tbuckley/cabot-search huggingface dataset:
Pharmacoeconomic study of stable COPD in Northern Greece
Authors: Dionisios Spyratos, Diamantis Chloros, Dionisia Mihalopoulou, Lazaros Sichletidis
Journal: European Respiratory Journal (2014)

Aim: To investigate if the current financial burden of inhaled drugs for stable COPD differs from the ideal cost according to GOLD guidelines.  Methods: During a 2 year period (1/2/2012-31/1/2014) we examined subjects (age >40 years, current/former smokers, excluding asthmatics) of the general population in Northern Greece after invitation with advertisement posters in collaboration with GPs. We identified three subgroups: correct diagnosis for COPD (I), underdiagnosis (II) and overdiagnosis (III, those who had a medical diagnosis of COPD and received inhaled drugs for > 1 year while their current spirometry was within normal limits). We considered ideal treatment the recommended first or alternative pharmacological choices of GOLD guidelines distributed to equal percentages across patients.  Results: We examined 2,662 subjects (mean age: 61.1±13.4 years, 67.5% males) of whom 308 were diagnosed with COPD (11.6 %). 90 out of 271 subjects with overdiagnosis were treated at the time of the study. Table 1. shows that the current annual cost was 37,456 € more than the ideal cost. Calculating the excess expenditure per patient per year for those with correct diagnosis was 353 € for stage A, 228 € for stage B and 327 € for stages C+D.  Conclusion: Direct economic burden of COPD is much more than the ideal cost if GOLD guidelines were strictly incorporated in everyday clinical practice.
Antitumor Activity of Tilorone Hydrochloride Against Some Rodent Tumors: Preliminary Report
Authors: Richard H. Adamson
Journal: JNCI Journal of the National Cancer Institute (1971)

Tilorone hydrochloride, a synthetic small molecular-weight inducer of interferon, had antitumor activity against Walker carcinosarcoma 256 and the reticulum cell sarcoma A-RCS in rodents. Tilorone hydrochloride was inactive when tested in several other rodent tumors including leukemias L1210 and P388. Tilorone hydrochloride also had cytotoxic activity in vitro against Walker carcinosarcoma 256, leukemia L5178Y, and the Novikoff hepatoma. In addition, the antitumor activity of tilorone hydrochloride and poly I · poly C in 3 rodent tumors was compared.
Production of the RANTES chemokine in delayed-type hypersensitivity reactions: involvement of macrophages and endothelial cells.
Authors: O Devergne, A Marfaing-Koka, T J Schall, M B Leger-Ravet, M Sadick, M Peuchmaur, M C Crevon, K J Kim, T T Schall, T Kim
Journal: The Journal of Experimental Medicine (1994)

To understand the selective accumulation of memory T helper lymphocytes and of macrophages in delayed-type hypersensitivity (DTH) granulomas, we studied the in situ production of RANTES, a chemokine initially characterized on the basis of its in vitro chemotactic properties for each of these cell populations. RANTES gene expression was studied by in situ hybridization in 15 human lymph nodes presenting typical DTH lesions related to either sarcoidosis or tuberculosis. A positive signal was detected in all cases. Labeling was specific for the DTH lesions, as very few if any positive cells were detected in the normal residual lymphoid tissue surrounding them or in reactive lymph nodes involved in a B lymphocyte response. RANTES gene expression was associated with the production of the protein, which was detected by immunochemistry in DTH lymph nodes. The morphological characteristics and distribution of positive cells in in situ hybridization and immunochemical experiments indicated that macrophages and endothelial cells, two cell populations not previously reported to produce RANTES, contributed to its production in DTH reactions. The ability of macrophages and endothelial cells to produce RANTES was confirmed by in vitro studies with alveolar macrophages and umbilical vein endothelial cells. In view of the chemotactic properties of RANTES for a limited range of cell populations, these results suggest that RANTES production in DTH granulomas may play a role in the selective accumulation of macrophages and memory T helper lymphocytes characterizing this type of cell-mediated immune reaction, and that macrophages and endothelial cells are involved in this production.
Combinatorial Immunoprofiling in Latent Tuberculosis Infection. Toward Better Risk Stratification
Authors: Patricio Escalante, Tobias Peikert, Virginia P. Van Keulen, Courtney L. Erskine, Cathy L. Bornhorst, Boleyn R. Andrist, Kevin McCoy, Larry R. Pease, Roshini S. Abraham, Keith L. Knutson, Hirohito Kita, Adam G. Schrum, Andrew H. Limper
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Most immunocompetent patients diagnosed with latent tuberculosis infection (LTBI) will not progress to tuberculosis (TB) reactivation. However, current diagnostic tools cannot reliably distinguish nonprogressing from progressing patients a priori, and thus LTBI therapy must be prescribed with suboptimal patient specificity. We hypothesized that LTBI diagnostics could be improved by generating immunomarker profiles capable of categorizing distinct patient subsets by a combinatorial immunoassay approach.A combinatorial immunoassay analysis was applied to identify potential immunomarker combinations that distinguish among unexposed subjects, untreated patients with LTBI, and treated patients with LTBI and to differentiate risk of reactivation.IFN-γ release assay (IGRA) was combined with a flow cytometric assay that detects induction of CD25(+)CD134(+) coexpression on TB antigen-stimulated T cells from peripheral blood. The combinatorial immunoassay analysis was based on receiver operating characteristic curves, technical cut-offs, 95% bivariate normal density ellipse prediction, and statistical analysis. Risk of reactivation was estimated with a prediction formula.Sixty-five out of 150 subjects were included. The combinatorial immunoassay approach identified at least four different T-cell subsets. The representation of these immune phenotypes was more heterogeneous in untreated patients with LTBI than in treated patients with LTBI or unexposed groups. Patients with IGRA(+) CD4(+)CD25(+)CD134(+) T-cell phenotypes had the highest estimated reactivation risk (4.11 ± 2.11%).These findings suggest that immune phenotypes defined by combinatorial assays may potentially have a role in identifying those at risk of developing TB; this potential role is supported by risk of reactivation modeling. Prospective studies will be needed to test this novel approach.
Consultant contracts in England: how many SPAs do you have?
Authors: Timothy Barlow, David Barlow, Alison Edwards
Journal: BMJ (2012)

Tim Barlow and colleagues ask how consultants spend their time on the job

Supporting professional activities (SPAs) are written into consultant contracts to offer time for “teaching, training, education, CPD [continuing professional development] (including reading journals), audit, appraisal, research, clinical management, clinical governance, service development etc.”[1] This is time that is considered necessary to maintain and improve the overall level of service within the NHS.[1] [2]
Coexistence of central diabetes insipidus and salt wasting
Authors: S Laredo, K Yuen, B Sonnenberg, M L Halperin
Journal: Journal of the American Society of Nephrology (1996)

Both central diabetes insipidus (DI) and a high rate of excretion of sodium (Na) and chloride (Cl) contributed to the development of polyuria and dysnatremia in two patients during the acute postoperative period after neurosurgery. To minimize difficulties in diagnosis and projections for therapy, two available (but not often used) clinical tools were helpful. First, the osmole excretion rate early on revealed the co-existence of central DI and an osmotic diuresis. The osmoles excreted were largely Na salts; after antidiuretic hormone acted, this electrolyte diuresis caused the urine flow rate to be much higher than otherwise anticipated. Interestingly, part of this saline diuresis occurred when the extracellular fluid volume was contracted. The tool to explain the basis for the dysnatremias was a tonicity balance. Hypernatremia, which developed before treatment of central DI, was primarily a result of a positive balance for Na rather than a large negative balance for water. Moreover, hyponatremia that developed once antidiuretic hormone acted was primarily a result of a negative balance for Na; the urine volume was large and its Na concentration was hypertonic. To prevent a further decline in the plasma Na concentration, either the Na concentration in the urine should be decreased by provision of urea or a loop diuretic while replacing all unwanted water and electrolyte losses; alternatively, the fluid infused should have a similar Na concentration and volume as the urine (infuse hypertonic saline).
Utility of Endosonographic Mediastinal Lymph Node Staging in Lung Cancer, Withdrawal of Inhaled Steroids in Chronic Obstructive Pulmonary Disease, and Use of Mepolizumab in Severe Eosinophilic Asthma
Authors: Jad Harb, MaryEllen Antkowiak, Sivajothi Kanagalingam
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
CAT (COPD assessment test) as outcome parameter of pulmonary rehabilitation (PR) in COPD
Authors: Konrad Schultz, Oliver Göhl, Dragan Stojanovic, Michael Wittmann, Juliane Rudnik, Monika Schwarze
Journal: European Respiratory Journal (2011)

Background:  The COPD Assessment Test (CAT) is a newly developed questionnaire for COPD-patients. The CAT is designed to measure the impact of COPD on a patient9s life, and how this changes over the time. The test contains 8 items.   Methods:  In a prospective observational study 124 patients with COPD were included, 71.6% male, 45.2% with GOLD Stage 1-2, 26.6% with stage 3, 28.2% with stage 4. Mean FEV1 was 1.66 l. Outcome parameters were 6-MWD, FEV1, MRC-dyspnoea scale and in addition the CAT was used for the first time in Germany as an outcome parameter in PR.   Results:  Mean CAT score at admission (T0) was 21.97±6.49 and at discharge from PR (T1) 18.94±7,56 (p   Conclusions:  In this prospective observational study all COPD-patients were included, regardless of comorbidity or exacerbations. In spite of these circumstances there was a statistically significant and clinically relevant improvement. More than 50% of the patients improved the CAT score for at least 2 points (MCID). The test was answered by our patients without relevant problems and so, since July 2010, the CAT is used as a routine outcome parameter in our PR program.
Very-high-dose short-term chemotherapy for poor-risk peripheral primitive neuroectodermal tumors, including Ewing's sarcoma, in children and young adults.
Authors: B H Kushner, P A Meyers, W L Gerald, J H Healey, M P La Quaglia, P Boland, N Wollner, E S Casper, A Aledo, G Heller
Journal: Journal of Clinical Oncology (1995)

PURPOSE To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV). PATIENTS AND METHODS This report concerns previously untreated patients with newly diagnosed pPNET deemed poor-risk because of a tumor volume more than 100 cm3 or metastases to bone or bone marrow. The P6 protocol consists of seven courses of chemotherapy. Courses 1, 2, 3, and 6 include 6-hour infusions of cyclophosphamide on days 1 and 2 for a total of 4,200 mg/m2 per course (140 mg/kg per course for patients &lt; 10 years old), plus 72-hour infusions of doxorubicin 75 mg/m2 and vincristine 2.0 mg/m2 beginning on day 1 (HD-CAV). Courses 4, 5, and 7 consist of 1-hour infusions of ifosfamide 1.8 g/m2/d and etoposide (VP-16) 100 mg/m2/d, for 5 days. Granulocyte colony-stimulating factor (G-CSF) and mesna are used. Courses start after neutrophil counts reach 500/microL and platelet counts reach 100,000/uL. Surgical resection follows course 3 and radiotherapy follows completion of all chemotherapy. RESULTS Among the first 36 consecutive assessable patients (median age, 17 years), HD-CAV achieved excellent histopathologic or clinical responses in 34 patients and partial responses (PRs) in two patients. For 24 patients with locoregional disease, the 2-year event-free survival rate was 77%; adverse events were two locoregional relapses, one distant relapse, and one secondary leukemia. All six patients with metastatic disease limited to lungs achieved a complete response (CR) and did not relapse; one is in remission 36+ months from diagnosis, but the other patients are not assessable in terms of long-term efficacy of the P6 protocol because of short follow-up time (n = 3), additional systemic therapy (bone marrow transplantation), or septic death (autopsy showed no residual pPNET). All six patients with widespread metastases had major responses, including eradication of extensive bone marrow involvement, but distant relapses ensued. Myelosuppression was severe, but most patients received the first three courses of HD-CAV within 6 to 7 weeks. Major nonhematologic toxicities were mucositis and peripheral neuropathy. CONCLUSION Excellent antitumor efficacy and manageable toxicity support the dose-intensive use of HD-CAV for pPNET in children, as well as in young adults. Consolidation of remissions of pPNET metastatic to bone and bone marrow remains a therapeutic challenge.
Preliminary results of noninvasive ventilation during a pulmonary rehabilitation program in patients with COPD
Authors: Kris M.H. Ides, Lieve De Backer, Denise Daems, Erwin Boelen, Glenn Leemans, Dirk Vissers, Wilfried De Backer
Journal: European Respiratory Journal (2012)

Introduction   Exercise training at higher intensities seems to result in a better training effect. However, in some patients with COPD this intensity is limited due to decreased ventilatory pump capacity. Noninvasive ventilation (NIV) relieves the work of breathing, so higher intensities are reached and could result in a better exercise tolerance.   Objective   Analysis of the effects of Bi-pap during an exercise training program in COPD on lung function and maximal exercise capacity.   Methods 8 patients were randomized in a NIV (n=5) or control group (n=3). Patients trained with or without NIV for a period of 6 weeks. Lungfunction and exercise tests were taken before and after 6 weeks. NIV was set on I/E pressure of 8/4 and 1 or 2 leakage valves were added for patients comfort.   Results   Ventilation at maximal tolerated load (VE max) changed significantly in the experimental group and did not reach significance in the control group compare to baseline (p=0.043). In the same test setting there was no significant drop in heart rate.   Conclusions   Noninvasive ventilation during exercise training may change ventilation at maximal tolerated load and heart rate after 6 weeks. This allows patients to train at a higher level and achieve better training results because of a better ventilatory adaption during exercise.
Randomised controlled trials: understanding power
Authors: P. Sedgwick
Journal: BMJ (2015)

The effects of manual lymph drainage on the development of lymphoedema related to breast cancer were investigated using a randomised controlled trial.1 The intervention was a six months’ treatment programme consisting of guidelines about prevention of lymphoedema, exercise therapy, and manual lymph drainage. Control treatment consisted of the same programme as the intervention but without the guidelines about manual lymph drainage. Participants were consecutive patients with breast cancer and unilateral axillary lymph node dissection. The length of follow-up was 12 months after surgery. The setting was hospitals in Belgium.

The outcome measures included the cumulative incidence of arm lymphoedema by follow-up. Arm lymphoedema was defined as an increase in arm volume of 200 mL or more in the value before surgery. The sample size was based on having 80% power to detect a difference between treatment groups of 20% in the cumulative incidence of arm lymphoedema, assuming a cumulative incidence of 30% for the control group at follow-up. The sample size calculation assumed a two sided hypothesis test and critical level of significance of 0.05 (5%). In total, 146 patients were required. To account for an estimated dropout rate of 10%, the required sample size was adjusted to 160 patients. In total, 160 patients were recruited, with 79 allocated to the intervention, and 81 allocated to control.

Overall, 154 (96.3%) patients completed follow-up, with four patients in the intervention group and two in the control group lost to follow-up. At 12 months after surgery, the percentage of patients with arm lymphoedema was higher in the intervention group than in the control group, although the difference was not significant (24% (n=18) versus 19% (n=15); difference 5%, 95% confidence interval −8% to 18%; P=0.45). It was concluded that there was no evidence that manual lymph drainage in addition to guidelines and …
Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study.
Authors: K Höffken, W Jonat, K Possinger, M Kölbel, T Kunz, H Wagner, R Becher, R Callies, P Friederich, W Willmanns
Journal: Journal of Clinical Oncology (1990)

Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.
Comparison of two different O2-delivery systems during exercise in patients with chronic hypoxia
Authors: János Juhász, Júlia Juhász
Journal: European Respiratory Journal (2011)

Results from case studies using a high-flow oxygen delivery system (TNI®) suggest advantage regarding the oxygenation compared to conventional O 2 -therapy (LTOT). Aim of the study was to verify the feasibility, safety and clinical significance of TNI® compared to LTOT.   Method:  14 patients (pts) with chronic hypoxia underwent standardized treadmill six-minute walk test (6MWT) in a prospective, randomized study. All pts completed 6MWT on room air (basis). Then, they underwent consecutive 6MWTs applying TNI® and LTOT in a random order (40% O 2 -admixture each). Between 6MWTs, pts had a rest of 30 minutes. We measured walking distance (m), workload performance (Watt), energy expenditure (kcal), and collected data from Borg-dyspnoea-scale (BDS) and blood gas analysis (BGA) before 6MWT and at maximum workload (WLm). Primary outcome measures were ΔPaO 2  and ΔPaCO 2  from rest to WLm and their relation to walking distance (m/ΔPaO 2 ), exercise performance (Watt/ΔPaO 2 ) and energy expenditure (kJ/ΔPaO 2 ).   Results:  BDS scores increased from rest to WLm by 5,58±2,15 (basis), 2,67±1,78 (TNI®) and 3,38±2,04 (LTOT) scores. Waking distances during basis, TNI® and LTOT were 182,14 m, 235,86 m and 232,86 m respectively. ΔPaO 2  from rest to WLm was higher during LTOT compared to TNI® (-10,19 mmHg vs. -7,80 mmHg respectively) at identical workload performance (43,21 Watt). Workload economy, performance- and energy efficacy was better during TNI® vs. LTOT (30,22 vs. 22,85 m/mmHg; 5,53 vs. 4,24 Watt/mmHg and 2.02 vs. 1,51 kJ/mmHg respectively).   Conclusion:  TNI® compared to LTOT was safe to deliver O 2  for pts with hypoxia during exercise and superior in regard to workload economy, performance- and energy efficiency.
Alteration of Skin in Gross Leukemia. I. Syngeneic Skin-Graft Rejection and Tumor Development&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T. Mariani, P. B. Dent, R. A. Good
Journal: JNCI Journal of the National Cancer Institute (1970)

Recent studies showed that tumor induction by virus may be accompanied by antigenic alteration in the host tissue. In this study, syngeneic skin grafts from (C3H/Bi × DBA/2)F1 donors with ascites or solid transplantable Gross lymphoma were rejected, and in addition, tumors developed at the graft site. These phenomena were observed through seven successive passages. Transfer of the tumor from the graft site indicated no alteration in its biologic behavior. Histologic examination revealed that the donor skin contained tumor cells, which suggests skin rejection is caused by tumor cells in the graft. Preliminary experiments also showed that syngeneic skin transplants from preleukemic animals can be rejected without tumor development at the graft site, indicating that antigenic alteration may be due to a virus rather than neoplastic cells.
Studies on Carcinogenic Properties of Bracken, &lt;italic&gt;Pteridium aquilinum&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Iwao Hirono, Chiken Shibuya, Katsumasa Fushimi, Masanobu Haga
Journal: JNCI Journal of the National Cancer Institute (1970)

The carcinogenicity of young bracken (Pteridium aquilinum) used as a human food was studied in inbred strain ACI rats. Experimental groups were divided into 3 groups: Group I received for 4 months the pellets containing unprocessed bracken; Group II received for 4 months the pellets containing processed bracken that had been treated with boiling water; and Group III received for 18–27 days the extracted water of bracken. A control group was fed a normal diet. All Group I rats surviving beyond 7 months after the start of feeding developed tumors in the ileal regions. These tumors were not only epithelial, such as adenoma and adenocarcinoma, but also sarcomas. Cecal tumors were also induced. In Group II, the latent period of the tumor was longer than that in Group I. Furthermore, the incidence of intestinal tumors was lower than that in Group I, and sarcomas were not observed. However, the incidence of urinary bladder tumors was higher than that in the control group. Compared with the control group, Group III rats had no significant difference in the incidence of tumor. These results suggest that carcinogen in bracken can be removed to some extent by treatment with boiling water and that administration of a relatively small amount of bracken carcinogen for a long period results in a high incidence of tumors of the urinary bladder and the intestine.