultaneously respecting the normal-tissue tolerance doses of the juxtaposed normal tissues (rectum and bladder). In particular, patients with nonpalpable (T1c) lesions, a biopsy Gleason sum < or = 6 (ideally < or = 4), and a PSA level less than 10 ng/mL represent the optimal implant candidates. Differential loading of the implant away from the geometric center and not accepting patients with large prostate glands (> or = 60 cm3) or history of a transurethral resection of the prostate (TURP) as implant candidates, may reduce urethral toxicity. Further follow-up evaluation of prostate cancer patients treated with interstitial radiotherapy will verify if favorable potency preservation rates and rates of freedom from biochemical failure equivalent to those achieved with radical prostatectomy or external-beam radiation therapy are maintained.
Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: an Eastern Cooperative Oncology Group study.
Authors: Cole B F , Gelber R D , Kirkwood J M , Goldhirsch A , Barylak E , Borden E
Published: February 2017

PURPOSE

To evaluate the quality-of-life effects of adjuvant high-dose interferon alfa-2b (IFN alpha 2b) treatment of high-risk melanoma.

PATIENTS AND METHODS

A quality-of-life-adjusted survival analysis (Quality-Adjusted Time Without Symptoms, and Toxicity [Q-TWiST]) was applied to the Eastern Cooperative Oncology Group Trial E1684, which compared high-dose IFN alpha 2b treatment for 1 year versus observation in 280 high-risk patients. IFN alpha 2b was administered at a dosage of 20 mU/m2 intravenously daily for 5 days per week for 4 weeks, and then three times weekly at 10 mU/m2 subcutaneously for 48 weeks.

RESULTS

After 84 months of median follow-up time, the IFN alpha 2b group gained a mean of 8.9 months without disease relapse (P = .03) and 7.0 months of overall survival (P = .07) as compared with the observation group, but had severe treatment-related toxicity for 5.8 months, on average. The IFN alpha 2b group had more quality-of-life-adjusted time than the observation group regardless of the relative valuations placed on time with toxicity (Tox) and time with relapse (Rel). This gain was significant (P < .05) for patients who consider Tox to have a high relative value and Rel to have a low relative value. In contrast, for patients who value Tox about the same as Rel, the quality-adjusted gain for IFN alpha 2b was not statistically significant. An analysis stratified according to tumor burden indicated that the benefit of IFN alpha 2b was greatest in the node-positive strata.

CONCLUSION

For patients with high-risk melanoma, the clinical benefits of high-dose IFN alpha 2b can offset the toxic effects. The optimal treatment for an individual patient depends on the patient's tumor burden and preferences regarding toxicity and disease relapse.
Fluorouracil and leucovorin with or without interferon alfa-2b in advanced colorectal cancer: analysis of a prospective randomized phase III trial. Hellenic Cooperative Oncology Group.
Authors: Kosmidis P A , Tsavaris N , Skarlos D , Theocharis D , Samantas E , Pavlidis N , Briassoulis E , Fountzilas G
Published: February 2017

PURPOSE

To investigate if double modulation of fluorouracil (5-FU) with leucovorin (folinic acid [FA]) and interferon alfa-2b (IFN 2b) improves responses and survival in comparison to single modulation of 5-FU with FA.

PATIENTS AND METHODS

One hundred six patients with histologically confirmed advanced colorectal cancer, measurable disease, and without previous chemotherapy were prospectively randomized into two groups. Patients in group A received 5-FU 450 mg/m2 as an intravenous bolus in the midinfusion of FA weekly. FA was given at a dose of 200 mg/m2 in 500 mL 0.9% normal saline solution in 2-hour infusion. Patients in group B received exactly the same regimen plus IFN 2b 5 million units subcutaneously three times weekly.

RESULTS

All patients were well balanced in both groups regarding age, sex, performance status, number, and site of metastasis. One hundred two patients were assessable. All patients have died. There was no difference in response between the two groups (7.8% v 9.8%). Median survival was 10.1 months in group A, and 7.2 months in group B (P = .00189). Median time to progression was 8.4 and 5.2 months, respectively (P = .00196). Overall, better performance status and older age had a positive impact on survival. Toxicity was the most important and catastrophic aspect of this study. Patients who received IFN 2b had significantly worse anemia, neutropenia, diarrhea, anorexia, weight loss, flu-like syndrome, and psychological reactions.

CONCLUSION

Based on this final analysis, the addition of IFN 2b to the combination of 5-FU and FA enhances toxicity and contributes to decreased survival.
The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study.
Authors: Sprangers M A , Groenvold M , Arraras J I , Franklin J , te Velde A , Muller M , Franzini L , Williams A , de Haes H C , Hopwood P , Cull A , Aaronson N K
Published: February 2017

PURPOSE

To construct a breast cancer-specific quality-of-life questionnaire (QLQ) module to be used in conjunction with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and to test its reliability and validity cross-culturally.

PATIENTS AND METHODS

Module construction took place after the EORTC guidelines for module development. The module--the QLQ-BR23--consists of 23 items covering symptoms and side effects related to different treatment modalities, body image, sexuality, and future perspective. This module was tested in 170 Dutch, 168 Spanish, and 158 American cancer patients at two points in time. The timing for the Dutch and Spanish patients was before and during treatment with radiotherapy or chemotherapy. For the American patients, the questionnaire was administered at admission at the breast clinic and 3 months after the first assessment.

RESULTS

Multitrait scaling analysis confirmed the hypothesized structure of four of the five scales. Cronbach's alpha coefficients were, in general, lowest in Spain (range; .46 to .94) and highest in the United States (range; .70 to .91). On the basis of known-groups comparisons, selective scales distinguished clearly between patients differing in disease stage, previous surgery, performance status, and treatment modality, according to expectation. Additionally, selective scales detected change over time as a function of changes in performance status and treatment-induced change.

CONCLUSION

These results lend support to the clinical and cross-cultural validity of the QLQ-BR23 as a supplementary questionnaire for assessing specific quality-of-life issues relevant to patients with breast cancer.
Peripheral blast counts at diagnosis of late isolated bone marrow relapse of childhood acute lymphoblastic leukemia predict response to salvage chemotherapy and outcome. Berlin-Frankfurt-Münster Relapse Study Group.
Authors: Bührer C , Hartmann R , Fengler R , Rath B , Schrappe M , Janka-Schaub G , Henze G
Published: February 2017

PURPOSE

In newly diagnosed childhood acute lymphoblastic leukemia (ALL), a high tumor burden indicates a poor prognosis, while no such link has been established yet after relapse. The impact of the absolute peripheral blast count (PBC) at the time of relapse on the response to salvage chemotherapy after a late isolated bone marrow (BM) relapse is the subject of this prospective analysis.

PATIENTS AND METHODS

Since 1983, 260 children with a first isolated BM relapse of ALL that occurred 6 months or later after elective cessation of front-line therapy were enrolled onto four consecutive multicenter trials of the Berlin-Frankfurt-Münster (BFM) Relapse Study Group. All patients received intensive multiagent induction and consolidation chemotherapy for 6 months, followed by maintenance therapy with methotrexate (MTX) and thioguanine for 2 years. Treatment of subclinical meningeal leukemia consisted of high-dose intravenous MTX and intrathecally administered cytostatic drugs, which was augmented by cranial irradiation since 1988.

RESULTS

At the time relapse was diagnosed, PBC varied considerably among patients (median, 1,060/microL; range, 0 to 106,800/microL). Achievement of a second complete remission (CR) was not significantly different in children without detectable circulating blasts at relapse (37 of 38) and those with moderate (1 to 9,999/microL) PBC (165 of 171). In contrast, only 42 of 51 children with high PBC (> or = 10,000/microL) achieved a second CR (P = .0015). At a median follow-up time of 40 months, the 10-year event-free survival (EFS) probability was significantly (P = .0001) higher in children without circulating blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There was a preponderance of boys in the group without detectable circulating blasts, while the three PBC-defined groups did not differ with respect to frontline treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage treatment protocol. On sequential univariate and multivariate analysis, only duration of first remission > or = 48 months was an additional independent indicator of adverse prognosis, while preventive cranial irradiation improved outcome independently of PBC.

CONCLUSION

The absence of blasts on peripheral-blood smears at the time of a first late isolated BM relapse of childhood ALL is associated with a favorable response and prognosis in chemotherapy-treated children, who should be regarded as ineligible for bone marrow transplantation (BMT) unless a second round of chemotherapy has failed to produce a response.
Adjuvant radiation versus observation: a cost analysis of alternate management schemes in early-stage testicular seminoma.
Authors: Sharda N N , Kinsella T J , Ritter M A
Published: February 2017

PURPOSE

This study was designed to compare costs of adjuvant radiation versus observation in the management of early-stage testicular seminoma after inguinal orchiectomy.

MATERIALS AND METHODS

A line-by-line inspection of the charges generated during a course of adjuvant pelvic and paraaortic radiotherapy and of three cycles of bleomycin, etoposide, and platinum salvage chemotherapy was performed for five patients who received irradiation and five patients who received salvage chemotherapy. The average charge for either treatment was then calculated. Only those charges directly associated with the diagnosis of seminoma were included in the analysis. Follow-up charges were also generated from the patients' billing records. The optimum follow-up regimen for either management option was derived from a synthesis of the international literature. A 5% rate of failure was assumed if adjuvant irradiation was administered, and a 15% rate of failure was assumed if observation was the option chosen. Charges were truncated at 5 years.

RESULTS

The total charge generated over 5 years based on following a policy of observation is $27,223 per patient versus $19,557 if the option of adjuvant irradiation in chosen. Using University of Wisconsin institutional reimbursement rates, the estimated costs were $20,487 and $14,722 for the option of observation and adjuvant radiation, respectively. The cost equivalence point between the two options occurs at 2.5 years, when the initial cost of adjuvant radiotherapy is matched by the cost generated during the period of observation. The maximum cost difference is achieved by 5 years.

CONCLUSION

Following a policy of observation postorchiectomy for early-stage testicular seminoma generates 39% more medical costs per patient over a 5-year follow-up period than does following the standard policy of adjuvant irradiation to the pelvic and paraaortic regions, with no reported difference in outcome.
Impact of preexisting CNS involvement on the outcome of bone marrow transplantation in adult hematologic malignancies.
Authors: van Besien K , Przepiorka D , Mehra R , Giralt S , Khouri I , Gajewski J , Andersson B , Champlin R
Published: February 2017

PURPOSE

To determine the impact of prior or current CNS disease on the outcome of high-dose chemotherapy for patients with hematologic malignancies.

PATIENTS AND METHODS

In a 54-month period, 373 patients with hematologic malignancies underwent allogeneic or autologous bone marrow transplantation (BMT) or blood stem-cell transplantation using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen. Four patients with active CNS disease at BMT and 20 patients with a history of prior CNS disease were identified. The outcomes of those with a history of CNS disease were compared with those of a matched control group.

RESULTS

Of four patients with active CNS disease at the time of BMT, two had CNS recurrences and one recurred in the bone marrow. One patient died of treatment-related toxicity. Four of 20 patients with prior CNS involvement currently remain free of disease. At 2 years, the disease-free survival (DFS) rate was 23% +/- 19%, and the DFS rate for the control group 39% +/- 24% (P = .053). An increased rate of treatment-related toxicity and especially grades II to IV CNS toxicity accounted for the poorer outcome of patients who had a history of CNS disease. Recurrence rates were not significantly different between the two groups. Prior radiation to the CNS correlated with CNS complications posttransplant (p = .01).

CONCLUSION

Consolidation with TBC and BMT can induce prolonged DFS in a proportion of patients with a history of CNS disease. Such patients are at increased risk for CNS complications that lead to an inferior overall outcome when compared with a control group.
Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study.
Authors: Creemers G J , Bolis G , Gore M , Scarfone G , Lacave A J , Guastalla J P , Despax R , Favalli G , Kreinberg R , Van Belle S , Hudson I , Verweij J , Ten Bokkel Huinink W W
Published: February 2017

PURPOSE

Topotecan is a topoisomerase I inhibitor with preclinical activity against various tumor types. We conducted a large multicenter phase II study with topotecan in ovarian cancer in patients who had failed to respond to one prior cisplatin-based chemotherapeutic regimen.

PATIENTS AND METHODS

Topotecan 1.5 mg/m2/d was administered intravenously by 30-minute infusion for 5 days repeated every 3 weeks. As the cisplatin-free interval relates to response in subsequent treatment, patients were stratified in subgroups, ie, cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive.

RESULTS

One-hundred eleven patients entered the study. Nineteen patients were considered to be ineligible; 92 patients were assessable for response. A total of 552 courses were given (median, four per patient; range, one to 17). The major toxicities were leukocytopenia and neutropenia, which were grade 3 to 4 in 54.2% and 69.1% of courses, respectively, but with only 4.3% of these being grade 4 neutropenia plus fever or infectious complications. Prophylactic granulocyte colony-stimulating factor (G-CSF) was given in 20.5% of courses to maintain dose-intensity. Other relatively frequent side effects were alopecia (82%), nausea (36.4%), and vomiting (17.5%). The overall response rate was 16.3%, with one complete response (CR) and 14 partial responses (PRs). In the cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive strata, the response rates were 5.9%, 17.8%, and 26.7%, respectively. The median duration of time of documented response was 21.7 weeks (range, 4.6 to 41.9).

CONCLUSION

Topotecan in a daily-times-five schedule is an effective regimen as second-line treatment in ovarian cancer. Further investigations of topotecan in ovarian cancer, including first-line use and combination with other active agents, are indicated.
Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms.
Authors: Dieckmann K P , Loy V
Published: February 2017

PURPOSE

Testicular intraepithelial neoplasia ([TIN], so-called carcinoma in situ of the testis) is hypothesized to be the precursor of testicular germ cell neoplasms. According to previous studies, it can be detected by testicular biopsy. Since patients with a unilateral testicular tumor are at high risk of a second testicular tumor, it seemed feasible to examine the prevalence of contralateral TIN in patients with testicular germ cell cancer and correlate it with the known prevalence of bilateral testicular tumors. The aim was to provide more evidence for the role of TIN as the preinvasive stage of testicular cancer.

PATIENTS AND METHODS

Nineteen hundred fifty-four consecutive patients with a unilateral testicular germ cell tumor underwent contralateral biopsy. All specimens were examined immunohistologically.

RESULTS

TIN was observed in 4.9% (95% confidence interval [CI], 3.95% to 5.91%). Testicular atrophy and a history of undescended testis were more frequently observed in patients with contralateral TIN, but only atrophy was shown to be independently associated by multivariate analysis. Patients with testicular atrophy have a 4.3-fold increased risk of having contralateral TIN. Sixty-four percent of TIN cases were found in normal testes. Patients with TIN were significantly younger than those without (P < .0017). Three patients developed a second testicular tumor despite a negative biopsy for TIN.

CONCLUSION

The prevalence of contralateral TIN corresponds well to the known prevalence of bilateral testicular tumors. Testicular atrophy is a strong indicator for the presence of TIN, but approximately 60% of TIN cases occur without atrophy. The present data are in accordance with the theory that TIN is an early step in the histogenesis of testicular germ cell neoplasms.
Vinblastine, bleomycin, and methotrexate chemotherapy plus extended-field radiotherapy in early, favorably presenting, clinically staged Hodgkin's patients: the Gruppo Italiano per lo Studio dei Linfomi Experience.
Authors: Gobbi P G , Pieresca C , Frassoldati A , Carotenuto M , Di Renzo N , La Sala A , Berté R , Avanzini P , Federico M , Silingardi V , Ascari E
Published: February 2017

PURPOSE

To ascertain whether vinblastine, bleomycin, and methotrexate (VBM) (CT) combined with extended-field radiotherapy (EF RT) is effective enough to spare laparotomy in early, favorably presenting Hodgkin's disease (HD) patients.

PATIENTS AND METHODS

Fifty patients with clinical stage IA or IIA HD with favorable histology and no bulky masses entered a prospective multicenter study started in January 1988. The median follow-up time was 38 months.

RESULTS

All patients achieved a complete remission (CR). Five relapsed after 3 to 40 months and underwent successful salvage therapy. The actuarial remission rate was 0.89% at 3 years and 0.82% at 5 years. Two patients died in CR: one of severe pulmonary toxicity, the other of a second neoplasia (adenocarcinoma of the lung), 2 and 43 months after the end of therapy, respectively. The hematologic toxicity recorded during VBM CT was mild on the whole. Major toxicity was represented by pulmonary side effects and neurologic symptoms. Multiple regression analysis demonstrated that pulmonary toxicity was significantly related only to the amount of RT delivered to the mediastinum and not to the relative dose of bleomycin, to the dose-intensities of the three drugs in the regimen, or to patient age or sex. The same statistical technique showed that the only clinical factor related to grade of neurotoxicity was vinblastine dosage.

CONCLUSION

VBM CT combined with EF RT is an effective treatment for early, clinically staged, favorable HD patients. However, the toxicity of this combination suggests that certain modifications should be evaluated.
Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma.
Authors: Travis L B , Weeks J , Curtis R E , Chaffey J T , Stovall M , Banks P M , Boice J D
Published: February 2017

PURPOSE

Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae.

PATIENTS AND METHODS

A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed.

RESULTS

Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively.

CONCLUSIONS

Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years.