tbuckley/cabot-search huggingface dataset:
Five-year quality of life (QOL) follow-up of adjuvant endocrine therapy for postmenopausal women in the Arimidex (A), Tamoxifen (T), Alone or in Combination (ATAC) Trial
Authors: D. Cella, L. Fallowfield
Journal: Journal of Clinical Oncology (2005)

577 Background: The 5-year treatment completion analysis of the ATAC Trial established that compared with T, A had superior efficacy in terms of disease-free survival, time to recurrence and contralateral breast cancer with superior tolerability. The 2-year QOL data from an accompanying subprotocol involving 1021 of 9366 ATAC trial patients has already been published (JCO, 2004, 22(21):4261–4271). We report below the first results from a longitudinal follow-up of the impact of 5 years’ adjuvant hormonal therapy on QOL. Methods: QOL assessments using the FACT-B and endocrine symptom subscale (ES) were made at baseline, 3 months, 6 months, and every 6 months thereafter, up until and including confirmation of disease recurrence, cessation of trial therapy or withdrawal from the subprotocol. The primary endpoint was Trial Outcome Index (TOI), a summation of physical components of QOL. Formal analyses compared A (n=335) with T (n=347). Results: Over the 5-year period, 17% of expected evaluations were missing. The missing data rate increased with time. TOI showed continued slight improvement in both A and T groups. There was no significant difference in TOI between treatments (p=0.65). Furthermore 67% of patients in both A and T experienced a clinically meaningful TOI improvement (at least 5 pts) from baseline at some point in their follow-up. Following the initial worsening of endocrine symptoms seen at 3 months (already reported) ES stabilized, although ES never recovered to baseline levels. Overall ES showed no significant difference between A and T (p=0.51) but some differences consistent with those previously reported remained, including increased vaginal discharge and bleeding on T and increased vaginal dryness and dyspareunia on A. Conclusions: Endocrine therapy with A or T was well tolerated over 5 years of treatment. FACT-B TOI showed steady improvements, which continued beyond 2 years among women who remained on study. After an initial decrease, ES score was relatively stable until 5 years. The efficacy benefits of A are achieved without a detrimental impact on overall QOL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Mutations of the gyrA gene of mycobacterium tuberculosis leading to XDR tuberculosis in Kyrgyz Republic
Authors: Jainagul Isakova, Nurmira Sovhozova, Almaz Aldashev
Journal: European Respiratory Journal (2011)

In the treatment of multidrug-resistant tuberculosis (MDR) the second line drugs are prescribed and among them the most ones are fluroquinolones. But the emergency problem of the recent years is the development of fluroquinolone resistance or XDR tuberculosis. The XDR is associated with mutations in the gyrA gene which controles the proliferation of M.tb.   Aim:  Analysis of mutations of the gyrA gene of M. tuberculosis (M.Tb) strains from patients of penitentiary system and civilian hospitals of Kyrgyz Republic.   Materials and methods:  Sputum samples of 79 pulmonary tuberculosis (TB) patients were analyzed by biochip assay to detect the gyrA mutations of M.tb. From all samples the 33 sputum samples were taken from patients in the penitentiary system and 46 sputum samples were taken from patients in the civilian sector.   Results:  M.tb resistant to fluroquinolone were found in 8.7% of TB patients from the civilian sector and in 6% of TB patients from the penitentiary system which gives the resistance to fluroquinolones of about 7.6% in general TB patients subpopulation. The detailed analysis of the mutations of gyrA gene revealed its location mainly in codons 90 and 94. The most frequent mutations was Asp94Gly (66.6%) than it was Ala90Val (16.6%). One case had the combination of both mutations Asp94Gly and Ala90Val.   Conclusion:  In XDR tuberculosis patients from Kyrgyz Republic the resistance of M.tb to fluroquinolones is mainly caused by Asp94Gly and Ala90Val mutations of gyrA gene.
TN categorization for rectal and colon cancers based on national survival outcome data
Authors: L. L. Gunderson, J. M. Jessup, D. J. Sargent, F. L. Greene, A. Stewart
Journal: Journal of Clinical Oncology (2008)

4020 Background: The 6th edition (ed) of AJCC staging subdivided Stage II into IIA(T3N0)/IIB(T4N0) and Stage III into IIIA(T1–2N1M0), IIIB(T3–4N1M0), IIIC(anyTN2M0). Subsequent analyses supported further substaging of Stage III due to improved survival with T1–2N2 cancers. Before making such changes in the AJCC 7th ed, the HTF sought validation in a population-based dataset that depth of invasion interacts with nodal status to affect survival. Methods: SEER population-based data from Jan 1, 1992 to Dec 2004 for 35,829 rectal and 109,953 colon cancer pts was compared to Cooperative Group rectal data on 2551 pts (Rectal Pooled Analysis). Tumors were stratified by SEER’s ‘extent of disease’ and ‘number of positive nodes’ coding schemes. T4N0 cancers were stratified by ‘tumors that perforate visceral peritoneum’ vs ‘tumors that invade or are adherent to adjacent organs or structures’. N1 and N2 were stratified by number of N+: N1(1 vs 2–3), N2(4–6 vs >7). Observed 5-y survival (∼ overall survival, OS) was obtained for each TN category. Results: Survival outcomes for rectal and colon cancer were similar by TN category (Table). T1–2N2 cancers have better prognosis than T3–4N2, and T4bN1 lesions have prognosis similar to T4N2 in both rectal and colon datasets. Prognosis for T4a lesions (Tumor penetrates visceral peritoneum) is better than T4b(Tumor directly invades or is adherent to other organs or structures) by N category (Table,N0/N1). Number of N+ affects prognosis. N1a(1N+) has 5–10% better 5y OS than N1b(2–3+); N2a(4–6+) ∼12% better 5y OS than N2b(>7+) by T category. Conclusions: This population- based outcomes analysis validates the Rectal Pooled Analysis data and supports the shift of T1–2N2 cancers from IIIC to IIIA/IIIB and T4bN1 from IIIB to IIIC. It also supports subdividing IIB into IIB(T4aN0) or IIC(T4bN0) and shifting favorable TN2 categories from IIIC to IIIA(T1N2a) or IIIB(T1N2b, T2N2a-b, T3N2a, T4aN2a). Outcomes by TN category suggest a complex biological interaction between depth of primary invasion and nodal metastases. TN Category Rectal Pooled 5y OS Pt Proposed TNM 7th Ed. SEER, Rectal 5y Observed SR Pt SEER, Colon 5y Observed SR Pt No. % No. % SE No. % SE T1–2N0 – – I 9,961 77.6 0.5% 23,861 76.3 0.3% T3N0 668 74 IIA 10,615 64.0 0.5 40,338 66.7 0.3 T4N0 95 65 IIB, T4a 818 55.7 1.9 5,020 60.6 0.8 IIC, T4b 769 44.7 2.1 3,088 45.7 1.0 T1–2N1 225 81 IIIA 2,008 72.1 1.2 3,134 71.1 1.0 T1–2N2 180 69 IIIA/IIIB* 508 56.1 2.6 499 61.5 2.6 T3N1 544 61 IIIB 5,787 52.4 0.8 17,866 54.9 0.4 T4N1 59 33 IIIB, T4a 480 48.2 2.5 2,771 47.0 1.1 IIIC, T4b 423 24.3 2.5 1,774 27.9 1.2 T3N2 663 48 IIIC 3,755 37.5 0.9 8,566 38.1 0.6 T4N2 84 38 IIIC 705 26.4 1.9 3,036 21.7 0.9 * IIIA-T1N2a; IIIB-T2N2a, T1–2N2b No significant financial relationships to disclose.
Pregnant women are advised to seek medical advice if they need paracetamol for more than one day
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Pregnant women are being advised to see their doctor if they need to take paracetamol for more than a day, after researchers found in an animal study that prolonged use of the analgesic reduced the production of testosterone.1

Four previous studies have linked the use of paracetamol in pregnancy with an increased risk of cryptorchidism in male babies, but a causal effect has not been shown because it is not possible to test the association in women. To overcome this, researchers from the University of Edinburgh developed an animal model using castrated mice, into which they grafted human testicular tissue. These grafts have been shown to mimic how the developing testes grow and function in pregnancy.

The researchers gave the mice a typical dose of paracetamol that a woman would take (20 …
Clinical and functional differences, exercise capacity and physical activity among frequent and not frequent exacerbators in COPD patients
Authors: Agustin Valido, Ana Gomez-Bastero, Virginia Almadana, Estefania Luque, Teodoro Montemayor
Journal: European Respiratory Journal (2014)

Aim:to assess the differences in exercise capacity and physical activity based on the number of exacerbations.  Material and Methods:Observational and retrospective study of COPD patients during the last 4 months. We analyzed several variables: epidemiological, clinical and functional, quality of life(CAT), 6 minutes walking test – 6MWT and physical activity. We divided the patients based on the number of exacerbations within the last year (ex-year): no frequent exacerbators (NF) (l2 ex-year) and frequent exacerbators (F) (≥2 ex-year).  Results:100 patients were included: 39 showed l 2 ex-year vs 61 ≥ 2 ex-year. Significant differences were found in age,MRC dyspnea, presence of respiratory failure,BODE, GOLD 2011 and GesEPOC when comparing both groups in terms of general and clinical characteristics and scores on quality of life questionnaires and rate of severity and prognosis. There were differences in the characteristics of exacerbations and the lung function parameters (FEV1 and IC / TLC), but not in exercise tolerance and physical activity of patients in both groups.  Conclusions:1.With the patients presenting a greater number of exacerbations leads to a worse clinical and functional status.  2.Our patient9s capacity or tolerance to exercise is not influenced by having more or less exacerbations nor by the degree of physical activity.
A novel mutation in <i>CDSN</i> causes peeling skin disease in a patient from Morocco
Authors: J. Mazereeuw-Hautier, E.A. Leclerc, M. Simon, G. Serre, N. Jonca
Journal: British Journal of Dermatology (2011)

Journal Article A novel mutation in CDSN causes peeling skin disease in a patient from Morocco Get access J. Mazereeuw‐Hautier, J. Mazereeuw‐Hautier UMR 5165/U1056 'Différenciation Epidermique et Autoimmunité Rhumatoïde' (CNRS – INSERM – Université Toulouse III – CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, FranceCentre de Référence des Maladies Rares de la Peau, Service de Dermatologie, Hôpital Larrey, 24 Chemin de Pouvourville, TSA 30030, 31059 Toulouse Cedex 9, France Search for other works by this author on: Oxford Academic Google Scholar E.A. Leclerc, E.A. Leclerc UMR 5165/U1056 'Différenciation Epidermique et Autoimmunité Rhumatoïde' (CNRS – INSERM – Université Toulouse III – CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France Search for other works by this author on: Oxford Academic Google Scholar M. Simon, M. Simon UMR 5165/U1056 'Différenciation Epidermique et Autoimmunité Rhumatoïde' (CNRS – INSERM – Université Toulouse III – CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France Search for other works by this author on: Oxford Academic Google Scholar G. Serre, G. Serre UMR 5165/U1056 'Différenciation Epidermique et Autoimmunité Rhumatoïde' (CNRS – INSERM – Université Toulouse III – CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France Guy Serre. E‐mail guy.serre@udear.cnrs.fr Search for other works by this author on: Oxford Academic Google Scholar N. Jonca N. Jonca UMR 5165/U1056 'Différenciation Epidermique et Autoimmunité Rhumatoïde' (CNRS – INSERM – Université Toulouse III – CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 5, 1 November 2011, Pages 1152–1155, https://doi.org/10.1111/j.1365-2133.2011.10529.x Published: 01 November 2011
Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study.
Authors: J P Simons, N K Aaronson, J F Vansteenkiste, G P ten Velde, M J Muller, B M Drenth, F L Erdkamp, E G Cobben, E J Schoon, J B Smeets, H C Schouten, M Demedts, H F Hillen, G H Blijham, E F Wouters
Journal: Journal of Clinical Oncology (1996)

PURPOSE To investigate the effects of medroxyprogesterone acetate (MPA) on appetite, weight, and quality of life (QL) in patients with advanced-stage, incurable, non-hormone-sensitive cancer. PATIENTS AND METHODS Two hundred six eligible patients were randomized between double-blind MPA 500 mg twice daily or placebo. Appetite (0 to 10 numerical rating scale), weight, and QL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ-C30]) were assessed before the start of treatment (t = 0), and 6 weeks (t = 6) and 12 weeks (t = 12) thereafter. RESULTS One hundred thirty-four patients (68 MPA and 66 placebo) were assessable at t = 6 and 99 patients (53 MPA and 46 placebo) at t = 12. A beneficial effect of MPA on appetite was observed after both 6 weeks (P = .008) and 12 weeks (P = .01) of treatment. After 12 weeks, a mean weight gain of 0.6 +/- 4.4 kg was seen in the MPA, versus an ongoing mean weight loss of 1.4 +/- 4.6 kg in the placebo group. This difference of 2.0 kg was statistically significant (P = .04). During the study, several areas of QL deteriorated in the total group of patients. With the exception of an improvement in appetite and possible also a reduction in nausea and vomiting, no measurable beneficial effects of MPA on QL could be demonstrated. The side effects profile of MPA was favorable: only a trend toward an increase in (usually mild) peripheral edema was observed. CONCLUSION In weight-losing, advanced-stage non-hormone-sensitive cancer patients, MPA exhibits a mild side effects profile, has a beneficial effect on appetite, and may prevent further weight loss. However, general QL in the present study was not measurably influenced by MPA treatment.
Prevalence and diagnosis of asthma in General Practice after computerized Spanish guideline on the management of asthma (GEMA) and collaborative care environment
Authors: Sandra Dorado, Silvia Pascual, Isabel Urrutia, Carlos Salinas, Leire Sainz de Aja, Urko Aguirre, Ane Antón, Mateo Larrauri, Rafael Arruabarrena, Iñaki Intxausti, Santos Antonio Cea, José Ferri, José Luis Bilbao
Journal: European Respiratory Journal (2014)

INTRODUCTION: There is evidence of asthma overdiagnosis in association to the lack of objective diagnosis tests. The effectiveness of a collaborative multidisciplinary care environment and the recommendations of GEMA is probed.  AIM: Assess the impact in the prevalence and diagnosis of asthma after a collaborative care environment and the implementation of GEMA in computerized medical records of General Practice (GP).  METHODS: Prospective and multidisciplinary observational cohort study. The intervention was started in November of 2010 and based on the implementation of GEMA in computerized medical records of GP and a collaborative care environment in the East region of Biscay. Pulmonology Department of Galdakao-Usansolo Hospital, 4 centres of GP and Information Technology managers are involved. All the asthmatic patients who were attended in GP clinic are included and randomized, doing a descriptive statistical analysis.  RESULTS: 6128 patients from 4 centres of GP: 50.08% in the intervention group (IG) and 49.92% in the control group (CG). Prevalence of asthma diagnosis: 4.59% in IG and 11.80% in CG (p  Randomized selection of 160 patients: Conclusive diagnosis of asthma (at least one positive objective test accepted by GEMA) in 80% of IG and in only 35% of CG (p  CONCLUSIONS: The prevalence of asthma diagnosis after the mentioned intervention is similar to the known one in our region according to the results obtained in the European Community Respiratory Health Survey in Adults (ECRHS II).  The referred intervention avoids overdiagnosis of asthma and stimulates the diagnosis based in objective methods.
QVA149 improves dyspnoea and lung function versus tiotropium in symptomatic patients using LABA/ICS preceding study enrolment: The BLAZE study
Authors: Anthony D'Urzo, Donald A. Mahler, Caglar Karakurum, Hungta Chen, Robert Fogel, Donald Banerji
Journal: European Respiratory Journal (2014)

Introduction 

In the BLAZE study, QVA149 showed superior improvements in dyspnoea (assessed by self-administered computerised-transition dyspnoea index [SAC-TDI]) and lung function vs placebo (PBO) and tiotropium (TIO).1 In this post-hoc analysis, we report these outcomes from the subgroup population using LABA/ICS prior to study enrolment, primarily because of inappropriate use of ICS, despite not being recommended for patients (pts) with moderate COPD (GOLD B).

Method 

This blinded, crossover study randomised pts with moderate-to-severe COPD (mMRC≥2) to once-daily QVA149 110/50µg, PBO or TIO 18µg.1 Outcomes reported were SAC-TDI, FEV1, FEV1AUC0-4 h, and rescue medication use.

Results 

Of the 247 pts randomised, 82 pts were on prior LABA/ICS therapy. At Wk 6, the proportion of pts who achieved the SAC-TDI score (≥1unit) was higher with QVA149 (39.5%) than PBO (19.0%; odds ratio [OR] 3.16) or TIO (20.0%; OR 3.31; both p<0.01). QVA149 significantly improved mean FEV1 up to 4h post-dose and FEV1AUC0-4h (table), and reduced mean daily rescue medication use (puffs/day) by 1.53 (p<0.001) and 0.44 (p=0.128) vs PBO and TIO, respectively.

View this table:

LSMTD in FEV1 and FEV1AUC0-4h, mL





Conclusion 

Improvements in dyspnoea and lung function, and reduction in rescue medication use with QVA149 vs PBO and TIO have been shown in overall population. Similar significant improvements were seen in subgroup population using LABA/ICS prior to study enrolment.

Reference 

1. Mahler et al. Eur Respir J 2013.
Abstract 1000: Do Vascular Closure Devices Reduce Vascular Complications in Patients Undergoing Percutaneous Coronary Interventions: Insights From the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2)
Authors: Hitinder S Gurm, Thomas Lalonde, Arthur Riba, Dean E Smith, David Share, Mauro Moscucci
Journal: Circulation (2009)
A comparison between the airway response to isocapnic hyperventilation and hypertonic saline in subjects with asthma
Authors: CM Smith, SD Anderson
Journal: European Respiratory Journal (1989)

We compared the response to isocapnic hyperventilation (ISH), where both cooling and drying of the mucosa occur, with the response to inhaling aerosols of hypertonic saline (HS), where airway osmolarity increases without airway cooling. We studied nine subjects on two days. For ISH, subjects ventilated at 70% of their estimated maximum voluntary ventilation (MVV). For HS, they inhaled aerosols of 2.7, 3.6, or 4.5% saline. The concentration that was used depended on the rate of ventilation during ISH. For both challenges the stimulus was given for one minute. Forced expiratory volume in one second (FEV1) was measured once between each minute, and the challenge ceased when the FEV1 did not change for two successive minutes. A plateau in FEV1 occurred after 8.1 +/- 2.4 (mean +/- 1 SD) min of ISH, and 8.3 +/- 2.4 min of HS. The lowest FEV1 (% predicted) after ISH was 45 +/- 16% and after HS was 51 +/- 18% (r = 0.93). However, the maximum responses occurred after the final challenge and were not the same as the plateau. For HS, the plateau represented 89 +/- 11% of the maximum response which developed within one minute of the final challenge. For ISH, the plateau was only 56 +/- 26% of the maximum response, which developed within 5.2 +/- 2.9 min after challenge. The similarities in the response to these challenges are consistent with the hypothesis that ISH induces asthma via hyperosmolarity. The delayed response to ISH suggests that cooling may delay the response to hyperosmolarity.
Hemodynamic and clinical relevance of "borderline pulmonary hypertension"
Authors: Gabor Kovacs, Alexander Avian, Vasile Foris, Maria Tscherner, Andrea Olschewski, Horst Olschewski
Journal: European Respiratory Journal (2013)

The clinical relevance of borderline mean pulmonary arterial pressure (mPAP: 21-24mmHg) is not entirely clear.  We retrospectively analyzed hemodynamic measurements at rest and during exercise of patients with resting mPAP  We included n=141 patients (borderline: n=32). Borderline patients were older (65.8±12.5yr vs. 57.3±12.5yr, p=0.001) and had more often an underlying cardiac (53% vs. 15%, p  Patients with “borderline PH” represent a distinct group of patients with higher resistance, lower compliance and decreased exercise capacity compared to patients with resting mPAP≤20mmHg. Borderline PH is often associated with a mild respiratory or left heart disease.
Increased expression of cell adhesion molecule 1 by mast cells as a cause of enhanced nerve-mast cell interaction in a hapten-induced mouse model of atopic dermatitis
Authors: M. Hagiyama, T. Inoue, T. Furuno, T. Iino, S. Itami, M. Nakanishi, H. Asada, Y. Hosokawa, A. Ito
Journal: British Journal of Dermatology (2012)

Neuroimmunological disorders are involved in the pathogenesis of atopic dermatitis (AD), partly through enhanced sensory nerve-skin mast cell interaction. Cell adhesion molecule 1 (CADM1) is a mast-cell adhesion molecule that mediates the adhesion to, and communication with, sympathetic nerves.To investigate the role of mast cell CADM1 in the pathogenesis of AD, CADM1 expression levels by comparing between lesional and nonlesional skin mast cells of an AD mouse model, which was developed by repeated application of trinitrochlorobenzene, and to examine, in cocultures, how the alterations in CADM1 detected in lesional mast cells might affect the sensory nerve-mast cell interaction.AD-like lesional and nonlesional skin mast cells were collected separately by laser capture microdissection. CADM1 expression was examined by reverse transcription-polymerase chain reaction and CADM1 immunohistochemistry. In cocultures, adhesion between dorsal root ganglion (DRG) neurites and IC2 mast cells was analysed by loading a femtosecond laser-induced impulsive force on neurite-attendant IC2 cells, while cellular communication was monitored as the IC2 cellular response ([Ca(2+)]i increase) after nerve-specific stimulant-induced DRG activation.AD-like lesional mast cells expressed three-fold more CADM1 transcripts than nonlesional cells. This was supported at the protein level, shown by immunohistochemistry. In coculture, CADM1 overexpression in IC2 cells strengthened DRG neurite-IC2 cell adhesion and doubled the population of IC2 cells responding to DRG activation. A function-blocking anti-CADM1 antibody abolished these effects in a dose-dependent manner.Increased expression of CADM1 in mast cells appeared to be a cause of enhanced sensory nerve-mast cell interaction in a hapten-induced mouse model of AD.